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

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Vitamin D: 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: 0-597-84233-7 1. Vitamin D-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 vitamin D. 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 VITAMIN D................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Vitamin D ..................................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 77 CHAPTER 2. NUTRITION AND VITAMIN D.................................................................................... 125 Overview.................................................................................................................................... 125 Finding Nutrition Studies on Vitamin D.................................................................................. 125 Federal Resources on Nutrition ................................................................................................. 131 Additional Web Resources ......................................................................................................... 131 CHAPTER 3. ALTERNATIVE MEDICINE AND VITAMIN D ............................................................. 135 Overview.................................................................................................................................... 135 National Center for Complementary and Alternative Medicine................................................ 135 Additional Web Resources ......................................................................................................... 153 General References ..................................................................................................................... 162 CHAPTER 4. DISSERTATIONS ON VITAMIN D ............................................................................... 163 Overview.................................................................................................................................... 163 Dissertations on Vitamin D....................................................................................................... 163 Keeping Current ........................................................................................................................ 165 CHAPTER 5. CLINICAL TRIALS AND VITAMIN D .......................................................................... 167 Overview.................................................................................................................................... 167 Recent Trials on Vitamin D....................................................................................................... 167 Keeping Current on Clinical Trials ........................................................................................... 170 CHAPTER 6. PATENTS ON VITAMIN D .......................................................................................... 173 Overview.................................................................................................................................... 173 Patents on Vitamin D................................................................................................................ 173 Patent Applications on Vitamin D ............................................................................................ 190 Keeping Current ........................................................................................................................ 220 CHAPTER 7. BOOKS ON VITAMIN D.............................................................................................. 221 Overview.................................................................................................................................... 221 Book Summaries: Federal Agencies............................................................................................ 221 Book Summaries: Online Booksellers......................................................................................... 222 Chapters on Vitamin D.............................................................................................................. 224 CHAPTER 8. MULTIMEDIA ON VITAMIN D ................................................................................... 227 Overview.................................................................................................................................... 227 Video Recordings ....................................................................................................................... 227 CHAPTER 9. PERIODICALS AND NEWS ON VITAMIN D ................................................................ 229 Overview.................................................................................................................................... 229 News Services and Press Releases.............................................................................................. 229 Newsletters on Vitamin D ......................................................................................................... 233 Newsletter Articles .................................................................................................................... 234 Academic Periodicals covering Vitamin D ................................................................................ 235 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 237 Overview.................................................................................................................................... 237 U.S. Pharmacopeia..................................................................................................................... 237 Commercial Databases ............................................................................................................... 238 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 243 Overview.................................................................................................................................... 243 NIH Guidelines.......................................................................................................................... 243

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NIH Databases........................................................................................................................... 245 Other Commercial Databases..................................................................................................... 247 The Genome Project and Vitamin D.......................................................................................... 247 APPENDIX B. PATIENT RESOURCES ............................................................................................... 253 Overview.................................................................................................................................... 253 Patient Guideline Sources.......................................................................................................... 253 Finding Associations.................................................................................................................. 256 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 259 Overview.................................................................................................................................... 259 Preparation................................................................................................................................. 259 Finding a Local Medical Library................................................................................................ 259 Medical Libraries in the U.S. and Canada ................................................................................. 259 ONLINE GLOSSARIES................................................................................................................ 265 Online Dictionary Directories ................................................................................................... 266 VITAMIN D DICTIONARY........................................................................................................ 267 INDEX .............................................................................................................................................. 351

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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 vitamin D is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about vitamin D, 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 vitamin D, 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 vitamin D. 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 vitamin D, 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 vitamin D. 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 VITAMIN D Overview In this chapter, we will show you how to locate peer-reviewed references and studies on vitamin D.

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

Treatment with Vitamin D and Calcium Reduces Bone Loss After Renal Transplantation: A Randomized Study Source: JASN. Journal of the American Society of Nephrology. 13(6): 1608-1614. June 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: A decrease in bone mineral density (BMD) is a major complication of renal (kidney) transplantation (RTx), predominantly occurring within the first 6 months after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examined the effect of treatment with calcium and active vitamin D on the loss of

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BMD in the first 6 months after RTx. A total of 111 kidney transplant recipients (65 men, 46 women; mean age 46 years, plus or minus 13 years) were randomized to treatment with active vitamin D plus calcium (CaD group) or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1, 3, and 6 months after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 months. Between the third month and the sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group. As a result, the amount of bone loss at 6 months was significantly lower in the CaD group. Loss of BMD at the different femoral (thigh or hip) sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia (high levels of calcium in the blood), no clinical or biochemical differences existed between the groups. The authors conclude that treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 months after kidney transplantation. 1 figure. 4 tables. 32 references. •

Secondary Hyperparathyroidism and Vitamin D Hormone Replacement Therapy: New Treatment Perspectives Source: Dialysis and Transplantation. 30(2): 109-111, 125. February 2001. Contact: Available from Dialysis and Transplantation, Attn.: Subscriptions. P.O. Box 10535, Riverton, NJ 08076. (800) 624-4196 or (609) 786-0871. Summary: Secondary hyperparathyroidism (SHPT) affects nearly all patients with chronic renal (kidney) failure (CRF). Recent evidence indicates that complications of SHPT are systemic, and not merely limited to renal bone disease. The link between SHPT and these co morbid conditions has prompted clinicians to make SHPT management a higher patient care priority. This article reviews the development of SHPT, the historical lack of appropriate treatment, and how vitamin D hormone replacement therapies could be used to prevent or limit its effects. In recent years, two vitamin D analogs that have been shown to be less calcemic, paricalcitol (Zemplar IV) and doxercalciferol (Hectorol oral and IV), have been approved for the treatment of SHPT in renal patients. Paricalcitol is active upon administration, with similar pharmacokinetic (how the drug works in the body) characteristics. However, doxercalciferol is a prohormone that, like endogenous vitamin D, must undergo metabolic transformation in the liver in order to form the active vitamin D hormone. This results in a pharmacokinetic profile that, at normal doses, provides blood levels of active vitamin D hormones that peak in 8 hours and remain in the physiologic range for more than 40 hours. This mimics the body's natural metabolism of vitamin D hormone, the ideal treatment for vitamin D hormone deficiency. 19 references.

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Secondary Hyperparathyroidism in Elderly People: Combined Effect of Renal Insufficiency and Vitamin D Deficiency Source: American Journal of Clinical Nutrition. 58(2): 187-191. August 1993. Summary: This article discusses a research study in which the relative effects of renal insufficiency and vitamin D deficiency on parathyroid gland function were assessed in 29 free-living elderly subjects by using a sensitive assay for intact parathyroid hormone (PTH). Serum calcium, phosphate, alkaline phosphatase, creatinine, 25-hydroxyvitamin D, and PTH were measured after an overnight fast during wintertime, after oral vitamin D therapy, and at the end of the subsequent summer. Hypovitaminosis D was evident in

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86 percent of the subjects during wintertime and 52 percent had elevated PTH concentrations. The researchers conclude that secondary hyperparathyroidism is common in elderly people, and in Ireland is the result of both renal insufficiency and hypovitaminosis D. •

Dental Problems Associated with Hypophosphataemic Vitamin D Resistant Rickets Source: International Journal of Paediatric Dentistry. 8(1): 19-28. March 1998. Contact: Available from Blackwell Science Ltd. Journal Subscriptions, P.O. Box 88, Oxford OX2 0NE, United Kingdom. +44 1865 206180. Fax +44 1865 206219. E-mail: [email protected]. Summary: This article reports on a study that reviewed a series of cases of hypophosphatemic vitamin D resistant rickets. Seventeen cases, aged between 2 years 1 month and 15 years 9 months at first referral, and with an established diagnosis of vitamin D resistant rickets from twelve families were included in the review. Information was drawn from patient records for follow up periods between 9 months and 20 years 4 months. Abscessed non-carious (without cavities) primary or permanent teeth were a presenting feature in eleven of the seventeen cases. Although attrition and exposure of the abnormally formed dentine accounted for the route of infection in primary teeth, the route for microbial invasion of pulpal tissues in permanent teeth remained unexplained in a number of patients. The authors discuss the possible part played by infractures of the enamel as a portal of entry for infection. Enamel defects were observed in only six patients, in three of whom these changes were limited to the primary dentition. Taurodontism (prism-shaped molars with large pulp spaces) of permanent molar teeth was confirmed as a feature of the condition in the more severely affected male subjects. 9 figures. 1 table. 13 references. (AA-M).

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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 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).

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Role of Vitamin D in the Pathogenesis and Treatment of Osteoporosis Source: Journal of Rheumatology. 23(Supplement 45):15-18. 1996.

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Summary: This journal article for physicians explains the pathogenesis of osteoporosis types 1 and 2, the effects of 1,25-dihydroxyvitamin D (calcitriol) on calcium balance, changes in bone mineral density during calcitriol treatment and maintenance of the treatment effect. Evidence on reducing vertebral fractures with calcitriol treatment is also provided. The author explains that patients with postmenopausal osteoporosis usually exhibit some degree of calcium malabsorption and commonly have low serum concentrations of calcitriol. Administration of calcitriol has been shown to normalize calcium absorption in patients with osteoporosis and, over the long term may stimulate bone formation. Clinical trials have shown a significant reduction in osteoporotic fractures among calcitriol-treated patients. Hypercalcemia and hypercalciuria are infrequent complications of calcitriol therapy with physiologic doses (0.25 microgram twice daily), and are most commonly related to excessive calcium intake (i.e., greater than 1,000 milligrams daily). 7 figures, and 25 references. (AA-M).

Federally Funded Research on Vitamin D The U.S. Government supports a variety of research studies relating to vitamin D. 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 vitamin D. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore vitamin D. The following is typical of the type of information found when searching the CRISP database for vitamin D: •

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

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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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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 •

Project Title: ADJUVANT NUTRITION IN CHEMOTHERAPEUTIC RESPONSE Principal Investigator & Institution: Muga, Stephanie; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2002; Project Start 29-SEP-2002; Project End 31-AUG-2007 Summary: Colorectal cancer remains a pre-eminent health concern in the United States today and is increasing in incidence worldwide. While chemotherapy for colon cancer is virtually standardized in this country (5-fluorouracil (FUra) and leucovorin), the reasons for only a 30-40% response rate are poorly understood. One highly under-explored variable in cancer chemotherapy is the effect of the patient's nutrient or dietary profile at the initiation of therapy and duration throughout therapy; dietary modification may significantly alter chemotherapeutic response. This project focuses on devising methods to prevent, treat, and control the development and progression of colorectal cancer. The novel approach to be explored in this project combines standard chemotherapeutic treatment with diet and nutrition modification to maximize drug efficacy thereby maintaining balances between key biochemical events that regulate cellular growth and differentiation. To date, very little research has examined the impact of dietary modulation on drug efficacy. This project will explore the effects of modifying the dietary environment in improving the response to FUra in a human colon cell culture system and the Ape Min/+ mouse model. Recent experiments in mice have shown that a diet high in fat, and low in vitamin D, calcium, methionine, choline, and folate induced colon cancer in the absence of a carcinogen. Studies on the chemopreventive elements in the diet indicate that many nutrients and non-nutrient components of diets are chemopreventive. We hypothesize that a diet enriched in chemopreventive factors (folate, calcium, vitamin D, and conjugated linoleic acid (CLA)) will potentiate the therapeutic ratio of FUra in the Apc Min/+ mouse. We postulate that a "cancer preventive" diet will enhance FUra-induced programmed cell death (apoptosis) in the colon, whereas a Western Stress diet will inhibit the effects of FUra treatment. In Aim 1, we will identify the molecular mechanisms by which pro-apoptotic dietary factors modulate the therapeutic efficacy of 5-fluoro-2'-deoxyuridine (FdUrd; nueleoside derivative of FUra) by examining biomarkers related to inflammation, proliferation, differentiation, and apoptosis in human colon cancer cell lines. In Aim 2, we will evaluate the therapeutic efficacy of administration of FUra on tumor incidence in the Apd Min/+ mouse. In Aim 3, we will evaluate the effects that (1) a supplemented diet enriched in folate, calcium, vitamin D, and conjugated linoleic acid and (2) a diet deficient in these factors has on 5-FU efficacy in the Apc Min/+ mouse. Results from this work will provide novel insight into the mechanisms of how dietary factors benefit colon tumorigenesis and how these dietary agents influence the ability of FUra to

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modulate colon carcinogenesis. Data obtained from these studies will be used to generate NIH R01 funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOCRINE TGFBETA AND BREAST CANCER CELL GROWTH Principal Investigator & Institution: Brattain, Michael G.; Professor and Chairman; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUN-1997; Project End 31-AUG-2006 Summary: State the application's broad long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This description is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this During the present cycle of funding we found that autocrine TGFbeta was induced by vitamin D3 analogs in ER+ breast cancer and pre-malignant mammary epithelial cells. Vitamin D3 analog response was 100 fold more resistant to inhibition in the absence of autocrine TGFbeta and preliminary evidence suggests that Smad3 activated by TGFbeta signaling enhances vitamin D3 receptor VDR directed transcription. However, while transfection of the type II TGFbeta receptor (RII) into RII null MCF-7 cells completely restores vitamin D analog sensitivity, transfection of Smad3 does not. This indicates that a second aspect of TGFbeta signaling is required in addition to Smad3. Thus, in Specific Aim I we will test the hypothesis that Smad3 interactions with the VDR are required for TGFbeta/VDR crosstalk, but that in addition to this Smad3 pathway, TGFbeta mediated activation of the MAPK pathway is also required. We and others have observed that vitamin D analogs cause apoptosis. The mechanism by which apoptosis is induced is largely unexplored, particularly with respect to the role of TGFbeta crosstalk. TGFbeta itself also induces apoptosis. Consequently, we will test the hypothesis that vitamin D3 analog induced apoptosis is mediated by the enhanced autocrine TGFbeta activity resulting from treatment with the drug. During the present period of funding we found that TGFbeta receptor expression in ER+ breast cancer cells is transcriptionally repressed. The repression can be blocked by treatment with the methylase inhibitor, 5 aza deoxycytidine. Surprisingly, this agent did not reverse methylation of the RII promoter, but instead increased the cellular level of Sp1 which is underexpressed in ER+ breast cancer cells. Sp1 is required for RII transcription. Interestingly, Sp1 transcription was not targeted by 5 aza deoxycytidine. Further, investigation showed that Sp3 transcription factor which represses Sp1 mediated transcription was elevated in ER+ breast cancer cell lines. Sp3 was shown to be a repressor of RII by southwestern, gel shift and blockade of RII promoter-reporter activity after Sp3 transfection. In addition Sp3 transcripts were decreased as a result of 5 aza cytidine treatment. Consequently, it appears as though Sp1/Sp3 homeostasis is responsible for repression of RII transcription in ER+ breast cancer cells. This hypothesis will be tested in Specific Aim III. The Specific Aims for the renewal project are: 1. Determine the mechanism of crosstalk between vitamin D3 analogs and TGFbeta in ER+ breast cancer cells, immortalized mammary epithelial cells and normal mammary epithelial cells. Determine whether vitamin D3 response in ER- cells is also associated with TGFbeta crosstalk. II. Determine the mechanism of induction of apoptosis by vitamin D3 analogs in the cell types listed in Specific Aim I and determine whether apoptosis inhibition is dependent upon autocrine TGFbeta. III. Determine how Sp1 and Sp3 homeostasis is controlled in ER+ breast cancer to regulate RII transcription. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIO-ACTIVATION OF VITAMIN D IN MAMMARY GLAND Principal Investigator & Institution: Welsh, Joellen E.; Professor; Biological Sciences; University of Notre Dame 511 Main Bldg Notre Dame, in 46556 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The biologically active form of vitamin D3 (cholecalciferol) is 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the ligand for the vitamin D receptor (VDR). In addition to its well characterized role in bone metabolism, vitamin D is recognized as a potent regulator of cell proliferation and differentiation. In mammary gland, 1,25(OH)2D3 opposes estrogen and progesterone stimulated proliferation and branching through VDR dependent pathways. 1,25(OH)2D3 is produced from 25(OH)D, the major circulating metabolite of vitamin D. The enzyme that catalyzes the production of 1,25(OH)2D3 is the vitamin D 1-hydroxylase (1OHASE). The long term goal of the proposed studies is to validate the vitamin D 1OHASE as a target for breast cancer prevention. Although initially thought to be exclusively expressed in kidney, the 1-OHASE has recently been localized to numerous extra-renal tissues, including epidermis, colon, and prostate gland. In preliminary experiments, we have demonstrated expression of 1-OHASE in non transformed human mammary epithelial cells, and we propose to confirm and extend these findings in the pilot studies described here. We hypothesize that normal breast tissue expresses 1OHASE and generates 1,25(OH)2D3, which acts locally to inhibit growth and maintain differentiation of mammary epithelial cells. A corollary to this hypothesis is that deregulation of 1-OHASE and loss of 1,25(OH)2D3 mediated growth regulation may be associated with neoplastic progression. Two specific aims have been designed to test this hypothesis. In Specific Aim 1, we will examine the expression and regulation of the vitamin D 1-OHASE during normal development in mice (Specific Aim 1a) and in nontransformed human mammary cells in vitro. In Specific Aim 2, we will assess the expression and activity of the vitamin D 1-OHASE as a function of neoplastic progression in tissues and tumors derived from MMTV-neu mice (Specific Aim 2a) and in progressively transformed human mammary epithelial cell lines (Specific Aim 2b). Techniques will include real time quantitative polymerase chain reaction (PCR), immunohistochemistry, laser capture microdissection and immunoblotting. The data on 1-OHASE expression and activity will be interpreted in relation to expression of the VDR and sensitivity to 25(OH)D mediated growth inhibition. These studies will provide important information regarding the expression and function of the vitamin D signaling pathway in normal mammary gland, which might have implications for breast cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOCHEMICAL MARKERS IN THE NURSES' HEALTH STUDY COHORT Principal Investigator & Institution: Hankinson, Susan E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUN-1989; Project End 31-MAR-2004 Summary: We propose to analyze blood samples in a nested case-control manner from the 32,826 participants in the Nurses' Health Study (NHS) who provided samples in 1989-90 and were 43 to 69 years of age at that time. The samples have been stored at greater than or equal to 130 C in liquid nitrogen freezers since collection. We will assay samples from women who were diagnosed after blood collection and matched controls who remained disease-free, thus efficiently utilizing these prospectively collected

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samples. We propose to build upon our recent positive findings for several plasma hormones and nutrients in relation to breast and colon cancer risk, and to address new hormonal hypotheses in relation to risk of breast, ovarian and colon cancers and myocardial infarction. Specifically, we will examine (1) plasma estrogens, androgens and prolactin levels in relation to breast cancer risk in postmenopausal women, (2) a polymorphism in the catechol-O- methyl transferase (COMT) gene and risk of breast cancer, (3) DHEA, DHEAS and 5-androstene-3beta,17beta-diol and risk of breast and ovarian cancers and myocardial infarction, (4) insulin-like growth factor I and its binding proteins 1 and 3, plasma vitamin D and polymorphisms in the vitamin D receptor, and plasma antioxidant levels - all in relation to risk of breast and colon cancers. The ongoing NHS (CA40356 and HL34594) will provide follow-up and documentation of disease outcomes in addition to providing information on important covariates (such as exogenous hormone use, diet, smoking status, among others) for the proposed study. Participation in the NHS has been high: among the 32,826 women who provided a blood sample, 98 percent continue to complete questionnaires, and vital status has been documented for 99 percent. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed exposure data, and the availability of archived blood specimens provide a unique opportunity to test several hypotheses of public health importance. We also propose to collect a second blood sample from about 18,000 of the women who provided a first blood sample in 1989-90. This will increase our statistical power in future analyses, and allow us to assess in detail the temporal relationships between biomarkers and disease risk and to reduce the attenuating effects of measurement error. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE DENSITY IN AGING MEN OF DIVERSE RACE AND ETHNICITY Principal Investigator & Institution: Mckinlay, John B.; Senior Vice President and Director; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 31-MAR-2006 Summary: (provided by applicant): The National Institutes of Health (NIH) has identified the prospective investigation of osteoporosis in gender, age, and racially/ethnically diverse populations as an urgent research priority (Consensus Development Conference on Osteoporosis Prevention, Diagnosis, and Therapy. 2000). Male osteoporosis is a highly prevalent medical condition, with enormous impact on the health, medical-care expenditures, and quality of life of the aging U.S. male population. Race/ethnic-specific estimates of the prevalence of osteoporosis from population based. cross-sectional data are limited by: (1) Incomplete information on the range of variables that may be related to both bone density and race/ethnicity (e.g., bone turnover, hormone levels, lifestyle, nutrition, vitamin D status, and others) that might account for the racial/ethnic difference in prevalence; and (2) Limited data on Hispanics other than Mexican Americans, despite the well-known heterogeneity of ethnicities within Hispanic populations. The New England Research Institutes (NERI) has received an award from NIDDK to begin a large epidemiological research study of 3,000 randomly selected, community dwelling Hispanic, non-Hispanic African American, and nonHispanic Caucasian men ages 40-79 years (1,000 per racial/ethnic group), to provide normative data on four urologic conditions. The proposed study will take advantage of this newly assembled cohort by adding a cross-sectional, population-based sub-study of bone density and osteoporosis in men. We will recruit 900 men from the parent study and describe the distribution of bone mineral density (BMD) and low BMD by

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race/ethnicity and determine to what extent variables (e.g., health status, lifestyle, sociodemographics, biochemical measures of bone turnover and hormone levels, fracture history) correlate with BMD, and whether the effect of these variables on BMD varies with race/ethnicity. To prepare for the possibility of a future, separately funded prospective study, we will initiate panel maintenance activities with the cohort. This design represents a cost-efficient approach to gathering detailed information focused on bone health in a randomly selected, population-based sample, while taking advantage of the activities currently underway as part of the parent study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONY EFFECTS OF TRANSIENT NONSKELETAL ILLNESS Principal Investigator & Institution: Heaney, Robert P.; John A. Creighton University Professor; None; Creighton University 2500 California Plaza Omaha, Ne 68178 Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted from the Applicant's Abstract): This project seeks to quantify the extent and time course of the bone loss produced by episodes of temporary illness of a sort associated with bed rest and catabolic influences. The underlying hypothesis is that recovery of bone lost under these circumstances is often incomplete, particularly in critical regions such as the spine and hip. If true, this would mean that some portion of age-related bone loss is a punctuated phenomenon, related to illness and/or immobilization, rather than being continuous and inexorable. This finding would open up additional opportunities for osteoporosis prevention. As a surrogate for a wide variety of catabolic episodes, the investigators will use routine, elective abdominal or pelvic surgery performed on individuals 55-70 years of age. They will measure bone mass by DEXA at spine and hip in 150 individuals before surgery, at 4-8 weeks post surgery, and then at 4, 8, and 12 months, to quantify and characterize the extent of bone lost under these circumstances. They will also measure various potentially modifying covariates, such as degree of temporary disability, Ca intake, hormonal therapy, vitamin D status, age, and life-style factors, any of which might plausibly influence extent of bone loss or degree of recovery. They will compare decreases at various time points after surgery to baseline values in each woman and will compare mean bone mass changes at 12 months with a non-operated control group matched for age and estrogen replacement therapy and measured twice across a 12-month interval. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CA2+ HYPERPARATHYROIDISM

SENSING

RECEPTOR

EXPRESSION

IN

Principal Investigator & Institution: Brown, Alex J.; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2003 Summary: Parathyroid glands (PTGs) express a calcium-sensing receptor (CaR) that detects the concentration of extracellular calcium and signals the glands to secrete the proper amount of parathyroid hormone (PTH) to maintain normal calcium levels. The calcium-PTH relationship is sigmoidal and can be defined by four parameters: maximum PTH, minimum PTH, the midpoint of the curve (set-point), and the slope at the midpoint. The CaR levels are decreased in the hyperplastic PTGs of patients with secondary HPT (2oHPT) due to chronic renal failure (CRF), but the factors responsible are not known. The impact of this down-regulation on calcium sensitivity remains controversial. In vitro studies indicate decreased calcium sensitivity (elevated set-point)

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in parathyroid cells from CRF patients, but in vivo assessment of the set-point in CRF patients have yielded mixed results. Furthermore, in patients it is not possible to relate CaR levels to the four parameters of the calcium-PTH relationship. We have now observed a similar reduced CaR expression in hyperplastic PTGs of CRF rats. This model can be used to determine the role of decreased CaR in PTG hyperplasia and the abnormal calcium-PTH relationship, and to identify the factors that regulate the CaR. Definitive identification of the factors that directly control CaR levels requires an in vitro model with stable expression of the CaR. Traditional monolayer cultures do not respond to calcium. We have developed a unique parathyroid cell culture system that preserves the normal cellular architecture, allowing stable CaR expression and calcium response for several weeks. These cultures, which we refer to as pseudoglands or psGs, provide the best available model for studying the regulation off parathyroid cell CaR expression and provide a unique in vitro model t9o examine the effects in CaR levels on the calcium-PTH relationship. This grant presents an experimental approach that utilizes these in vivo and in vitro models to examine both the causes and effects of the downregulation of the CaR in renal failure. The specific aims are: 1. To define the relationships, temporal and spatial, between parathyroid gland hyperplasia and downregulation of the CaR in vivo. 2. To examine the effects of established therapies for uremic secondary hyperparathyroidism (phosphate restriction and vitamin D compounds) on CaR expression in uremic rats. 3. To determine the direct effects of potential regulators of CaR expression in vitro using the psG model. 4. To determine the effects of down-regulation of CaR on the calcium- PTH relationship and PTH expression in vivo and in vitro. These studies will provide new information about the effect of decreased CaR in CRF on the calcium-PTH relationship, define the factors responsible for the decrease, and test therapeutic strategies to correct the abnormality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCIUM ABSORPTION AND BONE FORMATION DURING PUBERTY Principal Investigator & Institution: Abrams, Steven A.; Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-MAR-1996; Project End 31-MAY-2006 Summary: (Scanned from the applicant's abstract) Background: Rapid increases in bone mass occur during Liberty Optimizing calcium absorption (Ca abs) and bone calcium deposition (V0+) during puberty can enhance peak bone mass and ultimately decrease the lifetime risk of osteoporosis. In this study, we will determine the influence of hormonal, genetic and dietary factors that lead to maximal Ca-abs and Vo+ in pubertal boys and girls. This proposal is a logical extension of our recent findings that; 1) changes in calcium metabolism in early puberty are correlated to serum luteimzing hormone (LH) level, ethnicity, family history of osteoporosis, and the genotype of vitamin D receptor polymorphisms, and 2) the addition of small amounts of nondigestible oligosaccharides (NDO) can significantly increase calcium absorption in pubertal children on relatively high calcium-containing diets. Hypotheses: Our overall hypotheses are that dynamic changes in mineral metabolism in early adolescence are based on identifiable hormonal and genetic factors and that specific nutritional interventions can enhance bone mass accumulation. Specifically, in this proposal we will evaluate the following: 1) Early nighttime increases in pubertal hormones will be closely correlated to Ca-abs and V0+ in both boys and girls. In contrast, serum leptin will be negatively correlated with V0+; 2) Putative genetic markers of osteoporosis, including vitamin D receptor polymorphisms, will be significantly correlated to Ca-abs and V0+;

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3) The addition of NDO will increase Ca-abs and Vo+ in pubertal children receiving recommended dietary calcium intakes. Study Methods: We will enroll 50 girls and 50 boys who are healthy, 5th to 95th percentile body mass index for age, and Tanner Stage 2 or 3. They will participate in comprehensive dual-tracer calcium stable isotopic kinetic studies. Results will be compared with pubertal hormonal studies, biochemical bone turnover markers, and dual-energy X-ray absorptiometry (DXA) measures of whole body and regional bone mineral content. Genetic markers related to bone mass will be assessed and related to both hormonal and calcium kinetic measurements. After these baseline studies, subjects will be randomized to receive calcium fortified foods either with or without added NDO. Calcium absorption will be measured again after 2 months. After 12 months, the baseline calcium kinetic, hormonal and DXA studies will be repeated to assess the effects both of pubertal development and the dietary intervention. At the conclusion of that study, supplementation with NDO will be stopped and a final DXA study performed 12 months later to assess whether bone mass differences identified during supplementation were maintained post-intervention. Conclusions: By identifying the relationships among hormonal changes of puberty, genetics and calcium metabolism, the characteristics leading to maximal calcium absorption and utilization can be identified. These insights will enable interventional strategies to enhance bone mass to be specifically related to identifiable population characteristics, with the ultimate goal of decreasing the incidence and severity of bone loss and osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER AND LEUKEMIA GROUP B Principal Investigator & Institution: Hurd, David D.; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 01-APR-1979; Project End 31-MAR-2009 Summary: (provided by applicant): This Ul0 application is in support of the CALGB Cooperative Group Clinical Trials conducted through the Wake Forest University School of Medicine (WFUSM) and its affiliate Members. WFUSM has been continuously awarded a CALGB U10 Grant for 45 years (CA03927) as the key support of the infrastructure for data management, the required administrative interactions with our Affiliate Members, and for the support of scientific and administrative contributions to CALGB. In addition to support for the Main Member, this U10 Grant supports the oversight of activity at our two current Affiliate Members, East Carolina University, Greenville, North Carolina and Carolina Oncology Associates of Salisbury, Salisbury, North Carolina. The specific aims of this grant application are: * To increase our scientific contributions to Disease and Modality Committee activities * To enhance the participation of our clinical research investigators through the development of pilot data at the Comprehensive Cancer Center of Wake Forest University that can be developed into CALGB protocols * To expand the Affiliate Network of the Comprehensive Cancer Center of Wake Forest University in order to provide improved care of the cancer patient through access to CALGB Cancer Clinical Trials * To provide a clinical trials mechanism by which minority populations can accrue to clinical trails; to improve their proportional participation in clinical trials research; and to develop specific strategies to address regional barriers to minority recruitment and retention in clinical research studies * To continue our participation as a funded Prevention Member Center Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Vitamin D

