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

ONES 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 ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Bones: 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: 0-597-84259-0 1. Bones-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 bones. 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 BONES ....................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bones ........................................................................................... 13 E-Journals: PubMed Central ....................................................................................................... 70 The National Library of Medicine: PubMed ................................................................................ 83 Academic Periodicals covering Bones .......................................................................................... 99 Dissertations on Bones................................................................................................................. 99 CHAPTER 2. NUTRITION AND BONES ........................................................................................... 101 Overview.................................................................................................................................... 101 Finding Nutrition Studies on Bones.......................................................................................... 101 Federal Resources on Nutrition ................................................................................................. 110 Additional Web Resources ......................................................................................................... 110 CHAPTER 3. ALTERNATIVE MEDICINE AND BONES ..................................................................... 121 Overview.................................................................................................................................... 121 The Combined Health Information Database............................................................................. 121 National Center for Complementary and Alternative Medicine................................................ 122 Additional Web Resources ......................................................................................................... 128 General References ..................................................................................................................... 153 CHAPTER 4. CLINICAL TRIALS AND BONES .................................................................................. 155 Overview.................................................................................................................................... 155 Recent Trials on Bones............................................................................................................... 155 Keeping Current on Clinical Trials ........................................................................................... 178 CHAPTER 5. PATENTS ON BONES .................................................................................................. 181 Overview.................................................................................................................................... 181 Patents on Bones ........................................................................................................................ 181 Patent Applications on Bones .................................................................................................... 185 Keeping Current ........................................................................................................................ 192 CHAPTER 6. BOOKS ON BONES...................................................................................................... 193 Overview.................................................................................................................................... 193 Book Summaries: Federal Agencies............................................................................................ 193 Book Summaries: Online Booksellers......................................................................................... 195 The National Library of Medicine Book Index ........................................................................... 195 Chapters on Bones...................................................................................................................... 196 CHAPTER 7. MULTIMEDIA ON BONES ........................................................................................... 201 Overview.................................................................................................................................... 201 Video Recordings ....................................................................................................................... 201 Bibliography: Multimedia on Bones........................................................................................... 203 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 205 Overview.................................................................................................................................... 205 U.S. Pharmacopeia..................................................................................................................... 205 Commercial Databases ............................................................................................................... 210 Researching Orphan Drugs ....................................................................................................... 211 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 217 Overview.................................................................................................................................... 217 NIH Guidelines.......................................................................................................................... 217 NIH Databases........................................................................................................................... 219 Other Commercial Databases..................................................................................................... 222 The Genome Project and Bones.................................................................................................. 222 APPENDIX B. PATIENT RESOURCES ............................................................................................... 227

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Overview.................................................................................................................................... 227 Patient Guideline Sources.......................................................................................................... 227 News Services and Press Releases.............................................................................................. 239 Newsletters on Bones ................................................................................................................. 240 Newsletter Articles .................................................................................................................... 241 Associations and Bones .............................................................................................................. 243 Finding Associations.................................................................................................................. 246 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 249 Overview.................................................................................................................................... 249 Preparation................................................................................................................................. 249 Finding a Local Medical Library................................................................................................ 249 Medical Libraries in the U.S. and Canada ................................................................................. 249 ONLINE GLOSSARIES................................................................................................................ 255 Online Dictionary Directories ................................................................................................... 260 BONES DICTIONARY ................................................................................................................. 261 INDEX .............................................................................................................................................. 347

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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 bones is indexed in search engines, such as www.google.com or others, a nonsystematic 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 bones, 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 bones, 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 bones. 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 bones, 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 bones. 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 BONES Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bones.

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

Bone Mass Drops in Anorexia Source: Healthy Weight Journal. 15(5): 66. September/October 2001. Summary: According to a Massachusetts study, body weight, rather than estrogen deficiency, predicts bone density in anorexic women. Thinner women have weaker, less dense bones. In a study of 130 women with anorexia nervosa, bone mineral density was reduced at least one standard deviation at one or more sites in 92 percent of the patients. Some of the patients were taking estrogen and others had a history of estrogen use, yet the findings remain the same. Bone loss for these women was comparable to that of women many decades older, despite estrogen therapy. The researchers recommend screening for osteoporosis and counseling about the adverse effects of low weight, especially for women with anorexia.

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A Bone to Pick Source: The Walking Magazine. p.34-36. July/August 2000. Summary: Calcium may be overemphasized in the prevention of osteoporosis, according to some researchers. One conclusion of a March 2000 National Institutes of Health consensus conference was that calcium matters but so do other nutrients such as vitamins D and K. Another conclusion was that exercise may be even more important in protecting bones. One osteoporosis researcher noted that consuming a calcium-rich diet can improve bone strength by only 5 percent whereas regular physical activity can improve it by 15 percent. The new emphasis on exercise as the key to osteoporosis prevention is backed by strong science. Many studies have shown that physical activity determines the strength, shape, and mass of bone, and that bone strength increases in tandem with increasing exercise frequency. Calcium is useless if someone is inactive, as illustrated by the rapid bone loss that occurs when people are bedridden, even when they are fed 1,000 milligrams of calcium daily. The article concludes by pointing out that very low body weight throughout life is one of the strongest predictors of bone thinning later in life.

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Guided Bone Regeneration Using Bone Grafts and Collagen Membranes Source: Quintessence International. 32(7): 504-515. July-August 2001. 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. Summary: Dental prostheses made on dental implants have increased stability and retention compared to traditional removable partial dentures and are more conservative of tooth structure than are fixed appliances. Guided bone regeneration (GBR) is a surgical technique used to regenerate alveolar bone defects prior to, in conjunction with, or subsequent to the placement of implants. When nonabsorbable membranes are used for GBR, second surgeries are required for membrane retrieval. In addition, these types of membranes show a high incidence of flap sloughing and membrane exposure that often lead to infection and unfavorable results. Absorbable barriers such as collagen membranes were developed to overcome these drawbacks. This article presents the principles and the clinical procedure of using barrier membranes composed of absorbable collagen in GBR aimed at the repair and regeneration of ridge dehiscence defects around implants. The unique properties of collagen membranes that make them ideally suited to GBR procedures are reviewed. In addition, the authors outline the indications and contraindications for using collagen membranes for GBR procedures. Finally, the authors present cases to demonstrate details of surgical principles and techniques; black and white photographs illustrate each case. 26 figures. 1 table. 31 references.

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Bones and Crohn's: Problems and Solutions Source: Inflammatory Bowel Diseases. 5(3): 212-227. August 1999. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030. Fax (301) 824-7390. Summary: Inflammatory bowel disease (IBD) may manifest in various extra intestinal ways. In this review article, the author describes the various manifestations of skeletal abnormalities associated with IBD, their possible pathophysiology, and possible methods of prevention and treatment. The author notes that much of the experience on

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solutions to the problem is based on the extrapolation from studies in patients with other systemic inflammatory conditions (such as rheumatoid arthritis) because in some cases the data available from patients with IBD is limited or nonexistent. The author focuses on osteopenia (subnormally mineralized bone), noting that osteopenia and various arthropathies may be very debilitating. These may be related to the disease itself, patient genetics, lifestyle, or disease treatment. Calcium and vitamin D malabsorption, vitamin K deficiency, malnutrition, corticosteroid and other immunosuppressive medications, smoking, lack of exercise, and postmenopausal state may all play important roles. Treatment may be undertaken to correct nutrient deficiencies, inhibit bone resorption, and increase bone formation. 2 figures. 3 tables. 214 references. •

Post-Menopausal Bone Loss and Its Relationship to Oral Bone Loss Source: Periodontology 2000. 23(1): 94-102. June 2000. Contact: Available from Munksgaard International Publishers Ltd. Commerce Place, 350 Main Street, Malden, MA 02148-5018. (781) 388-8273. Fax (781) 388-8274. Summary: Osteoporosis and osteopenia are characterized by reductions in bone mass and both may lead to skeletal fragility and fracture. This article reviews postmenopausal bone loss and its relationship to oral bone loss. Women are at greater risk for osteoporosis after menopause. The authors review this risk factor and others, discuss methods used to measure of bone mass and density, consider the relationship between systemic and mandibular (lower jaw) bone density, report preliminary data from the Women's Health Initiative Oral Ancillary Study, and outline common strategies for treatment of osteoporosis and periodontal disease. The authors conclude that while a possible relationship between osteoporosis and oral bone loss has long been postulated, the existing studies have been preliminary in nature. Longitudinal studies will make it possible to determine if the progression of periodontal disease is more rapid in patients with osteopenia than in patients with normal bone density. 6 figures. 3 tables. 52 references.

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The Seeds of Stronger Bones Source: Health. 115(3):58, 60, 62. April 2001. Summary: Researchers at the University of Arkansas found a direct correlation between yard work and healthy bone density among 3,310 women aged 50 and older. Women gardeners had denser bones than women who regularly engaged in jogging, swimming, walking, and aerobics. The researchers found that gardening was as effective as weight training at preventing osteoporosis. Yard work puts much more pressure on bones than is immediately apparent notes Lori Turner, the dietitian who led the study. 'Digging holes, pulling weeds, pushing equipment, and hefting a wheelbarrow,' are weightbearing motions. Turner recommends gardening two to three times a week, depending on the strenuousness of the chores. A sidebar provides the calories burned in a half hour of a variety of gardening tasks.

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A Big Leap for Stronger Bones Source: Health. p.46,48,50. September 1998. Summary: Sharp reports on research indicating that weight-bearing exercise is not the best way to prevent bone density loss. Studies at Oregon State University have shown that exercise involving shock or impact is more important. According to exercise

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physiologist Christine Snow, the impacts of wrestling and gymnastics are better at bone building than exercise such as walking, swimming, or bicycling. Sharp offers several alternatives for bone-building exercise, such as backcountry hiking, racket sports, stair climbing, step aerobics, and simple jumping. A sidebar offers a sample exercise program of lunges, jumps, squats, and chair raises to increase bone density. •

Relationship Between Bone Mineral Density and Periodontitis in Postmenopausal Women Source: Journal of Periodontology. 71(9): 1492-1498. September 2000. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Systemic bone loss has been proposed as a risk factor for periodontal disease; however, the relationship between these two diseases is still not clear. This article reports on a study undertaken to assess the relationship between systemic bone density and periodontal disease (controlling for known cofounders). The study population included 70 postmenopausal Caucasian women aged 51 to 78 years (mean 62.10 years plus or minus 7.1 years). Skeletal bone mineral density (BMD) was assessed and periodontal disease severity was represented by clinical attachment loss (CAL) and interproximal alveolar bone loss (ABL). Other measures of periodontal status included probing depth (PD), supragingival plaque, gingival (gum) bleeding on probing, and calculus. Results showed that the mean alveolar bone loss was significantly correlated with BMD of the trochanter (the trunk end of the femur), Ward's triangle, and total regions of the femur (thigh bone). Mean CAL appeared to be related to BMD consistently at all regions of the skeleton, although the association did not reach statistical significance. The authors conclude that skeletal BMD is related to interproximal alveolar bone loss and, to a lesser extent, to clinical attachment loss, implicating postmenopausal osteopenia (subnormally mineralized bone) as a risk indicator for periodontal disease in postmenopausal Caucasian women. 1 figure. 4 tables. 45 references.

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Menopause-Related Oral Alveolar Bone Resorption: A Review of Relatively Unexplored Consequences of Estrogen Deficiency Source: Menopause: The Journal of the American Menopause Society. 6(2): 129-133. Summer 1999. Summary: The alveolar processes of the maxilla (upper jaw) and mandible (lower jaw) provide the bony framework for tooth support. Osteoporotic changes of these bones may directly affect tooth stability and retention. This article reviews studies that have evaluated the relationship between systemic osteoporosis and oral alveolar bone mass as well as the effect of estrogen use on oral alveolar bone and tooth retention. The literature review covered the years 1989 to 1998. Studies reviewed demonstrate a positive correlation between systemic bone mass and systemic osteoporosis to oral bone resorption. Estrogen replacement therapy affects oral bone in a manner similar to the way it affects other sites. The authors conclude that postmenopausal estrogen users may retain more teeth after menopause. Sustained oral health and better tooth retention are potentially additional benefits for hormone replacement therapy users after menopause. 25 references.

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Relationships Between Clinical Attachment Level and Spine and Hip Bone Mineral Density: Data from Health Postmenopausal Women Source: Journal of Periodontology. 73(3): 298-301. March 2002. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: There are physiological reasons to expect an association between bone mineral density of the spine and hip and attachment loss. To this point, however, most studies have found no correlation. The 135 patients reported on in this article were part of a randomized, controlled trial of estrogen replacement. All patients were in good oral health at entry and received annual oral prophylaxis as part of the study. Standard probing measurements were made with a pressure sensitive probe at 6 sites on each tooth. Bone mineral density was measured at the lumbar spine and proximal femur (thigh bone). These procedures were performed at baseline and at annual intervals for 3 years. Correlations between cross sectional measurements of clinical attachment level and bone mineral density were very weak and did not approach statistical significance. A few somewhat stronger correlations were found between longitudinal changes in bone mineral density and attachment. Although the correlations in the longitudinal changes were weak, they were consistently in the direction of greater bone mineral density being associated with less attachment loss. The authors conclude that there is no clear association between clinical attachment level and bone mineral density of the lumbar spine and proximal femur, whether examined on a cross sectional or longitudinal basis. 1 figure. 1 table. 7 references.

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Postmenopausal Bone Loss and Osteoporosis as Possible Risk Factors in Periodontal Disease: An Update Source: Ontario Dentist. 78(1): 31-36. January-February 2001. Contact: Available from 4 New Street, Toronto, ON M5R 1P6. (800) 387-1393. Fax (416) 922-9005. Website: www.oda.on.ca/. E-mail: [email protected]. Summary: This article considers the role of postmenopausal bone loss and osteoporosis as possible risk factors in periodontal disease. The author reviews current research and conclusions in the areas of peak bone mass and bone loss, osteoporosis and osteopenia, the relationship between systemic and mandibular (lower jaw) bone density, common risk factors for both osteoporosis and periodontal disease, and common strategies for the treatment of osteoporosis and periodontal disease. The author concludes that while a relationship between osteoporosis and oral bone loss has long been postulated, the existing studies have been preliminary in nature. The author calls for longitudinal studies that could make it possible to determine if the progression of periodontal disease is more rapid in patients with osteopenia than in patients with normal bone density. This, in turn, may lead to better diagnostic measures and treatment outcomes for both periodontal disease and osteoporosis. 4 tables. 22 references.

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Exploring the Damaged Ear: The NIDCD National Temporal Bone Registry Source: ASHA. American Speech-Language-Hearing Association. 41(1): 29-33. JanuaryFebruary 1999. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org.

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Summary: This article describes the NIDCD (National Institute on Deafness and Other Communication Disorders) National Temporal Bone Registry and the types of research conducted there. The authors note that many important questions in audiology remain unanswered because of the inaccessibility of the cochlea. The ability to study the temporal bone posthumously (after death) may offer a better understanding of the diseased or damaged cochlea in each particular case. The Registry was established in 1992 and not only enrolls new volunteers for posthumous temporal bone donation, but also coordinates the collection of temporal bones nationally, sponsors professional educational activities, and works closely with the 26 temporal bone laboratories in the U.S. The authors describe the research undertaken at these bone laboratories, the use of the cytocochleogram, and how the research findings can be used by audiologists to provide better service for people with hearing loss. Audiologists are also encouraged to keep donation in mind when seeing patients, and to make full use of the resources of the NIDCD National Temporal Bone Registry. Brochures that describe the donation process and importance of temporal bone research are available from the Registry, free of charge, for display in clinics. One sidebar notes the name and affiliation of the collaborating temporal bone laboratories. 2 figures. 7 references. •

Osteoporosis and Oral Bone Loss Source: Dentomaxillofacial Radiology. 26(1): 3-15. January 1997. Contact: Available from Stockton Press. 345 Park Avenue South, 10th Floor, New York, NY 10010-1707. (212) 689-9200. Fax (212) 689-9711. Summary: This article is a review of the literature on the possible association between osteoporosis and oral bone loss, with an emphasis of radiological studies. This association was first suggested in 1960. Subsequent studies showed that after the age of 50, there was a marked increase in the cortical porosity of the mandible (lower jaw), with this increase being greater in the alveolar bone than the mandibular body. With this increase in porosity, there was a concomitant decrease in bone mass, which appeared to be more pronounced in females than in males. The loss in bone mineral content was estimated to be 1.5 percent per year in females and 0.9 percent in males. Subsequent clinical studies reported associations between the bone densities of jaws and metacarpals, forearm bones, vertebrae, and femurs. The researchers suggested that systemic factors responsible for osteoporotic bone loss may combine with local factors (i.e., periodontal diseases) to increase rates of periodontal alveolar bone loss. Although not all studies found associations between osteoporosis and oral bone loss, the conclusion of this review is that such an association exists. Additional longitudinal investigations are needed to confirm this and inexpensive methods must be developed for sensitive and specific measures of oral bone loss. 141 references.

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Techniques for Human Temporal Bone Removal: Information for the Scientific Community Source: Otolaryngology: Head and Neck Surgery. 115(4): 298-305. October 1996. Summary: This article provides information for physicians on how to harvest temporal bones and brain stem tissue. Techniques are described for temporal bone and auditory brain stem removal, including intracranial and extracranial approaches and methods to minimize postmortem autolysis and cosmetic defects. The authors describe why human temporal bones are an irreplaceable resource for studying the pathology and pathophysiology of disorders of hearing, balance, taste, and facial nerve function. The authors emphasize the need for additional specimens to study disorders for which there

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are few human specimens; to increase the number of specimens for a given disorder to understand the natural variability and expression of the disease entity; to evaluate the accuracy of otologic diagnoses and the efficacy of otologic treatment modalities; to apply newly available scientific methods, including immunohistochemistry and molecular biologic or genetic techniques; and to teach the anatomy of the human ear and modern otologic surgical techniques. 7 figures. 1 table. 7 references. •

Hearing Loss in Paget's Disease of Bone: Evidence of Auditory Nerve Integrity Source: American Journal of Otology. 16(1): 27-33. January 1995. Summary: This article reports on a study in which auditory brainstem responses (ABRs) were recorded in 64 ears with radiographically confirmed Paget's disease involving the skull. Responses were absent in eight ears, all of which had elevated high pure-tone thresholds. ABRs were interpreted as normal in 56 ears; none were abnormal. Computed tomography (CT scan) and digital image analysis were used to quantify internal auditory canal (IAC) dimensions. The midlength diameter and minimum diameter of the IAC of 68 temporal bones from subjects with Paget's disease were found to have no statistically significant relation to hearing thresholds. Increased IAC length showed a limited relation to reduced hearing level in individuals with Paget's disease, possibly consistent with bossing adjacent to the porus acusticus. Findings support the principle that hearing loss in Paget's disease of bone is generally associated with intact auditory nerve function and also support a cochlear site of lesion. 4 figures. 4 tables. 17 references. (AA).

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Glycemic Control and Alveolar Bone Loss Progression in Type 2 Diabetes Source: Annals of Periodontology. 3(1): 30-39. July 1998. Contact: Available from American Academy of Periodontology. 737 North Michigan Avenue, Suite 800, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: This article reports on a study that investigated whether the risk for alveolar bone loss (the bones supporting the teeth) is greater, and bone loss progression more severe, for patients with poorly controlled (PC) type 2 diabetes mellitus (DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed. Of the 359 subjects, aged 15 to 57 with less than 25 percent radiographic bone loss at baseline, 338 did not have type 2 DM, 14 were BC, and 7 were PC. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score. The results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM between the other two groups. 1 figure. 4 tables. 52 references.

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Dental, Visual, Auditory and Olfactory Complications in Paget's Disease of Bone Source: Journal of the American Geriatrics Society. 43(12): 1384-1391. December 1995. Summary: This article reports on a study undertaken to determine the prevalence of dental problems in people with Paget's disease and in a control population without Paget's disease. The researchers examine the relationship of localization of bony involvement of Paget's disease with the prevalence of dental, auditory, visual, and smell changes. Each subject (n=498), randomly generated from the mailing list of the Paget Foundation, was sent two questionnaires, one for themselves and one for an unaffected

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spouse or similar-aged friend (the controls). All subjects were asked about their socioeconomic status, chronic medical conditions, self-rating of their general physical and dental health, the number of teeth present, and the presence of dental, auditory, visual, and olfactory problems. Results show that patients with Paget's disease assessed their oral health to be poorer than the controls. Those patients with Paget's disease of bone involving facial or maxillo-mandibular parts of the skeleton have a higher prevalence of change in hearing, sight, smell, and dental problems. 1 figure. 5 tables. 43 references. (AA-M). •

Prevalence of Bone Marrow Signal Abnormalities Observed in the Temporomandibular Joint Using Magnetic Resonance Imaging Source: Journal of Oral and Maxillofacial Surgery. 54(4): 434-440. April 1996. Summary: This article reports on an investigation undertaken to determine the prevalence of bone marrow signal abnormalities in patients referred for temporomandibular joint (TMJ) magnetic resonance imaging (MRI). This investigation was done because of prior studies suggesting that condylar marrow signal abnormalities indicate avascular necrosis. Retrospective review was done of 449 consecutive TMJ MRI examinations in 415 patients from 1991 to 1994. Condylar marrow signal abnormalities were reviewed and classified into either a bone marrow edema pattern or a sclerosis pattern. Patients with typical findings of osteoarthritis were excluded from the sclerosis category. Condylar marrow signal abnormalities were present in 37 patients (9 percent); 26 patients (6 percent) had the edema pattern, 14 patients (3 percent) had the sclerosis patterns, and 3 patients had both. The authors conclude that condylar marrow signal abnormalities are not rare in patients referred for TMJ MRI. The clinical significance of the changes is uncertain. The article includes a separate commentary written by a different author. 4 figures. 20 references.

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New Knowledge From Temporal Bone Archives Source: House Ear Institute Review. p. 5, 13. Summer 1993. Summary: This article reports on temporal bone archives and the research conducted on temporal bones. The article describes the Temporal Bone Laboratory, a department of the House Ear Institute (HEI). Topics covered include the history of the Temporal Bone Laboratory; how new techniques enable research to continue, even on bones donated long ago; research conducted on hair cells removed during surgery; the information available through the HEI's computerized temporal bone bank; research projects, including those on otosclerosis and Meniere's disease; asking patients to pledge their temporal bones and related structures; and the research fellows program of the HEI.

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Usher Syndrome: A Temporal Bone Report Source: Archives of Otolaryngology-Head and Neck Surgery. 121(8): 916-921. August 1995. Summary: This article reports the results of a light microscopy examination of the bilateral temporal bones of a deceased 84 year old man who had Usher syndrome. Histopathologic examination disclosed degeneration of the organ of Corti that was most profound in the basal turn, degeneration of cochlear neurons in all of the turns, and severe loss of spiral ganglia in both cochleas. Endolymphatic hydrops of unknown cause and a functionally unimportant pit malformation in the macular utricle were observed in the right cochlea. The authors compare their findings with temporal bone reports cited in the literature. 4 figures. 2 tables. 43 references. (AA-M).

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Osteoporosis, Alveolar Bone Loss, and Drug Development Source: General Dentistry. 48(3): 218-225. May-June 2000. Contact: Available from Academy of General Dentistry (AGD). 211 East Chicago Avenue, Chicago, IL 60611. 312-440-4300. E-mail: [email protected]. Website: www.agd.org. Summary: This article reviews research in the areas of osteoporosis, alveolar bone loss, and drug development. The author first summarizes research showing the connection between osteoporosis and alveolar (jaw bones) loss, then discusses studies on inflammatory factors for alveolar bone metabolism. The final section focuses on drug development studies. Drug development to arrest alveolar bone loss is predicated on agents that arrest the course of osteoporosis, such as the biphosphonates, and agents that block the production of inflammatory factors, such as the NSAIDs (nonsteroidal anti-inflammatory drugs). 37 references.

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Diagnosis and Treatment of Paget's Disease of Bone Source: American Family Physician. 65(10): 2069-2072. May 15, 2002. Summary: This journal article describes Paget's disease of bone (also known as osteitis deformans), a nonmalignant disease involving accelerated bone resorption followed by deposition of dense, chaotic, and ineffectively mineralized bone matrix. The origin of the disease is unknown, and it is frequently asymptomatic; however the patient may present with symptoms depending on the bones involved. The most common symptom is pain in the affected bone. Neurologic, hearing, vision, cardiac, and oncologic complications are also possible. Diagnosis is primarily made by radiographs. Biphosphonates are the most common treatment. 1 figure, 4 tables, 23 references. (AA).

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Association Between Bone Mineral Density and Cognitive Decline in Older Women Source: JAGS. Journal of the American Geriatrics Society. 47: 1176-1182. 1999. Summary: This journal article examines the association between bone mineral density (BMD) and cognitive decline in older women without dementia. The sample consisted of 8,333 community-dwelling women aged 65 years and older, recruited from four sites across the United States, who were enrolled in the Study of Osteoporotic Fractures and not taking estrogen replacement. Calcaneal and hip BMD were measured at baseline and at followup 4-6 years later; vertebral fractures were ascertained radiologically at year 6. Cognitive function was assessed with a modified Mini-Mental State Examination, Trails B, and Digit Symbol at baseline and followup. Compared with women with higher BMD, those with low baseline BMD had up to 8 percent worse baseline cognitive scores and 6 percent worse repeat scores, even after multivariate adjustment. A onestandard deviation decrease in baseline hip BMD or calcaneal BMD was associated with a 32 percent or 33 percent greater risk of cognitive deterioration. Women with vertebral fractures had lower cognitive test scores and greater odds of cognitive deterioration than those without fractures. The findings suggest a link between osteoporosis and cognitive decline in older women. 1 figure, 3 tables, 56 references.

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Vitamin D and Bone Status in Elderly Women Source: Orthopaedic Nursing. 15(3):67-71; May/June 1996. Summary: This journal article for health professionals discusses the role of vitamin D in the maintenance of healthy bones in elderly women. They are the fastest growing

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segment of the population, and, because of their longevity, they are more likely to develop chronic bone diseases such as osteoporosis. Women in northern climates may be particularly susceptible to the development of osteoporosis as a result of their lack of exposure to sunlight, which ultimately leads to vitamin D deficiencies. The article also describes a study that determined the relationships between reported vitamin D supplementation, vitamin D serum levels, serum parathyroid hormone (PATH), and femoral bone density in a sample of 53 elderly women with osteoporosis. The study was conducted in a metabolic bone clinic in northern New England during the early winter months. Results indicate that, overall, the individuals in the study had a wide variety of reported vitamin D intake, elevated serum PATH levels, low femoral bone density, and low normal serum vitamin D levels. Vitamin D intake by self-report was associated with serum vitamin D levels for the women. Femoral bone density was inversely related to the subject's age, and it was below normal despite self-reports of vitamin D supplementation in varying amounts. Serum PATH and vitamin D were negatively related. The nursing implications of the findings are discussed, and recommendations for research are presented. 32 references and 2 tables. (AA-M). •

Osteoporosis: It Steals More than Bone Source: American Journal of Nursing. AJN. 96(6):27-33. June 1996. Summary: This journal article for nurses examines osteoporosis, its adverse effects on a patient's quality of life, and primary and secondary prevention strategies, i.e., preventing the disease from developing (primary), and preventing fractures in those who have the disease (secondary). How breaking a bone can permanently alter a person's life is illustrated, and management of one case is continued throughout the article to describe the disease and strategies to prevent it. How a patient can severely alter their life to avoid potential bone fractures is discussed along with advice on steps that can be taken in limiting the toll of the disease. The article describes who is most at risk for osteoporosis, then explores the role of dietary changes and exercise as well as improvements in medical management, including the use of hormone replacement therapy and sodium fluoride. Nonhormonal treatment for osteoporosis using alendronate sodium to increase bone mineral density in women at risk is also highlighted. 10 references.

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Exercise-Related Lower Leg Pain: Bone Source: Medicine and Science in Sports and Exercise. 32(3 Supplement): S15-S26. March Supplement 2000. Summary: This journal article provides health professionals with information on the diagnosis and treatment of bony pathologies that cause exercise related lower leg pain. The two most frequently seen are traction periostitis and stress fractures. Traction periostitis is thought to be caused by chronic traction on the periosteum at the periosteal fascial junction. Symptoms include pain and tenderness along the medial border of the tibia. Plain x ray shows no abnormality in this condition. Initial treatment involves using rest, nonsteroidal anti-inflammatory drugs, ice, and electrotherapeutic modalities to reduce inflammation. Other important management components are podiatric assessment and advice on stretching and training. The most effective treatment is deep massage therapy. The diagnosis of stress fracture involves obtaining a thorough history, performing a detailed musculoskeletal examination, and conducting appropriate imaging studies such as plain radiography, scintigraphy, computerized tomography, and magnetic resonance imaging. The primary treatment for stress fractures is modified activity. Care can be divided into two phases. Phase I involves early treatment using

Studies 13

modified activity. Important considerations in phase I include pain management, bracing, electrical stimulation, muscular strength and endurance, maintenance of fitness, and modification of risk factors. Phase II encompasses the period of time from the reintroduction of physical activity to full return to sport. Less common stress fractures, such as longitudinal stress fractures and anterior cortex stress fractures, have special considerations. 9 figures, 3 tables, and 73 references. •

Bone Grafting-Part I: Treatment Considerations and Recommendations Source: Contemporary Oral Hygiene. 1(2): 12-18. October 2001. Contact: Available from Contemporary Oral Hygiene. 241 Forsgate Drive, Jamesburg, NJ 08831. (800) 926-7636. Summary: With bone grafting procedures becoming more commonplace, dental hygienists are frequently asked to render preoperative and postoperative care for their patients with bone grafts. This article, the first in a two part series that offers hygienists a comprehensive guide to managing these patients, summarizes treatment considerations and recommendations. An overview of bone healing dynamics is presented as a foundation for therapy rationale. The authors also summarize various types of bone grafting materials and their respective long term prognosis. Bone grafting may be offered shortly after tooth extraction (especially if implant therapy is a viable option), for treatment of periodontal defects (vertical and horizontal bone loss as well as furcations), after treatment for bony cysts or other intrabony trauma to minimize bone fracture, for repositioning the mandibular (lower jaw) canals, and for treatment of peri implantitis. Appropriate patient selection criteria for bone grafting is offered to provide the dental hygienist with an understanding of when these procedures may be recommended to patients seeking their care. After reading this continuing education article, dental hygienists will be ready to recognize and collaborate with the dentist on patient selection criteria for bone grafting procedures based on systemic and oral health status. A posttest with which readers can qualify for continuing education credits is appended to the article. 3 figures. 3 tables. 22 references.

Federally Funded Research on Bones The U.S. Government supports a variety of research studies relating to bones. 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 bones. 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

2

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

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animals or simulated models to explore bones. The following is typical of the type of information found when searching the CRISP database for bones: •

Project Title: 2003 BONES & TEETH GORDON CONFERENCE Principal Investigator & Institution: Nissenson, Robert A.; Professor; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 02892 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): The Gordon Research Conference on the Cell and Molecular Biology of Bones and Teeth originated in 1954 and has a distinguished history as a proving ground for new ideas in the field of skeletal research and the study of calciotropic hormones and how they relate to bone biology. The Bones and Teeth Conference is said to be unique in the breadth and depth of its coverage of new developments in the physiology and molecular biology of cartilage, bones, and teeth. The Gordon Research Conference format differs from virtually all other scientific meetings in providing an extensive opportunity for open, free, and informal discussion. The number of participants is limited to about 130, and attendees include international leaders in the field, young investigators, postdoctoral fellows and students. The success of the Gordon Conference as a forum for the discussion of state-of-the-art research advances is attributable to its limited size, geographical isolation and overall structure. The 2003 Conference will focus on areas in which important new developments have occurred within the past two years. It will include sessions on: vitamin D action, osteoblast signaling, osteoclasts and bone resorption, craniofacial biology and tooth development, parathyroid hormone (PTH) and PTH-related protein, genetic determinants of bone mass, skeletal development, and bone extracellular matrix. The purpose of this proposal is to request funds to partially defray the costs of speakers' transportation and subsistence. These funds, if granted will aid in allowing the Gordon Research Conference to fulfill its function to stimulate further creativity in bone, cartilage and tooth research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A NOVEL YEAST VACCINE AGAINST COCCIDIOIDES IMMITIS Principal Investigator & Institution: Selitrennikoff, Claude P.; Professor; Mycologics, Inc. 12635 E Montview Blvd, Ste 131 Aurora, Co 800107336 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 30-NOV-2003 Summary: (provided by applicant): Coccidioidomycosis, also known as San Joaquin Valley Fever, is a fungal disease caused by Coccidioides immitis that is endemic in portions of Southern Arizona, central California, southern New Mexico and west Texas. The migration of not only permanent residents, but also agricultural workers to these areas increases exposure to C. immitis spores that lie dormant in the soil, and as the soil is turned, the spores become airborne and are inhaled. Once in the lungs, the arthroconidia transform into spherules. An acute respiratory infection occurs between seven days to three weeks after exposure and often resolves rapidly. However, in a significant number of cases, chronic pulmonary conditions or dissemination to the meninges, bones, and joints can result, leading to acute, life-threatening disease. Migrant laborers who are exposed to C. immitis are a highly mobile and underrepresented population, and unfortunately, this disease goes largely unacknowledged in the medical community. A variety of approaches have been used to fight coccidioidomycosis, including soil treatments, but only a vaccine can completely eliminate this "emerging disease." Currently, there are a number of C. immitis vaccine

Studies 15

efforts that use a variety of approaches including selected recombinantly-expressed antigens. Our long-term goal is to develop a safe and effective vaccine against C. immitis. In this SBIR Phase I proposal, we will collaborate with Dr. Garry T. Cole, Dr. John Galgiani, Dr. David A. Stevens, and Dr. R. Duke of Globelmmune, Inc., and use Globelmmune's novel, proprietary recombinant yeast delivery system and test heatkilled yeast cells expressing C. immitis proteins as vaccine candidates. We will accomplish this in two specific aims: Aim One: Engineer yeast cells to express three C. immitis antigens using recombinant DNA technology. Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of C. immitis. This work will be a prelude to work in Phase II that will include detailed testing for in vivo efficacy and safety of each vaccine candidate in several C. immitis infection models. Ultimately, the Phase I and subsequent Phase II/III research will lead to the development of a vaccine against C. immitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A SCHOOL PROGRAM TO ENHANCE BONE HEALTH IN GIRLS Principal Investigator & Institution: Hoelscher, Deanna M.; Assistant Professor; Human Nutrition Center; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 20-AUG-1999; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Description): Osteoporosis is a geriatric disease that has pediatric origins. Development of peak bone mass, which is achieved by the third decade of life, is influenced by behaviors during childhood and adolescence, most notably calcium consumption and physical activity. During the pubertal years, 45% of the adult skeletal mass and 15% of adult height are gained. National and local surveys indicate that adolescent girls have inadequate calcium intakes and lower than recommended levels of physical activity. Although school-based programs have shown promise in affecting risk factors for cardiovascular health, application of behaviorallybased programs to target bone health have been limited. The primary goal of this proposal is to develop and evaluate a school-based nutrition and physical activity program, called BONES (Beat Osteoporosis Now by Exercising and Eating Smart), to enhance future bone health in girls. Elements of the BONES program will be based on Social Cognitive Theory (SCT) and will include both behavioral (student-oriented classroom lessons) and environmental (school food service, physical education) components. The program will consist of two phases: a feasibility trial in which intervention materials and measures will be pre-tested and validated, and the main intervention trial. Eighteen ethnically diverse middle schools from central Texas will be randomized into control or intervention conditions, with schools serving as the unit of randomization and analysis. Nine of the schools will receive the 2-year intervention (BONES), while the control schools will continue their usual health programs. It is hypothesized that students in intervention schools will, on average, (1) have a 3% greater calcaneus ultrasound Stiffness Index, (2) consume 2 more servings/day of calcium- containing foods, and (3) engage in 17 more minutes/day of vigorous physical activity compared to students in the control schools. Secondary hypotheses at the student level are: intervention students will (1) demonstrate higher scores in selfefficacy, knowledge of bone health, calcium-containing foods and exercise; and (2) have higher mean intakes of calcium and average greater frequencies of weight bearing type exercises per day compared to students in the control schools. Secondary hypotheses at the school level are: intervention schools will offer (1) more calcium-containing foods; and (2) more opportunities for weight-bearing activities than control schools.

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

Project Title: IMPERFECTA

ALENDRONATE

USE

IN

MODELS

OF

OSTEOGENESIS

Principal Investigator & Institution: Raggio, Cathleen L.; Associate Professor; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (Taken from the application): Recent clinical reports of apparent successful bisphosphonate therapy in children with osteogenesis imperfecta (OI) appear very promising. Previously, we demonstrated that the bisphosphonate, alendronate significantly, reduces fracture incidence and increase density in the growing oirn/oim mouse, an animal model of moderate-severe OI. However, data from that study also indicated that the quality of the newly formed bone was not optimal, and that reductions in long bone growth, might occur with treatment. However, since OI. is a heterogeneous disease clinically and most patients have unique mutations in collagen I formation, there may be a difference in response to treatment with bisphosphonates both short and long term. The long range goal of our studies is to evaluate bisphosphonate treatment in mouse models which have collagen abnormalities analogous to humans, i.e. ,decreased collagen content, abnormal collagen fibers, abnormal collagen packing. The proposed study will test the hypothesis that in 3 different mouse models of O.I. The first is the oim/oim mouse; the second a transgenic mouse which resembles mild-moderate O.I. The third is the new knock-in mouse (Brtl) which resembles mild O.I. The mice will be treated from age 2-14 weeks with alendronate. Bone quality will be assessed before and after treatment by radiographic analysis of the number of fractures, of bone and tooth density and geometry. Analysis of bone ultra structure and histology, and mechanical testing of whole bones; methodologies that have all been used successfully in our previous studies with oimj/oim mice. Investigation of specific aspects of alendronate treatment will provide information critical to the determination of how to proceed with individualized treatment of infants and children with different types of O.I. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF C ELEGANS TGF BETA SIGNAL TRANSDUCTION Principal Investigator & Institution: Padgett, Richard W.; Professor; None; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 01-JUN-1996; Project End 31-MAY-2006 Summary: Revised Abtract: The TGFbeta signal transduction pathways regulate cell growth and differentiation, cell migrations, and cell death. Some of the pathways are involved in establishing the basic body plan during embryogenesis in nematodes, flies, and vertebrates, while others regulate the development of specific tissues such as kidneys or bones. They also regulate wound healing and some immunological processes. Not surprisingly, TGFbeta components are implicated in a wide variety of human diseases and cancer-multiple components of the pathway are confirmed tumor suppressors. For these reasons, TGFbeta is one of the most important signaling pathways. Elucidating how its signals are mediated is of considerable interest. The overall goals of this project are to identify components of the signaling pathway in C. elegans, to determine how these proteins function during development, and to examine in detail one of the outputs of the pathway--the regulation of body/cell size. During the first funding period of this grant , we characterized three genes in C. elegans, sma-2,

Studies 17

sma-3, and sma-4, that participate in TGFbeta signaling (the Sma/Mab pathway). These three genes, along with the Drosophila Mad gene, comprise the founders of the Smad family. Smads are the primary TGFbeta signal transducer, and have had a major impact on our understanding of how signals are sent. In addition, we cloned the first mouse Smads and showed they function downstream of the receptors. Based upon the mutant phenotypes exhibited from the C. elegans Smad genes, we performed genetic screens to find new components of the Sma/Mab pathway in C. elegans, which has resulted in the identification of the ligand, the type I receptor, schnurri, and several other new loci. We now propose 1) to characterize and clone other loci from our genetic screens, 2) to use RNAi and "reverse genetic" techniques to make mutants in C. elegans homologs that have been proposed to function in TGFbeta signaling, but for which there is little supporting molecular genetic data, 3) to use cellular and biochemical methods to further characterize the Smads and other genes cloned from our screen, and 4) to determine how TGFbeta regulates body/cell size in C. elegans. Understanding how TGFbeta signals will provide insights into its important developmental roles how to eventually manipulate the pathway to control cellular proliferation of cancerous cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANGIOGENESIS IN SKELETAL DEVELOPMENT AND REPAIR Principal Investigator & Institution: Werb, Zena; Professor and Vice Chair; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: Bone is a highly vascularized tissue. During development of the skeleton and regeneration of bone in adult animals, the process of angiogenesis is highly coordinated with the process of bone formation by osteoblasts. In endochondral bone formation an avascular cartilage model is laid down. Blood vessels grow into the hypertrophic cartilage, which then dies, followed by bone formation. During intramembranous bone development, osteoblasts differentiate from mesenchymal precursors, and lay down matrix and mineral, closely coordinated with capillary development. The mechanism by which the vascular response is coordinated with skeletal formation is unknown. The goal of this proposal is to elucidate the molecular and cellular mechanisms regulating capillary formation during bone growth and regeneration. We will determine the spatial and temporal distribution of key angiogenic factors in developing bones using morphologic approaches. This will be coupled with functional angiogenesis assays and perturbations of angiogenic activities in vivo and in culture. We will exploit mice with genetic mutations that affect skeletal development (e.g., gelatinase B/matrix metalloproteinase-9 null mice) to dissect specific steps in the process. We will then determine how angiogenesis is regulated during the programs of cartilage and bone differentiation using in vivo and in culture models. We will determine whether the angiogenic processes operating during skeletal development are recapitulated during bone regeneration after injury. We will explore the molecular and cellular mechanisms and mechanical forces that regulate angiogenesis during bone regeneration in normal mice, and in mice with genetic mutations that affect bone formation. Conditions that allow bone to repair by intramembranous ossification or endochondral ossification will be used so that the effects of different mechanical environments on angiogenesis can be evaluated. Because angiogenesis is a key process in bone formation, the capacity to develop strong, functional bone during fetal development and to repair bone and maintain skeletal integrity in adults may critically depend on it. Once the molecular signals required for regulating angiogenesis are understood, they will provide targets

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for new therapies for skeletal lesions occurring in development, bone regeneration and in osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AROMATASE INHIBITOR METHYL TESTOSTERONE AND TESTOSTERONE INDUCED BONE SPARING Principal Investigator & Institution: Naftolin, Frederick; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Osteoporosis is a common disease in postmenopausal women and aging men resulting in considerably morbidity and mortality. While estrogen is a recognized bonesparing agent, reports on the effect of testosterone (T) on bone mass are controversial and variable. T's variable action on bones could be due to the requirement of aromatization of T to estrogen, followed by action on bone cell estrogen receptors: This laboratory was first to report the presence of immunoreactive aromatase in osteoblasts in culture. 17alpha-methyl testosterone (MT) is a synthetic steroidal androgen with low affinity for the androgen receptor. It is widely used in hormone replacement therapy in women. MT is also a powerful aromatase (estrogen synthetase) inhibitor that may block local estrogen formation. We have shown that MT inhibits both aromatization of androstenedione and T-induced proliferation of breast cancer cells by inhibiting aromatase. We propose to use a similar preclinical experimental approach to assess the mechanism of action of T on rat bone mass: We will test the effect of T alone and of T plus MT on bone maintenance in ovariectomized female rats. If MT blocks T's bone maintenance, this will indicate that T's action is indirect, via aromatization, and justify clinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUGMENTATION OF PEAK BONE MASS Principal Investigator & Institution: Gross, Ted S.; Associate Professor; Orthopaedics/Sports Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: One of the primary risk factors associated with osteoporotic fractures is the failure to achieve sufficient bone mass during early adulthood. Exercise holds substantial potential for non-invasive bone accretion, but general exercise protocols only minimally enhance bone mass over normal levels and rely upon high impact, high magnitude loading to achieve these bone gains. Recently, we found that inserting a brief rest interval between each load cycle of a low magnitude loading regimen is sufficient to transform the protocol from one that does not influence bone cell populations into a signal that is potently osteogenic. This regimen may therefore be particularly amenable to application in conditions where enhanced bone properties are desirable, but high impact exercise is not feasible. Based upon our preliminary data and a review of the literature, we hypothesize that low magnitude, rest-inserted, mechanical loading initiated during skeletal growth will enhance the cortical bone properties of adult mammals. To explore this hypothesis, we will capitalize on our recently developed noninvasive murine tibia loading device. A series of five Specific Aims have been designed to determine if rest-inserted, low magnitude loading can serve to build and maintain augmented tibial cortical bone properties in female C57BLI6J mice. The studies culminate with our final Aim, in which we will assess whether enhanced cortical bone

Studies 19

properties induced by the rest-inserted loading are sufficient to counteract the degradation caused by aging and estrogen depletion. At a basic level, these studies will provide unique insight toward how young growing bones respond to mechanical loading, and will provide a baseline of information from which we will, in the future, begin to explore how specific genetic alterations (e.g., via transgenic or knockout mice) affect mechanotransduction in bone. At the applied level, an outcome in which restinserted, low magnitude, non-invasive loading significantly augments and maintains murine cortical bone properties would place our group in position to begin to explore the efficacy of this concept in human subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BAG-75: UNIQUE MARKER OF PRIMARY BONE FORMATION Principal Investigator & Institution: Gorski, Jeff P.; Molecular Biology and Biochem; University of Missouri Kansas City Kansas City, Mo 64110 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Primary bone is defined morphologically as bone formed directly from soft mesenchymal tissue without a calcified cartilage or mineralized precursor stage. Long bones develop postnatally by the apposition of primary bone upon cartilaginous remnants in the primary spongiosa, while all or parts of the frontal, parietal, occipital, temporal, maxilla, and mandible bones of the craniofacial system form and remain as primary bone. Research on primary bone has received less emphasis in the past and the true extent of cellular and biochemical differences between primary and lamellar bone are unknown. While lamellar bone represents the mature structure, primary bone is the precursor of lamellar bone-capable of being formed de novo. Primary bone can be distinguished from lamellar (cortical) bone on the basis of the faster speed of its deposition, exquisite spatial patterning and mineralization, its apparent specific enrichment in acidic phosphoprotein BAG-75, and its increased sensitivity to applied biomechanical forces and systemic hormones. We propose that BAG-75, through its strong propensity to self-associate into supramolecular microfibrillar complexes, serves as a structural framework defining the volume of primary bone matrix to be subsequently calcified. The goal of this proposal is to address the hypothesis that BAG-75 (bone acidic glycoprotein-75) is a unique gene product whose expression is restricted to active de novo calcification reactions, and, which contains more than 40 casein kinase phosphorylation sites, one or more polyglutamic acid calcium-binding motifs, N- and O-linked oligosaccharide attachment sites, and a repetitive modular primary structure facilitating home-and heteropolymeric associations required for formation and mineralization of primary bone. This project fits two main objectives of the R2 1 mechanism: to support innovative and high-risk research relevant to the primary research mission areas of NIDCR, and, initial development of a line of research upon which significant future studies can be based. For example, if a BAG-75 framework serves a key organizational role, a surface coating of BAG-75 could improve the stability of dental and orthopedic implants; 8-9 percent of the 1 37,000 hip implants in the U.S. each year require revision surgery within 5-10 years. We envision that a BAG-75 coated, non-cemented implant would self-associate with host-derived BAG-75 to form a seamless natural framework leading to deposition of other matrix components and mineralization within submicron distances of the implant surface--improving functional longevity of implants. Since primary bone is capable of being formed de novo, future determination of the BAG-75 promoter structure could form the basis of a new gene therapy approach to reverse losses in trabecular bone connectivity and alveolar bone volume with aging by targeting local

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stimulatory agents to primary bone osteoprogenitor cells expressing BAG-75, thus enhancing bone volume and restoring lost trabecular connectivity. Stimulation of appositional formation by lamellar bone would not be expected to have the same effect. These future functional studies require determination of the BAG-75 cDNA sequence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BAYESIAN NEURAL NETWORKS FOR PROSTATE CANCER STUDY Principal Investigator & Institution: Ghosh, Malay; Statistics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: Prostate cancer is one of the most common cancers among men over the age 50. Staging serves as a road map for the treatment selection and helps in differentiating organ-confined cancers from the non-organ confined ones (those which have already spread to the outside of prostate-seminal vesicles, lymph nodes and bones). Outcome of treatment varies significantly between these different kinds of cancers. Only organ confined cancers are amenable to curative intent of surgery and radiation therapy. The main objective of this proposal is to explore the neural network technique for the prediction of certain features indicative on non-organ confined prostate cancer on the basis of the results of certain diagnostic tests administered to patients suffering from prostate cancer. The approach is going to be Bayesian, and the goal is to provide the posterior (or predictive) probabilities of the presence of these features in the patients based on certain inputs. The doctors can then make decisions on the basis of these probabilities, and in particular, in marginal cases (for example, when these posterior probabilities are in the neighborhood of 50 percent) go for further diagnostic tests rather than making an immediate decision of whether or not to suggest surgical intervention. Within the Bayesian framework, several methods, both parametric and nonparametric, will be compared. Also, the Bayesian procedures will be compared against some classical frequentist procedures. It may be added here that the Bayesian neural network methods to be proposed are versatile enough, and can be adapted for other nonlinear modeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BEAT OSTEOPOROSIS: NOURISH & EXERCISE SKELETONS (BONE) Principal Investigator & Institution: Economos, Christina D.; None; Tufts University Medford Boston Ave Medford, Ma 02155 Timing: Fiscal Year 2002; Project Start 04-JUN-1999; Project End 31-MAY-2004 Summary: Osteoporosis affects more than 28 million Americans and accounts for more than 1.5 million fractures annually, at a cost of 513.8 billion. One of the most effective ways to prevent osteoporosis is to build a strong, dense skeleton during the growing years to act as a reserve in later life. Furthermore, changes in individual behaviors and lifestyle preferences in younger children may last through the critical adolescent period and continue into adulthood, providing a lifetime of optimal bone health. The primary aim of this study is to develop, implement and evaluate a multi-faceted intervention in after-school programs that will increase bone accretion and muscular strength in early elementary school children. The intervention will include weight loading physical activity and calcium-rich snacks for children as well as age- appropriate, behaviorally focused active learning to promote skill building and self-competence. It will also include a parent/caregiver communications module that by provides specific activities

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and practical information to complement and reinforce the direct intervention with the children. A mascot and logo will be used to foster positive attitudes about calcium-rich foods and physical activity; incentives and goal setting will be used to encourage sustained behavior. One thousand eight hundred first and second grade children from 60 after-school programs in up to 10 diverse communities throughout Massachusetts will be randomized and studied for 24 months. Matched program groups will receive either The BONES Project (n=24), The BONES Project plus a parent/caregiver component (n=12); or they will serve as controls (n=24). Follow-up will continue for 12 months after the intervention period. The primary outcomes will be bone quality and muscular strength. Secondary outcomes will include physical activity levels, calcium consumption, body composition, self-perception of physical abilities and appearance, and influencing factors toward relevant healthy lifestyle behaviors, such as knowledge and attitudes. The control group will receive a "delayed" intervention after termination of the 36-month study. Focus group research with after-school program leaders, parents/caregivers, and children prior to initiation will provide information to optimize the campaign design. Findings from this study will promote our understanding of health behaviors in young children and the effect of parental involvement on these behaviors. Implementation of the same intervention within this widely diverse set of communities will guide appropriate cultural, community and socioeconomic-specific modifications and permit easier replication of the program. Because the intervention utilizes the existing after-school framework large numbers of children can be reached. Results from this study will provide an appropriate model for national replication and sustainability of a program to beat osteoporosis by nourishing and exercising skeletons early in life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE GROWTH, PERIOSTEAL MIGRATION AND MUSCLE FUNCTION Principal Investigator & Institution: Herring, Susan W.; Professor & Acting Chair; Orthodontics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-MAY-1990; Project End 31-MAR-2008 Summary: (provided by applicant): Our overall goal is to clarify the influence of function on the growth and ultimate morphology of the head. The mechanical environment influences skull growth at every level from individual cells to gross structure. Although usually neglected, soft tissues such as muscles, ligaments and cartilages play a critical role in cranial mechanics and growth. This proposal focuses on two ways in which soft tissue mechanics may direct the growth of skull bones, using the pig as a model. First, the osteogenic activity of the periosteum is linked to its blood supply, which originates from muscles and ligaments. We hypothesize that the deformation of these soft tissues during function can modify periosteal perfusion. In Specific Aim 1, new methodology will be employed to map the three-dimensional deformation of muscles and ligaments during awake mastication and to test whether buccinator contraction places significant pressure on the alveolar periosteum. Specific Aim 2 addresses the periosteal vascular system directly with both immunocytochemical assays of cellular activity and in vivo measures of blood flow. These studies will provide evidence for or against a causal linkage between soft tissue behavior and periosteal perfusion. The second way in which soft tissues may direct skull growth involves the nasal septum. Despite being an unmineralized cartilage, the septum has been considered an important mechanical support of the face. Moreover, forces generated by septal growth are claimed to separate the sutures between facial bones, causing

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compensatory growth. These assertions have never been tested directly. In Specific Aim 3 a novel indwelling transducer will be used to reveal the mechanical loading pattern of the septum and to investigate the timing of its growth in relation to that of facial sutures. Specific Aim 4 will test the mechanical plausibility of the hypothesis that the septum controls facial growth by comparing the viscoelastic stiffness of the cartilaginous septum to the resistance of the facial sutures. Taken together, these studies will develop new techniques for monitoring soft tissue function, provide fundamental new information about the mechanical behavior of the head, and test hypotheses about how soft tissues influence skull growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE QUALITY: A COMPOSITE OF COMPLEX PHENOTYPIC TRAITS Principal Investigator & Institution: Sharkey, Neil A.; Professor; Center for Locomotion Studies; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Osteoporosis, skeletal fragility, and fracture are well-known pathological conditions associated with aging. The ability of bone to resist fracture, i.e. bone quality, can be viewed as a composite of phenotypic traits, each under polygenic and environmental regulation. The principal aim of this study is to positively identify chromosomal regions (termed quantitative trait loci, or QTLs) that contain genes influencing bone quality across the lifespan. The long-term goal is to elucidate the causal fields created by genes, environment, gene-gene, and gene-environment interactions that ultimately dictate the quality of our bones in old age. Phenotypic traits encompassing bone morphology, composition, and mechanical performance will be assessed in two types of descendents from crosses of C57BL/6 (B6) and DBN2J (D2) inbred strains of mice: (a) a BXD F2 intercross, and (b) twenty-two different BXD recombinant inbred (RI) strains. Traits related to muscle mass, activity, and general health will also be quantitatively measured. Over twenty-five hundred animals, equally divided between male and female, will be examined at three ages representative of young adulthood (150 days), midlife (450 days), and advanced age (750 days). Quantitative bone quality data will be analyzed against corresponding genetic marker information from each individual F2 animal and from pre-existing RI databases. Univariate screening will be used to conduct genome-wide scans for QTLs associated with bone quality and potentially useful marker arrays correlating with distinct skeletal phenotypes will be identified. Regressions will be performed between skeletal phenotypes and phenotypes from other domains to determine relationships across physiologic systems and multivariate analyses will be conducted to identify QTLs that have pleiotropic effects on the correlated phenotypes. QTLs strongly associated with age-related reductions in bone quality will be sought by deriving novel phenotypes of bone loss from the longitudinal data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BUILDING BETTER BONES IN CHILDREN Principal Investigator & Institution: Zemel, Babette S.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004

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Summary: Increased calcium intake has proven effective in increasing bone mineral density in children, but the effect disappears when calcium supplements are discontinued. Increased dietary calcium from daily and other food sources may have an even greater impact on bone density than that achieved by calcium supplements, but achieving sustained increased calcium from food sources has not been demonstrated. In addition, the effects of baseline characteristics of calcium intake and bone density and puberty status may influence the response to intervention. This study will develop and implement a Behavioral Modification-Nutrition Education (BM-NE) Intervention Program aimed at increasing dietary calcium Male and female subjects (n=154), ages 710 years (Tanner stage I or II), will be randomly assigned to participate in an intensive BM-NE intervention group to increase intake to 1500 mg/d or a group that will receive usual care (UC) as counseling on bone health. The BM-NE Program will consist of five separate group sessions for parents and children over a five to six week period, and use individualized plans to increase calcium intake. Participants will be recruited into two groups: a group of healthy children (i.e.,no known chronic disease or previous oral steroid exposure) with no known risk factors, and a group of healthy children with potential risk factors for low bone density (previous fracture from usual childhood activities, daily refusal, or lactose intolerance, family history of osteoporosis). These two groups will be equally represented in their assignment to BM-NE and UC groups. This latter strategy will be used to determine whether the presence of risk factors influences participant compliance with the programs. We hypothesize that (a) at the end of 36 months the BM-NE group will have increased dietary calcium of at least 300 mg/d in the no-risk BM-NE group compared to those receiving UC, (b) baseline calcium intake and presence of risk factors will be associated with changes in calcium intake over the course of the study, and (c) after controlling for important co-variates such as increases in body size and sexual and skeletal maturation, changes in BMD will be associated with calcium intake and physical activity. These findings will help define important behavioral strategies for increasing peak bone mass and prevention of osteoporosis later in life that can be implemented in a short period of time with long-lasting effects. Furthermore, it will help quantify the impact of increased dietary calcium on bone density during growth and development with possible identification of the characteristics of children most in need of and responsive to this treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CBL-B IN OSTEOCLAST FUNCTION Principal Investigator & Institution: Sanjay, Archana; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: Hypothesis: In Ocs and lymphoid and myeloid cells, Cbl proteins (c-Cbl and Cbl-b) have emerged as prominent components of signaling cascades downstream of a variety of surface receptors (lymphokines, cytokines, immunoglobulin receptors and integrins). Cbl proteins mediate the assembling of signaling complexes downstream of receptor and non-receptor tyrosine kinases (RTKs and NRTKs) and, by directly interacting with them, also initiate their ubiquitination and subsequent downregulation. The embryonic death of c-Cb1/Cb1-b double-knock out mice indicates a redundancy of key functions, consistent with the high degree of identity between Cbl proteins. However, although c-Cbl and Cbl-b are highly homologous, especially in their N-terminal phosphotyrosine binding (PTB) and the RING finger domains, there are significant differences between the two proteins in the C-terminal proline-rich (PR) and acidic regions. These differences in structural motifs will result in different patterns of

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molecular interactions that are likely to contribute to specific functions of each of the two proteins that cannot be compensated by the other. This is emphasized by the differences in the T cell regulation seen in the c-Cbl-/- versus Cbl- b-/- mice. These features of Cbl knockout mice have therefore raised the possibility that c-Cbl and Cbl-b regulate different signaling pathways, a fact relevant to this proposal. We have shown that c-Cbl lies downstream of the vitronectin receptor and Src and forms a tri-molecular complex with Src and Pyk2 in a signaling pathway that regulates cell adhesion and motility in Ocs and other cell types. We have also shown that deletion of the c-cbl gene altered the migration of OC both in vitro and in vivo during development, although detailed histomorphometric analysis of adult bones failed to demonstrate any changes in bone volume or resorption parameters. To further characterize the role of Cbl family proteins in Ocs, we analyzed the bones of the Cbl-b-/- mice and found that Cbl-b-/mice were osteopenic in contrast to c-Cbl-/- mcie, indicating that Cbl-b plays a role in OC function that cannot be compensated by c-Cbl. The goal of this pilot project is to acquire data that will serve as the basis for applying for a standard R01 application for NIH. The aim of this study is to test the hypothesis that Cbl-b plays a unique role in promoting OC function and to identify the functions of Cbl-b that are required for normal regulation of osteoclastic bone resorption. The hypothesis stems from the following observations: (a) the osteopenia in Cbl-b-/- mice (b) the normal expression of c-Cbl in Cbl-b-/- Ocs, which implies that c-Cbl protein cannot compensate for Cbl-b deletion in OC function and (c) the detection of a four-fold increase in cell surface expression of receptor activator of NfkappaB (RANK) in Cbl-b-/-OCLs. (c-Cbl protein promotes the down-regulation of various receptors, and the increased levels of RANK suggest that Cbl-b may play a similar role in regulating RANK activity in OC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL-MATRIX INTERACTIONS IN LIMB DEVELOPMENT Principal Investigator & Institution: Linsenmayer, Thomas F.; Professor; Anatomy and Cellular Biology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-MAR-1988; Project End 31-AUG-2004 Summary: The overall theme of this Program Project is to elucidate the mechanisms involved in the development of the vertebrate limb. The projects that are proposed involve five separate but closely related topics. They encompass most of the major organ systems and tissue types of the limb, including: the cartilagenous growth region of long bones, the dense connective tissue that comprises tendons, the cellular and molecular components of skeletal muscle, and the endothelial and smooth muscle cells of the vascular system. The Project Leaders, and their associates and collaborators, combine a diversity of backgrounds, skills and technical expertise allowing for broadly-based investigations that require the application of a variety approaches. Experiments will be done at levels ranging from the molecular (e.g., transcriptional regulation), to the cellular (e.g., proliferation and apoptosis), to whole organs (e.g., long bones). The methodologies employed will be equally broad, and will include: molecular isolations and identifications by cDNA cloning and sequencing, manipulations of gene function by transfection, biochemical and immunohistochemical analysis, elctron microscopy, and cell and organ cultures. The first will investigate the growth and differentiation that occurs within the cartilagenous growth region of long bones. The studies will range from the transcriptional regulation of the type X collagen in hypertrophic chondrocytes, to functional analyses of other molecular components upregulated during hypertrophy, to the regulatory functions of the the perichondrium on chondrocyte proliferaton and differentiation. Dr. Sarkar's project will examine the roles of developmentally-expressed

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isoforms of troponin T, a key component of the Ca++ regulatory myofibrillar protein complex of skeletal muscle. It will also address the mechanism of cytoplasmic RNAmediated translational control during muscle development. The next project will examine two cellular and molecular mechanisms involved I formation of the vascular system in development: apoptosis of endothelial cells via activation of the Akt family of kinases, and control of smooth muscle during cell proliferation by acquisition of the heparin-responsive phenotype. The last project will also examine the differentiation of skeletal muscle. These studies, however, will focu on the proliferation and survival of myocytes, and how these events are coordinately regulated through the ability of cell cycle activity o modulate the induction of Akt1 and Akt2--protein kinases thought to be involved in survival. Through these various studies we hope to elucidate the mechanisms involved in a variety of aspects of limb develop. We also hope to gain insight into the etiologies of congenital defects in limbs, and in other embryological organ systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CERVICAL SPINE INJURIES IN FRONT, REAR AND SIDE IMPACTS Principal Investigator & Institution: Panjabi, Manohar M.; Professor & Director Biomechanics Lab; Orthopedics and Rehabilitation; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 04-APR-2000; Project End 31-MAR-2005 Summary: (adapted from the Investigator's abstract): Most injuries of the cervical spine are soft tissue injuries, due to low-energy impacts from rear-end collisions. The accident victims with soft tissue injuries have been known to have residual pain for many years after the accident. Less frequent, but more severe are neck injuries due to frontal and side collisions. The overall objective of the proposed research is to provide a better understanding of these injuries. The available research studies have used volunteers, whole cadavers, anthropometric dummies, and mathematical models to simulate the injury-causing events. The traumatic event in these experiments is studied from outside and not at the site of injury in the cervical spine. The uniqueness of the proposed research lies in its ability to directly study the site of injury during the trauma. Fresh cadaveric human cervical spine specimens (occiput to T1) will be utilized. The specimen is provided with an appropriate head surrogate. The specimen is stabilized with the help of compression springs simulating overall muscle function. The trauma is produced in a specially constructed apparatus where the acceleration at the base of the specimen, i.e. the T1 vertebra, is simulated to be similar to that documented in real life car crashes. Radiographs are taken, and multidimensional instability is measured before and immediately after the traumas. During the trauma, loads at occiput and T1, accelerations of the head, intervertebral motions, and deformations of the ligaments and vertebral artery are continuously measured. After the trauma, CT scan and MRI are performed, and the specimen is dissected and the injuries to the soft tissues and bones are described and quantified. The investigators propose to study four traumas: rearimpacts with head-forward and head-turned to side, and frontal and side impacts. Injury thresholds and injury mechanisms for low and moderate energy traumas will be determined. The significance of the research lies in helping provide better understanding of the mechanisms of low-and moderate energy traumas to the cervical spine. Significant advances can be made in prevention of these injuries by designing optimal automotive seats and safety equipment; in diagnosis by developing radiographic tests that are more sensitive to soft tissue injuries; and, in treatment by better assessment of the anatomic injuries and multidirectional instabilities.