Project Title: CCCWFU RESEARCH BASE GRANT Principal Investigator & Institution: Shaw, Edward G.; Professor and Chairman, Radiation Oncolo; Radiation Oncology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 07-SEP-1999; Project End 31-MAY-2005 Summary: (provided by applicant): The Comprehensive Cancer Center of Wake Forest University (CCCWFU) Community Clinical Oncology Program (CCOP) Research Base was funded in 9/99 (retroactive to 6/99) for three years. This application describes the administrative structure, including safety and monitoring procedures and clinical research activities of the Research Base for its five-year competitive renewal as a control/treatment CCOP Research Base. Participants in the Research Base include three CCOPs (Southeast Cancer Control Consortium, Winston-Salem, NC; Upstate Carolina CCOP, Spartanburg, SC; Greenville CCOP, Greenville SC) and four non-CCOP Prevention Members (East Carolina University, Greenville, NC; High Point Regional Health System, High Point, NC; InterCommunity Cancer Center, Rome, GA; WakeMed System, Cary, NC. The geographic region covered by these three CCOPs and four Prevention Members includes seven states (NC, SC, VA, WV, KY, TN, GA) with a population of approximately 12 million people, one-quarter of whom are minorities (60% minorities in coastal NC communities), served by 28 cancer centers. It is anticipated that an additional 3-6 CCOPs and Minority-Based CCOPs will join the CCCWFU CCOP Research Base by 12/01. Active and developing clinical trials of the Research Base are described in the application. In cancer control, there are 4 active and 13 developing studies, focusing on the following areas: complimentary and alternative medicine, symptom management, and quality of life, particularly in the setting of cancer related fatigue, anorexia/weight loss, depression, hot flashes, cognition and chemoprevention. In cancer treatment, there are 6 active and 7 developing studies, focusing on complementary, alternative, and conventional therapies primarily in lung, pancreas, and brain cancer. The spectrum of clinical research studies offered by the CCCWFU CCOP Research Base is complementary to, rather than competitive with, the cancer control/treatment protocols offered by the Cooperative Group Research Bases. Under the direction of Principal Investigator Edward G. Shaw, M.D., the Clinical Research Management administrative structure of the CCCWFU, and key leadership from the CCCWFU, CCOPs, and Prevention Members, the CCCWFU CCOP Research Base is fulfilling its primary goal of providing state-of-the-art intervention oriented clinical research studies in cancer prevention/control to CCOPs and patients (including minorities) in the Southeast United States. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CELIAC DISEASE IN OSTEOPOROSIS Principal Investigator & Institution: Stenson, William F.; Professor; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-JUN-2000; Project End 31-MAY-2003 Summary: (Abstract of the application) There is compelling evidence that the prevalence of celiac disease in the general population in the United States is higher than is generally appreciated and that patients with the symptoms classically associated with celiac disease, primarily diarrhea and weight loss, form a relatively small portion of the total celiac population. Some patients with celiac disease have medical problems associated with the malabsorption of specific nutrients without having problems with diarrhea and weight loss. Celiac disease is associated with the malabsorption of calcium and vitamin

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D resulting in osteoporosis. Although the prevalence of osteoporosis in the population of patients with celiac disease is known to be increased compared to the prevalence in the general population, the contribution of celiac disease to osteoporosis in the general population and the prevalence of celiac disease in the population of patients with osteoporosis are unknown. The central hypotheses of this proposal are: 1. The prevalence of celiac disease in the population of patients with osteoporosis is significantly increased above that of the general population. 2. Management of osteoporotic patients with celiac disease would be facilitated by the diagnosis and treatment of their celiac disease. These two premises taken together would justify a public health recommendation for screening patients with osteoporosis with serological tests for celiac disease. We have the unique resource of a Bone Health Clinic with a database that includes more than 2,000 individuals with osteoporosis as well as an even larger number of patients with normal bone density. In addition, the Bone Health Clinic sees more than 750 new patients per year of which 50% have osteoporosis. We propose to use the resources of our Bone Health Clinic to test this hypothesis. We have two Specific Aims: 1. To define the prevalence of celiac disease in a population of patients with osteoporosis and to compare the prevalence in a case control group of individuals with normal bone mass indices. This Specific Aim will be pursued using patients from the Bone Health Clinic database that will already have been defined as having osteoporosis and new patients accrued to the Bone Health Clinic. If the prevalence of celiac disease in the osteoporotic population is high enough one could justify a public health recommendation that all patients with osteoporosis undergo serologic screening for celiac disease. Studies under this Specific Aim will also allow recommendation for which sequence of serologic tests is most likely to be helpful in identifying patients with osteoporosis who also have celiac disease. 2. To determine if there are any significant differences in the clinical histories, laboratory studies or response to therapy between the populations of newly diagnosed and previously untreated osteoporotic patients with and without celiac disease. Specific studies will include: a. We will compare the population of patients with osteoporosis and celiac disease with the population of patients with osteoporosis without celiac disease in terms of their clinical characteristics and biochemical parameters determined at the time of diagnosis. b. We will compare patients with osteoporosis and celiac disease with patients with osteoporosis without celiac disease in terms of their response to therapy. Patients with osteoporosis without celiac disease will receive calcium and vitamin D for one year, whereas patients with osteoporosis and celiac disease will receive calcium, vitamin D and a gluten-free diet for one year. At the end of the year of therapy, bone mass indices will be repeated and the response to the therapy of the two groups will be compared. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR CALCIUM TRANSPORT IN URINARY EPITHELIA Principal Investigator & Institution: Friedman, Peter A.; Professor; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-MAR-2003 Summary: The long-term objective of our work is directed toward a complete understanding of the cellular mechanisms and regulation of calcium transport by renal tubular epithelial cells. Although most calcium absorption proceeds in proximal tubules, distal tubules are the site of the physiological regulation of calcium transport by parathyroid hormone (PTH), calcitonin and vitamin D3. The specific aims of the present proposal are to: 1) characterize the mechanism of calcium entry across apical plasma membranes of distal convoluted tubule (DCT) cells; 2) evaluate the participation and

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Vitamin D

regulation of Na+/Ca2+ exchange in mediating calcium efflux; and, 3) define the signaling pathways activated by PTH and calcitonin in DCT cells, and to examine the coordinate regulation of PTH-dependent calcium transport by 1,25(OH)2 vitamin D3 and estradiol. We identified and partially characterized a novel calcium channel that mediates calcium entry. To acquire additional information about these channels we will: 1) characterize the properties of these channels with regard to their ion selectivity, pharmacologic sensitivity and voltage- dependence; 2) determine the regulation of these calcium channels by protein kinases; 3) define the participation of G-proteins in regulating calcium entry channels; and, 4) identify and clone calcium channel transcripts. Extrusion of calcium across basolateral plasma membranes of distal tubules is mediated by Na+/Ca2+ exchange and by /ca2+-ATPase. Pilot studies suggest that Na+/Ca2+ exchange is the dominant efflux mechanism in DCT cells. We will: 1) Test the hypothesis that thiazide diuretics can inhibit Na+/Ca2+ exchange; and 2) Characterize the stimulatory effects of PTH on Na+/Ca2+ exchange. Calcium transport in distal nephrons is regulated by PTH, calcitonin and 1,25(OH)2 vitamin D3. The following studies will evaluate the mechanism mediating the hormonal regulation of calcium transport in DCT cells. The goals of these experiments are to: 1) Characterize the signaling pathways with particular regard to the phospholipases responsible for activating PKA and PKC and characterize the temporal sequence in which PKA and PKC are activated. We will test the hypothesis that PTH and calcitonin activate PKC via phospholipase D. 2) Identify the mechanism by which PTH activates C1- channels, a primary event in membrane hyperpolarization and stimulation of calcium transport in DCT cells. We will test the hypothesis that these chloride channels are regulated by the PKA limb of the PTH-activated signaling pathway. 3) Examine the regulation of vitamin D3 and estradiol accelerate PTH dependent calcium transport by up-regulating PTH receptor expression. The specific aims will be achieved by applying single cell fluorescence, patch clamp, tracer flux measurements, biochemical and molecular techniques to a DCT cell line that we developed, which expresses an appropriate phenotype. In selected studies, primary cell cultures of proximal or distal tubule cells will be used to verify results in transformed cells or as controls. All procedures are established in our lab. Results from the proposed experiments will provide new information on the mechanism and regulation of calcium transport in the kidney under normal conditions, but also in calcium-wasting syndromes including hyperparathyroidism, renal failure, osteoporosis and malignancy- associated hypercalcemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITORS

CELLULAR

EFFLUX

AND

METABOLISM

OF

PROTEASE

Principal Investigator & Institution: Mitra, Ashim K.; Professor and Chairman; Pharmaceutical Sciences; University of Missouri Kansas City Kansas City, Mo 64110 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (Provided by the applicant): Cytochrome P450 3A4 (CYP3A4), most abundantly presently both in the liver and upper intestinal enterocytes, limits the systemic bioavailability of anti-HIV agents. P-glycoprotein (P-gp), the MDR-1 gene product is also known to reduce the oral bioavailability of protease inhibitors. Moreover the existence of "sanctuary" sites of HIV-1 may potentially endanger the efficacy of highly active antiretroviral therapy (HAART). High cellular expression of P-gp in brain capillary endothelial cells, P-gp and CYP3A4 in mature enterocytes and alveolar cells and their similar substrate specificity suggest that the function of these proteins may be

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complementary and may form a coordinated intestinal, blood-brain and pulmonary barrier. The purpose of this study is to classify all anti-AIDS drugs, currently used clinically, under a new proposed Absorption-Metabolism Classification System (AMCS). Under AMCS, four classes of drugs, A, B, C and D, will be proposed based on their specificity towards P-gp and/or CYP3A4. We propose to investigate the simultaneous P-gp mediated efflux and CYP3A4 mediated metabolism of the above mentioned 14 anti-AIDS compounds across l alpha, 2,5-di-OH vitamin D3 treated Caco-2 cell monolayers expressing high levels of P-gp and CYP3A4. Moreover, in some experiments, isolated hepatocytes containing liver CYP3A, representing first pass liver metabolism, wil1 also be included. Under AMCS we hypothesize that apparent order of oral bioavailability will be A > BEC > D. Our proposed classification system may prove to be an important tool in screening anti-AIDS compounds for their oral absorption potential. According to this hypothesis Class A compounds should not interact with any other class. There should be no interaction between compounds of class B and C, whereas Class B and C compounds are expected to interact with Class D compounds. Also, maximum interaction is anticipated within Class D compounds compared to interaction with Class B and Class C compound. Our proposed theoretical model may predict, a priori, the extent of drug absorption and more importantly drug interactions among four WCS classes. Therefore, the specific aims of this project are: 1) to develop an in vitro Caco-2 cell culture model expressing high levels of P-gp and CYP3A4 to a priori predict oral absorption potential and drug interactions among the four AMCS class drugs, to utilize the model in predicting first pass metabolism using human hepatocytes. Specific inhibitors of P-gp and CYP3A4 will be used to demonstrate the involvement of each of these proteins. In addition, the expression of these proteins will be determined by Western Blot and RT PCR. 2) to develop a quantitative model for oral drug absorption and interactions based on mathematical expression of passive influx, saturable efflux, and saturable CYP3A4 metabolism and to correlate model predicted effluxes with experimentally determined efflux values. This theoretical model will also predict the fluxes of each of the A, B, C, and D classes of drugs. The theoretical model will be first validated using model compound in each class: Tolbutamide - Class-A, Rhodamine 123 - Class-B, Carbamazepine - Class-C, and Cortisol - Class-D. 3) to study the transport and metabolism across two other in vitro cell culture models, bovine brain microvessels endothelial cell (BBMEC) and Calu-3 monolayers representing blood-brain and alveolar cells respectively. The brain parenchymal and alveolar lining - two sanctuary sites that are 'protected' from optimal antiretroviral drug access. 4) to study the effect of protein binding on the influx and efflux of model compounds, and anti-HIV drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHROMATIN STRUCTURE IN EXPRESSION OF OSTEOCALCIN GENE Principal Investigator & Institution: Stein, Gary S.; Professor and Chairman; Cell Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2004 Summary: (provided by applicant) Chromatin remodeling of the bone-specific osteocalcin (OC) gene accompanies transcriptional activation during late stages of osteoblast differentiation. Defining the molecular, cellular, and physiological mechanisms that regulate osteoblast growth and differentiation, within the context of skeletal development and bone formation in vivo, is the long term goal of the NIH grant

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Vitamin D

"Control of Osteoblast Growth and Differentiation (R0l AR39588)," that serves as the parent grant for this FIRCA proposal. The studies proposed in this renewal will be done primarily in Chile. During the initial funding period of our collaborative program, we established mechanisms mediating nucleosome positioning and specific protein-DNA interactions on the osteocalcin gene promoter. The studies proposed in this renewal application will reveal molecular mechanisms operating in chromatin remodeling of the OC gene during osteoblast differentiation. We will be focused on establishing the components of the chromatin remodeling complexes that promote the changes in chromatin structure associated with basal and vitamin D-enhanced OC transcriptional activity. We hypothesize that BRG-1 containing complexes are responsible for alterations in OC gene chromatin structure. We will also examine the molecular mechanisms involved in targeting these chromatin-remodeling activities to the OC promoter. We hypothesize that sequence-specific transcription factors such as Cbfa1 play a major role in targeting chromatin-remodeling activities to the OC promoter We also propose that the translational positioning of nucleosomes in the OC promoter result from the activity of these targeted chromatin remodeling complexes. To test these hypotheses we will carry out studies using intact osteoblastic cell cultures as well as cellfree systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLC-5 INACTIVATION AND HYPERCALCIURIA IN DENT'S DISEASE Principal Investigator & Institution: Scheinman, Steven J.; Professor; Medicine; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Hypercalciuria is the most common risk factor for calcium oxalate stone disease and often has an hereditary component. The first inherited hypercalciuric syndrome for which the gene was identified was X-linked nephrolithiasis (Dent's disease), which is caused by inactivating mutations in the CLCN5 gene encoding the voltage-gated chloride channel C1C-5, expressed in subapical endosomes of renal proximal tubular cells. However, other than low molecular-weight (LMW) proteinuria, we do not know how this explains other features of the disease such as hypercalciuria, which is the major risk factor for calcium oxalate stone formation in patients with Dent' s disease, nor why proximal tubular production of 1,25(OH)2 vitamin D is excessive. Our hypothesis is that defective function of C1C-5 in endosomes leads to altered membrane and protein trafficking that perturbs the integrity of the cellular vesicular transport network. This could explain altered function of apical Na-dependent transport processes such as reabsorption of phosphate. Further, since 1a-hydroxylation of 25(OH)2 D occurs in proximal tubular cells, it is possible that dysregulation of the 1ahydroxylase is a secondary consequence of altered membrane trafficking. We will address this hypothesis in cultured HK-2 human proximal tubular cells in which we have used a ribozyme to reduce C1C-5 expression. In preliminary studies we have demonstrated changes in membrane trafficking and solute transport in these knockdown cells. Using this model our specific aims are to determine the consequences of reduced C1C-5 expression on: (1) membrane trafficking, (2) solute transport (particularly Na-dependent phosphate transport), and (3) 1a-hydroxylation of vitamin D. We expect that these pilot studies will offer significant insights into the mechanisms of calcium oxalate stone formation in Dent's disease and provide the foundation for further studies using this in vitro cell culture model to address mechanisms of hypercalciuria and renal failure.

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

Project Title: CLINICAL TRAILS IN PEDIATRIC RHEUMATOLOGY Principal Investigator & Institution: Lovell, Daniel J.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Taken from the applicant's abstract): This application is focused on the performance of two prospective, multicentered trials in children with juvenile rheumatoid arthritis (JRA). In addition, this career development grant is intended to enhance the ability of many pediatric rheumatology centers in North America to perform trials to determine the efficacy and safety of currently used but untested and also newly developed drugs in children with JRA by increasing the ability of the principal investigator (PI) to focus on the direction and coordination of the efforts of the Pediatric Rheumatology Collaborative Study Group (PRCSG) of which the PI is the chairman. The PRCSG is a consortium of over 45 academic pediatric rheumatology centers that have performed over 30 trials in children with JRA. Trial 1: Osteopenia is a significant and frequent complication of JRA. This research proposal includes a prospective, randomized, multicenter, placebo-controlled trial (RCT) to determine the efficacy of daily oral calcium supplementation (1000 mg/day of calcium carbonate) for two years to increase total body bone mineral density (TB BMD) by 10% (1.5 SD) compared to placebo treatment. In addition, the persistence of the treatment effect will be determined for 1.5 years after the RCT. This will be the first longitudinal study of bone mineralization in JRA and the control group will demonstrate the natural history of bone mineralization. Trial 2: This research proposal also includes a prospective, randomized, actively controlled, open clinical trial to determine the efficacy of combination drug therapy to induce prolonged drug-free remission in children with severe systemic JRA (sJRA). Patients will be enrolled early in the disease course but eligibility criteria will select those with a 115% risk of developing severe, erosive polyarthritis. One therapy regimen is composed of intravenous methylprednisolone for 3 consecutive days, intravenous cyclophosphamide on the third day, and up to 20 mg/M2/wk of methotrexate. The second pulse therapy regimen is identical to the first, except no cyclophosphamide is given. Up to 5 cycles of these regimens may be given over a 9-month period. Patients in both groups may also receive background medications including 1 non-steroidal anti-inflammatory drug and up to 0.5 mg/kg/d of oral prednisone. The short and intermediate (0-18 months) safety of these treatment regimens will be compared. Long-term goals: 1. Assess the efficacy and safety of current and emerging pharmacologic and biologic treatments as adjunctive therapy to calcium in JRA patients with osteopenia. 2. Determine the long-term efficacy and safety of these treatment regimens in sJRA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLONING AND CHARACTERIZATION OF HUMAN CYP25 Principal Investigator & Institution: Bell, Norman H.; Va Medical Investigator; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): Vitamin D must undergo hydroxylation to 25-hydroxyvitamin D [25(OH)D] by the enzyme vitamin D-25hydroxylase (CYP25) to become biologically active. Porcine CYP25 cDNA was cloned and characterized. The gene encodes a cytochrome P450 microsomal enzyme expressed

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in liver and kidney that catalyzes the conversion of vitamins D2 and D3 to 25(OH)D3, respectively. Patients with isolated 25(OH)D deficiency and rickets who respond to pharmacologic doses of vitamin D and physiologic doses of 25(OH)D3, 1alpha(OH)D3, or related drugs are presumed to have CYP25 deficiency. The specific aims of this proposal are to use portions of porcine CYP25 cDNA to isolate and characterize human CYP25 cDNA, to clone and characterize the human CYP25 gene, to determine chromosome locus of CYP25 DNA and tissue expression of CYP25 mRNA, to use gene mapping, linkage analysis and positional cloning, to characterize family pedigrees and determine molecular mechanisms of patients with isolated 25(OH)D deficiency and rickets, to characterize CYP25 gene polymorphisms in affected populations, and to correlate genotype with phenotype. The fact that porcine CYP25 cDNA has 83 percent homology with human CYP2D6 cDNA, a cytochrome P450 microsomal enzyme that plays a role in drug metabolism, has interfered with cloning of human CYP25 cDNA. Pig liver extracts are reported to have no CYP2DK activity. Using a radiation hybrid cell panel (ImpRH), we found that the porcine CYP25 gene maps to pig chromosome 5p1415 close to the ACO2 gene, a region syntenic ot human chromosome 22q12-13 where human CYP2D6 was mapped. We used haplotype analysis of family pedigrees of patients with isolated CYP25 deficiency and rickets and found that the disease does not map to either the CYP2D6 gene locus or chromosome 22. The results of the proposed studies should provide important new information about the molecular structure and chromosomal locus of the CYP25 gene and the molecular causes of isolated 25(OH)D and rickets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLORECTAL CHEMOPREVENTION WITH CALCIUM AND VITAMIN D Principal Investigator & Institution: Baron, John A.; Professor of Medicine; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 17-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Epidemiological and experimental data indicate that both vitamin D and calcium exert anti-neoplastic effects in the large bowel. However, evidence from clinical trials is required to clarify the synergistic and independent chemo preventive effects of these two agents. Neoplastic polyps (adenomas) of the bowel are recognized pre-malignant lesions and effective endpoints for chemoprevention studies. Our research consortium has successfully conducted several chemoprevention trials using these endpoints, and in this resubmission, we propose a multi-centered randomized, double blind, partial factorial trial of the efficacy of calcium carbonate and vitamin D in preventing the recurrence of neoplastic polyps of the large bowel. The study will involve 10 clinical centers in North America, a pathology center and a coordinating center. Each subject will have had at least one large bowel adenoma removed in the 4 months prior to study entry, with complete colonoscopic visualization of the colorectal mucosa and no known polyps remaining in the bowel. Participants will agree to avoid taking study agents outside the trial and will initially be observed in a 3month placebo run-in period during which suitability for the study will be assessed. Suitable subjects will be randomized in a 2 x 2 factorial manner to calcium carbonate (1200 mg calcium/day), vitamin D (1000 IU/day), both agents, or placebo. Since many women may decline to forgo calcium supplementation, we will offer women the choice of being randomized to calcium alone or calcium plus vitamin D. Colonoscopic followup will occur at either 3 years or 5 years after the qualifying exam, as planned by each subject's physician. As safety measures, serum calcium, creatinine and 25-(OH) vitamin

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D levels will be obtained at baseline, and 1 year and 3 years after randomization. We anticipate enrolling about 2456 participants to reach a total of 1966 randomized subjects. Under conservative assumptions regarding event rates and study conduct, we will have greater than 89 percent power to detect a 20 percent reduction in adenoma recurrence with vitamin D versus placebo, and 85 percent power to detect a 25 percent reduction in recurrence with calcium plus vitamin D versus calcium alone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONFERENCE ON NUCLEAR RECEPTOR SUPERFAMILY Principal Investigator & Institution: Mangelsdorf, David J.; Professor; Keystone Symposia Drawer 1630, 221 Summit Pl #272 Silverthorne, Co 80498 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: (provided by applicant): Nuclear receptors belong to a highly conserved superfamily of transducers that process extracellular signals into gene expression responses during development, differentiation, reproduction and intermediary metabolism in all vertebrates and many invertebrates. These receptors act as transcriptional regulators and respond to lipophilic ligands, such as steroid and thyroid hormones, retinoids, vitamin D, oxysterols, bile acids and certain fatty acids. The family also includes a number of orphan receptors whose ligands and biological functions are currently being elucidated. Because of their unique ability to specifically regulate so many cellular functions, nuclear receptors have become important drug targets for numerous medical applications, including endocrine and metabolic disorders, hypertension, cancer, inflammation, and reproductive functions. Of particular interest is the role of a number of these receptors in diabetes, obesity, and other "so-called Syndrome X" disorders. This meting will bring together leading experts, as well as younger investigators and trainees, in a manner that integrates the latest on-going and future research in this field. Present challenges that will be addressed include 1) elucidating the three dimensional structure of multiprotein-receptor complexes, 2) characterizing the molecular mechanisms by which nuclear receptors and their coregulators modulate target gene expression, 3) genetically dissecting receptormediated physiological functions during development and postnatal life through conditional somatic mutagenesis, 4) identifying ligands and physiological roles for orphan receptors, 5) utilizing rational ligand design and the use of functional genomics to characterize receptor-regulated gene networks and develop new technologies to aid in drug discovery. By capturing, the intensity of the remarkable progress that is now being made in the nuclear receptor field, the goal of this meeting is to send participants back to their academic and industrial laboratories with an advanced understanding of this rapidly moving field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY & GENETIC CONTRIBUTIONS TO INTESTINAL TUMORIGENE Principal Investigator & Institution: Edelmann, Winfried; Associate Professor; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Project 1 is fundamental to the overall program. In this project, we will develop a matrix of data that defines how the major nutritional and genetic factors responsible for colonic cancer interact to alter intestinal homeostasis and probability of tumor formation. We will use three mouse genetic models: two already

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established and well characterized by us - the Apc1638 and the Muc2 mouse - and a third under construction, the Msh2G674S mutant mouse. Each of these will be compared to wild-type mice. Each model will be maintained on control AIN76A diet as well as a new western style high risk diet (nwdiet#1) that is sufficient to induce premalignant changes and tumor formation in wild-type mice - a diet high in fat and phosphate, low in calcium, vitamin D, choline, methionine and folate. Additional groups will consist of wild-type mice and each of the genetic models maintained on the nwdiet#1 with calcium and vitamin D reconstituted back to control levels, and for the Apc1638 mice and wild type mice, groups in which each of the other constituents of the nwdiet#1 will be reconstituted individually. The primary endpoint is tumor formation, with detailed, standardized analysis also carried out by the Histopathology Core to evaluate alterations in cell proliferation, apoptosis, lineage specific differentiation, and cell migration. The Genomics Core will perform microarray analysis utilizing RNA from each of four mice in each dietary/genetic group. Microarray analysis of the wild-type mice maintained on the control and nwdiet#1, as well as the nwdiet#1 with each component added back, has already been completed. The arrays are 27,000 member mouse cDNA arrays fabricated by the Albert Einstein Core Microarray facility, and the methodology for generation and analysis of the data has been well-established in our group. These data will be analyzed by the Genomics and the Biostatistics Cores in collaboration, and altered expression of important sequences confirmed through a combination of Real-Time PCR, laser capture microdissection and related methodologies in the Histopathology Core. The data will be fundamental in identifying genes and pathways that are modified by genetic and/or dietary factors in establishing relative risk for tumor formation, and the analysis will be instructed by microarray data bases we have already developed (published and unpublished) that dissect intestinal cell maturation pathways. These data will be highly interactive in interpreting similar data to be generated from biopsies of patients in Project 3. The data will also be integrated with data to be generated by the Genomics Core on genome wide alterations in methylation, to determine the extent to which altered gene expression is dependent upon altered locus methylation, and to identify subsets of genes regulated in this manner. Sequences identified in this Project will be prioritized for application of unique technological resources in the Genomics Core for functional studies, utilizing methods of Imaging of Transcription Sites in situ, and high-throughput Structural Proteomics. Finally, the tissue from the mice in this Project will be banked by the Histopathology Core. The tissues will be distributed to Project 2 for studies on the role of the ?-cateninTcf -- c-myc/cyclin D1/cdk4 -- p21/p27 pathway, and its intersections with machinery of the cell cycle, and investigation of a novel method of regulation of c-myc transcription by nutritional factors. The tissue is also used by the Histopathology Core for the generation of Tissue Arrays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF VITAMIN D AND CALCIUM ON BONE IN PEDIATRIC HIV Principal Investigator & Institution: Arpadi, Stephen M.; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, Ny 10019 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): We have recently observed that HIV-infected children, living in an urban setting in the northeastern United States, have decreased bone mass compared to healthy children. As childhood and adolescence are the critical periods during life for skeletal development and, as it is widely recognized that optimal