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

Project Title: CHARACTERIZATION OF THE STRUCTURE AND FUNCTION OF DMP2 Principal Investigator & Institution: George, Anne; Associate Professor; Oral Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: The proper mineralization of bones and teeth has great importance in normal human growth and development including musculo-skeletal functions. The mineral phase in these tissues contributes to the hardness and comprehensive strength of the structure and also has a major physiological role as the metabolic reservoir of calcium and magnesium. Problems in the mineralization process are evident in a number of skeletal pathologies. One of the most interesting questions in mineralized tissue research is how, within the physiological environments, circulating calcium and phosphate and other mineral phase ions can be concentrated in specific, localized organs or tissues. Up until this point we have defined little about the process by which this cascade is initiated and regulated. However, the organic matrix has been implicated to have a major role in regulating the mineralization process. We have focussed our efforts primarily on dentin mineralization because it is a simpler system than bone, but the two mechanisms are probably closely related. Our basic hypothesis for matrix-mediated mineralization, is that acidic macromolecules first bind within the collagen matrix and these are responsible for nucleating and starting the mineralization cascade. Probably these acidic macromolecules also regulate the size of carbonated hydroxyapatite crystals. In the search for the gene encoding for the principle acidic noncollagenous protein (NCP) of dentin, namely phosphophoryn (PP) we identified 2 clones one representing phosphophoryn now named DMP2 (dentin matrix protein 2) and the other DMP3 (dentin matrix protein 3) which is a compound of dentin sialoprotein and a mini "phosphophoryn"like domain. The amino acid sequence deduced from the partial DMP2 cDNA is of special interest because it clearly represents an aspartic acid and serine rich acidic protein of the type to be expected of a dentin matrix component. This gene has been tightly localized to mouse chromosome 5q21, equivalent to human chromosome 4Q21. This chromosome location is especially interesting because of the linkage of human chromosome 4q13-21 with the dentin mineralization disorder dentinogenesis imperfecta type II. In order to expand our understanding of the DMP2 gene structure and its function we propose the following specific aims: (1) To determine the complete primary structure of rat DMP2 (2) To delineate DMP2 promoter sequences and identify elements involved in tissue -specific regulation (3) To clone the human DMP2 gene in order to ultimately identify gene alterations in patients with Dentinogenesis Imperfecta Type II (4) To examine the temporal and spatial patterns of DMP2 expression during tooth development (5) To determine the calcium binding property of DMP2. The longterm goal is to understand the regulatory mechanism of DMP2 in dentin mineralization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMBINING K AND L XRF FOR IN VIVO LEAD IN BONE MEASURE Principal Investigator & Institution: Gardner, Robin P.; Nuclear Engineering; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, Nc 27695 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 31-MAY-2004

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Summary: Chronic low-level lead poisoning is widespread, causing irreversible neurological problems in children. Assays of blood samples provide data on the amount of lead in circulation, but not on the accumulated lead concentration in the body - which is that contained in the skeleton. In vivo measurement of lead in the tibia by X-Ray fluorescence (XRF) is the present accepted method for determining lead in the skeleton. There are presently two XRF methods; one (the K XRF) uses the lead K X rays excited by the radioisotope source 109Cd while the other (the L XRF) uses the lead L X rays excited by the polarized X rays from an X-ray tube. Our previous research concentrated on improving the minimum detectable concentration (mdc) limits of both methods. This was accomplished by first developing a very comprehensive and accurate Monte Carlo model for simulating X-ray transport and the resulting spectra. It included L X rays, a detailed Compton scatter treatment, and polarized X rays. This model was then used to quantitatively determine errors in the two methods including variable skin covering thickness, variable and unknown sample position, and the presence of unknown lead concentration profiles in the bone. The Monte Carlo model was then used to investigate various methods of improving the minimum detectable lead limits. The primary improvement in both cases (a factor of about three in the reduction of statistical uncertainties) was found in using the entire spectral information rather than just the characteristic K and L peaks. The approach used is called the Monte Carlo - Library Least-Squares (MCLLS) approach. It is based on determining the elemental spectral libraries for any sample composition and analysis geometry by Monte Carlo simulation and then using these libraries in a linear least-squares analysis of the unknown sample spectrum for lead amount. An even more comprehensive and promising approach was identified and investigated in a very preliminary way. That approach is the combined use of the K and L methods by the MCLLS approach; thereby providing a direct basis for eliminating or at least minimizing the previously identified errors even more. The proposed method would use the radioisotope source 109Cd for excitation of both K and L X rays via the 88 keV gamma ray and silver K X rays, respectively. The major advantages of this approach are: (1) all the available spectral information is used in an optimum way, (2) one can determine if a lead concentration profile exists since the K and L X rays penetrate different bone thicknesses, and (3) the possibility exists that the spectral data taken can be used to eliminate the effect of unknown sample position variations and other patient-dependent variables that interfere with the lead measurement. The development and testing of this approach is the research proposed here. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMMON MEDIATORS OF VASCULAR CALCIFICATION AND BONE DIS* Principal Investigator & Institution: Giachelli, Cecilia M.; Associate Professor; Bioengineering; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Vascular calcification is an actively regulated process contributing to increased morbidity and mortality in, patients with uremia, diabetes, aortic stenosis and bioprosthetic heart valves. Epidemiological studies have linked vascular calcification with osteoporosis and cardiovascular disease, suggesting that common regulatory mechanisms exist, and that ectopic calcification may increase the risk of heart disease. In human blood vessels and valves, both diffuse calcification and ectopic bone have been observed under pathological conditions. The relationship between these types of mineralization is unclear. It is also unknown if media or intimal

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vascular calcification contributes to formation and/or progression of atherosclerotic lesions. We hypothesize that mineral deposition in blood vessels involves mediators including osteopontin (OPN), osteoprotegerin (OPG) and matrix gla proteins (MGP), that also critically control formation of the skeleton, and that once mineral forms in the vessel wall, an adaptive response ensues and initiates cellular differentiation and inflammatory mechanisms that 1) lead to neointima formation and hence increased susceptibility to plaque formation, and 2) mimic endochondral bone formation that may explain the appearance of ectopic bones in calcified vascular lesions. In order to identify common mechanisms! controlling bone and vascular calcification, and to understand the relationship between vascular calcification, cartilaginous metaplasia, and arterial lesion development, three aims are proposed. Aim I will determine the mechanism of medial vascular calcification, neointimal formation, and cartilaginous metaplasia in MGP X OPN mutant mice. Aim 2 will determine the mechanism of bone and tooth defects found in MGP X OPN mice. Aim 3 will determine the effect of hyperlipidemia on cartilaginous metaplasia, vascular calcification and osteoporosis in a mouse model of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF BONE FORMATION IN CRANIOMETAPHYSEAL DYSPLASIA Principal Investigator & Institution: Reichenberger, Ernst J.; Biostructure and Function; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Craniometaphyseal dysplasia (CMD) is a rare craniotubular bone disorder, characterized by life-long mineralization and bone deposition in craniofacial bones, while decreased bone deposition and flaring is seen in the metaphyses of long bones. Recently, we discovered mutations in a transmembrane protein, ANK, which is responsible for the autosomal dominant form of CMD. ANK is likely to be involved in pyrophosphate transport and the loss of ANK protein in mice causes progressive ankylosis with increased cartilage calcification. However, ANK's molecular properties, its interaction with other proteins, and its mode of action are unknown. The clustering of the mutations in the ANK gene of CMD patients and the bone matrix phenotype caused by mutant ANK protein suggests that CMD is not solely caused by a quantitative effect of pyrophosphate transport, but by a more complex mechanism. The goal of this proposal is to provide tools and to perform experiments that will eventually lead to the discovery of 1) the role of ANK in bone homeostasis and 2) the mechanism of mutant ANK causing the CMD phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT AND DEFORMITIES OF THE MAMMALIAN LIMB Principal Investigator & Institution: Capecchi, Mario R.; Professor; Human Genetics; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 15-DEC-1994; Project End 30-NOV-2003 Summary: One in two hundred children is born with limb deformities. An understanding of the teleology of these defects, whether induced by taratogens, caused from a stochastic dysfunction of the developmental program, or the result of congenital defects, will require an under- standing of the normal process of limb development. Many of the genes that are suspected of mediating the formation of the limbs are now being identified. Particularly prominent among these genes is the set of Hox genes that may be

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required to specify the positional information needed for the establishment of the correct set of limb cartilages and bones. Gene targeting in mouse embryo-derived stem cells provides the means for generating mice with disruptions in each of these genes. The goal of this grant is to use gene targeting to undertake a systematic analysis of this gene complex and thereby directly establish the role of each of these genes in limb development. Not only will the phenotypic consequences of disrupting any particular gene be determined, but also through epistasis and molecular genetic analysis, it is hoped that insight will be gained as to how this set of genes functions as a network to determine the overall three-dimensional structure of the limb. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL REGULATION OF BONE MORPHOGENESIS Principal Investigator & Institution: Tabin, Clifford J.; Professor; Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 20-AUG-1999; Project End 31-JUL-2004 Summary: OVERALL (Taken directly from the application) This program project consists of four closely related and integrated projects focusing on signals that regulate skeletal morphogenesis during embryonic development. Because the same regulatory network is utilized postnatally as the skeleton grows, remodels, and repairs itself, these studies will increase understanding of medically important problems. Moreover the unique tools available for developmental studies will provide insights not obtained as readily by other approaches. The four projects are highly coordinated because they have grown out of a long history of collaborative efforts. The program project will encourage the exchange of expertise between laboratories whose primary focus has been either developmental biology or bone biology. By establishing core facilities for morphologic analysis and transgenic mice, the technical capabilities of each individual laboratory will be extended. In Project 1 the physiologic roles of the parathyroid hormone (PTH), parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and bone morphogenic protein (BMP) secreted signals will be explored in mice, by studying targeted deletions and chimeric embryos. The dual role of the PTH/PTHrP receptor as a regulator of bone development and calcium homeostasis will be explored. In Project 2, genetic interactions between the Ihh and PTHrP pathways will be studied; the cellautonomy of Ihh signaling, the modulation of BMP signaling by antagonistic factors such as Noggin, and the modulation of signaling by Hox gene products will be analyzed; and the function of an additional class of secreted signals, exemplified by Wnt5a, will be studied in mouse skeletal development. In Project 3, the strengths of the chick embryo system for gene misexpression will be utilized in studying the possible role of the secreted factor Autotaxin in initiation of chondrogenesis, the function of two additional Wnt genes, Wnt5b, and Wnt14, in regulation of bone growth, differentiation and segmentation, and the role of Hox genes in modulating signals to achieve bone patterning. In Project 4, signals involved in segmentation of the forming skeletal elements will be studied taking advantage of a unique insertional mouse mutation, and studying the relationship of the signals studied in the other three projects to the segmentation of individual bones. Together these highly related projects will achieve a new level of understanding of the regulation of bone morphogenesis, which could not be attained by independent efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIAGNOSTIC TECHNOLOGY BASED ON ACOUSTIC RADIATION FORCE Principal Investigator & Institution: Sarvazyan, Armen; Chief Scientist; Artann Laboratories, Inc. 1753 Linvale Harbourton Rd Lambertville, Nj 08530 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The goal of the project is development of a physical and technical foundation for novel medical diagnostic technologies based on the use of ultrasonic RF as a virtual finger for remote probing of internal tissues. The milestones of the project include development of an experimental system for RF generation in model objects, for testing and validation of RF transmitters operating over a wide range of frequencies, design of a Doppler system for remote detection of RF induced acoustic signals, comprehensive mathematical analysis of RF generation in biological tissues, and laboratory model studies on RF induced local and oscillations waves in bones and heterogeneous soft tissues. The project will culminate in analyzing the applications of RF based methods in areas of medical diagnostics where the proposed technology has advantages over conventional approaches such as brain assessment; evaluation of muscle dynamic characteristics, assessment of hip fragility and monitoring the growth and ossification of infant's bones. The project is based on several innovations in different areas of physical and medical acoustics, such as use of acoustic RF for remote assessment of bones, Shear Wave Elasticity Imaging, Time Reversal focusing of ultrasonic beams, and remote evaluation of soft tissue shear viscosity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DYSFUNCTIONAL FGFR SIGNALING IN CRANIOSYNOSTOSIS Principal Investigator & Institution: Friesel, Robert E.; Scientist Ii and Assistant Director; Maine Medical Center 22 Bramhall St Portland, Me 04102 Timing: Fiscal Year 2002; Project Start 20-SEP-1998; Project End 31-JUL-2004 Summary: Craniosynostosis, an abnormality of skull development in which the sutures of the growing calvarial bones fuse prematurely, occurs with a frequency of approximately 1 in 2500 live births. Recently, six autosomal dominant craniosynostotic syndromes, Crouzon, Jackson-Weiss, Pfeiffer, Apert, Crouzon with acanthosis nigricans and Beare-Stevenson cutis gyra were shown to be associated with mutations in either fibroblast growth factor receptor (FGFR)-l, FGFR-2 or FGFR-3. In addition, several dwarfing syndromes, achondroplasia, thanatophoric dysplasia types I and II, and hypochondroplasia were shown to be associated with mutations in FGFR-3. The FGFRs consist of a family of four high affinity transmembrane tyrosine kinase receptors. The prototype FGFR is comprised of an extracellular ligand-binding domain made up of three immunoglobulin (Ig)-like domains, a hydrophobic membrane-spanning region and a cytoplasmic tyrosine kinase domain. Mutations in the extracellular ligand-binding domain and the transmembrane domain of FGFR-1, FGFR-2 and FGFR-3 have been associated with craniosynostotic syndromes while mutations in the extracellular, transmembrane and tyrosine kinase domains of FGFR-3 have been associated with dwarfing syndromes. Our recent studies indicate that mutations in the extracellular, transmembrane and tyrosine kinase domains that are associated with craniosynostosis and other skeletal dysplasias result in ligand-independent constitutive activation of the mutant receptors. The central hypothesis of this application is that point mutations in FGFRs that are associated with craniosynostosis and other skeletal dysplasias result in constitutive activation of these receptors and that these receptors have altered signal transduction capabilities compared to their wild-type counterparts. This altered

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signaling capacity may in part be responsible for the phenotypic manifestations of these mutations. Accordingly, the specific aims of the proposal are: 1) to determine whether additional mutations identified in FGFRs that are associated with skeletal dysplasias result in constitutive receptor activation; 2) to determine whether these different mutations impart the mutant receptors with altered signal transduction properties, and 3) to determine whether constitutively activating mutations in FGFRs result in altered stability or intracellular trafficking. Together, these studies should begin to elucidate the role of mutant FGFRs in the pathogenesis of craniosynostotic conditions, as well as the role of FGFRs in normal bone growth and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTRON MICROSCOPY OF THE HUMAN INNER EAR Principal Investigator & Institution: Nadol, Joseph B.; Chief of Otolaryngology; Massachusetts Eye and Ear Infirmary 243 Charles St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-DEC-1979; Project End 31-MAY-2006 Summary: This competing grant renewal proposes continued study of the pathologic human inner ear following the basic strategy of the previous grant period, that is the use of light and electron microscopy. We plan a sharply focused area of investigation, namely cochlear neuronal degeneration in the human cochlear implant patient and its impact on speech recognition. We now have collected temporal bones from 16 individuals who were implanted during life. In nine of these, the auditory brainstem is also available. Initially we will plan to studythe implanted cochleas and morphometric parameters of thecochlear nucleus on both the stimulated and nonstimulated sides and to correlate these parameters with individual performance during life using the cochlear implant. Since the most dramatic central change might be expected in the neuropil of the cochlear nucleus, we also propose synaptophysin immunostaining to evaluate the density of synapses in the cochlear nucleus on stimulated and nonstimulated sides. This investigation can be expected to better predict remaining neuronal elements in human patients who are candidates for cochlear implantation and perhaps to explain the variability in speech recognition scores of these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENERGY RESOLVED DIGITAL HPGE X OR Y-RAY IMAGING DETECTOR Principal Investigator & Institution: Warburton, William K.; President; X-Ray Instrumentation Associates 2513 Charleston Rd, Ste 207 Mountain View, Ca 94043 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-AUG-2004 Summary: Imaging detectors for 10 to 150 keV photons have many uses in medical technology, including tumor imaging, SPECT, and radiography. Digital output is particularly useful since it allows image enhancement, analysis, transmission and storage. In Phase I we proposed a new technology that could capture images with 100 microm spatial resolution and 1 keV energy resolution or better. This capability would facilitate entirely new classes of medical diagnostic procedures, particularly for transgenic small animal imaging. Our Phase I work demonstrated the feasibility of this approach. In this Phase II effort, collaborating with Paul Luke at LBNL, we will construct 1 cm thick crossed-strip HPGe detectors having 10 x 10 strips, each 2 mm x 20 mm. We will develop cooled FET preamplifiers having low noise and large bandwidth properties specifically required by this approach. We will also develop analog filtering electronics to condition the detector's novel signals and employ digital pulse processing

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electronics to acquire these signals at rates up to 10/6 cps. Finally, we will devise procedures to test the detector's linearity and develop processing algorithms to perfect this quality. Phase II will conclude with a working and tested prototype. Phase III will entail primarily production engineering efforts. PROPOSED COMMERCIAL APPLICATION: As an energy resolved digital detector with 100 microm spatial resolution, the proposed detector technology could find many medical applications, including SPECT, energy resolved angiography for small mammals, bone densitometry on rodent bones, and small, hand-held gamma cameras. Non-medical applications would include non-destructive testing, astrophysical gamma imaging, nuclear cleanup uses, and x-ray diffraction detectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOLATE AND HOX GENES IN CRANIOFACIAL DEVELOPMENT Principal Investigator & Institution: Kappen, Claudia T.; Associate Professor; MunroeMeyer Institute; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The crucial role of homeobox genes in craniofacial development is well established. Changes in Hox gene expression result in severe craniofacial defects, involving the branchial arches, the primordia for palate shelf formation. Recent evidence shows that Hox genes act through regulating cell condensation and growth m the skeleton, the craniofacial bones and the palate. Folate supplementation protects against craniofacial abnormalities, indicating a functional interaction with developmental pathways. Common to the action of Hox genes and folate are (i) their effects on cell proliferation, (ii) their involvement m Retinoic Acidmediated teratogenesis and (iii) their actions on specific craniofacial structures. We here propose to investigate the functional relationship of defects induced by folate-deficiency to those mediated by Hox genes. Our central hypothesis is that folate and Hox genes mediate cell growth in craniofacial structures through common cellular and molecular mechanisms. This will be investigated using two animal models with craniofacial defects: mice with genetic modifications in folate metabolism, and mice with genetic manipulations in Hox genes. The specific aims of this study are: (1) To define the role of folate and Hox genes in craniofacial development by analyzing cell proliferation in BrdU incorporation and apoptosis assays. (2) To examine the expression of folate pathway genes m Hox mutants. This will be done by in situ hybridization on embryos from transgenic mice with conditional expression of Hoxd-4 and Hoxc-8 directed specifically to branchial arch 2. (3) To analyze Hox gene expression in folate pathway mutants. These studies will use Folbp1 knockout mice and will identify which folatedependent defects are mediated by particular Hox genes in specific craniofacial regions. (4) To determine the functional relationship of folate and Hox genes in the morphogenesis of craniofacial defects. This will be accomplished genetically, by combining mutations in the folate pathway and those in Hox genes. This will allow us to ascertain whether folate acts through Hox genes or vice versa, and how both act m the pathogenesis of specific craniofacial defects. Our long-term goal is to integrate the control of gene expression by Hox transcription factors and metabolic regulation m the proper morphogenesis of craniofacial structures. Knowledge about the interactions of genes with environmental factors will be important for designing therapeutic strategies and preventive measures against craniofacial defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FRZB PROFILES AS OSTEOARTHRITIS BIOMARKERS Principal Investigator & Institution: Corr, Mary P.; Assistant Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: Provided by Applicant): Accumulating evidence has demonstrated that the products of the wnt, frizzled [fzd], secreted frizzled- Irelated protein [SFRP] and LDL receptor-related protein [LRP1 gene families play a critical role in the ]development and maintenance of joints and bones. Consequently, polymorphisms of these genes that alter protein expression or function are potential biomarker candidates for osteoarthritis [OA] susceptibility and progression. The overall goal of this project is to confirm this hypothesis. Several prior genetic studies of familial OA have mapped a major susceptibility locus to chromosome 2q31, a region that encodes FRZB [also known as SFRP3], a SFRP family member that antagonizes wnt signaling. Preliminary experiments from our laboratory, performed in collaboration with John Loughlin of the University of Oxford, have demonstrated that a specific mutation of the FRZB gene is significantly more common in both familial and sporadic female patients with hip OA, than in female controls. In transfecfion experiments, the mutated FRZB genes have diminished wntinhibitory function compared to wild type genes. Excessive wnt signaling can increase subchondral bone density and possibly chondrocyte metabolic activity at the bonecartilage junctions. Indeed, other preliminary experiments using surface enhanced laser desorption and ionization mass spectrometric analysis of OA sera have revealed increased concentrations of anionic proteins with molecular masses corresponding to several wnt-associated proteins. Accordingly, we postulate that the FRZB mutants are biomarkers for hip OA in women, and that they alter the serum concentrations of wntregulated proteins. To test this hypothesis, we aim [1] to confirm the association of the observed FRZB mutations in an additional series of female patients with hip OA characterized by Nancy Lane and Michael Nevitt at UCSF, [2] to assess the association between the FRZB mutants and increased hip bone density in these women, and [3] to compare the patterns of expression, and the levels, of wnt-inducible proteins in the blood of OA patients with defined FRZB polymorphisms, and of controls, by surfaceenhanced laser desorption and ionization mass spectrometry, and by immunoassay. The results of these studies will both contribute to, and will utilize, the resources of the OA biomarker consortium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTION AND REGULATION OF OSTEONECTIN IN BONE Principal Investigator & Institution: Delany, Anne M.; Research Scientist; St. Francis Hosp/Med Ctr (Hartford, Ct) 114 Woodland St Hartford, Ct 061051299 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): Osteonectin or SPARC (secreted protein acidic and rich in cysteine) is one of the most abundant non-collagenous matrix proteins in bone. It is synthesized by osteoblasts, binds Ca2+ and type I collagen, and inhibits mineralization in vitro. Studies in non-skeletal cells indicate that osteonectin regulates angiogenesis, metalloproteinase expression, cell proliferation, cell shape and cell-matrix interactions. Although osteonectin is abundant in bone, its function remains unknown. Specific Aim 1 of this proposal is to define the function of osteonectin in bone utilizing a SPARC knock-out mouse. The bones of wild-type and knock-out mice will be analyzed by histomorphometry and Fourier transform infrared microspectroscopy. The function and responsiveness of bone cells will be evaluated, in vitro, using organ and

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Bones

cell culture assays. In Specific Aim 2, over-expression of osteonectin and its fragments in MC3T3 osteoblasts will be used to further define the function of osteonectin in bone. Cell proliferation assays and Northern blot analysis of metalloproteinase and matrix RNAs will be used to assess changes in osteoblast gene expression. It is suggested that osteonectin plays an important role in development, wound healing and matrix remodeling, and fibroblast growth factors (FGFs) have been implicated in the regulation of skeletal development and fracture repair. Preliminary data indicate that basic FGF (bFGF) down-regulates osteonectin expression in osteoblasts by a post-transcriptional mechanism. Specific Aim 3 of this proposal is to determine the mechanisms by which bFGF destabilizes osteonectin mRNA in osteoblasts. Regions of the osteonectin transcript that mediate changes in RNA stability will be determined by deletion/substitution mutagenesis and RNase protection assay. Osteonectin RNA binding proteins will be characterized by RNA mobility shift assay, UV crosslinking studies and Western blot analyses. If necessary, a yeast 3-hybrid system for detecting RNA-protein interactions will be used to clone osteonectin RNA binding proteins. It is suggested by the applicant that these studies will provide critical information on the function of osteonectin in bone, and its regulation by a key morphogen, bGF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GDF REGULATION OF ENDOCHONDRAL BONE GROWTH Principal Investigator & Institution: Mikic, Borjana; Associate Professor; Engineering; Smith College Northampton, Ma 01063 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Taken from the application): In recent years, numerous advances have been made towards understanding the molecular regulation of chondrocyte maturation within the growth plate through the production of growth factors and the regulation of their receptors and receptor-mediated transmembrane signaling processes. The growth/differentiation factors (GDFs) represent a distinct subset of the TGF-beta family which may play a role in regulating endochondral bone growth. Evidence for GDF involvement comes largely from the documented mutation in GDF-5/CDMP-1 in individuals with acromesomelic chondrodysplasia of the Hunter-Thompson and Grebe types, and a reduction in the length of the long bones of GDF-5 deficient brachypodism mice. Given the link between GDF-5/CDMP-1 and chondrodysplasia in humans, it is likely that other chondrodysplastic disorders are linked to mutations in related GDF/CDMP family members. The goal of this research is to examine the effect of GDFs 5, 6, & 7 on endochondral bone growth by studying animals with a deficiency in these signaling peptides. We will examine mice with mutations in the genes which code for GDF 5, 6 or 7. For each gene of interest, three groups of ten healthy male mice will be studied, representing mutant (-/-) and heterozygous (+/-) control littermates at 4 weeks of age. Using classical methods of stereology and chondrocyte kinetics, growth plates from the proximal tibia, proximal humerus, and fourth rib will be carefully examined to test the hypothesis that mice deficient in GDF 5, 6, or 7 will exhibit impaired endochondral bone growth. The proposed detailed analyses of stereologic and chondrocyte kinetic parameters will help to identify precisely which growth plate cell populations are affected by the absence of GDFs 5, 6, & 7. Future studies will extend these investigations to double and triple GDF family member mutations, as well as molecular characterization of other important growth plate signaling molecules in the various single, double, and triple GDF mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE DEFECT IN INFANTILE CORTICAL HYPEROSTOSIS Principal Investigator & Institution: Gensure, Robert C.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by candidate): Infantile cortical hyperostosis (Caffey's disease) is a rare genetic disorder with localized thickening of the bone cortex and medullary stenosis, which can appear quite prominently on x-ray. Often, painful swelling occurs over the involved bones. Onset of symptoms is in infancy, and spontaneous resolution occurs before two years of age with no residual effects or recurrences. These clinical findings suggest a transitory, localized defect in the regulation of cortical bone growth, and identification of the responsible genetic defect may serve to enhance the understanding of the growth and maintenance of cortical bone, which remains poorly understood. Pedigrees of families with this disorder show an autosomal dominant pattern of inheritance. No genetic defect associated with this disorder has yet been described, nor has a genetic locus been identified. The candidate has thus far obtained DNA samples from 26 members (19 affected, 1 presumed unaffected, and 6 unrelated spouses) of a large French-Canadian kindred with autosomal dominant inheritance of infantile cortical hyperostosis, and he proposes to use linkage studies to determine the gene locus responsible for this disorder. Once this locus has been identified, the genomic region which is linked to the disease will be delimited by chromosomal crossing-over events in family under study and, potentially, other families with the same disorder. Utilizing sequence information available through the Human Genome Project, genes contained within this linked region will be identified and candidate genes will be selected. Coding regions of candidate genes will be sequenced in genomic DNA from affected individuals (familial and sporadic cases will be studied) to search for mutations which may be responsible for the disorder. Southern blot analyses will also be performed to search for DNA deletions. Once a deletion or mutation (Caffey mutation) is identified in all affected members of the large kindred, the candidate will search for mutations in the same gene in other (smaller) kindreds with Caffey's disease and in sporadic cases, and he will exclude the presence of this mutation in DNA from numerous healthy individuals. Subsequently, the candidate will isolate the murine cDNA homolog and, if this is a novel gene, will study the gene's temporal and spatial patterns of expression by Northern blot analysis. The function of the wild-type protein, along the effects of the Caffey mutation on protein function, will be studied using invitro systems. Ultimately, the identification of a protein which may be involved in regulating the thickness and diameter of cortical bone might provide important new insights into the regulation of bone formation and remodeling, and may provide a new target for pharmaceutical agents aimed at reducing the risk of fractures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC CONTROL OF OSTEOBLAST DIFFERENTIATION Principal Investigator & Institution: De Crombrugghe, Benoit; Professor and Chair; Molecular Genetics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Similarly to the formation of other organs, skeletogenesis involves two broad classes of regulatory factors. Patterning factors control the shape, size and number of skeletal element, as well as initial decisions regarding the body plan of the embryo, whereas differentiation factors control the fate

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of the constituent cells of the skeleton. Previous cell biological experiments suggested that osteoblast differentiation occurs along a multistep pathway. More recently, the transcription factor Cbfa1/Runx2 was shown to be needed for osteoblast differentiation. Very recently, we have discovered that a novel member of the Kruppel family of transcription factors, called Osterix (Osx), is required for bone formation and osteoblast differentiation. Osx null mice have no membranous, and no endochondral bones, although chondrocyte differentiation and cartilage formation occur normally. Furthermore, our experiments indicate that Osx acts downstream of Cbfa1/Runx2. This application proposes to characterize the mechanisms by which Osx controls osteoblast differentiation. We plan to examine the extent of the osteoblast-genetic program that is controlled by Osx and identify sequences in target genes that directly mediate the transcriptional activation by Osx of these genes in osteoblasts in vivo. Our studies will also identify the proteins that either physically or functionally interact with Osx, or control its activity. Finally, we will determine whether Osx is a negative regulator of Sox9 expression and of the chondrocyte differentiation program. Overall, these experiments should greatly improve our understanding of the molecular mechanisms of osteoblast differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC DEVELOPMENT

CONTROL

OF

SKELETAL

PATTERNING

AND

Principal Investigator & Institution: Lufkin, Thomas C.; Associate Professor; Molecular, Cellular & Dev Biol; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 16-FEB-2000; Project End 31-JAN-2005 Summary: The vertebrate skeleton is almost entirely mesodermal in origin, aside from several bones in the skull which are derived from neural crest (Noden, 1992; Couly et al., 1993). In Drosophila one of the principal genes controlling mesoderm differentiation is the bagpipe homeobox gene (Azpiazu and Frasch, 1993; Azpiazu et al., 1996). We have previously isolated from mouse and human, homologues of bagpipe termed Bapx1. Examination of the expression of Bapx1 during embryogenesis revealed an expression almost exclusively restricted to paraxial and lateral plate mesoderm, with earliest expression detectable in the presclerotome cells of the somite (Tribioli et al., 1997; Tribioli and Lufkin, 1997). During subsequent stages of embryogenesis, Bapx1 is expressed in essentially all cartilaginous condensations which will subsequently undergo endochondral ossification. To investigate the role of Bapx1 in embryonic skeletogenesis, this proposal focuses primarily on loss-of-function (gene knockout) and gain-of-function studies in vitro and in vivo. Preliminary results from mice lacking Bapx1 indicate that it plays an essential role in chondroblast differentiation within the axial skeleton, which in turn leads to failed endochondral ossification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS AND PEDIATRIC NONSYNDROMIC HEARING LOSS Principal Investigator & Institution: Kenna, Margaret A.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Sensorineural hearing loss (SNHL) occurs in 4/1000 newborns. Until recently the work-up used a "shotgun" approach; many tests were ordered but the etiology remained unknown in 50% of cases. However, the recent use of

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genetic testing and high-resolution imaging has increased the yield of the SNHL evaluation. Mutations in the connexin 26 gene (Cx26) are responsible for approximately 50% of all recessive nonsyndromic SNHL allowing Cx26 gene testing to greatly expand the ability to provide an etiology for SNHL. This information can provide diagnostic as well as prognostic information to the patients, their families, and their physicians. The current proposal seeks to address several areas that have not been addressed by our studies or those of others. First, the audiologic phenotype of infants and children with SNHL and Cx26 mutations, both at the time of presentation and longitudinally, needs further definition. Second, it is not clear whether the audiologic phenotype varies with specific mutations or combination of mutations. Third, it is not clear whether CT scans of the temporal bones are ever routinely indicated in a patient with biallelic Cx26 mutations. Finally, in families of children with SNHL, it is not clear how well patients and families are being counseled to understand the benefits, drawbacks, and limitations of genetic testing or the results and implications of their genetic tests. It is also unclear why parents choose or decline genetic testing, and whether proper consent is obtained for such testing. We propose a clinical study to evaluate infants and children with Cx26related nonsyndromic SNHL. To accomplish these aims we will use 2 large patient populations from Children's Hospital Boston (CHB) including 1.Newborns referred after failing a newborn hearing screen; 2.Non-newborns with newly identified SNHL. There are four areas of concentration: 1.) Identification of Cx26 positive infants and children using genetic testing as part of the initial evaluation for newly-identified SNHL. 2.) The phenotype of the Cx26 related hearing loss will be studied, both at the time of diagnosis and prospectively over time. The rate and percentage of progression of Cx26 related hearing loss will also be evaluated. 3.) The diagnostic evaluation of the hearing loss will include temporal bone imaging studies, as the presence of anatomic temporal bone abnormalities is frequently associated with progression of the hearing loss and thus would affect the prognosis if present. Although temporal bone abnormalities have not been sought in large numbers of Cx26 positive patients, they are thought to be uncommon, at least for the two most frequently identified mutations, 35deIG and 67delT. However, recent studies suggest that temporal bone abnormalities may be present in some patients with Cx26 mutations. If this were so, the prognosis of the hearing loss would be affected. 4.) For families of children with SNHL, we will utilize a questionnaire to determine why parents choose to have/not have genetic testing and to ascertain parents understanding of genetic testing. This information will be used to evaluate the effectiveness of genetic counseling associated with gene testing for deafness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERTROPHIC CHONDROCYTE AND ITS PERICELLULAR MATRIX Principal Investigator & Institution: Wilsman, Norman J.; Professor; Comparative Biosciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 31-MAY-2004 Summary: Bone growth in children occurs by endochondral ossification in cartilaginous growth plates at the ends of long bones. In any given growth plate, chondrocytes occur in a characteristic spatial organization that also is a representation of the temporal progression of individual chondrocytic differentiation. This research focuses on understanding the chondrocytic differentiation cascade in relationship to growth. The long term objective is to understand the interrelationships among multiple controls, acting through systemic, paracrine, and autocrine mechanisms that are responsible for

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coordinated long bone growth from embryonic life through adolescence, and to analyze perturbations of growth with the intent of designing and implementing optimal strategies for managing the correction of abnormalities of long bone growth. Using an approach of quantitative measurement of multiple chondrocytic kinetic parameters that completely describe the dynamics of cellular contributions to growth, the Specific Aims of the current proposal are: To test the hypothesis that patterns of differential growth characteristic of specific bones are absent prenatally, but are established starting in the perinatal period and become well defined during early postnatal development, and that this translation is reflected in different cellular control mechanisms; To test the hypothesis that postnatal bone elongation occurs by a pattern of brief intense growth saltations followed by much longer periods of no growth (stasis); To test the hypothesis that the primary action of growth hormone, either circulating systemically or delivered locally, is to increase all rate-dependent phases of chondrocytic differentiation during the postnatal period, thus accelerating rates of differential growth and increasing growth velocity; To test the hypothesis that decreased rate of growth following minimal total nutritional deprivation postnatally, as well as catch-up growth following return to normal nutritional status, are controlled through altering the rate at which chondrocytes at all levels of the growth plate proceed through the differentiation cascade, amplified by volume changes at the level of the hypertrophic chondrocyte. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IGF-1 MEDIATES THE ANABOLIC EFFECTS OF PTH ON BONE Principal Investigator & Institution: Bikle, Daniel D.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: (Verbatim from the Applicant): Parathyroid hormone (PTH) promises to be a useful anabolic agent for bone. However, the mechanism by which PTH stimulates bone formation remains imperfectly understood. We propose that at least part of the means by which PTH stimulates bone formation is through other growth factors, in particular insulin like growth factor 1 (IGF-1). IGF-1 plays an important role in bone formation, and modulates the ability of PTH to do likewise. The availability of an animal model in which IGF-1 production has been eliminated by homologous recombination provides an opportunity to test the degree to which IGF-1 mediates and/or regulates the skeletal response to PTH. The hypothesis we propose to test is: IGF-1 mediates the anabolic action of PTH on bone by stimulating osteoprogenitor cell proliferation and inhibiting osteoblast apoptosis. We will test this hypothesis by accomplishing three Specific Aims. 1. Determine the role of IGF-1 in regulating the in vivo response of the mouse skeleton to the intermittent administration of PTH. This will be performed by analyzing the ability of PTH to stimulate bone formation in IGF-1 deficient mice as assessed by fat free weight and calcium content of bone, bone histomorphometry to quantitate cell numbers and bone formation rates, bone microstructure using micro-CT, location and identity of proliferating bone cells by Bride labeling, localization and quantitation of the mRNA and protein levels of IGF-1, the receptors for PTH and IGF-1, and the markers of bone formation, and localization and quantitation of apoptotic cells. 2. Determine the role of IGF-1 in regulating the in vitro response of bone cells to PTH. This will be performed using bone marrow stromal cells and osteoblasts obtained following in vivo administration of PTH or studied in vitro in the presence of PTH. The response of these cells to PTH with respect to markers of proliferation, differentiation, and apoptosis will be assessed. In the event IGF-1 is found to mediate the PTH response, the roles of the MAPK and P13K pathways in this process will be explored. 3. Determine

Studies 39

whether transgenic mice with targeted expression of IGF-1 in their osteoblasts can restore PTH responsiveness to the bones of IGF-1 deficient mice. To accomplish this aim mice overexpressing the IGF-1 gene in osteoblasts either under the osteocalcin or the alpha1(1) procollagen promoter will be bred with the IGF-1 deficient mouse and the response to PTH evaluated using the assays developed in the preceding Specific Aims. The results of these experiments should determine the degree to which PTH is dependent on IGF-1 for producing its anabolic actions on bone, and initiate the exploration into the mechanisms by which this occurs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IL-12 GENE THERAPY FOR METASTATIC OSTEOSARCOMA Principal Investigator & Institution: Worth, Laura L.; Pediatrics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 11-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Osteosarcoma is the most common primary bone malignancy that usually presents during the adolescent and young adult years when the long bones are undergoing rapid growth. At diagnosis children with osteosarcoma frequently have pulmonary micrometastases that are not detected by chest X ray or CT. Despite aggressive chemotherapy and surgical intervention, 30-40% of patients will relapse with pulmonary metastases. The 2-year disease-free survival has not changed significantly in the past 15 years. New agents and novel approaches are needed to increase the survival rate in these children. Using a nude mouse model with human osteosarcoma lung metastases, intranasal therapy with an adenoviral vector expressing interleukin-12 resulted in a dramatic decrease in the number and size of pulmonary metastases in mice. The antitumor immunity induced by this therapy is mediated primary by natural killer cells and antiangiogenic mechanisms. IL-12 has two main antitumor activities that are immune-dependent and immune-independent. The nude mouse model is useful for determining the immune-independent mechanisms. Recently an orthotopic, syngenic murine osteosarcoma model was developed. After the intraosseous injection of murine tumor cells, a tumor forms in bone at the site of injection. These mice go on to spontaneously develop pulmonary metastases. This model, with an intact immune system, will allow the immune-dependent mechanisms of IL-12's antitumor activity to be determined. Four specific aims will be pursued: 1) To determine the identity and timing of cells that infiltrate tumor cells after the administration of Ad.mIL-12. 2) To determine if IL-12 activates NK cells to eradicate pulmonary osteosarcoma metastases. 3) To determine the role IL-12 (the primary inducer of interferon-?) plays in stimulating macrophage and dendritic activity. 4) To determine the role T cells play in the anti-tumor activity of gene therapy with IL-12. Successful completion of these studies will result in a better understanding of the role the immune system (when activated with IL-12 and T cells receptor agonists). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INHIBITED INTRAMEMBRANEOUS BONE HEALING IN DIABETES Principal Investigator & Institution: Trackman, Philip C.; Periodontology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Complications of diabetes result in part from elevated serum glucose levels. This leads to non-enzymatic glycation of proteins to form advanced glycation end products (AGE's). AGE's play a significant role in many

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complications of diabetes. Osteopenia and low mineral density and weak bones is a complication of Type 1 diabetes and is known as "diabetic bone disease". Surprisingly little is known regarding the role of AGE's in modulating bone healing, bone formation, and osteoblast function. For example, the presence and activity of the receptor for advanced glycation end products (RAGE) has not been reported in osteoblasts. The principal hypothesis of the proposed research is that AGE's inhibit bone healing and formation by binding and activating RAGE in osteoblasts. We propose that this results in NFKB activation and transcriptional repression and down-regulation of key osteoblast growth factors and extracellular matrix genes. Aim 1 will measure in vivo the expression of selected growth factors and extracellular matrix products (BMP-1, BMP- 2, BMP-4, and type I collagen) in healing calvaria defects made in diabetic and nondiabetic mice. Diabetes will be induced by the multiple low dose streptozotocin protocol in Balb/c mice; selected studies will be performed in the nonchemically-induced murine diabetic model (NOD strain). The degree of inhibition of bone healing in diabetic animals and expression patterns of RAGE will be determined by quantitative histomorphometric and quantitative immunohistochemical measurements. Studies will directly determine the role of AGE's in diminished diabetic bone formation by local application of AGE's to calvaria defects in non-diabetic mice. The degree to which this mimics diabetic bone will be determined by measuring inhibition of healing and regulation of the same growth factors and extracellular matrix products. Aim 2 will determine in vitro in primary rat osteoblast cell cultures that AGE's inhibit production of osteoblast growth factors and type I collagen via RAGE activated NF-KB. RAGE function blocking antibody studies will identify the AGE/RAGE-dependent NF-KB activation mechanism in the regulation of the specified osteoblast genes. The role of NFKB activation in down-regulating target osteoblast genes will be directly determined by transfection with the super-repressor 32A/36A IKB-alpha, a potent and specific inhibitor of NF-KB activation. These studies will identify a new mechanism that contributes to diabetic bone disease; and should lead to the identification of new therapeutic treatment targets for this increasingly prevalent clinical condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTEGRINS AND BONE MATRIX IN PROSTATE CANCER Principal Investigator & Institution: Byzova, Tatiana V.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 30-NOV-2003 Summary: (provided by applicant): This proposal centers on the mechanisms of the functional communications between a major family of cell surface adhesion receptors, the integrins, and a subset of its ligands, the bone matrix proteins, with an emphasis on osteonectin (SPARC) and a major family of angiogenic growth factors, the VEGFs and its receptors. The context in which these relationships will be examined is prostate cancer. The central hypothesis to be tested in this proposal is that the process of integrin activation preferentially enhances recognition of bone matrix ligands, thereby selectively increasing the metastasis of prostate cancer cells to bone. One of the mechanisms of regulation of integrin activation is via VEGFdependent autocrine loop. The corollary to this hypothesis that the bone matrix ligands alter the VEGF/VEGFR2 expression and further amplify proposed VEGF autocrine loop will also be tested. Our Specific Aims are: Aim I. How does integrin activation influence recognition of the bone matrix? We will introduce wild-type and mutant forms of integrin into prostate cancer cells which result in a resting, constitutively activated state or a non-activatable receptor and determine how these states influence recognition of bone matrix ligands. The

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emphasis of our studies will be the bone protein that is responsible for prostate cancer bone interactions, SPARC (osteonectin). We will then determine the mechanisms of SPARC interactions with integrins on prostate cancer cells that are known to metastasize to bone relative to those with low metastatic potential. We will determine whether activation or neutralization of the V-ALIA pathway alters integrin function and SPARC recognition on these cells. Aim II. What is the role of newly identified regulatory circuits in the V-ALIA pathway in prostate cancer? We will assess how the bone matrix protein SPARC influences the expression of VEGFs and VEGFRs. We will use purified protein as well as bone extracts from normal and SPARC (-/-) mice. Aim III. What is the role of the V-ALIA pathway in vivo? We will determine the integrin activation states of human prostate tumors that have metastasized to bone as compared to tumors localized to the prostate. We will compare the growth characteristics in bone environment of cell lines expressing inactive and active integrins. We will compare the tumor growth characteristics within the bones of WT and SPARC (-/-) mice. Our efforts to determine how the recognition of bone specific matrix proteins by prostate tumor cells occurs and what mechanisms regulate this recognition will provide insights into a basic and potentially important process operative in the growth and metastasis of prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERFACIAL PROPERTIES OF HAVERSIAN BONE Principal Investigator & Institution: Griffin, Lanny V.; Materials Engineering; California State Poly U San Louis Obispo Building 38, Room 102 San Luis Obispo, Ca 93407 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from the Applicant's Abstract): Cortical bone is a brittle, circumferentially laminated, multiphase composite structure that has been shown to exhibit microdamage similar to that found in advanced composite materials. Microcracks are an important manifestation of fatigue damage and are clinically associated with stress fractures, bone fragility, and remodeling. The goal of this study is to quantitatively investigate properties, such as fracture toughness and shear strength, of major interfaces in cortical bone, such as cement lines and interlamellar interfaces of osteons. Additionally, the effects of collagen fiber orientation and physiologic region on these fracture properties will be evaluated. The relevance to structural fracture resistance is that these bone interfaces have been shown to deflect microcracks, and may contribute to the overall fracture resistance of whole bones. The experiments are based on a standard fiber push-out procedure used for testing interfacial properties of fiberreinforced composite materials. Human bone will be used to evaluate the dependence of interfacial properties of osteons as a function of collagen fiber orientation within the osteon and the adjacent matrix, and to assess the effect of the anatomic region. Equine bone will be used to evaluate differences between primary and secondary osteons. Micromechanics and constitutive modeling will be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LUNG GROWTH AT HIGH ALTITUDE AND MAXIMAL O2 TRANSPORT Principal Investigator & Institution: Johnson, Robert L.; Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-MAR-2006 Summary: (Applicant's abstract): Human natives of high altitude (HA) develop increased lung volume and diffusing capacity consistent with enhanced alveolar

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growth, and increase blood volumes that facilitate 02 transport. However, other adaptation to HA (muscularization of pulmonary arterioles, dysanaptic airway growth and retardation of thoracic growth) may impair O2 transport. The interplay among these factors at different altitudes is not known. Functional consequences of these structural changes can be isolated only after re-acclimatization to sea level (SL) when reversible changes in blood volume and pulmonary vascular reactivity have subsided. We employ this approach to address long-term structure-function relationships of maturation at HA in dogs. Hypotheses are 1) Hypoxia stimulates alveolar hyperplasia and enhances diffusive gas exchange. 2) Airway growth lags behind alveolar growth at HA, leading to uneven distribution of ventilation and increased ventilatory work. 3) Pulmonary vascular changes at HA significantly limits maximal cardiac output at SL. 4) Structural changes at HA persist after reacclimatization to SL and exert opposing effects on O2 transport, i.e., persistent vascular and airway abnormalities offset benefits derived from enhanced alveolar growth. 5) Growth of thorax is impaired in an altitudedependent way; at extreme altitude, the restricted thoracic size sets an upper limit to lung growth and O2 transport. We plan to raise immature dogs (age 2 mo.) to somatic maturity (12 mo.) at 3 levels of HA (3, 100m, 3,800m or 4,500m in separate groups) compared with controls raised at SL. Dogs will be returned to SL at maturity for cardiopulmonary testing at rest and exercise, including pressure-volume curves, maximal 02 uptake, efficiency of gas exchange and diffusing capacity of lungs (DL) and muscles, ventilatory work, hemodynamics and blood volume. Dimensions of airways, diaphragm, rib cage, lungs and spleen will be assessed by spiral CT scan. Components of DL, septal tissue volume and pulmonary blood flow will be measured at regular intervals and correlated with blood volume. After 1 yr. of re-acclimatization to SL, studies will be repeated to determine regression of changes. Terminally, detailed structural analysis will be performed on the lungs, respiratory, locomotive and ventricular muscles, as well as ribs and long bones. Growth patterns of the acini, airways, vasculature, thoracic structures and their functional correlates will be compared at the 3 levels of hypoxia to determine the altitude-dependence of adaptation in O2 transport. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANICAL MODULATION OF GROWTH IN PHYSES Principal Investigator & Institution: Stokes, Ian A.; Research Professor; Orthopedics and Rehabilitation; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Progressive deformities in bones and growth cartilages are commonly thought to be controlled by the 'Hueter-Volkmann Law' which states that growth is retarded by increased mechanical compression, and accelerated by reduced loading of the growth plate in comparison with normal values. It has been confirmed by previous studies that a constant load, superimposed on the ambient in vivo loading of a growth plate will modulate its rate of growth. This phenomenon has only been quantified for a few individual bones of individual species, and the general rules which determine a particular bone's response to load as a function of its physiologically normal growth rate, dimensions and activity of the growth plate cells are unknown. Many of the variables which covary with (and probably govern) bone growth rates have been identified. This work will provide greater understanding of the mechanical regulation of bone growth and eventually permit quantitative design of mechanical treatment by techniques such as bracing, muscle stimulation and surgery. The proposed studies will

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quantity the rate of endochondral growth of long bones and vertebrae under normal conditions and with mechanical compression and distraction. Four different species will be studied at an early stage of growth and nearer to skeletal maturity when the bones are growing more slowly. In additional experiments the feasibility of 'part-time' treatment will be investigated by studying the effects of physis loading during nighttime and day-time only. The characteristic properties of the growth plate (dimensions, numbers of cells and measures of cellular activity) will be documented and compared between growth plates which had experienced different applied mechanical stresses. Statistical models will be developed to show how the mechanical modulation of growth varies in relationship to characteristic properties of each growth plate. These analyses will be guided in part by known physiological relationships between properties of growth plates. The result of this work will be an understanding of how a given physis should be expected to respond to a given stress, and this will be helpful to understand the progression of skeletal deformities and to guide their treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANICAL TESTING SYSTEM Principal Investigator & Institution: An, Kai-Nan; Professor & Chair; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: The Orthopedic Biomechanics Laboratory has more than 20 years of experience in material testing and tissue property characterization. Such studies have provided useful basic science information about normal and pathologic tissues of the musculoskeletal system. Our success has been driven by the quality and number of collaborators at the Mayo Clinic and the large number of research projects funded by NIH. Our expertise with material testing was recognized by the institution by establishing us as a Material Testing Core Facility, which is available to all investigators at Mayo. This grant application is submitted to request to request the purchase of a lowforce material testing system (858 Mini Bionix, MTS, Minneapolis, MN). The current systems that we have are sub-optimal for the testing and detecting subtle changes in properties of soft tissues and small animal bones. We also request an environmental chamber to allow us to test materials in a controlled environment stimulating the in vivo condition Shared use of this equipment is planned at this time among eight investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANICS OF THE MCL IN NORMAL AND ACL DEFICIENT KNEES Principal Investigator & Institution: Weiss, Jeffrey A.; Bioengineering; University of Utah Salt Lake City, Ut 84102

Associate

Professor;

Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: Knee ligament injury can lead to ligamentous laxity, joint instability and degenerative joint disease. Methodologies that improve the diagnosis, treatment and prevention of ligament injuries are crucial to prevent this progression. The medial collateral ligament (MCL) is one of the most commonly injured knee ligaments, provides primary stabilization against valgus rotation, and is a secondary restraint to anterior tibial translation and external tibial rotation. The structure experiences extreme variations in strain as a function of knee flexion angle. The broad aims of this project are to develop and validate a constitutive model for the MCL, a finite element model of the

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superficial MCL, and to determine the stress/strain distribution within the MCL under varus-valgus (V-V) torques and anterior-posterior (A-P) tibial force in intact, ACLdeficient, and ACL-deficient+meniscus compromised knees. Following acquisition of volumetric CT data for individual knees, experimental kinematic testing will be performed under V-V and A-P loading conditions as a function of knee flexion angle. Knee kinematics and MCL surface strains will be continuously monitored during all kinematic testing. The MCL will then be isolated from the joint to measure regional in situ strain at 0 degrees knee flexion. Material testing of the MCL will be performed to determine coefficients for a three-dimensional constitutive model. Using the volumetric CT data, detailed geometric and finite element (FE) models of the MCL, distal femur and proximal tibia will be constructed. Appropriate boundary conditions, including representation of contact between the MCL and bones, will be applied to the model, using the experimentally measured joint kinematics to drive the motion of the model. The experimentally measured in situ strains will be applied to the FE model using numerical algorithms developed by the PI. Predictions of MCL stress/strain under V-V and A-P loading will be obtained from FE simulations. The regional MCL strain predictions will be statistically compared with experimental measurements to validate the model. The results for the normal and ACL-deficient knee will be compared to determine the effect of ACL deficiency on MCL stresses under V-V and A-P loading. Information obtained from this study will yield a detailed understanding of the function of the superficial MCL and its propensity for injury in the ACL-deficient and meniscuscompromised knee. The methods developed in conjunction with this research will facilitate future modeling of other ligamentous structures, and the eventual modeling of entire joints. This work will form the basis for the PI's long term research program aimed at the computational modeling of ligaments and joints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF MMP GENE INDUCTION IN OSTEOARTHRITIS Principal Investigator & Institution: Ray, Bimal K.; Associate Professor; Veterinary Pathobiology; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The goal proposed research is to elucidate the induction mechanism of matrix metalloproteinases (MMP) in chondrocyte cells of the osteoarthritis-affected joint tissue. Osteoarthritis (OA) is manifested by the degradation of cartilage leading to a total loss of the cushion between the bones of the joints causing stiffness, swelling and limitation of joint mobility. In normal cartilage, expression of each MMP is tightly regulated. During OA condition, however, MMPs are overexpressed resulting in the degradation of Collagen and other joint tissue-associated proteins necessary for maintaining normal environment of the cartilage. We hypothesize that a set of transcription factors, responsible for the increased expression of MMPs, is present at a higher active level in the chondrocyte cells of OA-cartilage. Consistent with this hypothesis, preliminary studies indicated that chondrocyte cells of the OA joint tissue contain a significantly higher level of several transcription factors, of which one is identified as SAF-1, an inflammation-responsive transcription factor. Over-expression of SAF-1 enhances MMP-1 expression in cultured chondrocyte cells. SAF-1 also interacts with the promoters of MMP-9 and -14 genes indicating its possible role in regulating expression of these MMP genes in OA condition. Identification of the involved transcription factors will provide a molecular basis for regulating their activity for future therapeutic efforts against OA. This research thus focuses on defining the role of SAF-1 in regulating expression of MMP-1, -9 and -14 genes. Another goal of this

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proposal is to identify other transcription factors involved in this process. Although pathology of OA most likely starts with biomechanical stress on the cartilage, cytokines appear at later stages of the disease. Therefore, an OA-like condition will be created by combining both biomechanical stress and cytokines and mechanisms of MMP gene induction will be studied in response to these signals. Towards this goal, the following specific aims are planned: 1) Characterize the role of SAF-1 in MMP-1 gene induction in chondrocytes of OA-cartilage. Define other responsive elements and factors involved in increasing MMP-1 expression in OA condition. 2) Investigate the role of SAF-1 in the induction of MMP-9 gene expression in OA-cartilage. Identify other regulatory elements and factors involved in this process. 3) Assess the role of SAF-1 in the induction of MMP-1 4 gene and identify other regulatory elements and factors involved in increasing MMP-1 4 expression in chondrocytes under OA-like condition. Completion of the above experimental objectives will form the basis for future investigation on: a) transmembrane signaling pathways in OA chondrocytes that enhance transcriptional activity, and b) evaluation of inhibitors of involved signaling pathway as potential therapeutic agents to control abnormal MMP expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISTIC ROLE OF NELL-1 IN PREMATURE SUTURE CLOSURE Principal Investigator & Institution: Ting, Kang; Dental Research Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant) We have isolated a novel gene, NELL-1, that is highly expressed during premature suture fusion in craniosynostosis (CS) patients. Our initial structure analysis demonstrated that NELL-1 is a secretory protein with a signal peptide, an NH2-terminal thrombospondin (TSP)-like module, five von Willebrand factor C domains, and six epidermal growth factor-like domains. Our preliminary data indicated preferential NELL-1 expression in neural crest origin cranial osteoblasts and during cranial suture closure. We have shown that NELL-1 over-expression in rat primary calvarial osteoblasts (FRCC) and MC3T3 osteoblast cell cultures significantly enhances osteoblast mineralization through increased osteoblast differentiation. Microarrays show up-regulation of osteoblast differentiation marker like osteopontin and osteocalcin. To further delineate the in vivo effects of NELL-1, we have constructed NELL-1 over-expression transgenic mice in which NELL-1 expression is regulated by the general CMV promoter. Initial morphologic analysis of the CMV transgenic mice demonstrate multiple cranial abnormalities including obliteration of ventricles, premature closure of cranial sutures, and deformities of cranial bones. CBFA1 has recently been shown to play an important role in FGFR1 induced CS. TGF-beta1 and FGF2, which affect CBFA1 expression and induce cranial suture closure, induce NELL-1 expression in FRCC cells. IGF 1 & 2, PDGF, VEFG, and BMP2, on the other hand, have no effect on NELL-1 expression. NELL-1?s predicted promoter sequence contains a highly conserved OSE2 (CBFA1 binding site) sequence and a MSX2 binding sequence. CBFA1 can induce NELL-1 over-expression in osteoblasts. We have provided evidence that NELL-1 over-expression induces dysregulation of bone formation/modeling processes in the cranial suture, resulting in premature suture closure. We also suggest that NELL-1 may be a common down-steam target/effector of several known CS candiate genes like FGFRs, MSX-2, and TGF-beta, in causing local premature suture closure. In this proposal, we hypothesize that NELL-1 is a down-stream effector/target of TGFbeta and FGF in osteoblast-like cells with CBFA1 and MSX2 as its direct

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transcriptional regulators. Furthermore, CBFA1 and MSX2 may synergistically induce NELL-1. We will examine the interactions of known CS candidate genes like FGFs, FGFRs, TGF-betas, and MXS-2 with NELL-1. In addition, we will characterize NELL-1?s promoter to understand its promoter regulatory mechanisms. Since NELL-1 is preferentially/specifically expressed in neural crest origin calvarial osteoblasts, we will identify neural crest and/or osteoblast specific transcription factor. Finally, we will integrate NELL-1 into the suture closure pathway with these known candidate genes. In the future, we will analyze NELL-1?s down-stream mechanism to further complete the premature closure mechanism in CS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MODELS OF CANCER, BONE DISEASE, AND LACTATION Principal Investigator & Institution: Rosol, Thomas J.; Professor of Veterinary Pathobiology; Veterinary Biosciences; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): The K26 Award will be utilized to devote 50% effort to research in mouse pathobiology and to mentoring veterinarians and PhD graduate students in Veterinary Biosciences and other graduate programs at OSU in experimental pathophysiology of mouse models of human disease. There will be four major research projects: 1) develop a mammary gland-specific 'knock-out' model to investigate the function of parathyroid hormone-related protein (PTHrP) during lactation and in the neonate during suckling (ongoing project); 2) investigate the pathogenesis of humoral hypercalcemia of malignancy in a new SCID/beige mouse model of human HTLV-1-associated lymphoma (ongoing project); 3) investigate the pathogenesis of bone formation induced by bone metastases of human prostate cancer ("osteoblastic" metastases) by xenotransplantation of prostate epithelial cells in bones of athymic mice (new project); and 4) examine the effects of disruption (knock-out) of the genes for estrogen receptor alpha and beta on bone remodeling in normal, ovariectomized, and estrogen-treated mice (new collaborative project). The models have been carefully chosen and developed to mimic human disease and to provide unique opportunities to gain knowledge and train mouse pathobiologists in areas that are poorly understood, namely bone disease, cancer in bone, osteoporosis, and humoral hypercalcemia of malignancy. The projects will build on the long-term expertise of the applicant's laboratory in the pathophysiology of bone, cancer, and hypercalcemia in mice. Mentorship will consist of: 1) serving as advisor for veterinarians pursuing a PhD in experimental mouse pathobiology (currently advisor for five DVMs); 2) serving as collaborative mentor on research projects by veterinarians and basic scientist PhD candidates in the Department of Veterinary Biosciences (currently 17 projects) and PhD candidates in the Molecular, Cellular, and Developmental Biology Program and Comprehensive Cancer Center at OSU; 3) participating in training programs offered by the Transgenic Animal Shared Resource; 4) collaborating on research projects involving experimental pathobiology of mice; and 5) developing a training program in mouse pathobiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MYELOMA-MICROENVIRONMENT INTERACTION DYNAMICS Principal Investigator & Institution: Yaccoby, Shmuel; Myeloma Inst for Res & Therapy; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205

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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: The proposed research seeks to elucidate the roles of various cells in the bone marrow (BM) microenvironment in the pathogenesis of multiple myeloma (MM), a once rare but increasingly more common hematologic malignancy that currently afflicts nearly 14,000 people in the U.S. each year. Despite treatment advances, MM remains incurable. The central hypothesis is that myeloma cells alter the cellular and cytokine milieu in the BM microenvironment to their growth and survival advantage. We will identify cellular elements critical for supporting the growth of MM, as well as other cell types that may restrain tumor growth. We recently developed the SCID-hu host system for primary human myeloma. In this in vivo system, primary myeloma cells grow exclusively in a human BM environment. As in patients, interaction of myeloma cells with the human BM microenvironment is associated with typical MM manifestations, providing an excellent tool for studying this interaction mechanism. In this study, we will concentrate on the role of osteoclasts and osteoblasts in the MM disease process. Our Specific Aims include the following: Specific Aim 1: Elucidate the reciprocal relationship between myeloma cells and osteoclasts. Myeloma cells induce osteoclastogenesis. We will test whether osteoclast activity is required for the growth of primary myeloma by treating myeloma-bearing SCID-hu hosts with osteoclast inhibitors. Using both in vitro and in vivo approaches, we will also test the ability of isolated osteoclasts to support myeloma growth. Specific Aim 2: Unravel the molecular mechanisms by which myeloma cells and osteoblasts affect each other. We hypothesize that osteoblasts produce factors that interfere with myeloma growth. We will test the ability of osteoblasts to affect the growth and survival of myeloma cells in vitro and in SCID-hu hosts. We will also test the effect of myeloma cells on the survival of osteoblasts in myelomatous bone, and examine the effect of these cells on the differentiation pathways of mesenchymal stem cells. By its conclusion, work under this study will have determined the importance of increased osteoclast activity to myeloma cell growth and survival, and whether interfering with myeloma-induced osteoclastogenesis will prevent and control MM. It will also have determined the involvement of osteoblasts in MM, and whether increasing bone formation in myelomatous bones will affect myeloma progression. This study will help develop an effective treatment for patients with MM or at risk of it, as well as its prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NON INVASIVE CHARACTERIZATION OF BONE MICRODAMAGE Principal Investigator & Institution: Nicolella, Daniel P.; Southwest Research Institute 6220 Culebra Rd San Antonio, Tx 78238 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Humans experience an age-related increase in the incidence of skeletal fractures and this increase may be due to a variety of factors including a decrease in bone mineral density, impaired balance and reflexes, changes in the shape and size of bones, changes in bone porosity and microarchitecture, alterations in bone mineral and organic constituents, and microdamage accumulation. The latter three factors, often referred to as "bone quality," are increasingly recognized as important determinants of fracture risk, especially for osteoporotic patients. Quantification of measures of bone quality such as microdamage accumulation and other microstructural characteristics may lead to a more accurate measure of bone strength and therefore fracture risk. Unfortunately, current technology does not allow the nondestructive and non-invasive detection of cortical bone microdamage or other measures of bone quality including microporosity. On the other hand, NMR proton

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spin-spin (T2) or spin-lattice (T1) relaxation time measurements and analytical processing techniques have been used to determine microstructural characteristics including porosity, pore size distribution, and permeability of various types of fluid filled porous materials with characteristic pore sizes ranging from sub-micron to submillimeter. We propose to develop a rapid, non-destructive and non-invasive technique based on low field pulsed NMR to detect and quantify bone microdamage and porosity and relate these measurements to bone mechanical properties. This new information may then be used in combination with or replace existing methods to more accurately assess fracture risk. The objective of the proposed research project is to develop a nondestructive technique to assess bone quality by quantifying microdamage, porosity, and pore size distribution in cortical bone. The major hypothesis to be tested in this proposal is that non-invasive NMR relaxation time measurements can be used to characterize cortical bone microdamage, porosity, and pore size distribution (measures of bone quality) and can subsequently augment or replace traditional bone mineral measurements to predict cortical bone mechanical properties. We expect our findings will allow the non-destructive and possibly in-vivo assessment of cortical bone microdamage and porosity and correlate these measures of cortical bone quality to cortical bone strength. Although this is a high-risk proposal, this new knowledge will be significant since it may ultimately lead to the development of a more accurate, less complicated, and less expensive technique to clinically assess the risk of fracture compared to currently available technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOCYTE INTEGRITY AND BONE REMODELING Principal Investigator & Institution: Schaffler, Mitchell B.; Professor; Orthopedics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 15-SEP-1992; Project End 31-JUL-2007 Summary: (provided by applicant): Turnover of cells and matrix occurs in a wide spectrum of organs and tissues and is essential to maintenance of tissue integrity. In bone, numerous investigators have suggested that a major function of osteonal remodeling is to maintain tissue, wherein remodeling serves to remove and replace microscopic regions of compact bone, which have become microdamaged due to fatigue. Left undetected and unrepaired, microdamage in bone leads to compromised mechanical properties and bone fragility. How bone remodeling units "target" microscopically damaged areas of bone remains a mystery. Previously, we found that osteocytes undergo apoptosis in bone areas immediately surrounding bone fatigue microdamage. This apoptosis precedes the onset of osteoclastic resorption. The resulting areas of osteocyte apoptosis co-localize exactly with the areas of bone, which subsequently undergo resorption by osteoclasts. These observations are the first demonstration of a potential cellular mechanism to explain how microdamage can initiate focal bone remodeling. In the current studies, we will determine whether osteocyte apoptosis is also highly associated with bone resorption stimulated by metabolic challenge (i.e. ovariectomy in rats) and mechanical challenge (i.e. immobilization in rats). Osteocyte apoptosis will be assessed by TUNEL and Bax expression in situ, and quantitated by histomorphometry. In the second series of studies, osteocyte apoptosis and targeted remodeling will be activated using ulnar bending to fatigue long bones in adult rats. Osteocyte apoptosis will then be pharmacologically modulated in vivo using a caspase inhibitor, in order to determine whether the extent of osteocyte apoptosis directly influences the activation, targeting and/or progression of osteoclastic resorption. In the third series of studies, we will examine changes in bone

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lining cells overlying regions of osteocyte apoptosis. We will determine whether lining cells also change their integrity in concert with underlying osteocytes, and thereby potentially present phagocytic markers to responding osteoclasts and precursors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS, COLLAGEN CROSS-LINKS & BIOMECHANICS Principal Investigator & Institution: Paschalis, Eleftherios P.; Associate Scientist; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant): During studies of the variation in mineral properties in osteoporotic bone, an apparent alteration in the quality of the organic matrix as a function of anatomical location within the same individual was observed. The overall goal of this proposal is to test the hypothesis that there are consistent alterations in the organic matrix of osteoporotic patients compared with normals, which are dependent on the anatomical site, and are due to differences in collagen properties. This will be accomplished through the investigation of three specific aims: Aim 1: To test the hypothesis that there are significant differences in collage/matrix properties between normal and osteoporotic human bones. Furthermore, that these differences are evident in actively bone forming surfaces. This hypothesis will be addressed by comparison of iliac crest biopsies from individuals in whom osteoporosis has been determined based on histologic/histomorphometric parameters, with biopsies from those without morphometric evidence of osteopenia. These studies will be based on histology, and FTIR Imaging (FTIRI) techniques. Aim 2: To test the hypothesis that the observed differences are a function of variations in the biochemical properties of collagen, primarily cross-linking pattern (extent, maturity, origin). This will be verified by a comparison of biochemical and FTIR analyses of a series of highly purified collagen peptides. Additionally. quantitation of the spectroscopic parameters describing collagen cross-links will be achieved utilizing well-established chemical methods to modify predentin. Aim 3: To test the hypothesis that variation in the mechanical properties of bone is dependent part on the quality of the organic matrix. This aim will document the effect of changes in collagen-cross linking pattern observed by FTIRI on the mechanical properties of bone in a well-documented animal model system. Bulk collagen quality will be analyzed by chemical means, and geometric/anatomical variations by FTIRI. These studies will be performed using bones from the beta-aminoproprionitrile rat animal model in which collagen/structure is known to be modified, and for which both geometric and structural properties will be determined. The proposed studies will be based on histology, FTIR Imaging (FTIRI), biomechanical, and biochemical techniques and represent a novel approach to evaluating the organic matrix inosteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OTITIS MEDIA CORE CENTER Principal Investigator & Institution: Daly, Kathleen A.; Associate Professor Sr. Research Assista; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Otitis media is among the most common childhood diseases, and otitis media sequelae are frequent in adults. A multidisciplinary team of basic and clinical scientists has led otitis media research at the University of Minnesota since 1978, when the University's Otitis Media Research Center (OMRC) was formed.