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bone mass accretion during childhood and adolescence may prevent osteoporosis later in life, this observation has serious implications for future risk of osteoporosis and fractures in HIV-infected children. While Highly Active Antiretroviral Treatment (HAART) has been implicated in the etiology of the skeletal demineralization in adults, it remains possible that other factors important for skeletal health, such as vitamin D deficiency, could contribute to or exacerbate bone loss in HIV-infected children. In this regard, we have found that 50% of a small group of HIV-infected children have deficient or insufficient body stores of vitamin D, as measured by serum 25-hydroxyvitamin D levels below 20 ng/ml. The central hypotheses of this proposal are that the prevalence of vitamin D deficiency and insufficiency is increased in HIV-infected children receiving HAART and is related to the decreased bone mass observed in these children. We also hypothesize that supplementation with vitamin D and the recommended daily allowance of calcium will improve bone mineral accrual in these patients, as it does in healthy individuals. We will test these hypotheses in 1. a crosssectional study comparing HIV-infected and healthy children and adolescents with respect to relationships between HIV-infection, vitamin D status, and bone mass, and in 2. a twoyear randomized, controlled clinical trial in which the effects of vitamin D and calcium supplementation on bone mass accrual are compared to placebo in HIV-infected children and adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF OVARIAN CANCER:NEW HYPOTHESES Principal Investigator & Institution: Rossing, Mary A.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Much of the previous epidemiologic research on ovarian cancer has been conducted within the conceptual with conceptual framework of the ovulation and gonadotropin. However, additional mechanisms must be operative to account for epidemiologic findings regarding this disease. In this study, we will address the hypothesis that progesterone reduces risk of epithelial ovarian cancer. We will examine the relation of exogenous progestins administered as a component of hormone replacement therapy (HRT) with disease risk. We will further assess whether sunlight and dietary sources of vitamin D influence risk. The study will contribute to a better understanding of pathogenic mechanisms of epithelial ovarian cancer, and may provide information leading to new means of reducing the occurrence of this disease. We propose to conduct a population-based, case-control study of epithelial ovarian cancer among women aged 35-74 years residing in thirteen counties of Washington State. Cases will be identified through a population-based cancer registry operating as part of the Surveillance, Epidemiology and End Results Program. Controls will be identified through random digit telephone dialing, and will be selected to be similar in age and area of residence to cases. In-person interviews will be conducted and blood samples will be collected. The findings of this study will have appreciable public health importance. Study of the impact of different HRT regimens, particularly estrogen/progestin combinations, on ovarian cancer risk has been deemed an urgent task for research. Recent calls for reappraisals of the risk/benefit ratio of unopposed estrogen and combined estrogen/progestin HRT highlight the need to understand the relation of these medications with ovarian cancer risk, and to incorporate this knowledge into risk/benefit considerations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EVALUATION OF VITAMIN D REQUIREMENTS DURING PREGNANCY Principal Investigator & Institution: Hollis, Bruce W.; Professor; Pediatrics; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The prevalence of hypovitaminosis D in reproductive age African-American women occurs at a rate of >40%. Two factors have contributed to this public health problem: an inadequate DRI for vitamin D and avoidance of sun exposure/use of sunscreen. This startling rate of hypovitaminosis D requires that the DRI for vitamin D in pregnancy be evaluated in a detailed manner. The Cochrane Library (2002) released a report stating that there is insufficient data to evaluate the effects of vitamin D supplementation during pregnancy. Recently, the safety of prolonged supplementation with up to 25x's DRI (10,000 IU/day) was demonstrated in nonpregnant adults. It is essential to determine what dose of vitamin D is required to eliminate hypovitaminosis D during pregnancy and provide the fetus/neonate with adequate vitamin D stores during development and growth, particularly in darkly pigmented individuals. The aim of this research proposal, then, is to determine the efficacy, effectiveness, and safety of maternal vitamin D supplementation (as a function of ethnicity and UV exposure) in the prevention of hypovitaminosis D in the pregnant mother and her fetus/neonate. We hypothesize that darkly pigmented mothers will require substantially higher oral supplementation with vitamin D to eliminate hypovitaminosis D as compared to their Caucasian counterparts. We propose a comprehensive clinical trial to test our hypothesis. Mothers at 12 weeks' gestation will be randomized to one of three vitamin D treatment groups: (1) Control, 400-, (2) 2,000-, or (3) 4,000 IU/day to be continued throughout pregnancy. Calcium and vitamin D homeostasis and skeletal remodeling in mother will be monitored closely throughout pregnancy. Bone density of mother will be measured at 12 weeks' gestation and one-month postpartum. Follow-up growth and skeletal integrity assessments of the infant will be performed at birth, 1, 6 and 12 months stratified by infant feeding regime. Through these proposed studies, the prevalence of hypovitaminosis D among mothers, their developing fetuses and neonates, and the utility of maternal therapeutic intervention with vitamin D for both mother and fetus/infant will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FAT REDUCTION, HRT USE AND BENIGN BREAST DISEASE RISK Principal Investigator & Institution: Rohan, Thomas E.; Professor and Chair; Epidemiology & Population Health; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 22-JUL-1998; Project End 31-JUL-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FLUORIDE AND OTHER FACTORS IN CHILDHOOD BONE DEVELOPMENT Principal Investigator & Institution: Levy, Steven M.; Professor; Prev and Community Dentistry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-APR-1998; Project End 31-DEC-2007

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Summary: (provided by application): Although the link between skeletal development in childhood and bone health later in life is increasingly well established, much remains to be learned about the determinants of bone development during childhood and how they contribute to risk of osteoporosis and bone fracture. This is, in part, because relatively few studies have longitudinally assessed bone development and mineral accretion in childhood. Even for well-known dietary factors such as fluoride, calcium, and vitamin D, no large cohort of children has been followed from birth through adolescence. The objective of our current application is to extend our ongoing longitudinal study into adolescence. Currently in its 5th year, our study is a broad investigation of the effects of key dietary factors, physical activity, candidate gene polymorphisms and parental information dual-energy X-ray absorptiometry (DXA), diet, physical activity and candidate genes) on important endpoints that include periodic DXA bone measures. Age 5 bone and physical activity assessments (n=470) were conducted and age 8 assessments are in progress (n=190 so far). Analyses thus far indicate age 5 bone measures are positively associated with height and weight, physical activity, COL1A2 and osteocalcin gene polymorphisms, fluoride, calcium and vitamin D. The overall objective of this renewal is to continue longitudinal assessment through the critical years of puberty. DXA analyses (including Hip Structural Analysis (HSA)) and peripheral quantitative computed tomography (pQCT) will be used to assess bone measures at ages 11 and 13. Dietary and physical activity questionnaire and accelerometry data will be collected, additional candidate gene analyses undertaken, and sexual maturation assessed. Bone measures will be analyzed cross-sectionally (ages 8, 11, and 13) and longitudinally (ages 5 to 13), and related to children's demographic, anthropometric, fluoride and other dietary, physical activity, sexual maturity, and genetic factors. An important focus will be statistical analysis of gene-environment interaction effects (e.g., calcium intake and vitamin D receptor genotype) and correlation with parental genotypes and bone measures. Continued study of this cohort with longitudinal dietary data collected from birth provides a unique opportunity to reveal major insights into the relative importance of modifiable and non-modifiable factors on bone development during childhood and adolescence, with implications for prevention of osteoporosis and bone fractures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY Principal Investigator & Institution: Giuliano, Anna R.; Associate Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract) The incidence of breast and endometrial cancers varies almost three-fold between non-Hispanic white populations and Native American and Hispanic populations living in the 4-Corners area of the United States (Arizona, New Mexico, Colorado, and Utah). Interestingly, although American Indian and Hispanic women have higher prevalences of many risk factors for breast and endometrial cancer identified in non-Hispanic white women (e.g., obesity, low levels of vigorous physical activity, low intakes of fruits and vegetables, high rates of insulin resistance) they have lower cancer incidence rates. In this study the investigators focus on the metabolic factors of obesity/weight changes and indicators of insulin status as they relate to breast and endometrial cancers. Obesity is associated both with estrogen and insulin by two interrelated disease pathways. Insulin may influence cancer risk directly through its effects on insulin-like growth factor (IGF) and its binding proteins (IGFBPs) and well as indirectly through its effect on estrogen levels. The investigators

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propose focusing on the insulin pathway because of the high levels of insulin pathway dysfunction in this population. A multi-center case-control study is proposed that targets women living in the 4-Corners area; the study will consist of a 2.5 hour in-person interview and a blood draw. Over a three-year case ascertainment period, the study will enroll 3000 breast cancer cases, 450 endometrial cancer cases and 3000 controls, half of whom will be Hispanic/Native American and half of whom will be non-Hispanic white women between the ages of 25 and 79. Molecular variants of genes that influence obesity and insulin (androgen receptor gene (AR), vitamin D receptor gene(VDR), insulin receptor (ADRB3)) will be examined both independently and in conjunction with metabolic factors to determine differences in genetic susceptibility in the population. Because of the diverse population (Hispanics, Native American, and non-Hispanic white women), the investigators propose to evaluate ethnic background and genetic admixture in relationship to gene markers, environmental factors, and breast and endometrial cancer risk. Genetic admixture (Ameridian to European genetic mixture) is a novel and innovative way to study the continuum of ethnic diversity. C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOUR-CORNERS BREAST CANCER STUDY Principal Investigator & Institution: Byers, Tim E.; Professor of Preventive Medicine; Preventive Med and Biometrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract) The incidence of breast and endometrial cancers varies almost three-fold between non-Hispanic white populations and Native American and Hispanic populations living in the 4-Corners area of the United States (Arizona, New Mexico, Colorado, and Utah). Interestingly, although American Indian and Hispanic women have higher prevalences of many risk factors for breast and endometrial cancer identified in non-Hispanic white women (e.g., obesity, low levels of vigorous physical activity, low intakes of fruits and vegetables, high rates of insulin resistance) they have lower cancer incidence rates. In this study the investigators focus on the metabolic factors of obesity/weight changes and indicators of insulin status as they relate to breast and endometrial cancers. Obesity is associated both with estrogen and insulin by two interrelated disease pathways. Insulin may influence cancer risk directly through its effects on insulin-like growth factor (IGF) and its binding proteins (IGFBPs) and well as indirectly through its effect on estrogen levels. The investigators propose focusing on the insulin pathway because of the high levels of insulin pathway dysfunction in this population. A multi-center case-control study is proposed that targets women living in the 4-Corners area; the study will consist of a 2.5 hour in-person interview and a blood draw. Over a three-year case ascertainment period, the study will enroll 3000 breast cancer cases, 450 endometrial cancer cases and 3000 controls, half of whom will be Hispanic/Native American and half of whom will be non-Hispanic white women between the ages of 25 and 79. Molecular variants of genes that influence obesity and insulin (androgen receptor gene (AR), vitamin D receptor gene(VDR), insulin receptor (ADRB3)) will be examined both independently and in conjunction with metabolic factors to determine differences in genetic susceptibility in the population. Because of the diverse population (Hispanics, Native American, and non-Hispanic white women), the investigators propose to evaluate ethnic background and genetic admixture in relationship to gene markers, environmental factors, and breast and

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endometrial cancer risk. Genetic admixture (Ameridian to European genetic mixture) is a novel and innovative way to study the continuum of ethnic diversity. C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF THE HAIRLESS PROTEIN Principal Investigator & Institution: Christiano, Angela M.; Associate Professor; Dermatology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 24-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) - In recent years, significant progress has been achieved in the understanding of the morphogenic aspects of hair follicle biology, nevertheless, the cellular, molecular and genetic aspects of hair growth control remain largely unknown, Our previous studies implicate the mouse hairless (hr) gene as a key factor in coordinating basic cellular processes during hair follicle catagen, including club hair formation, maintenance of dermal papilla-epithelial integrity, inner root sheath disintegration, and particularly, keratinocyte apoptosis in the hair matrix cells. In the hair follicle, hairless appears to function in the cellular transition to the first adult hair cycle. In its absence, in hairless (hr/hr) or rhino (rh/rh) mice, hair growth completely ceases, a new hair is never induced, and the result is a complete form of inherited atrichia. We have established that the disorder papular atrichia represents the human counterpart of the hairless and rhino mouse phenotypes, resulting from mutations in the hairless gene. However, at the molecular and cellular level, the mechanism(s) of function of the hairless protein remains largely unknown. Hairless is a single zinc-finger protein which is thought to function as a putative transcription factor. We have recently shown unequivocally that hairless is localized to the nucleus, and interestingly, that it is associated with the nuclear matrix. Protein analysis software has identified three LXXLL motifs, known as NR (nuclear receptor) boxes, which are signatures of the transcriptional coactivator family of proteins. We have compiled several lines of new evidence which implicate hairless in a pathway of genes regulated by the vitamin D receptor (VDR). These include the clinical and histological similarities between hairless mice and both VDR and retinoid X receptor (RXRa) null mice. In addition, we provide evidence that the human papular atrichia is clinically and histologically indistinguishable from vitamin D dependent rickets, with mutations in the VDR. Finally, we have identified a putative target pathway for hairless regulation which involves the upregulation of ornithine decarboxylase. We have combined our preliminary studies with several emerging lines of biological data to formulate a hypothesis which asks three questions. First, is hairless a DNA-binding protein, and if yes, what is its signature sequence? Secondly, is hairless a transcriptional coactivator, and if yes, what are its interaction partners? Finally, what are the downstream targets of hairless gene regulation? We anticipate that this approach will allow us to gain novel insights into the function of the hairless protein for the first time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL ROLE OF CAT1 AND CALBINDIN D IN CA TRANSPORT Principal Investigator & Institution: Wood, Richard J.; Associate Professor; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2006

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Summary: (provided by applicant): Absorbing too little calcium (Ca) in the intestine can be a risk factor for negative Ca balance and the development of osteoporosis. An important gap in our knowledge is that the molecular determinants of Ca influx into the enterocyte and transcellular Ca transport have not been unambiguously identified. This lack of knowledge limits the development of specifically targeted therapeutic agents to manipulate Ca absorption. The long-range goal of our research program is to identify the molecular factors responsible for age-related calcium malabsorption, and to target the development of safe and effective therapeutic agents that can modulate active calcium absorption. The recent discovery of the CaT1 (also known as ECaC2 and TRPV6) gene and the demonstration that its protein product functions in non-intestinal cells as a membrane Ca transporter, and our recent report that the expression of CaT1 in the Caco-2 human intestinal cell line is regulated by 1,25-dihydroxyvitamin D, offers an exciting new opportunity to further knowledge of the molecular mechanisms of vitamin D-mediated intestinal Ca absorption. We have two specific aims in this proposal (1) to establish the role of CaT1 and calbindin D in vitamin D-mediated calcium transport and (2) to identify to what extent CaT1 expression is a modulator of the rapid non-genomic vitamin D response in the enterocyte. We will determine the functional role of these proteins in the enterocyte by using Caco-2 cells transfected with sense and antisense CaT1 and calbindin D cDNA to alter the level of these proteins independently of vitamin D. The central hypothesis of our first research aim is that CaT1 acts as the primary gatekeeper of intestinal Ca absorption by controlling, under regulation by 1,25dihydroxyvitamin D, the rate of Ca entry across the apical brush border membrane of the enterocyte. The cytosolic vitamin D-dependent calbindin D acts in concert with CaT1 as both intracellular buffer and transporter, delivering Ca that has crossed the brush border membrane to the basolateral membrane of the enterocyte for Ca exit into the blood. We hypothesize in our second research aim that the CaT1 molecule either is responsible for or modulates the rapid 'non-genomic' response to 1,25dihydroxyvitamin D in Caco-2 cells by determining the rate of Ca entry into the enterocyte following 1,25-dihydroxyvitamin D treatment and thereby modulating the rise of free intracellular Ca and subsequent downstream activation of protein kinase C and phospholipase D. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER DIFFERENCES IN OSTEOPOROSIS Principal Investigator & Institution: Barrett-Connor, Elizabeth L.; Professor and Chair; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 01-AUG-1987; Project End 31-MAY-2003 Summary: This is a proposal to extend the Rancho Bernardo Study (RBS) of osteoporosis in order to prospectively examine sex specific rates and risk factors for bone loss and fracture (clinical and vertebral) in older adults. Nearly 1500 men and women aged 55 and older were studied in 1988- 1991 and again in 1992-1995 under a MERIT award, when they were characterized for multiple behavioral, biological and genetic risk factors for osteoporosis and had measurements of bone mineral density (BMD) at the hip and spine obtained four years apart. RBS is the largest prospective community-based study of osteoporosis in the United States in which men and women were studied concurrently using dual energy x-ray absorptiometry (DEXA). Work to date shows striking similarities in accelerated bone loss in the older men and women (greater than or equal to 75 years of age) over four years, and striking differences in the association of BMD with diabetes, insulin IGF-1, and serum testosterone. The cause of gender

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differences (and their absence) can provide new insights into the etiology, prevention and treatment of osteoporosis in both men and women. In the present study, 550 men and 650 women (>60% aged 70+ years) will have repeat evaluations for selected risk factors and bone turnover markers, repeated BMD measures at the hip and spine; repeat radiographs of the thoracic and lumbar spine; continued follow-up for new clinical fractures; reassessment of functional status, quality of life and fall- related comorbidities (including vision, cognition, and muscle strength); and first time evaluation of 25 OH vitamin D; 1, 25 (OH)/2 vitamin D, intact parathyroid hormone, and selected measures of bone size and geometry. This study was designed to provide (1) measures of BMD over a 10 year interval, necessary to determine the timing, frequency and antecedents of accelerated bone loss in both men and women, and (2) continued followup for fractures, necessary to provide adequate numbers of vertebral fractures and clinical fractures to determine fracture risk, risk factors, and consequences in both sexes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE-ENVIRONMENT INTERACTION IN PROSTATE CANCER Principal Investigator & Institution: Rybicki, Benjamin A.; Associate Professor and Senior Research; Biostatistics and Epidemiology; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from applicant's abstract): Prostate carcinogenesis likely involves a complex interplay between inherited genetic susceptibility and exogenous and endogenous exposures. Based on our current understanding of prostate carcinogenesis, we propose a hybrid case-only/case-control study designed to measure the joint effects of putative genetic and environmental risk factors. We plan to enroll 440 incident prostate cancer cases under age 70 and 220 race and age frequency-matched healthy controls. This study will be carried out in a population evenly divided between Caucasians and African-Americans, so that race-specific risk factors and interactions can be identified. The main goals of our study are: 1) to determine whether selected occupational (i.e., cadmium, zinc and polycyclic hydrocarbons), environmental (i.e., diet, ultraviolet radiation), lifestyle (i.e., physical activity) and genetic (i.e., CYP17, CYP3A4, GSTP1, SRD5A2, vitamin D receptor, androgen receptor, metallothionein 2A, HSD3B2polyhmorphisms) risk factors are associated with increased risk for prostate cancer; and 2) to test combinations of the above genetic and environmental risk factors for putative gene-environment and gene-gene interactions based on their posited role in prostate carcinogenesis. The inclusion of controls in our study design will allow us to estimate main effects and test whether genetic and environmental risk factors are independent. If the latter is true, then we can use our larger case sample to test for specific gene-environment interactions based on biologically plausible scenarios. The analysis will be conducted using log-linear models, which uniquely allow us to include or exclude control data depending upon our specific analytic goals (e.g., estimation of main effects vs. interaction terms). This study will be the first known effort specifically designed to test for gene-environmental interaction in prostate carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF PROSTATE CANCER RISK & AGRESSIVENESS Principal Investigator & Institution: Casey, Graham; Associate; Molecular Medicine; Cleveland Clinic Lerner Col/Med-Cwru Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 31-AUG-2008

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Summary: (provided by applicant): We hypothesize that multiple genes are involved in risk of prostate cancer and tumor aggressiveness and that many of these genetic risk factors will be represented by low penetrance gene mutations, each accounting for a small effect on risk. We propose to build upon two promising areas of our research program concerned with the influence of genes on prostate cancer risk and tumor aggressiveness. We have localized prostate tumor aggressiveness genes to 7q32-q33 and 19q13.1 through whole genome linkage analysis of sib pairs and loss of heterozygosity studies. We have identified a strong candidate, podocalyxin (PODXL), on 7q32-q33 in which in-frame deletions and SNPs independently are associated with markers of tumor aggressiveness. We will also build upon our studies investigating the impact of single nucleotide polymorphisms (SNPs) in candidate genes involved in metabolic pathways involved in prostate growth on prostate cancer risk and tumor aggressiveness. Thus our Specific Aims are: Specific Aim 1: To further characterize candidate prostate tumor aggressiveness loci identified through whole genome linkage analysis. We will determine whether PODXL functions as a prostate tumor aggressiveness gene by developing stable transfectants expressing wild-type or variant-containing PODXL and assessing their effect on in vitro and in vivo growth of prostate cancer cells. We will also determine PODXL expression in prostate tumors by in situ hybridization and immunohistochemical staining using tissue microarrays. We will further pursue the identification of the 19q13.1 aggressiveness gene using complementary approaches, including positional cloning methods and use of the public Human Genome Project (HGP) and Celera databases. The relationship between the 19q13.1 candidate gene(s) and prostate tumor aggressiveness will be evaluated by mutation analyses followed by association studies. Candidates will be further evaluated by in situ hybridization and immunohistochemical staining. Specific Aim 2: To determine the impact of single nucleotide polymorphisms (SNPs) in candidate genes on prostate cancer risk and tumor aggressiveness. We will study SNPs in candidate genes involved in 1) vitamin D metabolism (vitamin D receptor, 1-alpha-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24)), 2) insulin-like growth factor signaling (IGFBP-3), 3) folate metabolism (5,10Methylene-tetrahydrofolate reductase (MTHFR) and Methionine Synthase (MTR)), and 4) steroid hormone metabolism (CYP3A7). For SNP association studies, we will employ a fully recruited population consisting of 943 men in 431 families with at least one brother affected with prostate cancer. Epidemiologic and clinical data have been collected, as well as biospecimens and banked DNA. The relationship between these genetic factors and prostate cancer risk and aggressiveness will be statistically evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH FACTORS AND COLON CANCER Principal Investigator & Institution: Slattery, Martha L.; Professor; Family and Preventive Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-AUG-2006 Summary: Cell growth and proliferation are central to carcinogenesis. Scientific evidence that growth hormones, and genetic variants that influence these growth hormones, are importantly related to colorectal cancer is increasing. Furthermore, insulin and insulin-like growth factors (IGF), growth hormones that appear to be important for colorectal cancer, are influenced by previously identified risk factors for colorectal cancer such as body size and physical activity. In this study we will use existing lifestyle and metabolic exposure data; known tumor mutational status of microsatellite instability and K-ras mutations; and available germline DNA from an

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incident colorectal cancer case-control study of approximately 3000 cases and 3000 controls to study how genetic variants that influence growth hormones and cell growth and proliferation relate to development of colorectal cancer and subsequent survival after diagnosis. The study focuses on genetic and environmental interaction. Specific genes examined are molecular variants of genes along insulin pathway, including the IGF1 gene, insulin- like growth factor binding protein-3 (IGFBP3), the insulin receptor substrate gene 1 (IRS-1), the insulin receptor substrate gene-2 (IRS-2); the peroxisome proliferator-activated receptor gamma gene (PPARgamma), apolipoprotein E gene (ApoE), and the vitamin D receptor gene (VDR). We hypothesize that these variants are associated with altered risk of colorectal cancer in conjunction with genetic, diet, and lifestyle factors. Specially, we hypothesize that molecular variants of IGF1, IGFBP3, IRS1, IRS-2, PPARgamma, ApoE, and VDR interact with dietary such as calcium, vitamin D, sugar, and glycemic index; sunshine exposure, physical activity, aspirin use, and body size to alter risk of colorectal cancer; that molecular variants of IGF1, IGFBP3, IRS1, IRS-2, PPARgamma, ApoE, and VDR are associated with specific types of mutations in tumors including microsatellite instability and K-ras mutations; and that molecular variants of IGF1, IGFBP3, IRS-1, IRS-2, PPARgamma, ApoE, and VDR are associated with survival after diagnosis. To test the hypothesis that these variants interact with dietary and other factors, it is necessary to have a large sample size, such as the one available. Molecular variants of these genes that are involved in the insulin and growth factor disease pathway will be determined. Statistical analyses will use logistic regression and survival methods. This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST AND VIRAL GENETIC VARIABILITY IN HBV CARRIERS Principal Investigator & Institution: Evans, Alison A.; Assistant Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: Chronic carriers of hepatitis B virus (HBV) are at increased risk for hepatocellular carcinoma (HCC). Worldwide, however, the risk of HCC and other adverse outcomes varies substantially both between and within populations of HBV carriers. The reasons for these differences in the natural history of infection are not known. Our analysis of cohort studies in three endemic populations have suggested that the long term maintenance of high-titer viremia (i.e., equal to or > 1 pg/ml) is an important predictor of HCC. The mechanism behind the maintenance of viremia is, however, not well understood although it is clear that the host immune response plays a key role. In this application, we focus on molecular variants of the virus itself and polymorphisms of human immunoregulatory genes as potential predictive or explanatory factors in maintenance of viremia. We will draw upon established prospective cohorts of chronic HBV carriers in China, West Africa, and AsianAmericans. Our preliminary data support a relationship between deletions in the C ORF of HBV and clearance of active viral replication. In the proposed project we will test this hypothesis and extend our studies of molecular variation of HBV by application of novel statistical methods to sequence data. We will also test the hypothesis that maintenance of HBV viremia is associated with polymorphisms of the vitamin D receptor (VDR) and tumor necrosis factor alpha (TNFalpha) promoter. Allele frequencies for polymorphisms of lesser-studied immunomodulatory genes in our

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cohorts will be estimated in order to develop hypotheses about their relationship to maintenance of viremia in HBV carriers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN CHEMOPREVENTION CLINICAL TRIALS AT THE ROCKEFELLER UNIVERSITY HOSPITAL Principal Investigator & Institution: Lipkin, Martin D.; Professor/Director; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Project 3 extends the investigations of nutritional modulation of gene expression and histopathology to human subjects. Experiments are carried out in the GCRC at Rockefeller University by a well-organized team of investigators. Subjects are recruited from a number of different registries, and used in crossover design studies to evaluate how individual nutritional factors can modulate profiles of gene expression in a rigorously controlled and monitored dietary environment. The first two protocols described compare: 1. high and low dietary calcium; 2. high dietary vitamin D on a high or low calcium background. Additional protocols will be developed based on the outcome of these studies, data from Project 1, and progress from a pilot project (Weber) that will develop a registry of genetically wellcharacterized subjects. Biopsies from subjects are evaluated by the Histopathology Core for alterations in cell proliferation, apoptosis, and lineage-specific differentiation. RNA is extracted for microarray analysis, using well established procedures, and a 27,000 member human cDNA array fabricated by the Albert Einstein Core facility. Analysis of the array data will be carried out by the Genomics and Biostatistics Cores, in collaboration, and will be instructed by the extensive data bases we will generate on nutritional - genetic interactions in mice in Project 1, and by microarray data bases we have already generated, both published and unpublished, that dissect pathways of cell intestinal cell maturation. Important changes in gene expression will be confirmed by a combination of Real-Time PCR and laser capture microdissection, and will be prioritized for pursuit of functional role by application of novel technologies in the Genomics Core, including imaging of transcription sites in situ and high-throughput structural proteomics. Core C will also use DNA from the biopsies and a highthroughput assay of genome-wide methylation to determine the extent to which alterations in gene expression are linked to altered locus methylation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: JUVENILE OSTEOPETROSIS: DBP-MAF, A NEW THERAPEUTIC AGENT Principal Investigator & Institution: Swamy, Narasimha Ms.; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, Ri 02905 Timing: Fiscal Year 2002; Project Start 21-MAY-2001; Project End 31-JAN-2004 Summary: Juvenile osteopetrosis is an inherited skeletal disorder resulting from reduced osteoclast-mediated bone resorption. Activation of osteoclasts is known to promote bone resorption and alleviate the disease and associated symptoms. Vitamin D-binding protein-macrophage activating factor (DBP-MAF) is a newly discovered osteoclast activator, which has shown therapeutic potential in animal models. An impaired osteoclast activity (leading to osteopetrosis) has been recently shown to be due to a generalized defect in enzymatic conversion of DBP (vitamin D binding protein) to DBPMAF by T- and B- lymphocytes in both humans and animal models. Infusions of ex vivo

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generated DBP-MAF has been shown to increase osteoclast mediated bone resorption in animal models. This warrants further research to evaluate the therapeutic potential of DBP-MAF human osteopetrosis. A clear understanding of the underlying mechanism of osteoclast activation by DBP-MAF in humans is necessary to develop DBP-MAF as a therapeutic agent for osteopetrosis. We propose to achieve this goal by (i) Systematic evaluation of DBP- MAF mediated activation of osteoclasts from normal and osteopetrotic subjects and (ii) Determining the functionality of DBP, osteoclasts and DBP-MAF from osteopetrotic children. The proposed research not only intends to gain an insight towards the cellular and/or molecular defects leading to an excessive accumulation of bone in osteopetrotic subjects, but also offers a unique opportunity of methodology development to determine the underlying defect in a given 'clinical case', which would lead to a better course of therapeutic options. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAGNESIUM DEFICIENCY: EFFECT ON BONE AND MINERAL Principal Investigator & Institution: Rude, Robert K.; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2005 Summary: The objective of this proposal is to increase our understanding of the role of magnesium (Mg) deficiency in the etiology of osteoporosis. While sex steroid deficiency is a major factor in postmenopausal osteoporosis, nutrition is also important. Dietary Mg intake has been associated with bone mass in aging and postmenopausal osteoporosis. Disorders in which Mg deficiency is common such as alcoholism, malabsorption syndrome and diabetes also have an increased risk of osteoporosis. The average dietary Mg intake in women is 68 percent of the RDA indicating that a large proportion of our population have substantial dietary Mg deficits. Severe Mg deficiency in the rat results in impaired bone growth, osteopenia and skeletal fragility. The level of dietary Mg intake that results in osteoporosis in rat or human is unknown. In our proposal, we will employ dietary Mg deprivation in the rat at 10 percent, 25 percent, and 50 percent of recommended nutrient requirement. This reduction in Mg intake reflects levels of dietary Mg inadequacy in our population. Our first specific aim is to determine the dietary intake that will result in Mg deficiency as assessed by bone Mg content. Another specific aim is directed at assessing the effect of these dietary Mg intakes on bone histology, histomorphometry and bone turnover; ie. at what level of Mg intake does osteoporosis occur and is it reflected by alteration in osteoblast and osteoclast activity. The mechanism for the previously observed osteoporosis in severe Mg deficiency is unclear but may involve systemic hormones or local factors regulating bone cell activity. Severe Mg deficiency in humans and rats result in low serum parathyroid hormone (PTH) and 1,25(OH)2-vitamin D which may contribute to reduced bone formation. We will quantify the effects of low Mg intake on calcium homeostasis by determining serum calcium, PTH and 1,25(OH)2-vitamin D levels. The cause of increased osteoclastic bone resorption in severe Mg deficiency is unclear. Cytokines can increase osteoclastic bone resorption and are implicated in postmenopausal osteoporosis. Mg deficiency in the rat results in an increase in serum substance P which in turn stimulates production of various cytokines. We will therefore measure serum substance P, TNFalpha, IL1beta, and IL6 in the Mg deficient rat and perform immunohistochemical staining of bone for these cytokines. Parallel studies will be performed in which a specific substance P receptor inhibitor will be administered to directly test whether generation of these cytokines are responsible for Mg deficiency-