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The OMRC mission is to create a collaborative environment for interdisciplinary research that stimulates advancement in understanding otitis media pathogenesis, to inspire new developments in diagnostic technology, treatment and prevention modalities, and to generate and disseminate fundamental and clinical knowledge, thereby, enhancing patient care. The Otitis Media Core Center will support 16 currently NIH-funded base research projects (12 NIDCD-funded) and an additional two recently submitted projects. OMRC research is focused in basic molecular, cellular, microbial, immunological, animal modeling, population science, and clinical studies. Research productivity is demonstrated in the more than 400 peer-reviewed publications from OMRC faculty. Most of the proposed Core Laboratories were developed under NIDCD P01 support from 1978 to 1996. The Analytical Pathobiology Core will continue to provide expertise and techniques in microbiology, immunology, biochemistry, molecular biology, and histopathology. It will also provide antibodies, probes, archival samples, bacteria or bacterial components, and a complete range of histological and molecular biological services on human and animal temporal bones. Services include light and electron microscopy, histochemistry, immunohistochemistry, immunogold, quantitative image analysis, Northern blot, RNA protection assay, Western blot, in situ hybridization, competitive RT-PCR, representative differential display, and molecular expression and cloning. Immunological expertise includes immunoassay development, immunological reagent production, molecular characterization of a pneumococcal library used in otitis media animal modeling, and refinement of animal modeling surgical techniques. The Human Subjects & Biostatistics Core will continue to be responsible for assisting base project PIs in study design, data collection and processing, quality control, data storage and retrieval, and data analysis of all studies to provide all investigators with a high level and broad range of expertise in data management and analysis. A unique feature of the Core will be the provision of pilot data for new projects drawing from databases and participants from previous OM studies. The key areas are quality control and standardization of data analyses. The key areas are in both Cores are quality assurance, assay standardization, and utilization of the most sensitive methodologies available. Together, the Cores will greatly enhance the OMRC infrastructure, allowing highly productive basic and clinical scientists to conduct research on a broad range of middle and inner ear disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--CONNECTIVE TISSUE ONCOLOGY Principal Investigator & Institution: Baker, Laurence Howard.; Professor and Director for Clinical Rese; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: The Connective Tissue Oncology Program (CTOP) studies two populations of patients with cancer of the connective tissues: the skeleton and its supporting soft tissues. It is composed of 26 members from 11 department with more than $3.3 million in annual direct support. The cancers studied are either primary or metastatic to these groups of tissues. Sarcomas, or primary cancers of connective tissues, are uncommon forms of malignancy, particularly in comparison to the epithelial cancers, yet represent a raison d'etre of cancer centers: multi-disciplinary oncology. All current practice guidelines underscore the need to have multi- disciplinary teams of physicians and other professionals to care for patients with these uncommon malignancies. Success has been clearly achieved with the approach of combining the medical or pediatric oncologist with the surgeon to produce markedly improved cure rates for bone cancer

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(osteosarcoma, Ewing's sarcoma), and to a lesser extent, of soft tissue sarcomas. While cancers of the connective tissue are much more common in soft tissue than in bone, the reverse is true when one considers metastatic cancers where metastasis to the skeleton is far more common that metastasis to the soft tissue supporting that skeleton. Metastasis to the skeleton is a very common phenomenon associated with human cancer. The prevalence and predilection of metastasis to the bones, despite its commonality, is one of the more poorly understood processes associated with cancer. Even more devastating are the symptoms caused by the metastasis and the relative ineffectiveness of current treatments. The research areas related to sarcomas and metastatic bone tumors represent a common research foci. For example, the bone microenvironment primarily consists of mesenchymal cells similar to the cells from which sarcomas originates from. Additionally, the biology of sarcomas and metastatic cancers is similar in terms of growth characteristics (e.g. slow growth). Accordingly, we think combining these two areas of concern into a single program makes good sense, and in particular, unifies the strengths at this Cancer Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEASES IN PROSTATE CANCER BONE METASTASIS Principal Investigator & Institution: Cher, Michael L.; Associate Professor; Urology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): In prostate cancer, proteases are well known to regulate cell proliferation and death, tumor invasion, metastasis, and angiogenesis. Proteolysis is also essential for normal and tumor-induced bone remodeling. Although protease inhibitors have been tested in some patients with cancer, none have entered into clinical trials specifically for patients with bone metastasis. We must apply a broad and comprehensive strategy to choose the appropriate protease targets specific for bone metastasis, and we must improve our understanding of the interplay between tumor cells and bone with regard to protease activity in the bone microenvironment. We must also develop systems for monitoring the inhibition of proteases as a key endpoint in clinical trials. Therefore, our Specific Aims are to: (1) Analyze the effects of prostate tumor cell-bone interactions on the proteolysis associated with prostate cancer bone metastases; (2) confirm that the proteases identified in the organotypic model system of Aim 1 are expressed and active during the colonization of bone by prostate cancer cells in vivo; (3) validate that the protease classes and individual proteases identified above contribute to the proteolysis induced by prostate tumor cell-bone interactions; and (4) use protease-activated probes to image both activities of proteases validated as contributing to prostate cancer bone metastasis as well as the abrogation of those activities by protease inhibitors. To accomplish these goals will use novel bone organotypic models, bone metastasis models, and clinical human bone metastasis tissues. Gene profiling methods will be used to monitor changes in protease gene expression in tumor and bone marrow stromal cells. Prostate cancer-induced proteolysis of bone or relevant substrates will be monitored, and a variety of methods will be used to measure and visualize activity of individual proteases. The roles of specific stromal-derived proteases in bone metastasis models will be examined using general and specific protease inhibitors and as well as cells, bones, and mice rendered genetically null for specific proteases. As clinical trials with protease inhibitors will be more informative if protease activity can be monitored non-invasively, we will validate protease-activated imaging probes for their ability to selectively image protease activity

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and its abrogation by protease inhibitors in both in vitro and in vivo models of prostate cancer bone metastasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RACE DIFFERENCES IN HIP STRENGTH, DENSITY AND GEOMETRY Principal Investigator & Institution: Lang, Thomas F.; Associate Professor; Radiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant): In the clinical setting, areal bone mineral density (BMD) measurements by dual x-ray absorptiometry (DXA) estimate hip fracture risk by providing a surrogate measure for proximal femoral strength. Because DXA is a planar imaging modality, it has potentially important limitations. First, DXA quantifies integral bone mass and density, whereas the influence of the cortical and trabecular compartments on mechanical strength may exceed their contributions to the integral bone mass. Second, DXA BMD measurements scale with bone size; larger bones appear to be denser. The overall goal of our study is to understand how the projectional nature of DXA imaging affects its ability to depict proximal femoral strength in two populations with known differences in hip fracture rates, volumetric BMID, bone size and cortical thickness. To achieve this goal, we will carry out a study in vivo comparing proximal femoral strength, compartmental BMD and geometry in 400 elderly Caucasian and African-American women. To estimate femoral strength, we will image the subjects with volumetric quantitative computed tomography (vQCT) of the proximal femur and construct finite element (FE) models using the vQCT scans. We will calculate proximal femoral failure load (FL) by loading these models to failure with forces simulating a fall to the side with impact on the posterolateral aspect of the greater trochanter and a joint reaction force simulating a spontaneous fracture. In order to determine the relationship between DXA BMD and FL in these two race groups, we will acquire DXA hip scans in all of the subjects. To determine the relationship between FL, compartmental BMD and 3-D bone geometry, we will analyze the vQCT scans with a computer algorithm, which extracts measures of trabecular/cortical BMD and cross-sectional geometry. By determining the 3-D geometric and/or BMD factors which result in greater proximal femoral bone strength and understanding how these measures are modified by planar projection, we will gain considerable insight into the performance of DXA, the principal technique used to estimate proximal femoral strength and therefore, hip fracture risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RAMAN IMAGING OF BONE TISSUE MINERALIZATION Principal Investigator & Institution: Morris, Michael D.; Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 10-JAN-2003; Project End 30-NOV-2006 Summary: (provided by applicant): Bone is a complex system consisting of a carbonated apatitic calcium phosphate phase supported on a collagen-rich extracellular matrix. While the macroscopic properties of bone have been extensively investigated using different techniques in various biological systems, the early steps in bone tissue mineralization are not well understood. In an effort to characterize bone growth, numerous studies have been conducted to understand the chemical mechanisms involved in both de novo bone formation and bone remodeling. Despite this increased

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interest, an understanding of the processes governing early mineralization of bone is still incomplete. This proposal will use near-infrared Raman microspectroscopy and Raman imaging to study early mineralization in the mouse calvaria (the flat bones that comprise the top of the skull). The goal is to understand the steps leading to the deposition of new mineral and the chemical and physical transformations that the mineral undergoes during fetal and early postnatal development. Because Raman microspectroscopy is a relatively new tool in bone research, the work will begin with validation of protocols for Raman spectroscopy of bone tissue. The effects of standard specimen fLxing and embedding protocols and the potential Raman or fluorescence interference from a set of common histological stains will be examined. It is proposed that there will be few or no problems encountered beyond the known effects, such as protein cross-linking, of certain fixing protocols. If interferences due to the staining protocols occur, multivariate spectral and image processing will be used to overcome them. Because the progress of mineralization is accompanied by shifts in mineral spectral bands, the interpretation of small spectral band shifts will be put on a fawn foundation. In a subcontract to Central Michigan University, vibrational spectra (band positions and frequencies) of substituted hydroxyapatites will be computed by density functional theory and compared to Raman spectral measurements of model compounds (synthetic non-substituted and substituted hydroxyapatites) and on murine calvarial bone tissue. Systematic Raman imaging will be performed on calvarial sections harvested from normal mice just prior to the onset of mineralization (fetal day 15.5) until postnatal day 14. Raman imaging will be carried out at 1-day intervals during the prenatal period and at 2-day intervals during the postnatal period. Correlative immunohistological staining and Raman imaging will be used to understand the effects of bone sialoprotein and osteocalcin on the course of mineralization. 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

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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: REGULATION OF COLLAGEN MATRIX MINERALIZATION Principal Investigator & Institution: Yamauchi, Mitsuo; Director of Collagen Biochemistry Lab; Periodontology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 01-JUL-1993; Project End 30-NOV-2007 Summary: (provided by applicant): The long-term goal of this study is to understand the regulatory mechanisms of collagen matrix mineralization in bones and teeth. During the last grant period, we have partially characterized the unique aspects of collagen crosslinking, and specific tissue distribution as well as mRNA expression pattern of collagenbinding small leucine-rich proteoglycans (CB-SLRPs) in mineralized tissues. These and other findings have led us to hypothesize: 1. the covalent intermolecular cross-linking of type I collagen is involved in regulating the spatial aspect of mineralization, and 2. a collagen-binding proteoglycan, decorin (DCN), partially regulates the timing and quality of collagen mineralization. To test these hypotheses, we would like: 1a. To establish osteoblastic cell clones that synthesize low levels of lysyl hydroxylase-2 to switch the cross-linking pathway from mineralized to non-mineralized tissue phenotype, 1b. To characterize the lysine hydroxylation and cross-linking chemistries (type, quantity and molecular distribution) of collagen matrix, and the mineralization pattern produced by the clones in vitro and in vivo. 2a. To investigate the roles of DCN in collagen maturation and mineralization in vitro and in vivo by employing overexpression and antisense approaches in osteoblastic cell line. 2b. To characterize the matrix mineralization (collagen and mineral) in bones/dentin in DCN-deficient and DCN/biglycan-double deficient mice. 2c. To evaluate the effects of DCN-collagen interaction on collagen maturation in vitro. The data obtained from this study may provide insights into the regulatory mechanisms of collagen mineralization in bones and teeth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF CRANIALSUTURE MORPHOGENESIS Principal Investigator & Institution: Ogle, Roy C.; Professor; Neurological Surgery; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-FEB-1994; Project End 31-JUL-2004 Summary: (Adapted from the Applicant's Abstract): Premature fusion of the cranial sutures is the primary cause of many severe craniofacial abnormalities. The long term goal of this project is to understand how cranial sutures develop and resist osseous obliteration until neurocranial growth is complete. This renewal application focuses on the function of the fibroblast growth factor (FGF) signaling system in the development and fusion of sutures. The hypotheses are that certain FGFs released from bone matrix (FGF2), the suture cells, and the dura mater (other that FGF2 or 7) diffuse to the extracellular matrix of the developing suture. There the cells express fibroblast growth factor receptors (FGFRs) 1,2 and 3 in specific, overlapping patterns where they mediate signals for cellular activities required for suture morphogenesis-- proliferation, differentiation, or apoptosis. FGFR1 and FGFR2, negatively regulate growth of the bones and fibrous tissues, respectively. FGFRs may also signal apoptosis during

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remodeling of the suture. The cellular response to the FGFs may vary as a function of the available concentration of FGF, the types of FGFs present, and the repertoire of the FGFR(s) expressed. Obliteration of the suture may occur as a result of excess FGF differentiative signalling in the osteoblasts or loss of the proliferative suture stem cells. Specific aims to test the hypotheses include to may FGF and FGFr expression pattern during suture development and fusion (aim 1), characterize FGF signaling in formation and fusion of sutures in vitro (aim 2) and in vivo (aim 3), and investigate FGF/FGFR signalling pathways in primary suture and calvarial cells (aim 4). The study will employ the rat, in which the sutures are formed during fetal days 19-21 (F19-F21). Methodology includes immunohistochemical localization, in situ hybridization and PT/PCR analysis of mRNA of dissected tissues from nonfusing (coronal), fusing (posterior intrafrontal), and experimentally- induced fusing sutures. Suture development in vitro will be used to test the ability of appropriate FGFs to substitute for dura in preventing fusion. FGFs inhibitors of the FGFs and FGRFs (neutralizing antibodies and antisense oligonucleotides) and a specific inhibitor of tyrosine kinase activity of FGFRs, SU5402, will be employed in vitro and in vivo, delivered by bead implantation in F19 fetuses by ex utero surgery and to N1 neonates to block or cause suture fusion. In each case the extent of bone and suture growth and obliteration will be determined by histomorphometry. The cellular distribution pattern of FGFRs and markers of proliferation, osteogenic differentiation, and apoptosis will be determined by colocalization. Finally, isolated suture and osteoblastic cells will be used to test the appropriate FGF(s) over a range of concentrations for influence on proliferation and differentiation and potential intermediated in the tyrosine kinase signalling pathway in suture cells will be compared to those identified in fibroblasts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF DMP1 GENE EXPRESSION IN BONE AND TOOTH Principal Investigator & Institution: Chen, Shuo; Pediatric Dentistry; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 09-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Dentin matrix protein (DMP1) is an acidic phosphorylated protein that is an important component of the mineralized extracellular matrix of tooth and bone. Spatial-temporal expression patterns of DMP1 are highly restricted to mineralized tissues. Understanding the processes that regulate tissuespecific gene expression is an important fundamental issue in developmental biology. Currently, very little is known regarding the regulation of DMP1 expression during bone and tooth development. The purpose of this R03 proposal is to investigate through in vitro promoter studies the regulatory mechanisms of DMP1 gene expression in the highly specialized mineralized cells of bones and teeth versus other non-expressing, non-mineralizing cell types. Our preliminary studies have identified a novel element in the DMP1 promoter that potentially controls DMP1 gene expression in mineralizing versus non-mineralizing cells. DNA database analysis reveals that similar DNA consensus sequences are found in the promoters of a number of other dentin/bone genes. These in vitro studies will provide initial information to further define this novel cis-element and its function related to gene regulation. Our hypothesis is that the DMP1 gene expression in mineralizing versus non-mineralizing cells is regulated in part by a novel conserved cis-element through discrete interactions with corresponding transcription factors. In order to achieve this goal, two Specific Aims are proposed: 1) To determine consensus sequence(s) of the DNA-protein binding site by using selected and

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amplified binding and mutagenesis methods by electrophoretic mobility shift assay; 2) To determine the biological role of the consensus sequence(s) regulating DMP1 gene expression in the cell-specific manner by examining the cis/trans interactions using in vitro promoter-reporter analysis. Our proposed work is innovative because we have identified a novel DNA-protein binding element in DMP1 gene promoter that is conserved in the promoters of other dentin/tooth collagenous and non-collagenous genes. Results of these studies are expected to provide the foundation for in vivo studies investigating the molecular mechanisms of spatial-temporal expression patterns of DMP1 in bones and teeth as well as mineralizing and non-mineralizing tissues. These experiments will also provide significant new knowledge concerning the basic mechanism of mineralized tissue gene regulation. These studies will therefore make an important contribution toward an overall understanding of the molecular basis of bone/tooth specific gene expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF MINERALIZATION IN SKELETAL TISSUES Principal Investigator & Institution: Kirsch, Thorsten; Associate Professor; Orthopaedics; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 28-SEP-2002; Project End 31-AUG-2004 Summary: Biomineralization plays a crucial role during skeletal and tooth development and allows skeletal tissues to exert their proper functions during adulthood. Despite its obvious importance little is known about its regulation. Regulation of mineral formation in tissues is critical for their proper function. For example, excessive mineral deposition accompanies atheriosclerosis and osteoarthritis. In the latter, crystal formation in the articular surface area may play a major role in the onset of inflammation and the progression of joint destruction. On the other hand, loss of mineralization as seen in osteoporosis leads to fragile bones and bone fractures. Matrix vesicles, small membrane-enclosed particles, have the critical role of initiating mineralization in many tissues, including craniofacial bones, long bones, cartilage and dentin. While it is well established that these particles are released from the plasma membrane, it is unclear how the release of matrix vesicles is regulated and how, following their release into the extracellular matrix, vesicles initiate mineral formation. In our Preliminary Studies it is shown for the first time that only cells undergoing mineralization release annexins II and V-rich, Ca2+/Pi complexes (nucleational core)-containing matrix vesicles which are able to initiate mineralization, while nonmineralizing cells release vesicles which do not mineralize. In addition, we provide evidence that annexins II and V form Ca2+ channels in matrix vesicles, allowing Ca2+ influx into these particles and the formation and growth of the first intralumenal crystals. Release of these annexins II and V-rich matrix vesicles is accompanied by increases in annexins II and V expression and cytosolic Ca2+ concentration, [Ca2+]i. Our hypotheses are that (i) increases in both cytosolic Ca2+ concentration and annexins II and V expression are required for the release of mineralization-competent matrix vesicles, and that (ii) annexins II and V cooperate with the nucleational core to enable Ca2+ influx into the vesicles, formation of the first mineral phase and initiation of mineralization. This project will test these hypotheses directly by the use of diverse experimental strategies, including cell culture, Ca2+ channel studies, site-directed mutagenesis and expression of mutated annexin molecules. The present proposal will provide new insights into some of the most intriguing and important features which regulate mineralization in vivo. This information will be of critical importance for the prevention of uncontrolled mineralization in several tissues during pathological conditions.

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

Project Title: REGULATORY CHONDROCYTES

MECHANISMS

OF

GROWTH-PLATE

Principal Investigator & Institution: Olney, Robert C.; Assistant Professor of Pediatric Endocri; Nemours Children's Clinic 807 Children's Way Jacksonville, Fl 322078482 Timing: Fiscal Year 2002; Project Start 28-SEP-1999; Project End 31-AUG-2004 Summary: There is a gap in the field of growth research. There is a large body of work on growth on the whole body level in humans. There is also a large and rapidly growing body of work on growth-plate regulation in animals. There is little data, however, on growth- plate regulation in humans. We propose to bridge this gap. Linear growth is the result of the lengthening of the long bones of the skeleton; a process that occurs within the epiphyseal growth-plates. The regulation of longitudinal growth on the cellular level remains poorly understood, due to the difficulty of studying growth-plate chondrocytes in vitro. Recently, new techniques have been described that now permit us to study these cells. We will study human cells to answer basic questions about the hormonal regulation of the growth-plate and hence, linear growth. Growth-plate chondrocytes undergo two distinct phases of growth; a proliferative phase and a differentiation or "hyper-trophic" phase. These phases are closely linked and must be tightly regulated. This project has the following specific aims: A) to outline the effects of known growthregulating factors on human chondrocyte proliferation and differentiation and B) to identify possible regulatory pathways intrinsic to the growth-plate. These aims will be met by testing four hypotheses. 1) GH directly increases expression and production of IGF-I in human growth- plate chondrocytes. 2) IGF-I is the primary stimulatory factor for human growth-plate chondrocyte proliferation. 3) Other factors, independent of GH and IGF-I, enhance growth-plate chondrocyte hypertrophy and differentiation. 4) IGF-I's effect is modulated by a factor(s) produced by hypertrophic chondrocytes, creating a negative feedback loop linking the two phases of chondrocyte growth. These hypotheses will be tested using chondrocytes from human growth-plates obtained at the time of epiphysiodesis. The cells will be fractionated by discontinuous Percoll gradients and cultured in alginate gel beads. Proliferation will be evaluated by [3H] thymidine uptake; differentiation by collagen type X expression and alkaline phosphatase production. A variety of known and suspected growth factors will be added to the cells to determine their role in growth-plate regulation. We propose to take what is known about animal growth-plate regulation and determine its relevance and importance in the human growth-plate, and to expand our knowledge of growth regulation in general. By identifying how these hormones alter the regulation in the growth-plate, we should be able to identify factors that can counteract them when their deficiency or excess causes growth-failure. These may represent future therapies for the treatment of growth failure. In addition, clinical genetics is identifying the mutations that result in osteochondrodyplasias. We will be in a position to study the role these genes play in growth-plate regulation and possibly identify therapeutic options. Conversely, by identifying the important regulators of the human growth-plate, we will provide clues to direct the search for the genes responsible for some of the osteochondrodysplasias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF DLX-5 IN CHONDROCYTE DIFFERENTIATION Principal Investigator & Institution: Kosher, Robert A.; Professor; Biostructure and Function; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806

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Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The process of endochondral ossification in which the bones of the limb are formed after generation of cartilage models is dependent on a carefully regulated program of chondrocyte maturation. Identification of the genes and signaling molecules that control hypertrophic chondrocyte maturation and the regulatory interactions among them is crucial to understanding bone growth and development. The goal of this research is to investigate the hypothesis that the homeodomain transcription factor Dlx5 is a key positive regulator of chondrocyte maturation during endochondral ossification, and to unravel the relationships between Dlx5 and other factors involved in controlling the process. Dlx5 is expressed during the conversion of immature proliferating chondrocytes to post-mitotic prehypertrophic chondrocytes, a critical step in maturation. Retroviral misexpression of Dlx5 during differentiation of the skeletal elements of the chick limb in vivo results in formation of severely shortened skeletal elements that contain excess numbers of hypertrophying chondrocytes, expanded and upregulated domains of expression of some molecular markers of hypertrophic differentiation including osteopontin and type X collagen, and expansion of mineralized cartilage matrix. Dlx5 misexpression also markedly reduces cell proliferation concomitant with promoting hypertrophic maturation. These results suggest Dlx5 positively regulates maturation at least in part by promoting conversion of immature proliferating chondrocytes to hypertrophying chondrocytes. The role of Dlx5 in chondrocyte maturation will be further investigated by examining effects of Dlx5 misexpression in the chick limb on expression of additional markers of hypertrophic maturation, and determining if chondrocyte maturation is promoted when Dlx5 misexpression is specifically targeted to the cartilage models of the limbs of transgenic mouse embryos. It will also be determined if maturation is promoted by Dlx6, a putative functionally redundant member of the Dlx family. The mechanism of Dlx5 regulation of maturation will be investigated using gain- and loss-of-function approaches in limb mesenchymal cell and chondrocyte model culture systems. The possible regulatory relationships between Dlx5 and other positive regulators of chondrocyte maturation including RMPs, Cbfal/Runx2, and (-catenin-mediated Wnt signaling will be investigated. A variety of molecular agonists and antagonists will be used to begin to unravel how Dlx5 and the other factors interact and cooperate in regulating hypertrophic maturation. It will also be determined if Dlx5 participates in transcriptional regulation of the osteopontin, bone sialoprotein, and type X collagen genes during chondrocyte maturation. The possibility that Dlx5 interacts and cooperates with the BMP signaling pathway and/or Cbfal/Runx2 in the transcriptional regulation of the promoters of one or more of these candidate target genes will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ENDOTHELINS IN SKELETAL PATTERNING IN ZEBRAFISH Principal Investigator & Institution: Schilling, Thomas F.; Assistant Professor; Developmental and Cell Biology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Adapted from the Investigator's Abstract): Craniofacial defects result from disruptions of the normal mechanisms that control head development. Thus understanding the basis for inherited craniofacial disorders requires knowledge of the embryonic molecular and genetic processes that direct pattern formation in the head. These include the tissue interactions that establish skeletogenic mesenchyme, its condensation and differentiation into cartilages and bones, and their interconnections to

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form a functional skeletal network. This proposal examines these issues using the genetics and embryological advantages of zebrafish as a model. Zebrafish embryos form a simple, segmentally organized pharyngeal skeleton, where homologies with human skeletal elements are recognizable, and many of the genes that pattern these segments have been conserved between fish and humans. It is thought that a major component of patterning within each pharyngeal segment is endothelin-1 (Et-1), a signal that directs patterns of chondrogenesis and osteogenesis. Experiments are proposed to dissect the role of this signal using a set of zebrafish mutants including one mutant in Et-1 itself as well as mutants and antagonists of Et receptors. Aim 1 is to characterize genes of the ephrin and eph receptor tyrosine kinase families that we have implicated in controlling neural crest morphogenesis and their responses to Et-1. Aim 2 is to analyze one mutant called schmerle, which phenotypically resembles loss of Et-1 function, in more detail and to clone its underlying genetic basis. Aim 3 focuses on defining which specific tissue interactions require Et-1, between either the pharyngeal epithelium or mesoderm and the skeletogenic neural crest, by using cell transplantation in Et-1 mutants to dissect the biochemical basis for skeletal patterning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF FGF SIGNALING IN BONE DEVELOPMENT Principal Investigator & Institution: Basilico, Claudio; Professor and Chairman; Microbiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-DEC-2005 Summary: Skeletal morphogenesis is controlled by a network of signaling molecules that first determine the fate of undifferentiated stem cells of the mesenchymal lineage and then regulate the proliferation and differentiation of committed osteogenic cells. Among the signaling molecules which influence bone morphogenesis, fibroblast growth factors (FGF) and their cognate receptors (FGFR) have been recently shown to play a major role both in endochondral and intramembranous bone formation. Activating mutations in FGFR3 have been shown to be responsible for several genetic forms of human dwarfism, and other activating mutations in FGFR1, FGFR2 and FGFR3 have been linked to many craniosynostosis syndromes. Mouse genetic experiments have confirmed that unregulated FGF signaling causes bone malformations and suggested that FGFs may act as negative regulators of bone growth. However, the molecular mechanisms through which FGFs influence the proliferation of differentiation of osteogenic cells (e.g. chondrocytes and osteoblasts) remain to be elucidated. The goal of this research project is to study the response to FGF signaling of chondrocytes. We have shown that FGF treatment inhibits the proliferation of chondrocytes, and that this inhibition requires activation of the STAT-1 pathway. Using organ cultures of metatarsal bones rudiments of E15 murine embryos we have also shown that FGFs regulate chondrocyte proliferation and bone development and that this effect also requires STAT-1. We wish to understand the molecular mechanisms underlying the growth inhibitory response of chondrocytes to FGF signaling and how FGF signaling affects chondrocyte proliferation and differentiation. We will study 1) the signal transduction pathways activated by FGF receptors in chondrocytes with an emphasis on the mechanisms leading to activation on STAT-1, which plays an essential role in the chondrocyte response to FGF; 2) how the progress of the differentiation program which takes place during organ culture of bone rudiments from murine embryos is affected by FGF treatment or by molecules in the FGF signaling pathways; 3) the effect of modulating FGF signaling on bone morphogenesis in vivo, using transgenic and

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knockout mice, to verify how STAT-1 influences long bone development and chondrodysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF IL18 IN SPREAD OF PROSTATE CANCER TO BONE Principal Investigator & Institution: Russell, Pamela J.; University of New South Wales Sydney 2052, Australia Sydney, Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Prostate cancer (PCa), a major health problem, is now the most commonly diagnosed male malignancy. In 85% of cases, PCa spreads to and grows in the bone, causing a breakdown in normal bone biology and extreme pain. The role of factors made by immune cells called immune modulators in allowing PCa to grow in bone is not known. This study investigates the interaction between PCa, bone and immune cells. Based on the hypothesis that overexpression by PCa cells of the immune modulator, interleukin-18 (IL18) inhibits bone degradation (osteoclastogenesis) and bone building (osteoblastogenesis), and induces an immune response with release of the modulator, interferon gamma, to prevent bone growth, experiments will be performed to see if IL18 can inhibit the PCa growth in the bone in animal models. Specific aims are to construct mouse PCa cells that overexpress and secrete IL18 (PCaIL18), and to test their effects on activating immune cells, (cytotoxic T cells and Natural Killer cells that kill tumor cells) and on bone cell proliferation and differentiation in tissue culture and in mouse models in which PCa-IL18 are implanted in the bone, or can spread to the bone. The ability of PCa-IL18 cells to stimulate an immune response and to suppress tumor growth in the bone will then be assessed. Immune cells from the experimental mice, will be characterized (FACscan) and assessed for their ability to kill tumor cells in tissue culture. In the circulation, such immune cells would kill cancer cells preventing their spread to the bone. As IL18 can stop PCa cells from entering bone by stimulating T cells to secrete interferon gamma, and by increasing expression of osteoprotegerin (OPG) by osteoblasts, both of which inhibit osteoclastogenesis, the levels of these modulators in mice implanted with PCa-IL18 will also be measured. The effects of PCa-IL18 on bone biology will be assessed by X-ray analysis of the bones (Faxitron analysis) and by morphological studies (histomorphometry). Lastly, the ability of PCa-IL18 to inhibit the growth of established PCa deposits in bone will be assessed. These PCa deposits are engineered to fluoresce allowing their visualisation in the bones. This study will clarify the relationship between PCa spread and the bone microenvironment. If IL18 inhibits PCa growth in bone, its delivery by adenovirus vectors into the prostate of patients prior to radical prostatectomy may prevent the development of bone metastasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLES OF CHORDIN AND NOGGIN IN CRANIOFACIAL DEVELOPMENT Principal Investigator & Institution: Klingensmith, John A.; Cell Biology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 30-NOV-2006 Summary: (Adapted from the Investigator's Abstract): Craniofacial development is a uniquely complex morphogenetic process in vertebrate ontogeny, creating evolutionary plasticity but also developmental vulnerability. The head and face are derived from many tissue precursors, which require a precise orchestration of pattern formation, cell

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migration, proliferation, apoptosis, and inductive interactions to achieve a functional end. Many of these events are mediated by secreted cytokines, whose activity must be precisely regulated to preclude inappropriate cellular responses. Bone Morphogenetic Proteins (BMPs) are a family of secreted ligands which have potent effects on many aspects of craniofacial development, particularly the closely related proteins BMP2 and BMP4. Their activity is thought to be important in the growth or patterning of such diverse tissues as the brain, the skull, the pituitary gland, the teeth, and the precursors of the face. Research from Drosophila and Xenopus indicate that BMP2/4 signal transduction is regulated in large part by antagonistic proteins such as Chordin (Chd) and Noggin (Nog). In frogs, Chd and Nog promote anterior development, and Chd is essential for normal head development in zebrafish. Preliminary work described in this proposal shows that these genes are required for development of the mammalian head. Lack of Chd in an inbred genetic background results in a group of craniofacial skeletal and soft-tissue defects involving neural crest derivatives, similar to those seen in certain human syndromes. Chd and Nog together are required early for head development, but are also involved specifically in development of the forebrain, mouth, nose, mandible, numerous bones of the skull, and other craniofacial tissues. The major aims of this proposal are: 1) to characterize the spatiotemporal expression patterns of Chd and Nog to clarify their roles in craniofacial development; 2) to determine the critical sites and times of action for Chd and Nog in head induction using embryonic stem cell chimeras and tissue recombinants; 3) to determine the functions of these genes in growth and patterning of craniofacial tissues; and 4) to assess whether ectopic BMP signaling reproduces the craniofacial defects of the mutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECOND HARMONIC GENERATION IMAGING MICROSCOPY Principal Investigator & Institution: Campagnola, Paul J.; Assistant Professor; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Type I collagen is the most abundant extra-cellular matrix protein being the primary structural component of bone, skin tendon and to a lesser extent blood vessels. Although its biochemical and ultrastructural properties are well understood, there are still gaps in our knowledge the precludes genotype/phenotype predictions in diseases affecting its primary structure or its gene regulation. This proposal will evaluate a new method for visualizing extra-cellular matrix Type I collagen fibers in cell culture or in intact tissues in real time utilizing second harmonic generation (SHG) imaging microscopy. This is a new and novel imaging technique that can be used to probe endogenous structural proteins with high contrast without the need for exogenous labels. Furthermore, this method provides intrinsic 3-dimensionality and is ideal for intact tissues since samples (up to 1 mm) can be imaged in situ. This method provides resolution on the order of 500 nm and is ideal for probing higher-level organization of collagen fibrils and fibers. SHG imaging will allow the direct visualization of some of the physical properties of the collagen triple helices. Studying the organization of collagen fibrillar structure by SHG imaging will in fact complement existing ultrastructural (X-ray diffraction and electron microscopy) and non-imaging (NMR, CD) methods. The value of this approach will be assessed in two disease of type I collagen that are a consequence of either under accumulation (osteogenesis imperfecta, OI) or excessive accumulation (tight skin, Tsk) of type I fibers in bone or skin respectively. In both cases, the relationship between the underlying genetic abnormality and the severity of the disease is not understood and a unique insight into this relationship may

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come from this method. We will first establish quantitative measurements of the collagen fibers in the ECM of normal murine tissues by SHG where we will utilize both tissue culture cells, and as well as tissues and decalcified bones from wild type mice. This methodology may ultimately become a powerful clinical tool both in terms of predictive value of musculo-skeletal diseases as well as in the assessment of the efficacy of drug and gene therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING MOLECULES AND LONG BONE FORMATION Principal Investigator & Institution: Pacifici, Maurizio; Professor; Orthopaedic Surgery; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 30-NOV-2005 Summary: Long bones are morphologically complex structures. When they begin to form in the embryo, they are entirely cartilaginous. The chondrocytes then undergo maturation, involving a proliferative, prehypertrophic and hypertrophic phase. Once formed, hypertrophic cartilage is invaded by perichondrial cells and replaced by endochondral bone. Perichondrial cells produce also an intramembranous bone collar around prehypertrophic and hypertrophic cartilage that determines size and shape of the shaft. Thus, long bone formation involves a multi-step chondrocyte maturation process, intramembranous and endochondral ossification, and topographically related events in cartilage and perichondrial tissues. It is far from clear how all these processes and events are regulated. Indian hedgehog (IHH) and retinoids are powerful signaling molecules. Studies from this and other groups have suggested that IHH, a product of prehypertrophic chondrocytes, influences chondrocyte proliferation and intramembranous bone collar formation and inhibits hypertrophy. On the other hand, retinoids which are present in hypertrophic cartilage and surrounding perichondrial tissue, stimulate hypertrophy and endochondral bone formation. These and many additional data indicate that IHH and retinoids are signaling molecules regulating steps in chondrocyte maturation and coordinating events in cartilage and perichondrial tissues. Our central hypotheses are: (A) IHH is a direct inducer of chondrocyte proliferation and intramembranous collar formation, and an inhibitor of chondrocyte hypertrophy; and (B) Retinoids shut off IHH expression, stimulate chondrocyte hypertrophy, and permit endochondral ossification. This project aims to determine how IHH and retinoids exert these distinct but interrelated roles and thus allow normal progression of long bone development. We will use avian and murine animals, microsurgical limb manipulations, and cell cultures to analyze: (a) expression and function of receptors and nuclear mediators of IHH and retinoid action; (b) pathways of synthesis, degradation and delivery of retinoids; and (c) effects of ectopic protein expression. We will also determine whether abnormalities in above mechanisms underlie the defects in long bones seen in IHH- null mice. The results will provide much needed information on the regulation of long bone formation, and will have relevance to questions of skeletal growth, fracture repair and congenital conditions of cartilage and bone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STEM CELL THERAPY FOR DISEASES OF BONE IN A MOUSE MODEL Principal Investigator & Institution: Niyibizi, Christopher; Associate Professor; Orthopaedic Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2006 Summary: The focus of the present proposal is to utilize a mouse model of osteogenesis imperfecta (oim) as a model system to evaluate the potential of the bone marrow derived mesenchymal stem cells (BMSCs) to engraft and participate in repair and regeneration of bone. The mouse has a natural occurring mutation that results in nonexpression of proa2(I) chains leading to the accumulation of al(I) homotrimers in tissues. The mouse exhibits osteopenia, cortical thinning and easy fracturing and is an excellent model for evaluating the potential of BMSCs as targets for the treatment of genetic and non-genetic diseases of bone. Recent clinical trial by Horwitz et al. using whole marrow in children with a severe form of OI, demonstrated that BMSCs may offer treatment options for O1. Therefore, the hypotheses to be tested are: BMSCs from normal donor mice administered systemically or locally into syngeneic recipient mice will engraft in the bones of the recipient mice, synthesize authentic bone extracellular matrix and contribute to the structural integrity of the host bone. The following specific aims will be used to test these hypotheses: 1) Demonstrate that the cells infused into oim mice will engraft in bone and in fracture sites created in oim mice 2) Demonstrate that the cells which engraft in bone differentiate into osteoblasts and synthesize the authentic bone extracellular matrix and 3) Demonstrate that the cells that engraft in bone contribute to the structural integrity of bone. To accomplish the above aims, BMSCs will be established from femurs and tibiae of normal donor mice and either marked with retroviruses expressing LacZ or GFP genes to aid in cell tracking or unmarked prior to infusion in oim mice. The fate of the infused cells will be tracked by following expression of the marker genes in tissue and by fluorescent in situ hybridization (fish). Differentiation of the transplanted cells into osteoblasts in vivo will be determined by co-localization of osteocalcin and marker genes and also by in situ hybridization. Synthesis of authentic extraceltular matrix by the infused cells will be analyzed by the determination of the presence of type I collagen comprised of 1 and 2 heterotrimers. Structural integrity of the host bone, will be determined by histophotometry, crosslinking, and collagen content and bone mineral density. The proposed studies may lead to the development of better treatments for genetic and non-genetic diseases of bone based on BMSCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL CONSEQUENCES OF POST-YIELD BEHAVIOR OF BONE Principal Investigator & Institution: Keaveny, Tony M.; Professor; Mechanical Engineering; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 15-SEP-1992; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): In this renewal request, the applicants continue to seek to investigate the structural consequences of post-yield behavior of bone, which has important biomechanical implications for understanding the etiology of age-related osteoporotic spine fractures and perhaps developing new diagnostics and treatments. Their previous work has shown that there are substantial reductions in stiffness and strength of trabecular bone when overloaded, i.e., substantial

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mechanical damage occurs. The mechanisms of this damage are unclear, but involve microdamage and fracture of individual trabeculae. At the whole vertebral level, significant permanent deformations result from overloads. Together, these findings provide a plausible mechanism for development of clinical spine fractures based on accumulative effects of isolated overloads. New preliminary data point towards collagen cross-linking as being a significant source of age-related brittleness in bone that would affect such a mechanism. They now propose to investigate age-related changes in brittleness and damage behavior, in a hierarchical manner, from the collagen to the whole vertebral body. Further, they intend to demonstrate how aging can change parameters such as collagen cross-linking and other structural assays of the collagen molecule, percent mineralization, trabecular architecture, and trabecular bone volume fraction. Biomechanical test experiments on human cadaveric material to determine mechanical damage and ductility will be performed on cortical bone, demineralized cortical bone, trabecular hard tissue, trabecular bone, and whole vertebral bodies, spanning an age range of 20-100 years. This will be accompanied by a comprehensive set of biochemical and microstructural assays. Finite element computer simulations on the effects of bone brittleness, trabecular architecture, and bone volume fraction will also be performed to help interpret and generalize the experimental results and so separate out the effects of the different explanatory variables. Specifically, their hypotheses are that: 1) significant age changes occur in collagen in both cortical and trabecular bone; 2) these cause both types of bone to become more brittle; 3) aging causes more damage and permanent deformations to develop when the bone is subjected to an isolated overload beyond its elastic regime. This is true for trabecular bone and the whole vertebral body; and 4) these changes in post-yield mechanical properties of the bone are associated with changes in the collagen biochemistry, independently of factors such as mineralization and trabecular architecture. This work is intended to provide a mechanistic description of how older bones are damaged more after an isolated overload than younger bones, and identify mechanisms which dominate such behavior. It is suggested that results should lead, therefore, to improved understanding of vertebral fracture etiology, and may motivate development of new drug treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF MATRIX PROTEINS IN TEETH AND BONES Principal Investigator & Institution: Weiner, Stephen; Weizmann Institute of Science Box 26 Rehovot, 76100 Timing: Fiscal Year 2002; Project Start 01-MAR-1985; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract): This research program aims at improving understanding of structure - mechanical function relations of whole human teeth and adult human osteonal bone. The holistic approach to understanding tooth function is inspired by the observation made by the applicant that a zone some 200 microns thick beneath the dentino-enamel junction (DEJ) absorbs most of the applied stress. In essence it functions as a cushion separating the stiff enamel cap from the bulk crown dentin. Proposed is to develop and apply two complimentary new methods for mapping strain in tooth crowns, and relating this to structure. Strain will be mapped as a function of humidity variations using an environmental scanning electron microscope and holographic interferometry to map strain variations when whole teeth are subjected to compressive forces similar to those in mastication. Also to be investigated are the effects of cavities and restorations on strain distribution. Variations in sub-layer thicknesses of a lamellar unit within an osteonal bone will be investigated to determine

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if this is the variable that reflects prevailing stress fields at the time of formation. osteonal bone differs in mechanical behavior from circumferential lamellar bone mainly in the manner in which osteonal bone absorbs damage and fractures. The mechanical properties of small portions from different parts of osteonal bone of humans of different ages will be studied by drilling out cylinders of 100 to 200 microns in diameter and measuring their elastic and other properties. The aim is to understand the extent of variation within a bone, and the structural basis for the measured variations. The results will improve understanding of the aging process of human osteonal bone, and will allow better evaluation of possible effects that treatments for osteoporosis may have on mechanical function of bone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURFACE-CHARGED HA/TIO2 ULTRATHIN FILM Principal Investigator & Institution: Liu, Jiankai; Chemat Technology, Inc. 9036 Winnetka Ave Los Angeles, Ca 91324 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): A functionally graded HA/TiO2 ultrathin film (tens manometers), with a charged surface, on pure titanium Dental implant will be developed using functionally graded /self-assembled sol-gel coating process. A threelayer functionally graded coating structure which consists of sub-layers of 100%Ti - 0% HA, 50%Ti - 50% HA, and 0%Ti - 100%HA enhance the adherence of HA film to Titanium implant surface. Ionic self-assembled process provides ultrathin coating (tens nm or less) for each layer with positive/negative charged surface, this induces an early and accelerated osteoblast adhesion thereby reducing the healing time during implantation due to the maintenance of the rough surfaces of the commercial titanium implants and electrically polarization. Sol-gel low temperature processing yields pure HA coating, which reduce the dissolution of non-HA phosphate calcium in body solution. These advantages should benefit the patients with inadequate bones or significant load bearing implant designs, for whom no definite treatments are available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TGF-BETA SIGNALING IN CHONDROCYTE DIFFERENTIATION Principal Investigator & Institution: Serra, Rosa A.; Assistant Professor; Cell Biology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 30-SEP-1998; Project End 31-MAR-2008 Summary: (provided by applicant): Endochondral bone formation is complex and requires the coordination of several signals. Defects in the regulation of chondrocyte differentiation can result in chondrodysplasias and osteoarthritis. Factors that coordinate the formation of endochondral bones are just beginning to be defined. The long-term objective of this study is to understand, at the molecular level, the signals involved in the regulation of endochondral bone formation and how alterations in these signals contribute to diseases of the skeletal system with emphasis on the mechanism of action of members of the Transforming Growth Factor-beta (TGF-beta) superfamily. Members of the TGF-beta superfamily are secreted growth factors that regulate many aspects of growth and differentiation. Expression of a dominant-negative form of the TGF-beta type II receptor in mouse skeletal tissue results in increased terminal chondrocyte differentiation and osteoarthritis, suggesting TGF-betas act to regulate chondrocyte differentiation in vivo. During the previous granting period we used an embryonic metatarsal organ culture model, which can be easily manipulated, to dissect

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out interactions between specific signaling cascades. Our studies suggested that the perichondrium mediates the effects of TGF-beta on both the exit of chondrocytes from the cell cycle through an unknown factor, and their subsequent differentiation through the Indian Hedgehog-Parathyroid Hormone related Peptide feedback loop. Based on these observations and potential clinical significance to chondrodysplasias and osteoarthritis, studies to determine the mechanistic basis of how TGF-beta regulates cartilage differentiation will continue through the following Specific Aims: (1) to test the hypothesis that TGF-beta2 acts in a negative feed back loop with Ihh and PTHrP to regulate hypertrophic differentiation; (2) to determine if differentially modified forms of Hedgehog proteins regulate specific aspects of endochondral bone formation; (3) to test the hypothesis that TGF-beta acts on the perichondrium through the Insulin-like Growth Factor (IGF) and/or Fibroblast Growth Factor (FGF) signaling systems to regulate chondrocyte proliferation; and (4) to determine the role of TGF-beta signaling directly in chondrocytes using conditional deletion of the TGF-beta receptor in transgenic mice. The results of these studies will enhance our understanding of molecular events involved in development and maintenance of the skeletal system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE EFFECT OF DELAYED MENARCHE ON PEAK BONE MASS IN RATS Principal Investigator & Institution: Yingling, Vanessa R.; Biology; Brooklyn College 2900 Bedford Ave New York, Ny 11210 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): This project will provide a foundation for future investigations regarding the optimization of peak bone mass obtained during adolescence. Osteoporosis, once thought to be a natural part of aging among women, is no longer considered age- or gender-dependent. Low bone mass in young women has emerged as a crucial factor that may contribute to the development of osteoporosis. Studies have reported bone densities in young athletic women similar to 51-year-old women. In a recent study, 72% of amenorrheic athletes had bone densities that met the diagnostic criterion for osteopenia or osteoporosis. Multiple factors have been found to correlate with low bone mass in young women including low estrogen scores and increased age at menarche. Therefore, the effect of delayed estrogen levels during bone development may decrease the peak bone mass in young adults and lead to an increase risk of fractures later in life. Few studies have been focused on the relationship between delayed menarche and peak bone mass. The aim of this research is to develop an animal model that will delay menarche and, in turn, alter peak bone mass. Rats will be injected with GnRH antagonists to delay the increase of estrogen levels prior to reproductive maturation. GnRH antagonists will be withdrawn at age 8 weeks. Bone slices of rat tibiae and lumbar spine will be analyzed using histomorphometric measurements and compared between groups. Cross-sectional slices of the tibia midshaft will be analyzed. Specifically, cross-sectional area and the polar moment of inertia will be measured. Ash content values of bones will be measured to assess bone quality (mineral content). Blood will be taken from the tail vein bi-weekly and serum estrogen levels (pg/mL) will be measured using an estradiol ultra-sensitive double antibody RIA. LH and FSH measures will be measured using ELISA kits. All groups will be sacrificed by anesthesia overdose at 24 weeks of age. A one-way ANOVA will be used for this study with a significance level of 0.05. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF NEURAL CREST IN FACIAL PATTERNING Principal Investigator & Institution: Schneider, Richard A.; Assistant Professor; Orthopaedic Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): My long-term career objective is to investigate the cellular and molecular bases for normal and abnormal facial development. My research will provide a foundation for generating biologically based therapies to treat facial malformations in humans. To prepare for my career, I have received multidisciplinary training in embryology, anatomy, developmental molecular biology, and craniofacial anomalies. Through this diverse background I have acquired skills for studying complex cellular and molecular mechanisms that pattern the developing face. Future progress in understanding normal and abnormal facial morphogenesis will come from discovering and experimentally manipulating molecular and cellular signals that pattern the skeletal, muscular, nervous, and vascular systems of the head. Therefore, in order to provide a substantial contribution to this area of research, I am focusing my work on the regulation of cell differentiation, which is an essential component of craniofacial development. Disruptions to this process result in a range of human birth defects. For example, premature cell differentiation within the osteogenic front of cranial sutures causes craniosynostoses. Conversely, a delay in differentiation of median edge epithelium leads to clefting of the secondary palate. Thus, the timing of differentiation among multiple populations of embryonic cells is a prerequisite for normal facial patterning. Cellular and molecular mechanisms through which cranial populations of neural crest, ectoderm, and mesoderm learn when to differentiate into discrete facial structures such as bone, epidermis, and muscle are unknown. I hypothesize that in the developing face, neural crest cells regulate their own temporal differentiation as well as that of ectoderm and mesoderm. To test this hypothesis, I will perform a series of neural crest transplants between two avian species that have significantly different maturation rates, which will alter temporal information being conveyed among populations of donor and host cells. Using a variety of morphological, cellular, and molecular approaches, my analyses will determine whether donor neural crest-derived cartilages and bones, as well as host-derived epidermal and muscular structures develop on a timetable of the donor, host, or a combination of both species. This project is significant in using a novel approach to investigate regulation of facial growth and will provide valuable insights on birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TOGAVIRUS TROPISM FOR BONES, JOINTS, AND CNS Principal Investigator & Institution: Heise, Mark T.; Microbiology and Immunology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: Togavirus infection of humans is characterized by acute and persistent arthritis/arthralgia, as well as viral encephalitis. Infection of adult mice with S.A.AR86, an alphavirus in the family Togaviridae, provides an excellent and unique model system to examine the molecular basis for both of these human disease pathologies. Attractive features of these models include: a) S.A.AR86 and related viruses cause acute and persistent arthralgia in humans. b) We have sequenced the genomes of S.A.AR86 and several of its closest relatives, constructed an authentic S.A.AR86 infectious cDNA clone,

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and successfully utilized expression systems based on S.A.AR86 for in vitro and in vivo experiments. c) Preliminary data demonstrated acute S.A.AR86 tropism for mouse bone and joint tissue following peripheral inoculation and persistence in these tissues for at least 3 months. d) Unlike other members of the Sindbis-group of alphaviruses, S.A.AR86 is neurovirulent in mice of all ages, and this phenotype maps to the viral nonstructural genes responsible for RNA synthesis. We propose the following Specific Aims. 1) Identify cellular targets of S.A.AR86 replication within bone/joint tissue, characterize S.A.AR86 persistence within these tissues, and evaluate other arthritis/arthralgia associated Togaviruses, including rubella and Ross River virus, for replication and/or persistence in bone/joint tissue. 2) Nine putative genetic determinants of neurovirulence within the nonstructural genes will be evaluated by changing these codons within the S.A.AR86 genome to the codons found in non-neurovirulent viruses and screening for loss of neurovirulence. In addition, the candidate S.A.AR86 codons will be introduced into non-neurovirulent virus genomes and screened for gain of virulence. 3) The mechanism(s) by which mutations modulate neurovirulence in adult mice will be examined using the nonstructural gene mutants identified in Aim 2, as well as a mutation at nsP1 538, which has already been identified, cloned and partially characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOOLS FOR TISSUE ENGINEERING TOOTH STRUCTURE Principal Investigator & Institution: Denbesten, Pamela K.; Professor and Chair; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-1991; Project End 31-JAN-2007 Summary: The main objective of Project 11, Tools for Tissue Engineering Tooth Structure, is to make a mouse model applicable to tissue engineering of dental hard tissues. We seek to understand how the structure and properties of mouse dentin are related to human dentin. Second, we must understand how biological factors acting in the in vivo model are related to actions in vitro, as tissue engineering strategies often require tissue formation in culture and subsequent implantation. These premises led to our objectives aimed at developing tissue engineering tools for dental hard tissues. We will determine: 1) if the mouse model is relevant to human dental hard tissues; and 2) if members of the TGF-B superfamily of growth factors can provide insight into dental tissue mineralization processes. The understanding of this mineralization process is prerequisite to developing tissue engineering approaches in restorative dentistry. In order to understand how TGF-B affects relevant cellular activity, incisors and molars of transgenic mouse models with altered production of or response to, TGF-B in odontoblasts and cementoblasts, as well as cell cultures will be used. Initially, we will study two mouse lines, one that expresses a dominant negative form of the type II TGFB receptor (IIRDN mice), and the other that over expresses TGF-B2, both driven by the osteocalcin promotor. Based on previous findings in the bones of these mice and our preliminary studies of their teeth, it is expected that the tooth phenotype of TGF-B2 mice to be inverse of that found in IIRDN mice. The specific aims are: 1) To characterize the structural, biomechanical, and biochemical properties of mouse teeth to validate their use as models of human teeth; 2) To determine the effect of TGF-B on matrix metabolism and mineralized tissue architecture by using transgenic mice with altered production of, or response to, TGF-B; 3) To determine the role of TGF-B in tissue repair by examining reparative dentin formation in IIRDN, and TGF-B2 transgenic mice; 4) To determine the effects of TGF-B1 and B2 on proliferation and differentiation of pulp stem cells in vitro. These studies will help determine how TGF-B affects normal dentin/cementum

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formation through odontoblast/cementoblast responsiveness, if cementum turnover is similar to that of bone, and how the effects of TGF-B on matrix production are related to the physical properties of mineralized tissues, as well as provide insight into effects of these growth factors in vivo and in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VESTIBULAR PATHOLOGY IN MENIERE'S DISEASE Principal Investigator & Institution: Ishiyama, Akira; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 07-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The Overall goal of the proposed project is to describe the effects of Meniere's disease on the individual endorgans and vestibular ganglion, and how the pathology relates to the clinical history and vestibular function on routine testing. We propose a prospective study of the vestibular periphery in Meniere's disease using specimens obtained from ablative inner ear surgery and postmortem specimens. The project will use 1) histopathologic analysis, immunohistochemistry, and electron microscopy to study vestibular pathology 2) unbiased stereology to obtain morphometric measures at multiple levels: neuroepithelium, the nerve fibers, and Scarpa's ganglion neurons in the same subject 3) clinico-pathological correlations and comparisons between morphometric parameters and standarized vestibular testing. Morphometric parameters to be studied include 1) regional total type I, type II, and supporting cell counts in each of the five vestibular endorgans 2) vestibular nerve fiber counts and diameter distribution 3) Scarpa's ganglion neuronal counts and volume distribution. Archival temporal bones from patients with Meniere's disease will be used for Scarpa's ganglion neuronal counts. Using this systematic, prospective design we hope to answer important clinical questions such as 1) Does Meniere's disease affect the individual endorgans differently? 2) Can the patterns of neuroepithelial endorgan damage be correlated with clinical history? 3) Does Meniere's disease affect the vestibular nerve and ganglion? 4) Is Meniere's disease associated with an atrophy of the Scarpa's ganglion neurons? 5) Are clinical phenomenon such as Tumarkin falls, delayed endolymphatic hydrops, and chronic dysequilibrium associated with particular patterns of neuroepithelial or differential endorgan damage? or with alterations in neuronal number or size? 6) What are the morphometric correlates to abnormalities on traditional vestibular testing: caloric paresis, and decreased gain and time constant on step rotational testing? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: XENOGRAFT MODELS OF HUMAN NEUROBLASTOMA BONE METASTASES. Principal Investigator & Institution: Reynolds, Charles P.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Neurobtastoma is an enigmatic tumor, in which some patients who have widespread disease do well, even with no therapy, while others relentlessly progress, in spite of myeloablative therapy. A key clinical feature associated with bad outcome in neurobtastoma is the presence of bone metastases. In spite of the association of bone metastases with poor outcome in neurobtastoma, and the important contribution that bony disease makes to end-of-life suffering, there have been a paucity of biological studies on neurobtastoma bone metastases, and no clinical tdals. We

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propose to utilize our large (> 200) panel of human neuroblastoma cell lines to identify cell lines, which readily form metastases in bones of immunocompromised (SCID) mice. We will employ high-resolution small animal radiographic imaging to monitor the animals for bone metastases, and to identify sites for directed histopathology and cell culture at the time of necropsy. We then propose to use Affymetrix otigonucleotide array gene expression profiling in a highly selected panel of cell lines (6 shown to readily form bone metastases and 6 that do not when tested by i.v. injection into SCID mice) to identify genes in which altered expression (especially over-expression) correlates with the ability to form bone metastases in SCID mice. We will select for cells with an increased predilection to form bone metastases by repeated cycles of intravenous injection into SCID mice and harvest and re-culture of cells found growing in bone, and we will compare the selected cell lines to the original parental lines, and to cell lines that do not "home" to bone, using Affymetrix expression profiling. We will confirm a relationship between gene over-expression (or under-expression) and bone metastases in our large panel of cell lines by quantitative RT-PCR for genes identified by expression profiling. RT-PCR will be conducted for all cell lines in the panel known to form or to not form bone metastases, and also will be conducted using xenograft tumors from mouse bone and compared to non-bone metastasizing xenografts grown subcutaneously or in other non-bony sites. This project will provide cell lines and animal models that will be useful for understanding the biology of bone metastases in neuroblastoma, and also for pre-clinical therapeutic studies. We will also identify candidate genes that are key for bone metastases in neuroblastoma. In future studies, beyond the scope of this proposal, we and/or other investigators can determine the ability of the identified candidate genes, when over expressed via transduction, to confer an ability to form bone metastases in SCID mice to cell lines known to rarely form bone metastases. Those candidate genes are likely to be applicable to tumors other than neuroblastoma. We anticipate that this project will increase our understanding of the biology of bone metastases and will develop mouse models for pre-clinical testing of new therapeutic approaches to high risk neuroblastoma. 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 “bones” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bones in the PubMed Central database:

3 4

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

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

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A crucial role for thiol antioxidants in estrogen-deficiency bone loss. by Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, Urry ZL, Chambers TJ.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193670

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A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor --deficient mice. by Sims NA, Clement-Lacroix P, Minet D, Fraslon-Vanhulle C, Gaillard-Kelly M, Resche-Rigon M, Baron R.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154447

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A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. by Weiss MJ, Cole DE, Ray K, Whyte MP, Lafferty MA, Mulivor RA, Harris H.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282253

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A new hypothesis for how sex steroid hormones regulate bone mass. by Lorenzo J.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156115

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A potent analog of 1[alpha],25-dihydroxyvitamin D3 selectively induces bone formation. by Shevde NK, Plum LA, Clagett-Dame M, Yamamoto H, Pike JW, DeLuca HF.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129700

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A simple and efficient method for PCR amplifiable DNA extraction from ancient bones. by Kalmar T, Bachrati CZ, Marcsik A, Rasko I.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102752

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Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. by Coffin JD, Florkiewicz RZ, Neumann J, MortHopkins T, Dorn GW 2nd, Lightfoot P, German R, Howles PN, Kier A, O'Toole BA, et al.; 1995 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301338

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Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. by Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hughes DE, Masarachia PJ, Wesolowski G, Russell RG, Rodan GA, Reszka AA.; 1999 Jan 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15105

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An EP2 receptor-selective prostaglandin E2 agonist induces bone healing. by Paralkar VM, Borovecki F, Ke HZ, Cameron KO, Lefker B, Grasser WA, Owen TA, Li M, DaSilvaJardine P, Zhou M, Dunn RL, Dumont F, Korsmeyer R, Krasney P, Brown TA, Plowchalk D, Vukicevic S, Thompson DD.; 2003 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164516

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Azlocillin and cefonicid penetration into bone enhanced by probenecid. by Summersgill JT, Harrod LG, Raff MJ.; 1984 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176154

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Aztreonam penetration into synovial fluid and bone. by MacLeod CM, Bartley EA, Galante JO, Friedhoff LT, Dhruv R.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180473

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Bacterial porins stimulate bone resorption. by Meghji S, Henderson B, Nair SP, Tufano MA.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175133

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Bone homeostasis. by Rodan GA.; 1998 Nov 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33917

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Bone infection caused by debaryomyces hansenii in a normal host: a case report. by Wong B, Kiehn TE, Edwards F, Bernard EM, Marcove RC, de Harven E, Armstrong D.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=272406

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Bone Lead Content Assessed by L-Line X-Ray Fluorescence in Lead-Exposed and Non-Lead-Exposed Suburban Populations in the United States. by Rosen JF, Crocetti AF, Balbi K, Balbi J, Bailey C, Clemente I, Redkey N, Grainger S.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46181

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Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine. by Quint E, Smith A, Avaron F, Laforest L, Miles J, Gaffield W, Akimenko MA.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124364

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Bone penetration of enoxacin in patients with and without osteomyelitis. by Fong IW, Rittenhouse BR, Simbul M, Vandenbroucke AC.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172291

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Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin. by Zubery Y, Dunstan CR, Story BM, Kesavalu L, Ebersole JL, Holt SC, Boyce BF.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108500

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Bones of the Skull: A 3-D Learning Tool. by Anderson PF.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34575

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Bone-Specific Expression of the Alpha Chain of the Nascent Polypeptide-Associated Complex, a Coactivator Potentiating c-Jun-Mediated Transcription. by Moreau A, Yotov WV, Glorieux FH, St-Arnaud R.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108844

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Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture. by Bhattacharyya MH, Whelton BD, Stern PH, Peterson DP.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282541

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Calcitonin and bone formation: a knockout full of surprises. by Zaidi M, Moonga BS, Abe E.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151662

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Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model. by Masse PG, Boskey AL, Ziv I, Hauschka P, Donovan SM, Howell DS, Cole DE.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151688

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Chondromodulin I Is a Bone Remodeling Factor. by Nakamichi Y, Shukunami C, Yamada T, Aihara KI, Kawano H, Sato T, Nishizaki Y, Yamamoto Y, Shindo M, Yoshimura K, Nakamura T, Takahashi N, Kawaguchi H, Hiraki Y, Kato S.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151528

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Ciprofloxacin concentrations in bone and muscle after oral dosing. by Fong IW, Ledbetter WH, Vandenbroucke AC, Simbul M, Rahm V.; 1986 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180403

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Circulating levels of IGF-1 directly regulate bone growth and density. by Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D.; 2002 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151128

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Cloned endothelial cells from fetal bovine bone. by Streeten EA, Ornberg R, Curcio F, Sakaguchi K, Marx S, Aurbach GD, Brandi ML.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286589

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Collagenase 3 Is a Target of Cbfa1, a Transcription Factor of the runt Gene Family Involved in Bone Formation. by Jimenez MJ, Balbin M, Lopez JM, Alvarez J, Komori T, Lopez-Otin C.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104402

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Community water fluoridation, bone mineral density, and fractures: prospective study of effects in older women. by Phipps KR, Orwoll ES, Mason JD, Cauley JA.; 2000 Oct 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27493

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Comparative penetration of metronidazole, clindamycin, chloramphenicol, cefoxitin, ticarcillin, and moxalactam into bone. by Summersgill JT, Schupp LG, Raff MJ.; 1982 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181949

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Comparison of concentrations of rifampin and a new rifamycin derivative, DL 473, in canine bone. by Iversen P, Nielsen OS, Jensen KM, Madsen PO.; 1983 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186051

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Concentrations of ticarcillin and clavulanic acid in human bone after prophylactic administration of 5.2 g of timentin. by Adam D, Heilmann HD, Weismeier K.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284215

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Concentrations of vancomycin in bone and serum of normal rabbits and those with osteomyelitis. by Wilson KJ, Mader JT.; 1984 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185454

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Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation. by Scheijen B, Bronk M, van der Meer T, Bernards R.; 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164752

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Contribution of Interleukin-11 and Prostaglandin(s) in Lipopolysaccharide-Induced Bone Resorption In Vivo. by Li L, Khansari A, Shapira L, Graves DT, Amar S.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128103

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Cultured Adherent Cells from Marrow can Serve as Long-Lasting Precursor Cells for Bone, Cartilage, and Lung in Irradiated Mice. by Pereira RF, Halford KW, O'Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ.; 1995 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41806

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Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. by Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ.; 2002 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151001

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DAP12 signaling: from immune cells to bone modeling and brain myelination. by Colonna M.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151875

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Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17. by Bank RA, Robins SP, Wijmenga C, Breslau-Siderius LJ, Bardoel AF, Van der Sluijs HA, Pruijs HE, TeKoppele JM.; 1999 Feb 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15349

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Deletion of the GATA Domain of TRPS1 Causes an Absence of Facial Hair and Provides New Insights into the Bone Disorder in Inherited Tricho-Rhino-Phalangeal Syndromes. by Malik TH, von Stechow D, Bronson RT, Shivdasani RA.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139891

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Direct action of the parathyroid hormone-like human hypercalcemic factor on bone. by Thompson DD, Seedor JG, Fisher JE, Rosenblatt M, Rodan GA.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281822

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Direct and sex-specific stimulation by sex steroids of creatine kinase activity and DNA synthesis in rat bone. by Somjen D, Weisman Y, Harell A, Berger E, Kaye AM.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287132

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Direct Effects of 17[beta]-Estradiol on Trabecular Bone in Ovariectomized Rats. by Takano-Yamamoto T, Rodan GA.; 1990 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53648

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Discordant effect of body mass index on bone mineral density and speed of sound. by Steinschneider M, Hagag P, Rapoport MJ, Weiss M.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=183832

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Distribution of Trace Levels of Therapeutic Gallium in Bone as Mapped by Synchrotron X-Ray Microscopy. by Bockman RS, Repo MA, Warrell RP Jr, Pounds JG, Schidlovsky G, Gordon BM, Jones KW.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54065

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Does simvastatin stimulate bone formation in vivo? by von Stechow D, Fish S, Yahalom D, Bab I, Chorev M, Muller R, Alexander JM.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156891

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Effect of MALP-2, a Lipopeptide from Mycoplasma fermentans, on Bone Resorption In Vitro. by Piec G, Mirkovitch J, Palacio S, Muhlradt PF, Felix R.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97030

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Effect of Pasteurella multocida toxin on bone resorption in vitro. by Felix R, Fleisch H, Frandsen PL.; 1992 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258266

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Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. by Westerlind KC, Wronski TJ, Ritman EL, Luo ZP, An KN, Bell NH, Turner RT.; 1997 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20601

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Evaluation of Bone Strength During Aflatoxicosis and Ochratoxicosis. by Huff WE, Doerr JA, Hamilton PB, Hamann DD, Peterson RE, Ciegler A.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291531

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Evidence for a bone-kidney axis regulating phosphate homeostasis. by Quarles LD.; 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182218

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Expression of galanin and a galanin receptor in several sensory systems and bone anlage of rat embryos. by Xu ZQ, Shi TJ, Hokfelt T.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26234

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FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. by Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P.; 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182207

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Functional selectin ligands mediating human CD34 + cell interactions with bone marrow endothelium are enhanced postnatally. by Hidalgo A, Weiss LA, Frenette PS.; 2002 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150411

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Heme compounds in dinosaur trabecular bone. by Schweitzer MH, Marshall M, Carron K, Bohle DS, Busse SC, Arnold EV, Barnard D, Horner JR, Starkey JR.; 1997 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21042

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High Bone Resorption in Adult Aging Transgenic Mice Overexpressing Cbfa1/Runx2 in Cells of the Osteoblastic Lineage. by Geoffroy V, Kneissel M, Fournier B, Boyde A, Matthias P.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134019

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Hypothalamic Y2 receptors regulate bone formation. by Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, Herzog H.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150931

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Identification and Characterization of Cellular Binding Proteins (Receptors) for Recombinant Human Bone Morphogenetic Protein 2B, an Initiator of Bone Differentiation Cascade. by Paralkar VM, Hammonds RG, Reddi AH.; 1991 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51454

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Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML /CBF-[alpha] transcription factors. by Zeng C, van Wijnen AJ, Stein JL, Meyers S, Sun W, Shopland L, Lawrence JB, Penman S, Lian JB, Stein GS, Hiebert SW.; 1997 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21229

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Identification of Transforming Growth Factor [beta] Family Members Present in Bone-Inductive Protein Purified from Bovine Bone. by Celeste AJ, Iannazzi JA, Taylor RC, Hewick RM, Rosen V, Wang EA, Wozney JM.; 1990 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=55270

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IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. by Chabaud M, Lubberts E, Joosten L, van den Berg W, Miossec P.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30709

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Impaired Bone Resorption by Lipopolysaccharide In Vivo in Mice Deficient in the Prostaglandin E Receptor EP4 Subtype. by Sakuma Y, Tanaka K, Suda M, Komatsu Y, Yasoda A, Miura M, Ozasa A, Narumiya S, Sugimoto Y, Ichikawa A, Ushikubi F, Nakao K.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97785

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Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. by Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193662

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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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In vitro and in vivo evidence for orphan nuclear receptor ROR[alpha] function in bone metabolism. by Meyer T, Kneissel M, Mariani J, Fournier B.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16845

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Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: Similarity to estrogen deficiency. by Miyaura C, Onoe Y, Inada M, Maki K, Ikuta K, Ito M, Suda T.; 1997 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23193

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Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. by Hoff AO, Catala-Lehnen P, Thomas PM, Priemel M, Rueger JM, Nasonkin I, Bradley A, Hughes MR, Ordonez N, Cote GJ, Amling M, Gagel RF.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151647

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Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. by Weitzmann MN, Roggia C, Toraldo G, Weitzmann L, Pacifici R.; 2002 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151629

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Interleukin-1 and Tumor Necrosis Factor Activities Partially Account for Calvarial Bone Resorption Induced by Local Injection of Lipopolysaccharide. by Chiang CY, Kyritsis G, Graves DT, Amar S.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96729

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Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action. by Mohan S, Bautista CM, Wergedal J, Baylink DJ.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298276

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Isolation of osteogenin, an extracellular matrix-associated, bone-inductive protein, by heparin affinity chromatography. by Sampath TK, Muthukumaran N, Reddi AH.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299239

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Kinase-mediated regulation of common transcription factors accounts for the boneprotective effects of sex steroids. by Kousteni S, Han L, Chen JR, Almeida M, Plotkin LI, Bellido T, Manolagas SC.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156107

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Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study. by Zuluaga AF, Galvis W, Jaimes F, Vesga O.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115844

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L-line x-ray fluorescence of cortical bone lead compared with the CaNa2EDTA test in lead-toxic children: public health implications. by Rosen JF, Markowitz ME, Bijur PE, Jenks ST, Wielopolski L, Kalef-Ezra JA, Slatkin DN.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286538

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Magnesium deficiency: effect on bone mineral density in the mouse appendicular skeleton. by Gruber HE, Rude RK, Wei L, Frausto A, Mills BG, Norton HJ.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155646

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Modulation of bone metabolism by two chemically distinct lipopolysaccharide fractions from Bacteroides gingivalis. by Millar SJ, Goldstein EG, Levine MJ, Hausmann E.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261102

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Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. by Pfeilschifter J, Mundy GR.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304576

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Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates. by Wu Y, Chesler DA, Glimcher MJ, Garrido L, Wang J, Jiang HJ, Ackerman JL.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15521

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Nucleation of Hydroxyapatite by Bone Sialoprotein. by Hunter GK, Goldberg HA.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47397

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Oncogenesis of mammary glands, skin, and bones by polyomavirus correlates with viral persistence and prolonged genome replication potential. by Wirth JJ, Martin LG, Fluck MM.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191158

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Oral contraceptive use and bone mineral density in premenopausal women: crosssectional, population-based data from the Canadian Multicentre Osteoporosis Study. by Prior JC, Kirkland SA, Joseph L, Kreiger N, Murray TM, Hanley DA, Adachi JD, Vigna YM, Berger C, Blondeau L, Jackson SA, Tenenhouse A.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81536

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Osteoblastic Responses to TGF-[beta] during Bone Remodeling. by Erlebacher A, Filvaroff EH, Ye JQ, Derynck R.; 1998 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25433

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Osteopontin-A Possible Anchor of Osteoclast to Bone. by Reinholt FP, Hultenby K, Oldberg A, Heinegard D.; 1990 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54137

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Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. by Yoshitake H, Rittling SR, Denhardt DT, Noda M.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22204

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Ovariectomy Selectively Reduces the Concentration of Transforming Growth Factor [beta] in Rat Bone: Implications for Estrogen Deficiency-Associated Bone Loss. by Finkelman RD, Bell NH, Strong DD, Demers LM, Baylink DJ.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50724

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Parathyroid hormone is essential for normal fetal bone formation. by Miao D, He B, Karaplis AC, Goltzman D.; 2002 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150965

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Parathyroid hormone modulates transforming growth factor beta activity and binding in osteoblast-enriched cell cultures from fetal rat parietal bone. by Centrella M, McCarthy TL, Canalis E.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281870

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Partial Rescue of a Lethal Phenotype of Fragile Bones in Transgenic Mice with a Chimeric Antisense Gene Directed Against a Mutated Collagen Gene. by Khillan JS, Li S, Prockop DJ.; 1994 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44188

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Pasteurella pneumotropica isolated from bone and joint infections. by Gadberry JL, Zipper R, Taylor JA, Wink C.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=271216

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Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study. by Jakes RW, Khaw KT, Day NE, Bingham S, Welch A, Oakes S, Luben R, Dalzell N, Reeve J, Wareham NJ.; 2001 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26592

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Penetration of cefazolin into normal and osteomyelitic canine cortical bone. by Daly RC, Fitzgerald RH Jr, Washington JA 2nd.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183766

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Penetration of ciprofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans. by Mertes PM, Voiriot P, Dopff C, Scholl H, Clavey M, Villemot JP, Canton P, Dureux JB.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171604

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Penetration of ofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans. by Mertes PM, Jehl F, Burtin P, Dopff C, Pinelli G, Villemot JP, Monteil H, Dureux JB.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284360

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Penetration of piperacillin-tazobactam into cancellous and cortical bone tissues. by Incavo SJ, Ronchetti PJ, Choi JH, Wu H, Kinzig M, Sorgel F.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284568

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Penetration of vancomycin in uninfected sternal bone. by Massias L, Dubois C, de Lentdecker P, Brodaty O, Fischler M, Farinotti R.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284370

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Pharmacokinetic study of cefodizime and ceftriaxone in sera and bones of patients undergoing hip arthroplasty. by Scaglione F, De Martini G, Peretto L, Ghezzi R, Baratelli M, Arcidiacono MM, Fraschini F.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164111

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Phosphatic Shell Plate of the Barnacle Ibla (Cirripedia): A Bone-Like Structure. by Lowenstam HA, Weiner S.; 1992 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50383

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Porphyromonas gingivalis fimbriae stimulate bone resorption in vitro. by Kawata Y, Hanazawa S, Amano S, Murakami Y, Matsumoto T, Nishida K, Kitano S.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302914

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Porphyromonas gingivalis fimbria-stimulated bone resorption is inhibited through binding of the fimbriae to fibronectin. by Kawata Y, Iwasaka H, Kitano S, Hanazawa S.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176132

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Porphyromonas gingivalis lipopolysaccharide-stimulated bone resorption via CD14 is inhibited by broad-spectrum antibiotics. by Miyata Y, Takeda H, Kitano S, Hanazawa S.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175501

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Potentiation of Osteoclast Bone-Resorption Activity by Inhibition of Nitric Oxide Synthase. by Kasten TP, Collin-Osdoby P, Patel N, Osdoby P, Krukowski M, Misko TP, Settle SL, Currie MG, Nickols GA.; 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43621

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Premature Suture Closure and Ectopic Cranial Bone in Mice Expressing Msx2 Transgenes in the Developing Skull. by Liu YH, Kundu R, Wu L, Luo W, Ignelzi MA Jr, Snead ML, Maxson RE Jr.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41657

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Primary hyperparathyroidism: pathophysiology and impact on bone. by Khan A, Bilezikian J.; 2000 Jul 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80211

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Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis. by Joosten LA, Lubberts E, Helsen MM, Saxne T, Coenen-de Roo CJ, Heinegard D, van den Berg WB.; 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17779

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Radiocarbon dates on bones of extinct birds from Hawaii. by James HF, Stafford TW Jr, Steadman DW, Olson SL, Martin PS, Jull AJ, McCoy PC.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304648

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RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. by Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle WJ.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26475

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Recombinant Human Bone Morphogenetic Protein Induces Bone Formation. by Wang EA, Rosen V, D'Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM, LaPan P, Luxenberg DH, McQuid D, Moutsatsos IK, Nove J, Wozney JM.; 1990 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53658

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Regression of adjuvant-induced arthritis in rats following bone marrow transplantation. by van Bekkum DW, Bohre EP, Houben PF, Knaan-Shanzer S.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298650

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Regulation of the Bone-Specific Osteocalcin Gene by p300 Requires Runx2/Cbfa1 and the Vitamin D3 Receptor but Not p300 Intrinsic Histone Acetyltransferase Activity. by Sierra J, Villagra A, Paredes R, Cruzat F, Gutierrez S, Javed A, Arriagada G, Olate J, Imschenetzky M, van Wijnen AJ, Lian JB, Stein GS, Stein JL, Montecino M.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153185

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Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin. by O'Reilly T, Kunz S, Sande E, Zak O, Sande MA, Tauber MG.; 1992 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245530

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Relationship Between NMR Transverse Relaxation, Trabecular Bone Architecture, and Strength. by Chung H, Wehrli FW, Williams JL, Kugelmass SD.; 1993 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47752

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Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption. by van't Hof RJ, Armour KJ, Smith LM, Armour KE, Wei XQ, Liew FY, Ralston SH.; 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16658

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Role of Porphyromonas gingivalis-derived fibroblast-activating factor in bone resorption. by Mihara J, Yoneda T, Holt SC.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281042

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Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. by Garrett IR, Chen D, Gutierrez G, Zhao M, Escobedo A, Rossini G, Harris SE, Gallwitz W, Kim KB, Hu S, Crews CM, Mundy GR.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156102

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Sindbis-Group Alphavirus Replication in Periosteum and Endosteum of Long Bones in Adult Mice. by Heise MT, Simpson DA, Johnston RE.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102128

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Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. by Pacifici R, Rifas L, Teitelbaum S, Slatopolsky E, McCracken R, Bergfeld M, Lee W, Avioli LV, Peck WA.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305141

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Statins as modulators of bone formation. by Edwards CJ, Spector TD.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128924

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Stimulation of bone resorption by inflamed nasal mucosa, dermonecrotic toxincontaining conditioned medium from Pasteurella multocida, and purified dermonecrotic toxin from P. multocida. by Kimman TG, Lowik CW, van de Wee-Pals LJ, Thesingh CW, Defize P, Kamp EM, Bijvoet OL.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260664

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Synergistic Effects of Y2 and Y4 Receptors on Adiposity and Bone Mass Revealed in Double Knockout Mice. by Sainsbury A, Baldock PA, Schwarzer C, Ueno N, Enriquez RF, Couzens M, Inui A, Herzog H, Gardiner EM.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165708

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Synergistic enhancement of bone formation and healing by stem cell --expressed VEGF and bone morphogenetic protein-4. by Peng H, Wright V, Usas A, Gearhart B, Shen HC, Cummins J, Huard J.; 2002 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151123

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Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss. by Fitzpatrick LA, Buzas E,

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Gagne TJ, Nagy A, Horvath C, Ferencz V, Mester A, Kari B, Ruan M, Falus A, Barsony J.; 2003 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156320 •

Targeted expression of constitutively active receptors for parathyroid hormone and parathyroid hormone-related peptide delays endochondral bone formation and rescues mice that lack parathyroid hormone-related peptide. by Schipani E, Lanske B, Hunzelman J, Luz A, Kovacs CS, Lee K, Pirro A, Kronenberg HM, Juppner H.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28367

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Targeted Overexpression of Parathyroid Hormone-Related Peptide in Chondrocytes Causes Chondrodysplasia and Delayed Endochondral Bone Formation. by Weir EC, Philbrick WM, Amling M, Neff LA, Baron R, Broadus AE.; 1996 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38368

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The 2002 Canadian bone densitometry recommendations: take-home messages. by Khan AA, Brown JP, Kendler DL, Leslie WD, Lentle BC, Lewiecki EM, Miller PD, Nicholson RL, Olszynski WP, Watts NB.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134295

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The anatomy of a World Wide Web library service: the BONES demonstration project. Biomedically Oriented Navigator of Electronic Services. by Schnell EH.; 1995 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=226061

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The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones. by Huang W, Chung UI, Kronenberg HM, de Crombrugghe B.; 2001 Jan 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14561

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The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. by Rauch F, Travers R, Plotkin H, Glorieux FH.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151613

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The parathyroid hormone /parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation. by Chung UI, Lanske B, Lee K, Li E, Kronenberg H.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23697

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The role of statins as potential targets for bone formation. by Garrett IR, Mundy GR.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128929

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The shoulder bone's connected to the. by Hobbs BB, Thain LM.; 2000 Jul 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80200

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Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. by Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Goding JW, Terkeltaub R, Millan JL.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123160

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Toll-Like Receptor 4-Deficient Mice Have Reduced Bone Destruction following Mixed Anaerobic Infection. by Hou L, Sasaki H, Stashenko P.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98410

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Transgenic Mouse Model for Neurocristopathy: Schwannomas and Facial Bone Tumors. by Jensen NA, Rodriguez ML, Garvey JS, Miller CA, Hood L.; 1993 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46265

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Up-regulation of TNF-producing T cells in the bone marrow: A key mechanism by which estrogen deficiency induces bone loss in vivo. by Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G, Pacifici R.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61149

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Vancomycin concentrations in infected and noninfected human bone. by Graziani AL, Lawson LA, Gibson GA, Steinberg MA, MacGregor RR.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175859

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Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. by Street J, Bao M, deGuzman L, Bunting S, Peale FV Jr, Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RA, Filvaroff EH.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124965

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Vitamin D Deficiency Causes a Selective Reduction in Deposition of Transforming Growth Factor [beta] in Rat Bone: Possible Mechanism for Impaired Osteoinduction. by Finkelman RD, Linkhart TA, Mohan S, Lau KW, Baylink DJ, Bell NH.; 1991 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51511

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What can you do with a bone fragment? by Shipman P.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33379

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YY1 activates Msx2 gene independent of bone morphogenetic protein signaling. by Tan DP, Nonaka K, Nuckolls GH, Liu YH, Maxson RE, Slavkin HC, Shum L.; 2002 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101235

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Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. by Bergo MO, Gavino B, Ross J, Schmidt WK, Hong C, Kendall LV, Mohr A, Meta M, Genant H, Jiang Y, Wisner ER, van Bruggen N, Carano RA, Michaelis S, Griffey SM, Young SG.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130584

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

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

2003 W.O. Atwater Memorial Lecture: Defining nutrient requirements from a perspective of bone-related nutrients. Author(s): Weaver CM. Source: The Journal of Nutrition. 2003 December; 133(12): 4063-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652347&dopt=Abstract

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A non-invasive technique for assessing innominate bone motion. Author(s): Bussey MD, Yanai T, Milburn P. Source: Clinical Biomechanics (Bristol, Avon). 2004 January; 19(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14659935&dopt=Abstract

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Activation of p38 and Smads mediates BMP-2 effects on human trabecular bonederived osteoblasts. Author(s): Noth U, Tuli R, Seghatoleslami R, Howard M, Shah A, Hall DJ, Hickok NJ, Tuan RS. Source: Experimental Cell Research. 2003 November 15; 291(1): 201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597420&dopt=Abstract

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Advances and challenges in the surgical treatment of metastatic bone disease. Author(s): Jacofsky DJ, Papagelopoulos PJ, Sim FH. Source: Clinical Orthopaedics and Related Research. 2003 October; (415 Suppl): S14-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600588&dopt=Abstract

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Advances in imaging: impact on studying craniofacial bone structure. Author(s): Majumdar S. Source: Orthodontics & Craniofacial Research. 2003; 6 Suppl 1: 48-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606534&dopt=Abstract

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Advances in the treatment of bone metastases. Author(s): Reich CD. Source: Clinical Journal of Oncology Nursing. 2003 November-December; 7(6): 641-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14705479&dopt=Abstract

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Analgesia issues in palliative care: bone pain, controlled release opioids, managing opioid-induced constipation and nifedipine as an analgesic. Author(s): Fine PG. Source: Journal of Pain & Palliative Care Pharmacotherapy. 2002; 16(1): 93-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650452&dopt=Abstract

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Analysis of bone resorption after secondary alveolar cleft bone grafts before and after canine eruption in connection with orthodontic gap closure or prosthodontic treatment. Author(s): Schultze-Mosgau S, Nkenke E, Schlegel AK, Hirschfelder U, Wiltfang J. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 November; 61(11): 1245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14613077&dopt=Abstract

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Aneurysmal bone cyst of the temporal bone: case report. Author(s): Tuna H, Karatas A, Yilmaz ER, Yagmurlu B, Erekul S. Source: Surgical Neurology. 2003 December; 60(6): 571-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14670683&dopt=Abstract

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Angiogenesis and bone repair. Author(s): Carano RA, Filvaroff EH. Source: Drug Discovery Today. 2003 November 1; 8(21): 980-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14643161&dopt=Abstract

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Aromatase in bone: roles of Vitamin D3 and androgens. Author(s): Yanase T, Suzuki S, Goto K, Nomura M, Okabe T, Takayanagi R, Nawata H. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 September; 86(3-5): 393-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623536&dopt=Abstract

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Assessment of trabecular bone structure in postmenopausal and senile osteoporosis in women by image analysis. Author(s): Jakubas-Przewlocka J, Sawicki A, Przewlocki P. Source: Scandinavian Journal of Rheumatology. 2003; 32(5): 295-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14690143&dopt=Abstract

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Asymmetry of the sphenoid bone and its suitability as a reference for analyzing craniofacial asymmetry. Author(s): Kim YH, Sato K, Mitani H, Shimizu Y, Kikuchi M. Source: American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. 2003 December; 124(6): 656-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14666078&dopt=Abstract

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Benign fibro-osseous diseases of the maxillofacial bones. A review and differential diagnosis. Author(s): Alawi F. Source: American Journal of Clinical Pathology. 2002 December; 118 Suppl: S50-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14569813&dopt=Abstract

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Birth-related fractures of long bones. Author(s): Al-Habdan I. Source: Indian J Pediatr. 2003 December; 70(12): 959-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14719783&dopt=Abstract

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Bone archives face prospect of dispersal. Author(s): Giles J. Source: Nature. 2003 November 13; 426(6963): 109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614466&dopt=Abstract

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Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Author(s): Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Source: Arthritis and Rheumatism. 2003 November; 48(11): 3224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14613287&dopt=Abstract

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Bone graft for revision hip arthroplasty: biology and future applications. Author(s): Gamradt SC, Lieberman JR. Source: Clinical Orthopaedics and Related Research. 2003 December; (417): 183-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14646716&dopt=Abstract

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Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome. Author(s): Jensen T, Klarlund M, Hansen M, Jensen KE, Podenphant J, Hansen TM, Skjodt H, Hyldstrup L; TIRA Group. Source: Annals of the Rheumatic Diseases. 2004 January; 63(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672886&dopt=Abstract

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Bone mineral density in premenopausal women with systemic lupus erythematosus. Author(s): Uaratanawong S, Deesomchoke U, Lertmaharit S, Uaratanawong S. Source: The Journal of Rheumatology. 2003 November; 30(11): 2365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677178&dopt=Abstract

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Bone mineral density levels of college-aged women in northwest Arkansas. Author(s): Tokar K, Ford MA, Turner LW, Denny G. Source: J Ark Med Soc. 2003 November; 100(5): 170-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606227&dopt=Abstract

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Bone regeneration through transplantation of genetically modified cells. Author(s): Blum JS, Barry MA, Mikos AG. Source: Clin Plast Surg. 2003 October; 30(4): 611-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621309&dopt=Abstract

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Bone wax as a cause of a foreign body granuloma in a cranial defect: a case report. Author(s): Wolvius EB, van der Wal KG. Source: International Journal of Oral and Maxillofacial Surgery. 2003 December; 32(6): 656-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636621&dopt=Abstract

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Buccal and coronal bone augmentation using forced eruption and buccal root torque: a case report. Author(s): Nozawa T, Sugiyama T, Yamaguchi S, Ramos T, Komatsu S, Enomoto H, Ito K. Source: Int J Periodontics Restorative Dent. 2003 December; 23(6): 585-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14703762&dopt=Abstract

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Calcium and bone health in infants. Author(s): Koo WW, Warren L. Source: Neonatal Netw. 2003 September-October; 22(5): 23-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598978&dopt=Abstract

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Case report--odontogenic keratocysts: enucleation, bone grafting and implant placement: an early return to function. Author(s): Barry CP, Kearns GJ. Source: J Ir Dent Assoc. 2003; 49(3): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14603664&dopt=Abstract

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Characterization of the development of ectopic chondroid/bone matrix and chondrogenic/osteogenic cells during osteoinduction by rhBMP-2: a histochemical and ultrastructural study. Author(s): Nakagawa T, Sugiyama T, Shimizu K, Murata T, Narita M, Nakamura S, Tagawa T. Source: Oral Diseases. 2003 September; 9(5): 255-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14628893&dopt=Abstract

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Chondrosarcoma of the bones of the feet. Author(s): Patil S, de Silva MV, Crossan J, Reid R. Source: The Journal of Foot and Ankle Surgery : Official Publication of the American College of Foot and Ankle Surgeons. 2003 September-October; 42(5): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14566721&dopt=Abstract

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Cochlear involvement in a temporal bone fracture. Author(s): Gross M, Yaacov AB, Eliashar R. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 November; 24(6): 958-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600482&dopt=Abstract

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Comparison of direct digital and conventional intraoral radiographs in detecting alveolar bone loss. Author(s): Khocht A, Janal M, Harasty L, Chang KM. Source: The Journal of the American Dental Association. 2003 November; 134(11): 146875. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14664265&dopt=Abstract

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Confirmation of the early prognostic value of bone scanning and pinhole imaging of the hip in Legg-Calve-Perthes disease. Author(s): Comte F, De Rosa V, Zekri H, Eberle MC, Dimeglio A, Rossi M, MarianoGoulart D. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 November; 44(11): 1761-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602857&dopt=Abstract

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Cortical bone density is normal in prepubertal children with growth hormone (GH) deficiency, but initially decreases during GH replacement due to early bone remodeling. Author(s): Schweizer R, Martin DD, Schwarze CP, Binder G, Georgiadou A, Ihle J, Ranke MB. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5266-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602760&dopt=Abstract

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COX-2 selective inhibitors and bone. Author(s): Goodman SB, Ma T, Genovese M, Lane Smith R. Source: Int J Immunopathol Pharmacol. 2003 September-December; 16(3): 201-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14611721&dopt=Abstract

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Diet for the heart or the bone: a biological tradeoff. Author(s): Ott SM. Source: The American Journal of Clinical Nutrition. 2004 January; 79(1): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684390&dopt=Abstract

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DNA sequences of Mycobacterium leprae recovered from ancient bones. Author(s): Montiel R, Garcia C, Canadas MP, Isidro A, Guijo JM, Malgosa A. Source: Fems Microbiology Letters. 2003 September 26; 226(2): 413-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14553941&dopt=Abstract

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Early kidney transplantation may prevent aluminium-related bone disease. Author(s): Nordal KP, Dahl E, Halse J, Flatmark A. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S98-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621745&dopt=Abstract

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Efferent system degeneration in the human temporal bone. Author(s): Gacek RR. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 November; 112(11): 947-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14653363&dopt=Abstract

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Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis. Author(s): Hodsman AB, Hanley DA, Ettinger MP, Bolognese MA, Fox J, Metcalfe AJ, Lindsay R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5212-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602752&dopt=Abstract

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Endoprosthetic reconstructions for bone metastases. Author(s): Eckardt JJ, Kabo JM, Kelly CM, Ward WG Sr, Cannon CP. Source: Clinical Orthopaedics and Related Research. 2003 October; (415 Suppl): S254-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600617&dopt=Abstract

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Evaluation of bone with quantitative ultrasound in healthy Turkish children. Author(s): Tuzun S, Karacan I, Akarirmak U, Kasapcopur O, Arisoy N. Source: Turk J Pediatr. 2003 July-September; 45(3): 240-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696803&dopt=Abstract

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Evaluation of hormonal response and ultrasonic changes in the heel bone by aquatic exercise in sedentary postmenopausal women. Author(s): Ay A, Yurtkuran M. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 December; 82(12): 942-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627931&dopt=Abstract

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Exogenous bone morphogenetic protein may improve distraction osteogenesis outcomes. Author(s): Jensen OT. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 December; 61(12): 1505-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14666938&dopt=Abstract

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Falls, bones and the primary care team. Author(s): McMurdo ME, Harper JR. Source: Eur J Gen Pract. 2003 March; 9(1): 10-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14611008&dopt=Abstract

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Forensic microradiology: micro-computed tomography (Micro-CT) and analysis of patterned injuries inside of bone. Author(s): Thali MJ, Taubenreuther U, Karolczak M, Braun M, Brueschweiler W, Kalender WA, Dirnhofer R. Source: J Forensic Sci. 2003 November; 48(6): 1336-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640282&dopt=Abstract

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Functional reconstruction of a massive defect in the two forearm bones. Author(s): Chen SH, Jeng SF, Liu HC. Source: The Journal of Trauma. 2003 October; 55(4): 774-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14566137&dopt=Abstract

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GBR using bovine bone matrix and resorbable and nonresorbable membranes. Part 2: Clinical results. Author(s): Fugazzotto PA. Source: Int J Periodontics Restorative Dent. 2003 December; 23(6): 599-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14703764&dopt=Abstract

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Hydroxyapatite cement in temporal bone surgery: a 10 year experience. Author(s): Kveton JF, Coelho DH. Source: The Laryngoscope. 2004 January; 114(1): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14709991&dopt=Abstract

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Hyoid bone fracture from a gunshot wound. Author(s): Zendehrouh P, Tandon M, Frankel H, Rabinovici R. Source: The Journal of Trauma. 2003 November; 55(5): 1003. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14608187&dopt=Abstract

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Iliac bone grafts for orbital wall reconstruction. Author(s): Dancey A, Rayatt S, Perry M. Source: Plastic and Reconstructive Surgery. 2004 January; 113(1): 451. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707679&dopt=Abstract

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Immediate replacement of a maxillary central incisor associated with severe facial bone loss: use of Bio-Oss collagen--case report. Author(s): Danan M, Degrange M, Vaideanu T, Brion M. Source: Int J Periodontics Restorative Dent. 2003 October; 23(5): 491-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14620123&dopt=Abstract

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Improvements in the biokinetic model for strontium with allowance for age and gender differences in bone mineral metabolism. Author(s): Shagina NB, Tolstykh EI, Degteva MO. Source: Radiat Prot Dosimetry. 2003; 105(1-4): 619-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527037&dopt=Abstract

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Inflammatory myofibroblastic tumor of the temporal bone. Author(s): Gasparotti R, Zanetti D, Bolzoni A, Gamba P, Morassi ML, Ungari M. Source: Ajnr. American Journal of Neuroradiology. 2003 November-December; 24(10): 2092-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14625240&dopt=Abstract

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Linezolid penetration into bone and joint tissues infected with methicillin-resistant staphylococci. Author(s): Kutscha-Lissberg F, Hebler U, Muhr G, Koller M. Source: Antimicrobial Agents and Chemotherapy. 2003 December; 47(12): 3964-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638510&dopt=Abstract

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Localized pericochlear hypoattenuating foci at temporal-bone thin-section CT in pediatric patients: nonpathologic differential diagnostic entity? Author(s): Pekkola J, Pitkaranta A, Jappel A, Czerny C, Baumgartner WD, Heliovaara M, Robinson S. Source: Radiology. 2004 January; 230(1): 88-92. Epub 2003 November 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617763&dopt=Abstract

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Long stemmed total knee arthroplasty with interlocking screws: a computational bone adaptation study. Author(s): Nyman JS, Hazelwood SJ, Rodrigo JJ, Martin RB, Yeh OC. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 2004 January; 22(1): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14656659&dopt=Abstract

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Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. Author(s): Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S, Lucani B, Dal Canto N, Valenti R, Gennari C, Nuti R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602769&dopt=Abstract

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Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet. Author(s): Barera G, Beccio S, Proverbio MC, Mora S. Source: The American Journal of Clinical Nutrition. 2004 January; 79(1): 148-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684411&dopt=Abstract

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Low vitamin D status, high bone turnover, and bone fractures in centenarians. Author(s): Passeri G, Pini G, Troiano L, Vescovini R, Sansoni P, Passeri M, Gueresi P, Delsignore R, Pedrazzoni M, Franceschi C. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602735&dopt=Abstract

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Lower estimates of net endogenous non-carbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women. Author(s): New SA, MacDonald HM, Campbell MK, Martin JC, Garton MJ, Robins SP, Reid DM. Source: The American Journal of Clinical Nutrition. 2004 January; 79(1): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684409&dopt=Abstract

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Metastatic disease in long bones: A proposed scoring system for diagnosing impending pathologic fractures. 1989. Author(s): Mirels H. Source: Clinical Orthopaedics and Related Research. 2003 October; (415 Suppl): S4-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600587&dopt=Abstract

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Milk--good for bones, good for reducing childhood obesity? Author(s): Weaver CM, Boushey CJ. Source: Journal of the American Dietetic Association. 2003 December; 103(12): 1598-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14647084&dopt=Abstract

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MR imaging findings of bone marrow changes in patients with cystic fibrosis. Author(s): De Maeseneer M, Desprechins B, Dab I, Machiels F, Shahabpour M, Osteaux M. Source: Jbr-Btr. 2003 September-October; 86(5): 265-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14651080&dopt=Abstract

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New frontiers in bone tissue engineering. Author(s): Calvert JW, Weiss LE, Sundine MJ. Source: Clin Plast Surg. 2003 October; 30(4): 641-8, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621311&dopt=Abstract

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No bones about it: the unique side of orthopedic management in the child with SCI. Author(s): Merenda LA. Source: Sci Nurs. 2003 Spring; 20(1): 48-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14626020&dopt=Abstract

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Orthodontic fine adjustment after vertical callus distraction of an ankylosed incisor using the floating bone concept. Author(s): Kinzinger GS, Janicke S, Riediger D, Diedrich PR. Source: American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. 2003 November; 124(5): 582-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14614427&dopt=Abstract

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Palmar dislocation of the lunate bone with complete disruption of all ligaments. A report on two cases. Author(s): Draaijers LJ, Kreulen M, Maas M. Source: Acta Orthop Belg. 2003 October; 69(5): 452-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14648956&dopt=Abstract

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Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal. Author(s): Wergedal JE, Veskovic K, Hellan M, Nyght C, Balemans W, Libanati C, Vanhoenacker FM, Tan J, Baylink DJ, Van Hul W. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 5778-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671168&dopt=Abstract

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Posterior iliac crest bone harvest: review of technique, complications, and use of an epidural catheter for postoperative pain control. Author(s): Mazock JB, Schow SR, Triplett RG. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 December; 61(12): 1497-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663819&dopt=Abstract

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Primary bone lymphoma: radiographic-MR imaging correlation. Author(s): Krishnan A, Shirkhoda A, Tehranzadeh J, Armin AR, Irwin R, Les K. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. 2003 November-December; 23(6): 1371-83; Discussion 1384-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14615550&dopt=Abstract

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Primary Rosai-Dorfman disease of bone without lymphadenopathy diagnosed by fine needle aspiration cytology. A case report. Author(s): Goel MM, Agarwal PK, Agarwal S. Source: Acta Cytol. 2003 November-December; 47(6): 1119-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14674094&dopt=Abstract

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Primary stability of bone-patellar tendon-bone graft fixation with biodegradable pins. Author(s): Weimann A, Zantop T, Rummler M, Hassenpflug J, Petersen W. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2003 December; 19(10): 1097-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14673452&dopt=Abstract

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Primary stability of implants in the posterior maxilla with autogenous bone rings harvested in the mandible. Author(s): Palti A. Source: Dent Implantol Update. 2003 September; 14(9): 65-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14692291&dopt=Abstract

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Reconstruction of skull bone defects using the hydroxyapatite cement with calvarial split transplants. Author(s): Wiltfang J, Kessler P, Buchfelder M, Merten HA, Neukam FW, Rupprecht S. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2004 January; 62(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14699545&dopt=Abstract

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Recurrence of a unicameral bone cyst in the proximal part of the fibula after en bloc resection. A case report. Author(s): Bowen RE, Morrissy RT. Source: The Journal of Bone and Joint Surgery. American Volume. 2004 January; 86-A(1): 154-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14711960&dopt=Abstract

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Regional thickness of parietal bone in Korean adults. Author(s): Jung YS, Kim HJ, Choi SW, Kang JW, Cha IH. Source: International Journal of Oral and Maxillofacial Surgery. 2003 December; 32(6): 638-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636616&dopt=Abstract

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Roentgenographic and direct observation of experimental lesions in bone: I. 1961. Author(s): Bender IB, Seltzer S. Source: Journal of Endodontics. 2003 November; 29(11): 702-6; Discussion 701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14651274&dopt=Abstract

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Rotational panoramic versus intraoral rectangular radiographs for evaluation of periimplant bone loss in the anterior atrophic mandible. Author(s): Zechner W, Watzak G, Gahleitner A, Busenlechner D, Tepper G, Watzek G. Source: Int J Oral Maxillofac Implants. 2003 November-December; 18(6): 873-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696663&dopt=Abstract

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Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency. Author(s): Bakalov VK, Axelrod L, Baron J, Hanton L, Nelson LM, Reynolds JC, Hill S, Troendle J, Bondy CA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 5717-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671158&dopt=Abstract

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Sentinel lymph node imaging and research after bone scintigraphy in breast cancer patients. Author(s): Bourgeois P, Nogaret JM, Veys I, Hertens D, Noterman D, Dagnelie J, Vanhaudenarde C, Barette M, Larsimont D. Source: Breast (Edinburgh, Scotland). 2003 June; 12(3): 194-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14659326&dopt=Abstract

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Septal fracture in simple nasal bone fracture. Author(s): Rhee SC, Kim YK, Cha JH, Kang SR, Park HS. Source: Plastic and Reconstructive Surgery. 2004 January; 113(1): 45-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707621&dopt=Abstract

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Sequential vascularized iliac bone graft and a superficial circumflex iliac artery perforator flap with a single source vessel for established mandibular defects. Author(s): Koshima I, Nanba Y, Tsutsui T, Itoh S. Source: Plastic and Reconstructive Surgery. 2004 January; 113(1): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707627&dopt=Abstract

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Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation. Author(s): Naylor KE, Rogers A, Fraser RB, Hall V, Eastell R, Blumsohn A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5361-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602774&dopt=Abstract

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Significance of bone marrow examination in the diagnostic process of paraspinal mass in children: a case report. Author(s): Buyukavci M, Karacan M, Olgun H, Tan H. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 October; 25(10): 822-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528110&dopt=Abstract

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Simultaneous correction of major hypertelorism, frontal bone defect, nasal aplasia, and cleft of the upper lip (Tessier 0-14). Author(s): Pittet B, Jaquinet A, Rilliet B, Montandon D. Source: Plastic and Reconstructive Surgery. 2004 January; 113(1): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707650&dopt=Abstract

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Sinus/alveolar crest tenting (SACT): a new technique for implant placement in atrophic maxillary ridges without bone grafts or membranes. Author(s): Winter AA, Pollack AS, Odrich RB. Source: Int J Periodontics Restorative Dent. 2003 December; 23(6): 557-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14703759&dopt=Abstract

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Stimulators of bone healing. Biologic and biomechanical. Author(s): Childs SG. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2003 November-December; 22(6): 421-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14705472&dopt=Abstract

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Subperiosteal aneurysmal bone cysts: 2 case reports. Author(s): Malfair D, Munk PL, O'Connell JX. Source: Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes. 2003 December; 54(5): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14689805&dopt=Abstract

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Temporal bone abnormalities associated with hearing loss in Waardenburg syndrome. Author(s): Madden C, Halsted MJ, Hopkin RJ, Choo DI, Benton C, Greinwald JH Jr. Source: The Laryngoscope. 2003 November; 113(11): 2035-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14603070&dopt=Abstract

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Temporal bone infection caused by atypical mycobacterium: case report and review of the literature. Author(s): Redaelli de Zinis LO, Tironi A, Nassif N, Ghizzardi D. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 November; 24(6): 843-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600461&dopt=Abstract

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The assessment of cortical heat during intramedullary reaming of long bones. Author(s): Giannoudis PV, Snowden S, Smye SW. Source: Injury. 2003 October; 34(10): 806; Author Reply 806-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519372&dopt=Abstract

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The effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty. Author(s): Wang CJ, Wang JW, Weng LH, Hsu CC, Huang CC, Chen HS. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 November; 85A(11): 2121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14630840&dopt=Abstract

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The effects of transdermal estrogen therapy on bone mass and turnover in early postmenopausal smokers: a prospective, controlled study. Author(s): Valimaki MJ, Laitinen KA, Tahtela RK, Hirvonen EJ, Risteli JP. Source: American Journal of Obstetrics and Gynecology. 2003 November; 189(5): 121320. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634543&dopt=Abstract

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The evaluation of a synthetic long bone structure as a substitute for human tissue in gunshot experiments. Author(s): Kneubuehl BP, Thali MJ. Source: Forensic Science International. 2003 December 17; 138(1-3): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642718&dopt=Abstract

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The mystery of the broken bones. Author(s): Sathiaseelan S, Rayar U. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 November 25; 169(11): 1189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638659&dopt=Abstract

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The viability of autoclaved dysplastic bone graft. Author(s): Basterzi Y, Isik I, Yavuzer R. Source: Plastic and Reconstructive Surgery. 2004 January; 113(1): 469-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14707698&dopt=Abstract

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Ultrasound registration of the bone surface for surgical navigation. Author(s): Amin DV, Kanade T, DiGioia AM 3rd, Jaramaz B. Source: Computer Aided Surgery : Official Journal of the International Society for Computer Aided Surgery. 2003; 8(1): 1-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14708753&dopt=Abstract

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Uterine intramural bone after mid-trimester termination of pregnancy may not affect fertility: a case report. Author(s): Van den Bosch T, Van Schoubroeck D, Timmerman D, Deprest J. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 October; 22(4): 407-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528479&dopt=Abstract

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Variations in clinical presentations of the simple bone cyst: report of cases. Author(s): Tong AC, Ng IO, Yan BS. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 December; 61(12): 1487-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663817&dopt=Abstract

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Vertebral osteopenia due to bone marrow hyperplasia during interferon-alpha and ribavirin therapy for chronic hepatitis C. Author(s): Framarin L, Avataneo T, Salzedo E, Badalamenti S, Tappero G, Rosina F. Source: Dig Liver Dis. 2003 October; 35(10): 732-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14620624&dopt=Abstract

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Weight loss: a determinant of hip bone loss in older men and women. The Rancho Bernardo Study. Author(s): Knoke JD, Barrett-Connor E. Source: American Journal of Epidemiology. 2003 December 15; 158(12): 1132-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652297&dopt=Abstract

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Academic Periodicals covering Bones Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bones. 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, 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.”

Dissertations on Bones ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to bones. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “bones” (or a synonym) in their titles. The following covers recent dissertations found when using this search procedure: •

A Microsphere Method to Investigate the Acute Effects of Simulated Weightlessness on Bone Blood Flow (Spaceflight, Cannulation, Skeletal, Catheterization, Rats) by Garshnek, Victoria, PhD from University of Oregon, 1985, 136 pages http://wwwlib.umi.com/dissertations/fullcit/8520712

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'I Write These Words with Blood and Bones': Two Nineteenth Century American Indian Intellectuals and a Rhetoric of Survivance (Sarah Winnemucca Hopkins, Charles Alexander Eastman) by Powell, Malea Dawn, PhD from Miami University, 1998, 211 pages http://wwwlib.umi.com/dissertations/fullcit/9841243

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Masticatory Muscle Architecture and Bone Morphology in Primates (Macaca) by Anton, Susan Carol, PhD from University of California, Berkeley, 1994, 334 pages http://wwwlib.umi.com/dissertations/fullcit/9529205

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

Finding Nutrition Studies on Bones 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. Once you have entered 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 “bones” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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The following is a typical result when searching for recently indexed consumer information on bones: •

Do calcium's disease-fighting roles go beyond bone buildings? Source: Wein, D.A. Environmental-nutrition (USA). (August 1994). volume 17(8) page 1, 6.

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For avoiding broken bones, more vitamin D. Source: Tufts-University-diet-and-nutrition-letter (USA). (July 1995). volume 13(5) page 1-2.

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Silicon: a nutritional beneficence for bones, brains and blood vessels? Source: Seaborn, C.D. Nielsen, F.H. Nutrition-today (USA). (August 1993). volume 28(4) page 13-18.

Additional consumer oriented references include: •

A health-conscious friend told me that carbonated drinks leach calcium from bones. Is this true? I'm wondering whether taking my calcium pills with seltzer counteracts their good effects. Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 May; 5(9): 8 1070-910X

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Beyond calcium: nutrition strategies to protect your bones. Source: Welland, D. Environ-nutr. New York : Environmental Nutrition, Inc.,. December 1996. volume 19 (12) page 1, 6. 0893-4452

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Bone builders support your bones with healthy habits. Source: Webb, D. FDA-consum. Rockville, Md. : Food and Drug Administration, Department of Health & Human Services. Sept/October 1997. volume 31 (6) page 27-30. 0362-1332

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Brittle bones. Source: Liebman, B. Nutr-Action-Health-Lett. Washington, D.C. : Center for Science in the Public Interest. July/August 1985. volume 12 (6) page 4-8. ill., charts. 0199-5510

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Calcium enhances HRT for bones. Author(s): Tufts University, Boston, Massachusetts, USA. Source: Dawson Hughes, B Health-News. 1998 March 10; 4(3): 2 1081-5880

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Can taking magnesium supplements help keep my bones strong? Source: Anonymous Mayo-Clin-Health-Lett. 1999 September; 17(9): 8 0741-6245

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Diet, genetics and peak bone mass of adolescent girls. Source: Forbes, G.B. Nutr-Today. Baltimore, Md. : Williams & Wilkins. April 1991. volume 26 (2) page 21-24. 0029-666X

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I am 51 years old, perimenopausal, have irritable bowel syndrome and a family history of breast cancer, and am told my bones are thinning. These conditions would seem to rule out my use of estrogen or Fosamax. I weight train and take 1,500 mg of calcium a day to stave off osteoporosis. What's left? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 November; 6(3): 8 1070910X

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Look to 3 E's of bone health: extra calcium, exercise, estrogen. Source: Forman, A. Environmental-nutrition (USA). (April 1993). volume 16(4) page 1, 6. bones strength calcium physical activity oestrogens adults 0893-4452

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More people are fracturing more bones more often. Source: Ruderman, N. Apelian, A.Z. Schneider, S.H. Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. January 1991. volume 49 (1) page 24-25. 0029-6643

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Obesity is not protective for bones in childhood and adolescence. Author(s): College of Pharmacy and Nutrition University of Saskatchewan, Saskatoon, Canada. Source: Whiting, Susan J Nutr-Revolume 2002 January; 60(1): 27-30 0029-6643

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Pubertal growth in IDDM is determined by HbA1c levels, sex, and bone age. Author(s): Department of Paediatrics, University of Oxford, U.K. Source: Ahmed, M L Connors, M H Drayer, N M Jones, J S Dunger, D B Diabetes-Care. 1998 May; 21(5): 831-5 0149-5992

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Strong bones: a balancing act. Source: Anonymous Harv-Womens-Health-Watch. 2001 May; 8(9): 2 1070-910X

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Trace element nutrition and bone metabolism. Source: Morgan, J.B. Kovar, I.Z. Nutr-Res-Rev. Cambridge [England] : Cambridge University Press. 1992. volume 5 page 167-188. 0954-4224

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

Influence of vitamin E dietary supplementation on some bone characteristics in broiler chicks. Author(s): Cairo Univ. (Egypt). Faculty of Veterinary Medicine Source: Mohamed, F.F. Abou El Soud, S.B.: Osman, M. Veterinary-Medical-Journal,Cairo-Univ. (Egypt). (April 2001). volume 49(2) page 331-344. Issued 2002.

Additional physician-oriented references include: •

A cysteine protease inhibitor prevents suspension-induced declines in bone weight and strength in rats. Author(s): Department of Nutrition, School of Medicine, University of Tokushima. [email protected] Source: Nikawa, Takeshi Ikemoto, Madoka Watanabe, Chiho Kitano, Takako Kano, Mihoko Yoshimoto, Makoto Towatari, Takae Katunuma, Nobuhiko Shizuka, Fujiko Kishi, Kyoichi J-Physiol-Anthropol-Appl-Human-Sci. 2002 January; 21(1): 51-7 1345-3475

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A Harvard study reported in my newspaper showed that drinking milk correlates with a higher incidence of prostate cancer. But we were always told that as we age, we need more calcium to keep bones healthy, and milk is a good source. Should we stop drinking milk? Source: Simon, H B Harv-Mens-Health-Watch. 2002 September; 7(2): 8 1089-1102

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Abnormal bone turnover in cystic fibrosis adults. Author(s): Divisions of Pulmonary Medicine,The University of North Carolina at Chapel Hill, 27599-7524, USA. [email protected] Source: Aris, R M Ontjes, D A Buell, H E Blackwood, A D Lark, R K Caminiti, M Brown, S A Renner, J B Chalermskulrat, W Lester, G E Osteoporos-Int. 2002; 13(2): 151-7 0937941X

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Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells. Author(s): Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. Source: Rubin, J Murphy, T C Fan, X Goldschmidt, M Taylor, W R J-Bone-Miner-Res. 2002 August; 17(8): 1452-60 0884-0431

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Alkaline phosphatase and tartrate-resistant acid phosphatase in osteoblasts of normal and pathologic bone. Author(s): Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy. [email protected] Source: Bonucci, E Nanci, A Ital-J-Anat-Embryol. 2001; 106(2 Suppl 1): 129-33 1122-6714

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Bare bones: how to keep yours strong. Source: Liebman, B. Nutr-action-health-lett. [Washington, D.C. : Center for Science in the Public Interest,. Jan/February 2002. volume 29 (1) page 1, 3-8. 0885-7792

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Bone changes due to glucocorticoid application in an ovariectomized animal model for fracture treatment in osteoporosis. Author(s): AO Research Institute Davos, Switzerland. [email protected] Source: Lill, C A Gerlach, U V Eckhardt, C Goldhahn, J Schneider, E Osteoporos-Int. 2002 May; 13(5): 407-14 0937-941X

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Bone formulas: not just about calcium anymore. Source: Klausner, A. Environ-nutr. New York : Environmental Nutrition, Inc.,. Sept 2000. volume 23 (9) page 5. 0893-4452

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Bone growth stimulators. New tools for treating bone loss and mending fractures. Author(s): Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6. Source: Whitfield, J F Morley, P Willick, G E Vitam-Horm. 2002; 65: 1-80 0083-6729

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Bone marrow edema of the forefoot after chevron osteotomy--a rare cause of metatarsalgia: a case report. Author(s): First General Orthopaedic Department, Orthopaedic Hospital Vienna-Speising, Austria. [email protected] Source: Aigner, Nicolas Petje, Gerd Steinboeck, Gunther Schneider, Wolfgang Krasny, Christian Landsiedl, Franz Foot-Ankle-Int. 2002 May; 23(5): 447-51 1071-1007

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By the way, Doctor. My doctor sent me a copy of my bone density test, and I was confused by seeing two measurements: a T-score and a Z-score. Could you please explain the difference? Is one more important than the other? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 2001 November; 9(4): 8 1070910X

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Calcium crisis bodes ill for bones. Source: Anonymous J-Calif-Dent-Assoc. 2002 February; 30(2): 113 1043-2256

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Cellular and molecular mechanisms for the bone response to mechanical loading. Author(s): Department of Health & Kinesiology, Texas A&M University, College Station 77843-4243, USA. Source: Bloomfield, S A Int-J-Sport-Nutr-Exerc-Metab. 2001 December; 11 Suppl: S128-36 1526-484X

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Characterization of the increase in bone 66 kDa protein component with healing rat fractures: stimulatory effect of zinc. Author(s): Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.

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Source: Igarashi, A Yamaguchi, M Int-J-Mol-Med. 2002 May; 9(5): 503-8 1107-3756 •

Comparative effects of intermittent administration of human parathyroid hormone (134) on cancellous and cortical bone loss in tail-suspended and sciatic neurectomized young rats. Author(s): Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Source: Moriyama, Ichiro Iwamoto, June Takeda, Tsuyoshi Toyama, Yoshiaki J-OrthopSci. 2002; 7(3): 379-85 0949-2658

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Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19 ). Author(s): Department of Medical Chemistry, Kochi Medical School, Nankoku, Japan. [email protected] Source: Toda, Katsumi Miyaura, Chisato Okada, Teruhiko Shizuta, Yutaka Eur-JBiochem. 2002 April; 269(8): 2214-22 0014-2956

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Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression. Author(s): Department of Orthopedics, Mayo Clinic, Rochester, MN 55905, USA. [email protected] Source: Lotinun, S Sibonga, J D Turner, R T Endocrine. 2002 February; 17(1): 29-36 0969711X

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Does bone change after biliopancreatic diversion? Author(s): Department of Surgery, Laval Hospital, Quebec City, Quebec, Canada. [email protected] Source: Marceau, P Biron, S Lebel, S Marceau, S Hould, F S Simard, S Dumont, M Fitzpatrick, L A J-Gastrointest-Surg. 2002 Sep-October; 6(5): 690-8 1091-255X

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Donor age and mechanosensitivity of human bone cells. Author(s): Department of Oral Cell Biology, Academic Centre for Dentistry, Amsterdam-Vrije Universiteit, Amsterdam, The Netherlands. [email protected] Source: Klein Nulend, J Sterck, J G H Semeins, C M Lips, P Joldersma, M Baart, J A Burger, E H Osteoporos-Int. 2002; 13(2): 137-46 0937-941X

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Don't be swayed into taking boron for your bones. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. August 1999. volume 17 (6) page 3.

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Effect of age on bone mineral density and the serum concentration of endogenous nitric oxide synthase inhibitors in rats. Author(s): Department of Pharmacology, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China. Source: Lu, R Hu, C P Wu, X P Liao, E Y Li, Y J Comp-Med. 2002 June; 52(3): 224-8

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Effect of ovariectomy, malnutrition and glucocorticoid application on bone properties in sheep: a pilot study. Author(s): AO Research Institute Davos, Davos, Switzerland. [email protected] Source: Lill, C A Fluegel, A K Schneider, E Osteoporos-Int. 2002; 13(6): 480-6 0937-941X

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Effects of cadmium intake on bone metabolism of mothers during pregnancy and lactation. Author(s): Department of Environmental and Occupational Health and Toxicology, Graduate School of Medical Sciences, Kitasato University, Kanagawa 228-8555, Japan. [email protected]

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Source: Ohta, H Ichikawa, M Seki, Y Tohoku-J-Exp-Med. 2002 January; 196(1): 33-42 0040-8727 •

Effects of vitamin K2, vitamin D, and calcium on the bone metabolism of rats in the growth phase. Author(s): Department of Orthopaedic Surgery, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. Source: Hirano, June Ishii, Yoshiaki J-Orthop-Sci. 2002; 7(3): 364-9 0949-2658

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Fatty acids, calcium and bone metabolism. Author(s): Department of Medical-Surgical Sciences, University of Padova, Italy. [email protected] Source: Baggio, B J-Nephrol. 2002 Nov-December; 15(6): 601-4 1120-3625

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For better bones, green vegetables. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. March 1999. volume 17 (1) page 1.