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induced bone loss. These studies should substantiate our hypothesis that Mg depletion contributes to osteoporosis and provide mechanistic explanations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MAPPING AND CLONING PROSTATE CANCER PREDISPOSITION LOCI Principal Investigator & Institution: Cannon Albright, Lisa A.; Professor; Medical Informatics; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: The identification of prostate cancer predisposition genes has proven to be a challenge for the prostate research community. Although several predisposition loci have been identified, none of these localizations has led to gene isolation, and only one of these findings has been significantly validated (Neuhausen et al.,1999). In Utah we have very recently isolated the first prostate cancer predisposition gene (see Tavtigian et al, submitted, in Appendix), and some confirmatory evidence has already been observed (Rebbeck et al., submitted). During our over 10 years of prostate cancer research we have collected a resource of almost 300 high-risk prostate cancer pedigrees, with approximately 8,000 DNA samples stored. These significant prostate cancer resources and contributions are evidence of the importance of the Utah prostate cancer effort, which we hope to continue through this proposal. We have previously had NIH funding (1994- 1998), and funding through a partnership with Schering Plough (19972000); both have ended. Our collaboration with Myriad Genetics continues. We are in the process of finalizing a collaborative agreement between our group, Myriad Genetics, NIH and Johns Hopkins (letters of support will follow), that will result in an open exchange of data, results, and genomic and genetic resources from all groups, and which we hope will contribute significantly to prostate genetic research. This proposal supports the University of Utah high-risk pedigree collection and analysis, and some Myriad genotyping effort towards this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEMBRANE RECEPTOR FOR 1 ALPHA, 25(OH)2 - VITAMIN D3 Principal Investigator & Institution: Olivera, Christopher J.; Biochemistry; University of California Riverside 900 University Ave Riverside, Ca 92521 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Vitamin D is a prohormone for the daughter metabolite 1 alpha,25(OH)2D3, which is a steroid hormone. As a consequence of being highly conformationally flexible, la,25(OH)2D3 presents a wide variety of shapes to its cellular environment. This in turn allows the generation of a variety of biological responses by activation of signal transduction pathways via one or more receptors involved in the production of either classic genotropic transcription of genes and/or rapid non-geriotropic biological responses. The 1 alpha,25(OH)2D3-mediated transcription of genes has been well studied and it is known to regulate a variety of cells and tissues. Conversely, the non-genotropic responses being activated by 1alpha,25(OH)2D3 appear to be mediated by a different signal pathway since the time frame of these responses which occur from seconds to minutes contrary to the genotropic frame of hours. Additionally, these types of responses can be separated from each other using a variety of path or action-specific derived analogs for 1 alpha,25(OH)2D3. The relevance to this proposal occurs in the study of the latter mechanism, in which a putative membrane receptor is believed to be responsible for

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mediating these responses. Thus, I propose to isolate and biochemical characterize the protein(s) responsible of 1 a,25(OH)2D3-mediated nongenotropic responses in plasma membrane invaginations or vesicles called caveolae. In other systems, caveolae have been linked to other steroid mediated rapid responses in which receptors to the respective ligands were shown to reside. We aim to isolate and purify the proposed membrane receptor which selectively binds 1 a,25(OH)2D3 with high affinity. This followed by characterization of the protein, leading to cloning and expression to learn its biological properties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MISSING DATA, MEASUREMENT ERROR AND APPLICATIONS Principal Investigator & Institution: Wang, Ching-Yun; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 15-DEC-1997; Project End 31-MAY-2004 Summary: (Adapted from Investigator's Abstract) Missing or mismeasured regression variables are frequently encountered in the analysis of cancer research data. This problem is a major issue in dietary research, for example. The broad goal of this research is to develop statistical methods for data analysis in the presence of missing or mismeasured regression variables, and to apply these methods to epidemiologic and clinical studies. Specific areas of research include the following: 1) development of a nonparametric regression calibration method for Cox regression when validation data are available; 2) development of methods for Cox regression with reliability data; 3) development of methods for logistic regression analysis using conditional exposure mean for missing or mismeasured exposures; and 4) development of methods for characterizing associations between multiple variables. Asymptotic theory will be developed and simulation studies will be conducted. The methods will be applied to data from the Women's Health Initiative, a large disease prevention trial and observational study involving 164,500 women with the objective of evaluating the benefits and risks of dietary modification, hormone replacement therapy and supplementation with calcium and vitamin D on the overall health of postmenopausal women. The investigator states that the proposed methods will also accommodate twostage designs which are becoming popular in epidemiologic research and particular in genetic epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR INTOBAGONIANS

EPIDEMIOLOGY

OF

PROSTATE

CANCER

Principal Investigator & Institution: Bunker, Clareann H.; Assistant Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Preliminary prostate cancer screening data from the Afro- Caribbean population aged 50-79 on the Caribbean island of Tobago revealed a high rate (29 percent) of elevated PSA (greater than 4ng/ml). Of the 79 percent undergoing biopsy, 51 percent were diagnosed with prostate cancer. High incidence of prostate cancer has recently been reported among Afro-Caribbean Jamaicans. These data suggest that the elevated risk for prostate cancer, observed in African Americans, is present in other populations of West African descent. This strongly suggests that prostate cancer risk is influenced by genetic component(s) in combination with lifestyles/metabolic factors

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common across populations of African descent living in diverse environments. We propose to conduct a molecular epidemiology study of prostate cancer in the Tobago male population, aged 40-79 (n=5121), (92 percent of African descent). We are currently screening the population, aged 50-79 (n=3000) using serum (prostate specific antigen) PSA (greater than 4 ng/ml) and digital rectal exam (DRE). This proposed study will screen men aged 40-49 (n=1800) for elevated PSA (greater than 2ng/ml) or abnormal DRE, in addition to men aged 50-79. We expect to study 300 screening detected cases compared with 300 frequency age matched controls. We will determine whether variants in candidate genes related to sex hormone metabolism, growth factor, vitamin D, PSA transport and toxic substance metabolism, or to loci for familial prostate cancer of chromosomes 1 and X, are associated with prostate cancer, and whether gene frequencies differ from published studies of Caucasian and African American populations. Other molecular markers will include serum arachidonic acid and IGF-1 (for each, hypothesize high levels in cases). Bone mineral density, a surrogate for long term IGF-1 and sex hormone exposure, and central fat distribution will be measured (for each, hypothesize elevated in cases). This large, very cooperative, male population of West African descent, provides a unique opportunity for the study of prostate cancer risk because prostate cancer risk is high, the population is primarily of West African descent, and there is less admixture than among African Americans. Understanding the contribution of environment, genetic and metabolic factors will lead to measures to reduce the risk for prostate cancer among men of West African descent in the U.S., the Caribbean and other geographic areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR REGULATION OF 1,25(OH)2D PRODUCTION Principal Investigator & Institution: Portale, Anthony A.; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted from the Applicant's Abstract): The overall objective of this proposal is to gain a detailed understanding of the molecular regulation of the synthesis of 1,25-dihydroxyvitamin D (1,25D). Although this steroid hormone plays a crucial role in calcium metabolism, bone growth, and tissue differentiation, little is known about the molecular mechanisms of regulation of its synthesis. The key quantitative regulatory step in the synthesis of 1,25D is its 1alpha-hydroxylation from its endogenous precursor, 25-hydroxyvitaminD (25(OH)D), catalyzed by the enzyme 25(OH)D-1alpha-hydroxylase (1-OHase). The 1-OHase is a mitochondrial cytochrome P450 enzyme similar to the steroidogenic enzymes in the adrenal and gonad. Dr. Portale's laboratory has recently cloned the cDNA and gene for the human 1alpha-hydroxylase enzyme, designated P450c1. They now propose to study the molecular mechanisms of regulation of 1,25D production, and specifically how PTH, phosphorus, and 1,25D regulate the synthesis of 1,25D. Production of 1,25D is disordered in acute and chronic renal failure, X-linked hypophosphatemic rickets, autosomal recessive vitamin D dependent rickets Type 1, renal Fanconi syndrome, and with advanced age. The proposed studies of the physiologic regulation of the 1-OHase at the molecular level will provide the basis for subsequent studies of the potential molecular mechanisms by which regulation of this enzyme is altered by aging and renal disease: 1) They will clone a cDNA for rodent P450c1 and raise antibodies to human P450c1 protein; 2) They will examine hormonal regulation of P450c1 mRNA and protein abundance in mice in vivo and in isolated mouse proximal tubules, in vitro, and determine if induced changes are mediated by transcriptional events. 3) Using immortalized human proximal tubule cells, they will

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study transcriptional regulation using functional assays of promoter/reporter constructs, and will examine protein/DNA interactions in the relevant regions by bandshift assays, UV-crosslinking, and Southwestern blotting to localize specific ciselements and their cognate DNA binding proteins; and 4) They will determine the tissue distribution of P450c1 mRNA and protein in kidney and will localize P4501 gene expression in microdissected rat nephron segments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER

MOLECULAR-NUTRIENT

INTERACTIONS

IN

INTESTINAL

Principal Investigator & Institution: Augenlicht, Leonard H.; Professor and Associate Director for Tra; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This application is submitted by the New York Colon Cancer Study Group (NYCCSG) investigators who have been exceptionally successful, individually and in collaboration, in studying genetic/molecular and dietary factors, and their interaction, in the development of intestinal cancer. This application brings powerful technologies at the Albert Einstein/Montefiore Cancer Center, the Strang Cancer Prevention Center at Rockefeller University, and the University of Nebraska School of Medicine, to the question of how a Western-style diet that mimics the major risk factors for colon cancer - high in fat and phosphate, low in calcium, vitamin D, choline, methionine, folate and fiber - interacts with genetic factors to increase probability of tumor formation in the intestinal tract. In project 1, novel mouse genetic models of intestinal cancer made at Einstein/Montefiore, including the Apc1636+/- mouse, the Muc2-/- mouse and a new mouse model with a point mutation that mimics a true human pathogenic allele, the Msh2G674S mouse, will be studied for modulation of cell maturation and tumor formation by the Western-style diet and the effects of partial reversal with calcium and vitamin D3. For the Apc1638 mouse, this will be extended to understanding the contribution of each component of the diet. Microarray analysis, utilizing a 27,000 member cDNA array, will establish a matrix of data, which defines the contributions of each dietary and each genetic component to the response, the underlying mechanisms, and how they interact on a molecular level. In Project 2, tissues from Project 1 will be utilized to specifically determine how the genetic and dietary factors, alone and in combination, recruit and modulate the b-catenin-Tcf -c-myc/cyclinD1 -- cdk4/p21/p27 pathway, and Augenlicht, L related signaling and cell cycle machinery. Moreover, we will extend our analysis of the utilization, as well as mechanisms, of a block to c-myc transcription, which may be a key to how some nutritional factors can modulate tumor formation. This will make use of novel transcriptional imaging methods developed at Einstein and used by collaborating investigators in this Program. Project 3 extends the work of Projects 1 and 2 to human subjects, who will be maintained in the Rockefeller General Clinical Research Center (GCRC) and fed diets in which defined components (e.g., calcium and vitamin D3) are modulated. Biopsies taken during, and at completion of cross-over design studies will permit us to dissect how specific dietary components modulate intestinal cell maturation, biomarkers and profiles of gene expression, and how this relates to the alterations by similar dietary components in the mouse models, and to extensive gene expression data bases we have already developed that dissect cell maturation pathways in colonic cells. The four cores are Administration, Histopathology, Genomics, and Biostatistics. The Histopathology Core has extensive experience and standardized methodologies, and also incorporates laser capture microdissection, Real-Time PCR

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analysis, and tissue arrays. The Genomics Core capitalizes on the Einstein Microarray Facility, which is at the forefront of development and implementation of methods of gene expression profiling, and the extensive experience the facility, and members of this program have with such analyses. Moreover, this Core also includes sophisticated and novel methodology for analysis of locus specific and genome wide DNA methylation, transcriptional imaging of multiple genes simultaneously in situ, and high-throughput structural proteomics for determination of three dimensional structure of sequences with particularly interesting profiles of expression, but of currently unknown function. The Biostatistics Core at the North Shore University Hospital has already participated with members of this program on another National Cancer Institute (NCI) supported program that makes extensive use of microarray analysis of gene expression. Finally, a Pilot Project Program will provide new technologies to the Cores and new projects to supplement those proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTER OSTEOARTHRITIS STUDY (MOST) Principal Investigator & Institution: Lewis, Cora Elizabeth.; Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and disease in the knee is a leading cause of disability. Most epidemiologic studies of knee OA have focused on radiographic disease, but symptomatic OA should be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting,kneeling, stair climbing, quadriceps weakness and proprioceptive deficits), boneand structural factors (bone density,bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a populationbased sample of men and women aged 50 to 79. We propose to recruit a communitybased sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High risk groups will include those who are overweight, those with knee symptoms or those with a history of knee injuries or operations. Subjects will be evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted and comprehensive study of persons with knee OA, or at high

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risk of disease, offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for prevention Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEGATIVE REGULATION OF GENE EXPRESSION BY VITAMIN D Principal Investigator & Institution: Koszewski, Nicholas J.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Parathyroid hormone (PTH) and calcitriol (1,25(OH)2D3) are key participants in the maintenance of calcium homeostasis in the body. Previous work has demonstrated that 1,25(OH)2D3, acting through its nuclear receptor (VDR), can directly suppress transcription of the PTH gene and DNA sequences that mediate this action have been identified. The broad objective of the proposed study is to elucidate the molecular basis for the effects of the steroid-receptor complex on suppressing PTH gene transcription. The hypothesis to be tested is that the transcriptional potential of the VDR complex is intrinsically coupled to the DNA sequence of the specific binding site. In this model, the DNA binding site acts as an allosteric effector to modulate the conformation of the VDR complex and thereby coordinate the ability of specific factors to associate with this complex to produce the desired transcriptional response. The proposed research will concentrate on a DNA sequence from the avian PTH (cPTH) gene previously characterized by the PI. The specific aims of the proposed study include to 1) examine conformational changes that occur in the receptor binding to this negative sequence versus other DNA sequences known to elicit positive transcriptional responses to 1,25(OH)2D3 and 2) identify proteins that interact with the VDR complex as it drives expression from the cPTH response element and characterize their capacity to mediate repression of gene transcription by the vitamin in biochemical assays. Conformational changes in receptor structure will be monitored by protease mapping experiments that contrast VDR complexes bound to repressor and enhancer sequences. DNA-bending and phasing array analyses will also be conducted to determine if complex binding to these sequences results in an altered ability to bend DNA or in the orientation of the DNA bend. Parallel studies will identify and characterize protein factors that associate with an intact VDR complex as it drives expression from the cPTH DNA element in a yeast one-hybrid screen. Cloned proteins identified from this screen will be analyzed for their ability to mediate interactions with both negative and positive DNA response elements in transient transfection studies, pull-down assays, DNA affinity chromatography experiments and electrophoretic mobility shift assays. Investigation of the factors involved in vitamin D-dependent repression of PTH gene transcription will make significant contributions to our overall understanding of the less well-studied area of negative gene transcription by nuclear proteins. Moreover, it will provide new opportunities for investigating the underlying causes to the resistance to 1,25(OH)2D3 observed in patients with secondary hyperparathyroidism associated with impaired renal function, with the possibility of devising treatment modalities that focus on the factors identified in this study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NONGENOMIC SIGNALING BY STEROIDS AT THE CELL MEMBRANE Principal Investigator & Institution: Hammes, Stephen R.; Assistant Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105

40

Vitamin D

Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): A longstanding question in steroid physiology is how steroids mediate nongenomic, or transcription-independent, effects. Examples of rapid, steroid-triggered nongenomic signaling are myriad, including estrogen-mediated up-regulation of nitric oxide synthase (NOS) in endothelial cells, vitamin D-induced calcium mobilization in osteosarcoma cells, and progesterone-induced maturation of frog and fish oocytes. These signaling events may mediate important biological functions such as blood vessel relaxation, bone metabolism, and fertilization. Unfortunately, most of these processes are part of complex biological systems that are difficult to manipulate in vitro, which presents a serious problem when trying to understand the biology behind them. This proposal uses the phenomenon of steroidinduced maturation of frog oocytes as an experimental model for studying nongenomic steroid signaling. The maturation of an oocyte refers to the meiotic stage at which an oocyte rests. "Immature" oocytes are arrested in prophase of meiosis I, while "mature" oocytes rest in metaphase II. Steroids induce this re-entry into the cell cycle via a transcription-independent process that appears to involve membrane bound classical steroid receptors and possibly signaling via G proteins. Although controversial, the primary physiological mediator of oocyte maturation in Xenopus appears to be the androgen, testosterone. This system offers many advantages in studying nongenomic signaling by steroids. Steroid-induced oocyte maturation is reproducible, easy to detect, and biologically relevant. Furthermore, oocytes are easily manipulated in vitro for protein expression and signaling studies. The aims of this proposal are: 1) to improve our knowledge of the early signaling pathways induced by steroids in oocytes, including the role of G proteins, in the maturation process; and 2) to elucidate the role of the classical androgen receptor in the maturation process. Understanding nongenomic steroid-induced signaling in oocytes should prove helpful in elucidating the mechanisms involved in other nongenomic signaling pathways and may lead to new insights toward controlling their associated biological processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL CONFORMATION-BASED NUCLEAR RECEPTOR ACTIVITY ASSAY Principal Investigator & Institution: Archdeacon, John; Active Motif, Llc 1914 Palomar Oaks Way, Ste 150 Carlsbad, Ca 920086510 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): The objective of this proposal is the development of novel methods for the study of the Class II Nuclear Receptors Thyroid hormone receptor (TR), Retinoic Acid Receptor (RAR), and Vitamin D3 Receptor (VDR). Like other members of the nuclear receptor superfamily, these transcription factors directly activate or repress target genes by binding to DNA response elements in the regulatory regions of target genes. A ligand-mediated conformational change in the nuclear receptor serves as the basic mechanism for switching gene repression to activation. Liganded receptors have a high affinity for proteins that activate transcription (coactivators), while un-liganded receptors have a high affinity for transcriptional repressors. Unlike many of the members of the nuclear receptor superfamily, unliganded TR, RAR, and VDR are not sequestered in the cytoplasm via an interaction with HSP90. In the presence or absence of ligand, these proteins are bound to their response elements on nuclear DNA as heterodimers with Retinoid X Receptor (RXR). In addition, there are no reliable post-translation modifications (such as acetylation or phosphorylation) associated with activation of these receptors. Thus, there are no

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currently available methods to rapidly quantify ligand-mediated conversion of TR, RAR, and VDR from transcription repressors to transcriptional activators. Recent studies have identified the peptide sequence (LXXLL) of the transcriptional activator SCR-1, which is responsible for this protein's ligand-dependent interaction with nuclear receptors. In this study, we will use this information to develop a peptide-based assay for the quantification of active-conformation receptors contained in nuclear extracts. Further, the peptide sequence (LXX(I/H)IXXX(I/L)) of the transcriptional repressor SMRT (silencing mediator for retinoid and thyroid receptors) responsible for its interaction with non-liganded nuclear receptor has been identified. We will use this peptide to develop an assay to quantify receptors that is in the non-activating conformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARATHYROID HORMONE AND OSTEOBLAST MITOGENESIS Principal Investigator & Institution: Luttrell, Louis M.; Associate Professor of Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Osteoblasts regulate the deposition of bone matrix protein and its subsequent mineralization. In situ, regulation of osteoblast proliferation, differentiation and function occurs via the complex interplay of extracellular signals mediated by steroid hormone and vitamin D receptors, receptor tyrosine kinases, and G protein-coupled receptors (GPCRs), such as those for parathyroid hormone (PTH) and prostaglandins. While it is clear that GPCRs transmit signals that are critical for the regulation of osteoblast metabolism, their significance as potential regulators of osteoblast growth and differentiation has only recently been appreciated. The broad goal of this research proposal is to determine how GPCRs regulate the growth and differentiation of osteoblasts through activation of the ERK mitogen-activated protein kinase (MAP) cascade, a key regulatory pathway in terms of both cell proliferation and differentiation. We provide preliminary data that demonstrate that GPCRs employ two novel mechanisms to direct the temporal and spatial activation of MAP kinases. First, matrix metalloprotease-mediated ectodomain shedding causes the release of autocrine ligands that induce "transactivation" of epidermal growth factor receptors (EGFRs). Second, beta-arrestins, proteins which bind to agonist-occupied GPCRs and uncouple them from their cognate G proteins, function as scaffolds for the component kinases of the ERK cascade and lead to the targeted activation of MAP kinase within specific cellular compartments. The first Aim of this proposal is to characterize the molecular mechanisms whereby PTH and prostaglandin receptors regulate the activity of MAP kinase cascades in osteoblasts. The second Aim is to determine the role of EGFR and beta-arrestin-dependent signals in regulating osteoblast proliferation, differentiation, and matrix production in vitro. These studies will employ osteoblastic cell lines and primary cultures of osteoblasts from mice in which EGFR or beta-arrestin function has been selectively inhibited. The third Aim of the proposal is to determine the role of EGFR and beta-arrestin-dependent signals in the control of anabolic bone metabolism by PTH in vivo. These studies will employ transgenic mouse models, in which betaarrestins have been knocked out by homologous recombination or EGFR function has been impaired through osteoblast-specific expression of a dominant inhibitory mutant EGFR. By increasing our understanding of the mechanisms of GPCR signaling in bone, these studies may permit the rational development of safe strategies for employing PTH analogues to modulate osteoblast number and/or function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Vitamin D

Project Title: PATHOGENESIS OF VITAMIN D REFRACTORY DISEASES Principal Investigator & Institution: Drezner, Marc K.; Professor; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-AUG-1980; Project End 31-AUG-2008 Summary: (provided by applicant): Recently, we reported cloning PHEX, the gene causal in the pathogenesis of XLH and potentially contributing to the regulation of P homeostasis and vitamin D metabolism. Whereas studies have clearly identified PHEX mutations as the genetic defect in XLH and documented inactivating mutations in affected subjects, the mechanism(s) by which these mutations influence bone mineralization, vitamin D metabolism and P transport remains unknown. Nevertheless, continued advances have provided the framework to improve our understanding of P balance and vitamin D metabolism, as well as the pathogenesis of XLH. These accomplishments should permit definition of the interrelationships between null mutations of PHEX, renal P wasting and 25(OH)D-1alpha-hydroxylase activity and the impact of these abnormalities on bone and cartilage mineralization. In the current application, we propose to investigate the factor(s) underlying the characteristic phenotypic abnormalities in the hyp-mouse and the dependency of disease expression on mutated Phex in the osteoblast/osteocyte. Using animals with transgenic overexpression of Npt2 in renal proximal convoluted tubules, we will determine the role of abnormal renal P transport and consequent hypophosphatemia in the aberrant bone mineralization and vitamin D metabolism of mutant mice. Studies of bone mineralization will encompass an investigation of P effects during embryogenesis, youth and adult life. Investigation of vitamin D metabolism will focus on the effects of normal renal P transport on 1,25(OH)2D production in adults. In parallel studies, we will use mice with conditional Phex knockout in osteoblasts/osteocytes to determine whether these cells are the physiologically relevant sites for the mutated gene. These investigations will explore the effects of abnormal Phex function in osteoblasts/osteocytes on bone mineralization, renal P transport and vitamin D metabolism. As a complement to these studies, we will perform experiments designed to further examine the abnormal vitamin D metabolism in hyp-mice, which is characterized by dissociation between mRNA expression and renal 25(OH)D-alphahydroxylase activity. We will emphasize exploring if diminished protein translation or increased protein turnover underlies the decreased enzyme function. Our studies are significant, as they will clarify the PHEX dependent aspects of the XLH phenotype, while enhancing our understanding of vitamin D metabolism and P homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PDGF ALVEOLIZATION

GENE

REGULATION

BY

VITAMINS

A

&

D

IN

Principal Investigator & Institution: Kaetzel, David M.; Pharmacology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-JUL-2004 Summary: The investigator proposes to assess the effect of RA, VitD, analogs, and dexamethasone individually or in combination on cell proliferation and expression of PDGFs and their receptors during lung development in vitro (Aim 1) and in vivo (Aim 2). This will include an evaluation of the effect of these treatments on alveolar formation and on lung function (Aim 2). Then, an analysis of the mechanisms regulating PDGF expression will be performed, aiming to characterize cis and trans elements potentially

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important on mediating transcriptional activation of the PDGF-A chain promoter during lung development (Aims 3 and 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEX FUNCTION IN OSTEOBLASTS Principal Investigator & Institution: Quarles, L Darryl.; Professor of Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 05-APR-1999; Project End 31-MAR-2004 Summary: X-linked hypophosphatemic rickets (XLH) is a dominant disorder caused by inactivating mutations of PEX, a novel endopeptidase of unknown function. The molecular/biochemical events that link loss-of-function mutations of PEX to impaired mineralization and phosphaturia in XLH are poorly understood. We have compelling data that osteoblasts are a physiologically relevant site of PEX expression. In addition, we have identified putative substrates for Pex in osteoblast cultures, including inhibitors of mineralization and renal tubular phosphate transport. These findings suggest that osteoblasts are directly involved in the pathogenesis of XLH. Our current goal is to advance our hypothesis that Pex in the mature osteoblast plays an important role in regulating mineralization of extracellular matrix and possibly phosphate homeostasis. Based on our recent isolation and cloning of the full-length Pex coding sequence from an osteoblast cDNA library, and our demonstration of an intrinsic mineralization defect in immortalized osteoblasts derived from the hyp-mouse homologue of XLH, it is possible for the first time to express recombinant Pex and study its function in a physiologically relevant model system. Our Specific Aims are to: (1) Characterize the structure and activity of recombinant Pex (rPex) and (2) Establish a cause and effect relationship between Pex mutations in osteoblasts and impaired mineralization of extracellular matrix. For the first aim, we will generate rPex protein and isolate synthetic peptide substrates by screening a random phage substrate library with rPex. These substrates will be used to investigate the activity of both wild-type and mutated Pex proteins in vitro and in osteoblast cultures. For the second aim, the function of Pex in osteoblasts will be examined in tissue cultures and in transgenic animals. Using retroviral mediated expression of Pex, we will overexpress wild-type Pex in hyp-mice osteoblast cultures to attempt correction of the mineralization defect in vitro. Using a complementary transgenic mouse approach, we will determine the ability of Pex expression in osteoblasts to rescue the HYP phenotype. We will achieve osteoblast-specific overexpression of the Pex transgene using the mouse osteocalcin promoter and evaluate whether the selective correction of the Pex abnormality in osteoblasts normalizes mineralization and phosphate homeostasis in hyp-mice. These studies will provide insights into the function of Pex in osteoblasts, explore the mechanisms whereby abnormalities of Pex lead to impaired mineralization and phosphaturia, and define the mechanism of dominant inheritance in XLH. These results are fundamental to the future development of drug and/or gene therapy, whose design is predicated upon an understanding of the role of the osteoblast in the pathogenesis of XLH and the importance of Pex in regulating osteoblast-mediated mineralization. The study of Pex may yield an entirely new view of mineral metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PLACENTAL CAROTENOIDS: METABOLISM AND DEVELOPMENT Principal Investigator & Institution: Rubin, Lewis P.; Professor; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, Ri 02905

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Vitamin D

Timing: Fiscal Year 2002; Project Start 27-JUN-2002; Project End 31-MAY-2007 Summary: (Provided By Applicant) Vitamin A (retinol) supplied by the mother to her fetus is essential for normal embryogenesis, fetal development, and neonatal survival. The major source of vitamin A in mammals is oxidative cleavage of the principal dietary provitamin A carotenoid, beta-carotene (betaC). Epidemiologic and animal investigations indicate betaC and other carotenoids have pregnancy-promoting actions. An intriguing finding is that several of these properties apparently are independent of provitamin A activity. In Preliminary Studies, we have shown that placental trophoblast metabolizes betaC to retinol via the principal betaC cleavage enzyme, betaC-15,15'dioxygenase (betaCDO). In addition, we have shown specific provitamin A and non-pro vitamin A carotenoids modulate placental growth and differentiation by actions on trophoblast gene expression. These observations have prompted the following experimental questions: (a) Does placental regulation of BetaC to retinoid metabolism serve a physiologic role akin to the placental enzymatic barrier functions which maintain intrauterine glucocorticoid and vitamin D homeostasis?; and (b) Do specific dietary carotenoids promote normal pregnancy by a combination of genomic and nongenomic events in uteroplacental target cells? This proposal addresses deficiencies of current understanding about nutritional regulation of intrauterine physiology. In order to characterize the cellular changes induced by carotenoids and to determine relevant molecular mechanisms, we will combine: well-characterized trophoblast cell culture models, systems for uniform delivery of bioavailable carotenoids over a wide concentration range, and biochemical and molecular biological analysis of carotenoid metabolism in intact cells and placental tissue. We will test the hypotheses: (a) Placental betaC-1 5,1 5'-dioxygenase (betaCDO) activity is the major (or sole) enzymatic route for fetal biotransformation to retinal, the precursor of retinoic acids. (b) Nutrient and hormonal regulation of placental betaCDO gene expression and enzyme activity modulate fetal exposure to potentially deleterious fluctuations of maternal vitamin A. We also will determine which specific carotenoids are important gestational agedependent regulators of placental gene expression and trophoblast proliferation, migration/invasiveness and survival. Finally, we will establish whether these biological activities require carotenoid conversion to retinoids or carotenoid antioxidant activities. These studies will provide new information about potentially critical aspects of intrauterine homeostasis. Consequently, this research will increase understanding and suggest interventional strategies for vitamin A deficiency in pregnancy, a major global public health problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISMS IN PROSTATE CANCER CARCINOGENESIS Principal Investigator & Institution: Everson, Richard; Internal Medicine; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 23-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): Incidence and mortality rates for prostate cancer among African-American men in Detroit are among the highest in the world. The extraordinary impact of this disease on our community has led to the development of several large NIH funded research studies of prostate cancer. Two of these studies focus on the etiology of prostate cancer. One, a study of the frequency and extent of prostatic intraepithelial neoplasia and latent prostate cancer at autopsy of sudden death victims, documents frequencies of the earliest microscopic precursors of prostate cancer. The second, a population-based case-control study, characterizes determinants of clinical disease. The autopsy study includes over 600 subjects cases and

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the case-control study over 700 cases and an equivalent number of controls. Both include a high proportion of African-American men. Although extensive, these studies do not address the role of genetic susceptibility in the etiology of prostate cancer. Recent studies reporting associations between genetic polymorphisms and prostate cancer risk provide important opportunities for determining the etiology of prostate cancer using the data and tissue resources from our ongoing studies. The polymorphisms include factors governing the biological effects of androgens, (polymorphisms in the androgen receptor gene itself and enzymes determining the synthesis and degradation of active forms of testosterone) and the biological effectiveness of vitamin D (polymorphisms in the receptor). Analysis of specimens from our ongoing studies will allow investigations of the impact of these polymorphisms on both the earliest detectable phase of prostate cancer in the autopsy study and its progression to clinical disease in the case-control study. Our analysis will emphasize comparisons of findings for African-American and Caucasian males from the same community. This project will provide a valuable opportunity to define the role of the individual effects and the interplay of androgens, vitamin D, and race in the etiology of prostate cancer, and to distinguish their effects on its preclinical initiation and progression to clinical disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURVIVORS

PREVENTION

OF

OSTEOPOROSIS

IN

BREAST

CANCER

Principal Investigator & Institution: Waltman, Nancy L.; Adult Health and Illness; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-DEC-2006 Summary: Osteoporosis can be a major debilitating, expensive, long term, irreversible condition, and breast cancer survivors are particularly at risk for osteoporosis. As a result of some chemotherapy agents, many of these women experience premature ovarian failure. At least 60% of women with breast cancer have estrogen receptor positive tumor status; thus, they are not candidates for hormone replacement therapy. Without estrogen, bone loss occurs rapidly the first five years of menopause and continues over time but at a slower rate. The purpose of this study is to test whether strength/weight training exercises enhance the effectiveness of risedronate (5 mg/day), calcium (1200 mg/day), and vitamin D (400 IU/day) in improving bone mineral density (BMD) in post-menopausal breast cancer survivors. The sample will be 218 subjects recruited within a 100 mile radius of r sites across Nebraska (Omaha, Lincoln, Kearney and Scottsbluff). Post-menopausal women with a history of stage O (in situ), stage I or II breast cancer, with a BMD DEXA T-score of -1.0 SD or lower at any of 3 sites (hip, spine, forearm) will be stratified by time since menopause (5 yrs or less: > 5 years) and randomly assigned to one of two treatment groups (G1 and G2), with approximately 109 per group. Differences in tamoxifen, smoking, intake of calcium, and body mass index (BMI) between the two groups at baseline will be examined; if differences exist they will be controlled statistically. Both groups will receive risedronate, calcium and vitamin D; G1 also will receive strength/weight training exercises for upper and lower extremities and spine. Facilitative strategies based on Bandura's (1997) Self-Efficacy Theory are designed and used to encourage long-term adherence for both groups. The multicomponent intervention is 24 months with follow-up at 30 and 36 months. The primary outcome measure is BMD of the hip, spine and forearm (via DEXA): secondary outcome measures are muscle strength and fractures. The impact of the multi-component intervention on outcomes will be assessed using General Estimating Equation methodology Measurement of outcomes will occur at 6 and/or 12 month intervals

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Vitamin D

through 36 months. In addition, relationships will be examined between level of confidence in goal accomplishment and adherence to intervention components over time. This study may provide evidence of an effective alternative to HRT for treatment of osteoporosis in breast cancer survivors who are not candidates for HRT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF STERIOD INDUCED OSTEOPOROSIS IN CHILDREN Principal Investigator & Institution: Green, Rebecca P.; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Taken from the applicants abstract): Glucocorticoid-induced bone disease is an under addressed and potentially devastating problem in the pediatric population. Less than half of the patients on chronic steroid therapy will sustain at least one nontraumatic fracture. In addition, glucocorticoid therapy during childhood may reduce peak bone mineral density, increasing the risk of osteoporotic fractures later in life. Although bisphosphonates appear to be effective at preventing glucocorticoid induced bone loss in adults, the safety and efficacy, of these drugs for the treatment glucocorticoid induced bone disease in children is not known. Children are unique due to the potential adverse effects on growing bone. The long-term objectives of this study are to determine if a bisphosphonate, pamidronate, can be safely and effectively used to treat and prevent glucocorticoid mediated bone loss in children. Specific aim 1 is designed to test the hypothesis that pamidronate in combination with calcium and vitamin D is more effective then calcium and vitamin D alone at treating existing glucocorticoid induced bone disease. It is a 24-month single-blind, placebo-controlled study. Specific aim 2 is designed to test the hypothesis that pamidronate in combination with calcium and vitamin D, initiated within 90 days of initiating glucocorticoid therapy, is more effective then calcium and vitamin D alone at preventing a decrease in bone density in children anticipated to require long term glucocorticoid therapy. It is a 12-month single- blind, placebo-controlled study with a 12-month post-treatment follow-up period. The primary endpoint of specific aim 1 and 2 is volume corrected lumbar spine bone mineral density (BMD). Secondary endpoints include proximal femur and whole body BMD, fractures, markers of bone turnover, growth, and skeletal changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSTATE CANCER IN MEXICANS AMERICANS & AFRICAN AMERICAN Principal Investigator & Institution: Strom, Sara S.; Assistant Professor; Epidemiology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Prostate cancer is the leading incident cancer and the second leading cause of cancer deaths among men in the three major U.S. ethnic groups. However, those rates differ markedly among these groups. The racial differences in prostate cancer incidence and mortality could provide important clues to the etiology of the disease that could be exploited to further our understanding of prostate carcinogenesis. Prostate cancer is a model site for the study of the interplay of gene-environment interactions. In this proposed study, we will examine environmental factors in concert with genetic susceptibility in two ethnic groups with contrasting prostate cancer rates, African

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Americans and Mexican Americans, from a well-defined geographic area. We propose a population-based case-control study of genotypic, phenotypic, environmental and sociodemographic contributors to the etiology of prostate cancer in African Americans and Mexican Americans who are residents of the Houston area (Harris County, Texas). We will enroll 550 prostate cancer cases (200 Mexican Americans and 350 African Americans) and 750 controls (400 Mexican Americans and 350 African Americans) matched on age and race/ethnicity. Constitutional markers of genetic susceptibility and hormonal modulation, such as androgen receptor, 5-alpha-reductase type II, CYP17, CYP1B1, 3-beta-hydroxsteroid type II and vitamin D receptor, will be analyzed to determine if genotypic differences are associated with prostate cancer risk. Few studies have focused on minority populations, especially Hispanics, from a defined geographic area. Understanding how genetic predisposition and exogenous exposures interact to determine prostate cancer susceptibility will allow the development of more effective ethnic-specific prevention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PTH-RELATED PEPTIDE AND VIT D IN PROSTATE CANCER GROWTH Principal Investigator & Institution: Falzon, Miriam; Pharmacology and Toxicology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 07-JAN-2000; Project End 31-DEC-2003 Summary: Prostate cancer is the largest cause of cancer death among men in the United States. Prostate cancer cells produce a variety of autocrine growth factors, among them the parathyroid hormone- related peptide (PTHrP). The first aim of this project will use two approaches to examine the effects of PTHrP on prostate cell growth: establishing cell lines over- or under-expressing PTHrP, and treating cells with recombinant PTHrP (1-139). Thus we can distinguish between the autocrine/paracrine (cell surface) vs. intracrine (nuclear) effects of the peptide. Vitamin D decreases prostate cancer cell growth and epidemiological studies have shown that vitamin D deficiency is a risk factor for prostate cancer. The long-term objective of our research is to determine whether vitamin D or its analogues are useful as chemopreventative or chemotherapeutic agents in prostate cancer. The PTHrP gene is down-regulated by 1,25dihydroxyvitamin D (1,25(OH)2D), the hormonally active form of vitamin D, in prostate cancer cells. Therefore, vitamin D not only has antiproliferative effects, but decreases PTHrP secretion in prostate cells. This project seeks to define the mechanism(s) by which 1,25(OH)2D, alone and in combination with 9-cis-retinoic acid, represses PTHrP gene expression in normal and cancerous prostate cell lines. The human PTHrP gene is a complex transcriptional unit with at least three different promoters. Different cell lines and tissues exhibit different promoter utilization patterns. The responsiveness of each promoter to 1,25(OH)2D will be assessed using transient transfection assays. The precise sequence elements conferring responsiveness to 1,25(OH)2D within a particular promoter will be located by deletion mapping. Trans-acting nuclear proteins interacting with these promoter elements will be characterized by gel retardation and nuclease protection assays. The hypercalcemic effects of 1,25(OH)2D itself have thus far prevented its prophylactic and therapeutic use, but various non-hypercalcemic vitamin D analogues have recently been synthesized. Some of these analogues will be tested for their ability to down-regulate PTHrP gene expression and decrease PTHrP secretion, thereby addressing whether these derivatives exert the same net desirable effects as the parent compound. These studies should thus provide a molecular basis for use of nonhypercalcemic vitamin D analogues as chemopreventive and chemotherapeutic agents

48

Vitamin D

targeted at both PTHrP-mediated prostate cancer cell proliferation and humoral hypercalcemia of malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAT INTESTINAL MEMBRANE--VITAMIN D-MEDIATED EFFECTS Principal Investigator & Institution: Sitrin, Michael D.; Associate Professor of Medicine; Medicine; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 01-JUL-1989; Project End 31-MAR-2004 Summary: This proposal examines the ability of vitamin-D and its derivatives to regulate cell growth in colonic cancer. The applicant and his coworkers have shown that F6-D3, a fluorinated, non-calcemic analog of 1-alpha,25 (OH)2-D3 reduced the incidence of colonic adenomas and prevented the development of adenocarcinomas in experimental models. In order to understand the role of vitamin D3 in colonic normal and abnormal function, studies are proposed in normal rat colon and in CaCo-2 cells, a cell line derived from a human colonic adenocarcinoma. The cells exhibit similar signal transduction mechanisms and respond in similar fashion to vitamin D as their normal counterparts. Previous studies have shown that vitamin D and F6-D3 decreased cellular proliferation in these cells, while more recent studies have shown that they induce growth arrest in the G1 phase of cell cycle and bring about apoptosis. Accordingly the specific aims of the proposal are to characterize the mechanisms involved in inhibition of cellular proliferation in CaCo-2 cells and the actions of the secosteroids in inducing apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF ANP RECEPTOR ACTIVITY IN VASCULAR CELLS Principal Investigator & Institution: Gardner, David G.; Professor; Metabolic Research Unit; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-1992; Project End 31-MAR-2006 Summary: (provided by the applicant): The natriuretic peptides play an important role in the regulation of cardiovascular and renal homeostasis. They bind with high affinity to surface receptors present on target cells and initiate a series of signal transduction events that, in the whole animal, result in reductions in blood pressure and an increase in renal excretion of sodium and water. There are three natriuretic peptide receptors, NPR-A, -B and -C. NPR-A binds to two cardiac hormones, atrial and brain natriuretic peptide (ANP and BNP, respectively) while NPR-B associates predominantly with the C-type natriuretic peptide (CNP) which is produced in the nervous system, reproductive tract and endothelium. NPR-C, the so-called clearance receptor, is expressed in a wide variety of tissues. While it may possess independent signaling activity, it is primarily responsible for sequestering NPs from the extracellular space. While a large body of information exists regarding the signal transduction activity associated with these receptors and the physiological role that each plays in the whole animal, very little information is available regarding their regulation, particularly at a transcriptional level. We have shown previously that expression of the NPR-A gene is controlled by three Sp1 sites and a single NF-Y site in the proximal promoter of that gene. We have also shown that the gene is down regulated by the receptor ligand ANP and upregulated by increases in extracellular tonicity and a number of nuclear receptor

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ligands, including vitamin D and retinoic acid. In the present application, we will attempt to determine the transcriptional regulatory controls that govern expression of the human NPR-B gene. Both the cis-acting regulatory elements and the trans-acting proteins that associate with them will be explored in detail. We have cloned and sequenced approximately 6 kb of 5'-flanking sequence from this gene as a prelude to these studies. We will also investigate the mechanism(s) underlying suppression of NPR-B and NPR-C gene expression by glucocorticoids and activation of NPR-A by 1,25dihydroxyvitamin D and extracellular tonicity in relevant target cell or whole animal models. Collectively, these studies should define the transcriptional regulatory control of these important genes in detail and add significantly to our understanding of their respective roles in the maintenance of cardiovascular and renal homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OSTEOBLASTS

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CHANNEL

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Principal Investigator & Institution: Farach-Carson, Mary C.; Professor; Biological Sciences; University of Delaware Newark, De 19716 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Calcium signals in target cells, including osteoblasts, serve as early effectors of external stimuli, including those that are either hormonal or mechanical in nature. For bone, these calcium signals play a major role in cell growth differentiation and coupling which occur during bone remodeling and ion homeostasis. A key molecule involved in mediating calcium signals is the dihydropyridine-binding, voltage sensitive calcium channel (VSCC) that is located in the plasma membrane. In response to specific stimuli, VSCCs open to allow extracellular calcium to enter the cell. The VSCC itself is a large, multi-subunit protein complex. The ion translocating subunit, alpha, has been cloned from several tissues, where it displays tissue-specific structural and functional properties. The alpha, subunit in osteoblasts has been identified at the functional and molecular level in our laboratory. In this proposal, we provide a logical plan for systematic study of the expression and regulation of the osteoblast VSCC, focusing on the alpha, subunit. The three aims address our basic hypothesis that the VSCC serves a vital function in controlling calcium permeability of the osteoblast plasma membrane during development of calcium signals which occur in response to hormonal or mechanical stimuli. A combination of functional, biochemical, immunological, imaging and molecular biological experiments are proposed. Together, these studies will provide new insights to the expression and function of VSCCs in osteoblasts as they impact on normal bone physiology as well as pathological conditions of bone loss. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS FOR ADVANCED PROSTATE CANCER Principal Investigator & Institution: Ingles, Sue A.; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Risk factors for advanced prostate cancer are poorly understood, but appear to differ from risk factors for occult disease. Although previous studies implicate both genetic and dietary factors in prostate cancer progression, attributable risk estimates for any single factor are not high. The possibility that genetic susceptibility might be expressed only in combination with dietary or other environmental exposures is the focus of this proposal. By examining genetic and dietary influences together, we may be

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able to identify important risk factors that are obscured when genes or diet are examined in isolation. Specifically, we hypothesize that allelic variation in genes controlling proliferation (androgen pathway genes) and differentiation (the vitamin D receptor gene) of prostate epithelium will influence risk of advanced prostate cancer, and that risk will be further modified by environmental (especially dietary) factors. We will address the following questions. 1. Are polymorphisms in androgen pathway genes associated with risk of advanced prostate cancer? 2. Does dietary fat or fiber intake modify risk of advanced prostate cancer among men with high- or low-risk genotypes? 3. Are polymorphisms in the vitamin D receptor gene associated with risk of advanced prostate cancer? 4. Does dietary calcium intake or vitamin D status (as measured by sunlight exposure and dietary intake) modify risk of advanced prostate cancer among men with high- or low-risk VDR genotypes? To address these questions, we propose to conduct a case-control study of 1000 men with advanced prostate cancer (500 Latino and 500 non-Latino white) ascertained through the Los Angeles County Cancer Surveillance Program, using neighborhood controls. Dietary and risk-factor questionnaires and blood samples will be collected. Odds ratios and effect modification will be evaluated using standard epidemiologic methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ADIPOSE TISSUE IN VITAMIN D METABOLISM Principal Investigator & Institution: Blum, Miriam; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Vitamin D has important effects upon calcium and bone metabolism and may be involved in the functioning of many other systems. Vitamin D insufficiency contributes to bone loss in the elderly and has recently been found to be quite prevalent in the northeast US. In both rodents and humans, adipose tissue is a major repository for vitamin D, however the function of adipose tissue in vitamin D metabolism is uncertain and factors affecting the assimilation and release of vitamin D from adipose tissue need to be elucidated. The overall purpose of this research project is to begin to define the role of adipose tissue in vitamin D metabolism. In this regard, we hypothesize that: 1. Vitamin D intake influences the level of vitamin D in adipose tissue 2. The vitamin D content of adipose tissue varies with season 3. Higher fat stores of vitamin D at the end of the summer will reduce the wintertime decline in blood 25-hydroxy vitamin D levels. To test these hypotheses, detailed investigations of vitamin D content in adipose tissue, body composition measurements, blood tests and dietary intake will be conducted in adult men and women participating in a longitudinal study. The proposed study consists of a seasonal observational period followed by a randomized placebo control trial of varying doses of oral vitamin D. In preparation for this study, I will train in vitamin D assay techniques and help refine the method for extracting and measuring vitamin D content in adipose tissue. Studying the role of adipose tissue in vitamin D metabolism will help increase our understanding of vitamin D physiology. It may also enable us to better understand the mechanisms involved in vitamin D insufficiency and give us greater insight into the management of this prevalent condition. In addition, the proposed study sets the groundwork for future studies that are essential to my development as an independent investigator. The proposed study as well as the other components of the K23 Award will enable me to broaden my skills in clinical research and increase my depth of knowledge and technical skills. The supportive environment and distinguished collaborators that are part of this

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proposal will provide me with the guidance that I need to pursue my research plans as I make the transition to independent clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF CELLULAR DIFFERENTIATION Principal Investigator & Institution: Maytin, Edward V.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: APPLICANT'S (Provided by Applicant) This is a proposal to use cellular differentiation as a way to modify ALA-mediated photodynamic therapy (PDT) in the treatment of cancer and other hyperproliferative diseases. Differentiation therapy is the principle of converting cells to a more differentiated state in order to enhance the response to specific therapies. Here, we take advantage of the fact that differentiated cells are more susceptible to ALA-dependent PDT than are undifferentiated cells. ALA is the initial precursor for heme biosynthesis within cells. When administered exogenously t o cells, ALA is taken up and metabolized by endogenous enzymes of the heme synthetic pathway to produce a photosensitizing intermediate, protoporphyrin IX (PPIX) which can be exploited for cell killing. Preliminary data in several cell types demonstrate that accumulation of PPIX during ALA exposure is greater in terminallydifferentiated cells than in undifferentiated cells. Further, PPIX accumulates in the differentiated cells largely as a result of increased transcription of coproporphyrinogen oxidase (CPO), one of the heme-synthetic enzymes. Proposed studies would seek to optimize the expression of CPO, through the understanding and manipulation of differentiation-specific mechanisms regulating CPO gene expression. One physiologically normal cell type (skin keratinocytes) and one neoplastic cell type (LNCaP prostate carcinoma) will be used as models for study. Epidermal keratinocytes were chosen as the normal model because the keratinocyte differentiation program is well-defined both in vitro and in vivo, and because C/EBP transcription factors have been shown to regulate differentiation- associated genes in the skin. Similarly, prostate carcinoma (LNCaP) cells are useful because their state of differentiation can be hormonally altered by androgens, retinoids, or vitamin D. Using these two cell systems, the role of C/EBPs in regulating CPO gene expression during differentiation will be studied. Ways to increase photosensitized cell death by upregulating CPO, perhaps via C/EBPs, will be sought. Ultimately, we will test the feasibility of exploiting differentiation as a means for enhancing ALA-PDT efficacy for neoplastic conditions in which cells are well-differentiated, or in which differentiation can be transiently induced. Overall, these studies may fill a gap in current cancer therapy, providing new way to effectively target cells that are resistant to standard radiation or chemotherapy regimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF ESTROGEN RECEPTORS AND TUMOR SUPPRESSORS Principal Investigator & Institution: Hilakivi-Clarke, Leena A.; Professor; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: Prepubertal exposures to estradiol and some dietary estrogens, including genistein and n-3 polyunsaturated fatty acids (PUFA), have been shown to reduce carcinogen-induced mammary tumorigenesis, while an exposure during pregnancy to dietary estrogens appears to increase dams' mammary tumor incidence. It is not known

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whether prepubertal or pregnancy exposure to a diet composed of both genistein and n3 PUFAs; i.e., a typical Asian diet, affects breast cancer risk. Further, the mechanisms mediating the opposing effects of prepubertal and pregnancy dietary estrogenic exposures on breast cancer risk remains to be determined. Our preliminary data suggest the prepubertal estrogen exposures up-regulate the expression of BRCA1, a tumor suppressor that participates in repairing DNA damage. High estrogenicity during pregnancy may promote the growth of premalignant cells. The goal of this study is to determine how prepubertal and pregnancy exposures to dietary estrogens mediate their effects on the breast. We will focus on BRCA1, estrogen receptor (ER) a, and cyclin D1. The three hypotheses are: HYPOTHESIS-1. Prepubertal exposure to the dietary estrogens present in soy and/or n-3 PUFA will reduce sporadic mammary tumorigenesis. HYPOTHESIS-2. Prepubertal exposure to genistein and/or n-3 PUFAs increases BRCA1 expression, which in turn alters expression of genes regulated by this tumor suppressor, including ER-a and cyclin D1. Consequently, prepubertal exposure to estrogens will increase the risk of breast cancer in BRCA1 mutant mice. HYPOTHESIS-3. An exposure during pregnancy to estrogens and dietary estrogens increases mammary tumorigenesis in dams who either have acquired mutations in tumor suppressor genes or otherwise have undergone first events of malignant transformation. The increase in risk is related to elevated ER-a expression and unopposed cellular proliferation.These hypotheses will be studied using carcinogen-initiated mammary tumors in rats, conditional BRCA1 mutant mice, and cyclin D1 transgenic mice. Further, gene microarray approach will be used to identify genes that could be regulated by altered expression of BRCA1, ER-a and cyclin D1. The results obtained in this study will be used to develop childhood and pregnancy dietary intervention strategies to prevent some breast cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF THE VITAMIN D RECEPTOR Principal Investigator & Institution: Gewirth, Daniel T.; Assistant Professor; Biochemistry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 05-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The steroid and nuclear hormone receptors are the largest known class of eukaryotic transcriptional regulators and modulate transcription in response to non-peptide lipophillic signals. The members of this superfamily include the vitamin D receptor (VDR), which regulates genes related to calcium homeostasis and plays a role in the differentiation of hematopoietic and skin cells, and the androgen receptor (AR), which directly regulates the expression of prostate-specific genes, among others. Hormone receptors exert their effects by binding as homo- or hetero-dimers to DNA targets - called response elements - composed of two hexanucleotide half-sites that are distinguished from one another by the sequence of the half site and the orientation and spacing of one half site relative to the other. VDR binds to response elements composed of two half-sites arranged as a direct repeat with three base pairs of spacer in between (DR-3). AR binds to inverted repeat, three-spacer response elements (IR-3), although recently a novel AR response element was identified that closely resembles the DR-3 type and may serve to distinguish AR responsive genes from those responsive to glucocorticoids and other steroids. An understanding of the underlying stereochemistry of the role of VDR and AR in transcriptional activation and DNA target selection requires the structural analysis of the relevant macromolecular species and complexes. We plan to solve and analyze, using X-ray crystallography, the structures of the DNA binding domain of VDR homodimers and RXR-VDR heterodimers in complex with a

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variety of DNA targets, and the structure of the AR DNA binding domain in complex with its novel direct repeat DNA target. These studies are aimed at elucidating the structural basis for both VDR and AR DNA target recognition, their shared preference for DR-3 type response elements, and the mechanisms employed to distinguish correct from incorrect DNA targets. We will correlate our structural results with measurements of the protein's binding affinity to consensus and wild-type response elements. NMR and crystallography will be used in parallel and synergistically to examine the structure of full-length VDR, in order to understand the interplay between the DNA and ligand binding domains. These analyses may lead to the design of novel anti-cancer or therapeutic compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE 4 CORNERS BREAST AND ENDOMETRIAL CANCER STUDY Principal Investigator & Institution: Baumgartner, Kathy B.; Phd; Internal Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract) The incidence of breast and endometrial cancers varies almost three-fold between non-Hispanic white populations and Native American and Hispanic populations living in the 4-Corners area of the United States (Arizona, New Mexico, Colorado, and Utah). Interestingly, although American Indian and Hispanic women have higher prevalences of many risk factors for breast and endometrial cancer identified in non-Hispanic white women (e.g., obesity, low levels of vigorous physical activity, low intakes of fruits and vegetables, high rates of insulin resistance) they have lower cancer incidence rates. In this study the investigators focus on the metabolic factors of obesity/weight changes and indicators of insulin status as they relate to breast and endometrial cancers. Obesity is associated both with estrogen and insulin by two interrelated disease pathways. Insulin may influence cancer risk directly through its effects on insulin-like growth factor (IGF) and its binding proteins (IGFBPs) and well as indirectly through its effect on estrogen levels. The investigators propose focusing on the insulin pathway because of the high levels of insulin pathway dysfunction in this population. A multi-center case-control study is proposed that targets women living in the 4-Corners area; the study will consist of a 2.5 hour in-person interview and a blood draw. Over a three-year case ascertainment period, the study will enroll 3000 breast cancer cases, 450 endometrial cancer cases and 3000 controls, half of whom will be Hispanic/Native American and half of whom will be non-Hispanic white women between the ages of 25 and 79. Molecular variants of genes that influence obesity and insulin (androgen receptor gene (AR), vitamin D receptor gene(VDR), insulin receptor (ADRB3)) will be examined both independently and in conjunction with metabolic factors to determine differences in genetic susceptibility in the population. Because of the diverse population (Hispanics, Native American, and non-Hispanic white women), the investigators propose to evaluate ethnic background and genetic admixture in relationship to gene markers, environmental factors, and breast and endometrial cancer risk. Genetic admixture (Ameridian to European genetic mixture) is a novel and innovative way to study the continuum of ethnic diversity. C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE PHOTOBIOLOGY OF VITAMIN D Principal Investigator & Institution: Holick, Michael F.; Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 31-MAR-2006 Summary: (provided by applicant): The goal of this research program is to develop a better understanding about how vitamin D3 is made and processed in the skin. During the past four years, we have accomplished the major Specific Aims that we had proposed in our last grant period and established a very sensitive high performance liquid chromatography methodology that will be important for continuing studies on the photobiology of previtamin D and vitamin D3. Ten photoproducts of previtamin D3 and six photoproducts of vitamin D3 have now been identified after exposure to ultraviolet radiation that is comparable to human exposure levels. We plan to study the photoproduction of toxisterols and suprasterols in a liposomal model and human skin equivalent, and in cultured human keratinocytes and human skin. The biologic activity of the various toxisterols and suprasterols will be investigated in cultured human keratinocytes with specific emphasis on regulation of cellular proliferation and terminal differentiation. In addition, we will evaluate the metabolism of the most prominent toxisterols and sprasterols that are produced in the skin. This will be accomplished by making tritium-labeled toxisterols and sprasterols, and evaluating their metabolism in cultured human keratinocytes. Results from this study should provide important new insights into the photoproduction of toxisterols and suprasterols in human skin and provide new information about their potential biologic functions in the skin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE PHYSIOLOGY AND METABOLISM OF VITAMIN D Principal Investigator & Institution: Kumar, Rajiv M.; Chair, Mayo Proteomics Research Center; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-1979; Project End 31-JUL-2004 Summary: The objectives of this grant application are to determine whether 1alpha,25dihydroxyvitamin D3 (1alpha,25(OH)2D3) alters bone turnover and osteoblast growth by altering transforming growth factor beta (TGF beta) signaling and immediate early gene expression in bone. 1alpha,25(OH)2D3 and TGF beta play an important and interactive role in bone. It is, however, not known whether changes in the osseous expression of TGF beta in vivo are necessary for the action of 1alpha,25(OH)2D3 in bone, and it is unknown as to how 1alpha,25(OH)2D3 alters TGF beta signaling pathways. The hypotheses of the application are: 1) 1alpha,25(OH)2D3 requires and regulates TGF beta and TGF beta signaling pathways to exert its biological effect in osteoblasts and bone, and 2) 1alpha,25(OH)2D3 and TGF beta effects in osteoblasts are mediated, in part, by changes in the expression of a novel immediate early gene, IEX-1. Our specific aims are: 1) To determine whether 1alpha,25(OH)2D3 requires TGF beta and TGF beta signaling pathways to exert its biological effects in bone. We will determine the responses of mice that express a truncated, dominant negative, TGF beta type II receptor in osteoblasts to 1alpha,25(OH)2D3. 2) To identify the mechanisms by which 1alpha,25(OH)2D3 alters the expression of TGF beta type I and II receptors in osteoblasts. We will determine whether 1alpha,25(OH)2D3 increases cell surface TGF beta type I and II receptors. If transcriptional mechanisms are found to be important in controlling TGF beta type I and II receptor expression, we will identify 1alpha,25(OH)2D3-response elements in the receptor genes. 3) To determine if 1alpha,25(OH)2D3 alters Smad phosphorylation and synthesis in human osteoblasts. We will treat osteoblasts with 1 1alpha,25(OH)2D3 and