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High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone. Author(s): Unit of Academic Radiotherapy and Clinical Oncology, Royal Marsden NHS Trust, Sutton, Surrey SM2 5PT, UK. [email protected] Source: O'Sullivan, J M McCready, V R Flux, G Norman, A R Buffa, F M Chittenden, S Guy, M Pomeroy, K Cook, G Gadd, J Treleaven, J Al Deen, A Horwich, A Huddart, R A Dearnaley, D P Br-J-Cancer. 2002 June 5; 86(11): 1715-20 0007-0920

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How to build better bones: overview of all the new osteoporosis options. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. Sept 2001. volume 24 (9) page 1, 4-5. 0893-4452

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Influence of dietary phosphorus deficiency with or without addition of fumaric acid to a diet in pigs on bone parameters. Author(s): Institute of Animal Nutrition, Zurich, Switzerland, Novartis, Basel, Switzerland. [email protected] Source: Liesegang, A Ursprung, R Gasser, J Sassi, M L Risteli, J Riond, J L Wanner, M JAnim-Physiol-Anim-Nutr-(Berl). 2002 February; 86(1-2): 1-16 0931-2439

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Inhibitory effect of Carthamus tinctorius L. seed extracts on bone resorption mediated by tyrosine kinase, COX-2 (cyclooxygenase) and PG (prostaglandin) E2. Author(s): Department of Acupuncture and Moxibustion, College of Oriental Medicine, Woosuk University, Chonbuk, Korea. Source: Yuk, T H Kang, J H Lee, S R Yuk, S W Lee, K G Song, B Y Kim, C H Kim, D W Dong, I K Lee, T K Lee, C H Am-J-Chin-Med. 2002; 30(1): 95-108 0192-415X

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Leptin predicts bone and fat mass after accounting for the effects of diet and glucocorticoid treatment in piglets. Author(s): Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2. [email protected] Source: Weiler, H A Kovacs, H Murdock, C Adolphe, J Fitzpatrick Wong, S Exp-BiolMed-(Maywood). 2002 September; 227(8): 639-44 1535-3702

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Maintenance of trabecular structure and bone volume by vitamin K(2) in mature rats with long-term tail suspension. Author(s): Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Japan. Source: Iwasaki, Y Yamato, H Murayama, H Sato, M Takahashi, T Ezawa, I Kurokawa, K Fukagawa, M J-Bone-Miner-Metab. 2002; 20(4): 216-22 0914-8779

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Measuring elastic properties of bones and silicon from V(z) curve generated by multiply reflected signals. Author(s): Department of Civil Engineering and Engineering Mechanics, The University of Arizona, Tucson 85721-0072, USA. [email protected] Source: Kundu, T Jorgensen, C S Ultrasonics. 2002 April; 39(7): 515-24 0041-624X

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Mechanical strain and bone cell function: a review. Author(s): Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK. Source: Ehrlich, P J Lanyon, L E Osteoporos-Int. 2002 September; 13(9): 688-700 0937941X

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Mechanisms of bone loss and gain in untreated and treated osteoporosis. Author(s): Department of Medicine, University of Cambridge School of Clinical Medicine, UK. [email protected] Source: Compston, J Endocrine. 2002 February; 17(1): 21-7 0969-711X

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Mechanisms of proton transport in isolated rat osteoclasts attached to bone. Author(s): Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Japan. [email protected] Source: Shibata, T Amano, H Yamada, S Ohya, K J-Med-Dent-Sci. 2000 September; 47(3): 177-85 1342-8810

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Molecular genetics of calcium sensing in bone cells. Author(s): Discovery Genetics, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK. Source: Purroy, J Spurr, N K Hum-Mol-Genet. 2002 October 1; 11(20): 2377-84 0964-6906

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'Mom & me' and healthy bones. An innovative approach to teaching bone health. Author(s): Creighton University School of Nursing and Clinical Research Nurse, Osteoporosis Research Center, Omaha, Nebraska, USA. Source: Lypaczewski, Gina Lappe, Joan Stubby, Julie Orthop-Nurs. 2002 Mar-April; 21(2): 35-42 0744-6020

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Not just for healthy bones and teeth. Source: MacDonald, H B Alta-RN. 2001 October; 57(5): 5 1481-9988

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Nutrition and molecular markers of bone remodelling. Author(s): ANZAC Research Institute and Department of Endocrinology & Metabolism, Concord Hospital Medical Centre, The University of Sydney, Sydney, New South Wales, Australia. [email protected] Source: Seibel, M J Curr-Opin-Clin-Nutr-Metab-Care. 2002 September; 5(5): 525-31 13631950

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Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors. Author(s): Department of Medicine, University of Tokyo School of Medicine, Japan. Source: Takeuchi, Y Fukumoto, S Nakayama, K Tamura, Y Yanagisawa, A Fujita, T JBone-Miner-Res. 2002 May; 17(5): 753-7 0884-0431

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Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1alpha,25-dihydroxyvitamin D3. Author(s): Institute of Physiology, Physiological Chemistry, and Animal Nutrition, Ludwig Maximilians University, Munich, Germany. Source: Erben, R G Mosekilde, L Thomsen, J S Weber, K Stahr, K Leyshon, A Smith, S Y Phipps, R J-Bone-Miner-Res. 2002 August; 17(8): 1498-511 0884-0431

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Project Healthy Bones: An osteoporosis prevention program for older adults. Source: Klotzbach Shimomura, K. J-ext. United States : Extension Journal, Inc., [1987-. June 2001. volume 39 (3) page n/a. 1077-5315

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Responses of bone turnover markers and bone mineral density to growth hormone therapy in children with isolated growth hormone deficiency and multiple pituitary hormone deficiencies. Author(s): Division of Pediatric Endocrinology, Ihsan Dogramaci Children's Hospital, Hacettepe University, Ankara, Turkey. Source: Kandemir, N Gonc, E N Yordam, N J-Pediatr-Endocrinol-Metab. 2002 June; 15(6): 809-16

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Restoring aging bones. Source: Rosen, C J Sci-Am. 2003 March; 288(3): 70-7 0036-8733

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Side benefits of cutting back on salt: better diet and bone health. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. Sept 2000. volume 23 (9) page 1, 4. 0893-4452

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The effects of growth hormone replacement therapy on bone metabolism in adultonset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. Author(s): Department of Endocrinology, University Hospital Gasthuisberg, Leuven, Belgium. Source: Bex, M Abs, R Maiter, D Beckers, A Lamberigts, G Bouillon, R J-Bone-Miner-Res. 2002 June; 17(6): 1081-94 0884-0431

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The effects of synthetic conjugated estrogens, a (cenestin) on trabecular bone structure and strength in the ovariectomized rat model. Author(s): Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA. [email protected] Source: Lane, N E Kumer, J L Majumdar, S Khan, M Lotz, J Stevens, R E Klein, R Phelps, K V Osteoporos-Int. 2002 October; 13(10): 816-23 0937-941X

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The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat. Author(s): Department of Clinical Biochemistry, Silesian Medical Academy, Zabrze, Poland. [email protected] Source: Ostrowska, Z Kos Kudla, B Marek, B Kajdaniuk, D Staszewicz, P Szapska, B Strzelczyk, J Neuroendocrinol-Lett. 2002 April; 23 Suppl 1: 104-9 0172-780X

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The interaction of glucocorticoids with the growth hormone-insulin-like growth factor axis and its effects on growth plate chondrocytes and bone cells. Author(s): Division of Pediatric Nephrology, University Children 's Hospital of Heidelberg, Germany. [email protected] Source: Mehls, O Himmele, R Homme, M Kiepe, D Klaus, G J-Pediatr-EndocrinolMetab. 2001; 14 Suppl 6: 1475-82

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The relationship between the daily profile of chosen biochemical markers of bone metabolism and melatonin and other hormone secretion in rats under physiological conditions. Author(s): Department of Clinical Biochemistry, Silesian Medical Academy, Pl. Traugutta 2, 41-800 Zabrze, Poland. [email protected] Source: Ostrowska, Z Kos Kudla, B Marek, B Kajdaniuk, D Ciesielska Kopacz, N Neuroendocrinol-Lett. 2002 Oct-December; 23(5-6): 417-25 0172-780X

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The role of bone density measurements in the evaluation of new treatments for osteoporosis. Author(s): Department of Nuclear Medicine, Guy's Hospital, St Thomas Street, London, SE1 9RT, UK. [email protected] Source: Blake, G M Fogelman, I Curr-Pharm-Des. 2002; 8(21): 1885-1905 1381-6128

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Tissue culture models for studies of hormone and vitamin action in bone cells. Author(s): Women's Health Research Institute, Wyeth-Ayerst Research, Collegeville, Pennsylvania 19426, USA. Source: Bodine, Peter V N Komm, Barry S Vitam-Horm. 2002; 64: 101-51 0083-6729

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Total body bone mineral content and tibial cortical bone measures in preschool children. Author(s): E.A. Martin Program in Human Nutrition, South Dakota State University, Brookings 57007, USA. Source: Specker, B L Johannsen, N Binkley, T Finn, K J-Bone-Miner-Res. 2001 December; 16(12): 2298-305 0884-0431

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Treatment of soft tissue defects with exposed bone in the head and face region with alginates and hydrocolloid dressings. Author(s): Department of Maxillofacial Surgery, University of Bonn, Germany. [email protected] Source: von Lindern, J J Niederhagen, B Appel, T Berge, S J-Oral-Maxillofac-Surg. 2002 October; 60(10): 1126-30 0278-2391

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Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. Author(s): Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Source: De Beur, S M Finnegan, R B Vassiliadis, J Cook, B Barberio, D Estes, S Manavalan, P Petroziello, J Madden, S L Cho, J Y KuMarch, R Levine, M A Schiavi, S C J-Bone-Miner-Res. 2002 June; 17(6): 1102-10 0884-0431

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VDR gene polymorphisms are overrepresented in german patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism. Author(s): Medical Dept. I, Johann-Wolfgang-Goethe-University, Frankfurt, Germany. Source: Fassbender, W J Goertz, B Weismuller, K Steinhauer, B Stracke, H Auch, D Linn, T Bretzel, R G Horm-Metab-Res. 2002 June; 34(6): 330-7 0018-5043

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Vitamin D receptor and estrogen receptor gene polymorphisms in postmenopausal Danish women: no relation to bone markers or serum lipoproteins. Author(s): Center for Clinical and Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. Source: Bagger, Y Z Hassager, C Heegaard, A M Christiansen, C Climacteric. 2000 June; 3(2): 84-91 1369-7137

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Vitamins Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin B12 (Cobalamin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html Vitamin K Source: Healthnotes, Inc.; www.healthnotes.com

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Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin K Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10068,00.html •

Minerals Boron Source: Healthnotes, Inc.; www.healthnotes.com Boron Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Calcium: Which Form Is Best? Source: Healthnotes, Inc.; www.healthnotes.com Chromium Source: Integrative Medicine Communications; www.drkoop.com Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: Integrative Medicine Communications; www.drkoop.com Copper Source: Prima Communications, Inc.www.personalhealthzone.com

Nutrition

Copper Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,886,00.html Folate Source: Integrative Medicine Communications; www.drkoop.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Iodine Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Manganese Source: Healthnotes, Inc.; www.healthnotes.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Manganese Source: Prima Communications, Inc.www.personalhealthzone.com Potassium Source: Integrative Medicine Communications; www.drkoop.com Potassium-sparing Diuretics Source: Integrative Medicine Communications; www.drkoop.com Retinol Source: Integrative Medicine Communications; www.drkoop.com Sodium Fluoride Source: Healthnotes, Inc.; www.healthnotes.com Sulfur Source: Healthnotes, Inc.; www.healthnotes.com

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Vanadium Source: Healthnotes, Inc.; www.healthnotes.com Vanadium Alternative names: Vanadate, Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Vanadium Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin A (Retinol) Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html •

Food and Diet Almonds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,113,00.html Arugula Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,123,00.html Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Barley Source: Healthnotes, Inc.; www.healthnotes.com Beef Source: Healthnotes, Inc.; www.healthnotes.com Beef Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,85,00.html Betaine (Trimethylglycine) Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Bluefish Source: Healthnotes, Inc.; www.healthnotes.com Bluefish Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,164,00.html Bok Choy Source: Healthnotes, Inc.; www.healthnotes.com Broccoli Source: Healthnotes, Inc.; www.healthnotes.com Buffalo Source: Healthnotes, Inc.; www.healthnotes.com Burdock Alternative names: Arctium lappa, Arctium minus, Arctium tomentosum Source: Integrative Medicine Communications; www.drkoop.com Carp Source: Healthnotes, Inc.; www.healthnotes.com Cartilage Alternative names: Shark Cartilage Source: Integrative Medicine Communications; www.drkoop.com Catfish Source: Healthnotes, Inc.; www.healthnotes.com Chicken Source: Healthnotes, Inc.; www.healthnotes.com Chicken Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,86,00.html Chicory Source: Healthnotes, Inc.; www.healthnotes.com Chondroitin Sulfate Source: Healthnotes, Inc.; www.healthnotes.com Cod Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com

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Collards Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Greens Source: Healthnotes, Inc.; www.healthnotes.com Duck Source: Healthnotes, Inc.; www.healthnotes.com Duck Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,87,00.html Flounder Source: Healthnotes, Inc.; www.healthnotes.com Gluten-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Goose Source: Healthnotes, Inc.; www.healthnotes.com Guinea Fowl Source: Healthnotes, Inc.; www.healthnotes.com Halibut Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com Homeopathic Remedies for Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Kombu Source: Healthnotes, Inc.; www.healthnotes.com Lamb Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,90,00.html Lamb and Mutton Source: Healthnotes, Inc.; www.healthnotes.com Low Back Pain Source: Healthnotes, Inc.; www.healthnotes.com Low-Fat Diet Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com Milk Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,95,00.html Monkfish Source: Healthnotes, Inc.; www.healthnotes.com Mullet Source: Healthnotes, Inc.; www.healthnotes.com Mustard Greens Source: Healthnotes, Inc.; www.healthnotes.com Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Perch Source: Healthnotes, Inc.; www.healthnotes.com Pork Source: Healthnotes, Inc.; www.healthnotes.com Rockfish Source: Healthnotes, Inc.; www.healthnotes.com Romaine Lettuce Source: Healthnotes, Inc.; www.healthnotes.com Rye Source: Healthnotes, Inc.; www.healthnotes.com Salmon Source: Healthnotes, Inc.; www.healthnotes.com Salmon Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,102,00.html Sardines Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,317,00.html Shark Source: Healthnotes, Inc.; www.healthnotes.com

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Smelt Source: Healthnotes, Inc.; www.healthnotes.com Soy Source: Healthnotes, Inc.; www.healthnotes.com Soybeans Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,105,00.html Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com Sucralfate Source: Healthnotes, Inc.; www.healthnotes.com Surimi Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com Tilefish Source: Healthnotes, Inc.; www.healthnotes.com Trout Source: Healthnotes, Inc.; www.healthnotes.com Turkey Source: Healthnotes, Inc.; www.healthnotes.com Turkey Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,92,00.html Variety Meats Source: Healthnotes, Inc.; www.healthnotes.com Veal Source: Healthnotes, Inc.; www.healthnotes.com Venison Source: Healthnotes, Inc.; www.healthnotes.com Water Source: Healthnotes, Inc.; www.healthnotes.com Wheat Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Whey Protein Source: Healthnotes, Inc.; www.healthnotes.com Winter Squash Source: Healthnotes, Inc.; www.healthnotes.com Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND BONES Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bones. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “bones” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •

Alternative Medicine Handbook: The Complete Reference Guide to Alternative and Complementary Therapies Source: New York, NY: W.W. Norton. 1998. 340 p. Contact: Available from W.W. Norton and Company, Inc. 500 Fifth Avenue, New York, NY 10110. (212) 354-5500; FAX: 212-869-0856. PRICE: $25.00. ISBN: 0393045668. Summary: This book describes 53 major alternative and complementary medicine practices. It does not recommend treatments, but instead provides information about their backgrounds, goals, benefits, and risks to help the reader make informed choices. It is divided into seven sections addressing different categories of alternative and complementary treatments: (1) traditional healing methods, which typically are ancient approaches that offer remedies in the context of spiritual or lifestyle guidance; (2) dietary and herbal remedies; (3) methods that involve active use of the mind to heal the body; (4) biologic therapies involving unproven pharmacologic and other types of

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medication; (5) bodywork, involving manipulation of muscles and bones; (6) use of the senses to enhance well-being; and (7) the application of external energies to restore health. Each section contains several chapters, each of which include a brief introduction, a description of the alternative or complementary therapy, and information about the claims of practitioners, theories or beliefs upon which the therapy is based, available research, potential benefits, and where to find additional information. This book contains a list of complementary therapies for common ailments, a glossary, a list of professional degrees and titles, and an index.

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 bones 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 “bones” (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 bones: •

99mTechnetium-labeled methylene diphosphonate uptake in maxillary bone during and after rapid maxillary expansion. Author(s): Arat ZM, Gokalp H, Atasever T, Turkkahraman H. Source: Angle Orthod. 2003 October; 73(5): 545-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14580022&dopt=Abstract

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Action of green tea catechin on bone metabolic disorder in chronic cadmiumpoisoned rats. Author(s): Choi JH, Rhee IK, Park KY, Park KY, Kim JK, Rhee SJ. Source: Life Sciences. 2003 August 8; 73(12): 1479-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865088&dopt=Abstract

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Bone augmentation using rhGDF-5-collagen composite. Author(s): Kuniyasu H, Hirose Y, Ochi M, Yajima A, Sakaguchi K, Murata M, Pohl J. Source: Clinical Oral Implants Research. 2003 August; 14(4): 490-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869012&dopt=Abstract

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Bone mineral density in premenopausal women with systemic lupus erythematosus. Author(s): Uaratanawong S, Deesomchoke U, Lertmaharit S, Uaratanawong S. Source: The Journal of Rheumatology. 2003 November; 30(11): 2365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677178&dopt=Abstract

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Bones and nutrition: common sense supplementation for osteoporosis. Author(s): Advani S, Wimalawansa SJ.

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Source: Curr Womens Health Rep. 2003 June; 3(3): 187-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734028&dopt=Abstract •

Calcium and bone health in infants. Author(s): Koo WW, Warren L. Source: Neonatal Netw. 2003 September-October; 22(5): 23-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598978&dopt=Abstract

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Calcium supplementation provides an extended window of opportunity for bone mass accretion after menarche. Author(s): Rozen GS, Rennert G, Dodiuk-Gad RP, Rennert HS, Ish-Shalom N, Diab G, Raz B, Ish-Shalom S. Source: The American Journal of Clinical Nutrition. 2003 November; 78(5): 993-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594787&dopt=Abstract

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Changes of resistance parameters of femoral bone in adult female rats after application of zoladex and vincristin. Author(s): Nadulska A, Klukowska L, Dyba S. Source: Ann Univ Mariae Curie Sklodowska [med]. 2002; 57(2): 426-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898874&dopt=Abstract

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Chinese herbs and bone disease. Author(s): Hoshino J, Ubara Y, Tagami T, Sawa N, Yokota M, Katori H, Takemoto F, Mikami Y, Hara S, Hara S. Source: Intern Med. 2003 April; 42(4): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729324&dopt=Abstract

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Competitive binding of Pu and Am with bone mineral and novel chelating agents. Author(s): Guilmette RA, Hakimi R, Durbin PW, Xu J, Raymond KN. Source: Radiat Prot Dosimetry. 2003; 105(1-4): 527-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527022&dopt=Abstract

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Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. Author(s): Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, Meunier PJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970287&dopt=Abstract

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Demonstration of altered signaling responses in bone marrow extracellular fluid during increased hematopoiesis in rats using a centrifugation method. Author(s): Wiig H, Berggreen E, Borge BA, Iversen PO.

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Source: American Journal of Physiology. Heart and Circulatory Physiology. 2004 January 8 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715508&dopt=Abstract •

Dentin sialoprotein in bone and dentin sialophosphoprotein gene expressed by osteoblasts. Author(s): Qin C, Brunn JC, Cadena E, Ridall A, Butler WT. Source: Connective Tissue Research. 2003; 44 Suppl 1: 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952194&dopt=Abstract

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Dietary intake and bone status with aging. Author(s): Tucker KL. Source: Current Pharmaceutical Design. 2003; 9(32): 2687-704. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529541&dopt=Abstract

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Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. Author(s): Setchell KD, Lydeking-Olsen E. Source: The American Journal of Clinical Nutrition. 2003 September; 78(3 Suppl): 593S609S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936954&dopt=Abstract

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Dose response of bone mass to dietary arachidonic acid in piglets fed cow milk-based formula. Author(s): Blanaru JL, Kohut JR, Fitzpatrick-Wong SC, Weiler HA. Source: The American Journal of Clinical Nutrition. 2004 January; 79(1): 139-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684410&dopt=Abstract

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Dynamics of bone tissue formation in tooth extraction sites. An experimental study in dogs. Author(s): Cardaropoli G, Araujo M, Lindhe J. Source: Journal of Clinical Periodontology. 2003 September; 30(9): 809-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956657&dopt=Abstract

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Effect of recombinant human bone morphogenetic protein-4 with carriers in rat calvarial defects. Author(s): Ahn SH, Kim CS, Suk HJ, Lee YJ, Choi SH, Chai JK, Kim CK, Han SB, Cho KS. Source: J Periodontol. 2003 June; 74(6): 787-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886988&dopt=Abstract

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Effect of Rehmannia glutinosa Libosch extracts on bone metabolism. Author(s): Oh KO, Kim SW, Kim JY, Ko SY, Kim HM, Baek JH, Ryoo HM, Kim JK.

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Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 August; 334(1-2): 185-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867291&dopt=Abstract •

Effects of a herbal extract on the bone density, strength and markers of bone turnover of mature ovariectomized rats. Author(s): Xu M, Dick IM, Day R, Randall D, Prince RL. Source: The American Journal of Chinese Medicine. 2003; 31(1): 87-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723758&dopt=Abstract

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Effects of dietary improvement on bone metabolism in elderly underweight women with osteoporosis: a randomised controlled trial. Author(s): Hampson G, Martin FC, Moffat K, Vaja S, Sankaralingam S, Cheung J, Blake GM, Fogelman I. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 September; 14(9): 750-6. Epub 2003 August 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904840&dopt=Abstract

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Effects of local administration of growth hormone in peri-implant bone: an experimental study with implants in rabbit tibiae. Author(s): Tresguerres IF, Blanco L, Clemente C, Tresguerres JA. Source: Int J Oral Maxillofac Implants. 2003 November-December; 18(6): 807-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696655&dopt=Abstract

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Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Author(s): Grados F, Brazier M, Kamel S, Duver S, Heurtebize N, Maamer M, Mathieu M, Garabedian M, Sebert JL, Fardellone P. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2003 June; 70(3): 203-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814763&dopt=Abstract

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Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation. Author(s): Li B, Yu S. Source: Biological & Pharmaceutical Bulletin. 2003 June; 26(6): 780-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808286&dopt=Abstract

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Guidelines for using in vitro methods to study the effects of phyto-oestrogens on bone. Author(s): Lieberherr M, Cournot G, Robins SP.

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Source: The British Journal of Nutrition. 2003 June; 89 Suppl 1: S59-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725651&dopt=Abstract •

Heat distribution and heat transport in bone during radiofrequency catheter ablation. Author(s): Rachbauer F, Mangat J, Bodner G, Eichberger P, Krismer M. Source: Archives of Orthopaedic and Trauma Surgery. 2003 April; 123(2-3): 86-90. Epub 2003 March 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721686&dopt=Abstract

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Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. Author(s): Chiba H, Uehara M, Wu J, Wang X, Masuyama R, Suzuki K, Kanazawa K, Ishimi Y. Source: The Journal of Nutrition. 2003 June; 133(6): 1892-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771335&dopt=Abstract

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Immediate placement of implants into periodontally infected sites in dogs: a histomorphometric study of bone-implant contact. Author(s): Novaes AB Jr, Marcaccini AM, Souza SL, Taba M Jr, Grisi MF. Source: Int J Oral Maxillofac Implants. 2003 May-June; 18(3): 391-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814314&dopt=Abstract

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In vivo administration of recombinant TNF-alpha promotes bone resorption in mice. Author(s): Gaspersic R, Stiblar-Martincic D, Osredkar J, Skaleric U. Source: Journal of Periodontal Research. 2003 August; 38(4): 446-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828665&dopt=Abstract

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Influence of demineralized bone matrix's embryonic origin on bone formation: an experimental study in rats. Author(s): Stavropoulos A, Kostopoulos L, Mardas N, Karring T. Source: Clinical Implant Dentistry and Related Research. 2003; 5(3): 184-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14575635&dopt=Abstract

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Intracellular membrane trafficking in bone resorbing osteoclasts. Author(s): Mulari M, Vaaraniemi J, Vaananen HK. Source: Microscopy Research and Technique. 2003 August 15; 61(6): 496-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879417&dopt=Abstract

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Langerhans' cell histiocytosis with bilateral temporal bone involvement. Author(s): Kleinjung T, Woenckhaus M, Bachthaler M, Wolff JE, Wolf SR.

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Source: American Journal of Otolaryngology. 2003 July-August; 24(4): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884222&dopt=Abstract •

Long-term supplementation of various dietary lipids alters bone mineral content, mechanical properties and histological characteristics of Japanese quail. Author(s): Liu D, Veit HP, Wilson JH, Denbow DM. Source: Poultry Science. 2003 May; 82(5): 831-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762407&dopt=Abstract

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Modulation of isoflavones on bone-nodule formation in rat calvaria osteoblasts in vitro. Author(s): Chang H, Jin TY, Jin WF, Gu SZ, Zhou YF. Source: Biomed Environ Sci. 2003 March; 16(1): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747011&dopt=Abstract

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Periodontal regeneration with a combination of enamel matrix proteins and autogenous bone grafting. Author(s): Cochran DL, Jones A, Heijl L, Mellonig JT, Schoolfield J, King GN. Source: J Periodontol. 2003 September; 74(9): 1269-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14584859&dopt=Abstract

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Purification and quantification of opioid peptides in bone and joint tissues--a methodological study in the rat. Author(s): Bergstrom J, Ahmed M, Kreicbergs A, Nylander I. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 2003 May; 21(3): 465-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706019&dopt=Abstract

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Radiologic characterization of new bone generated from distraction after maxillary bone transport. Author(s): Cheung LK, Zhang Q. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 August; 96(2): 234-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931099&dopt=Abstract

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Solitary bone metastasis from myxoid liposarcoma. Author(s): Mai SK, Voggenreiter G, Neff KW, Diehl S, Duber C, Wenz F. Source: Onkologie. 2003 August; 26(4): 341-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972699&dopt=Abstract

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Soy phytoestrogens do not prevent bone loss in postmenopausal monkeys. Author(s): Register TC, Jayo MJ, Anthony MS.

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Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4362-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970311&dopt=Abstract •

The effect of polyunsaturated fatty acids, including conjugated linoleic acid, on calcium absorption and bone metabolism and composition in young growing rats. Author(s): Kelly O, Cusack S, Jewell C, Cashman KD. Source: The British Journal of Nutrition. 2003 October; 90(4): 743-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129442&dopt=Abstract

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Tissue engineering and cell therapy of cartilage and bone. Author(s): Cancedda R, Dozin B, Giannoni P, Quarto R. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 2003 March; 22(1): 81-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714045&dopt=Abstract

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UK Food Standards Agency Optimal Nutrition Status Workshop: environmental factors that affect bone health throughout life. Author(s): Burns L, Ashwell M, Berry J, Bolton-Smith C, Cassidy A, Dunnigan M, Khaw KT, Macdonald H, New S, Prentice A, Powell J, Reeve J, Robins S, Teucher B. Source: The British Journal of Nutrition. 2003 June; 89(6): 835-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828800&dopt=Abstract

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Ultrastructural and histochemical examination of alveolar bone at the pressure areas of rat molars submitted to continuous orthodontic force. Author(s): Bonafe-Oliveira L, Faltin RM, Arana-Chavez VE. Source: European Journal of Oral Sciences. 2003 October; 111(5): 410-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974685&dopt=Abstract

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What families with children with brittle bones want to tell. Author(s): Bernehall Claesson I, Brodin J. Source: Child: Care, Health and Development. 2002 July; 28(4): 309-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211190&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/

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

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

Alternative Medicine

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

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

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

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

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

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

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

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

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

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

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

General Overview Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Allergic Rhinitis Source: Integrative Medicine Communications; www.drkoop.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Amenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Angina Source: Healthnotes, Inc.; www.healthnotes.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Birth Defects Prevention Source: Healthnotes, Inc.; www.healthnotes.com

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Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Bone Infection Source: Integrative Medicine Communications; www.drkoop.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Bone Marrow Disorders Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Integrative Medicine Communications; www.drkoop.com Carpal Tunnel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Carpal Tunnel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Myelogenous Leukemia Source: Integrative Medicine Communications; www.drkoop.com Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com Common Cold/Sore Throat Source: Healthnotes, Inc.; www.healthnotes.com Cough Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine

Dermatitis Herpetiformis Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Endometriosis Source: Integrative Medicine Communications; www.drkoop.com Epstein-Barr Virus Source: Integrative Medicine Communications; www.drkoop.com Fever of Unknown Origin Source: Integrative Medicine Communications; www.drkoop.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Gingivitis Source: Healthnotes, Inc.; www.healthnotes.com Hay Fever Source: Integrative Medicine Communications; www.drkoop.com Hemophilia Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Homocysteine Source: Healthnotes, Inc.; www.healthnotes.com Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Hypoparathyroidism Source: Integrative Medicine Communications; www.drkoop.com

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Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Influenza Source: Healthnotes, Inc.; www.healthnotes.com Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Macular Degeneration Source: Healthnotes, Inc.; www.healthnotes.com Macular Degeneration Source: Prima Communications, Inc.www.personalhealthzone.com Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine

Menopause Source: Integrative Medicine Communications; www.drkoop.com Menorrhagia Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Mononucleosis Source: Integrative Medicine Communications; www.drkoop.com Myelofibrosis Source: Integrative Medicine Communications; www.drkoop.com Myeloproliferative Disorders Source: Integrative Medicine Communications; www.drkoop.com Nausea Source: Prima Communications, Inc.www.personalhealthzone.com Night Vision (Impaired) Source: Prima Communications, Inc.www.personalhealthzone.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osgood-Schlatter Disease Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteomyelitis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com

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Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Periodontal Disease Alternative names: Gum Disease Source: Prima Communications, Inc.www.personalhealthzone.com Polycythemia Vera Source: Integrative Medicine Communications; www.drkoop.com Pregnancy and Postpartum Support Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Healthnotes, Inc.; www.healthnotes.com Rheumatoid Arthritis Source: Healthnotes, Inc.; www.healthnotes.com Rickets/Osteomalacia Source: Healthnotes, Inc.; www.healthnotes.com Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com Sinus Congestion Source: Healthnotes, Inc.; www.healthnotes.com Sinusitis Source: Healthnotes, Inc.; www.healthnotes.com Sprains and Strains Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Temporomandibular Joint Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Tendinitis Source: Integrative Medicine Communications; www.drkoop.com

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Thrombocytosis Source: Integrative Medicine Communications; www.drkoop.com TMJ Source: Integrative Medicine Communications; www.drkoop.com Tuberculosis Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Prima Communications, Inc.www.personalhealthzone.com Weight Loss and Obesity Source: Healthnotes, Inc.; www.healthnotes.com Wounds Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Acupressure Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,662,00.html Apraxia Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/a.html Aston-Patterning Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10118,00.html Ayurveda Source: Integrative Medicine Communications; www.drkoop.com Bone Marrow Nei Kung Alternative names: Iron Shirt Chi Kung III Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/b.html Cell Therapy Source: Healthnotes, Inc.; www.healthnotes.com Chi Weight Lifting Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/c.html

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Chiropractic Source: Healthnotes, Inc.; www.healthnotes.com Chiropractic Source: Integrative Medicine Communications; www.drkoop.com Chiropractic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,681,00.html Clean-Me-Out Program Alternative names: Arise Shine Cleanse Thyself Program Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/c.html Craniosacral Therapy Alternative names: cranial balancing cranial osteopathy cranial sacral manipulation cranial technique cranial work craniopathy craniosacral balancing Craniosacral Osteopathy Cranio-Sacral work Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/c.html Craniosacral Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,685,00.html Hellerwork Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,700,00.html Hypnotherapy Source: Integrative Medicine Communications; www.drkoop.com Hypnotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,706,00.html Myotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,931,00.html Naturopathy Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine

Osteokinetics Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/o.html Osteopathy Source: Integrative Medicine Communications; www.drkoop.com Osteopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724,00.html Periosteal Acupuncture Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/p.html Reiki Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,731,00.html Rolfing Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,732,00.html Sacral/Spinal Energy Balancing Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html Sexual Energy Massage Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html Tai Chi Source: Integrative Medicine Communications; www.drkoop.com Tai Chi Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,737,00.html Zero Balancing Alternative names: ZB Core Zero Balancing Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/z.html

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Zulu Sangoma Bones Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/z.html •

Chinese Medicine Bajitian Alternative names: Morinda Root; Radix Morindae Officinalis Source: Chinese Materia Medica Dieda Wan Alternative names: Dieda Pills; Dieda Wan (Die Da Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Dihuang Alternative names: Digitalis Leaf; Yangdihuangye; Folium Digitalis Source: Chinese Materia Medica Duzhong Alternative names: Eucommia Bark; Cortex Eucommiae Source: Chinese Materia Medica Fufang Qianzheng Gao Alternative names: Compound Qianzheng Plaster Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Goupi Gao Alternative names: Goupi Plaster Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Guijia Alternative names: Tortoise Shell; Carapax et Plastrum Testudinis Source: Chinese Materia Medica Guilu Bushen Wan Alternative names: Guilu Bushen Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Gusuibu Alternative names: Fortune's Drynaria Rhizome; Rhizoma Drynariae Source: Chinese Materia Medica Haipiaoxiao Alternative names: Cuttlebone; Os Sepiae Source: Chinese Materia Medica

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Heshouwu Alternative names: Fleeceflower Root; Radix Polygoni Multiflori Source: Chinese Materia Medica Hongyao Tiegao Alternative names: Hongyao Plaster Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hujisheng Alternative names: Colored Mistletoe Herb; Herba Visci Source: Chinese Materia Medica Jianbu Wan Alternative names: Jianbu Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Kanggu Zengsheng Wan Alternative names: Kanggu Zengsheng Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Lingbao Huxin Dan Alternative names: Lingbao Huxin Micropills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Lurong Alternative names: Hairy Deer-horn (Hairy Antler); Cornu Cervi Pantotrichum Source: Chinese Materia Medica Luxiancao Alternative names: Pyrola Herb; Herba Pyrolae Source: Chinese Materia Medica Miaoji Wan Alternative names: Miaoji Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Niuxi Alternative names: Twotoothed Achyranthes Root; Radix Achyranthis Bidentatae Source: Chinese Materia Medica Qiannianjian Alternative names: Obscured Homalomena Rhizome; Rhizoma Homalomenae Source: Chinese Materia Medica Qishe Alternative names: Long-noded Pit Viper; Qishe (Qi She); Agkistrodon Source: Chinese Materia Medica

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Qufeng Zhitong Pian Alternative names: Qufeng Zhitong Tablets; Qufeng Zhitong Pian(Qu Feng Zhi Tong Pi An) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Sangjisheng Alternative names: Chinese Taxillus Herb; Herba Taxilli Source: Chinese Materia Medica Shengxue Wan Alternative names: Shengxue Pills; Shengxue Wan (Sheng Xue Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Shouwu Wan Alternative names: Shouwu Pills; Shouwu Wan (Shou Wu Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Shudihuang Alternative names: Prepared Rehmannia Root; Radix Rehmanniae Preparata Source: Chinese Materia Medica Shujin Wan Alternative names: Qufeng Shujin Pills; Qufeng Shujin Wan Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Tubiechong Alternative names: Ground Beetle; Eupolyphaga seu Steleophaga Source: Chinese Materia Medica Weilingxian Alternative names: Chinese Clematis Root; Radix Clematidis Source: Chinese Materia Medica Wujiapi Alternative names: Sienderstyle Acanthopanax Bark; Cortex Acanthopanacis Source: Chinese Materia Medica Wushaoshe Alternative names: Black-tail Snake; Zaocys Source: Chinese Materia Medica Xiangjiapi Alternative names: Chinese Silkvine Root-bark; Cortex Periplocae Source: Chinese Materia Medica

Alternative Medicine

Xianmao Alternative names: Common Curculigo Rhizome; Rhizoma Curculiginis Source: Chinese Materia Medica Xuduan Alternative names: Himalayan Teasel Root; Radix Dipsaci Source: Chinese Materia Medica Yinyanghuo Alternative names: Epimedium Herb; Herba Epimedii Source: Chinese Materia Medica Zhiheshouwu Alternative names: Prepared FLeeceflower Root; Radix Polygoni Multiflori Preparata Source: Chinese Materia Medica Zirantong Alternative names: Pyrite; Pyritum Source: Chinese Materia Medica •

Homeopathy Arnica Source: Healthnotes, Inc.; www.healthnotes.com Bellis Perennis Source: Healthnotes, Inc.; www.healthnotes.com Bryonia Source: Healthnotes, Inc.; www.healthnotes.com Calcarea Phosphorica Source: Healthnotes, Inc.; www.healthnotes.com Eupatorium Perfoliatum Source: Healthnotes, Inc.; www.healthnotes.com Hypericum Source: Healthnotes, Inc.; www.healthnotes.com Ruta Graveolens Source: Healthnotes, Inc.; www.healthnotes.com Symphytum Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements 7-keto Source: Healthnotes, Inc.; www.healthnotes.com

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Acorus Alternative names: Sweet Flag; Acorus calamus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Alendronate Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Amino Acid K Source: Integrative Medicine Communications; www.drkoop.com Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Andrographis Alternative names: Andrographis paniculata Source: Healthnotes, Inc.; www.healthnotes.com Androstenedione Source: Healthnotes, Inc.; www.healthnotes.com Antibiotics (general) Source: Prima Communications, Inc.www.personalhealthzone.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Aortic Glycosaminoglycans Source: Prima Communications, Inc.www.personalhealthzone.com Arctium Lappa Source: Integrative Medicine Communications; www.drkoop.com Arctium Minus Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine

Arctostaphylos Alternative names: Bearberry; Arctostaphylos uva-ursi (L.) Spreng. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arnica Alternative names: Arnica montana Source: Integrative Medicine Communications; www.drkoop.com Arnica Montana Source: Integrative Medicine Communications; www.drkoop.com Ashwagandha Alternative names: Withania somniferum Source: Healthnotes, Inc.; www.healthnotes.com Ashwagandha Source: Prima Communications, Inc.www.personalhealthzone.com Astragalus Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com Bisphosphonate Derivatives Source: Integrative Medicine Communications; www.drkoop.com Bisphosphonates Source: Healthnotes, Inc.; www.healthnotes.com Black Cohosh Alternative names: Cimicifuga racemosa Source: Healthnotes, Inc.; www.healthnotes.com Bone-Building Formula Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,838,00.html

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Boneset Alternative names: Eupatorium perfoliatum Source: Healthnotes, Inc.; www.healthnotes.com Boneset Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Boswellia Alternative names: Frankincense; Boswellia serrata Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bupleurum Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc.; www.healthnotes.com Caffeine Source: Healthnotes, Inc.; www.healthnotes.com Calciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Calcitonin Source: Healthnotes, Inc.; www.healthnotes.com Calcitrol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Calendula Alternative names: Calendula officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cardiac Glycosides Source: Integrative Medicine Communications; www.drkoop.com Carotenoids Source: Healthnotes, Inc.; www.healthnotes.com Catnip Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Caulophyllum Alternative names: Blue Cohosh; Caulophyllum thalictroides (MICH.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine

Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Chinese Scullcap Alternative names: Scutellaria baicalensis Source: Healthnotes, Inc.; www.healthnotes.com Chitosan Source: Healthnotes, Inc.; www.healthnotes.com Cholecalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Cobalamin Source: Integrative Medicine Communications; www.drkoop.com Coleus Alternative names: Coleus forskohlii Source: Healthnotes, Inc.; www.healthnotes.com Comfrey Alternative names: Symphytum officinale Source: Healthnotes, Inc.; www.healthnotes.com Comfrey Alternative names: Symphytum officinale, Knitbone Source: Integrative Medicine Communications; www.drkoop.com Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Corydalis Alternative names: Corydalis turtschaninovii, Corydalis yanhusuo Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com

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Diclofenac Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com EDTA Source: Integrative Medicine Communications; www.drkoop.com Elder Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Eleuthero Source: Healthnotes, Inc.; www.healthnotes.com Equisetum Arvense Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc.; www.healthnotes.com Estrogen Source: Prima Communications, Inc.www.personalhealthzone.com Estrogens (Combined) Source: Healthnotes, Inc.; www.healthnotes.com Ethylenediaminetetraacetic Acid (EDTA) Source: Integrative Medicine Communications; www.drkoop.com Felodipine Source: Healthnotes, Inc.; www.healthnotes.com Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Fo-Ti Alternative names: Polygonum multiflorum Source: Healthnotes, Inc.; www.healthnotes.com Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc.; www.healthnotes.com Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.drkoop.com

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Ginger Source: Prima Communications, Inc.www.personalhealthzone.com GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glucosamine Source: Integrative Medicine Communications; www.drkoop.com Glucosamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,790,00.html Gotu Kola Alternative names: Centella asiatica Source: Healthnotes, Inc.; www.healthnotes.com Gotu Kola Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10031,00.html Gravel Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Greater Celandine Alternative names: Chelidonium majus Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Source: Prima Communications, Inc.www.personalhealthzone.com Guatteria Alternative names: Guatteria gaumeri Greenman Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Heparin Source: Healthnotes, Inc.; www.healthnotes.com Heparin Alternative names: Hep-Lock Source: Prima Communications, Inc.www.personalhealthzone.com Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com

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Horsetail Alternative names: Equisetum arvense Source: Healthnotes, Inc.; www.healthnotes.com Horsetail Alternative names: Equisetum arvense, Scouring Rush, Shave Grass Source: Integrative Medicine Communications; www.drkoop.com Horsetail Source: Prima Communications, Inc.www.personalhealthzone.com Horsetail Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10105,00.html Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ipriflavone Source: Healthnotes, Inc.; www.healthnotes.com Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Ipriflavone Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10039,00.html Isoflavones Source: Prima Communications, Inc.www.personalhealthzone.com Kava Alternative names: Piper methysticum Source: Healthnotes, Inc.; www.healthnotes.com Knitbone Source: Integrative Medicine Communications; www.drkoop.com L-lysine Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine

Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Lubricant Laxatives Source: Integrative Medicine Communications; www.drkoop.com Lutein Source: Prima Communications, Inc.www.personalhealthzone.com Lysine Alternative names: Amino Acid K, L-Lysine Source: Integrative Medicine Communications; www.drkoop.com Medroxyprogesterone Source: Healthnotes, Inc.; www.healthnotes.com Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Miscellaneous Preparations Source: Integrative Medicine Communications; www.drkoop.com Nitrous Oxide Source: Healthnotes, Inc.; www.healthnotes.com Nitrous Oxide Source: Prima Communications, Inc.www.personalhealthzone.com Noni Alternative names: Morinda citrifolia Source: Healthnotes, Inc.; www.healthnotes.com Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Phenobarbital Source: Healthnotes, Inc.; www.healthnotes.com Phenobarbital Alternative names: Bellatal, Solfoton Source: Prima Communications, Inc.www.personalhealthzone.com Phenytoin Alternative names: Dilantin Infatab, Dilantin-125 Oral Suspension Source: Prima Communications, Inc.www.personalhealthzone.com Phosphorus Source: Integrative Medicine Communications; www.drkoop.com Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Picrorhiza Alternative names: Picrorhiza kurroa Source: Healthnotes, Inc.; www.healthnotes.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Reverse Transcriptase Inhibitors Source: Integrative Medicine Communications; www.drkoop.com Ribes Alternative names: Black Currant; Ribes nigrum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Risedronate Source: Healthnotes, Inc.; www.healthnotes.com Salicylates Source: Integrative Medicine Communications; www.drkoop.com

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Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Scouring Rush Source: Integrative Medicine Communications; www.drkoop.com Shark Cartilage Source: Integrative Medicine Communications; www.drkoop.com Shave Grass Source: Integrative Medicine Communications; www.drkoop.com Silicon Source: Healthnotes, Inc.; www.healthnotes.com Soy Isoflavones Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10057,00.html Strontium Source: Healthnotes, Inc.; www.healthnotes.com Sweet Annie Alternative names: Artemisia annua Source: Healthnotes, Inc.; www.healthnotes.com Symphytum Alternative names: Comfrey; Symphytum officinale L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Symphytum Officinale Source: Integrative Medicine Communications; www.drkoop.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Thioridazine Source: Healthnotes, Inc.; www.healthnotes.com Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thymus Extracts Source: Healthnotes, Inc.; www.healthnotes.com Thyroid Hormones Source: Healthnotes, Inc.; www.healthnotes.com

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Trace Minerals Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10061,00.html Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tylophora Alternative names: Tylophora indica, Tylophora asthmatica Source: Healthnotes, Inc.; www.healthnotes.com Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Valproic Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Vanadate Source: Integrative Medicine Communications; www.drkoop.com Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com Verbascum Alternative names: Mullein; Verbascum thapsus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Vitex agnus-castus Source: Healthnotes, Inc.; www.healthnotes.com Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Yarrow Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zingiber Officinale Source: Integrative Medicine Communications; www.drkoop.com

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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 BONES Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bones.

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

Bone Marrow Transplantation and Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia Condition(s): adult acute lymphoblastic leukemia in remission; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI); Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of bone marrow transplantation with standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002514

8

These are listed at www.ClinicalTrials.gov.

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Bone Marrow Transplantation in Treating Patients With Hematologic Cancers Condition(s): acute leukemia; atypical chronic myeloid leukemia; chronic leukemia; chronic myeloproliferative disorders; myelodysplastic and myeloproliferative disease; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of donor bone marrow transplantation in treating patients who have hematologic cancers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005797

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Bone Marrow Transplantation in Treating Patients With Multiple Myeloma, Chronic Phase Chronic Myelogenous Leukemia, or Agnogenic Myeloid Metaplasia Condition(s): chronic idiopathic myelofibrosis; Chronic Myelogenous Leukemia; Multiple Myeloma; refractory plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation in treating patients who have multiple myeloma, chronic phase chronic myelogenous leukemia, or agnogenic myeloid metaplasia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004181

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Bone Regeneration Using Stromal Cells Condition(s): Bone Disease; Craniofacial Abnormality; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate the possible use of bone marrow stromal cells-a type of cell related to bone and fibrous tissue-for jaw bone grafting. When a tooth is lost or removed, there is usually a gradual loss of bony tissue from the jawbone at the site of the missing tooth. This bone loss causes fragility that can extend and contribute to further tooth loss, and can make the use of dental implants less feasible. Stromal cells may become a source of cells for jawbone grafting to strengthen these areas. Normal volunteers between the ages of 18 and 70 years may be eligible for this study. Participants will fill out a medical history questionnaire, donate a small sample of bone

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marrow, and undergo a marrow biopsy, if needed. Bone marrow is aspirated from the ridge of the pelvic (hip) bone. For this procedure, the area is anesthetized with an injection of lidocaine, a needle is inserted into the bone and some marrow is sucked out into a syringe attached to the needle. If a biopsy specimen is needed, a special instrument is passed through the same spot as the aspiration and a small piece of bone marrow is taken out. The procedure takes about half an hour. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001391 •

Busulfan and Cyclophosphamide Followed by Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome Condition(s): adult acute monocytic leukemia; adult acute myeloid leukemia; atypical chronic myeloid leukemia; childhood acute myeloid leukemia and other myeloid malignancies; Chronic Myelomonocytic Leukemia; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of busulfan and cyclophosphamide followed by bone marrow transplantation in treating patients who have acute myelogenous leukemia or myelodysplastic syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004896

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Cancer in Inherited Bone Marrow Failure Syndromes Condition(s): Fanconi's Anemia; Anemia, Diamond-Blackfan; Dyskeratosis Congenital; Thrombocytopenia; Neutropenia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will establish a cohort (a group of people followed over time) of patients and families affected by an inherited bone marrow failure syndrome (IBMFS) that may predispose them to leukemia or other cancers. These syndromes include Fanconi's anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Pearson's syndrome, amegakaryocytic thrombocytopenia, thrombocytopenia absent radii, dyskeratosis congenita, and others. The study will try to identify the types of cancer the patient may be at risk for; measure the rates at which these cancers develop; look for early indicators of cancer; determine what distinguishes family members who develop cancer from those who do not; try to identify new genes that may be involved in causing IBMFS; compare the biology of cancers in patients and family member with IBMFS with the same cancers in people without IBMFS; evaluate the medical condition

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of affected family members and offer recommendations for future health care and cancer risk reduction; and evaluate whether carriers of just one abnormal gene develop significant health problems. (A carrier is someone who has only one altered gene for a disease that requires two altered genes to cause illness.) This study does not involve treatment. Patients with an IBMFS and their family members are eligible for this study. Participants must provide written permission for the study investigators to 1) obtain medical records and pathology material (tissue samples) from hospitals or clinics where the patient has been treated for blood diseases, tumors, cancer, birth defects, or other illnesses; and 2) obtain medical records and pathology materials from deceased relatives for whom the patient or family member is the legally authorized representative. Participants will complete a family history questionnaire and individual information questionnaire at the start of the study and provide updates annually. In addition, the following tissue samples may be requested: blood or cheek cells, tissue from a scheduled bone marrow procedure, and tumor tissue from prior biopsies or cancer surgeries. Instructions for sending specimens will be provided. Additional samples for research may be requested over time as tests or surgeries are done as part of the patient's standard medical care. Patients who agree to participate in a second part of this study will travel to the NIH Clinical Center for a comprehensive clinical and laboratory evaluation and screening for cancer or pre-cancerous conditions. The evaluation will include a detailed medical history, complete physical examination, cancer screening, and routine tests that are part of the standard medical management of persons with, or at risk of, the particular disorder. These include blood drawing, bone marrow aspirate and biopsy, urinalysis, stool examination, diagnostic X-rays and scans, and biopsies of tumors or pre-cancerous sites. In addition, special consultations may be requested depending on the individual's medical condition. These may include audiology, cardiology, social work, dentistry, dermatology, endocrinology, gastroenterology, gynecology, hematology, nephrology (kidney), neurology, ophthalmology, otorhinolaryngology (ear, nose and throat), physiatry, radiology and nuclear medicine and urology. Finally, patients and family members may choose to participate in a part of the study to identify the specific genetic alteration (mutation) responsible for the IBMFS affecting them in order to learn whether knowing the mutation makes it possible to predict 1) the severity of disease or 2) which medical problems that can arise with the disorder are likely to affect a given patient. Genetic testing will be done on tissue samples already provided for the study, and confirmed on new samples. Patients and family members who want to learn the results of the genetic tests will receive face-toface genetic counseling either at the NIH Clinical Center or from a counselor in their home community. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027274 •

Chemotherapy Followed by Peripheral Stem Cell or Bone Marrow Transplantation Compared With Chemotherapy Alone in Treating Patients With Small Cell Lung Cancer Condition(s): limited stage small cell lung cancer; extensive stage small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): EBMT Solid Tumors Working Party Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy

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with peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known whether high-dose chemotherapy plus peripheral stem cell or bone marrow transplantation is more effective than chemotherapy alone for treating small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by peripheral stem cell or bone marrow transplantation with that of chemotherapy alone in treating patients who have limited-stage or extensivestage small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011921 •

Chemotherapy Plus Bone Marrow Transplantation and Filgrastim in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome Condition(s): Acute Myeloid Leukemia; adult acute monocytic leukemia; atypical chronic myeloid leukemia; childhood acute monocytic leukemia; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing and die. Bone marrow transplantation may be able to replace cells that were destroyed by chemotherapy. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of chemotherapy plus bone marrow transplantation and filgrastim in treating patients who have acute myelogenous leukemia or myelodysplastic syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004899

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Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia Condition(s): untreated adult acute lymphoblastic leukemia; stage I adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; contiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II adult lymphoblastic lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Leukemia Cooperative Group; Leucemies Aigues et Lymphomes de l'Adulte Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. Bone marrow transplantation can

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replace immune cells that were destroyed by chemotherapy. PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002700 •

Combination Chemotherapy and Bone Marrow and/or Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma Condition(s): adult Burkitt's lymphoma; adult diffuse large cell lymphoma; adult diffuse mixed cell lymphoma; adult diffuse small cleaved cell lymphoma; adult immunoblastic large cell lymphoma; adult lymphoblastic lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): Fox Chase Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bone marrow and peripheral stem cell transplantation may allow doctors to give high doses of chemotherapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with cyclophosphamide, etoposide and cisplatin followed by bone marrow and/or peripheral stem cell transplantation in patients with relapsed or refractory intermediate- or high-grade non-Hodgkin's lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002521

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Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer Condition(s): bone marrow ablation; Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with thiotepa, carboplatin, and topotecan followed by bone marrow transplantation in treating patients who have metastatic or progressive rare cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002515

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Combination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplantation in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia Condition(s): juvenile myelomonocytic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Donor bone marrow transplantation or umbilical cord blood transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Combining chemotherapy with donor bone marrow or umbilical cord blood transplantation may be an effective treatment for juvenile myelomonocytic leukemia. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor bone marrow or umbilical cord blood transplantation in treating children who have newly diagnosed juvenile myelomonocytic leukemia. Phase(s): Phase II; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025038

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Combined Bone Marrow and Kidney Transplant for Multiple Myeloma with Kidney Failure Condition(s): Kidney Failure, Chronic; Multiple Myeloma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance Network Purpose - Excerpt: The purpose of this study is to determine whether a combined bone marrow and kidney transplant will be effective in treating stage II or greater multiple myeloma and associated kidney failure. This study will determine whether transplant rejection and the need for immunosuppressive drugs are decreased with this combined transplant approach. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062621

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Donor Bone Marrow Transplantation in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders Condition(s): acute leukemia; atypical chronic myeloid leukemia; chronic leukemia; chronic myeloproliferative disorders; myelodysplastic and myeloproliferative disease; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI)

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Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or total-body irradiation used to kill leukemia and lymphoma cells. Bone marrow transplantation using donated bone marrow may be an effective treatment for malignant or nonmalignant hematologic disorders. PURPOSE: Phase II trial to study the effectiveness of donor bone marrow transplantation in treating patients who have leukemia, lymphoma, or nonmalignant hematologic disorders. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005622 •

Electromagnetic Treatment For Bone Loss After Forearm Fracture Condition(s): Bone Disease, Metabolic; Osteopenia; Osteoporosis, Post-Traumatic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will determine the usefulness of pulsing electromagnetic field (PEMF) technology to reverse or reduce the bone loss (osteopenia) that occurs in the forearm after fracture or surgery. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067834

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Filgrastim-Mobilized Peripheral Stem Cell Transplantation Compared With Bone Marrow Transplantation From Compatible Unrelated Donors in Treating Patients With Hematologic Malignancies Condition(s): acute leukemia; chronic leukemia; chronic myeloproliferative disorders; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Blood and Marrow Transplant Clinical Trials Network; National Heart, Lung, and Blood Institute (NHLBI); National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Colony-stimulating factors, such as filgrastim, stimulate the production of blood cells. Peripheral stem cell transplantation or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Giving filgrastim to stimulate peripheral stem cells that can be collected for peripheral stem cell transplant may result in fewer side effects after the transplant. Sometimes the transplanted cells from a donor can be rejected by the body's tissues. Methotrexate and cyclosporine or tacrolimus may prevent this from happening. It is not yet known whether filgrastim-mobilized donor peripheral stem cell transplantation is more effective than donor bone marrow transplantation in treating hematologic malignancies. PURPOSE: Randomized phase III trial to compare the effectiveness of filgrastim-mobilized donor peripheral stem cell transplantation with

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that of donor bone marrow transplantation in treating patients who have hematologic cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00075816 •

Monoclonal Antibody CAL Compared With Zoledronate in Treating Women With Breast Cancer and Bone Metastases Condition(s): stage IV breast cancer; bone metastases; Pain Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies, such as CAL, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Zoledronate may prevent bone loss, relieve pain, and stop the growth of tumor cells in bone. It is not yet known whether the monoclonal antibody CAL is more effective than zoledronate in treating women who have breast cancer and bone metastases. PURPOSE: Randomized phase I/II trial to compare the effectiveness of the monoclonal antibody CAL with that of zoledronate in treating women who have breast cancer and bone metastases. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070356

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Monoclonal Antibody Compared With Zoledronate in Treating Women With Breast Cancer and Bone Metastases Condition(s): Hypercalcemia; stage IV breast cancer; recurrent breast cancer; bone metastases; Pain Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. It is not yet known whether monoclonal antibody is more effective than zoledronate in treating women who have breast cancer and bone metastases. PURPOSE: Randomized phase I/II trial to compare the effectiveness of monoclonal antibody with that of zoledronate in treating women who have breast cancer and bone metastases. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060138

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Monoclonal Antibody Therapy Plus Combination Chemotherapy and Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia Condition(s): adult acute myeloid leukemia in remission Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy plus combination chemotherapy and bone marrow transplantation in treating patients who have acute myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005940

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Monoclonal Antibody, Cyclophosphamide, and Radiation Therapy Followed by Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome Condition(s): adult acute myeloid leukemia; childhood acute myeloid leukemia; Chronic Myelomonocytic Leukemia; juvenile myelomonocytic leukemia; Myelodysplastic Syndromes; secondary acute myeloid leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining monoclonal antibody therapy with chemotherapy and radiation therapy may kill more cancer cells. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody, cyclophosphamide, total-body irradiation, and bone marrow transplant in treating patients who have advanced acute myeloid leukemia or myelodysplastic syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003868

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Radiofrequency Ablation in Treating Patients With Bone Metastases Condition(s): bone metastases; Pain Study Status: This study is currently recruiting patients.

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Sponsor(s): American College of Radiology Imaging Network; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiofrequency ablation may be effective in decreasing pain from bone metastases. PURPOSE: Phase I/II trial to study the effectiveness of radiofrequency ablation in decreasing pain in patients who have bone metastases. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026247 •

Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant Condition(s): Kidney Failure; Bone Marrow Transplantation; Kidney Transplantation; Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance Network Purpose - Excerpt: This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063817

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Relationship Between Personality and Coping Styles in Bone Marrow Transplant Candidates Condition(s): Bone Marrow Transplantation; Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will look at how people cope with an upcoming bone marrow transplant and how personality characteristics influence coping styles in stressful medical situations. Personality traits, such as extraversion, optimism and selfesteem have been related to active, problem-focused coping styles, whereas neuroticism has been related to increased psychological distress and denial as a way of coping. Coping styles, in turn, have been related to disease outcome. For example, a fighting spirit and avoidance have been correlated with longer survival, whereas fatalism, anxious preoccupation and feelings of helplessness and hopelessness were related to a poor disease outcome. A better understanding of the relationship between coping styles and personality may help improve supportive care for people undergoing bone marrow transplants. This study will: - Explore the relationship between personality traits, coping styles and psychological stress in patients awaiting bone marrow transplantation -

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Identify what coping styles people use to prepare for bone marrow transplantation Identify what personality traits are related to particular coping styles in patients awaiting bone marrow transplantation - Identify the relationship between personality factors and level of psychological distress in patients awaiting bone marrow transplantation Cancer patients 18 years of age and older who are scheduled for bone marrow transplant are eligible for this study. Participants will fill out pencil-and-paper questionnaires providing demographic information (such as age, gender, marital status, ethnicity, and so forth) and answering questions about their opinions and preferences. The information will be used to assess the participants' personality characteristics, coping styles, and psychological distress. The questionnaires take about 45 to 50 minutes to complete. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048256 •

Sargramostim Following Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia; atypical chronic myeloid leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood, and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation followed by sargramostim in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002778

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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 currently recruiting patients. 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.

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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 •

Bone Development in Adolescent Girls: Effects of Calcium and Exercise Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Osteoporosis is a major public health problem. Prevention of osteoporosis depends in part on good bone development in childhood and adolescence. This study will evaluate a weight-bearing exercise program and high-calcium diet on bone development in adolescent girls. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063011

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Bone Marrow Injection to Replace Diseased Bone in Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome Condition(s): Polyostotic Fibrous Dysplasia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR) Purpose - Excerpt: This study will evaluate the effectiveness of a new bone injection technique for treating bone disease in patients with polyostotic fibrous dysplasia or McCune-Albright syndrome. In these patients, some bones develop areas with much less mineral, making the bones more prone to fracture or deformity and causing pain. This new treatment is intended to reduce the risk of fracture, minimize deformities and improve overall function in these patients. Patients 4 years of age and older with bone lesions that are highly likely to cause significant pain and illness may be eligible for this 2-year study. Participants must be simultaneously enrolled in NIDCR's research protocol 98-D-0145 (Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome) or 98-D-0146 (A Randomized, PlaceboControlled Trial of Alendronate in the Treatment of Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome). Within 14 days of the bone injection procedure, patients will have a medical history, routine blood tests, urinalysis and check of vital signs (blood pressure, pulse and temperature) and will complete a 30-minute quality-of-life questionnaire. Women of child-bearing potential will have a pregnancy test. Patients who do not have recent X-rays and bone density scans available for review will have new ones taken. When these studies are completed, patients will undergo the bone injection procedure, followed immediately by bone densitometry and coned-down X-

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rays, as follows: - Bone injection - Patients will be given an anesthetic either to make them sleepy or put them to sleep completely. A portion of bone marrow will be withdrawn through a needle inserted into the hip bone and, at the same time, abnormal bone in the arms and legs will be sucked out using a needle. The abnormal bone will be replaced with a mixture of bone marrow and collagen (connective tissue protein) injected into the hole in the bone. The areas of injection will be closed - Bone densitometry - X-rays of the operated bone and opposite normal bone will be taken. Coned-down X-rays - Magnified normal X-rays will be taken as close-ups of an active lesion. Patients will have a history and physical examination by their local physician or at NIH every month for the first 4 months after the procedure. Every 6 months after the procedure, patients will return to NIH for follow-up, including a physical examination and completion of a quality-of-life questionnaire. Imaging studies of the injected site will be done 3, 6, and 12 months after the procedure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001851 •

Bone Marrow Transplantation in Treating Patients With Hematologic Cancer Condition(s): Leukemia; Lymphoma; Multiple Myeloma; Eye Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have hematologic cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005804

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Chemotherapy, Interferon, and Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia Study Status: This study is no longer recruiting patients. Sponsor(s): German CML Study Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens or bone marrow transplantation in treating patients with chronic myelogenous leukemia.

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Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002771 •

Combination Chemotherapy Plus Bone Marrow or Peripheral Transplantation in Treating Patients With Myeloproliferative Disorders Condition(s): Polycythemia Thrombocythemia

Vera;

chronic

idiopathic

Stem

myelofibrosis;

Cell

Essential

Study Status: This study is no longer recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining bone marrow or peripheral stem cell transplantation with chemotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus either bone marrow or peripheral stem cell transplantation in treating patients with myeloproliferative disorders. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002792 •

Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome Condition(s): Myeloid Leukemia; Refractory Anemia Study Status: This study is no longer recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia or myelodysplastic syndrome. PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy regimens with or without bone marrow transplantation in treating children who have acute myelogenous leukemia or myelodysplastic syndrome. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002798

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Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia Condition(s): refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; childhood acute promyelocytic leukemia (M3); secondary myelodysplastic syndromes; de novo myelodysplastic syndromes; secondary acute myeloid leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies Study Status: This study is no longer recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow doctors to give higher doses of chemotherapy and kill more cancer cells. It is not yet known whether chemotherapy is more effective with or without bone marrow transplantation for acute myeloid leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without bone marrow transplantation in treating children who have acute myeloid leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003436

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Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Promyelocytic Leukemia Condition(s): untreated adult acute myeloid leukemia; adult acute promyelocytic leukemia (M3) Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Leukemia Cooperative Group; Gruppo Italiano di Malattie Ematologiche Maligne de l'Aduklto-Associazione Italiana de Ematologia e Oncologia Pediatric Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy to kill tumor cells. It is not yet known which regimen of combination chemotherapy with or without bone marrow transplantation is more effective in treating promyelocytic leukemia PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens with or without bone marrow transplantation in treating patients who have promyelocytic leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002701

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Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia Condition(s): Myeloid Leukemia; Neutropenia Study Status: This study is no longer recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of different treatment regimens in treating patients who have acute myeloid leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002658

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Effect of Androgen Suppression on Bone Loss in Patients With or Without Bone Metastases Secondary to Prostate Cancer Condition(s): stage I prostate cancer; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer; Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): James P. Wilmot Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Assessing the effect of androgen suppression on bone loss in prostate cancer patients may improve the ability to plan treatment, may decrease the risk of fractures and bony pain, and may help patients live more comfortably. PURPOSE: Clinical trial to determine the effect of androgen suppression on bone loss in patients who have prostate cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003903

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High Dose Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Intermediate- or High-Grade Non-Hodgkin's Lymphoma Condition(s): stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV grade III follicular large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; stage III grade III follicular large cell lymphoma Study Status: This study is no longer recruiting patients. Sponsor(s): British National Lymphoma Investigation Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy drugs and kill

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more cancer cells. It is not yet known whether high dose chemotherapy plus bone marrow transplantation is more effective than high dose chemotherapy alone for intermediate- or high-grade non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of high dose chemotherapy with or without bone marrow transplantation in treating patients who have intermediate- or high-grade nonHodgkin's lymphoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003578 •

Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Ewing's Sarcoma or Rhabdomyosarcoma That Has Spread to the Bone Condition(s): recurrent childhood rhabdomyosarcoma; recurrent adult soft tissue sarcoma; adult rhabdomyosarcoma; stage IVB adult soft tissue sarcoma; stage IVA adult soft tissue sarcoma; bone metastases; previously treated childhood rhabdomyosarcoma; metastatic tumors of the Ewing's family; recurrent tumors of the Ewing's family Study Status: This study is no longer recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radioactive drugs such as holmium Ho 166 DOTMP can kill cancer cells without harming healthy cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by radiation therapy. PURPOSE: Phase I/II trial to study the effectiveness of holmium Ho 166 DOTMP followed by peripheral stem cell transplantation in treating patients who have metastatic Ewing's sarcoma or rhabdomyosarcoma that has spread to the bone. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006234

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Radiation Therapy in Treating Patients With Bone Metastases From Breast or Prostate Cancer Condition(s): Pain; stage IV prostate cancer; stage IV breast cancer; recurrent breast cancer; bone metastases; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); North Central Cancer Treatment Group; Radiation Therapy Oncology Group Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which radiation therapy regimen is more effective for bone metastases. PURPOSE: Randomized phase III trial to compare different radiation therapy regimens in treating patients who have bone metastases from breast or prostate cancer. Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003162 •

Radiofrequency Ablation in Relieving Pain in Patients With Bones Metastases Condition(s): bone metastases; Pain Study Status: This study is no longer recruiting patients. Sponsor(s): RITA Medical Systems Purpose - Excerpt: RATIONALE: Radiofrequency ablation uses high-frequency electric current to kill tumor cells and may help to relieve pain caused by bone metastases. PURPOSE: Phase II trial to study the effectiveness of radiofrequency ablation in relieving pain in patients who have bone metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029029

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The BONES Project: Building Healthy Bones in Children Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The Beat Osteoporosis: Nourish and Exercise Skeletons (BONES) Project is an after-school program that includes weight loading physical activity, nutrition and bone health education, and calcium-rich snacks. The program is designed to improve bone health in early elementary school children. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065247

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Zometa - Femara Adjuvant Synergy Trial (ZFAST) - Cancer Treatment Related Bone Loss in Postmenopausal Women with Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Adjuvant Hormonal Therapy Condition(s): Breast Neoplasms; Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: This protocol is designed to compare the effect on bone of Zometa 4 mg every 6 months when given upfront versus delayed start ( based on a post-baseline BMD T- Score below -2.0 SD at either the lumbar spine or total hip, or any clinical fracture unrelated to trauma, or an asymptomatic fracture discovered at the month 36 scheduled visit) in stage I-IIIa postmenopausal women with hormone receptor positive breast cancer who will receive Femara 2.5 mg daily as an adjuvant therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00050011 •

Bone Estrogen Strength Training Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: We started the Bone, Estrogen, Strength Training (BEST) study in the fall of 1995 at the University of Arizona, Tucson, Arizona. The BEST study is the largest of its kind. It looks at the effects of hormone replacement therapy and strength training exercise on bone mineral density. (Bone mineral density affects bone strength and the risk of osteoporosis.) Six groups of about 300 women each participated in this osteoporosis prevention study. In 1998, the BEST study received additional funding to examine for another 2 years the long-term effects of strength training on bone mineral density. By 2001 we will have finished analyzing the results for all study groups on the 1-year effects of exercise on bone, as well as additional analyses on the effects of 2, 3, and 4 years of strength training and weight-bearing exercise on bone. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000399

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Bone Marrow and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer Condition(s): Leukemia; Lymphoma; Multiple Myeloma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center Purpose - Excerpt: RATIONALE: Bone marrow and peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. PURPOSE: Phase I trial to study the effectiveness of bone marrow and peripheral stem cell transplantation in treating patients who have hematologic cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004232

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Calcium and Bone Mass in Young Females Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

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Purpose - Excerpt: We originally suggested that calcium in the diet is important in determining the amount of bone (bone mass) that builds up in young adults. We are testing the effect of calcium on bone mass in 354 Caucasian (white) girls. At the start of this 7-year study, the average age of the girls was 11 years, and they had not yet reached puberty. The study will also provide information about the effect of calcium on body composition (body fat) and blood pressure in young women. We have been giving calcium to one group of participants in this study and giving a placebo (an inactive pill, or "sugar pill") to the other group. The results of this research will be important in preventing osteoporosis, because building more bone as a young person should reduce a woman's chances of developing osteoporosis later in life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000402 •

Effects of Jumping on Growing Bones Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: In this study we will investigate the effects of a high-impact exercise program involving jumping on bone mass (the amount of bone) of the hip and backbone in the growing skeleton. We will also look at the effects of gradually stopping the jumping program on bone mass in the growing skeleton. A high-impact exercise program may build more bone during childhood, while the skeleton is still growing. This may help prevent broken bones due to loss of bone mass later in life. We will recruit 200 children aged 5-10 to participate in the study. For 6 months we will train the children in either a jumping or stretching program. We will then gradually reduce the amount of exercise over 6 months. We will measure bone mass in the hip and backbone at the start of the study, after jumping, and 6 months after the jumping program is stopped. We will compare the results in the jumping and stretching groups. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000405

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Open-label Trial on the Effect of I.V. Zometa 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients with Bone Metastasis Condition(s): Prostate Cancer Study Status: This study is completed. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: The purpose of this trial with Zometa is to investigate the effect ZOMETA 4 mg (zoledronic acid for injection in 100mg solution ) has in preventing associated bone loss in prostate cancer patients with bone metastasis when administered in conjunction with hormonal cancer therapy. This trial will seek to

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determine the effect of ZOMETA in stabilizing and increasing bone mineral density in these patients. This prospective, open-label, single arm, multicenter study will enroll approximately 200 prostate cancer patients with a history of at least one documented bone lesion documented by bone scan or radiograph. Patients must already be receiving hormone therapy and meet the following additional criteria: * 18 years of age or older * Histologically confirmed diagnoses of prostate cancer * Confirmed objective evidence of metastatic bone disease as evidenced by bone scan or radiograph * Received or will receive hormonal treatment also know as androgen deprivation therapy with an LHRH agonist or other hormonal treatments Throughout the course of this 12-month trial, patients will be identified based on the duration of established hormonal treatment at the time of enrollment. Each patients duration of participation will be up to 56 weeks including a 4 week screening, 48 week treatment and a 4 week follow up. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035997 •

Reduced-Intensity Regimen Before Bone Marrow Transplantation in Treating Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma Condition(s): adult Hodgkin's lymphoma; adult non-Hodgkin's lymphoma Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing graft-versus-host disease following bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before bone marrow transplantation. PURPOSE: Phase II trial to study the effectiveness of photophoresis, pentostatin, and total-body irradiation as a reducedintensity regimen before allogeneic bone marrow transplantation in treating patients who have relapsed non-Hodgkin's or Hodgkin's lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057954

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Reduced-Intensity Regimen Before Donor Bone Marrow Transplantation in Treating Patients With Myelodysplastic Syndromes Condition(s): atypical chronic myeloid leukemia; Chronic Myelomonocytic Leukemia; myelodysplastic and myeloproliferative disease; Myelodysplastic Syndromes Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing

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graft-versus-host disease following donor bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before donor bone marrow transplantation. PURPOSE: Phase II trial to study the effectiveness of photophoresis, pentostatin, and total-body irradiation before donor bone marrow transplantation in treating patients who have myelodysplastic syndromes. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045305 •

Treatment of Bone Marrow to Prevent Graft-Versus-Host Disease in Patients With Acute or Chronic Leukemia Undergoing Bone Marrow Transplantation Condition(s): Leukemia Study Status: This study is completed. Sponsor(s): Chimeric Therapies Purpose - Excerpt: RATIONALE: Bone marrow that has been treated to remove certain white blood cells may reduce the chance of developing graft-versus-host disease following bone marrow transplantation. PURPOSE: Randomized phase II/III trial to compare the effectiveness of treated bone marrow with that of untreated bone marrow in preventing graft-versus-host disease in patients with acute or chronic leukemia who are undergoing bone marrow transplantation. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004255

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Use of Bone Biopsy to Better Understand the Causes of Decreased Bone Mineral Density in Depression Condition(s): Bone Diseases, Metabolic; Depression, Involutional; Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: In this study researchers would like to learn more about the low levels of bone mineral density seen in approximately half of women in their forties diagnosed as currently having or previously had depression. Bones are always undergoing a process of building (formation) and breakdown (resorption). This process is referred to as bone remodeling. When more bone is formed than resorbed, the density (level of calcium) in bone increases and the bones become stronger. However, if more bone is resorbed than formed the density of bone decreases and the bones become weak. This condition is called osteoporosis. It is unknown if women with depression have decreased bone mineral density as a result of too much breakdown of bone or not enough building. It is important to know the cause of low bone mineral density because it will influence the way a patient is treated. Medications like bisphosphonates are used when there is too much bone breakdown. Growth hormone replacement can be given in cases where there is not enough bone production. Presently, bone biopsy and a

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procedure known as histomorphometry can determine what processes are going on in bones. Researchers have decided to use a sample of bone (biopsy) from part of the hip bone (iliac crest). In addition, researchers will collect a sample of bone marrow (the soft tissue found in the center of bones) to tell them more about the biochemical, cellular, and molecular processes that may be contributing to the problem of decreased bone density in depressed premenopausal women. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001916

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 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “bones” (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/

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

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

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

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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

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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/

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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

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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

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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 BONES 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 “bones” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bones, we have not necessarily excluded non-medical patents in this bibliography.

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

9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on bones: •

Apparatus and method for bone positioning Inventor(s): Brown; Scott C. (Warsaw, IN), Crane; Hal S. (Denver, CO) Assignee(s): Depuy Orthopaedics, Inc. (warsaw, In) Patent Number: 6,645,214 Date filed: November 12, 2001 Abstract: An apparatus for use in an arrangement for measuring the relative position of two bones during surgery includes a clamp and a measurement arm. The clamp is adapted to engage and secure to an anchor in a fixed vertical position, the anchor being secured to a first bone location. The measurement arm comprises an elongate portion and a locator portion that extends angularly from the elongate portion. The measurement arm is slidably supported on the clamp. The measurement arm is further rotatably supported on the clamp at a position in which an axis of rotation of the measurement arm is spaced apart from a longitudinal axis of the anchor. Excerpt(s): The present invention relates generally to surgical methods and apparatus, and in particular, to methods and apparatus for bone positioning during surgery. An important aspect of certain types of surgery, particularly arthroplastic surgery, is proper bone positioning. Bone positioning involves proper selection and implantation of a prosthetic component such that it does not change the natural posture and attitude of the remaining bones. By way of example, total hip replacement surgery requires appropriate selection of the hip prosthesis to avoid changing the overall length and lateral offset of the leg. Unequal leg length and/or lateral offset can undesirably result in a persistent limp in the patient. However, if a hip prosthesis having the correct dimensions is selected, then appropriate leg length and lateral offset may be accomplished. Web site: http://www.delphion.com/details?pn=US06645214__

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Dental cortical plate alignment platform Inventor(s): Weathers, Jr.; Arthur K. (14 Hudson Rd., Griffin, GA 30224) Assignee(s): None Reported Patent Number: 6,592,368 Date filed: May 1, 2000 Abstract: This application relates to a dental apparatus for the initial and subsequent guidance of drills, hypodermic needles, or drug delivery devices into the cortical plate of human mandibular and maxillary bones. The invention comprises a thin platform with one or a plurality of angled or straight preformed perforations serving as entrance ports. Each port is optimally heralded by a radio-opaque marker to enable a view of the tooth root prior to drilling for a superior selection of a nerve deadening site and a whisker tubule visually displaying the drill's angle. The platform can be positioned on either the inner or outer side of the cortical plate, and is optimized for use with a dedicated indexing bite apparatus, a dedicated rubber dam style clamp, or by attachment to a RINN positioner or the like.

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Excerpt(s): This application relates to the field of medicine, and more specifically involves corrective measures to improve the success of intraosseous medication injections in Dentistry and related fields requiring anaesthesia. The art of deadening pain for the Dental industry was greatly improved by the discovery that smaller and more effective dosages of medication could be introduced beneath the cortical plate. Pivotally, U.S. Pat. No. 5,173,050 by Dillon in 1992 cited methods of and implements for drilling an initial perforation, thus allowing the dentist to remove the drill and re-enter the passageway with a hypodermic needle to deliver anaesthesia. However, difficulties as taught by Dillon mainly involving failures of re-entry caused the industry to respond with two U.S. Pat. No 5,762,639 by Gibbs, and U.S. Pat. No. 5,779,708 by Wu, both describing methods to leave an intraosseous channel in place subsequent to drilling. This channel served as a guidance system to allow re-entry for medicative purposes. Web site: http://www.delphion.com/details?pn=US06592368__ •

Intramedullary rod with interlocking oblique screw for tibio-calcaneal arthrodesis Inventor(s): Chandran; Rama E. (4477 W. 118th St., Suite 402, Rolling Hills, CA 90250) Assignee(s): None Reported Patent Number: 6,579,293 Date filed: August 2, 2000 Abstract: A surgical rod-and-screw kit is disclosed, for use in ankle arthrodesis in patients who suffer from severe bone defects in their ankles. This assembly has a vertical intramedullary rod that is inserted through the bottom of the calcaneum (i.e., the heel bone), and driven upward into the tibia (the shin bone). The assembly also has a threaded pin, referred to herein as an oblique screw, which is positioned at an acute angle with respect to the vertical rod. This oblique screw is inserted through the lower rear surface of the calcaneum, and passes through a slanted hole in the vertical rod. The screw has external threads in the tip region, and this threaded tip enters the lower end of the tibial bone. When this screw is tightened, it compresses the lower end of the tibia bone against the talus and/or calcaneum, which improves the stability of the ankle fixation. This rod-and-screw assembly also reduces the risk and extent of bone damage that can be caused by motion of either or both components during years of use inside a damaged ankle with softened bones. An alignment jig is used during surgery, to help the surgeon align the holes that must be drilled through hard bone for the oblique screw and for fixation screws. Excerpt(s): This invention is in the field of surgical devices, and more particularly relates to rigid fixation devices used to fuse bone structures in badly diseased or deformed ankle joints. Some patients suffer from various problems which require at least a portion of an ankle joint to be effectively immobilized. This is usually done by inserting one or more rigid rods or pins (typically made of stainless steel and having a diameter roughly the size of a patient's finger) into one or more bones in the ankle, and in the "hindfoot" portion of the foot (i.e., the portion of the foot which includes the heel). This will permanently affix certain bones to other bones. The medical term for this type of permanent bone fixation is "arthrodesis". As used herein, the terms "rod", "pin", and "nail" are used interchangeably. All three terms refer to a rigid component that is inserted into one or more bones, for the purpose of anchoring, stabilizing, repairing, or supporting the bone(s). Since this invention is limited to devices inserted into an ankle or foot, for the purpose of ankle arthrodesis, any references herein to rod, pin, or screw are limited to devices inserted into a calcaneal and/or tibial bone.

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Web site: http://www.delphion.com/details?pn=US06579293__ •

Light wave energy health magnetic ring Inventor(s): Fan; James (Taipei, TW) Assignee(s): Jamie Life International Co., Ltd. (taipei, Tw) Patent Number: 6,544,164 Date filed: November 13, 2001 Abstract: A light wave energy health magnetic ring includes a plurality of blocks of different shapes formed from superconductive magnetic materials, natural crystals containing strong natural magnetic fields, and infrared ceramic beads. Bottom portions of the superconductive magnetic materials are formed with recesses for embedding crude crystals therein. Round, flat and circular-shaped, or wheel-shaped natural crystals and ceramic beads are spacedly disposed between adjacent superconductive magnetic materials such that the natural crystals are arranged in diagonally opposite positions. These elements are connected in a ring shape for wearing by a user. The magnetic waves can penetrate the muscles and bones of the body of the user to magnetize the cells of the body to thereby improve the circulation functions of the body. Excerpt(s): This invention is related to a light wave energy health magnetic ring which includes a plurality of superconductive magnetic materials of different shapes, natural crystals and ceramic beads connected in a ring shape for wearing by a user. The magnetic properties of the superconductive magnetic materials are employed to magnetize the cells of the human body to thereby improve circulation functions. The natural crystals and ceramic beads disposed between the superconductive magnetic materials can stabilize the magnetic field. The basic units of all living creatures are cells, which are made up of protein, fat, sugar, phosphor, calcium and water. The cell surface is magnetic, and electromagnetic action takes place on the cell surface. The chemical components, due to the inter-attraction and repulsion of electrons, work together to make the cells active to perform physiological functions. The amount of electrons affects the activity of the cells. New cells contain the largest amount of electrons. Old cells produce bubbles and therefore contain fewer electrons. Cells like blood cells, muscles, bone marrow, etc., are also counted in terms of the number of electrons. Therefore, when a person has cells containing insufficient electrons and is weak, according to Fleming's right-hand rule, magnetization can cause the cells per se to produce electric power by cutting the magnetic field via a conductor. The primary object of the invention is to provide a light wave energy health magnetic ring, which includes a plurality of superconductive magnetic materials of different shapes, natural crystals and ceramic beads connected in a ring shape for wearing by a user. The magnetic properties of the superconductive magnetic materials are employed to magnetize the cells of the human body to thereby improve circulation functions. The natural crystals and ceramic beads disposed between the superconductive magnetic materials can stabilize the magnetic field. Web site: http://www.delphion.com/details?pn=US06544164__

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Patent Applications on Bones 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 bones: •

Apparatus and method of ligament balancing and component fit check in total knee arthroplasty Inventor(s): Whiteside, Leo A.; (Chesterfield, MO) Correspondence: Polster, Lieder, Woodruff & Lucchesi; 763 South New Ballas Road; ST. Louis; MO; 63141-8750; US Patent Application Number: 20030153978 Date filed: February 8, 2002 Abstract: Apparatus and method for determining the kinematics of a large joint (e.g., a knee) undergoing arthroplasty, for comparing the kinematics of the joint undergoing surgery with the kinematics of the normal joint, and for providing the surgeon with information allowing the balancing of the ligaments of the joint upon the installation of a prosthesis replacement joint. The apparatus includes optical targets mounted on joint replacement components fitted to the resected bones of the joint. One or more video cameras are used to obtain a series of images of the various optical targets as the extremity is flexed, extended, and rotated. A computer is responsive to the images of the targets to determine the kinematics of the joint as it is flexed, extended and rotated. The computer compares the kinematics of the observed joint with the kinematics of a normal joint and determines, based on anomalies of the observed joint relative to the normal joint, whether other implant components or spacers are required, and determines which ligaments must be relaxed or contracted so that the ligaments are balanced. The computer displays suggestions to the surgeon for changing components and for relaxing or contracting specific ligaments such that the ligaments of the joint is balanced with the prosthesis joint in place. A method of computer ligament balancing is also disclosed. Excerpt(s): It is oftentimes necessary to replace a patient's joint (e.g., a knee) because of chronic disease, such as arthritis or other degenerative bone or joint diseases. Over time, as such disease conditions progress, the bones forming the joint become deformed thus causing the ligaments of the joint to stretch or contract so as to accommodate to the deformed joint. Upon surgical replacement of the deformed joint with a prosthesis joint, the latter will be of proper size, position, and orientation with respect to size of the patient and with respect to the patient's anatomical landmarks and reference axes. In such joint replacement surgery, it is desirable that the ligaments of the joint remain in tact and remain attached to the bones immediately above and below the joint being replaced. However, because the ligaments have been stretched or contracted by the diseased joint, the ligaments oftentimes will not hold the prosthesis joint components in proper relation to one another as the joint is flexed and extended. This may result in improper kinematics for the joint which will impair the mobility of the patient and may result in excessive wear of the joint components. It is conventional in total knee arthroplasty for the surgeon, after the femoral and tibial bone cuts have been made, to fit trial implant components in the knee and then to flex, extend, and rotate the knee in order to assess varus, valgus, rotational motion, and the anterior and posterior stability

10

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

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of the knee. This information is conventionally used by the surgeon, based on the surgeon's subjective judgement, to determine which ligaments of the knee need to be released or contracted in order to insure that optimal knee function will result from the joint replacement surgery. Because the knee is complex and its behavior is difficult to accurately assess, the balancing of the ligaments has been difficult for surgeons. Heretofore, apparatus were known that aided the surgeon in determining the position of the bones of the joint and to aid in positioning the bone cuts to be made so that the prosthesis joint components will properly fit the bone cuts and so that the prosthesis joint is properly position with respect to the bones of the joint. Such prior art alignment and bone resection instruments are shown in my prior U.S. Pat. Nos. 4,467,801, 4,474,177, 4,721,104, 4,722,330, 4,731,086, 4,935,023, 5,002,545, 5,098,436, 5,019,104, 5,100,409, 5,176,684, 5,275,603, 5,342,367, 5,415,662, 5,431,656, 5,578,039, 5,609,642, 5,628,749, 5,667,511, 5,683,469, 5,683,470, and 6,683,397, which are herein incorporated by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Back leaning shoe shape Inventor(s): Wu, Chin Wang; (Yuan Shan Shiang, TW) Correspondence: Rosenberg, Klein & Lee; 3458 Ellicott Center Drive-suite 101; Ellicott City; MD; 21043; US Patent Application Number: 20030172552 Date filed: March 18, 2002 Abstract: A back leaning shoe shape has a shoe mold of increased height and waistline that is formed on the basis of practical applications to prevent the phalanx from directly rubbing against the shoe surface. The shoe mold leans backward by an predetermined angle between 5 to 25 degrees and has a height of at least 5 inches. The back leaning shoe shape is used for special applications to prevent hurting muscles or bones of wearer when it is worn for a long period. Excerpt(s): The present invention relates to a shoe shape, and more particularly to a back leaning shoe shape for preventing hurting muscles or bones of a wearer when it is worn for a long period. When the body leans backward, the redundant heel material of the conventional shoe shape 10 heaps around the bending position 14 of the heel and makes wearers uncomfortable. Most of the shoe shapes 25 have a heelpiece 15 with a thickness of 2 mm to prevent the fin strap from squeezing directly. However, such design facilitates the heaping of redundant material at the joint of soft and hard materials and the friction between the material and the skin. When the body leans backward, the conventional shoe shape 10 rises up partially at the position around the phalanx, especially between the second and third phalanxes, causing a friction between the skin of the phalanx and the fabric of the shoes and, as a result, a red and swollen skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Curable media for implantable medical device Inventor(s): Estes, Richard H.; (Buford, GA), Nguyen, Thanh Van; (Irvine, CA), Pham, To V.; (Trabuco Canyon, CA), Shaolian, Samuel M.; (Newport Beach, CA), Teitelbaum, George P.; (Santa Monica, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040006341 Date filed: December 20, 2002 Abstract: A subcutaneously formed in place orthopedic fixation device is provided, such as for fixation of the spine or other bone or bones. The device comprises an inflatable member, such as a tubular balloon. The balloon is positioned at a treatment site in the body while in a flexible, low crossing profile configuration. The balloon is thereafter inflated with a hardenable epoxy media comprising one or more epoxy compounds and one or more amine curing compounds that cures rapidly in place with low to moderate exotherm. Methods and delivery structures are also disclosed. Excerpt(s): The present invention relates to medical devices and, more particularly, to systems for forming orthopedic fixation or stabilization implants in place within the body, such as by infusing a formable media into a cavity. In one application, the present invention relates to minimally invasive procedures and devices for forming a spinal stabilization rod in situ. The human vertebrae and associated connective elements are subject to a variety of diseases and conditions which cause pain and disability. Among these diseases and conditions are spondylosis, spondylolisthesis, vertebral instability, spinal stenosis and degenerated, herniated, or degenerated and herniated intervertebral discs. Additionally, the vertebrae and associated connective elements are subject to injuries, including fractures and torn ligaments and surgical manipulations, including laminectomies. The pain and disability related to these diseases, conditions, injuries and manipulations often result from the displacement of all or part of a vertebra from the remainder of the vertebral column. A variety of methods have been developed to restore the displaced vertebrae or portions of displaced vertebrae to their normal position and to fix them within the vertebral column. For example, open reduction with screw fixation is one currently used method. The surgical procedure of attaching two or more parts of a bone with pins, screws, rods and plates requires an incision into the tissue surrounding the bone and the drilling of one or more holes through the bone parts to be joined. Due to the significant variation in bone size, configuration, and load requirements, a wide variety of bone fixation devices have been developed in the prior art. In general, the current standard of care relies upon a variety of metal wires, screws, rods, plates and clamps to stabilize the bone fragments during the healing or fusing process. These methods, however, are associated with a variety of disadvantages, such as morbidity, high costs, lengthy in-patient hospital stays and the pain associated with open procedures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Extramedullary fluoroscopic alignment guide Inventor(s): Irving, John F.; (Hamden, CT) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20040015173 Date filed: September 11, 2003 Abstract: An extramedullary fluoroscopic alignment guide is disclosed, along with a surgical method employing such an alignment guide. The extramedullary alignment guide includes both radiolucent and radiopaque material. The invention is useful in performing surgery on bones, for example, in performing surgery on the knee joint. The radiolucent material provides a support structure for the radiopaque material. The radiopaque material provides a radiopaque instrument reference that is sized, shaped and positioned so that the surgeon can simultaneously fluoroscopically view the patient's bone and the radiopaque instrument reference. The radiopaque instrument reference may be aligned with landmarks on the bone or other fluoroscopically viewable references, such as the mechanical or anatomic axis. The alignment guide can also include cutting guide surfaces. Excerpt(s): This application is a Utility Application based upon U.S. Provisional Patent Application Ser. No. 60/351,782, filed Jan. 25, 2002, and entitled EXTRAMEDULLARY FLUOROSCOPIC ALIGNMENT GUIDE, the complete disclosure of which is incorporated by reference herein. The present invention relates to an extramedullary fluoroscopic alignment guide for use in joint replacement surgery. The fluoroscopic alignment guide of the present invention may be particularly useful in less-invasive surgical procedures, such as in unicompartmental knee replacement. The present invention also relates to a surgical method for resection of a bone, and may be particularly useful in resecting a tibia for knee arthroplasty. The surgical preparation of bone endings for receiving prosthetic joints for either a total or partial joint replacement is a complex procedure. A number of bone cuts are made to effect the placement and orientation of the components of the prosthesis on the bone with the appropriate joint gaps in extension and flexion. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Preparation and use of radium-223 to target calcified tissues for pain palliation, bone cancer therapy, and bone surface conditioning Inventor(s): Bruland, Oyvind S.; (Hosle, NO), Henriksen, Gjermund; (Mjondalen, NO), Larsen, Roy H.; (Bekkestua, NO) Correspondence: Clark & Elbing Llp; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20030206857 Date filed: June 12, 2003 Abstract: Processes for the preparation, prepared solutions, and the use of radium-223 for the treatment of calcified tumors, bone tumors, treatment of bones, bone surfaces and soft tissues is described. Excerpt(s): The present invention relates to the preparation and use of the "calcium analogue" alkaline-earth radionuclide radium-223 for the targeting of calcified tissues, e.g., bone and a physiological acceptable solution comprising.sup.223Ra. Biomedical use

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of radionuclides for pain palliation and/or cancer treatment, including prophylactic treatment of bone surfaces to slow down/inactivate undetectable metastases has previously been based upon.beta.-emitters and conversion electron emitters. A substantial percentage of cancer patients is affected by skeletal metastases. As many as 85% of patients with advanced lung, prostate and breast carcinoma develop bony metastases (Garret, 1993; Nielsen et al., 1991). Established treatments such as hormone therapy, chemotherapy and external radiotherapy often causes temporary responses, but ultimately most bone cancer patients experience relapses (Kanis, 1995). There is thus a strong need for new therapies to relieve pain and slow down tumor progression. Bone targeting radioisotopes has been included in clinical trials for the treatment of cancer to the skeleton (De Klerk et al., 1992, Foss{dot over (a)} et al., 1992, Lee et al., 1996, Silberstein, 1996). These radiopharmaceuticals have been based on.beta.-particle emitters (Atkins, 1998) and lately also a conversion electron ermitter (Atkins et al., 1995). Among these compounds which have so far been approved by US Food and Drug Administration, Le., are strontium-89 (Metastron.TM.) and.sup.153Sm EDTMP (Lexidronam.TM.). The strontium-89 compound can only be administered in amounts sufficient for pain palliation, not for tumor therapy, because a significant myelotoxicity occurs before significant antitumour therapeutic dose levels can be reached (Silberman, 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Secreted human proteins Inventor(s): Garcia, Pablo D.; (San Francisco, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20040009950 Date filed: June 9, 2003 Abstract: Fifteen secreted human proteins and full-length cDNA sequences encoding the proteins have been identified. The proteins have various potential uses as therapeutics, such as for stimulating blood cell generation in patients receiving cancer chemotherapy, for treatment of bone marrow transplantation patients, and for healing fractured bones. The proteins and cDNA sequences can also be used, inter alia, for targeting other proteins to the membrane or extracellular milieu. Excerpt(s): This invention relates to proteins secreted from bone marrow and from fetal liver, and to polynucleotides encoding the secreted proteins. The invention also relates to therapeutic and diagnostic utilities for the polynucleotides and proteins. Human tissues, such as fetal liver and bone marrow stromal cells, secrete a variety of protein factors. Some of these factors are required for the formation of blood and bone cells and for other physiological processes. Regulatory factors which are known to be involved in hematopoiesis and/or bone development include SCF, IL-3, IL-6, GM-CSF, M-CSF, EPO, TPO, bone morphogenic proteins, erythroid potentiating factor, and TGF-.beta. However, it is believed that additional secreted protein factors which control hematopoiesis and bone morphogenesis remain to be identified. Other secreted proteins may play a role in cell-cell interaction and regulation of cell growth, both of which are related to cancer. There is a need to identify such proteins. It is an object of the invention to provide novel secreted proteins and polynucleotide sequences which encode the proteins. These and other objects of the invention are provided by one or more of the embodiments described below.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Surgical saw for cutting off cheek bones Inventor(s): Lee, Jae Hwa; (Seoul, KR) Correspondence: Ladas & Parry; 26 West 61st Street; New York; NY; 10023; US Patent Application Number: 20040024405 Date filed: April 16, 2003 Abstract: The surgical saw according to the present invention comprises an arm fixed by mounting the rear end portion thereof in a jaw of a handle; and a double saw blade part connected with the front end portion of the arm and having two saw blades arranged side by side in a certain distance. In case that the surgical saw is used in surgeries for cutting off cheek bones, the surgical saw can precisely cut off portions of the cheek bones in a width set in advance by precisely cutting off two positions of the cheek bones in a precise cutting-off length at the same time so that the portions of cheek bones can be conveniently cut off, the periods of time for surgeries can be reduced, and an occurrence frequency of surgery aftereffects due to different cutting-off widths for the left and right cheek bones can be reduced. Excerpt(s): The present invention relates to a surgical saw for cutting off cheek bones which is used for cutting off portions of cheek bones during plastic surgeries for smoothing bulged cheek bones, and more particularly to a surgical saw for cutting off cheek bones which has spacing-adjustable double saw blades capable of precisely cutting off cheek bones at one time in a predetermined width. The cheek bones such as the zygomatic buttresses, are bones bulged out below the tails of the eyes on the both sides of a face. Appropriate cheek bone bulges give a vigorous and good look and a three-dimensional effect, but excessive cheek bone bulges cause a face to look wide and a nose to look relatively low in front view so that the bulges may be a factor for a face appearance to be deteriorated. Particularly, the excessive bulges together with a square chin which is distinctly protruded and angled cause a strong and rough appearance so that they give an adverse feeling to others. Accordingly, plastic surgeries are being widely carried out to look mild in appearance by smoothing bulged cheek bones in recent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Transfer of cells, tissue, and other substances to bone Inventor(s): Ferree, Bret A.; (Cincinnati, OH) Correspondence: John G. Posa; Gifford, Krass, Groh, Sprinkle,; Anderson & Citkowski, P.C.; 280 N. Old Woodward AVE., Suite 400; Birmingham; MI; 48009-5394; US Patent Application Number: 20040022771 Date filed: July 30, 2003 Abstract: Human or animal bones are used to house and nurture other useful tissues. Once inside the bones, the transferred cells may become attached to the bone, and the blood vessels within the bone provide nutrition. The transferred cells or tissues can be injected as a solution of individual cells or small clumps of cells. Large numbers of cells supported with an extracellular matrix scaffold can be surgically implanted or injected.

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The extracellular matrix can be synthetic, resorbing, or derived from biologic sources. To assist with transfer, the cells or tissue may be contained in a bag before being placed in the bone. The non-bone materials may either be removed from the bone following sufficient growth and nourishment, or the biologic materials may remain in place to provide one or more desirable functions. For example, a bone's access to the blood stream should help the islet cells monitor blood glucose, and release insulin into the blood stream. Excerpt(s): This application claims priority from U.S. Provisional Patent Application Serial No. 60/399,597, filed Jul. 30, 2002, the entire content of which is incorporated herein by reference. This invention relates generally to cell culture and, in particular, to the implantation of non-bone tissue into bone to promote the growth of useful biologic materials. The bones of the human body serve many functions. In addition to providing support and protection of the body's soft tissues, many bones of the skeletal system also aid in the production of blood. The inner, cancellous, portion of bone contains marrow that houses the cells that reproduce to form the blood elements. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vitamin formulation for enhancing bone strength Inventor(s): Lovett, William E.; (Naples, FL) Correspondence: Dykema Gossett Pllc; Franklin Square, Third Floor West; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030190369 Date filed: April 9, 2003 Abstract: The present invention provides a method and composition for dietary vitamin supplementation utilizing a form and dosage of vitamins and minerals for enhanced calcium absorption. The method includes the steps of providing a pharmaceutically acceptable composition including calcium citrate, and supplementing the daily dietary regimen of a subject with calcium citrate within the range of approximately 100 mg calcium to approximately 2000 mg calcium, and preferably 1000 mg calcium. The chewable form of the supplement provided herein facilitates absorption of calcium in the teeth and bones of a subject, for enhanced physiological and psychological benefits. The supplement is especially beneficial for subjects experiencing osteoporosis, arthritis, demineralization of teeth and bones, bodily pain and lack of energy, as well as for the prevention of these ailments. Excerpt(s): This application claims benefit of priority of Provisional Application Serial No. 60/370,733, filed Apr. 9, 2002. The invention relates generally to dietary supplementation, and, more particularly to a novel method and composition for dietary vitamin supplementation utilizing a form and dosage of vitamins and minerals for enhanced calcium absorption. Vitamins and minerals are essential to life and vital for many functions such as the breaking down of digested food and for providing energy for each cell in the body. Many vitamins cannot be stored and therefore must be replenished on a daily basis. Minerals, which are primarily stored in bone and muscle tissue, likewise must be replenished daily. Replenishing vitamins and minerals appropriately can be a complex task and research has shown that there must be a balance of vitamins and minerals taken daily for optimal absorption. One key factor in determining a vitamin composition relates to the interaction of different vitamins and minerals. For example, a large dose of one "B" vitamin may cause a deficiency in another

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"B" vitamin. The same is true for minerals, which must also be taken in correct amounts and combinations to produce the synergistic effect of increasing the positive effect of each one alone. 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 bones, 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 “bones” (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 bones. You can also use this procedure to view pending patent applications concerning bones. 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 BONES Overview This chapter provides bibliographic book references relating to bones. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bones 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 “bones” (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 bones: •

Bone and Joint Disorders: Conventional Radiologic Differential Diagnosis Source: New York, NY: Thieme Medical Publishers, Inc. 1997. 328 p. Contact: Available from Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. Summary: This book for health professionals describes conventional radiographic findings and analyzes their differential diagnostic possibilities. Chapters examine osteopenia, osteosclerosis, periosteal reactions, trauma and fractures, localized bone lesions, joint diseases, and joint and soft-tissue calcifications. In addition, chapters discuss radiographic findings associated with problems of the skull; orbits; nasal fossa and paranasal sinuses; jaws and teeth; spine and pelvis; clavicles, ribs, and sternum; extremities; and hands and feet. 38 references, numerous figures, and 49 tables.

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Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3rd ed Source: Hagerstown, MD: Lippincott-Raven Publishers. 1996. 500 p. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1600, Hagerstown, MD 21741-1600. (800) 777-2295. Fax (301) 824-7390. E- mail: [email protected]. Web Site: www.lrpub.com. PRICE: $42.00 plus shipping and handling. ISBN 0397517637. Summary: This book provides health professionals with a comprehensive description of the clinical manifestations, pathophysiology, diagnosis, and treatment of metabolic bone diseases and disorders of mineral metabolism. Section one describes the gross anatomy and ultrastructure, physiology, biochemistry, structural features, and functions of the cellular elements of bone. Section two discusses calcium and other minerals and the biochemistry of calcium-regulating hormones. Section three describes the tests and imaging techniques used to evaluate patients suspected of having bone or mineral disorders. Section four examines the various clinical presentations seen with disordered levels of serum minerals. Sections five presents the genetic and acquired causes of metabolic bone diseases such as rickets, osteomalacia, osteoporosis, and renal osteodystrophy. Section six focuses on genetic, developmental, and dysplastic skeletal disorders, while section seven examines acquired disorders of cartilage and bone. Section eight is devoted to Paget's disease of bone, and section nine describes diseases characterized by pathologic calcification of soft tissue. Section 10 focuses on the nephrolithiasis, while the final section is an appendix containing growth charts, ossification center tables, normal values for commonly used biochemical analyses, recommended daily mineral and vitamin intake, a drug formulary, instructions on how to conduct and interpret dynamic tests, and bone density reference data. The book concludes with a subject index. 1 appendix, numerous figures, tables, and references.

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Good Bones: The Complete Guide To Building and Maintaining the Healthiest Bones Source: Palo Alto, CA: Bull Publishing Company. 1999. 184 p. Contact: Available from Bull Publishing Company. P.O. Box 208, Palo Alto, CA 943020208. (650) 322-2855. Fax (650) 327-3300. Website: www.bullpub.com. PRICE: $14.95 plus shipping and handling. ISBN 0923521445. Summary: This book provides women with guidelines on building and maintaining healthy bones. By examining 17 major risk factors for bone health, the book helps women assess their overall risk for osteoporosis. A chapter on normal bone physiology is followed by a chapter that discusses risk factors in the prenatal and infancy periods, childhood, adolescence, young adulthood, middle age, and older adulthood. Chapter three examines hereditary risk factors: race, ethnicity, and family history. The next chapter is devoted to factors affecting women: age at menarche, menstrual cycles, age at menopause, and total reproductive years. Other topics include oral contraceptives, treatments for endometriosis, pregnancy and breast feeding, and hysterectomy. The fifth chapter evaluates the role of body build, weight, and fat in bone health. Chapter six focuses on the effect of exercise and physical activity on bone health and presents an example of an exercise routine that includes both endurance and strength training. The next chapter discusses the impact of hormones, prescription medications, and calcium supplements on bone health, and presents the advantages and disadvantages of hormone replacement therapy (HRT), highlights alternatives to HRT, and explains how to select the best calcium supplements and use them most effectively. Other chapters examine lifestyle factors, such as alcohol and caffeine consumption and smoking that affects bone health; identify factors influencing calcium absorption; present calcium requirements for various age groups; and discuss the importance of good nutrition in

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building strong bones. The final chapter applies the 17 risk factors to case studies presented in the previous chapters. A glossary of terms and a list of suggested readings and resources are included. 15 figures, 21 tables, and numerous references.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: When following the link below, you may discover non-medical books that use the generic term “bones” (or a synonym) in their titles. •

Amazon.com: http://www.amazon.com/exec/obidos/externalsearch?tag=icongroupinterna&keyword=bones&mode=books

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 “bones” (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 •

90Sr content of human bones in Finland, 1960-1962, by K. Salo [et al.]. Author: Salo, Kalervo.; Year: 2003; Helsinki, 1964

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An atlas of surgical approaches to the bones of the dog and cat; [by] D. L. Piermattei [and] R. G. Greeley. Author: Piermattei, Donald L.; Year: 1964; Philadelphia, Saunders, 1966

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Bone biodynamics. Author: Frost, Harold M.,; Year: 1955; Boston, Little, Brown [c1964]

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Decyphering ancient bones: the research potential of bioarchaeological collections Author: Grupe, Gisela,; Year: 1958; Rahden [Germany]: M. Leidorf, 2003; ISBN: 389646616X

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Determination of the mineral content of human finger bones by the silver analysis of roentgenograms. Author: Virtama, Pekka.; Year: 1938; Basel, Karger, 1957

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Normal bones & joints Roentgenologically considered; two hundred and twenty Roentgen ray studies on sixty-one full page plates and thirty-four text illustrations, by Isidore Cohn. with a foreword by Rudolph Matas. Author: Cohn, Isidore,; Year: 1959; New York, P. B. Hoeber, inc., 1924

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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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Principles of bone X-ray diagnosis. Author: Simon, George.; Year: 1956; Washington, Butterworth, 1965

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Progress in development of methods in bone densitometry. [Editors: G. Donald Whedon et al.]. Author: United States. National Aeronautics and Space Administration.; Year: 1962; Washington, National Aeronautics and Space Administration, Scientific and Technical Information Division, 1966

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Roentgen diagnosis of diseases of bone [by] Jack Edeiken [and] Philip J. Hodes. Author: Edeiken, Jack,; Year: 1964; Baltimore, Williams; Wilkins, 1967

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Skeletal clearance of Sr85 and Ca47 and bone blood flow in both normal and arteriovenous fistula animals. Author: Weinman, Darrell Theodore,; Year: 1957; [Minneapolis] 1964

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Studies on the anatomy and function of bone and joints. Author: Evans, F. Gaynor (Francis Gaynor),; Year: 1966; New York, Springer, 1966

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The architecture of bone. Author: Hall, Michael C.; Year: 1964; Springfield, Ill., Thomas [c1966]

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The armor within us; the story of bone. Author: Samachson, Joseph.; Year: 1957; Chicago, Rand McNally [1966]

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The blood supply of the lower limb bones in man; descriptive and applied [by] Henry V. Crock, with the assistance of Carmel Crock. Author: Crock, Henry Vernon.; Year: 1947; Edinburgh, Livingstone, 1967

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The laws of bone structure. Author: Frost, Harold M.,; Year: 1964; Springfield, Ill., Thomas [c1964]

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

Bone in Health and Disease Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 1. New York, NY: Oxford University Press, Inc. 1993. p. 242-256. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals explores the normal physiology of bone and the changes in specific skeletal disorders. The structure of bone and the relationship of different bone cells are described. The functions of osteoblasts, osteocytes, and osteoclasts are highlighted. Boneformation and resorption is explained. Factors affecting bone mass are discussed, including genetic factors, nutrition, mechanical factors, and systemic hormones. The elements of the bone matrix are described, focusing on collagen and noncollagenic proteins. The hormones involved in controlling the calcium balance are identified. The features of various bone diseases are presented, including those of osteoporosis; osteomalacia and rickets; parathyroid bone disease; Paget's disease;

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disorders of bone matrix such as osteogenesis imperfecta, other inherited disorders of connective tissue, and skeletal dysplasias; enzyme disorders; disorders of cell biology; myositis ossificans progressiva; and hypercalcemia of malignancy. 79 references, 15 figures, and 9 tables. •

Temporal Bone Research and Donation Source: in Haybach, P.J. Meniere's Disease: What You Need to Know. Portland, OR: Vestibular Disorders Association. 1998. p. 267-274. Contact: Available from Vestibular Disorders Association. P.O. Box 4467, Portland, OR 97208-4467. (800) 837-8428. E-mail: [email protected]. Website: www.vestibular.org. PRICE: $24.95 plus shipping and handling. ISBN: 0963261118. Summary: This chapter is from a book that provides information for people who have or suspect they have Meniere's disease and want to know more about its diagnosis and treatment, as well as strategies for coping with its effects. Written in nontechnical language, the chapter discusses temporal bone research and the importance of donation. The temporal bone is a part of the skull that houses the outer, middle, and inner ears. The inner ear (also known as the labyrinth) is not accessible for direct examination and study during life. A surgical biopsy of the inner ear is impractical, since it would result in severe hearing loss or balance disorder. Therefore, one of the best ways to study the inner ear is to examine the temporal bone after death. Such bones are obtained from people who have donated or pledged their temporal bones for research after their death. A small part of the temporal bone (the part containing the middle and inner ears) is surgically removed soon after death (this does not affect the appearance of the donor's outer ear, face, or head). The temporal bone is then prepared for a variety of research techniques. The chapter outlines the information that has been gained from temporal bone research, including that related to endolymphatic hydrops, sensory and neural lesions, vestibular fibrosis, and endolymphatic sac abnormalities. The chapter concludes by encouraging readers affected by Meniere's disease to consider donating their temporal bones for research purposes after death. The author describes the NIDCD National Temporal Bone, Hearing and Balance Pathology Resource Registry and then answers common questions about temporal bone donations.

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Injuries to the Supporting Bone Source: in Andreasen, J.O.; Andreasen, F.M., eds. Textbook and Color Atlas of Traumatic Injuries to the Teeth. 3rd ed. Copenhagen, Denmark: Munksgaard International Publishers Ltd. 1994. p. 427-455. Contact: Available from Munksgaard International Publishers Ltd. 35 Norre Sogade, P.O. Box 2148, DK-1016 Copenhagen K, Denmark. Phone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail: [email protected]; http://www.munksgaard.dk. PRICE: $224.00 plus shipping and handling. ISBN: 8716106377. Summary: This chapter is from a medical textbook and color atlas that explores the treatment of traumatic injuries to the teeth. This chapter focuses on injuries to the supporting bone, divided into four types: comminution of the alveolar socket, fracture of the alveolar socket wall, fracture of the alveolar process, and fracture of mandible or maxilla (jaw fracture). Topics include terminology, frequency, etiology, history, clinical examination and findings, palpation of facial skeleton, radiographic examination, pathology, treatment, and prognosis. Extensive graphics, black and white photographs and radiographs, and full color photographs illustrate the chapter. 35 figures. 4 tables. 113 references. (AA-M).

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Cros, Bone-Conduction, and Implanted Hearing Aids Source: in Dillon, H. Hearing Aids. Sidney, Australia: Boomerang Press. 2001. p. 434450. Contact: Available from Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001. (800) 782-3488. Fax (212) 947-0108. E-mail: [email protected]. PRICE: $59.00 plus shipping and handling. ISBN: 1588900525. Summary: This chapter on CROS (contralateral routing of signals), bone conduction, and implanted hearing aids is from a comprehensive textbook that covers everything the audiologist needs to prescribe, select, and fit hearing aids, and evaluate their performance. In CROS, hearing aid components on opposite sides of the head are electrically linked. Basic CROS aids are most suitable for people with unilateral (one side) hearing loss. Bone conduction hearing aids output a mechanical vibration instead of an airborne sound wave. They are most suited to people who, for medical reasons, cannot wear a hearing aid that occludes the ear in any way. For patients with sensorineural loss, bone conduction hearing aids cannot stimulate the cochlea as effectively as do air conduction hearing aids because of the relative inefficiency of the bone conduction pathway. For patients with large conductive hearing losses, however, bone conduction hearing aids can stimulate the cochlea as strongly as air conduction hearing aids. An alternative form of bone conduction hearing aid is the bone anchored hearing aid, in which the vibrations are transmitted to the skull via an embedded titanium screw. Various experimental devices also enable vibrations to be transmitted directly to the tympanic membrane, to the bones in the middle ear, or to the round window. The author concludes that hearing aids in the CROS family are not extensively used, even for many patients with hearing losses for whom a CROS fitting would appear to have some advantages. The chapter includes a summary and highlighted key paragraphs for ease of access to the information provided. 6 figures. 4 tables.

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Chapter 46: Bones, Joints, and Muscles Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 3 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have musculoskeletal disorders with an overview of their causes, diagnosis, and treatment. The musculoskeletal system is composed of the skeleton, muscles, tendons, ligaments, and other components of joints. All the bones in the body make up the skeleton. Bones are either flat or long, and they consist of a hard outer part composed largely of proteins and hydroxyapatite. The center of each bone consists of marrow, which is softer and less dense than the rest of the bone. Marrow contains specialized cells that produce blood cells. Joints are formed where bones meet. Some joints do not move, while others allow a range of motion. In a joint, the ends of bones are covered with cartilage. Joints also consist of synovial tissue that encloses them to form the joint capsule. Muscles are fiber bundles that can contract. Tendons are tough bands of connective tissue that attach each end of a muscle to a bone. Ligaments surround joints and connect one bone to another. Bursas are fluid filled sacs that provide extra cushioning between adjacent structures. Musculoskeletal disorders are major causes of chronic pain and physical disability. Injuries to bones, muscles, and joints are very common. Inflammation, a natural response to tissue irritation or damage, causes swelling, redness, heat, and loss of

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function. An inflammation may be localized or widespread, and it may become chronic and persistent. Bone and joint infections require immediate treatment to prevent permanent joint damage. Bone can be affected by benign tumors and cancers, and metabolic and hormonal imbalances can also affect bones and joints. Laboratory tests and imaging studies may be used to diagnose musculoskeletal disorders. Treatment depends on the type of disorder diagnosed. Therapeutic options include conservative measures and drug therapy. 2 figures.

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CHAPTER 7. MULTIMEDIA ON BONES Overview In this chapter, we show you how to keep current on multimedia sources of information on bones. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on bones is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “bones” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, 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 “Videorecording (videotape, videocassette, etc.).” Type “bones” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on bones: •

Vitamin D: Not Just for Bones Source: Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, 1992, 60 minutes. Contact: WIN, 1 WIN WAY, Bethesda, MD 20892-3665. Summary: In this lecture, Dr. DeLuca discusses the major functions of Vitamin D in the body; studies demonstrating potential therapeutic uses for synthetic Vitamin D compounds; and his own laboratory's progress on developing several such compounds. According to Dr. DeLuca, Vitamin D is, in fact, not a vitamin but a prohormone that remains inactive until metabolized in the liver and the kidney. The principal active metabolite of Vitamin D, calcitrol, acts with parathyroid hormone (PTH) to regulate the blood calcium level. It also plays a role in building up bone and is an important regulator of intestinal calcium absorption. Disturbance of this regulatory mechanism can result in osteoporosis (brittle bones), as well as in several disorders characterized by a deficiency or an oversupply of calcium or PTH in the blood (hypo- and hypercalcemia; hypo-and hyperparathyroidism). Vitamin D deficiency results in rickets (soft, weak

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bones) and osteomalacia in adults. Dr. DeLuca discusses several clinical studies demonstrating an age-related decline in formation of the active Vitamin D metabolite in response to PTH. He describes research he is conducting to develop synthetic Vitamin D compounds that would stimulate bone formation in osteoporotic patients without producing hypercalcemia. He predicts that within a decade these compounds will be important contributors to the treatment of postmenopausal and age-related osteoporosis. Dr. DeLuca goes on to discuss evidence strongly suggesting that Vitamin D influences other biologic processes, including cellular differentiation and regulation of the immune system. Work is ongoing in his laboratory to develop Vitamin D "differentiation compounds" that may have a future role in cancer therapy. The lecture concludes with a discussion of other potential therapeutic uses for Vitamin D, including the treatment of psoriasis, renal osteodystropy (bone disease found with kidney failure), and infertility. •

Techniques for Human Temporal Bone Removal Source: Boston, MA: National Institute on Deafness and Other Communication Disorders (NIDCD) National Temporal Bone, Hearing and Balance Pathology Resource Registry, Massachusetts Eye and Ear Infirmary. November 1996. (videocassette). Contact: Available from National Institute on Deafness and Other Communication Disorders (NIDCD) National Temporal Bone, Hearing and Balance Pathology Resource Registry. Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 021143096. Voice (800) 822-1327 or (617) 573-3711; TTY (617) 573-3888; Fax (617) 573-3838; Email: [email protected]. PRICE: Free of charge to physicians (not suitable for consumers). Summary: This instructional videotape provides training for physicians on how to harvest temporal bones and brain stem tissue. The video, designed for physicians with no prior experience in removal techniques, provides technical information to assist otolaryngologists or pathologists to remove human temporal bones and to prevent postmortem damage to these specimens. Techniques are shown for temporal bone and auditory brain stem removal, including intracranial and extracranial approaches and methods to minimize postmortem autolysis and cosmetic defects. The videotape is accompanied by an article that describes why human temporal bones are an irreplaceable resource for study of the pathology and pathophysiology of disorders of hearing, balance, taste, and facial nerve function. The program emphasizes the need for additional specimens to study disorders for which there are few human specimens; to increase the number of specimens for a given disorder to understand the natural variability and expression of the disease entity; to evaluate the accuracy of otologic diagnoses and the efficacy of otologic treatment modalities; to apply newly available scientific methods, including immunohistochemistry and molecular biologic or genetic techniques; and to teach the anatomy of the human ear and modern otologic surgical techniques.

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Your Kidneys, Your Bones, and You Source: Abbott Park, IL: Abbott Renal Care, Abbott Laboratories. 1993. (videocassette). Contact: Available from Abbott Laboratories, Renal Care. Abbott Park, IL 60064-3537. (800) 457-9472. PRICE: Single copy free to select health care professionals for distribution to patients. Summary: This videotape program provides patients with kidney disease an overview of the causes of renal osteodystrophy. It describes the treatment for renal

Multimedia 203

osteodystrophy, with particular attention given to the role of calcitriol injection (Calcijex) during dialysis. Impaired renal function will decrease and eventually stop production of calcitriol, a hormone that regulates the body's ability to use calcium as a nutrient. This sets off a series of interactions that leads to renal osteodystrophy, a debilitating illness that adds to the already damaging effects of end-stage renal disease (ESRD). The videotape emphasizes the importance of preventing renal osteodystrophy as a way to maintain quality of life. The videotape is produced by the manufacturer of Calcijex. A manual with the same title is also available. (AA-M).

Bibliography: Multimedia on Bones The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in bones (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on bones: •

Bone [videorecording] Source: Division of Learning Resources, University of Kansas, College of Health Sciences and Hospital; Year: 1976; Format: Videorecording; Kansas City, Kan.: The College: [for sale by its Education Resources Center, [1976]

•

Correlation of bone absorptiometry with bone imaging [videorecording] Source: Society of Nuclear Medicine; Year: 1985; Format: Videorecording; [New York, N.Y.]: The Society, [1985]

•

Correlative orthopedic bone imaging [videorecording] Source: Society of Nuclear Medicine; Year: 1985; Format: Videorecording; [New York, N.Y.]: The Society, [1985]

•

Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. Year: 9999; New York: Mary Ann Liebert, Inc., c1986-

•

Trauma to the pelvis and long bones [slide] Source: James J. McCort; Year: 1975; Format: Slide; New York: Medcom, c1975

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to bones: Alendronate •

Systemic - U.S. Brands: Fosamax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202794.html

Androgens and Estrogens •

Systemic - U.S. Brands: Andrest 90-4; Andro-Estro 90-4; Androgyn L.A.; DeComberol; Deladumone; Delatestadiol; depAndrogyn; Depo-Testadiol; Depotestogen; Duo-Cyp; Duo-Gen L.A.; Dura-Dumone 90/4; Duratestin; Estratest; Estratest H.S.; Halodrin; Menoject-L.A.; OB; Premarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202037.html

Arsenic Trioxide •

Systemic - U.S. Brands: Trisenox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500241.html

Bleomycin •

Systemic - U.S. Brands: Blenoxane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202093.html

Busulfan •

Systemic - U.S. Brands: Busulfex; Myleran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202101.html

Calcitonin •

Nasal-Systemic - U.S. Brands: Miacalcin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203482.html

•

Systemic - U.S. Brands: Calcimar; Cibacalcin; Miacalcin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202106.html

Calcium Supplements •

Systemic - U.S. Brands: Alka-Mints; Amitone; Calcarb 600; Calci-Chew; Calciday 667; Calcilac; Calci-Mix; Calcionate; Calcium 600; Calglycine; Calphosan; CalPlus; Caltrate 600; Caltrate Jr; Chooz; Citracal; Citracal Liquitabs; Dicarbosil; Gencalc 600; Liquid Cal-600 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202108.html

Carmustine •

Systemic - U.S. Brands: BiCNU http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202117.html

Chlorambucil •

Systemic - U.S. Brands: Leukeran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202124.html

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Cinoxacin •

Systemic - U.S. Brands: Cinobac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202141.html

Cisplatin •

Systemic - U.S. Brands: Platinol; Platinol-AQ http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202143.html

Cladribine •

Systemic - U.S. Brands: Leustatin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202699.html

Colony Stimulating Factors •

Systemic - U.S. Brands: Leukine; Neupogen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202628.html

Conjugated Estrogens and Medroxyprogesterone for Ovarian Hormone Therapy (OHT) •

Systemic - U.S. Brands: Premphase; Prempro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/209441.html

Copper Supplements •

Systemic - U.S. Brands: Cupri-Pak http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202164.html

Cyclophosphamide •

Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html

Cyclosporine •

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.html

Dactinomycin •

Systemic - U.S. Brands: Cosmegen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202179.html

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed •

Systemic - U.S. Brands: Acel-Imune; Certiva; Infanrix; Tripedia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202201.html

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed and Haemophilus B Conjugate Vaccine •

Systemic - U.S. Brands: Tetramune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202911.html

Doxorubicin •

Systemic - U.S. Brands: Rubex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202209.html

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Epoetin •

Systemic - U.S. Brands: Epogen; Procrit http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202214.html

Estrogens •

Systemic - U.S. Brands: Alora; Aquest; Climara; Clinagen LA 40; Delestrogen; depGynogen; Depo-Estradiol; Depogen; Dioval 40; Dioval XX; Dura-Estrin; Duragen-20; E-Cypionate; Estinyl; Estrace; Estraderm; Estragyn 5; Estragyn LA 5; Estra-L 40; Estratab; Estro-A; Estro-Cyp http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202226.html

Estrogens and Progestins (Ovarian Hormone Therapy) •

Systemic - U.S. Brands: Activella; femhrt; Ortho-Prefest http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500070.html

Etidronate •

Systemic - U.S. Brands: Didronel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202233.html

Etoposide •

Systemic - U.S. Brands: Etopophos; Toposar; VePesid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202234.html

Fluoroquinolones •

Systemic - U.S. Brands: Avelox; Cipro; Cipro I.V.; Floxin; Floxin I.V.; Levaquin; Maxaquin; Noroxin; Penetrex; Tequin; Zagam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202656.html

Ganciclovir •

Systemic - U.S. Brands: Cytovene; Cytovene-IV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202255.html

Goserelin •

Systemic - U.S. Brands: Zoladex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202267.html

Granisetron •

Systemic - U.S. Brands: Kytril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202724.html

Histrelin •

Systemic - U.S. Brands: Supprelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203510.html

Ifosfamide •

Systemic - U.S. Brands: IFEX http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202293.html

Researching Medications

Lamivudine and Zidovudine •

Systemic - U.S. Brands: Combivir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203386.html

Leucovorin •

Systemic - U.S. Brands: Wellcovorin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202321.html

Leuprolide •

Systemic - U.S. Brands: Lupron; Viadur http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202322.html

Melphalan •

Systemic - U.S. Brands: Alkeran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202345.html

Nafarelin •

Systemic - U.S. Brands: Synarel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202646.html

Oprelvekin •

Systemic - U.S. Brands: Neumega http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203420.html

Pamidronate •

Systemic - U.S. Brands: Aredia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202662.html

Plicamycin •

Systemic - U.S. Brands: Mithracin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202467.html

Raloxifene •

Systemic - U.S. Brands: Evista http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203396.html

Risedronate •

Systemic - U.S. Brands: Actonel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203554.html

Samarium Sm 153 Lexidronam •

Therapeutic - U.S. Brands: Quadramet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203683.html

Sodium Fluoride •

Systemic - U.S. Brands: Fluoritab; Fluorodex; Flura; Flura-Drops; Flura-Loz; Karidium; Luride; Pediaflor; Pharmaflur; Phos-Flur http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202527.html

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Strontium Chloride Sr 89 •

Therapeutic - U.S. Brands: Metastron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202706.html

Sulfonamides and Trimethoprim •

Systemic - U.S. Brands: Bactrim; Bactrim DS; Bactrim I.V.; Bactrim Pediatric; Cofatrim Forte; Cotrim; Cotrim DS; Cotrim Pediatric; Septra; Sulfatrim http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202781.html

Tacrolimus •

Systemic - U.S. Brands: Prograf http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202914.html

Tetanus Immune Globulin •

Systemic - U.S. Brands: BayTet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202908.html

Tiludronate •

Systemic - U.S. Brands: Skelid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203480.html

Vitamin D and Related Compounds •

Systemic - U.S. Brands: Calciferol; Calciferol Drops; Calcijex; Calderol; DHT; DHT Intensol; Drisdol; Drisdol Drops; Hectorol; Hytakerol; Rocaltrol; Zemplar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202597.html

Zidovudine •

Systemic - U.S. Brands: Retrovir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202602.html

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

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

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information

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

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

Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=10

•

AP1903 http://www.rarediseases.org/nord/search/nodd_full?code=1002

•

Agiotensin 1-7 http://www.rarediseases.org/nord/search/nodd_full?code=1019

•

Alendronate disodium (trade name: Fosamax) http://www.rarediseases.org/nord/search/nodd_full?code=1082

•

Alendronate disodium (trade name: Fosamax) http://www.rarediseases.org/nord/search/nodd_full?code=1112

•

Alendronate disodium (trade name: Fosamax) http://www.rarediseases.org/nord/search/nodd_full?code=1143

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•

Cells produced using the AastromReplicelle System http://www.rarediseases.org/nord/search/nodd_full?code=1263

•

Monoclonal antibodies PM-81 and AML-2-23 http://www.rarediseases.org/nord/search/nodd_full?code=131

•

Sucralfate suspension http://www.rarediseases.org/nord/search/nodd_full?code=181

•

Trisaccharides A and B (trade name: Biosynject) http://www.rarediseases.org/nord/search/nodd_full?code=197

•

Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=5

•

Roquinimex (trade name: Linomide) http://www.rarediseases.org/nord/search/nodd_full?code=25

•

ST1-RTA immunotoxin (SR 44163) http://www.rarediseases.org/nord/search/nodd_full?code=27

•

Disodium clodronate tetrahydrate (trade name: Bonefos) http://www.rarediseases.org/nord/search/nodd_full?code=272

•

Sargramostim (trade name: Leukine) http://www.rarediseases.org/nord/search/nodd_full?code=33

•

Recombinant methionyl human stem cell factor http://www.rarediseases.org/nord/search/nodd_full?code=380

•

Cytomegalovirus immune globulin intravenous (human http://www.rarediseases.org/nord/search/nodd_full?code=434

•

Ricin (blocked) conjugated murine MCA (anti-my9) http://www.rarediseases.org/nord/search/nodd_full?code=465

•

Anti-thymocyte serum (trade name: Nashville Rabbit Anti-thymocyte Serum) http://www.rarediseases.org/nord/search/nodd_full?code=560

•

Ricin (blocked) conjugated murine mca (anti b-4) http://www.rarediseases.org/nord/search/nodd_full?code=6

•

Chlorhexidine gluconate mouthrinse (trade name: Peridex) http://www.rarediseases.org/nord/search/nodd_full?code=632

•

Busulfan http://www.rarediseases.org/nord/search/nodd_full?code=685

•

Bulsulfan http://www.rarediseases.org/nord/search/nodd_full?code=686

•

CD5-T lymphocyte immunotoxin (trade name: Xomazyme-H65) http://www.rarediseases.org/nord/search/nodd_full?code=693

•

Filgrastim (trade name: Neupogen) http://www.rarediseases.org/nord/search/nodd_full?code=702

•

Humanized anti-tac (trade name: Zenapax) http://www.rarediseases.org/nord/search/nodd_full?code=769

•

Ifosfamide (trade name: Ifex) http://www.rarediseases.org/nord/search/nodd_full?code=777

Researching Medications

•

Busulfan (trade name: Busulfanex) http://www.rarediseases.org/nord/search/nodd_full?code=880

•

Ricin (blocked) conjugated murine MCA (anti-my9) http://www.rarediseases.org/nord/search/nodd_full?code=895

•

Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=901

•

Liposomal Cyclosporin A (trade name: Cyclospire) http://www.rarediseases.org/nord/search/nodd_full?code=911

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

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APPENDICES

217

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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/

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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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “bones” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “bones” (or synonyms) into the “For these words:” box. The following is a sample result: •

Fluorides and oral health: Report of a WHO Expert Committee on Oral Health Status and Fluoride Use Source: Geneva, Switzerland: World Health Organization. 1994. 37 pp. Contact: Available from WHO Publications Center, USA, 49 Sheridan Avenue, Albany, NY 12210. Telephone: (518) 436-9686 / fax: (518) 436-7433. $7.20 plus $1.00 shipping and handling; prepayment required. Summary: This report briefly summarizes what is known about environmental sources of fluoride, its metabolism and excretion, and its incorporation into teeth and bones. The report also evaluates the various body fluids and tissues that can serve as markers for monitoring intakes of biologically available fluoride. Drawing on clinical research experience, the report discusses the relative merits of currently available methods of fluoride administration. Attention is also drawn to the role public health authorities can play in monitoring the population's total fluoride exposure and the prevalence of both caries and fluorsis in seeking oral health benefits.