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assess changes in Smad 2 and 3 phosphorylation and Smad 2, 3, 4, and 7 protein and mRNA concentrations. 4) To determine whether the effects of 1alpha,25(OH)2D3 and TGF beta in osteoblasts require regulation of the immediate early gene, IEX-1. We will determine if IEX-1 is regulated by 1alpha,25(OH)2D3 and TGF beta; the mechanisms of IEX-1 regulation will be assessed; and the effects of reduced or enhanced IEX-1 expression on 1alpha,25(OH)2D3 and TGF beta action will be studied. By combining in vivo and in vitro methods, we will be able to address mechanistic questions regarding the dependence of 1alpha,25(OH)2D3 on TGF beta in osteoblasts, and we will be able to elucidate the role of IEX-1 in 1alpha,25(OH)2D3 and TGF beta signaling in osteoblasts. Results of this investigation could lead to a better understanding of the pathogenesis of bone diseases and the formulation of new therapeutic strategies in disorders such as hyperparathyroidism and osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THYROID HORMONE RECEPTOR Principal Investigator & Institution: Baxter, John D.; Professor and Director of Medicine; Metabolic Research Unit; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 31-MAR-2007 Summary: Nuclear receptor genes comprise a large family and encode receptors for thyroid and steroid hormones, vitamin D, retinoids, prostaglandins, and other ligands. These receptors regulate most human processes and are important pharmaceutical targets. The receptors contain amino-terminal, DNA-binding and ligand-binding (LBD) domains. Ligand-induced receptor conformational changes induce receptor activities that regulate transcription. Receptors mediate effects through interactions with other proteins, including coactivators and heterodimerizing partners. Central to understanding receptor actions is knowing their atomic structures. The Principal Investigator and colleagues first solved the X-ray structure of a liganded nuclear receptor LBD, that of the thyroid hormone receptor- alpha (TRalpha) that revealed insights into receptor function, and subsequently solved other structures, including TRalpha LBD bound to several ligands, human (h) TRbeta bound to agonists, including one that is TRbeta-selective, hTRbeta bound to a coactivator peptide and mutated hTRbeta forms that cause thyroid hormone resistance. These structures have revealed more information about receptor function, have been useful for designing a ligand that selectively modulates hTRbeta bound to a coactivator peptide and mutated hTRbeta forms that cause thyroid hormone resistance. These structures have revealed more information about receptor function, have been useful for designing a ligand that selectively modulates hTRbeta thyroid hormone response sand may be a prototype drug for treating obesity and hypercholesterolemia, and for designing thyroid hormone antagonists that may be prototypes for treating hyperthyroidism. In the proposed studies it is planned to determine the X-ray crystal structure of the hTRbeta PBD bound to several different ligands that perturb the structure in different ways, hTRbeta complexed with a retinoid X-receptor (RXR) heterodimerizing partner, and liganded hTRbeta LBD complexed with a novel coactivator peptide and a cyclized high affinity binding coactivator peptide. It is also planned to determine X-ray structures of RXR and TR DBD-LBD proteins and the full-length TR. The new structures should provide information about hormone-induced conformational changes, mechanisms of receptor interaction with other protein, the multiple receptor domains, and relations between domains. The results should yield insights into TR function and how ligands act as

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agonists or antagonist, are applicable to nuclear receptors in general, and may facilitate pharmaceutical design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TIMING OF VITAMIN A & D EXPOSURES AND BREAST CANCER RISK Principal Investigator & Institution: Byers, Stephen W.; Professor; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: Epidemiological studies point to a relationship between the dietary intake of vitamins A and D and the incidence of breast cancer, this relationship indicates that these dietary factors may have a chemopreventive action. Animal studies confirm the preventive efficacy of vitamins A and D in breast cancer. In some instances these vitamins have been used successfully to treat overt disease but in other cases cancer cells and tumors become resistance to treatment. These data illustrate the need for investigations into two fundamental areas. Firstly, the failure of more advanced malignancies to respond to vitamin A or D therapy clearly indicates that timing and duration of exposure to these agents is of paramount importance. For example, it is possible that exposure to diets high in vitamins A and D early in life may well protect from the subsequent development of breast cancer whereas adult exposure may be less efficacious. Understanding, when, during breast development and malignancy, these vitamins are most efficacious is very important. Secondly, even though the anti-cancer actions of vitamins A and D are clearly mediated via interaction with their respective nuclear receptors it is still not clear exactly what the anti-proliferative/differentiation signals are. Studies that elucidate the precise mechanism(s) whereby vitamins A and D exert their anti-cancer effects are of great significance. For example a detailed understanding of these pathways may lead to the development of agents or dietary regimens that are effective in patients that are resistant to vitamin therapy. Recent work from the Byers' group demonstrates that the wnt/beta-catenin/TCF oncogenic pathway involved in mammary gland development and implicated in breast cancer is a key intermediary in the action of vitamins A and D. This project proposes a series of molecular studies to define this relationship more precisely and to investigate other vitamin A and D-sensitive pathways. These basic science studies are coupled to other studies in which transgenic animals are used to test the effects of vitamins A and D exposure on breast cancer development and the role of their receptors in protection from breast cancer. Finally, we will use gene microarrays and cluster analysis to identify, groups of genes that are commonly and perhaps inversely regulated by, the pathways that cause breast cancer (e.g. erbB2 or beta-catenin) and those which prevent it (e.g. vitamins A and D). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRAINING PROGRAM IN MOLECULAR ENDOCRINOLOGY Principal Investigator & Institution: Rosen, Jeffrey; Associate Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 05-SEP-1993; Project End 31-AUG-2008 Summary: (provided by applicant): The goal of this training program is to prepare scientists for careers as independent investigators in the field of molecular endocrinology. Elucidation of the basic mechanisms involved in signal transduction and the regulation of gene expression is essential for our understanding of the etiology and

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the design of effective treatments of major diseases affecting our society, such as diabetes, AIDS and cancer. This is an interdepartmental training program involving nineteen faculty from seven departments, including the Departments of Medicine, Pediatrics, Surgery, Molecular and Cellular Biology, Biochemistry and Molecular Biology, Molecular and Human Genetics and Pathology. Trainees are both predoctoral and postdoctoral (Ph.D. and M.D.) fellows with backgrounds in areas such as biochemistry, cell and molecular biology and endocrinology. The faculty for this training program were chosen to represent the major areas of signal transduction from ligand-receptor interactions at the cell surface to gene transcription. Major research programs include: (1) Structure/function analysis of sulfonylurea receptors and ATPsensitive K + channels and interactions with the somatostatin receptor. (2) structure/function analysis of G proteins and G protein mediated signal transduction and nuclear import. (3) The role of protein kinases and kinase inhibitors in signal transduction and cell cycle regulation. (4) Prolactin and cytokine regulation of gene expression. (5) Regulation of insulin gene transcription, the genetics of diabetes and insulin-like growth factor I action. (6) The molecular mechanisms of steroid receptor and vitamin D action (7) Hormonal control of lipid and fatty acid synthesis, and finally, (8) Hormonal regulation of development. Predoctoral candidates will be selected following their acceptance into the Graduate School at Baylor College of Medicine. During their first year in graduate school these students will all take a core curriculum designed to provide all graduate students with a broad-based coverage of the important concepts of biomedical science and more specialized courses, such as a course entitled "Cell Signaling" for trainees in the Molecular Endocrinology Program. Postdoctoral candidates with an interest in molecular endocrinology will be accepted upon completion of either their Ph.D. or M.D. degrees. The training facilities are located in modem, up-to-date laboratories at Baylor College of Medicine located in the Texas Medical Center. The proximity of two medical schools, Rice University and M.D. Anderson Cancer Center, and the presence of 60,000 professionals make this a unique environment in which to perform medical research Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSCRIPTION FACTOR FUNCTION OF HAIRLESS Principal Investigator & Institution: Engelhard, Andrew; Dermatology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Recently much progress has been made in the understanding of hair follicle (HF) biology. The HF is a dynamic structure whose multiple compartments undergo successive rounds of complex and highly synchronized architectural reorganization during the growth (anagen), regression (catagen) and resting (telogen) phases of the hair cycle. Several genes that are thought to play a role in the catagen stage of the normal hair cycle, including hairless (hr), the vitamin D receptor (VDR), and the retinoid X receptor alpha (RXRalpha) have been identified on the basis of mutations in these genes which cause hair loss phenotypes. In the case of hr mutations, which cause alopecia in mice and other animals and atrichia with papular lesions (APL, OMIM 209500) in humans, cellular and morphologic changes in the structure of the HF have been characterized, yet little is known about the molecular mechanisms disrupted by hr mutations. Although the function of the protein coded by the hr gene (Hr) remains unknown, several lines of evidence suggest that Hr functions as a transcription factor of the zinc finger type. 1) An Hr domain shares homology with the GATA-1 zinc finger domain, which is responsible for DNA binding. 2) A point

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mutation in an APL patient results in the substitution of glycine for a conserved, presumably zinc-coordinating cysteine residue at amino acid 622. 3) Hr mutations result in the complete Joss of functional hair follicles, and 4) Hr localizes to the nucleus. This proposal aims to demonstrate that Hr is, in fact, a zinc finger transcription factor by identifying a unique consensus sequence to which Hr binds and by assaying the ability of this sequence to act as a transcriptional regulator or Hairless Responsive Element (HRE). The former aim will be accomplished through random oligonucleotide selection and amplification, a procedure known as CASTing. The latter aim will be accomplished by incorporating any presumed HREs into the promoter of luciferase reporter contructs and assaying transcriptional activity of various constructs in the presence and absence of hairless. Because the hairless phenotype is associated with changes in hair follicle morphology, and one possible mechanism identified is aberrant apoptosis, downstream effectors ofhaMess function might be members of a broad group of cell cycle genes regulated in a tissue-specific manner. The assignment of a role for hairless would be a first step in examining these possibilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D ANALOGS AS ADJUVANTS IN CHEMOTHERAPY Principal Investigator & Institution: Studzinski, George P.; Chairman and Professor; Pathology and Lab Medicine; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 01-JUN-1987; Project End 31-JUL-2007 Summary: (provided by applicant): Acute and chronic myeloid leukemias are responsible for approximately 15,000 deaths in the USA every year. These diseases frequently afflict people in the prime of their lives, and substantially less than half of all achieve long-term remission with current therapies, Most treatment options are both intense and toxic, requiring anti-neoplastic poly-chemotherapy, and, in some cases, therapy as radical as allogeneic hematopoietic cell transplantation, with its attendant risks. The overall goal of this proposal is to develop differentiation therapy to supplement the treatment regimens for this group of diseases. We will focus on the identification of the most effective analogs (deltanoids) of the physiological form of vitamin D, 1,25- dihydroxyvitamin D3 (1,25D3) administered at low concentrations to leukemia cells in culture to study alterations in gene expression and other changes in cell physiology. The deltanoids and 1,25D3 will also be administered in combination with nontoxic substances currently used as food preservatives or additives, or with potential for such use, to maximize the differentiation activity of the deltanoids. Established lines of leukemia as well as samples of leukemic cells freshly obtained from patients will be used for studies of cell differentiation. Insight into differentiation control will be obtained by examination of signaling pathways with particular attention to MAPK pathways and into cell cycle regulation by the expression of cyclin-dependent kinases as well as their activators and inhibitors. This will be accomplished by adding pharmacological agents, antisense oligonucleotides, transcription factor decoys, and transfected plasmid constructs to study the molecular consequences of these manipulations, which will be determined by immunoblotting, Northern analysis, RTPCR, coimmunoprecipitation, and other standard techniques. Differentiating cells will be monitored by determination of surface makers as well as the activity of various kinases as and as their expression. The information obtained in basic studies will be utilized to guide development of a new generation of deltanoids and deltanoid combinations with co-inducers, while translational studies on leukemic cells ex vivo will serve to identify subgroups of myeloid leukemias most suitable for the initiation of clinical trials.

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

Project Title: VITAMIN D ANALOGS FOR CHEMOPREVENTION OF PROSTATE CANCER Principal Investigator & Institution: Foster, Barbara A.; Assistant Member; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Prostate cancer (CaP) is the most frequently diagnosed cancer and the second cause of cancer deaths in men in the US. Four potent anti-cancer activities have been ascribed to Vitamin D: 1) anti-proliferation, 2) antiangiogenesis, 3) pro-apoptosis and 4) pro-differentiation. However, vitamin D also mobilizes calcium stores causing toxic hypercalcemic effects. New analogs have been developed that retain the anti-cancer activities of vitamin D but without the associated systemic toxicity. Our hypothesis is that vitamin D compounds, that retain anti-cancer properties but have reduced calcemic activity, can be used as a chemopreventive agent to prevent/slow the progression and metastatic spread of CaP. We propose 4 specific aims: I: To determine if calcitriol and two vitamin D analogs with low systemic toxicity (1LX23-7553 & QW1624F2-2) can prevent/slow carcinogenesis in an autochthonous model of CaP (TRAMP) and characterize the molecular effects of these compounds during prostate cancer progression. II: To determine if calcitriol and the less calcemic vitamin D compounds ILX23-7553 & QW1624F2-2 can prevent/slow the development and metastatic spread of androgen-independent CaP in castrated TRAMP animals and characterize the molecular effects of these compounds on androgen-independent disease. III: To identify key molecular pathways involved in vitamin D?s anti-cancer activity by comparing the molecular phenotype of tumor-derived cells from naive TRAMP tumors and vitamin D-resistant TRAMP tumors. IV: To evaluate the in vivo response of human CaP to ILX23-7553 by treating men with localized CaP prior to prostatectomy with ILX23-7553 and characterizing the molecular phenotype of the response. Effects of calcitriol, ILX23-7553 and QWI1624F2-2 treatment on proliferation, apoptosis, angiogenesis and differentiation will be studied in androgen-dependent and independent CaP. Vitamin D resistant tumors will be induced in TRAMP and the molecular phenotype compared to naive TRAMP tumors. Finally a clinical trial examining the in vivo molecular response of organ confined human CaP to ILX23-7553 is proposed. These studies will provide preclinical data on the preventive activity of vitamin D compounds that can be used to design and initiate clinical trials using these compounds as a chemopreventive agent for human prostate cancer. These studies will identify key molecular pathways for vitamin D action that can be used to identify patients that are most/least likely to benefit from vitamin D therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN D AND THE DIFFERENTIATION OF KERATINOCYTES 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 01-MAY-1987; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract) - D3 regulates keratinocyte differentiation and proliferation, but the precise mechanisms by which it does so are not well defined and the outcomes appear to be dependent on experimental conditions including the presence of growth factors. Calcium and protein kinase C (PKC) also regulate keratinocyte differentiation, and are likely to modulate these actions of D3. D3

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induces the phospholipase C (PLC) family, enzymes which cleave phosphatidyl inositol bis phosphate (PIP2) into diacylglycerol (DAG) and inositol tris phosphate (1P3). These second messengers activate PKC and increase intracellular calcium (Cai). PLCg-1 is the most abundant member of the PLC family in keratinocytes, is regulated by calcium as well as D3, and is unique within the PLC family in its interaction with growth factor receptors such as EGFR and NGFR (trk). These characteristics have led the investigators to propose the following hypothesis. PLCg-l plays a critical role in the interaction between D3 and selected growth factors in their regulation of keratinocyte proliferation and differentiation. Dr. Bikle will test this hypothesis by achieving the following two objectives: 1. Determine the role of PLCg-1 in mediating the ability of D3 to regulate proliferation and differentiation. This will be accomplished by altering the production or activity of PLCg-1 in the cell and evaluating the effect of such maneuvers on the ability of D3 to regulate proliferation and differentiation. 2. determine whether the interaction between D3 and the growth factors EGF and NGF requires PLCg. To achieve this aim the ability of EGF and NGF to modulate the effect of D3 on proliferation and differentiation will be tested, the impact of induction of PLCg-1 by D3 on the acute effects of EGF and NGF with respect to increased Cai and PKC activity will be determined, and the requirement for PLCg-1 in the interactions between D3 and the growth factors EGF and NGF with respect to proliferation and differentiation will be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D IN PROSTATE CANCER: TUMOR VASCULATURE EFFECTS Principal Investigator & Institution: Trump, Donald L.; Professor; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): We have demonstrated that the most active vitamin D moiety 1,25 dihydroxycholecalciferol (calcitriol) has significant antiproliferative activity in vivo and in vitro. Calcitriol induces G0/G1 arrest, modulates p27/p21, induces apoptosis and enhances the antitumor activity of cisplatin, carboplatin, paclitaxel and docetaxel. In vitro and in vivo, dexamethasone (dex) potentiates calcitriolmediated antitumor activity and vitamin D receptor (VDR) ligand binding in vitro and in vivo and enhances VDR protein expression. Calcitriol/dex also suppress activated mitogen-activated protein kinase (MAPK), Ert 1/2) activity and phosphorylated Akt (PAkt). In a phase II clinical trial of hormone refractory prostate cancer with high dose oral calcitriol and dex, we observed a 50 percent reduction in serum prostate specific antigen (PSA) in 28 percent of patients with no hypercalcemia; modulation of VDR and other potential markers of calcitriol activity in peripheral blood monocytes. We have preliminary data indicating that calcitriol and dex induces apoptosis, modulates cell cycle, decreases P-Erk 1/2 and P-Ark and significantly up-regulated VDR expression of tumor-derived endothelial cells (TDEC) as compared to endothelial cells isolated from normal tissues (aortic). These studies suggest that the mechanism(s) of calcitriol/dex antitumor activity may involve effects on intratumor vasculature. We propose to examine this hypothesis by the following Specific Aims: 1) to determine the mechanisms involved in calcitriol/dex effects in TDEC isolated from prostate tumors as compared to normal by examining: a) effects on apoptosis and cell cycle; b) effects on invasiveness, motility, and angiogenesis; and c) whether activities require calcitriol binding to the VDR; 2) To determine the prostate tumor models the role of TDEC in calcitriol/dex antitumor effects by determining: a) effects on the vasculature within the tumor; b)

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effects on TDEC isolated from animals treated with calcitriol; and c) whether a relationship exists between modulation of effects on TDEC and antitumor effects and 3) To evaluate oral calcitriol (12mg QDx3) and/or dex (4mg QDx4) administered weekly x 4 to patients with localized prostate cancer immediately prior to prostatectomy to determine: a) effects on tumor endothelial cells; b) effects of cell cycle status, apoptosis markers and prostatic intraepithelial neoplasia (PIN) and c) prostate specific antigen (PSA) response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D METABOLISM THROUGH A RING MODIFICATION Principal Investigator & Institution: Reddy, Satyanarayana G.; Associate Professor; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, Ri 02905 Timing: Fiscal Year 2002; Project Start 15-JUN-1999; Project End 31-JUL-2003 Summary: We recently identified 1alpha,25-dihydroxy 3 epi-vitamin D3 (1alpha,25(OH)2-3-epi-D3) as a major metabolite of 1alpha,25- dihydroxy vitamin D3 (1alpha,25(OH)2D3) in the primary cultures of human keratinocytes. It is noted that the production of 1alpha,25(OH)2-3-epi-D3 is tissue specific. Also, 1alpha,25(OH)2-3-epi-D3 when compared to 1alph,25(OH)2D3 was found to be less active in generating some of the classical 1alpha,25(OH)2D3 mediated genomic biological responses. These biological activity findings indicated that the metabolism of 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi-D3 in target tissues leads to significant reduction in the activity of 1alpha,25(OH)2D3. Furthermore, we also identified 1alpha,25(OH)2-3-epi-D3 as a circulating metabolite in rats treated with pharmacological amounts of either 1alpha(OH)D3 or 1alpha,25(OH)2D3. Thus, this newly discovered metabolic pathway of 1alpha,25(OH)2D3 like the previously well established C-24 oxidation pathway, appears to play a significant role in the target tissue inactivation of 1alpha,25(OH)2D3. In the present grant proposal we coined the term "3beta-hydroxy epimerase", for the enzyme(s) responsible for epimerization of 3beta-hydroxyl of 1alha,25(OH)2D3. The following studies are proposed to elucidate the overall functional significance of our novel observation of the tissue specific metabolism of 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi-D3 in the vitamin D-endocrine system. 1) further investigations towards establishing the target tissue specificity for the production of 1alpha,25(OH)2-3epi-D3 in normal tissues from human, rat and chick species; 2) subcellular localization and enzyme kinetic studies to characterize the enzyme(s) responsible for the production of 1alpha,25(OH)2-3- epi-D3; 3) studies of further target tissue metabolism of 1alpha,25(OH)2-3-epi-D3; 4) comparative pharmacokinetic and biological activity studies between 1alpha,25(OH)2D3 and the newly discovered metabolite 1alpha,25(O2H)-3-epi-3-D. 5) studies of 1alpha,25(OH)2-3-epi-D3 production in mice that lack 24-hydroxylase to identify the 3beta-hydroxy epimerization as the possible alternate pathway for the inactivation of 1alpha,25(OH)2D3. It is anticipated that knowledge of target tissue specific metabolism of 1alpha,25(OH)2D3 will provide important information for our improved understanding of how 1alpha,25(OH)2D3 is inactivated in various different target tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN D REGULATION OF TYPE-2 HELPER T CELL RESPONSES Principal Investigator & Institution: Cantorna, Margherita T.; Assistant Professor; Nutritional Sciences; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802

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Timing: Fiscal Year 2002; Project Start 05-JAN-2001; Project End 31-DEC-2004 Summary: The objective of this proposal is to define molecular and cellular targets of vitamin D in the immune system. There is a large body of anecdotal data to suggest that there is a link between vitamin D status and the human autoimmune disease multiple sclerosis. Experimentally, vitamin D deficiency exacerbates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Furthermore supplementation of mice with vitamin D can suppress and prevent symptoms of EAE. Two targets of vitamin D in the immune system have been identified the interleukin (IL)-4. secreting type-2 helper T (Th2) cells and transforming growth factor (TGF)-beta1 (two cytokines shown to be protective in EAE) secreting cells. The hypotheses to be tested are: 1. Vitamin D status regulates Th cell differentiation. 2. Vitamin D treatment of EAE results because of the induction of Th2 cells. 3. Vitamin D induction of Th2 cells and protection from EAE depends on TGF-beta1 synthesis. 4. Vitamin D negatively regulates Th1 effector cells. Th cell differentiation and function will be measured as a function of increasing vitamin D both in vitro and in vivo in Th cells from T cell receptor transgenic mice. T cells from vitamin D treated mice will be isolated and tested for their ability to transfer protection from EAE. TGF-beta1 will be neutralized in vitro and in vivo to determine if vitamin D functions via the transcriptional upregulation of TGF-beta1. Similarly, TGF-beta1 supplementation will be done and compared to vitamin D treatment for the mechanisms by which they suppress EAE. Th2 cell deficient mice will be used as a source of Th1 effector cells and vitamin D will be tested as a direct regulator of Th1 function. A better understanding of how vitamin D effectively blocks EAE is necessary for proper nutritional counseling and optimal treatment of multiple sclerosis patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D SUPPLEMENTATION IN POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Aloia, John F.; Winthrop-University Hospital 259 1St St Mineola, Ny 11501 Timing: Fiscal Year 2002; Project Start 15-SEP-1998; Project End 31-JUL-2004 Summary: (Adapted from the Applicant's Abstract): The long-term goal of this project is to develop strategies for the prevention of osteoporotic fractures in black women. Most studies have excluded black women because of the mistaken belief that osteoporosis is not a major health problem in this population. It is true that black women have a higher bone density, protective anatomic geometry of the femur, and a larger muscle mass compared to white women. Nonetheless, the incidence of hip fracture in black women is as great as 40% of that in white women. As the black population ages, osteoporosis will become even a greater health problem for this ethnic minority. Black women have lower levels of calcidiol and higher levels of parathyroid hormone (PTH) than white women. Since black women have lower indices of bone turnover, they also appear to have a relative resistance to the effect of PTH. Dietary supplementation with vitamin D3 has been shown to safely reduce bone loss and prevent hip fractures in postmenopausal white women. The strategy of vitamin D3 supplementation to prevent osteoporosis is even more cogent in black postmenopausal women compared to white women because (a) they have lower calcidiol levels, (b) they have evidence of secondary hyperparathyroidism, (c) the long-term effects and risks of hormonal replacement therapy have not been evaluated in black women, and (d) because of their higher bone mass, low risk strategies are more appropriate. There are less black women with osteoporosis at menopause, so that a modest reduction in bone loss could have a great impact on prevention of osteoporosis. The specific aim of this project is to determine if

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daily dietary supplementation with 800 IU (20 ug) of vitamin D3 will reduce bone loss in postmenopausal black women. A secondary aim is to evaluate the changes in the vitamin D-endocrine system and indices of bone turnover that result from long term vitamin D3 augmentation. A positive response would provide a safe, inexpensive and acceptable strategy for prevention of osteoporotic fractures in black women. If this randomized clinical trial demonstrates a positive effect on prevention of bone loss, a large scale multi-centered trial with fracture prevention as an endpoint will have merit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D5 IN PREVENTION OF MAMMARY CARCINOGENESIS Principal Investigator & Institution: Mehta, Rajendra G.; Professor; Surgery; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 15-MAY-2000; Project End 31-AUG-2007 Summary: (provided by applicant): The vitamin D5 series of compounds are different from the D3 series. In vitamin D5, there is an ethyl group at the C-24 position. Earlier, we showed that an analog of vitamin D5, 1alpha-Hydroxyvitamin D5 (1alpha(OH)D5), is relatively nontoxic and non-calcemic compared to other vitamin D analogs (1). During the past 2 years of the funding period, we have shown that 1alpha(OH)D5 was effective in inhibiting both the tumor incidence and multiplicity of MNU- and DMBAinduced mammary carcinogenesis in rats. We also showed that the effect of 1alpha(OH)D5 was more prominent during the promotion phase of carcinogenesis. Here we will evaluate efficacy of 1alpha(OH)D5 in clinically relevant experimental protocol either singly or in combination with tamoxifen. More recently, the gene array profile of normal and transformed human mammary epithelial cells suggested that, among the differentially expressed genes, prohibitin, a cell cycle regulatory gene was upregulated in transformed cells. Moreover, prohibitin was down-regulated when transformed cells were treated with 1alpha(OH)D5. This provides a clue for understanding D5-mediated cell cycle regulation in transformed cells. We hypothesize that, in addition to vitamin D receptor, prohibitin may be an essential target for the action of 1alpha(OH)D5 in chemoprevention. Very little has been reported regarding the metabolism and pharmacokinetics of the D2, D4, and D5 series of vitamin D analogs. Recently, Jones and colleagues reported that C24 methyl or ethyl might be a metabolic determinant for vitamin D4 and D5 analogs (2). Dr. Glenville Jones will collaborate with us on this project to evaluate metabolism of 1alpha(OH)D5 in normal and neoplastic breast cells and tissues. Understanding of both the mechanism of action and metabolism of 1alpha(OH)D5 is crucial in developing this analog for clinical application. The following specific aims are proposed to determine: 1. Whether 1alpha (OH)D5 prevents development of tumors subsequent to surgical excision of the first palpable tumor? Whether the combination of 1alpha(OH)D5 and tamoxifen provide enhanced protection compared to either agent alone? 2. Whether prohibitin plays a role in cell transformation and chemopreventive efficacy in these cells? 3. How is 1alpha(OH)D5 metabolized in normal and neoplastic mammary epithelial cells and tissues? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

1 alpha,25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. by Reichel H, Koeffler HP, Tobler A, Norman AW.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304875

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1,25-Dihydroxy-16-ene-23-yne-Vitamin D3 Prolongs Survival Time of Leukemic Mice. by Zhou J, Norman AW, Chen D, Sun G, Uskokovic M, Koeffler HP.; 1990 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54017

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1,25-Dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line. by Wood RJ, Tchack L, Taparia S.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55338

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1,25-Dihydroxyvitamin D3 Induces Nitric Oxide Synthase and Suppresses Growth of Mycobacterium tuberculosis in a Human Macrophage-Like Cell Line. by Rockett KA, Brookes R, Udalova I, Vidal V, Hill AV, Kwiatkowski D.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108664

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1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. by Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP.; 2002 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151055

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1,25-Dihydroxyvitamin D3 Reversibly Blocks the Progression of Relapsing Encephalomyelitis, a Model of Multiple Sclerosis. by Cantorna MT, Hayes CE, DeLuca HF.; 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38839