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 “bones” (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.

15 16

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

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).

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 310005 2442 1743 109 716 315015

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 “bones” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

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/.

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

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

19 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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

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.

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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 Bones In the following section, we will discuss databases and references which relate to the Genome Project and bones. 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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “bones” (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 bones: •

Adamantinoma of Long Bones Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?102660

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Aneurysmal Bone Cysts Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606179

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Bone Fragility with Craniosynostosis, Ocular Proptosis, Hydrocephalus, and Distinctive Facial Features Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?112240

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Bone Pain, Periodic Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?112270

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Bowing of Long Bones, Asymmetric and Symmetric Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?211355

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.

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Brittle Bone Disorder Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603828

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Chondrodysplasia, Lethal, with Long Bone Angulation and Mixed Bone Density Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601376

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Cortical Defects, Wormian Bones, and Dentinogenesis Imperfecta Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604922

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Cystic Angiomatosis of Bone, Diffuse Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?123880

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Dentin Dysplasia with Sclerotic Bones Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?125440

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Expansile Bone Lesions Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603439

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Gracile Bone Dysplasia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602361

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Lipodystrophy, Generalized, with Mental Retardation, Deafness, Short Stature, and Slender Bones Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?608154

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Lissencephaly Type Iii and Bone Dysplasia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601160

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Mitral Regurgitation, Conductive Deafness, and Fusion of Cervical Vertebrae and of Carpal and Tarsal Bones Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?157800

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Nasal Bones, Absence of Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?161480

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Osteogenesis Imperfecta with Opalescent Teeth, Blue Sclerae and Wormian Bones, but without Fractures Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?166230

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Osteolysis, Hereditary, of Carpal Bones with Nephropathy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?166300

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Osteosclerotic Bone Dysplasia, Lethal Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259775

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Paget Disease of Bone Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602080

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Presenile Dementia with Bone Cysts Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?221770

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Pubic Bone Dysplasia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?178350 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

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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

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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

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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

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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

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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:

Physician Resources

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

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

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

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

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

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

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

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

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

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

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

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

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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 “bones” (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.

24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.

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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 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 “bones” (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).

25

Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 bones 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 bones. 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 bones. 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 “bones”:

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Guides on bones Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html

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Other guides 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

Within the health topic page dedicated to bones, the following was listed: •

Specific Conditions/Aspects Pilonidal Disease Source: American Society of Colon and Rectal Surgeons http://www.fascrs.org/displaycommon.cfm?an=1&subarticlenbr=15 Sacral Dimple (Pilonidal Dimple) Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01319

•

Organizations National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/

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 bones. 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:

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•

Hearing Loss and Bone Disorders Source: Washington, DC: Osteoporosis and Related Bone Diseases National Resource Center. 1996. 4 p. Contact: Available from Osteoporosis and Related Bone Diseases National Resource Center. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (800) 624-BONE or (202) 223-0344. TTY (202) 466-4315. Fax (202) 223-2237. Website: www.osteo.org. PRICE: Single copy free. Summary: For people with metabolic bone disorders such as Paget disease of bone or osteogenesis imperfecta, hearing loss is an often overlooked, yet serious, handicap. This fact sheet helps readers understand the basic mechanism of hearing and the nature of hearing loss in individuals with metabolic bone disorders. The fact sheet reviews the anatomy of the ear, the types of hearing loss, and management strategies for hearing loss in Paget disease of bone and in osteogenesis imperfecta. Hearing loss occurs in as many as 50 percent of people with osteogenesis imperfecta and is usually a conductive hearing loss due to problems with the small bones in the middle ear. A sensorineural loss may also develop. Paget disease appears to affect the cochlea, the coiled structure of the inner ear that converts sound vibration into nerve impulses. When the temporal bone is also involved, a more severe and progressive hearing loss may occur. The fact sheet concludes with an annotated list of four resource organizations through which readers can get additional information.

•

Questions and Answers About Paget's Disease of the Bone Source: New York, NY: Paget Foundation. 1999. [7 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: Paget's disease of bone is a chronic disorder that typically results in enlarged and deformed bones in one or more regions of the skeleton. Excessive bone breakdown and formation can cause the bone to weaken. This brochure, written in question and answer format, answers common questions about Paget's disease. Topics include the causes of the disease, the symptoms, how the diagnosis is established, the bones affected by Paget's disease, the relationship between Paget's disease and other problems (arthritis, osteoporosis, heart disease, diabetes, kidney diseases, hearing loss), the causes of pain in Paget's disease, complications of the nervous system, how Paget's disease affects the teeth, the role of diet and exercise, and treatment options, including drug therapy and surgery. One chart summarizes the administration, dosage, and cost of drugs that are approved in the U.S. for the treatment of Paget's disease (biphosphonates, calcitonin). The brochure briefly identifies the Paget Foundation, an organization that provides information and programs for consumers and medical professionals for bone disorders involving abnormal bone resorption, including Paget's disease of bone, primary hyperparathyroidism, fibrous dysplasia, osteopetrosis, and cancer metastatic to bone. 1 figure. 1 table.

•

Patient's Guide to Paget's Disease of Bone Source: New York, NY: Paget Foundation. 199x. 28 p. Contact: Available from Paget Foundation. 200 Varick Street, Suite 1004, New York, NY 10014-4810. (212) 229-1582; (800) 23-PAGET; FAX, (212) 229-1502. PRICE: $2.00 per copy for postage and handling; $21.00 for 25 copies; $39.00 for 50 copies.

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Summary: Paget's disease of bone, or osteitis deformans, is a chronic disorder which results in enlarged and deformed bones in one or more regions of the skeleton. This booklet reprints articles that were originally published in the newsletter of the Paget Foundation. Eleven articles are presented in four sections: general information about Paget's disease, diagnosis and treatment, complications of Paget's disease, and exercise. One article presents a summary of the dental/oral complications related to Paget's disease; the author focuses on the excessive loosening of teeth as a result of destruction of the supporting periodontal bone, tooth root resorption, or both. •

Gift of Hearing: Learning About Temporal Bone Donation Source: San Bruno, CA: Krames Communications. 1994. 15 p. Contact: Available from NIDCD National Temporal Bone Registry. c/o Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114-3096. Voice (800) 822-1327 or 9617) 573-3711; TTY (617) 573-3888; Fax (617) 573-3838. PRICE: Single copy free. Summary: This booklet discusses the anatomy and physiology of hearing and balance, and problems related to each. Written for patients with hearing loss, a balance problem, or facial nerve paralysis, the booklet introduces readers to the National Temporal Bone Registry, a nonprofit organization established to provide information about temporal bone donation and research. Topics covered include statistics on the prevalence and epidemiology of hearing and balance disorders; the anatomy of the outer, middle, and inner ear; the role of the hair cells; conductive hearing loss; sensorineural hearing loss; balance disorders; central auditory and vestibular disorders; facial nerve disorders; how the temporal bone is studies; the benefits of temporal bone research, including in the areas of hearing loss due to aging, otosclerosis, benign positional vertigo, and Meniere's disease; and questions about donation. The booklet shows readers how they can help find new treatments and cures for ear problems by donating their temporal bones to scientific research. The booklet includes a coupon with which readers can request donor enrollment forms.

•

Your Kidneys, Your Bones, and You: A Guide to Healthier Bones From Your Hemodialysis Team Source: Abbott Park, IL: Abbott Laboratories. 1994. 20 p. Contact: Available from Abbott Laboratories. Renal Care, Abbott Park, IL 60064-3500. (708) 937-6100 or (800) 457-9472. PRICE: Single copy free. Available to health professionals only. Summary: This booklet provides hemodialysis patients with information about renal osteodystrophy and its prevention. Topics include the functions of the bones; how kidney disease affects the bones; the interplay of calcitriol and parathyroid hormone (PTH); how calcitriol therapy helps to overcome bone problems; oral versus injectable calcitriol; why diet affects the bones; phosphorus, calcium, and aluminum; and how patients can take charge of their own bone health. The booklet concludes with a brief subject index and a copy of the insert information for Calcijex (Abbott Laboratories) brand of injectable calcitriol. The booklet includes numerous full-color photographs.

•

Medications and Bone Loss: Are You at Risk for Osteoporosis? Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 18 p.

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Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides the general public with information on the relationship between using certain medications and developing osteoporosis. This disease is characterized by inadequate bone formation, excessive bone removal, or both, leading to reduced bone strength and increased risk of fractures. The booklet briefly describes the bone remodeling process and identifies the risk factors for osteoporosis. One risk factor that is often overlooked is the use of certain medications that can damage bones and lead to osteoporosis. One class of drugs that has particularly damaging effects is glucocorticoids, which interfere with the bone remodeling process and calcium regulation in various ways. Bone loss increases with the dose and the duration of treatment. Other drugs that can cause osteoporosis are thyroid hormones, phenytoin and barbiturate anticonvulsants, aluminum-containing antacids, methotrexate, cyclosporine A, gonadotropic releasing hormone analogs, heparin, and cholestyramine. The booklet offers suggestions on minimizing the harmful effects of steroids and other medications. 2 figures, 2 tables, and 2 references. •

That Others May Hear: National Temporal Bone Donor Program Source: Boston, MA: NIDCD National Temporal Bone Registry. 1995. 2 p. Contact: Available from NIDCD National Temporal Bone Registry. c/o Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114-3096. Voice (800) 822-1327 or (617) 573-3711; TTY (617) 573-3888; Fax (617) 573-3838. PRICE: Single copy free. Summary: This brochure describes the National Temporal Bone Donor Program, a national resource for researchers and the public to promote human temporal bone research. The brochure describes how individuals can donate their temporal bones and associated brain structures after death. The bulk of the brochure consists of questions and answers regarding the temporal bone and the donation program. Topics covered include why the study of temporal bones is useful; the costs involved; the role of the donor's next of kin in deciding about organ donation; the national temporal bone procurement network; donating transplantable organs as well as the temporal bone; the need for an autopsy; the parts of the brain that are involved with hearing (brain stem) and their donation; and the entities involved in financially supporting the National Temporal Bone Registry. The brochure includes a postage-paid postcard with which readers can obtain more information about temporal bone research and donation.

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Banking on Beautiful Bones: A Lifelong Commitment to Calcium Source: Rosemont, IL: National Dairy Council, 10 panels, 1996. Contact: National Dairy Council, O'Hare International Center, 10255 West Higgins Road, Suite 9A, Rosemont, IL, 60018-5616. (800) 426- 8271. (708) 803-2000, ext. 306. Summary: This brochure focuses on the importance of calcium for nutritional health. The role of calcium in bone production is explained, and suggestions for increasing calcium intake are offered. The role of exercise in bone strength and maintenance is also emphasized, with a list of ideas for ways to easily increase activity.

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Questions and Answers About Paget's Disease of Bone Source: New York, NY: The Paget's Disease Foundation, Inc. 1999. 8 p.

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Contact: Paget Foundation for Paget's Disease of Bone and Related Disorders. 120 Wall Street, Suite 1602, New York, NY 10005-4001. (800) 23-PAGET or (212) 509-5335. Fax (212) 509-8492. E-mail: [email protected]. Website: www.paget.org. PRICE: $2.00 postage and handling. Summary: This brochure provides answers to general questions concerning Paget 's disease, related medical conditions, the importance of diet and exercise, and treatment options. Questions answered define what PD is and its symptoms; explains who is at risk for getting the disease; describes its diagnosis; and discusses the relationship it has with other medical conditions such as arthritis, osteoporosis, heart disease, diabetes, kidney problems, and central nervous system complications. The brochure reveals there is no relationship between diet and PD, that exercise is important in maintaining skeletal health and is recommended, and that treatment of PD involves two classes of drugs, calcitonin and bisophosphonates , which suppress the abnormal bone cell activity associated with PD. •

Maintaining Your Bone Health During Dialysis Source: Middleton, WI: Bone Care International. 2001. [7 p.]. Contact: Available from Bone Care International. 1600 Aspen Commons, Middleton, WI 53562. (888) 389-4242. Website: www.bonecare.com. E-mail: [email protected]. PRICE: Single copy free. Summary: This brochure provides information to kidney patients who are on dialysis and who have been prescribed doxercalciferol (Hectorol) therapy. The brochure is illustrated with cartoon figures representing the kidney and the bones; the text is written in nontechnical language. The brochure first explains how healthy kidneys work in partnership with the bones and other systems of the body. The brochure then describes what happens when kidney disease affects the functioning of the kidney in this interrelated system. The kidney produces active vitamin D and the parathyroid gland makes another hormone called parathyroid hormone (PTH). The bones control the amount of calcium in the system by either storing or releasing calcium. The bones depend on the amount of PTH in the body's system to decide to release or store calcium. Without active vitamin D, the parathyroid gland will make too much PTH and then the bones release large amounts of calcium into the system. Without enough calcium, the bones become weak and can break easily. The brochure outlines other problems that can be associated with too much calcium, then explains how doxercalciferol is used to trigger the liver the make the active vitamin D the system needs. The brochure includes the product information insert for Hectorol. 6 figures.

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How Strong Are Your Bones? Find Out If You Are at Risk for Osteoporosis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 15 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This brochure uses a question and answer format to provide the general public with information on osteoporosis and bone density testing. Osteoporosis is a disease that causes bones to weaken and break easily. The brochure describes the normal bone remodeling process, explains how osteoporosis occurs, identifies its causes and risk factors, and discusses the medical tests available to measure bone density. The brochure presents the features of these tests, explains the information that the test

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provides the patient and the doctor, identifies candidates test, and explains what the results of the test mean. In addition, the brochure highlights treatments that can slow bone loss and prevent osteoporotic fractures, such as estrogen replacement therapy, alendronate, and calcitonin. 8 figures, 1 table, and 1 reference. •

Bone Disease in Chronic Kidney Failure Source: New York, NY: The National Kidney Foundation. 1996. [4 p.]. Contact: National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. Website: www.kidney.org. PRICE: Single copy free; bulk copies available. Summary: This brochure, written in question and answer format, presents patient information about bone disease in chronic kidney failure. Topics include the causes of bone disease in people with kidney failure, the different types of bone disease, how phosphorus levels affect the bones, the role of the parathyroid glands, how aluminum levels in the bones are related to bone disease, the role of vitamin D, how diet and exercise can contribute to healthy bones, guidelines for calcium supplementation, how a kidney transplant will affect bone disease problems, and risk factors for bone disease. The brochure concludes with a list of patient education publications available from the National Kidney Foundation.

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Bone Grafting the Cleft Maxilla Source: Chapel Hill, NC: Cleft Palate Foundation (CPF). 1998. 1 p. Contact: Available from Cleft Palate Foundation, Inc. 104 South Estes Drive, Suite 204, Chapel Hill, NC 27514. (800) 242-5338 or (919) 933-9044. Fax (919) 933-9604. Website: www.cleft.com. PRICE: Single copy free. Summary: This fact sheet describes bone grafting in the dental ridge of the upper jaw (maxilla), a standard and reliable treatment for patients with facial clefts. Bone grafting is an operation which involves taking a small amount of bone from one place (usually the hip, head, ribs, or leg) and placing it in the area of the cleft near the teeth. The fact sheet lists the four goals that can be accomplished by bone grafting: to provide support for unerupted teeth and teeth next to the cleft, to provide support for the lip and nose and to improve symmetry, to form a continuous upper gum ridge, and to improve the stability of the front part of the roof of the mouth. The fact sheet notes patient selection issues, such as recommended age for the procedure. The fact sheet concludes by discussing the three options that may be considered to replace any missing teeth in the area of the graft: moving adjacent teeth into the bone graft, prosthetic replacement (dental bridge),; or dental metallic bone implants. The fact sheet includes the contact information for the Cleft Palate Foundation, including the informational CleftLine (80024-CLEFT).

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Understanding the Structure of Bone in OI Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1998. 3 p. Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: Single copy free. Summary: This fact sheet for health professionals and people who have osteogenesis imperfecta (OI) provides information on bone structure in OI, specifically the role of collagen rods and minerals. People with OI have abnormal collagen rods. The fact sheet

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describes the normal formation of collagen rods and explains why they are abnormal in people with OI and how the abnormality affects their bone structure. In severe forms of OI, the collagen fibers that form the rods are either kinked or broken so that the structure is inherently unstable; however, the milder forms of OI result from the underproduction of otherwise normal collagen fibers. The fact sheet also notes that a collagen mutation can have devastating effects on bone strength, because defective collagen rods do not provide a proper mold for bone mineral cement. Moreover, poorly formed collagen rods are more susceptible to the body's normal process of detecting and destroying broken molecules, and the cells that form bone are themselves affected by the nearby presence of bad collagen molecules. 2 figures. •

Osteoporosis and Your Bones Source: American Family Physician. 54(3): 995-996. September 1, 1996. 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 fact sheet for the general public discusses what osteoporosis is, how it can be prevented, symptoms, diagnosis, and treatment options. The sheet explains that osteoporosis is a decrease in density or thickness of bone and that prevention entails a diet containing enough calcium and vitamin D. A family history of osteoporosis, shortening of height, a deformity of the spine, and pain in the back or neck are all symptoms associated with osteoporosis. Bone density measurements and blood and urine laboratory tests can confirm a suspicion of osteoporosis, and if confirmed, treatment can involve drug therapy to reduce calcium loss.

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Kids and Their Bones: A Guide for Parents Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2002. 12 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 toll-free or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail: [email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-251. Summary: This fact sheet uses a question and answer format to provide parents with information on helping their children adopt healthy nutritional and lifestyle habits so that they have good lifelong skeletal health. During childhood and adolescence, bone tissue in the skeleton increases. Most girls reach their peak bone mass by age 18, and most boys do so by age 20. Optimizing peak bone mass and developing lifelong healthy bone habits during youth are ways to prevent or minimize the risk of osteoporosis as an adult. Factors affecting peak bone mass include gender, race, hormones, nutritional status, and physical activity. The most important lifelong bone health habits to encourage in children and adolescents are proper nutrition and physical activity. The information sheet answers questions about calcium intake, dieting, and physical activity, as well as listing ways parents can help their children develop healthy diet and exercise habits. Resources for additional information are also given. 3 tables.

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Bone Problems Contact: Project Inform, HIV Treatment Hotline, 205 13th St Ste 2001, San Francisco, CA, 94103, (415) 558-8669, http://www.projectinform.org. Summary: This fact sheet, for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses HIV/AIDS-related bone conditions. The fact sheet discusses bone problems, such as avascular necrosis and osteonecrosis, among individuals with HIV/AIDS. The fact sheet discusses the symptoms of bone conditions and preventative measures such as early intervention with surgery. Bone problems, caused by a lack of blood supply to the bone, lead to the deterioration and death of bone tissue, particularly bones that support much of an individual's body weight such as the hip.

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For great bones to support your beautiful body Source: Frankfort, KY: Kentucky Department of Education. n.d. 1 p. Contact: Available from Linda Dunsmore, Kentucky Department of Education, Division of School and Community Nutrition, 500 Mero Street, Frankfort, KY 40601. Telephone: (502) 564-4390. Contact source for price information. Summary: This self-adhesive 8 x 10 inch poster was designed to hang in public restrooms. It explains why calcium is needed in the diet, tells how much calcium adolescents and young adult women need each day, and shows pictorial equivalents of 300 mg of calcium. A list of low- calorie, high-calcium foods is included. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “bones” (or synonyms). The following was recently posted: •

ACR Appropriateness Criteria for osteoporosis and bone mineral density Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3263&nbr=2489&a mp;string=bones

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ACR Appropriateness Criteria for bone tumors Source: American College of Radiology - Medical Specialty Society; 1995 (revised 1999); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2418&nbr=1644&a mp;string=bones

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ACR Appropriateness Criteria for follow-up examinations for bone tumors, softtissue tumors, and suspected metastasis post therapy Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2002); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3556&nbr=2782&a mp;string=bones

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ACR Appropriateness Criteria for metastatic bone disease Source: American College of Radiology - Medical Specialty Society; 1995 (revised 1999); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2421&nbr=1647&a mp;string=bones

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Practice management guidelines for the optimal timing of long bone fracture stabilization in polytrauma patients Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2795&nbr=2021&a mp;string=bones

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Procedure guideline for bone pain treatment Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1362&nbr=620&am p;string=bones

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Procedure guideline for bone scintigraphy Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1333&nbr=601&am p;string=bones

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Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2003 March 14; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3766&nbr=2992&a mp;string=bones

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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Bone Cancer: Questions and Answers Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7052

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Caring for Children with OI (Osteogenesis Imperfecta) Summary: Osteogenesis imperfecta (OI) can literally be translated as imperfectly formed bones. Most forms of OI are caused by imperfectly formed bone collagen that results from a genetic defect. Source: Osteogenesis Imperfecta Foundation, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7010

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Childhood and Adolescent Nutrition: Why Milk Matters Now for Children and Teens Summary: This fact sheet focuses on the importance of including milk in the diet of adolescents -- more specifically, teenaged girls -- to build strong bones. Source: National Institute of Child Health and Human Development, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3782

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Osteoporosis: The Bone Thief Summary: Online patient education fact sheet that provides information about prevention, diagnosis and treatment options for this bone disease that thins and weakens bones to the point where they break Source: National Institute on Aging, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2375

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Powerful Bones, Powerful Girls: The National Bone Health Campaign Summary: This bone health campaign for girls features tips on nutrition and exercise. Girls have fun playing quizzes and games as they learn about how to keep their bones strong. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6362

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Questions and Answers about Avascular Necrosis Summary: Avascular necrosis is a disease resulting from the temporary or permanent loss of the blood supply to the bones. Without blood, the bone tissue dies and causes the bone to collapse. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6718

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Questions and Answers About Gout Summary: Gout is one of the most painful rheumatic diseases. It results from deposits of needle-like crystals of uric acid in connective tissue, in the joint space between two bones, or in both. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6721

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Questions and Answers about Scoliosis in Children and Adolescents Summary: Scoliosis is a musculoskeletal disorder in which there is a sideways curvature of the spine, or backbone. The bones that make up the spine are called vertebrae. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6732

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Synovial Sarcoma Summary: A fact sheet about a rare type of cancer that occurs in tendons, bursae, or the cavity that separates the bones of certain joints. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7099

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The Milk Maze Summary: Help LaMilka Bones deliver delicious Milk Group foods to the Food Guide Pyramid. Source: National Dairy Council http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5763 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 bones. The drawbacks of this approach are that the information is not

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organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

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

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

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

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

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

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

News Services and Press Releases One of the simplest ways of tracking press releases on bones 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 “bones” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to bones. 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 “bones” (or synonyms). 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.

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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 “bones” (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 “bones” (or synonyms). If you know the name of a company that is relevant to bones, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “bones” (or synonyms).

Newsletters on Bones Find newsletters on bones using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “bones.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “bones” (or synonyms) into the “For these words:” box. The following list was generated using the options described above:

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Kidney Failure in Sarcoidosis Source: Sarcoidosis Networking. 8(3): 3. 2000. Contact: Available from Sarcoid Network Association. Sarcoidosis Networking, 13925 80th Street East, Puyallup, WA 98372-3614. Email: [email protected]. Summary: Sarcoidosis is a chronic, progressive systemic granulomatous (causing lesions) disease of unknown cause (etiology), involving almost any organ or tissue, including the skin, lungs, lymph nodes, liver, spleen, eyes, and small bones of the hands or feet. This brief article, from a newsletter for patients with sarcoidosis, reviews the complications of kidney failure in sarcoidosis. Granulomatous infiltration of the kidney may be present in as many as 40 percent of patients with sarcoidosis, but it is rarely extensive enough to cause renal (kidney) dysfunction. The lesions are usually responsive to steroid therapy. Kidney failure has also been diagnosed in patients with sarcoidosis without the presence of lesions, possibly due to hypercalcemia (too much calcium in the blood), involvement of the glomerular filter system, and renal arteritis (inflammation of the arteries of the kidney), which may be associated with severe high blood pressure. It is recommended that all people with active sarcoidosis be screened for hypercalciuria (high levels of calcium in the urine). This may precede development of hypercalcemia, which should be treated. Glucocorticoids are the main choice of therapy and do seem to reduce levels of urinary calcium to normal within a few days. People with sarcoidosis may also have severe pain; the frequent use of pain medication can be another cause of kidney failure. People who take pain medication should ask their physicians to evaluate their kidneys on a regular basis. 9 references.

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “bones” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on bones: •

Tending Your Garden Means Tending Your Bones Source: University of California, Berkeley Wellness Letter. 21(2):8. April 2003. Contact: Health Letter Associates, P.O. Box 412, Prince Street Station, New York, New York. 10012-0007. www.wellnessletter.com. Summary: Researchers at the University of Arkansas looked at the activities and bone densities of more than 3,000 women aged 50 and older. Strength training and yard work were the only two physical activities highly correlated with strong bones. Heavy duty gardening or intense yard work is a form of strength training. Since gardening is not typically thought of as 'exercise,' promoting this activity could be a means for getting an inactive person started. 'Regardless of how vigorous the gardening is, people like it' notes lead researcher Lori Turner, Ph.D., R.D.

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Boning Up on Bone Health Source: University of California, Berkeley, Wellness Letter. 16(12):5. September 2000. Contact: Health Letter Associates. P.O. Box 412, Prince Street Station, New York, NY 10012-0007. Summary: Strong bones are dependent on more than just the mineral calcium. Depending on many factors, including testosterone in men and estrogen in women, calcium is laid down in bone and released from it. Weight-bearing exercise such as walking synergizes with nutrients and hormones to build up bone tissue. Lack of activity robs the body of bone mass. The article reviews the other nutrients besides calcium that are necessary for bone health: vitamin C, vitamin K, vitamin D, magnesium, potassium, zinc, copper, manganese, and boron. These nutrients can be found in diets rich in fruits, whole grains, vegetables, low-fat and non-fat dairy products, and fortified cereals. The author also recommends a daily multivitamin and mineral supplement for most people.

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Top Ten Tips to Help Celiacs Maintain Sturdy Bones Source: Gluten-Free Living. 1(5): 5. September-October 1996. Contact: Available from Gluten-Free Living. P.O. Box 105, Hastings-on-Hudson, NY 10706. Summary: This brief newsletter article lists ten tips to help people with celiac disease maintain sturdy bones. The tips include: have a bone densitometry test to diagnose bone disease; include foods that are naturally high in calcium in the daily diet; take calcium and Vitamin D supplements as necessary; consider estrogen replacement therapy, if appropriate; do weight-bearing exercises; restrict intake of coffee, alcohol, and salt; and don't smoke.

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Osteopenia: When You Have Weak Bones, but Not Osteoporosis Source: Harvard Health Letter. 28(12): 6. October 2003. Contact: Available from Harvard Health Publications. P.O. Box 421073, Palm Coast, FL 32141-1073. (800) 829-9045. Email: [email protected]. Summary: This newsletter article discusses osteopenia, a condition in which bone mineral density is lower than normal. This condition affects about half of Americans over the age of 50. Although women are more likely to have low bone density, approximately one-third of all white and Asian men over 50 are affected. Bone mineral density is measured by dual-energy x-ray absorptiometry. The bigger the negative number in the 'T-score' (the measurement of bone density) the more below standard and the more porous the bones are. There is also a greater chance that a fracture will occur. Risk factors for developing weak bones include not getting enough calcium or vitamin D, smoking, drinking too much, using certain medications such as corticosteroids and anticonvulsants, and not getting enough weight-bearing exercise. Osteopenia can be treated with exercise, nutrition, or medications. Medications used to treat osteopenia include alendronate, risedronate, and raloxifene. The National Osteoporosis Foundation recommends that women aged 65 years and older, postmenopausal women younger than 65 with at least one risk factor, and postmenopausal women who already have had a fracture should get a bone mineral density test.

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Injury Prevention: Keeping Old Bones Whole Source: Harvard Health Letter. 21(11):1-2; September 1996. Contact: Harvard Medical School Health Publications Group, 164 Longwood Avenue, Boston, MA 02115. Summary: This newsletter article for the general public discusses ways to prevent latelife fractures. Basic approaches to preventing fractures include averting a fall, decreasing the severity if a fall occurs, and keeping bone strong. Falls can be avoided by removing households obstacles or objects likely to cause falls and exercising to improve balance, flexibility, muscle strength, and reaction time. Various padding systems can be used to reduce the severity of a fall. Pads are built into a tight-fitting undergarment, and they protect the hip by absorbing energy from a fall or transferring the energy away from the bone and into surrounding tissues. In addition, maintaining bone density throughout life by performing regular weight-bearing exercise and consuming adequate amounts of calcium and vitamin D is essential. Estrogen replacement therapy can prevent postmenopausal bone loss, and various medications can help both men and women preserve bone. 1 figure.

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Growing Bones: Bone Expansion Treats Facial Deformities Source: FDA Consumer. 35(4): 17-18. July-August 2001. Contact: Available from Superintendent of Documents. Government Printing Office, Washington, DC 20402. (202) 512-1800. Summary: This newsletter article provides people who have bone deformities and their families with information on bone expansion to treat facial deformities. Although bone expansion was once applied only to big bones such as those in the legs, growing bone in the jaws has become one of the newest ways to correct facial deformities, especially in children. Bone distraction osteogenesis is a technique that involves cutting existing bone and inserting a bone distractor. The titanium distractor holds the two pieces of bone less than a millimeter apart and is inserted into the jaw with pins or screw attachments. The patient, or parent in the case of children, turns the screw twice a day to activate the stretching process. This technique has been successful in people with underdeveloped jaws and in those undergoing reconstruction after cancer surgery or accidents. Bone distraction requires surgery to implant and remove the device. Most distractors are manipulated manually. Bone distraction is considered a safer and less invasive procedure than bone grafting. 2 figures.

Associations and Bones The following is a list of associations that provide information on and resources relating to bones: •

Bone Marrow Foundation (The BMF) Telephone: (212) 828-3029 Toll-free: (800) 365-1336 Fax: (212) 223-0081 Email: [email protected] Web Site: http://www.bonemarrow.org

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Background: The Mission on the Bone Marrow Foundation is to improve the quality of life for bone marrow transplant patients and their families by providing financial aid, education, and emotional support. The BMF was created in 1992 to respond to the critical gap in financial coverage for patient support services. Its Patient Aid Program has assisted hundreds of patients with the cost of donor searches, compatibility testing, bone marrow harvesting, medications, home and child care services, medical equipment, transportation, cord blood banking, and housing expenses associated with the transplant. The BMF currently accepts applications for aid from over seventy bone marrow transplant centers throughout the United States. To fulfill the growing need for information and support for patients and their families, the BMF established the Marie M. Reynolds Resource and Education Center. It provides information to patients, their families and their clinicians. The Center also seeks to provide support and encouragement to patients and families dealing with the challenge of life-threatening diseases. •

Children's Brittle Bone Foundation Telephone: (866) 694-2223 Fax: (262) 947-0724 Email: [email protected] Web Site: http://www.cbbf.org Background: The Children's Brittle Bone Foundation (CBBF) is a voluntary health organization dedicated to promoting research into the causes, diagnosis, treatment, prevention, and eventual cure of osteogenesis imperfecta (OI). Osteogenesis imperfecta, a rare genetic disorder, is characterized by defective development of collagen. Collagen, the body's major structural protein, forms an essential part of bones, tendons, and connective tissues. Individuals with osteogenesis imperfecta have unusually fragile bones that break or fracture easily. There are four major types of the disorder that may vary greatly in severity. Osteogenesis imperfecta may be inherited as an autosomal dominant or autosomal recessive genetic trait or may be due to a new genetic mutation. More that 50 mutations in genes that encode type I collagen have been identified. Established in 1991 and currently consisting of approximately 45 members, the Children s Brittle Bone Foundation is committed to promoting basic and clinical scientific research and to encouraging biomedical research scientists interest in this currently underrepresented field.

•

International Bone Marrow Transplant Registry Telephone: (414) 456-8325 Fax: (414) 456-6530 Email: [email protected] Web Site: http://www.ibmtr.org Background: The International Bone Marrow Transplant Registry (IBMTR) and Autologous Blood and Marrow Transplant Registry (ABMTR) are voluntary research organizations that collect, organize, and collaborate information on blood and bone marrow transplants. Comprised of more than 300 worldwide transplant institutions, IBMTR/ABMTR have worked since 1972 to study transplantation, cancer treatments, and other related issues and medical possibilities. IBMTR/ABMTR also offer educational programs for both the professional and public communities, publish reports

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and a regular newsletter entitled 'IBMTR Newsletter,' as well as a selection of audiovisual aids. •

National Bone Marrow Transplant Link Telephone: (248) 358-1886 Toll-free: (800) 546-5268 Fax: (248) 358-1889 Email: [email protected] Web Site: http://www.mbmtlink.org Background: The National Bone Marrow Transplant Link is a not-for-profit voluntary organization dedicated to improving the quality of life of those undergoing bone marrow transplantation (BMT) and promoting public understanding of BMT through programs of education and research. Established in 1992, its primary goal is to assist individuals involved in the bone marrow transplantation process. However, the National BMT Link also educates the public about bone marrow transplantation; works as an advocate for national recognition of BMT as an effective, insurable procedure; supports the continuation of BMT research; and serves as a clearinghouse for information about transplants, transplant centers, donor centers, and bone marrow collection sites. In addition, the organization acts as a resource center of up-to-date medical and scientific reports on BMT and offers a networking service, which is a person-to-person connection that puts potential patients in touch with experienced and accessible peers. The National BMT Link is funded through private, foundation, and corporate donations.

•

NIDCD National Temporal Bone, Hearing and Balance Pathology ResourceRegistry Telephone: (617) 573-3711 Toll-free: (800) 822-1327 Fax: (617) 573-3838 Email: [email protected] Web Site: http://www.tbregistry.org Background: The NIDCD National Temporal Bone, Hearing and Balance Pathology Resource Registry is a not-for-profit research organization that serves as a national resource for researchers and the public to promote research into human temporal bone and balance disorders. The Registry continues and expands upon the activities of the former National Temporal Bone Banks Program established by the Deafness Research Foundation in 1960. The Registry seeks individuals with ear disorders such as hearing loss or balance problems to make an anatomical gift of their temporal bones and associated brain structures. These donations are vital for the advancement of knowledge and understanding of hearing and balance disorders. Established in 1992, the NIDCD National Temporal Bone Hearing and Balance Pathology Resource Registry produces a quarterly newsletter and brochures. In addition, the Registry maintains a computerized database of human temporal bone collections in the United States.

•

NIH Osteoporosis and Related Bone Diseases National Resource Center Telephone: (202) 223-0344 Toll-free: (800) 624-2663 Fax: (202) 293-2356 Email: [email protected]

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Web Site: http://www.osteo.org Background: The NIH Osteoporosis and Related Bone Diseases~National Resource Center (NIH ORBD~NRC) provides patients, health professionals, and the public with an important link to resources and information on metabolic bone diseases such as osteoporosis, Paget's disease of bone, osteogenesis imperfecta, and primary hyperparathyroidism. Specific populations include the elderly, men, women, adolescents, and minorities. The Resource Center offers materials in English, Spanish, Chinese, Korean, and Vietnamese. NIH ORBD~NRC is supported under a contract from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, with contributions from the National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, NIH Office of Research on Women's Health, DHHS Office on Women's Health, and the National Institute on Aging. NIH ORBD~NRC is operated by the National Osteoporosis Foundation. •

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.

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

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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 “bones” (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 “bones”. 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 “bones” (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 “bones” (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.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •

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

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

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

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

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

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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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/

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

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

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

Basic Guidelines for Bones Bone fracture repair Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002966.htm Bone graft Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002963.htm Bone lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003923.htm Bone marrow aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003658.htm Bone marrow biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003934.htm Bone marrow culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003682.htm

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Bone marrow transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003009.htm Bone pain or tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003180.htm Bone scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003833.htm Bone tumors Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001230.htm Bone X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003808.htm •

Signs & Symptoms for Bones Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Anemias Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Bleeding disorder Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001304.htm Bone pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003180.htm Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Joint pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Leukemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001299.htm Muscle pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Problems breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm

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Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm •

Diagnostics and Tests for Bones Alkaline phosphatase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm ALP (alkaline phosphatase) isoenzyme Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003497.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Blood differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm Bone biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003923.htm Bone marrow aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003658.htm Bone marrow biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003934.htm Bone scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003833.htm Bone X-rays Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003808.htm Calcium (ionized) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003486.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Complete blood count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Cyst Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003240.htm Extremity X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003461.htm

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Hands X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003811.htm HLA antigens Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm Joints X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003810.htm Platelets Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm PTH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003690.htm Serum calcium Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003477.htm Serum phosphorus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003478.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm X-ray of bone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003808.htm •

Nutrition for Bones Vitamin D Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002405.htm

•

Surgery and Procedures for Bones Bone graft Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002963.htm Bone grafts Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002963.htm

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Background Topics for Bones Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Benign Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002236.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm

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Bone fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Broken bone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Cancer - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002166.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Clot Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Distal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002346.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Fractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Hormone level Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003445.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Malignancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002253.htm Metabolism Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002257.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Pain relievers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm

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Physical activities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm Surgical excision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002305.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm

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

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

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

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

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

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BONES DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] 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] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [NIH] Accelerated phase: Refers to chronic myelogenous leukemia that is progressing. The number of immature, abnormal white blood cells in the bone marrow and blood is higher than in the chronic phase, but not as high as in the blast phase. [NIH] Acclimatization: Adaptation to a new environment or to a change in the old. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow.

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Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] 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 Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH]

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Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alendronate Sodium: A drug that affects bone metabolism. It is used in treating osteoporosis and Paget's disease, and is being studied in the treatment of hypercalcemia (abnormally high levels of calcium in the blood) and in treating and reducing the risk of bone pain caused by cancer. Alendronate sodium belongs to the family of drugs called bisphosphonates. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alginates: Salts of alginic acid that are extracted from marine kelp and used to make dental impressions and as absorbent material for surgical dressings. [NIH]

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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]

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] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [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] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU]

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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 Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]

Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] Androgen suppression: Treatment to suppress or block the production of male hormones. Androgen suppression is achieved by surgical removal of the testicles, by taking female sex hormones, or by taking other drugs. Also called androgen ablation. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and

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stimulate skeletal growth. [NIH] 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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Ankle Joint: The joint that is formed by the inferior articular and malleolar articular surfaces of the tibia, the malleolar articular surface of the fibula, and the medial malleolar, lateral malleolar, and superior surfaces of the talus. [NIH] Ankylosis: Fixation and immobility of a joint. [NIH] Anomalies: Birth defects; abnormalities. [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] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [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

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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] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] 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] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [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] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antrectomy: An operation to remove the upper portion of the stomach, called the antrum. This operation helps reduce the amount of stomach acid. It is used when a person has complications from ulcers. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells.

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[NIH]

Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appendicular skeleton: The framework around and within which the soft parts of the body are situated. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU]

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Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspiration: The act of inhaling. [NIH] 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] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiologist: Study of hearing including treatment of persons with hearing defects. [NIH] Audiology: The study of hearing and hearing impairment. [NIH] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [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]

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Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliopancreatic Diversion: A surgical procedure which diverts pancreatobiliary secretions via the duodenum and the jejunum into the colon, the remaining small intestine being anastomosed to the stomach after antrectomy. The procedure produces less diarrhea than does jejunoileal bypass. [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]

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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] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [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] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] Blasts: Immature blood cells. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] 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] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH]

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Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Conduction: Sound transmission through the bones of the skull to the inner ear. [NIH] Bone Cysts: Benign unilocular lytic areas in the proximal end of a long bone with well defined and narrow endosteal margins. The cysts contain fluid and the cyst walls may contain some giant cells. Bone cysts usually occur in males between the ages 3-15 years. [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 ablation: The destruction of bone marrow using radiation or drugs. [NIH] Bone Marrow Examination: Removal of bone marrow and evaluation of its histologic picture. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone Regeneration: Renewal or repair of lost bone tissue. It excludes bony callus formed after bone fracture but not yet replaced by hard bone. [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] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture

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therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]

Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcaneus: The largest of the tarsal bones and is situated at the lower and back part of the foot forming the heel. [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

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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] 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] Calcium Phosphates: Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements. [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] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Carbenicillin: Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function. [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] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is

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usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cefazolin: Semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. [NIH] Cefonicid: A second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is effective in the treatment of urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections. [NIH] Cefoxitin: Semisynthetic cephamycin antibiotic resistant to beta-lactamase. [NIH] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH]

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Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [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 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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] 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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH]

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Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chiasma: An anatomy term for an X-shaped crossing (for example, of nerves or tendons.) [NIH]

Child Care: Care of children in the home or institution. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [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] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [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] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [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 Disease: Disease or ailment of long duration. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic phase chronic myelogenous leukemia: A phase of chronic myelogenous leukemia that may last from several months to several years. Although there may be no symptoms of leukemia, there are too many white blood cells. [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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [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] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide

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inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Implantation: Surgical insertion of an electronic device implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [NIH] Cochlear Nucleus: The brain stem nucleus that receives the central input from the cochlear nerve. The cochlear nucleus is located lateral and dorsolateral to the inferior cerebellar peduncles and is functionally divided into dorsal and ventral parts. It is tonotopically organized, performs the first stage of central auditory processing, and projects (directly or indirectly) to higher auditory areas including the superior olivary nuclei, the medial geniculi, the inferior colliculi, and the auditory cortex. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or

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signals the beginning or end of the message. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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]

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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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [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] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH]

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Constipation: Infrequent or difficult evacuation of feces. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans)

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end of the body. [EU] Cranial Sutures: A type of fibrous joint between bones of the head. [NIH] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones. [NIH] Craniosynostoses: Premature closure of one or more sutures of the skull. [NIH] 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] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption

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maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [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] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification.

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[NIH]

Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dental implant: A small metal pin placed inside the jawbone to mimic the root of a tooth. Dental implants can be used to help anchor a false tooth or teeth, or a crown or bridge. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

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] 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]

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Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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]

Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dyskeratosis Congenita: A disturbance in normal keratinization, resulting, in the eye, in hornification of the epithelial layer of the cornea or conjunctiva. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU]

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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said

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of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endolymphatic Duct: Duct connecting the endolymphatic sac with the membranous labyrinth. [NIH] Endolymphatic Sac: The blind pouch at the end of the endolymphatic duct. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH]

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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] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enoxacin: An orally administered broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria. Its clinical efficacy has been confirmed in a variety of systemic infections and particularly in urinary tract infections. The drug is well tolerated by adults, but should not be used in children and pregnant women. [NIH]

Enucleation: Removal of the nucleus from an eucaryiotic cell. [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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] 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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [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] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which

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covers the inner or outer surfaces of the body. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [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] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [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] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensive-stage small cell lung cancer: Cancer that has spread outside the lung to other tissues in the chest or to other parts of the body. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU]

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Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] 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] 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] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] 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] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is

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a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] 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] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] 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] Flatus: Gas passed through the rectum. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoridation: The addition of fluorine usually as a fluoride to something, as the adding of a fluoride to drinking water or public water supplies for prevention of tooth decay in children. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH]

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Follicular large cell lymphoma: A rare type of non- Hodgkin's lymphoma (cancer of the lymphatic system) with large cells that look cleaved (split) or non-cleaved under the microscope. It is an indolent (slow-growing) type of lymphoma. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Formulary: A book containing a list of pharmaceutical products with their formulas and means of preparation. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Cameras: Electronic instruments that produce photographs or cathode-ray tube images of the gamma-ray emissions from organs containing radionuclide tracers. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of

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proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an

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increased risk for developing a specific disease or disorder. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [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]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] 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] 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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [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]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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]

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Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [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 earliest stage to maturity. [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] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders

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primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Handicap: A handicap occurs as a result of disability, but disability does not always constitute a handicap. A handicap may be said to exist when a disability causes a substantial and continuing reduction in a person's capacity to function socially and vocationally. [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] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated

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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] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [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]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [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] Herniated: Protrusion of a degenerated or fragmented intervertebral disc into the intervertebral foramen compressing the nerve root. [NIH] 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]

Hip Prosthesis: Replacement for a hip joint. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histidine Decarboxylase: An enzyme that catalyzes the decarboxylation of histidine to histamine and carbon dioxide. It requires pyridoxal phosphate in animal tissues, but not in

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microorganisms. EC 4.1.1.22. [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] Histology: The study of tissues and cells under a microscope. [NIH] Holmium: An element of the rare earth family of metals. It has the atomic symbol Ho, atomic number 67, and atomic weight 164.93. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [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] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by

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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] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperostosis: Increase in the mass of bone per unit volume. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertelorism: Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [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] Hypnotic: A drug that acts to induce sleep. [EU] Hypodermic: Applied or administered beneath the skin. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idiopathic myelofibrosis: A progressive disease in which the bone marrow is replaced by fibrous tissue and is unable to produce red blood cells; the cause is unknown. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Image Enhancement: Improvement of the quality of a picture by various techniques, including computer processing, digital filtering, echocardiographic techniques, light and ultrastructural microscopy, fluorescence spectrometry and microscopy, scintigraphy, and in vitro image processing at the molecular level. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

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Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

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of

foreign

Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [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] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] 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] Incision: A cut made in the body during surgery. [NIH] Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indolent: A type of cancer that grows slowly. [NIH] 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]

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Inertia: Inactivity, inability to move spontaneously. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [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]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [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] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune,

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genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [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] Interferometry: Measurement of distances or movements by means of the phenomena caused by the interference of two rays of light (optical interferometry) or of sound (acoustic interferometry). [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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy,

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implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, 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] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] 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] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Jejunoileal Bypass: A surgical procedure consisting of the anastomosis of the proximal part of the jejunum to the distal portion of the ileum, so as to bypass the nutrient-absorptive segment of the small intestine, to treat morbid obesity. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU]

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Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner synovial membrane. [NIH] Joint Instability: Lack of stability of a joint or joint prosthesis. Factors involved are intraarticular disease and integrity of extra-articular structures such as joint capsule, ligaments, and muscles. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetic: Pertaining to or producing motion. [EU] 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] Lactation: The period of the secretion of milk. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by

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indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] 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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lead Poisoning: Disease caused by the gradual accumulation of a significant body burden of lead. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [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] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] 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] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [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] Lipid: Fat. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH]

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Liposarcoma: A rare cancer of the fat cells. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lunate: A curved sulcus of the lateral surface which forms the anterior limit of the visual cortex. [NIH] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]

Lung volume: The amount of air the lungs hold. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [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]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph

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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] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macaca: A genus of the subfamily Cercopithecinae, family Cercopithecidae, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes. [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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

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

Mammary: Pertaining to the mamma, or breast. [EU]

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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] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meniscus: A fibro-cartilage within a joint, especially of the knee. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some

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primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [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 Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [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] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [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] Metatarsal Bones: The five long bones of the metatarsus articulating with the tarsal bones proximally and the toes (phalanges) distally. [NIH] Metatarsus: The part of the foot between the tarsa and the toes. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [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] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and

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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] 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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. [NIH] 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] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration,

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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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] 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] Moxalactam: Broad- spectrum beta-lactam antibiotic similar in structure to the cephalosporins except for the substitution of an oxaazabicyclo moiety for the thiaazabicyclo moiety of certain cephalosporins. It has been proposed especially for the meningitides because it passes the blood-brain barrier and for anaerobic infections. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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 relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

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Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Myositis Ossificans: A disease characterized by bony deposits or the ossification of muscle tissue. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nasal Bone: Either of two small elongated rectangular bones that together form the bridge of the nose. [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] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [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] Neck Injuries: General or unspecified injuries to the neck. It includes injuries to the skin, muscles, and other soft tissues of the neck. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH]

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Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrolithiasis: Kidney stones. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [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] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropil: A dense intricate feltwork of interwoven fine glial processes, fibrils, synaptic terminals, axons, and dendrites interspersed among the nerve cells in the gray matter of the central nervous system. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [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] Neutralization: An act or process of neutralizing. [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]

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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] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

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] Nonmalignant: Not cancerous. [NIH] Nonmalignant hematologic disorders: Disorders of the blood, some of which lead to leukemia. [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 Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [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] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH]

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Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oligoelement: A chemical substance, minute amounts of which can be found in living organisms. [EU] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [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 environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] 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] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] 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

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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] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] 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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of 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] Osteochondrodysplasias: Abnormal development of cartilage and bone. [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] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi. [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] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [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] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteonectin: Non-collagenous, calcium-binding glycoprotein of developing bone. It links

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collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for secreted protein, acidic and rich in cysteine. [NIH] 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] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Osteosclerosis: An abnormal hardening or increased density of bone tissue. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otorhinolaryngology: That branch of medicine concerned with medical and surgical treatment of the head and neck, including the ears, nose and throat. [EU] 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] Outer ear: The pinna and external meatus of the ear. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The 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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [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

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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] Papovaviridae: A family of small, non-enveloped DNA viruses affecting mostly mammals. Most members can induce tumors in hosts. There are two genera: Papillomavirus and Polyomavirus. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] 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]

Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A 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] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] 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] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic 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

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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]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentostatin: A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [NIH]

Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] 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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] 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 stem cell transplantation: A method of replacing blood-forming cells destroyed

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by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [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] Phallic: Pertaining to the phallus, or penis. [EU] 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] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. [NIH] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH]

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Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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] Pilot study: The initial study examining a new method or treatment. [NIH] Piperacillin: Semisynthetic, broad-spectrum, ampicillin-derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. [NIH]

Piperacillin-tazobactam: A combination of drugs used to fight infections in people who have cancer. Piperacillin is a synthetic penicillin; tazobactam enhances the effectiveness of piperacillin. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae".

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[NIH]

Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [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] Polyglutamic Acid: A peptide that is a homopolymer of glutamic acid. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH] Polyostotic Fibrous Dysplasia: Abnormal tissue development or growth occurring subsequent to the appearance of the primordial cells. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Porins: Protein molecules situated in the outer membrane of gram-negative bacteria that, in dimeric or trimeric form, constitute a water-filled transmembrane channel allowing passage of ions and other small molecules. Porins are also found in bacterial cell walls, and in plant, fungal, mammalian and other vertebrate cell and mitochondrial membranes. [NIH] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [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]

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Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of

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action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] 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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the

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configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [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] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]

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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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudomonas Infections: Infections with bacteria of the genus Pseudomonas. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] 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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [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]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH]

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Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyridoxal Phosphate: 3-Hydroxy-2-methyl-5-((phosphonooxy)methyl)-4pyridinecarboxaldehyde. An enzyme co-factor vitamin. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radioactive: Giving off radiation. [NIH] Radiofrequency ablation: The use of electrical current to destroy tissue. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [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] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [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] Radiolucent: Partly or wholly permeable to X-rays or other forms of radiation contrasted with radiopaque. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the

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diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [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] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]

of the alkaline earth series of metals. It has the atomic and atomic weight 226. Radium is the product of the present in pitchblende and all ores containing uranium. It of beta and gamma-rays in radiotherapy, particularly

Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recessive gene: A gene that is phenotypically expressed only when homozygous. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]

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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] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney 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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH]

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Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [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] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Round Window: Fenestra of the cochlea; an opening in the medial wall of the middle ear leading into the cochlea. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Salivary: The duct that convey saliva to the mouth. [NIH]

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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] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [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] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH]

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Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female

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or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological 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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [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] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft Tissue Injuries: Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as "soft tissue injuries of the hand". [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somite: One of the paired blocks of mesoderm present in each segment of the early embryo. [NIH]

Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH]

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Spectroscopic: The recognition of elements through their emission spectra. [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] Sphenoid Sinus: One of the paired paranasal sinuses, located in the body of the sphenoid bone and communicating with the highest meatus of the nasal cavity on the same side. [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 Stenosis: Narrowing of the spinal canal. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylolisthesis: Forward displacement of one vertebra over another. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [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

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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] Sternum: Breast bone. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] 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] Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62. [NIH] Strontium-89: A radioactive compound that is absorbed by the bone. It is used to treat bone pain associated with prostate cancer. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclavian Artery: Artery arising from the brachiocephalic trunk on the right side and from the arch of the aorta on the left side. It distributes to the neck, thoracic wall, spinal cord, brain, meninges, and upper limb. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by

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clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] 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]

Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [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] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptophysin: A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In Alzheimer disease and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains

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mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Tarsal Bones: The seven bones which form the tarsus - namely, calcaneus, talus, cuboid, navicular, and first, second and third cuneiforms. The tarsus is a skeletal part of the foot. [NIH]

Tarsus: The region of the articulation between the foot and the leg. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] 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] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [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] Thanatophoric Dysplasia: A severe form of neonatal dwarfism with very short limbs. All cases have died at birth or in the neonatal period. [NIH]

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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] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [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] 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]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [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] Tibiae: The long bone on the medial and pre-axial border of the leg. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Ticarcillin: An antibiotic derived from penicillin similar to carbenicillin in action. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases;

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vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] 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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Total-body irradiation: Radiation therapy to the entire body. Usually followed by bone marrow or peripheral stem cell transplantation. [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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the

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initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] 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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [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

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kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [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] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Umbilical cord blood transplantation: The injection of umbilical cord blood to restore an individual's own blood production system suppressed by anticancer drugs, radiation therapy, or both. It is being studied in the treatment of cancer and severe blood disorders such as aplastic anemia. Cord blood contains high concentrations of stem cells needed to produce new blood cells. [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] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [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] Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine

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urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [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] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together

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to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertebral Artery: The first branch of the subclavian artery with distribution to muscles of the neck, vertebrae, spinal cord, cerebellum and interior of the cerebrum. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] 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] Vestibular Nerve: The vestibular part of the 8th cranial nerve (vestibulocochlear nerve). The vestibular nerve fibers arise from neurons of Scarpa's ganglion and project peripherally to vestibular hair cells and centrally to the vestibular nuclei of the brain stem. These fibers mediate the sense of balance and head position. [NIH] 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] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [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]

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Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [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] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zoledronate: A drug that belongs to the family of drugs called bisphosphonates. It is used to prevent bone fractures and reduce bone pain in people who have cancer that has spread to the bone. [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]

347

INDEX 3 3-dimensional, 61, 261, 326 A Abdomen, 261, 273, 304, 307, 319, 320, 336, 337, 340 Abdominal, 261, 285, 300, 318, 330 Ablate, 261, 275 Ablation, 164, 165, 173, 261, 265 Abscess, 261, 333 Acanthosis Nigricans, 30, 261 Accelerated phase, 166, 261 Acclimatization, 42, 261 ACE, 197, 261 Acetylcholine, 261, 314, 315 Acid Phosphatase, 104, 261 Acoustic, 30, 261, 269, 303 Acrylonitrile, 261, 331 Actin, 261, 313, 342 Acute leukemia, 156, 161, 162, 261, 324 Acute lymphoblastic leukemia, 155, 159, 160, 261, 262 Acute lymphocytic leukemia, 261 Acute myelogenous leukemia, 157, 159, 164, 169, 262 Acute myeloid leukemia, 157, 164, 170, 171, 262, 325 Acute nonlymphocytic leukemia, 262 Adaptability, 262, 276 Adaptation, 42, 92, 261, 262, 322 Adenosine, 262, 273, 320, 321 Adenosine Deaminase, 262, 320 Adenovirus, 60, 262 Adjustment, 11, 93, 262 Adjuvant, 80, 173, 262 Adjuvant Therapy, 173, 262 Adolescence, 15, 38, 66, 103, 167, 194, 234, 262 Adrenal Cortex, 262, 266, 282, 290, 325 Adverse Effect, 3, 12, 262, 321, 334 Aerobic, 262, 312, 327 Afferent, 262, 291 Affinity, 18, 30, 77, 263, 335 Affinity Chromatography, 77, 263 Agar, 263, 322 Age Groups, 194, 263 Age of Onset, 263, 343 Aged, 80 and Over, 263 Agonist, 71, 176, 263, 329

Airway, 42, 263 Albumin, 263, 339 Alendronate, 12, 16, 71, 97, 142, 167, 206, 211, 233, 242, 263 Alendronate Sodium, 12, 263 Alertness, 263, 273 Alginates, 109, 263 Algorithms, 32, 44, 264, 271 Alkaline, 57, 71, 82, 104, 188, 257, 264, 265, 274, 329, 337, 339 Alkaline Phosphatase, 57, 71, 82, 257, 264 Alkylating Agents, 264, 273 Allogeneic, 156, 166, 176, 264, 321 Allogeneic bone marrow transplantation, 156, 166, 176, 264 Allylamine, 264 Alopecia, 264, 283 Alpha Particles, 264, 328 Alphavirus, 67, 81, 264, 334 Alternative medicine, 240, 264 Aluminum, 230, 231, 233, 264 Alveolar Bone Loss, 6, 8, 9, 11, 88, 264 Alveolar Process, 6, 197, 264, 330 Alveoli, 264, 344 Amebiasis, 264, 310 Amenorrhea, 129, 264, 266 Amine, 187, 264, 298 Amino Acid Motifs, 265, 281 Amino Acid Sequence, 26, 265, 266, 281, 325 Amino-terminal, 265, 325 Ammonia, 262, 264, 265, 343 Ampicillin, 265, 322 Anabolic, 38, 265 Anaerobic, 82, 265, 312 Anaesthesia, 183, 265, 301 Anal, 265, 292, 307 Analgesic, 85, 265 Analog, 31, 71, 265, 275, 279 Analogous, 16, 265, 342 Anaphylatoxins, 265, 280 Anatomical, 49, 185, 245, 265, 277, 287, 301, 332 Androgen suppression, 171, 265 Androgenic, 265, 266 Androgens, 85, 206, 262, 265, 268, 282 Androstenedione, 18, 142, 266

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Anemia, 134, 157, 166, 169, 170, 224, 256, 266, 273, 292, 312, 318 Anesthesia, 66, 263, 266, 325 Anesthetics, 266, 270, 289 Anginal, 266, 315 Angiogenesis, 17, 33, 51, 83, 85, 266, 309 Angiography, 32, 266 Animal model, 16, 32, 38, 49, 50, 60, 66, 70, 73, 104, 266 Anionic, 33, 266 Anions, 263, 266, 304, 324 Ankle, 88, 104, 183, 266 Ankle Joint, 183, 266 Ankylosis, 28, 266 Anomalies, 67, 185, 266 Anorexia, 3, 129, 266, 317 Anorexia Nervosa, 3, 129, 266 Antagonism, 266, 273 Antiangiogenic, 39, 266 Antibacterial, 266, 279, 289, 316, 324, 336, 344 Antibiotic, 81, 265, 266, 269, 273, 275, 279, 290, 306, 312, 320, 322, 331, 336, 340 Antibodies, 50, 55, 163, 164, 212, 266, 267, 297, 301, 308, 311, 322, 328 Antibody, 40, 66, 163, 164, 263, 267, 280, 297, 299, 301, 302, 304, 305, 312, 328, 329, 335, 346 Antibody therapy, 164, 267 Anticoagulant, 267, 326 Anticonvulsant, 267, 321 Antigen, 263, 266, 267, 280, 295, 299, 300, 301, 302, 303 Antigen-Antibody Complex, 267, 280 Anti-inflammatory, 11, 12, 267, 282, 295 Anti-Inflammatory Agents, 267, 282 Antimetabolite, 267, 310, 331 Antimicrobial, 91, 267, 278 Antineoplastic, 264, 267, 274, 282, 283, 310, 320, 323, 340, 341 Antineoplastic Agents, 264, 267, 320 Antioxidants, 71, 267 Antipruritic, 267, 277 Antitumour, 189, 267 Antiviral, 267, 303, 320, 331 Antrectomy, 267, 270 Anuria, 267, 305 Anus, 265, 267, 273, 280 Aorta, 267, 300, 337, 344 Aplasia, 96, 166, 267 Aplastic anemia, 267, 343 Aponeurosis, 268, 293

Apoptosis, 24, 32, 38, 48, 54, 61, 268, 275 Appendicular skeleton, 77, 268 Aqueous, 268, 270, 284, 287 Arachidonic Acid, 124, 268, 306, 325 Archaea, 268, 310 Arginine, 265, 268, 315 Aromatase, 18, 85, 105, 268 Arterial, 28, 264, 268, 300, 326 Arteries, 241, 267, 268, 271, 282, 300, 310, 340, 343 Arterioles, 42, 268, 271, 274 Arteriovenous, 196, 268 Arteriovenous Fistula, 196, 268 Arteritis, 241, 268 Artery, 268, 282, 309, 319, 327, 337 Arthralgia, 67, 268 Arthroplasty, 79, 86, 92, 97, 185, 188, 268 Articular, 56, 76, 266, 268, 305, 317 Aseptic, 268, 316, 337 Aspartic, 26, 269, 288 Aspartic Acid, 26, 269 Aspirate, 158, 269 Aspiration, 94, 157, 255, 257, 269 Assay, 34, 50, 53, 56, 269, 301, 331 Asymptomatic, 11, 173, 264, 269 Ataxia, 224, 269, 339 Atrophy, 69, 224, 269 Attenuation, 79, 269 Atypical, 97, 156, 157, 159, 161, 166, 176, 269 Audiologist, 198, 269 Audiology, 8, 158, 269 Audiovisual Aids, 245, 269 Auditory, 8, 9, 31, 202, 230, 269, 279, 297, 309, 343 Auditory Cortex, 269, 279 Auditory nerve, 9, 269, 309 Autoimmune disease, 269, 321 Autologous, 106, 244, 269, 321 Autolysis, 8, 202, 269 Autopsy, 231, 269 Avian, 62, 67, 269 Axons, 269, 314 Azithromycin, 81, 269 B Bacteria, 50, 266, 267, 268, 269, 270, 284, 291, 296, 310, 311, 312, 327, 336, 341, 342, 344 Bacterial Physiology, 262, 270 Bactericidal, 270, 275 Bacteriophage, 270, 322, 342 Bacteriuria, 270, 344