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1,25-Dihydroxyvitamin D3 Upregulates Functional CXCR4 Human Immunodeficiency Virus Type 1 Coreceptors in U937 Minus Clones: NF-[kappa]BIndependent Enhancement of Viral Replication. by Biswas P, Mengozzi M, Mantelli B, Delfanti F, Brambilla A, Vicenzi E, Poli G.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110220

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

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

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1,25-Dihydroxyvitamin D3 up-regulates the 1,25-dihydroxyvitamin D3 receptor in vivo. by Strom M, Sandgren ME, Brown TA, DeLuca HF.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298583

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1[alpha],25-Dihydroxyvitamin D3 Regulates the Expression of Carbonic Anhydrase II in Nonerythroid Avian Bone Marrow Cells. by Billecocq A, Emanuel JR, Levenson R, Baron R.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54556

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1[alpha],25-Dihydroxyvitamin D3 Regulates the Transcription of Carbonic Anhydrase II mRNA in Avian Myelomonocytes. by Lomri A, Baron R.; 1992 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49148

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24- and 26-homo-1,25-dihydroxyvitamin D3: preferential activity in inducing differentiation of human leukemia cells HL-60 in vitro. by Ostrem VK, Tanaka Y, Prahl J, DeLuca HF, Ikekawa N.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304707

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25-Hydroxyvitamin D3-1[alpha]-Hydroxylase in Porcine Hepatic Tissue: Subcellular Localization to Both Mitochondria and Microsomes. by Hollis BW.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54461

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A composite element binding the vitamin D receptor, retinoid X receptor alpha, and a member of the CTF/NF-1 family of transcription factors mediates the vitamin D responsiveness of the c-fos promoter. by Candeliere GA, Jurutka PW, Haussler MR, StArnaud R.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231037

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A Differential Screen for Ligand-Regulated Genes: Identification of HoxA10 as a Target of Vitamin D3 Induction in Myeloid Leukemic Cells. by Rots NY, Liu M, Anderson EC, Freedman LP.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121420

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A novel nuclear receptor superfamily member in Xenopus that associates with RXR, and shares extensive sequence similarity to the mammalian vitamin D3 receptor. by Smith DP, Mason CS, Jones EA, Old RW.; 1994 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=307747

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A Nuclear Protein Essential for Binding of Rat 1,25-Dihydroxyvitamin D3 Receptor to Its Response Elements. by Ross TK, Moss VE, Prahl JM, DeLuca HF.; 1992 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48215

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A Positive GATA Element and a Negative Vitamin D Receptor-Like Element Control Atrial Chamber-Specific Expression of a Slow Myosin Heavy-Chain Gene during Cardiac Morphogenesis. by Wang GF, Nikovits W Jr, Schleinitz M, Stockdale FE.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109188

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A Possible Role of Vitamin D Receptors in Regulating Vitamin D Activation in the Kidney. by Iida K, Shinki T, Yamaguchi A, DeLuca HF, Kurokawa K, Suda T.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41652

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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 Two-Hit Mechanism for Vitamin D3-Mediated Transcriptional Repression of the Granulocyte-Macrophage Colony-Stimulating Factor Gene: Vitamin D Receptor Competes for DNA Binding with NFAT1 and Stabilizes c-Jun. by Towers TL, Staeva TP, Freedman LP.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104378

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Activation of the fructose 1,6-bisphosphatase gene by 1,25-dihydroxyvitamin D3 during monocytic differentiation. by Solomon DH, Raynal MC, Tejwani GA, Cayre YE.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282087

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Allosteric interaction of the 1alpha,25-dihydroxyvitamin D3 receptor and the retinoid X receptor on DNA. by Kahlen JP, Carlberg C.; 1997 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147055

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An ochre mutation in the vitamin D receptor gene causes hereditary 1,25dihydroxyvitamin D3-resistant rickets in three families. by Ritchie HH, Hughes MR, Thompson ET, Malloy PJ, Hochberg Z, Feldman D, Pike JW, O'Malley BW.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298586

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ApaI dimorphism at the human vitamin D receptor gene locus. by Faraco JH, Morrison NA, Baker A, Shine J, Frossard PM.; 1989 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317576

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Association between the expression of the c-myc oncogene mRNA and the expression of the receptor protein for 1,25-dihydroxyvitamin D3. by Manolagas SC, Provvedini DM, Murray EJ, Murray SS, Tsonis PA, Spandidos DA.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304315

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Avian and mammalian receptors for 1,25-dihydroxyvitamin D3: in vitro translation to characterize size and hormone-dependent regulation. by Mangelsdorf DJ, Pike JW, Haussler MR.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304205

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Baculovirus-Mediated Expression of Retinoic Acid Receptor Type [gamma] in Cultured Insect Cells Reveals a Difference in Specific DNA-Binding Behavior with the 1,25-Dihydroxyvitamin D3 Receptor. by Ross TK, Prahl JM, Herzberg IM, DeLuca HF.; 1992 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50322

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Calbindin-D in peripheral nerve cells is vitamin D and calcium dependent. by Lee YS, Taylor AN, Reimers TJ, Edelstein S, Fullmer CS, Wasserman RH.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299289

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Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D31[alpha]-hydroxylase gene in normocalcemic rats. by Shinki T, Ueno Y, DeLuca HF, Suda T.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22221

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Calreticulin inhibits vitamin D3 signal transduction. by Wheeler DG, Horsford J, Michalak M, White JH, Hendy GN.; 1995 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=307187

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CD8 + T cells are not necessary for 1[alpha],25-dihydroxyvitamin D3 to suppress experimental autoimmune encephalomyelitis in mice. by Meehan TF, DeLuca HF.; 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122808

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Cloning and characterization of the mouse vitamin D receptor promoter. by Jehan F, DeLuca HF.; 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23328

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Cloning and expression of full-length cDNA encoding human vitamin D receptor. by Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O'Malley BW.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280195

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Cloning and expression of rat 25-hydroxyvitamin D3-1[alpha]-hydroxylase cDNA. by Shinki T, Shimada H, Wakino S, Anazawa H, Hayashi M, Saruta T, DeLuca HF, Suda T.; 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24239

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Conformational Change and Enhanced Stabilization of the Vitamin D Receptor by the 1,25-Dihydroxyvitamin D3 Analog KH1060. by Bemd GC, Pols HA, Birkenhager JC, Leeuwen JP.; 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38215

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Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin. by Morrison NA, Yeoman R, Kelly PJ, Eisman JA.; 1992 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49563

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Coordinate Occupancy of AP-1 Sites in the Vitamin D-Responsiveness and CCAAT Box Elements by Fos-Jun in the Aosteocalcin Gene: Model for Phenotype Suppression of Transcription. by Owen TA, Bortell R, Yocum SA, Smock SL, Zhang M, Abate C, Shalhoub V, Aronin N, Wright KL, van Wijnen AJ, Stein JL, Curran T, Lian JB, Stein GS.; 1990 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=55300

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Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. by Tocchini-Valentini G, Rochel N, Wurtz JM, Mitschler A, Moras D.; 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33240

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Crystal structures of the vitamin D-binding protein and its complex with actin: Structural basis of the actin-scavenger system. by Otterbein LR, Cosio C, Graceffa P, Dominguez R.; 2002 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123010

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Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D3. by Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, Ray R, Gliemann J, Willnow TE, Christensen EI.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61138

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Demonstration of a 1,25-Dihydroxyvitamin D3-Responsive Protein in Human Lymphocytes: Immunologic Crossreactivity and Inverse Regulation with the Vitamin D Receptor. by Yu X, Hustmyer FG, Garvey WT, Manolagas SC.; 1991 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52505

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Dendritic cell modulation by 1[alpha],25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. by Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R.; 2001 Jun 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34433

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Dietary vitamin D affects cell-mediated hypersensitivity but not resistance to experimental pulmonary tuberculosis in guinea pigs. by Hernandez-Frontera E, McMurray DN.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280811

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Disruption of Microfilament Organization in Living Nonmuscle Cells by Microinjection of Plasma Vitamin D-Binding Protein or DNase I. by Sanger JM, Dabiri G, Mittal B, Kowalski MA, Haddad JG, Sanger JW.; 1990 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54347

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DNA Sequences in the Rat Osteocalcin Gene That Bind the 1,25- Dihydroxyvitamin D3 Receptor and Confer Responsiveness to 1,25- Dihydroxyvitamin D3. by Demay MB, Gerardi JM, DeLuca HF, Kronenberg HM.; 1990 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53265

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Down-Regulation of NF-[kappa]B Protein Levels in Activated Human Lymphocytes by 1,25-Dihydroxyvitamin D3. by Yu X, Bellido T, Manolagas SC.; 1995 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40556

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Duodenal calcium absorption in vitamin D receptor --knockout mice: Functional and molecular aspects. by Van Cromphaut SJ, Dewerchin M, Hoenderop JG, Stockmans I, Van Herck E, Kato S, Bindels RJ, Collen D, Carmeliet P, Bouillon R, Carmeliet G.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60869

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Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. by Trivedi DP, Doll R, Khaw KT.; 2003 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150177

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Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates. by Heckman GA, Papaioannou A, Sebaldt RJ, Ioannidis G, Petrie A, Goldsmith C, Adachi JD.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65678

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Evolutionary Importance for the Membrane Enhancement of the Production of Vitamin D3 in the Skin of Poikilothermic Animals. by Holick MF, Tian XQ, Allen M.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42117

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GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. by Hong H, Kohli K, Garabedian MJ, Stallcup MR.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232124

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Heterogeneous nuclear ribonucleoprotein (hnRNP) binding to hormone response elements: A cause of vitamin D resistance. by Chen H, Hewison M, Hu B, Adams JS.; 2003 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156334

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Human TAFII55 Interacts with the Vitamin D3 and Thyroid Hormone Receptors and with Derivatives of the Retinoid X Receptor That Have Altered Transactivation Properties. by Lavigne AC, Mengus G, Gangloff YG, Wurtz JM, Davidson I.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84390

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Human Vitamin D Receptor is Selectively Phosphorylated by Protein Kinase C on Serine 51, a Residue Crucial to Its Trans-Activation Function. by Hsieh J, Jurutka PW, Galligan MA, Terpening CM, Haussler CA, Samuels DS, Shimizu Y, Shimizu N, Haussler MR.; 1991 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52705

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Human Vitamin D Receptor Phosphorylation by Casein Kinase II at Ser-208 Potentiates Transcriptional Activation. by Jurutka PW, Hsieh J, Nakajima S, Haussler CA, Whitfield GK, Haussler MR.; 1996 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39642

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Id Gene Expression and Its Suppression by 1,25-Dihydroxyvitamin D3 in Rat Osteoblastic Osteosarcoma Cells. by Kawaguchi N, DeLuca HF, Noda M.; 1992 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49124

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Identification of a 1,25-Dihydroxyvitamin D3-Response Element in the 5' Flanking Region of the Rat Calbindin D-9k Gene. by Darwish HM, Deluca HF.; 1992 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48287

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Identification of a DNA Sequence Responsible for Binding of the 1,25Dihydroxyvitamin D3 Receptor and 1,25-Dihydroxyvitamin D3 Enhancement of

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Mouse Secreted Phosphoprotein 1 (Spp-1 or Osteopontin) Gene Expression. by Noda M, Vogel RL, Craig AM, Prahl J, DeLuca HF, Denhardt DT.; 1990 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=55301 •

Identification of a vitamin D responsive element in the promoter of the rat cytochrome P450(24) gene. by Hahn CN, Kerry DM, Omdahl JL, May BK.; 1994 Jun 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331693

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Identification of a Vitamin D-Response Element in the Rat Calcidiol (25Hydroxyvitamin D3) 24-Hydroxylase Gene. by Zierold C, Darwish HM, DeLuca HF.; 1994 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43060

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Identification of a vitamin D-responsive protein on the surface of human osteosarcoma cells. by Shull S, Tracy RP, Mann KG.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297631

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Identification of Sequence Elements in Mouse Calbindin-D28k Gene that Confer 1,25-Dihydroxyvitamin D3- and Butyrate-Inducible Responses. by Gill RK, Christakos S.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46221

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Identification of the Porcine Intestinal Accessory Factor that Enables DNA Sequence Recognition by Vitamin D Receptor. by Munder M, Herzberg IM, Zierold C, Moss VE, Hanson K, Clagett-Dame M, DeLuca HF.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42305

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In vivo Occupancy of the Vitamin D Responsive Element in the Osteocalcin Gene Supports Vitamin D-Dependent Transcriptional Upregulation in Intact Cells. by Breen EC, van Wijnen AJ, Lian JB, Stein GS, Stein JL.; 1994 Dec 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45548

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Increased human immunodeficiency virus (HIV) expression in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of interferon and tumor necrosis factor in regulation of HIV production. by Locardi C, Petrini C, Boccoli G, Testa U, Dieffenbach C, Butto S, Belardelli F.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=248750

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Influence of 1,25-(OH)2 vitamin D3 and gamma interferon on the phenotype of human peripheral blood monocyte-derived macrophages. by Poulter LW, Rook GA, Steele J, Condez A.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260648

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Inhibition by 1,25(OH)2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. by Crowle AJ, Ross EJ, May MH.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260011

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Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D3. by Crowle AJ, May MH.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172025

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Inhibitory effect of erythromycin on interleukin 8 production by 1 alpha,25dihydroxyvitamin D3-stimulated THP-1 cells. by Fujii T, Kadota J, Morikawa T, Matsubara Y, Kawakami K, Iida K, Shirai R, Taniguchi H, Kaseda M, Kawamoto S, Kohno S.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163367

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Intron retention generates a novel isoform of the murine vitamin D receptor that acts in a dominant negative way on the vitamin D signaling pathway. by Ebihara K, Masuhiro Y, Kitamoto T, Suzawa M, Uematsu Y, Yoshizawa T, Ono T, Harada H, Matsuda K, Hasegawa T, Masushige S, Kato S.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231333

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Ion Microscopic Imaging of Calcium Transport in the Intestinal Tissue of Vitamin DDeficient and Vitamin D-Replete Chickens: A 44Ca Stable Isotope Study. by Chandra S, Fullmer CS, Smith CA, Wasserman RH, Morrison GH.; 1990 Aug 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54398

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Isolation and expression of rat 1,25-dihydroxyvitamin D3 receptor cDNA. by Burmester JK, Maeda N, DeLuca HF.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279689

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Liver Mitochondrial Cytochrome P450 CYP27 and Recombinant-Expressed Human CYP27 Catalyze 1[alpha]-Hydroxylation of 25-Hydroxyvitamin D3. by Axen E, Postlind H, Sjoberg H, Wikvall K.; 1994 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44948

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Modulation of Mycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D3. by Waters WR, Nonnecke BJ, Rahner TE, Palmer MV, Whipple DL, Horst RL.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96250

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Molecular cloning of the cDNA and chromosomal gene for vitamin D-dependent calcium-binding protein of rat intestine. by Darwish HM, Krisinger J, Strom M, DeLuca HF.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299017

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Molecular cloning, characterization, and promoter analysis of the human 25hydroxyvitamin D3-1[alpha]-hydroxylase gene. by Kong XF, Zhu XH, Pei YL, Jackson DM, Holick MF.; 1999 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22032

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Multiple Cbfa/AML Sites in the Rat Osteocalcin Promoter Are Required for Basal and Vitamin D-Responsive Transcription and Contribute to Chromatin Organization. by Javed A, Gutierrez S, Montecino M, van Wijnen AJ, Stein JL, Stein GS, Lian JB.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84749

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Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts. by Crofts LA, Hancock MS, Morrison NA, Eisman JA.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27928

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Natural vitamin D3 response elements formed by inverted palindromes: polaritydirected ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimermediated transactivation. by Schrader M, Nayeri S, Kahlen JP, Muller KM, Carlberg C.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230337

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Normal myelopoiesis but abnormal T lymphocyte responses in vitamin D receptor knockout mice. by O'Kelly J, Hisatake J, Hisatake Y, Bishop J, Norman A, Koeffler HP.; 2002 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150940

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Overproduction of Rat 1,25-Dihydroxyvitamin D3 Receptor in Insect Cells Using the Baculovirus Expression System. by Ross TK, Prahl JM, DeLuca HF.; 1991 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52125

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Parathyroid hormone activation of the 25-hydroxyvitamin D3-1[alpha]-hydroxylase gene promoter. by Brenza HL, Kimmel-Jehan C, Jehan F, Shinki T, Wakino S, Anazawa H, Suda T, DeLuca HF.; 1998 Feb 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19012

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Parathyroid hormone regulates 25-hydroxyvitamin D3-24-hydroxylase mRNA by altering its stability. by Zierold C, Mings JA, DeLuca HF.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61082

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Partial amino acid sequence of porcine 1,25-dihydroxyvitamin D3 receptor isolated by immunoaffinity chromatography. by Brown TA, Prahl JM, DeLuca HF.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280015

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Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis. by de Viragh PA, Haglid KG, Celio MR.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287246

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Postproliferative Transcription of the Rat Osteocalcin Gene is Reflected by Vitamin D-Responsive Developmental Modifications in Protein-DNA Interactions at Basal and Enhancer Promoter Elements. by Owen TA, Bortell R, Shalhoub V, Heinrichs A, Stein JL, Stein GS, Lian JB.; 1993 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45902

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Puzzling vitamin D results. by Hanley DA.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128393

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Puzzling vitamin D results. by Marshall TG.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128392

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Rapid Accumulation of Cyclic GMP Near Activated Vitamin D Receptors. by Barsony J, Marx SJ.; 1991 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51033

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Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo. by Miao D, Scutt A.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116579

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Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin. by Yamamoto N, Kumashiro R, Yamamoto M, Willett NP, Lindsay DD.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281327

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Regulation of metallothionein gene expression by 1 alpha,25-dihydroxyvitamin D3 in cultured cells and in mice. by Karasawa M, Hosoi J, Hashiba H, Nose K, Tohyama C, Abe E, Suda T, Kuroki T.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299640

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Regulation of renin expression and blood pressure by vitamin D3. by Sigmund CD.; 2002 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151071

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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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Retinoid X receptor:vitamin D3 receptor heterodimers promote stable preinitiation complex formation and direct 1,25-dihydroxyvitamin D3-dependent cell-free transcription. by Lemon BD, Fondell JD, Freedman LP.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232039

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Selective effects of ligands on vitamin D3 receptor- and retinoid X receptor-mediated gene activation in vivo. by Lemon BD, Freedman LP.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231083

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Selective Interaction of Vitamin D Receptor with Transcriptional Coactivators by a Vitamin D Analog. by Takeyama KI, Masuhiro Y, Fuse H, Endoh H, Murayama A, Kitanaka S, Suzawa M, Yanagisawa J, Kato S.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116035

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Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3. by Kerner SA, Scott RA, Pike JW.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287288

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Sequences in the Human Parathyroid Hormone Gene that Bind the 1,25Dihydroxyvitamin D3 Receptor and Mediate Transcriptional Repression in Response to 1,25-Dihydroxyvitamin D3. by Demay MB, Kiernan MS, DeLuca HF, Kronenberg HM.; 1992 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49863

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Sequential Induction of 5-Lipoxygenase Gene Expression and Activity in Mono Mac 6 Cells by Transforming Growth Factor [beta] and 1,25-Dihydroxyvitamin D3. by Brungs M, Radmark O, Samuelsson B, Steinhilber D.; 1995 Jan 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42826

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Serum Calcium and Vitamin D Regulate 1,25-Dihydroxyvitamin D3 Receptor Concentration in Rat Kidney in vivo. by Sandgren ME, DeLuca HF.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54099

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Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription. by Vidal M, Ramana CV, Dusso AS.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133712

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Structure and nucleotide sequence of the rat intestinal vitamin D-dependent calcium binding protein gene. by Krisinger J, Darwish H, Maeda N, DeLuca HF.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282647

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Structure and regulation of the rat 1,25-dihydroxyvitamin D3 receptor. by Burmester JK, Wiese RJ, Maeda N, DeLuca HF.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282780

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Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. by Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, Zambetti G, Stein G.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286642

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Targeted ablation of the 25-hydroxyvitamin D 1[alpha]-hydroxylase enzyme: Evidence for skeletal, reproductive, and immune dysfunction. by Panda DK, Miao D, Tremblay ML, Sirois J, Farookhi R, Hendy GN, Goltzman D.; 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34697

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Targeted ablation of the vitamin D receptor: An animal model of vitamin Ddependent rickets type II with alopecia. by Li YC, Pirro AE, Amling M, Delling G, Baron R, Bronson R, Demay MB.; 1997 Sep 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23277

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The Avian Vitamin D Receptors: Primary Structures and Their Origins. by Elaroussi MA, Prahl JM, DeLuca HF.; 1994 Nov 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45278

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The effects of 1[alpha],25-dihydroxyvitamin D3 on matrix metalloproteinase and prostaglandin E2 production by cells of the rheumatoid lesion. by Tetlow LC, Woolley DE.; 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17774

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The role of the T-box for the function of the vitamin D receptor on different types of response elements. by Quack M, Szafranski K, Rouvinen J, Carlberg C.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148003

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The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians. by Chiu KC, Chuang LM, Yoon C.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29095

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Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain. by Yamamoto K, Masuno H, Choi M, Nakashima K, Taga T, Ooizumi H, Umesono K, Sicinska W, VanHooke J, DeLuca HF, Yamada S.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26457

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Transcription Factor TFIIB and the Vitamin D Receptor Cooperatively Activate Ligand-Dependent Transcription. by Blanco JC, Wang I, Tsai SY, Tsai M, O'Malley BW, Jurutka PW, Haussler MR, Ozato K.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42554

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Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. by Alroy I, Towers TL, Freedman LP.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230831

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Transfected Human Liver Cytochrome P-450 Hydroxylates Vitamin D Analogs at Different Side-Chain Positions. by Guo Y, Strugnell S, Back DW, Jones G.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47419

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Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25dihydroxyvitamin D3 by using Streptomyces sp. strains. by Sasaki J, Mikami A, Mizoue K, Omura S.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183884

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Vitamin D and Adaptation to Dietary Calcium and Phosphate Deficiencies Increase Intestinal Plasma Membrane Calcium Pump Gene Expression. by Cai Q, Chandler JS, Wasserman RH, Kumar R, Penniston JT.; 1993 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45869

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Vitamin D concentrations in Asian children aged 2 years living in England: population survey. by Lawson M, Thomas M.; 1999 Jan 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27672

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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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Vitamin D insufficiency in a population of healthy western Canadians. by Rucker D, Allan JA, Fick GH, Hanley DA.; 2002 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113796

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Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. by Vieth R, Fraser D.; 2002 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113800

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Vitamin D interferes with transactivation of the growth hormone gene by thyroid hormone and retinoic acid. by Garcia-Villalba P, Jimenez-Lara AM, Aranda A.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231006

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Vitamin D receptor contains multiple dimerization interfaces that are functionally different. by Nishikawa J, Kitaura M, Imagawa M, Nishihara T.; 1995 Feb 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306727

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Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population. by Ban Y, Taniyama M, Yanagawa T, Yamada S, Maruyama T, Kasuga A, Ban Y.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34514

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Vitamin D Receptor Interaction with Specific DNA Requires a Nuclear Protein and 1,25-Dihydroxyvitamin D3. by Liao J, Ozono K, Sone T, McDonnell DP, Pike JW.; 1990 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=55251

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Vitamin D-Influenced Gene Expression via a Ligand-Independent, Receptor-DNA Complex Intermediate. by Ross TK, Darwish HM, Moss VE, DeLuca HF.; 1993 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47546

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Vitamin D-Mediated Modifications in Protein-DNA Interactions at Two Promoter Elements of the Osteocalcin Gene. by Markose ER, Stein JL, Stein GS, Lian JB.; 1990 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53550

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Vitamin D-Responsive Protein-DNA Interactions at Multiple Promoter Regulatory Elements that Contribute to the Level of Rat Osteocalcin Gene Expression. by Bortell R, Owen TA, Bidwell JP, Gavazzo P, Breen E, van Wijnen AJ, DeLuca HF, Stein JL, Lian JB, Stein GS.; 1992 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49449

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YY1 regulates vitamin D receptor /retinoid X receptor mediated transactivation of the vitamin D responsive osteocalcin gene. by Guo B, Aslam F, van Wijnen AJ, Roberts SG, Frenkel B, Green MR, DeLuca H, Lian JB, Stein GS, Stein JL.; 1997 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19252

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

A case of dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Author(s): Olgun H, Ceviz N, Ozkan B. Source: Turk J Pediatr. 2003 April-June; 45(2): 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921304&dopt=Abstract

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A composite element binding the vitamin D receptor and the retinoic X receptor alpha mediates the transforming growth factor-beta inhibition of decorin gene expression in articular chondrocytes. Author(s): Demoor-Fossard M, Galera P, Santra M, Iozzo RV, Pujol JP, Redini F. Source: The Journal of Biological Chemistry. 2001 October 5; 276(40): 36983-92. Epub 2001 June 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406617&dopt=Abstract

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A low-calcemic vitamin D analog (Ro 25-4020) inhibits the growth of LNCaP human prostate cancer cells with increased potency by producing an active 24-oxo metabolite (Ro 29-9970). Author(s): Swami S, Zhao XY, Sarabia S, Siu-Caldera ML, Uskokovic M, Reddy SG, Feldman D. Source: Recent Results Cancer Res. 2003; 164: 349-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899533&dopt=Abstract

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

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A novel vitamin D-regulated immediate-early gene, IEX-1, alters cellular growth and apoptosis. Author(s): Kumar R, Pittelkow MR, Salisbury JL, Grande JP, Im HJ, Feldmann KA, Schilling D. Source: Recent Results Cancer Res. 2003; 164: 123-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899517&dopt=Abstract

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A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma. Author(s): Dalhoff K, Dancey J, Astrup L, Skovsgaard T, Hamberg KJ, Lofts FJ, Rosmorduc O, Erlinger S, Bach Hansen J, Steward WP, Skov T, Burcharth F, Evans TR. Source: British Journal of Cancer. 2003 July 21; 89(2): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865912&dopt=Abstract

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A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn's disease. Author(s): Bartram SA, Peaston RT, Rawlings DJ, Francis RM, Thompson NP. Source: Alimentary Pharmacology & Therapeutics. 2003 December; 18(11-12): 1121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14653832&dopt=Abstract

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A rationale for vitamin D prescribing in a falls clinic population. Author(s): Dhesi JK, Moniz C, Close JC, Jackson SH, Allain TJ. Source: Age and Ageing. 2002 July; 31(4): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147564&dopt=Abstract

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Alteration of cellular phosphorylation state affects vitamin D receptor-mediated CYP3A4 mRNA induction in Caco-2 cells. Author(s): Hara H, Yasunami Y, Adachi T. Source: Biochemical and Biophysical Research Communications. 2002 August 9; 296(1): 182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147248&dopt=Abstract

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Amyotrophic lateral sclerosis, lead, and genetic susceptibility: polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin D receptor genes. Author(s): Kamel F, Umbach DM, Lehman TA, Park LP, Munsat TL, Shefner JM, Sandler DP, Hu H, Taylor JA. Source: Environmental Health Perspectives. 2003 August; 111(10): 1335-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12896855&dopt=Abstract

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Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Ialpha1 genes and their relationship with height in children with bone cancer. Author(s): Ruza E, Sotillo E, Sierrasesumaga L, Azcona C, Patino-Garcia A. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 October; 25(10): 780-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528100&dopt=Abstract

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Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer. Author(s): Friedrich M, Rafi L, Mitschele T, Tilgen W, Schmidt W, Reichrath J. Source: Recent Results Cancer Res. 2003; 164: 239-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899526&dopt=Abstract

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Analysis of the vitamin D system in cutaneous malignancies. Author(s): Kamradt J, Rafi L, Mitschele T, Meineke V, Gartner BC, Wolfgang T, Holick MF, Reichrath J. Source: Recent Results Cancer Res. 2003; 164: 259-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899528&dopt=Abstract

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Approaches to evaluating the association of vitamin D receptor gene polymorphisms with breast cancer risk. Author(s): Guy M, Lowe LC, Bretherton-Watt D, Mansi JL, Colston KW. Source: Recent Results Cancer Res. 2003; 164: 43-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899513&dopt=Abstract

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Association between vitamin D receptor gene haplotypes and bone mass in postmenopausal Korean women. Author(s): Kim JG, Kwon JH, Kim SH, Choi YM, Moon SY, Lee JY. Source: American Journal of Obstetrics and Gynecology. 2003 November; 189(5): 123440. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14634546&dopt=Abstract

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Association of polymorphisms of interleukin-6, osteocalcin, and vitamin D receptor genes, alone or in combination, with bone mineral density in community-dwelling Japanese women and men. Author(s): Yamada Y, Ando F, Niino N, Shimokata H. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3372-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843190&dopt=Abstract

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Association of vitamin D receptor gene polymorphism with periodontal diseases in Japanese and Chinese. Author(s): Tachi Y, Shimpuku H, Nosaka Y, Kawamura T, Shinohara M, Ueda M, Imai H, Ohura K, Sun J, Meng H, Cao C. Source: Nucleic Acids Res Suppl. 2001; (1): 111-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836289&dopt=Abstract