Index 349

Barbiturate, 231, 270 Basal Ganglia, 269, 270, 293 Basal Ganglia Diseases, 269, 270 Base, 25, 50, 270, 284, 305, 323, 339 Basement Membrane, 270, 291 Benign, 86, 166, 199, 230, 258, 270, 272, 293, 297, 313, 329, 331 Benzene, 270, 304 Bilateral, 10, 126, 270, 319 Bile, 143, 270, 277, 293, 299, 307, 337 Biliary, 270, 277 Biliopancreatic Diversion, 105, 270 Biochemical, 17, 19, 24, 49, 59, 61, 64, 68, 108, 109, 178, 194, 267, 270, 305, 317 Biological response modifier, 270, 271, 303 Biological therapy, 271, 296 Biomarkers, 33, 271 Biopsy, 157, 158, 177, 197, 255, 257, 271 Biopsy specimen, 157, 271 Biotechnology, 70, 83, 195, 219, 222, 223, 224, 225, 240, 271 Bladder, 271, 281, 293, 326, 330, 343, 344 Blast phase, 261, 271, 278 Blasts, 170, 271 Blood Coagulation, 271, 274, 331, 340 Blood Glucose, 191, 271, 298, 302 Blood Platelets, 271, 340 Blood pressure, 167, 175, 241, 271, 275, 300, 312, 315, 335 Blood vessel, 17, 27, 53, 61, 102, 190, 261, 266, 271, 272, 275, 277, 288, 295, 304, 307, 308, 310, 320, 335, 337, 339, 340, 344 Blood Volume, 42, 271 Blood-Brain Barrier, 271, 312 Blot, 34, 35, 50, 271 Body Burden, 271, 306 Body Composition, 21, 175, 271 Body Fluids, 220, 271, 286, 335, 343 Body Mass Index, 74, 272 Bone Cements, 272, 323 Bone Conduction, 198, 272 Bone Cysts, 96, 222, 223, 272 Bone Development, 17, 29, 59, 62, 66, 82, 167, 189, 272 Bone marrow ablation, 160, 272 Bone Marrow Examination, 96, 272 Bone metastases, 46, 51, 69, 84, 89, 163, 164, 165, 172, 173, 236, 272, 279, 329 Bone Regeneration, 4, 17, 156, 272 Bone Remodeling, 46, 48, 51, 52, 73, 78, 88, 177, 231, 232, 272 Bone scan, 88, 176, 256, 257, 272, 332

Bony Callus, 272 Boron, 105, 112, 242, 272, 273 Boron Neutron Capture Therapy, 273 Bowel, 4, 102, 265, 273, 285, 304, 337 Bowel Movement, 273, 285, 337 Brachytherapy, 273, 303, 304, 328, 329, 346 Bradykinin, 273, 315 Brain Stem, 8, 202, 231, 273, 276, 279, 345 Branch, 253, 273, 308, 309, 318, 319, 327, 335, 340, 345 Breakdown, 60, 177, 229, 273, 285, 294, 334 Broad-spectrum, 80, 265, 273, 274, 275, 276, 289, 316, 322 Buccal, 87, 273, 307 Bupivacaine, 273, 306 Busulfan, 157, 167, 206, 212, 213, 273 C Cadmium, 72, 105, 122, 273 Cadmium Poisoning, 273 Caffeine, 144, 194, 273, 327 Calcaneus, 15, 273, 339 Calcifediol, 273, 274 Calcification, 19, 27, 28, 194, 273 Calcitonin, 72, 76, 144, 206, 229, 232, 233, 274 Calcitriol, 203, 230, 274 Calcium Phosphates, 77, 274 Callus, 93, 274, 287 Capillary, 17, 273, 274, 275, 344 Capillary Fragility, 274, 275 Carbenicillin, 274, 340 Carbohydrate, 274, 282, 316, 323 Carbon Dioxide, 274, 284, 292, 294, 298, 322, 330 Carboplatin, 160, 274 Carcinogen, 274, 310, 340 Carcinogenesis, 274, 321 Carcinogenic, 264, 270, 274, 302, 316, 325, 337 Carcinoma, 189, 274 Cardiac, 11, 42, 144, 264, 273, 274, 289, 306, 313, 337 Cardiac Output, 42, 274 Cardiology, 158, 275 Cardiopulmonary, 42, 275 Cardiovascular, 15, 27, 275, 306 Cardiovascular disease, 27, 275 Case report, 72, 85, 87, 91, 94, 95, 96, 97, 98, 104, 275, 279 Case series, 275, 279 Caspase, 48, 275 Catechin, 122, 275

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Bones

Catheter, 94, 126, 275 Catheter Ablation, 126, 275 Cathode, 275, 293 Cations, 275, 304 Caudal, 72, 275, 300, 323 Causal, 21, 22, 275, 304 Cefazolin, 79, 275 Cefonicid, 71, 275 Cefoxitin, 73, 275 Ceftriaxone, 79, 275 Celiac Disease, 92, 130, 242, 276 Cell Adhesion, 24, 276, 303 Cell Count, 69, 276 Cell Death, 16, 268, 276, 290, 295 Cell Differentiation, 67, 74, 276, 334, 336 Cell Division, 224, 269, 276, 290, 296, 311, 322, 333 Cell membrane, 82, 276, 285, 293, 321 Cell proliferation, 25, 32, 33, 38, 51, 58, 60, 276, 334 Cell Size, 16, 276 Cell Survival, 276, 296 Cell Transplantation, 59, 160, 162, 169, 172, 174, 276 Central Nervous System, 232, 261, 270, 273, 276, 286, 287, 293, 295, 297, 306, 314, 323 Centrifugation, 123, 276 Cephalosporins, 276, 312 Cerebellar, 269, 276, 279, 329 Cerebellum, 276, 323, 329, 345 Cerebral, 269, 270, 271, 273, 276, 277, 282, 289, 319 Cerebral Cortex, 269, 276 Cerebral hemispheres, 270, 273, 276, 277 Cerebrovascular, 270, 275, 277, 339 Cerebrum, 276, 277, 342, 345 Cervical, 25, 223, 277, 331 Cervix, 277, 292 Character, 277, 284, 295 Chelating Agents, 123, 277 Chemotactic Factors, 277, 280 Chiasma, 277, 283 Child Care, 244, 277 Chimeras, 61, 277 Chin, 106, 186, 190, 277, 310 Chlorophyll, 277, 293 Cholesterol, 116, 131, 270, 277, 282, 307, 329, 334, 337 Cholestyramine, 231, 277 Chondrocytes, 24, 37, 45, 57, 58, 59, 62, 66, 82, 108, 277, 292

Chondrogenesis, 29, 53, 59, 277 Chromatin, 268, 277, 315 Chromosomal, 22, 35, 277, 278 Chromosome, 26, 33, 74, 166, 168, 278, 306, 333 Chronic, 10, 12, 14, 23, 27, 69, 77, 98, 122, 130, 156, 157, 159, 161, 162, 164, 166, 167, 168, 169, 176, 177, 185, 198, 224, 229, 230, 233, 241, 261, 264, 271, 278, 289, 302, 305, 307, 323, 327, 330, 337, 339, 346 Chronic Disease, 23, 185, 278 Chronic granulocytic leukemia, 278 Chronic leukemia, 156, 161, 162, 177, 278 Chronic lymphocytic leukemia, 278 Chronic myelogenous leukemia, 166, 168, 261, 271, 278 Chronic phase, 156, 166, 168, 261, 278 Chronic phase chronic myelogenous leukemia, 156, 166, 168, 278 Chronic renal, 278, 323 Ciliary, 278, 333 Ciliary Body, 278, 333 Ciprofloxacin, 73, 79, 278 CIS, 55, 278, 294 Cisplatin, 112, 160, 207, 278 Citrus, 126, 278 C-kit receptor, 278, 336 Clamp, 182, 278 Clavulanic Acid, 73, 278 Clear cell carcinoma, 279, 285 Clindamycin, 73, 81, 279 Clinical Medicine, 107, 279, 324 Clinical study, 37, 279 Clinical trial, 13, 51, 63, 155, 171, 178, 189, 219, 279, 282, 283, 312, 320, 327, 329 Clodronate, 212, 279 Clone, 17, 26, 34, 59, 67, 279 Cloning, 24, 50, 271, 279, 302 Coccidioidomycosis, 14, 279 Cochlea, 8, 10, 198, 229, 279, 302, 331 Cochlear, 9, 10, 31, 88, 279, 340, 345 Cochlear Implantation, 31, 279 Cochlear Nerve, 279, 345 Cochlear Nucleus, 31, 279, 345 Codons, 68, 279 Coenzyme, 280, 307, 334 Cofactor, 280, 326, 340 Collapse, 238, 273, 280 Colon, 224, 228, 270, 280, 306 Combination chemotherapy, 155, 160, 161, 164, 168, 169, 170, 280

Index 351

Combination Therapy, 280, 290 Complement, 21, 61, 265, 280, 281, 294, 303, 308 Complementary and alternative medicine, 121, 122, 153, 280 Complementary medicine, 121, 122, 281 Complete remission, 281, 330 Compliance, 23, 281 Computational Biology, 219, 222, 281 Computed tomography, 9, 52, 90, 272, 281, 332 Computer Simulation, 64, 281 Computerized tomography, 12, 281 Concomitant, 8, 58, 281 Conduction, 198, 275, 281 Conjugated, 108, 128, 207, 212, 213, 281, 283, 331 Conjunctiva, 281, 286 Connective Tissue Cells, 281 Consciousness, 265, 281, 284, 286 Consensus Sequence, 55, 265, 281 Conserved Sequence, 265, 281 Constipation, 85, 256, 282 Consumption, 15, 21, 92, 194, 282, 315, 330 Contraindications, ii, 4, 282 Contralateral, 198, 282, 329 Contrast medium, 266, 282 Control group, 21, 282, 329 Controlled study, 97, 282 Convulsions, 267, 270, 282 Coordination, 65, 276, 277, 282 Cornea, 282, 286 Corneum, 282, 289 Coronary, 275, 282, 310 Coronary heart disease, 275, 282 Coronary Thrombosis, 282, 310 Cortex, 13, 35, 138, 140, 282, 317, 329 Cortical, 8, 18, 19, 35, 41, 47, 52, 63, 64, 77, 79, 88, 95, 97, 105, 109, 182, 183, 223, 282, 333, 339 Corticosteroid, 5, 282, 337 Cranial, 21, 45, 54, 67, 80, 87, 136, 269, 276, 279, 282, 283, 290, 291, 297, 314, 319, 336, 345 Cranial Sutures, 45, 54, 67, 283 Craniofacial Abnormalities, 32, 54, 283 Craniosynostoses, 67, 283 Creatine, 74, 283 Creatine Kinase, 74, 283 Creatinine, 283, 305 Criterion, 66, 283 Crossing-over, 35, 283, 329

Crowns, 64, 283, 285 Cryptosporidiosis, 269, 283 Curative, 20, 166, 283, 331, 340 Cutaneous, 283, 307, 321 Cyclic, 273, 283, 296, 315, 326 Cyclophosphamide, 145, 157, 160, 164, 167, 207, 283 Cyclosporine, 162, 207, 231, 283 Cyst, 85, 95, 98, 257, 269, 272, 283 Cytochrome, 268, 283 Cytokine, 47, 284, 292, 303, 332 Cytoplasm, 268, 276, 284, 288, 312, 315, 331, 338 Cytoskeleton, 284, 303 Cytotoxic, 60, 284, 303, 328, 329, 334 Cytotoxicity, 264, 278, 284, 305 D Dairy Products, 242, 284 Data Collection, 50, 284 De novo, 19, 52, 170, 284 Decarboxylation, 284, 298 Defense Mechanisms, 284, 303 Degenerative, 43, 185, 284, 298, 317 Dehydroepiandrosterone, 145, 284, 285 Deletion, 24, 34, 35, 53, 66, 74, 76, 81, 268, 284 Dementia, 11, 223, 284, 314 Dendrites, 284, 314 Dendritic, 39, 284, 309 Dental Abutments, 284, 285 Dental Caries, 284, 292, 335 Dental Hygienists, 13, 285 Dental implant, 4, 65, 156, 285, 317 Dentures, 4, 285 Depolarization, 285, 334 Deprivation, 38, 176, 285 Dermatology, 158, 285 Dermis, 285, 342 DES, 33, 265, 285 Developmental Biology, 29, 46, 55, 285 DHEA, 145, 284, 285 Diagnostic procedure, 31, 181, 240, 285 Dialyzer, 285, 297 Diaphragm, 42, 285 Diarrhea, 264, 270, 277, 283, 285, 306 Dietitian, 5, 285 Digestion, 270, 273, 285, 301, 304, 307, 337 Digestive system, 179, 285, 294, 312 Dilatation, 285, 324 Direct, iii, 5, 21, 27, 45, 50, 57, 58, 61, 62, 74, 88, 95, 197, 205, 275, 279, 285, 295, 330, 337, 338

352

Bones

Discrete, 55, 67, 272, 285, 339 Disease-Free Survival, 39, 286 Dislocation, 93, 286 Dissociation, 263, 286, 304 Distal, 44, 97, 259, 275, 286, 304, 327 Diuresis, 273, 286 Dizziness, 286, 345 Dominance, 286, 289 Dorsal, 279, 286, 314, 323 Drive, ii, vi, 4, 13, 26, 44, 101, 233, 286, 306 Drug Interactions, 210, 211, 286 Duct, 286, 288, 331, 337 Duodenum, 270, 286, 304, 337 Dura mater, 54, 286 Dwarfism, 53, 59, 286, 339 Dynorphins, 286, 316 Dyskeratosis Congenita, 157, 286 Dyspareunia, 286, 290 Dysplasia, 28, 75, 167, 223, 224, 229, 246, 286 Dystrophy, 224, 286 E Ectoderm, 67, 286, 314 Ectopic, 27, 61, 62, 72, 80, 87, 286 Edema, 10, 104, 287 Effector, 45, 261, 280, 287, 305 Efferent, 89, 287, 291 Efficacy, 9, 15, 19, 62, 81, 89, 202, 287, 289, 342 Elastic, 64, 65, 107, 287, 295, 335 Elastin, 280, 287, 291 Elective, 81, 95, 287 Electrolyte, 282, 287, 305, 311, 324, 335 Electron microscope, 64, 287 Embryo, 29, 35, 62, 272, 276, 286, 287, 291, 295, 301, 310, 317, 335, 343 Embryogenesis, 16, 36, 53, 287, 336 Embryology, 67, 287 Emulsion, 287, 292 Enamel, 64, 127, 284, 287 Encephalitis, 67, 287 Encephalitis, Viral, 287 Endemic, 14, 287, 336 Endocrine Glands, 288, 319 Endocrine System, 288, 314 Endocrinology, 88, 89, 92, 93, 95, 96, 104, 106, 107, 108, 123, 128, 158, 288, 297 Endogenous, 61, 92, 105, 288, 289, 316, 321, 326, 341 Endolymphatic Duct, 288 Endolymphatic Sac, 197, 288 Endometrial, 288

Endometriosis, 131, 194, 288 Endometrium, 288, 309 Endopeptidases, 288, 326 Endorphins, 288, 314, 316, 325 Endothelial cell, 25, 73, 271, 288, 292, 340 Endothelium, 75, 288, 315 Endothelium, Lymphatic, 288 Endothelium, Vascular, 288 Endothelium-derived, 288, 315 Endotoxins, 280, 288, 305 End-stage renal, 203, 278, 289, 323 Enkephalins, 289, 314, 316 Enoxacin, 72, 289 Enucleation, 87, 289 Environmental Exposure, 289, 316 Environmental Health, 218, 220, 289 Enzymatic, 39, 265, 274, 280, 284, 289, 298 Epidemic, 289, 336 Epidermal, 45, 67, 289, 309 Epidermal Growth Factor, 45, 289 Epidermis, 67, 282, 285, 289, 299 Epidural, 94, 289 Epinephrine, 289, 314, 343 Epiphyseal, 53, 57, 289 Epistasis, 29, 289 Epithelial, 46, 50, 278, 286, 289, 298 Epithelial Cells, 46, 289, 298 Epithelium, 59, 67, 270, 288, 289 Erythrocyte Volume, 271, 290 Erythrocytes, 266, 272, 290, 329 Erythromycin, 269, 290 Esophagus, 285, 290, 294, 337 Essential Tremor, 224, 290 Estradiol, 66, 71, 74, 146, 208, 290 Estrogen receptor, 18, 46, 109, 290 Estrogen Replacement Therapy, 233, 242, 290 Ethmoid, 290, 319 Etoposide, 160, 208, 290 Eukaryotic Cells, 290, 301, 315, 317 Evacuation, 282, 290 Excitation, 27, 290, 314 Excrete, 267, 290, 305, 330 Exogenous, 61, 90, 288, 290, 294, 326, 343 Extensive-stage small cell lung cancer, 159, 290 Extensor, 290, 327 External-beam radiation, 290, 304, 328, 346 Extracellular Matrix, 14, 40, 52, 54, 55, 56, 63, 77, 190, 281, 291, 292, 303, 309, 317 Extracellular Matrix Proteins, 291, 309

Index 353

Extracellular Space, 291 Extracorporeal, 291, 321 Extraction, 13, 71, 124, 291 Extremity, 185, 257, 291, 319 Eye Infections, 262, 291 F Facial, 8, 10, 21, 67, 74, 83, 91, 197, 202, 222, 230, 233, 243, 283, 291, 309, 319 Facial Expression, 291 Facial Nerve, 8, 202, 230, 291, 319 Family Planning, 219, 291 Fat, 38, 79, 106, 116, 175, 184, 194, 242, 268, 271, 272, 282, 291, 306, 307, 316, 323, 331, 335, 339 Fatigue, 41, 48, 291 Fatty acids, 106, 263, 291, 325 Feces, 282, 291, 337 Femoral, 12, 52, 123, 185, 291 Femur, 6, 7, 44, 52, 97, 291, 340 Fetal Development, 17, 291 Fetus, 272, 291, 322, 324, 343, 344 Fibroblast Growth Factor, 30, 34, 54, 59, 66, 71, 291 Fibroblasts, 55, 281, 292 Fibrosis, 93, 103, 130, 197, 224, 264, 292, 332 Fibula, 95, 266, 292, 340 Filgrastim, 159, 162, 212, 292 Fixation, 94, 183, 187, 266, 292 Flatus, 292, 294 Flexion, 43, 188, 292 Fluorescence, 27, 53, 72, 77, 292 Fluoridation, 73, 292 Fluorine, 292 Folate, 32, 111, 113, 292 Fold, 24, 292 Folic Acid, 111, 292 Follicular large cell lymphoma, 171, 293 Foramen, 277, 293, 298, 309 Forearm, 8, 90, 162, 271, 293 Formulary, 194, 293 Fossa, 193, 276, 293 Fovea, 292, 293 Fractionation, 236, 293 Friction, 186, 293 Fundus, 292, 293 Fungi, 291, 293, 310, 311, 336, 346 Fungus, 276, 279, 293 G Galanin, 75, 293 Gallbladder, 261, 270, 285, 293, 294 Gamma Cameras, 32, 293

Gamma Rays, 293, 328, 329 Ganglia, 10, 261, 270, 293, 314 Ganglion, 69, 279, 293, 314, 345 Gap Junctions, 293 Gas, 42, 265, 274, 292, 294, 299, 301, 315, 344 Gas exchange, 42, 294, 344 Gastric, 274, 289, 294, 298 Gastrin, 294, 299 Gastroenterology, 158, 294 Gastrointestinal, 273, 278, 289, 294, 305, 306, 338, 340, 343 Gastrointestinal tract, 294, 305, 306, 343 Gene Expression, 32, 34, 45, 51, 53, 55, 70, 105, 225, 294 Gene Expression Profiling, 70, 294 Gene Products, rev, 294 Gene Targeting, 29, 294 Gene Therapy, 19, 39, 262, 294 Genes, env, 22, 294 Genetic Counseling, 37, 158, 294 Genetic Engineering, 271, 279, 294 Genetic testing, 37, 158, 294 Genetic transcription, 295, 325, 342 Genetics, 5, 28, 29, 35, 57, 59, 102, 107, 262, 286, 295 Genital, 278, 279, 295, 297, 344 Genotype, 61, 295, 321 Germ Layers, 272, 286, 295 Gestation, 295, 320, 322 Giant Cells, 272, 295, 332 Giardiasis, 295, 310 Ginseng, 149, 295 Gland, 46, 232, 262, 295, 307, 318, 319, 322, 326, 329, 332, 337, 338, 340 Glomerular, 241, 295, 305 Glomerulus, 295 Glucocorticoid, 86, 104, 105, 106, 295 Glucose, 39, 224, 271, 295, 298, 302, 332 Glucuronic Acid, 295, 298 Glutamic Acid, 292, 295, 314, 323, 325 Gluten, 92, 116, 242, 276, 295 Glycine, 265, 295, 314, 333 Glycoprotein, 19, 82, 295, 317, 338, 340 Glycosaminoglycans, 142, 291, 296, 326 Goats, 284, 296 Gonadal, 296, 337 Gonadotropic, 231, 296 Gonads, 296 Governing Board, 296, 324 Grade, 21, 160, 171, 172, 296

354

Bones

Graft, 86, 94, 96, 98, 166, 167, 176, 177, 233, 255, 258, 296, 299 Grafting, 13, 87, 127, 156, 233, 243, 296, 301 Graft-versus-host disease, 176, 177, 296 Gram-negative, 289, 296, 316, 323, 327 Gram-Negative Bacteria, 296, 323 Gram-positive, 289, 296, 312, 316 Gram-Positive Bacteria, 289, 296, 316 Granulocyte, 292, 296, 303 Granuloma, 87, 296 Growth factors, 34, 38, 40, 57, 65, 68, 296 Growth Plate, 34, 37, 42, 53, 82, 108, 296 Guanylate Cyclase, 296, 315 Gynecology, 97, 98, 158, 296 H Habitat, 297, 312 Hair Cells, 10, 230, 279, 297, 345 Hair follicles, 285, 297, 346 Half-Life, 275, 297 Handicap, 229, 297 Haptens, 263, 297 Headache, 256, 273, 297 Health Behavior, 21, 297 Health Education, 173, 297 Health Status, 220, 297 Hearing aid, 198, 297 Heart attack, 275, 297 Hematologic malignancies, 162, 297 Hematology, 96, 158, 297 Hematopoiesis, 123, 189, 297 Hemodialysis, 230, 285, 297, 305 Hemodynamics, 42, 297 Hemoglobin, 266, 277, 290, 297, 298, 306 Hemoglobin A, 277, 298 Hemoglobinopathies, 294, 298 Hemoglobinuria, 224, 298 Hemorrhage, 297, 298, 337 Hemostasis, 298, 303 Heparin, 25, 77, 147, 231, 298 Hepatic, 126, 263, 298, 334 Hepatitis, 98, 131, 298 Hepatocytes, 298 Hereditary, 194, 223, 298, 330 Heredity, 294, 295, 298 Herniated, 187, 298 Heterodimers, 298, 303, 342 Heterogeneity, 263, 298 Hip Prosthesis, 182, 298 Histamine, 147, 265, 298 Histidine, 81, 298 Histidine Decarboxylase, 81, 298

Histiocytosis, 126, 299 Histology, 16, 49, 299 Holmium, 172, 299 Homeobox, 32, 36, 299 Homeostasis, 28, 29, 72, 75, 272, 299 Homodimer, 299, 342 Homologous, 23, 38, 283, 294, 299, 333, 338 Hormonal, 57, 90, 173, 175, 199, 269, 282, 290, 299, 345 Hormone Replacement Therapy, 6, 12, 18, 108, 174, 194, 299 Hormone therapy, 108, 176, 189, 262, 299 Horny layer, 289, 299 Host, 19, 47, 63, 67, 72, 166, 167, 177, 270, 299, 306, 323, 345 Humoral, 46, 299 Humour, 299 Hybrid, 34, 279, 299 Hybridization, 63, 299 Hydrogen, 264, 270, 274, 291, 299, 300, 311, 314, 315, 318, 321, 327 Hydrolysis, 262, 269, 278, 299, 321, 327 Hydrophobic, 30, 299 Hydroxylation, 54, 274, 299 Hydroxylysine, 280, 300 Hydroxyproline, 265, 280, 300 Hypercalcemia, 46, 163, 197, 201, 241, 263, 279, 300 Hypercalciuria, 241, 300 Hyperlipidemia, 28, 300 Hyperostosis, 35, 300 Hyperplasia, 42, 98, 300 Hypersensitivity, 300, 306, 331 Hypertelorism, 96, 300 Hypertension, 275, 297, 300, 319, 341 Hypertrophy, 24, 57, 62, 300 Hypnotic, 270, 300 Hypodermic, 182, 183, 300 Hypothalamus, 300, 322, 325 Hypoxia, 42, 300, 339 Hypoxic, 300, 310 Hysterectomy, 194, 300 I Id, 110, 128, 228, 235, 236, 239, 252, 254, 300 Idiopathic, 81, 156, 169, 300, 332 Idiopathic myelofibrosis, 156, 169, 300 Iliac Artery, 96, 300, 343 Illusion, 300, 345 Image Enhancement, 31, 300 Immune function, 300, 342

Index 355

Immune response, 60, 262, 267, 269, 282, 297, 300, 301, 308, 338, 345 Immune system, 39, 159, 165, 166, 171, 176, 202, 267, 271, 300, 301, 306, 308, 344, 346 Immunity, 39, 301, 303, 308 Immunoassay, 33, 50, 301 Immunocompromised, 70, 301 Immunodeficiency, 224, 235, 301 Immunoglobulin, 23, 30, 266, 301, 312 Immunohistochemistry, 9, 50, 69, 202, 301 Immunologic, 277, 301, 329 Immunology, 50, 67, 262, 263, 301 Immunosuppressant, 264, 301, 310 Immunosuppressive, 5, 161, 283, 295, 301, 320, 339 Immunotoxin, 212, 301 Impairment, 269, 291, 301, 310, 324 Implant radiation, 301, 304, 328, 346 Implantation, 55, 65, 68, 182, 191, 301 In situ, 32, 44, 48, 50, 55, 61, 63, 187, 301 In Situ Hybridization, 32, 50, 55, 63, 301 Incision, 187, 301, 304, 326, 330 Incisor, 91, 93, 301 Indicative, 20, 301, 319, 344 Indigestion, 301, 306 Indolent, 293, 301 Induction, 25, 44, 61, 265, 301, 303, 334 Inertia, 66, 93, 302 Infancy, 35, 194, 302, 331 Infant, Newborn, 263, 302 Infarction, 282, 302, 310 Infertility, 202, 302, 344 Infiltration, 241, 302, 325 Infusion, 63, 302 Ingestion, 273, 302, 323, 339 Inhalation, 279, 302, 323 Initiation, 21, 29, 56, 302, 325, 342 Initiator, 76, 302, 303 Inner ear, 31, 50, 69, 197, 229, 230, 272, 275, 302, 344 Innervation, 291, 302 Inorganic, 278, 302, 335 Insertional, 29, 302 Insight, 19, 25, 29, 52, 61, 68, 302 Insulin, 38, 66, 77, 108, 191, 302, 303, 304, 343 Insulin-dependent diabetes mellitus, 302 Insulin-like, 66, 77, 108, 303 Integrins, 23, 40, 303 Interferometry, 64, 303 Interferon, 39, 60, 98, 168, 303, 308

Interferon-alpha, 98, 303 Interleukin-1, 39, 60, 74, 77, 303 Interleukin-12, 39, 303 Interleukin-18, 60, 303 Interleukin-2, 303 Interleukin-4, 80, 303 Intermittent, 38, 105, 303, 307 Internal Medicine, 41, 288, 294, 297, 303, 314 Internal radiation, 303, 304, 328, 346 Interstitial, 273, 291, 304, 346 Intervention Studies, 124, 304 Intervertebral, 25, 187, 298, 304 Intestinal, 4, 201, 274, 276, 283, 304, 308, 345 Intestinal Mucosa, 276, 304 Intestine, 273, 304, 306 Intracellular, 31, 126, 273, 302, 303, 304, 315, 324, 326, 334 Intravenous, 70, 82, 212, 259, 302, 304 Intrinsic, 57, 61, 80, 263, 270, 304 Invasive, 18, 47, 84, 187, 188, 243, 301, 304, 308 Involuntary, 270, 290, 304, 313, 340 Ionization, 33, 304 Ionizing, 264, 289, 304, 329 Ions, 26, 270, 277, 286, 287, 299, 304, 323 Irradiation, 176, 177, 273, 304, 310, 346 Ischemia, 269, 304 Islet, 107, 191, 304 Isoenzyme, 257, 283, 304 Isoflavones, 127, 148, 151, 304 J Jejunoileal Bypass, 270, 304 Jejunum, 270, 304 Joint Capsule, 198, 305, 339 Joint Instability, 43, 305 K Kb, 218, 305 Keto, 141, 305 Kidney Disease, 179, 201, 202, 218, 224, 229, 230, 232, 246, 305, 330 Kidney Failure, 161, 165, 202, 233, 241, 289, 305 Kidney Failure, Acute, 305 Kidney Failure, Chronic, 161, 165, 305 Kidney stone, 305, 314, 330, 343 Kidney Transplantation, 89, 165, 305 Killer Cells, 305 Kinetic, 34, 38, 304, 305 L Labile, 280, 305

356

Bones

Labyrinth, 197, 279, 288, 302, 305, 318, 333, 345 Lacrimal, 291, 305 Lactation, 46, 96, 105, 305 Lactose Intolerance, 23, 305 Large Intestine, 285, 304, 306, 329, 334 Latent, 306, 323 Lead Poisoning, 27, 306 Least-Squares Analysis, 27, 306 Lethal, 71, 78, 223, 270, 306 Leucine, 54, 306 Leukocytes, 272, 277, 303, 306, 312, 315 Leukotrienes, 268, 306 Libido, 265, 306 Library Services, 252, 306 Lidocaine, 157, 306 Ligament, 43, 74, 185, 306, 326 Ligands, 40, 61, 75, 303, 306 Lincomycin, 279, 306 Linkage, 21, 26, 35, 306 Lip, 96, 233, 306 Lipid, 302, 305, 306 Lipopolysaccharide, 74, 76, 77, 80, 296, 306 Liposarcoma, 127, 307 Liver scan, 307, 332 Localization, 9, 38, 55, 63, 301, 307 Localized, 26, 35, 41, 91, 193, 199, 261, 284, 292, 302, 307, 317, 322 Longitudinal Studies, 7, 307 Longitudinal study, 9, 96, 307 Long-Term Care, 67, 307 Loop, 40, 57, 66, 149, 307 Lovastatin, 307, 334 Lumbar, 7, 66, 173, 307 Lunate, 93, 307 Lung metastases, 39, 307 Lung volume, 41, 307 Lupus, 132, 134, 307, 339 Luxation, 286, 307 Lymph, 20, 94, 95, 241, 277, 288, 299, 307, 308, 331, 332, 338 Lymph node, 20, 95, 241, 277, 307, 308, 331, 332 Lymphadenopathy, 94, 307 Lymphatic, 288, 293, 302, 307, 308, 310, 331, 335, 336 Lymphatic system, 293, 307, 308, 331, 335, 336 Lymphoblastic, 155, 159, 160, 308 Lymphoblasts, 261, 308 Lymphocyte, 167, 212, 267, 305, 308

Lymphoid, 23, 267, 308 Lymphokines, 23, 308 Lymphoma, 46, 94, 132, 159, 160, 161, 162, 168, 171, 172, 174, 176, 224, 293, 297, 308, 321 Lymphoproliferative, 308, 320 Lysine, 54, 148, 149, 300, 308, 325 Lytic, 272, 308, 333 M Macaca, 99, 308 Macrophage, 39, 303, 308 Magnetic Resonance Imaging, 10, 12, 308, 332 Major Histocompatibility Complex, 303, 308 Malabsorption, 5, 132, 224, 276, 308 Malformation, 10, 308 Malignancy, 39, 46, 47, 50, 60, 197, 259, 261, 308 Malignant, 107, 162, 224, 267, 299, 308, 312, 313, 317, 329, 331, 332 Malignant tumor, 308, 312, 317, 331 Malnutrition, 5, 105, 263, 269, 308, 312 Mammary, 46, 78, 308, 329 Mammogram, 273, 309, 311 Mandible, 6, 8, 19, 61, 94, 95, 197, 264, 277, 309, 330 Manifest, 4, 309 Marital Status, 166, 309 Mastication, 21, 64, 309 Matrix metalloproteinase, 17, 44, 309 Maxillary, 91, 96, 122, 127, 182, 309, 319 Meatus, 309, 318, 336, 343 Medial, 12, 28, 43, 266, 279, 290, 309, 331, 336, 340 Mediate, 23, 32, 34, 36, 38, 54, 279, 305, 309, 345 Medical Records, 158, 309 MEDLINE, 219, 222, 224, 309 Medullary, 35, 309 Melanin, 309, 321, 343 Melanocytes, 309 Melanoma, 224, 273, 309 Melanosis, 261, 309 Memory, 266, 284, 309 Menarche, 66, 123, 194, 309 Meninges, 14, 275, 276, 286, 309, 337 Meniscus, 44, 309 Menopause, 5, 6, 132, 133, 194, 309, 320, 323, 324 Menstrual Cycle, 194, 309, 325 Menstruation, 264, 309, 310

Index 357

Mental, iv, 11, 13, 177, 179, 218, 221, 223, 225, 276, 277, 284, 286, 291, 309, 310, 327, 343 Mental Disorders, 179, 310, 327 Mental Health, iv, 13, 177, 179, 218, 221, 310, 327 Mesenchymal, 17, 19, 47, 51, 58, 59, 63, 74, 289, 310 Mesoderm, 36, 59, 67, 310, 335 Metabolic disorder, 122, 310 Metabolite, 201, 273, 307, 310 Metaplasia, 28, 156, 310 Metastasis, 40, 51, 60, 127, 175, 236, 259, 309, 310 Metastasize, 41, 310, 332 Metastatic, 41, 50, 84, 92, 106, 160, 172, 176, 229, 236, 310, 332 Metastatic cancer, 51, 310 Metatarsal Bones, 59, 310 Metatarsus, 310 Methotrexate, 149, 162, 231, 310 Methoxsalen, 310, 321 Metronidazole, 73, 310 MI, 260, 310 Microbiological, 77, 310 Microbiology, 50, 59, 67, 89, 262, 269, 270, 310 Microcalcifications, 274, 311 Microorganism, 280, 311, 345 Microscopy, 10, 24, 31, 50, 61, 69, 75, 126, 270, 300, 311, 315 Microscopy, Fluorescence, 300, 311 Migration, 14, 24, 61, 311 Milliliter, 272, 311 Millimeter, 48, 243, 311 Mineralization, 19, 26, 27, 28, 33, 45, 52, 54, 56, 64, 68, 82, 123, 311, 317 Mineralocorticoids, 262, 282, 311 Mitosis, 268, 311 Mitotic, 58, 290, 311 Mobility, 34, 44, 56, 185, 311 Modeling, 20, 41, 44, 45, 50, 74, 311 Modification, 13, 23, 265, 294, 311, 328 Modulator, 60, 311 Molecular mass, 33, 311 Monitor, 51, 70, 191, 283, 311, 315 Monoclonal, 163, 164, 212, 304, 312, 328, 346 Monocytes, 81, 303, 306, 312, 313 Mononuclear, 296, 312 Morphogenesis, 29, 32, 54, 59, 67, 189, 312 Morphological, 60, 67, 287, 293, 309, 312

Morphology, 21, 22, 99, 268, 297, 312 Motility, 24, 312 Moxalactam, 73, 312 Mucinous, 293, 312 Mucosa, 307, 312, 313, 337 Mucositis, 312, 340 Multicenter study, 176, 312 Multiple Myeloma, 47, 156, 161, 168, 174, 312 Muscle Fibers, 312, 313, 342 Muscle relaxant, 312, 321 Muscle Spindles, 312, 321 Muscular Atrophy, 224, 312 Muscular Dystrophies, 286, 312 Musculoskeletal System, 43, 198, 312 Mycobacterium, 89, 97, 269, 312 Myelodysplastic syndrome, 157, 159, 164, 169, 170, 177, 313, 335 Myelofibrosis, 133, 313 Myelogenous, 130, 156, 157, 159, 164, 166, 168, 169, 313 Myeloid Cells, 23, 313 Myeloma, 46, 47, 313 Myeloproliferative Disorders, 133, 156, 161, 162, 169, 313 Myocardium, 79, 310, 313 Myosin, 313, 342 Myositis, 197, 313 Myositis Ossificans, 197, 313 Myotonic Dystrophy, 224, 313 N Nasal Bone, 95, 223, 313 Nasal Cavity, 313, 319, 336 Nasal Mucosa, 81, 313 Nasal Septum, 21, 313 Natural killer cells, 39, 303, 313 Nausea, 133, 301, 313, 343 NCI, 1, 155, 156, 157, 159, 161, 162, 163, 164, 165, 168, 169, 171, 172, 174, 176, 178, 217, 278, 313 Neck Injuries, 25, 313 Neonatal, 87, 123, 313, 339 Neonatal period, 313, 339 Neoplasia, 224, 313, 314 Neoplasm, 156, 161, 313, 314, 332, 343 Neoplastic, 308, 314, 338 Nephrolithiasis, 194, 314 Nephrology, 106, 108, 158, 314 Nephropathy, 223, 305, 314 Nerve Fibers, 69, 279, 314, 345 Nervous System, 224, 229, 262, 276, 289, 297, 314, 319, 338

358

Bones

Neural, 20, 36, 45, 59, 61, 67, 197, 262, 299, 314 Neural Crest, 36, 45, 59, 61, 67, 314 Neuroblastoma, 70, 314 Neuroendocrine, 314, 338 Neurology, 85, 158, 314 Neuronal, 31, 69, 314 Neurons, 10, 69, 279, 284, 293, 312, 314, 338, 345 Neuropil, 31, 314 Neurosyphilis, 314, 319 Neurotransmitter, 261, 262, 265, 269, 273, 293, 295, 298, 314, 334, 338 Neutralization, 41, 314 Neutrons, 264, 273, 304, 314, 328 Neutrophils, 292, 296, 306, 315 Nifedipine, 85, 315 Nitric Oxide, 80, 81, 105, 315 Nitrogen, 264, 265, 283, 291, 292, 305, 311, 315, 342 Nonmalignant, 11, 161, 162, 315 Nonmalignant hematologic disorders, 162, 315 Nuclear, 26, 32, 62, 76, 88, 109, 158, 203, 236, 270, 290, 293, 294, 315, 343 Nuclear Matrix, 76, 315 Nuclear Medicine, 88, 109, 158, 203, 236, 315 Nuclear Pore, 315 Nuclei, 264, 279, 294, 308, 311, 314, 315, 327, 331, 345 Nucleic acid, 299, 301, 315, 327, 328, 331 Nucleic Acid Hybridization, 299, 315 Nucleolus, 315, 331 Nucleus, 31, 268, 270, 277, 279, 283, 284, 289, 290, 293, 312, 314, 315, 327, 339 Nutritional Status, 38, 234, 315 Nutritive Value, 316 O Observational study, 77, 316 Ofloxacin, 79, 316 Oligoelement, 316 Oliguria, 305, 316 Oncogene, 224, 316, 336 Oncogenic, 109, 303, 316, 323 Oncologist, 50, 316 Oncology, 50, 84, 96, 106, 155, 161, 169, 172, 176, 316 Opacity, 284, 316 Operon, 316, 325, 330 Ophthalmology, 158, 292, 316 Opiate, 316

Opioid Peptides, 127, 286, 288, 289, 316 Oral Health, 6, 7, 9, 10, 13, 220, 316 Orbit, 316 Orbital, 91, 316 Organ Culture, 24, 59, 65, 316, 341 Organelles, 276, 284, 309, 312, 317 Osseointegration, 272, 317 Ossicles, 317, 318 Ossification, 17, 30, 36, 37, 53, 58, 62, 194, 313, 317, 331 Osteitis Deformans, 11, 230, 317 Osteoarthritis, 10, 33, 44, 56, 65, 133, 317 Osteoblasts, 17, 18, 33, 36, 38, 40, 45, 47, 53, 55, 59, 60, 63, 84, 104, 124, 127, 196, 317 Osteocalcin, 39, 45, 53, 63, 68, 80, 317 Osteochondrodysplasias, 57, 317 Osteoclasts, 14, 47, 48, 53, 107, 126, 196, 274, 317 Osteocytes, 48, 196, 317 Osteodystrophy, 203, 317 Osteogenesis, 16, 59, 61, 63, 82, 90, 197, 223, 228, 229, 233, 237, 243, 244, 246, 272, 277, 317 Osteogenic sarcoma, 317, 318 Osteomalacia, 109, 134, 194, 196, 202, 273, 317 Osteomyelitis, 72, 73, 77, 81, 133, 317 Osteonecrosis, 235, 317 Osteonectin, 33, 40, 317 Osteopetrosis, 53, 76, 166, 229, 246, 318 Osteosarcoma, 39, 51, 317, 318 Osteosclerosis, 193, 318 Osteotomy, 104, 318 Otitis, 49, 318 Otitis Media, 49, 318 Otorhinolaryngology, 158, 318 Otosclerosis, 10, 230, 318 Outer ear, 197, 318 Ovariectomy, 48, 78, 81, 105, 318 Ovaries, 268, 318, 333 Ovary, 266, 290, 296, 318, 337 Overdose, 66, 318 Overexpress, 60, 318 Oxidation, 267, 283, 318 P Palate, 32, 67, 233, 318 Palliative, 85, 318, 340 Palpation, 197, 318 Pamidronate, 82, 209, 318 Pancreas, 261, 271, 285, 294, 302, 304, 318, 319, 343

Index 359

Pancreatic, 133, 224, 319 Pancreatic cancer, 224, 319 Papovaviridae, 319, 323 Paralysis, 230, 319 Paranasal Sinuses, 193, 319, 336 Paraparesis, 319 Parathyroid Glands, 233, 319, 331 Parathyroid hormone, 12, 14, 29, 38, 46, 74, 78, 82, 89, 105, 107, 201, 230, 232, 274, 319 Paresis, 69, 319 Parietal, 19, 78, 95, 319 Parietal Lobe, 319 Parotid, 319, 332 Paroxysmal, 224, 319 Partial remission, 319, 330 Patch, 319, 342 Pathogenesis, 31, 32, 46, 47, 50, 54, 319 Pathologic, 31, 43, 92, 104, 194, 268, 271, 282, 300, 319, 327, 330 Pathologic fracture, 92, 319 Pathologic Processes, 268, 319 Pathologies, 12, 26, 67, 320 Pathophysiology, 4, 8, 46, 80, 194, 202, 320 Patient Education, 228, 233, 237, 250, 252, 260, 320 Patient Selection, 13, 233, 320 Pelvic, 157, 288, 320, 326 Pelvis, 193, 203, 261, 300, 305, 307, 318, 320, 344 Penicillin, 265, 266, 274, 320, 322, 340 Pentostatin, 176, 320 Peptide, 45, 66, 82, 265, 274, 288, 291, 316, 320, 323, 325, 326, 327 Peptide T, 320, 323 Perception, 21, 320 Perforation, 183, 293, 320 Perfusion, 21, 300, 320, 341 Pericardium, 320, 339 Perimenopausal, 92, 102, 320 Perinatal, 38, 320 Perineal, 320, 328 Periodontal disease, 5, 6, 7, 8, 264, 320 Peripheral blood, 106, 159, 166, 303, 320, 321, 324 Peripheral stem cell transplantation, 159, 160, 162, 169, 172, 174, 320, 341 Peripheral stem cells, 162, 296, 321 PH, 72, 272, 321 Phallic, 292, 321 Pharmacologic, 121, 266, 297, 321, 341

Phenotype, 25, 28, 37, 54, 61, 68, 76, 78, 321 Phenylalanine, 321, 343 Phenytoin, 150, 231, 321 Phospholipases, 321, 334 Phospholipids, 291, 321 Phosphorus, 106, 150, 230, 233, 258, 274, 319, 321 Phosphorylated, 55, 280, 321 Phosphorylation, 19, 321 Phosphotyrosine, 23, 321 Photopheresis, 176, 321 Physical Examination, 158, 168, 322 Physiologic, 22, 29, 41, 263, 291, 297, 309, 310, 322, 325, 329, 330 Physiology, 14, 107, 124, 194, 196, 230, 275, 288, 294, 296, 297, 314, 322 Pilot study, 105, 322 Piperacillin, 79, 322 Piperacillin-tazobactam, 79, 322 Pituitary Gland, 61, 282, 291, 322, 325 Placenta, 268, 290, 322, 325, 343 Plana, 322, 333 Plants, 269, 274, 275, 277, 278, 295, 310, 312, 322, 323, 327, 332, 336, 341, 342 Plaque, 6, 28, 322 Plasma, 56, 82, 156, 161, 263, 267, 271, 274, 276, 288, 298, 305, 311, 312, 313, 322, 333, 341 Plasma cells, 267, 312, 313, 322 Plasticity, 60, 322 Platelet Activation, 322, 334 Platelet Aggregation, 265, 315, 322, 340 Platelets, 258, 315, 322, 332 Platinum, 278, 307, 322 Pneumonia, 282, 323 Podophyllotoxin, 290, 323 Point Mutation, 30, 323 Poisoning, 273, 277, 313, 323 Polyarthritis, 86, 323 Polycystic, 224, 323 Polyglutamic Acid, 19, 323 Polymerase, 323, 325, 330 Polyomavirus, 78, 319, 323 Polyostotic Fibrous Dysplasia, 167, 323 Polysaccharide, 267, 323, 326 Polyunsaturated fat, 128, 323, 340 Pons, 273, 323 Porins, 72, 323 Porosity, 8, 47, 323 Port, 182, 323 Port-a-cath, 323

360

Bones

Posterior, 20, 44, 55, 94, 185, 265, 269, 276, 286, 318, 323, 336 Postnatal, 38, 53, 324, 336 Postoperative, 13, 94, 324 Postsynaptic, 324, 334 Potassium, 113, 242, 311, 324 Potentiates, 303, 324 Potentiating, 72, 189, 324 Potentiation, 80, 324, 334 Practicability, 324, 342 Practice Guidelines, 50, 221, 235, 236, 324 Preclinical, 18, 324 Precursor, 19, 74, 266, 268, 277, 283, 287, 288, 289, 321, 324, 325, 342, 343, 345 Preleukemia, 313, 324, 335 Premenopausal, 78, 86, 92, 122, 178, 324 Prenatal, 53, 194, 287, 324 Preoperative, 13, 324 Presynaptic, 314, 324, 338 Prevalence, 9, 10, 51, 220, 230, 324 Probe, 7, 61, 324 Probenecid, 71, 324 Procaine, 306, 324 Procollagen, 39, 325 Progesterone, 150, 173, 325, 337 Progression, 5, 7, 9, 28, 33, 37, 43, 47, 48, 56, 62, 189, 266, 325 Progressive disease, 300, 325 Projection, 52, 284, 325, 329 Proline, 23, 280, 300, 325 Promoter, 19, 26, 39, 45, 55, 325 Promotor, 68, 325 Promyelocytic leukemia, 170, 325 Prone, 167, 325 Pro-Opiomelanocortin, 288, 316, 325 Prophylaxis, 7, 285, 325 Prospective study, 69, 73, 307, 325 Prostaglandin, 71, 72, 74, 76, 106, 325, 340 Prostaglandins A, 325, 326 Prostatectomy, 326, 328 Prosthesis, 182, 185, 188, 284, 305, 326 Protease, 51, 103, 280, 326 Protease Inhibitors, 51, 326 Protein Binding, 55, 326, 341 Protein C, 24, 25, 53, 104, 263, 265, 270, 317, 326, 342, 343 Protein Conformation, 265, 326 Protein Kinases, 25, 326 Protein S, 28, 83, 195, 224, 225, 271, 281, 290, 317, 326, 331 Proteinuria, 312, 326 Proteoglycan, 54, 326

Proteolytic, 280, 327 Protocol, 18, 40, 167, 173, 327 Protons, 264, 299, 304, 327, 328 Protozoa, 310, 311, 327, 336 Proximal, 7, 34, 44, 52, 95, 97, 272, 286, 304, 313, 324, 327, 333 Pseudomonas, 322, 327 Pseudomonas Infections, 322, 327 Psoriasis, 134, 202, 327 Psychiatry, 292, 327, 344 Psychic, 306, 310, 327, 333 Psyllium, 150, 327 Puberty, 23, 175, 327 Public Health, 77, 167, 220, 221, 327 Public Policy, 219, 327 Pulmonary, 14, 39, 42, 103, 271, 282, 305, 306, 327, 344 Pulmonary Artery, 271, 327, 344 Pulmonary Edema, 305, 327 Pulse, 31, 167, 312, 327 Purines, 327, 333 Pyogenic, 317, 328 Pyridoxal, 298, 328 Pyridoxal Phosphate, 298, 328 Pyrimidines, 328, 333 Q Quality of Life, 12, 203, 244, 245, 328, 338 R Race, 52, 194, 234, 311, 328 Radiation oncologist, 316, 328 Radical prostatectomy, 60, 328 Radioactive, 172, 271, 272, 297, 299, 301, 303, 304, 307, 315, 316, 328, 329, 332, 337, 343, 346 Radiofrequency ablation, 165, 173, 328 Radiography, 12, 31, 266, 328 Radioimmunotherapy, 328, 329 Radioisotope, 27, 290, 328 Radiolabeled, 304, 328, 346 Radiological, 8, 94, 328 Radiology, 8, 52, 91, 127, 158, 165, 235, 236, 315, 328 Radiolucent, 188, 328 Radiopharmaceuticals, 189, 328 Radiotherapy, 106, 167, 189, 236, 273, 304, 328, 329, 346 Radium, 188, 329 Raloxifene, 123, 209, 242, 329, 333 Random Allocation, 329 Randomization, 15, 329 Reaction Time, 243, 329 Reagent, 50, 329

Index 361

Recessive gene, 244, 329 Recombinant, 15, 22, 76, 80, 124, 126, 212, 329, 344 Recombination, 38, 294, 329 Rectum, 267, 273, 280, 285, 292, 294, 306, 326, 329 Red blood cells, 290, 300, 329, 332 Red Nucleus, 269, 329 Reductase, 268, 307, 310, 329, 334 Refer, 1, 183, 273, 280, 286, 288, 292, 293, 307, 314, 323, 328, 330, 333, 335, 341, 345 Refraction, 330, 336 Refractory, 106, 156, 160, 169, 170, 330 Regeneration, 4, 17, 63, 87, 127, 292, 330 Regimen, 18, 167, 169, 170, 172, 176, 191, 287, 330 Relapse, 39, 167, 330 Remission, 155, 164, 330 Renal Osteodystrophy, 194, 202, 230, 330 Renal tubular, 324, 330 Repressor, 40, 316, 330 Resection, 95, 186, 188, 326, 330 Resorption, 5, 6, 11, 14, 24, 48, 71, 72, 74, 75, 76, 77, 78, 79, 80, 81, 85, 106, 107, 125, 126, 177, 196, 229, 230, 264, 272, 274, 317, 330 Respiration, 274, 311, 330 Respiratory Physiology, 330, 344 Restoration, 283, 330, 346 Retina, 278, 330, 331, 333 Retinoblastoma, 224, 330 Retinoid, 62, 330 Retinol, 113, 114, 330 Retropubic, 326, 328, 330 Retropubic prostatectomy, 328, 330 Retroviral vector, 294, 331 Rhabdomyosarcoma, 172, 331 Rheumatic Diseases, 86, 238, 331 Rheumatism, 86, 331 Rheumatoid, 5, 76, 86, 134, 331 Rheumatoid arthritis, 5, 76, 86, 331 Ribavirin, 98, 331 Ribonucleoproteins, 315, 331 Ribosome, 331, 342 Rickets, 134, 194, 196, 201, 273, 331, 345 Risk factor, 5, 6, 7, 13, 15, 18, 23, 194, 231, 232, 233, 242, 325, 331 Ristocetin, 331, 344 Rod, 183, 187, 278, 327, 331 Round Window, 198, 331 Rubber, 182, 261, 331 Rubella, 68, 331

S Salivary, 285, 291, 319, 331, 332, 338 Salivary glands, 285, 291, 332 Saponins, 332, 337 Sarcoidosis, 241, 332 Sarcoma, 51, 172, 238, 332, 335 Sargramostim, 166, 212, 332 Scans, 22, 37, 52, 158, 167, 332 Scatter, 27, 332 Sclerosis, 10, 224, 332 Screening, 3, 22, 68, 158, 167, 176, 279, 332, 344 Sebaceous, 285, 332, 346 Secondary tumor, 310, 332 Secretion, 108, 282, 286, 289, 298, 299, 302, 305, 311, 332, 333, 342 Secretory, 45, 332 Sedative, 270, 332 Sedentary, 90, 332 Sediment, 332, 344 Sedimentation, 276, 332 Segmentation, 29, 332 Segregation, 270, 329, 333 Seizures, 319, 321, 333 Selective estrogen receptor modulator, 329, 333 Sella, 322, 333 Semen, 326, 333 Semicircular canal, 302, 333 Seminal vesicles, 20, 333 Semisynthetic, 274, 275, 279, 290, 322, 333 Senile, 85, 318, 333 Sensibility, 265, 333 Septal, 21, 42, 95, 333 Septum, 21, 333 Septum Pellucidum, 333 Sequencing, 24, 333 Serine, 26, 288, 333 Serologic, 301, 333 Serous, 288, 333 Serrata, 144, 278, 333 Serrated, 333 Sex Characteristics, 262, 265, 327, 333, 339 Sex Determination, 224, 333 Shock, 5, 275, 334, 342 Side effect, 159, 162, 166, 205, 211, 262, 271, 283, 334, 338, 341 Signal Transduction, 16, 30, 59, 61, 321, 334 Signs and Symptoms, 330, 334 Silicon, 102, 107, 151, 334 Silicon Dioxide, 334

362

Bones

Simvastatin, 75, 334 Sindbis Virus, 264, 334 Skull, 9, 21, 30, 36, 53, 61, 72, 80, 94, 193, 197, 198, 272, 283, 316, 334, 339 Small cell lung cancer, 158, 159, 334 Small intestine, 270, 286, 295, 299, 304, 334 Smoldering leukemia, 313, 335 Smooth muscle, 24, 264, 265, 273, 281, 298, 335, 338 Social Environment, 328, 335 Social Work, 158, 335 Sodium, 12, 113, 209, 263, 272, 311, 335 Sodium Fluoride, 12, 113, 209, 335 Soft tissue, 21, 25, 30, 43, 50, 109, 172, 178, 188, 191, 194, 272, 275, 313, 334, 335 Soft Tissue Injuries, 25, 335 Soft tissue sarcoma, 51, 172, 335 Solid tumor, 266, 335 Soma, 335 Somatic, 42, 262, 287, 299, 311, 335 Somite, 36, 335 Sound wave, 198, 281, 335 Soybean Oil, 323, 335 Specialist, 246, 335 Specificity, 263, 288, 324, 335, 341 Spectroscopic, 49, 336 Spectrum, 27, 48, 312, 336 Sperm, 265, 278, 336, 339 Sphenoid, 85, 300, 319, 333, 336 Sphenoid Sinus, 336 Spinal cord, 273, 276, 277, 286, 289, 293, 309, 314, 319, 336, 337, 345 Spinal Stenosis, 187, 336 Spinous, 289, 336 Spleen, 42, 241, 307, 308, 332, 336 Splenomegaly, 318, 336 Spondylolisthesis, 187, 336 Sporadic, 33, 35, 330, 336 Spores, 14, 279, 336 Stabilization, 43, 187, 236, 321, 336 Staging, 20, 332, 336 Standard therapy, 321, 336 Stasis, 38, 336 Statistically significant, 9, 336 Steel, 183, 278, 336 Stem Cell Factor, 212, 278, 336 Stem cell transplantation, 160, 162, 169, 172, 174, 336 Stem Cells, 29, 47, 55, 59, 63, 68, 264, 321, 336, 343 Stenosis, 27, 35, 337 Sterile, 268, 319, 337

Sterility, 283, 302, 337 Sternum, 193, 337 Steroid, 23, 71, 85, 241, 266, 268, 332, 334, 337 Steroid therapy, 241, 337 Stimulant, 273, 298, 337 Stimulus, 286, 290, 302, 329, 337, 340 Stomach, 261, 267, 270, 285, 290, 293, 294, 299, 313, 334, 336, 337 Stool, 158, 280, 306, 337 Stress, 12, 41, 43, 44, 45, 64, 165, 257, 274, 313, 331, 337 Stricture, 337 Stroke, 179, 218, 275, 337 Stromal, 38, 51, 104, 156, 189, 288, 337 Stromal Cells, 38, 51, 104, 156, 189, 337 Strontium, 91, 151, 189, 210, 337 Strontium-89, 189, 337 Styrene, 331, 337 Subacute, 302, 337 Subclavian, 337, 345 Subclavian Artery, 337, 345 Subclinical, 302, 333, 337 Subcutaneous, 287, 338 Submaxillary, 289, 338 Subspecies, 335, 338 Substance P, 271, 290, 310, 331, 332, 338 Supplementation, 12, 32, 103, 122, 123, 125, 127, 191, 233, 338 Support group, 259, 260, 338 Supportive care, 165, 338 Suppression, 171, 265, 282, 338 Survival Rate, 39, 338 Symphysis, 277, 326, 338 Synapse, 324, 338, 342 Synaptic, 314, 334, 338 Synaptic Vesicles, 338 Synaptophysin, 31, 338 Synergistic, 81, 192, 320, 338, 340 Synovial, 72, 198, 238, 305, 338, 339 Synovial Fluid, 72, 338, 339 Synovial Membrane, 305, 338, 339 Systemic lupus erythematosus, 86, 122, 339 T Tacrolimus, 162, 210, 339 Talus, 183, 266, 339, 340 Tarsal Bones, 223, 273, 310, 339 Tarsus, 339 Telangiectasia, 224, 339 Tendon, 61, 94, 293, 339 Teratogenesis, 32, 339

Index 363

Testicles, 265, 339 Testicular, 268, 339 Testis, 266, 290, 296, 339 Testosterone, 18, 242, 266, 329, 339 Tetany, 319, 339 Thalamic, 269, 339 Thalamic Diseases, 269, 339 Thanatophoric Dysplasia, 30, 339 Therapeutics, 189, 211, 340 Thigh, 6, 7, 291, 340 Thiotepa, 160, 340 Thoracic, 42, 285, 337, 340, 346 Thorax, 42, 261, 307, 340 Threonine, 320, 333, 340 Threshold, 86, 300, 340 Thrombin, 322, 326, 340 Thrombocytopenia, 157, 340 Thrombomodulin, 326, 340 Thrombosis, 303, 326, 337, 340 Thromboxanes, 268, 340 Thymidine, 57, 340 Thyroid, 151, 231, 274, 319, 340, 343 Thyroid Gland, 319, 340 Thyroid Hormones, 151, 231, 340, 343 Tibia, 12, 18, 27, 34, 44, 66, 97, 183, 188, 266, 292, 340 Tibiae, 63, 66, 125, 340 Tic, 244, 340 Ticarcillin, 73, 340 Tinnitus, 318, 340 Tissue Culture, 60, 62, 341 Tissue Distribution, 54, 341 Tomography, 281, 332, 341 Tone, 9, 341 Tonus, 341 Tooth Loss, 156, 341 Tooth Preparation, 262, 341 Topotecan, 160, 341 Total-body irradiation, 162, 164, 176, 177, 341 Toxic, iv, 77, 264, 270, 284, 289, 301, 323, 337, 340, 341, 344 Toxicity, 286, 331, 341 Toxicology, 105, 220, 341 Toxin, 75, 81, 341 Toxoplasmosis, 269, 341 Trace element, 103, 272, 292, 334, 341 Trachea, 340, 341 Traction, 12, 278, 341 Transcription Factors, 32, 36, 44, 53, 55, 76, 77, 341 Transdermal, 97, 342

Transduction, 31, 70, 334, 342 Transfection, 24, 40, 271, 294, 342 Transforming Growth Factor beta, 78, 342 Translation, 38, 43, 265, 290, 294, 342 Translational, 25, 71, 342 Transmitter, 261, 338, 342 Transplantation, 80, 87, 89, 155, 156, 157, 158, 159, 160, 161, 162, 164, 165, 166, 168, 169, 170, 171, 176, 177, 189, 244, 245, 272, 278, 308, 321, 342 Trauma, 13, 25, 90, 91, 126, 173, 193, 203, 236, 270, 297, 339, 341, 342 Treatment Outcome, 7, 342 Trees, 331, 342 Trichomoniasis, 310, 342 Trophic, 57, 342 Tropism, 68, 342 Tropomyosin, 342 Troponin, 25, 342 Tryptophan, 280, 342 Tuberous Sclerosis, 224, 342 Tumor marker, 271, 343 Tumour, 267, 293, 343 Tympanic membrane, 198, 317, 343 Type 2 diabetes, 9, 343 Tyrosine, 23, 30, 55, 59, 106, 321, 343 U Umbilical Arteries, 343 Umbilical Cord, 161, 343 Umbilical cord blood, 161, 343 Umbilical cord blood transplantation, 161, 343 Unconscious, 266, 284, 300, 343 Uranium, 329, 343 Urea, 305, 343 Uremia, 27, 305, 343 Urethra, 326, 343, 344 Uric, 238, 327, 343 Uricosuric, 324, 343 Urinalysis, 158, 167, 343 Urinary, 241, 270, 275, 278, 289, 316, 326, 330, 343, 344 Urinary tract, 270, 275, 289, 344 Urinary tract infection, 270, 275, 289, 344 Urine, 234, 241, 267, 270, 271, 275, 283, 286, 289, 298, 300, 305, 316, 326, 343, 344 Urology, 51, 158, 344 Uterus, 277, 288, 292, 293, 300, 310, 318, 325, 344 V Vaccine, 14, 207, 262, 327, 344 Vagina, 277, 285, 310, 344

364

Bones

Valves, 27, 79, 344 Vancomycin, 73, 79, 83, 344 Vascular, 17, 21, 24, 27, 42, 67, 83, 264, 285, 288, 302, 315, 322, 340, 344 Vasodilator, 273, 298, 315, 344 Vasomotor, 290, 344 Vector, 39, 302, 342, 344 Vein, 66, 268, 304, 315, 319, 337, 343, 344 Venous, 268, 326, 344 Ventilation, 42, 344 Ventral, 279, 300, 323, 344 Ventricle, 300, 327, 344 Ventricular, 42, 344 Venules, 271, 274, 288, 344 Vertebrae, 8, 43, 187, 223, 238, 304, 336, 345 Vertebral, 11, 25, 64, 86, 98, 187, 322, 345 Vertebral Artery, 25, 345 Vertigo, 230, 318, 345 Vestibular, 69, 197, 230, 297, 345 Vestibular Nerve, 69, 345 Vestibule, 279, 302, 333, 345 Vestibulocochlear Nerve, 269, 279, 341, 345 Veterinarians, 46, 345 Veterinary Medicine, 103, 219, 345 Villous, 276, 345 Viral, 67, 78, 287, 294, 295, 316, 342, 345 Virulence, 68, 341, 345 Virus, 68, 131, 235, 270, 294, 295, 303, 322, 323, 331, 342, 345

Viscosity, 30, 345 Visual Cortex, 307, 345 Vitamin A, 109, 330, 345 Vitamin D, 11, 12, 80, 83, 85, 109, 111, 144, 145, 146, 201, 210, 242, 258, 331, 345 Vitro, 24, 33, 35, 36, 38, 40, 47, 52, 53, 54, 55, 57, 68, 71, 75, 76, 79, 81, 124, 125, 127, 294, 298, 300, 301, 331, 339, 341, 345 Vivo, 15, 17, 21, 24, 27, 36, 38, 40, 41, 42, 43, 45, 47, 48, 51, 52, 54, 55, 56, 58, 59, 63, 65, 68, 72, 74, 75, 76, 81, 83, 124, 126, 294, 298, 301, 339, 340, 346 Vulgaris, 151, 346 W Weight Gain, 346 Weight-Bearing, 5, 15, 167, 174, 242, 243, 346 White blood cell, 176, 177, 261, 267, 271, 278, 292, 296, 306, 308, 313, 322, 346 Windpipe, 340, 346 Wound Healing, 16, 34, 119, 292, 303, 309, 346 X Xenograft, 70, 266, 346 X-ray therapy, 304, 346 Y Yeasts, 293, 321, 346 Z Zebrafish, 59, 61, 72, 346 Zoledronate, 163, 346 Zymogen, 326, 346

Index 365

366

Bones

Index 367

368

Bones