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Association of vitamin D receptor gene polymorphism with sporadic breast cancer in Taiwanese patients. Author(s): Hou MF, Tien YC, Lin GT, Chen CJ, Liu CS, Lin SY, Huang TJ. Source: Breast Cancer Research and Treatment. 2002 July; 74(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150447&dopt=Abstract

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Association of vitamin D receptor polymorphisms with osteoporosis in mexican postmenopausal women. Author(s): Lisker R, Lopez MA, Jasqui S, Ponce De Leon Rosales S, Correa-Rotter R, Sanchez S, Mutchinick OM. Source: Human Biology; an International Record of Research. 2003 June; 75(3): 399-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527203&dopt=Abstract

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Associations of polymorphisms in the vitamin D receptor gene (BsmI and FokI) with bone mineral density in postmenopausal women in Malta. Author(s): Vidal C, Grima C, Brincat M, Megally N, Xuereb-Anastasi A. 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 November; 14(11): 923-8. Epub 2003 October 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557853&dopt=Abstract

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Associations of renal function with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers. Author(s): Weaver VM, Schwartz BS, Ahn KD, Stewart WF, Kelsey KT, Todd AC, Wen J, Simon DJ, Lustberg ME, Parsons PJ, Silbergeld EK, Lee BK. Source: Environmental Health Perspectives. 2003 October; 111(13): 1613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527840&dopt=Abstract

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Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity. Author(s): Swamy N, Ghosh S, Schneider GB, Ray R. Source: Journal of Cellular Biochemistry. 2001; 81(3): 535-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255236&dopt=Abstract

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BAG-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway. Author(s): Witcher M, Yang X, Pater A, Tang SC. Source: Experimental Cell Research. 2001 April 15; 265(1): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281654&dopt=Abstract

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BB genotype of the vitamin D receptor gene polymorphism postpones parathyroidectomy in hemodialysis patients. Author(s): Borras M, Torregrossa V, Oliveras A, Almirall J, Ma Paz M, Betriu A, Martin M, Muray S, Fibla J, Fernandez E. Source: Journal of Nephrology. 2003 January-February; 16(1): 116-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649542&dopt=Abstract

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Binding of a C-terminal fragment (residues 369 to 435) of vitamin D-binding protein to actin. Author(s): Buch S, Gremm D, Wegner A, Mannherz HG. Source: Biological Chemistry. 2002 October; 383(10): 1621-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452439&dopt=Abstract

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Binding of liganded vitamin D receptor to the vitamin D receptor interacting protein coactivator complex induces interaction with RNA polymerase II holoenzyme. Author(s): Chiba N, Suldan Z, Freedman LP, Parvin JD. Source: The Journal of Biological Chemistry. 2000 April 14; 275(15): 10719-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753860&dopt=Abstract

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Bioavailability of vitamin D from wild edible mushrooms (Cantharellus tubaeformis) as measured with a human bioassay. Author(s): Outila TA, Mattila PH, Piironen VI, Lamberg-Allardt CJ. Source: The American Journal of Clinical Nutrition. 1999 January; 69(1): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9925129&dopt=Abstract

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Biochemical and preliminary crystallographic characterization of the vitamin D sterol- and actin-binding by human vitamin D-binding protein. Author(s): Swamy N, Head JF, Weitz D, Ray R. Source: Archives of Biochemistry and Biophysics. 2002 June 1; 402(1): 14-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051678&dopt=Abstract

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Biological dosimetry to determine the UV radiation climate inside the MIR station and its role in vitamin D biosynthesis. Author(s): Rettberg P, Horneck G, Zittermann A, Heer M. Source: Advances in Space Research : the Official Journal of the Committee on Space Research (Cospar). 1998; 22(12): 1643-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11542408&dopt=Abstract

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Birthweight, vitamin D receptor genotype and the programming of osteoporosis. Author(s): Dennison EM, Arden NK, Keen RW, Syddall H, Day IN, Spector TD, Cooper C. Source: Paediatric and Perinatal Epidemiology. 2001 July; 15(3): 211-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489147&dopt=Abstract

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Blood pressure is correlated with vitamin d(3) serum levels in dialysis patients. Author(s): Argiles A, Lorho R, Servel MF, Couret I, Chong G, Mourad G. Source: Blood Purification. 2002; 20(4): 370-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169847&dopt=Abstract

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Blunted response to vitamin D in uremia. Author(s): Glorieux G, Vanholder R. Source: Kidney International. Supplement. 2001 February; 78: S182-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169007&dopt=Abstract

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Bone density in axial and appendicular skeleton in patients with lactose intolerance: influence of calcium intake and vitamin D status. Author(s): Segal E, Dvorkin L, Lavy A, Rozen GS, Yaniv I, Raz B, Tamir A, Ish-Shalom S. Source: Journal of the American College of Nutrition. 2003 June; 22(3): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805246&dopt=Abstract

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Bone disease: a primer/Part I. Clinical differences among vitamin D hormone compounds. Author(s): Goode JL. Source: Nephrol News Issues. 2001 May; 15(6): 22-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108997&dopt=Abstract

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Bone mass, bone turnover, vitamin D, and estrogen receptor gene polymorphisms in male to female transsexuals: effects of estrogenic treatment on bone metabolism of the male. Author(s): Sosa M, Jodar E, Arbelo E, Dominguez C, Saavedra P, Torres A, Salido E, de Tejada MJ, Hernandez D. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2003 Fall; 6(3): 297-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515001&dopt=Abstract

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Bone mass, vitamin D deficiency and hyperparathyroidism in congestive heart failure. Author(s): Diez-Perez A, Nogues X, Mellibovsky L, Carbonell J. Source: The American Journal of Medicine. 1998 October; 105(4): 358-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809702&dopt=Abstract

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Bone turnover in prolonged critical illness: effect of vitamin D. Author(s): Van den Berghe G, Van Roosbroeck D, Vanhove P, Wouters PJ, De Pourcq L, Bouillon R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 October; 88(10): 4623-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557432&dopt=Abstract

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Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Author(s): Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Source: International Journal of Cancer. Journal International Du Cancer. 2004 January 1; 108(1): 104-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14618623&dopt=Abstract

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BsmI vitamin D receptor polymorphism and pathogenesis of parathyroid adenoma. Author(s): Pacheco D, Menarguez J, Cristobal E, Arribas B, Alcazar JA, Carrion R, Polo JR. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 July-August; 6(4): 658-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208387&dopt=Abstract

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Butyrate-induced differentiation of Caco-2 cells is mediated by vitamin D receptor. Author(s): Gaschott T, Werz O, Steinmeyer A, Steinhilber D, Stein J. Source: Biochemical and Biophysical Research Communications. 2001 November 2; 288(3): 690-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676498&dopt=Abstract

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By the way, doctor. I know I should use sunscreen when I go outdoors in order to reduce my risk for skin cancer. But I've heard that sunscreen blocks my skin's ability to make vitamin D. Is this true? I don't want to miss out on the vitamin D that I need for bone strength. Author(s): Olbricht S. Source: Harvard Women's Health Watch. 2003 June; 10(10): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835160&dopt=Abstract

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Calcium and vitamin D supplementation in nursing home residents. Author(s): Smith RL. Source: Journal of the American Medical Directors Association. 2003 March-April; 4(2 Suppl): S23-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807567&dopt=Abstract

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Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women. Author(s): Baeksgaard L, Andersen KP, Hyldstrup L. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1998; 8(3): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9797910&dopt=Abstract

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Calcium and vitamin D. Author(s): Heaney RP, Weaver CM. Source: Endocrinology and Metabolism Clinics of North America. 2003 March; 32(1): 181-94, Vii-Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699298&dopt=Abstract

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Calcium, magnesium, phosphorus and vitamin D fortification of complementary foods. Author(s): Abrams SA, Atkinson SA. Source: The Journal of Nutrition. 2003 September; 133(9): 2994S-9S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949399&dopt=Abstract

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Calcium, vitamin D and etidronate for the prevention and treatment of corticosteroidinduced osteoporosis in patients with rheumatic diseases. Author(s): Loddenkemper K, Grauer A, Burmester GR, Buttgereit F. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673885&dopt=Abstract

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Calcium, vitamin D, and nutrition in elderly adults. Author(s): Nieves JW. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 321-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916289&dopt=Abstract

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Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). Author(s): McCullough ML, Robertson AS, Rodriguez C, Jacobs EJ, Chao A, Carolyn J, Calle EE, Willett WC, Thun MJ. Source: Cancer Causes & Control : Ccc. 2003 February; 14(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708719&dopt=Abstract

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Change in plasma levels of vitamin D after consumption of cod-liver and fresh codliver oil as part of the traditional north Norwegian fish dish “Molje”. Author(s): Brustad M, Sandanger T, Wilsgaard T, Aksnes L, Lund E. Source: Int J Circumpolar Health. 2003 March; 62(1): 40-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725340&dopt=Abstract

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Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Author(s): Lamprecht SA, Lipkin M. Source: Nature Reviews. Cancer. 2003 August; 3(8): 601-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894248&dopt=Abstract

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Chemoprevention of mammary carcinogenesis by 1alpha-hydroxyvitamin D5, a synthetic analog of Vitamin D. Author(s): Mehta RG, Hussain EA, Mehta RR, Das Gupta TK. Source: Mutation Research. 2003 February-March; 523-524: 253-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628523&dopt=Abstract

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Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth. Author(s): Whitfield GK, Dang HT, Schluter SF, Bernstein RM, Bunag T, Manzon LA, Hsieh G, Dominguez CE, Youson JH, Haussler MR, Marchalonis JJ. Source: Endocrinology. 2003 June; 144(6): 2704-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746335&dopt=Abstract

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Combination of 22-oxa-1,25-dihydroxyvitamin D(3), a vitamin D(3) derivative, with vitamin K(2) (VK2) synergistically enhances cell differentiation but suppresses VK2inducing apoptosis in HL-60 cells. Author(s): Funato K, Miyazawa K, Yaguchi M, Gotoh A, Ohyashiki K. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 August; 16(8): 1519-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145693&dopt=Abstract

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Combination of vitamin D metabolites with selective inhibitors of vitamin D metabolism. Author(s): Schuster I, Egger H, Reddy GS, Vorisek G. Source: Recent Results Cancer Res. 2003; 164: 169-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899522&dopt=Abstract

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Combined radioguided parathyroidectomy and intravenous vitamin D therapy for the treatment of uraemic hyperparathyroidism. Author(s): Oyama Y, Kazama JJ, Maruyama H, Narita I, Kanbayashi C, Koyama Y, Omori T, Hatakeyama K, Gejyo F. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18 Suppl 3: Iii76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771307&dopt=Abstract

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Comparative study of bone mineral density, calcium, and vitamin D status in the Gujarati and white populations of Leicester. Author(s): Hamson C, Goh L, Sheldon P, Samanta A. Source: Postgraduate Medical Journal. 2003 May; 79(931): 279-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782775&dopt=Abstract

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Comparison of human facial UV exposure at high and low latitudes and the potential impact on dermal vitamin D production. Author(s): Kimlin MG, Downs NJ, Parisi AV. Source: Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. 2003 April; 2(4): 370-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760532&dopt=Abstract

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Congenital rickets due to maternal vitamin D deficiency in a sunny island of Greece. Author(s): Anatoliotaki M, Tsilimigaki A, Tsekoura T, Schinaki A, Stefanaki S, Nikolaidou P. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003; 92(3): 389-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725557&dopt=Abstract

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Crystal structure of the complex between actin and human vitamin D-binding protein at 2.5 A resolution. Author(s): Head JF, Swamy N, Ray R. Source: Biochemistry. 2002 July 23; 41(29): 9015-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119014&dopt=Abstract

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Current understanding of the function of the nuclear vitamin D receptor in response to its natural and synthetic ligands. Author(s): Carlberg C. Source: Recent Results Cancer Res. 2003; 164: 29-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899512&dopt=Abstract

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Current understanding of the molecular actions of vitamin D. Author(s): Jones G, Strugnell SA, DeLuca HF. Source: Physiological Reviews. 1998 October; 78(4): 1193-231. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9790574&dopt=Abstract

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Dairy products, calcium, and vitamin D and risk of prostate cancer. Author(s): Chan JM, Giovannucci EL. Source: Epidemiologic Reviews. 2001; 23(1): 87-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588859&dopt=Abstract

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Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas. Author(s): Yano S, Sugimoto T, Tsukamoto T, Chihara K, Kobayashi A, Kitazawa S, Maeda S, Kitazawa R. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 April; 148(4): 403-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656660&dopt=Abstract

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Decreased cutaneous vitamin D-synthesis in heavily melanized individuals: a rare cause for pathologic fractures of the hip. Author(s): Berger CE, Marteau R, Pabinger C, Kroner A, Ogris E, Engel A. Source: Wiener Klinische Wochenschrift. 2003 March 31; 115(5-6): 186-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741080&dopt=Abstract

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Dehydroepiandrosterone status in postmenopausal women is determined by the gene for the vitamin D receptor. Author(s): Zofkova I, Hill M, Zajickova K. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 March; 34(3): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972301&dopt=Abstract

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Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D. Author(s): Chaussain-Miller C, Sinding C, Wolikow M, Lasfargues JJ, Godeau G, Garabedian M. Source: The Journal of Pediatrics. 2003 March; 142(3): 324-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640383&dopt=Abstract

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De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. Author(s): Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. Source: The Journal of Biological Chemistry. 2003 September 26; 278(39): 38084-93. Epub 2003 July 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867411&dopt=Abstract

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Development and assessment of a short instrument for assessing dietary intakes of calcium and vitamin D. Author(s): Blalock SJ, Norton LL, Patel RA, Cabral K, Thomas CL. Source: J Am Pharm Assoc (Wash Dc). 2003 November-December; 43(6): 685-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14717265&dopt=Abstract

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Dietary calcium and vitamin D intake and risk of colorectal cancer: a prospective cohort study in women. Author(s): Terry P, Baron JA, Bergkvist L, Holmberg L, Wolk A. Source: Nutrition and Cancer. 2002; 43(1): 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467133&dopt=Abstract

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Dietary calcium intake and serum vitamin D are major determinants of bone mass variations in women. A longitudinal study. Author(s): del Puente A, Esposito A, Savastano S, Carpinelli A, Postiglione L, Oriente P. Source: Aging Clin Exp Res. 2002 October; 14(5): 382-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602573&dopt=Abstract

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Difference in height associated with a translation start site polymorphism in the vitamin D receptor gene. Author(s): Minamitani K, Takahashi Y, Minagawa M, Yasuda T, Niimi H. Source: Pediatric Research. 1998 November; 44(5): 628-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803441&dopt=Abstract

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Differential regulation of vitamin D receptor and its ligand in human monocytederived dendritic cells. Author(s): Hewison M, Freeman L, Hughes SV, Evans KN, Bland R, Eliopoulos AG, Kilby MD, Moss PA, Chakraverty R. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 June 1; 170(11): 5382-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759412&dopt=Abstract

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Distinct retinoid X receptor activation function-2 residues mediate transactivation in homodimeric and vitamin D receptor heterodimeric contexts. Author(s): Thompson PD, Remus LS, Hsieh JC, Jurutka PW, Whitfield GK, Galligan MA, Encinas Dominguez C, Haussler CA, Haussler MR. Source: Journal of Molecular Endocrinology. 2001 October; 27(2): 211-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564604&dopt=Abstract

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Distribution analysis of vitamin D highlights differences in population subgroups: preliminary observations from a pilot study in UK adults. Author(s): Pal BR, Marshall T, James C, Shaw NJ. Source: The Journal of Endocrinology. 2003 October; 179(1): 119-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529572&dopt=Abstract

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Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women: relationship to plasma parathyroid hormone and calcium and phosphate metabolism. Author(s): Rejnmark L, Lauridsen AL, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 May; 146(5): 635-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980618&dopt=Abstract

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Do the COL1A1 and Taq 1 vitamin D receptor polymorphisms have a role in identifying individuals at risk of developing osteoporosis? Author(s): McClean E, Archbold GP, Taggart HM. Source: Ulster Med J. 2003 May; 72(1): 26-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868700&dopt=Abstract

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Do we really need > or = 100 microg vitamin D/d, and is it safe for all of us? Author(s): Muskiet FA, Dijck-Brouwer DA, van der Veer E, Schaafsma A. Source: The American Journal of Clinical Nutrition. 2001 December; 74(6): 862-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722970&dopt=Abstract

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Does sunscreen block the skin's ability to make vitamin D? If so, how can I get enough of this vitamin without raising my risk of skin cancer? Author(s): Holick M. Source: Health News. 2002 July; 8(7): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132498&dopt=Abstract

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Double bond in the side chain of 1alpha,25-dihydroxy-22-ene-vitamin D(3) is reduced during its metabolism: studies in chronic myeloid leukemia (RWLeu-4) cells and rat kidney. Author(s): Sunita Rao D, Balkundi D, Uskokovic MR, Tserng K, Clark JW, Horst RL, Satyanarayana Reddy G. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 August; 78(2): 167-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566441&dopt=Abstract

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Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient. Author(s): Arekat MR, And G, Lemke S, Moses AM. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Fall; 5(3): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357064&dopt=Abstract

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Ectopic expression of CXCR5/BLR1 accelerates retinoic acid- and vitamin D(3)induced monocytic differentiation of U937 cells. Author(s): Battle TE, Yen A. Source: Experimental Biology and Medicine (Maywood, N.J.). 2002 October; 227(9): 75362. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324654&dopt=Abstract

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Effect of estrogen treatment and vitamin D status on differing bioavailabilities of calcium carbonate and calcium citrate. Author(s): Heller HJ, Poindexter JR, Adams-Huet B. Source: Journal of Clinical Pharmacology. 2002 November; 42(11): 1251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412824&dopt=Abstract

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Effect of pretreatment vitamin D levels on in vivo effects of atorvastatin on bone metabolism in patients with heterozygous familial hypercholesterolemia. Author(s): Kajinami K, Takekoshi N, Matsui S, Kanemitsu S, Okubo S, Kanayama S, Yamashita N, Sato R. Source: The American Journal of Cardiology. 2003 November 1; 92(9): 1113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583368&dopt=Abstract

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Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes. Author(s): Palomba S, Numis FG, Mossetti G, Rendina D, Vuotto P, Russo T, Zullo F, Nappi C, Nunziata V. Source: Clinical Endocrinology. 2003 March; 58(3): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608943&dopt=Abstract

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Effects of 'non-calcaemic' vitamin D analogues on 24-hydroxylase expression in MG63 osteoblast-like cells. Author(s): Schroeder NJ, Burrin JM, Noonan K, Makin HL, Cunningham J. Source: Nephron. Physiology [electronic Resource]. 2003; 94(4): P62-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972708&dopt=Abstract

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Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Author(s): Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 343-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568412&dopt=Abstract

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Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. Author(s): Kenny AM, Biskup B, Robbins B, Marcella G, Burleson JA. Source: Journal of the American Geriatrics Society. 2003 December; 51(12): 1762-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14687355&dopt=Abstract

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Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. Author(s): Latham NK, Anderson CS, Reid IR. Source: Journal of the American Geriatrics Society. 2003 September; 51(9): 1219-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919233&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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Efferent loop small intestinal vitamin D receptor concentration and bone mineral density after Billroth II (Polya) gastrectomy in humans. Author(s): Pazianas M, Zaidi M, Subhani JM, Finch PJ, Ang L, Maxwell JD. Source: Calcified Tissue International. 2003 April; 72(4): 485-90. Epub 2003 February 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574872&dopt=Abstract

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Efficacy of an oral, 10-day course of high-dose calciferol in correcting vitamin D deficiency. Author(s): Wu F, Staykova T, Horne A, Clearwater J, Ames R, Mason B, Orr-Walker B, Gamble G, Scott M, Reid I. Source: N Z Med J. 2003 August 8; 116(1179): U536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513083&dopt=Abstract

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Efficacy of Vitamin D compounds to modulate estrogen receptor negative breast cancer growth and invasion. Author(s): Flanagan L, Packman K, Juba B, O'Neill S, Tenniswood M, Welsh J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 181-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711002&dopt=Abstract

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Energy, protein, calcium, vitamin D and fibre intakes from meals in residential care establishments in Australia. Author(s): Nowson CA, Sherwin AJ, McPhee JG, Wark JD, Flicker L. Source: Asia Pacific Journal of Clinical Nutrition. 2003; 12(2): 172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810407&dopt=Abstract

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Estrogen receptor alpha and vitamin D receptor gene polymorphisms and bone mineral density: association study of healthy pre- and postmenopausal Chinese women. Author(s): Zhang YY, Long JR, Liu PY, Liu YJ, Shen H, Zhao LJ, Deng HW. Source: Biochemical and Biophysical Research Communications. 2003 September 5; 308(4): 777-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927786&dopt=Abstract

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Evaluation of vitamin D analogs as therapeutic agents for prostate cancer. Author(s): Chen TC, Holick MF, Lokeshwar BL, Burnstein KL, Schwartz GG. Source: Recent Results Cancer Res. 2003; 164: 273-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899529&dopt=Abstract

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Evidence for tissue- and cell-type selective activation of the vitamin D receptor by Ro26-9228, a noncalcemic analog of vitamin D3. Author(s): Peleg S, Ismail A, Uskokovic MR, Avnur Z. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520525&dopt=Abstract

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Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins. Author(s): Hunter DJ, Hart D, Snieder H, Bettica P, Swaminathan R, Spector TD. Source: Rheumatology (Oxford, England). 2003 November; 42(11): 1311-6. Epub 2003 July 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867590&dopt=Abstract

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Evolution and function of vitamin D. Author(s): Holick MF. Source: Recent Results Cancer Res. 2003; 164: 3-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899511&dopt=Abstract

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Exclusive underexpression of vitamin D receptor exon 1f transcripts in tumors of primary hyperparathyroidism. Author(s): Correa P, Akerstrom G, Westin G. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 November; 147(5): 671-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444900&dopt=Abstract

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Expression, structure-function, and molecular modeling of vitamin D P450s. Author(s): Omdahl JL, Bobrovnikova EV, Annalora A, Chen P, Serda R. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 356-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520537&dopt=Abstract

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Factors associated with the intention to use vitamin D supplements: quantitative study among a sample of elderly people in a medium-sized town in the Netherlands. Author(s): Engels Y, van Assema P, Dorant E, Lechner L. Source: Journal of Nutrition Education. 2001 May-June; 33(3): 134-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953228&dopt=Abstract

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Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel. Author(s): Stein MS, Wark JD, Scherer SC, Walton SL, Chick P, Di Carlantonio M, Zajac JD, Flicker L. Source: Journal of the American Geriatrics Society. 1999 October; 47(10): 1195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10522952&dopt=Abstract

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Familial calcium stone disease: TaqI polymorphism and the vitamin D receptor. Author(s): Jackman SV, Kibel AS, Ovuworie CA, Moore RG, Kavoussi LR, Jarrett TW. Source: Journal of Endourology / Endourological Society. 1999 May; 13(4): 313-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405913&dopt=Abstract

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Familial hypophosphatemic vitamin D-resistant rickets: dental findings and histologic study of teeth. Author(s): Murayama T, Iwatsubo R, Akiyama S, Amano A, Morisaki I. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2000 September; 90(3): 310-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982952&dopt=Abstract

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Family screening is effective in picking up undiagnosed Asian vitamin D deficient subjects. Author(s): Iqbal SJ, Featherstone S, Kaddam IM, Mortimer J, Manning D. Source: Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association. 2001 October; 14(5): 371-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906578&dopt=Abstract

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Final height of Japanese patients with X-linked hypophosphatemic rickets: effect of vitamin D and phosphate therapy. Author(s): Miyamoto J, Koto S, Hasegawa Y. Source: Endocrine Journal. 2000 April; 47(2): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943740&dopt=Abstract

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Fish as a major source of vitamin D in the Japanese diet. Author(s): Nakamura K, Nashimoto M, Okuda Y, Ota T, Yamamoto M. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 May; 18(5): 415-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985947&dopt=Abstract

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Fluoride salts are no better at preventing new vertebral fractures than calciumvitamin D in postmenopausal osteoporosis: the FAVOStudy. Author(s): Meunier PJ, Sebert JL, Reginster JY, Briancon D, Appelboom T, Netter P, Loeb G, Rouillon A, Barry S, Evreux JC, Avouac B, Marchandise X. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1998; 8(1): 4-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9692071&dopt=Abstract

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Fluorinated vitamin D analogs to probe the conformation of vitamin D in its receptor complex: 19F-NMR studies and biological activity. Author(s): Ohno A, Shimizu M, Yamada S. Source: Chemical & Pharmaceutical Bulletin. 2002 April; 50(4): 475-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11963993&dopt=Abstract

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Fok I polymorphism at the human vitamin D receptor gene locus in Europeans and Africans. Author(s): Lucotte G, Mercier G, Burckel A. Source: Clinical Genetics. 1999 April; 55(4): 281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10361992&dopt=Abstract

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FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women. Author(s): Gennari L, Becherini L, Mansani R, Masi L, Falchetti A, Morelli A, Colli E, Gonnelli S, Cepollaro C, Brandi ML. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1999 August; 14(8): 1379-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457270&dopt=Abstract

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Folate, vitamin D, and iron intakes are low among pregnant Finnish women. Author(s): Erkkola M, Karppinen M, Jarvinen A, Knip M, Virtanen SM. Source: European Journal of Clinical Nutrition. 1998 October; 52(10): 742-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9805222&dopt=Abstract

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Food patterns, flour fortification, and intakes of calcium and vitamin D: a longitudinal study of Danish adults. Author(s): Osler M, Heitmann BL. Source: Journal of Epidemiology and Community Health. 1998 March; 52(3): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9616420&dopt=Abstract

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Forgotten mysteries in the early history of vitamin D. Author(s): Carpenter KJ, Zhao L. Source: The Journal of Nutrition. 1999 May; 129(5): 923-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10222380&dopt=Abstract

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Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Author(s): Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Source: The American Journal of Clinical Nutrition. 2003 June; 77(6): 1478-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791627&dopt=Abstract

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Fractures in the elderly and vitamin D. Author(s): Simon J, Leboff M, Wright J, Glowacki J. Source: J Nutr Health Aging. 2002; 6(6): 406-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459891&dopt=Abstract

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Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism. Author(s): Ramalho AC, Lazaretti-Castro M, Hauache O, Kasamatsu T, Brandao C, Reis AF, Takata E, Cafalli F, Tavares F, Gimeno SG, Vieira JG. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 1998 July; 31(7): 921-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698755&dopt=Abstract

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Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor. Author(s): Rochel N, Tocchini-Valentini G, Egea PF, Juntunen K, Garnier JM, Vihko P, Moras D. Source: European Journal of Biochemistry / Febs. 2001 February; 268(4): 971-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179963&dopt=Abstract

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Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter. Author(s): Lee TH, Pelletier J. Source: Physiological Genomics. 2001 December 21; 7(2): 187-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773605&dopt=Abstract

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Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Author(s): Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR. Source: Molecular and Cellular Endocrinology. 2001 May 25; 177(1-2): 145-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377830&dopt=Abstract

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Gastric fundectomy in the rat: effects on mineral and bone metabolism, with emphasis on the gastrin-calcitonin-parathyroid hormone-vitamin D axis. Author(s): Rumenapf G, Schwille PO, Erben RG, Schreiber M, Berge B, Fries W, Schmiedl A, Koroma S, Hohenberger W. Source: Calcified Tissue International. 1998 November; 63(5): 433-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799830&dopt=Abstract

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Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus. Author(s): Gyorffy B, Vasarhelyi B, Krikovszky D, Madacsy L, Tordai A, Tulassay T, Szabo A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 December; 147(6): 803-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457456&dopt=Abstract

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Gene regulation by extracellular calcium, vitamin D and osmolarity. Author(s): Okazaki T. Source: Endocrine Journal. 1999 February; 46(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10426563&dopt=Abstract

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Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients. Canadian Collaborative Study Group. Author(s): Steckley JL, Dyment DA, Sadovnick AD, Risch N, Hayes C, Ebers GC. Source: Neurology. 2000 February 8; 54(3): 729-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10680811&dopt=Abstract

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Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. Author(s): Vogel A, Strassburg CP, Manns MP. Source: Hepatology (Baltimore, Md.). 2002 January; 35(1): 126-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786968&dopt=Abstract

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Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. Author(s): Hunter D, De Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 February; 16(2): 371-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204437&dopt=Abstract

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Genetic control of bone density and turnover: role of the collagen 1alpha1, estrogen receptor, and vitamin D receptor genes. Author(s): Brown MA, Haughton MA, Grant SF, Gunnell AS, Henderson NK, Eisman JA. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 April; 16(4): 758-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316004&dopt=Abstract

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Genetic disorders of vitamin D biosynthesis. Author(s): Miller WL, Portale AA. Source: Endocrinology and Metabolism Clinics of North America. 1999 December; 28(4): 825-40, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609122&dopt=Abstract

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Genetic influences on bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women. Notification of genotype corrections. Author(s): Howard G, Nguyen T, Morrison N, Watanabe T, Sambrook P, Eisman J, Kelly P. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 March; 83(3): 1043. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9506774&dopt=Abstract

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Genetic mutation in the human 25-hydroxyvitamin D3 1alpha-hydroxylase gene causes vitamin D-dependent rickets type I. Author(s): Kato S. Source: Molecular and Cellular Endocrinology. 1999 October 25; 156(1-2): 7-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10612418&dopt=Abstract

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Genetic variations in the vitamin D receptor, androgen receptor and enzymes that regulate androgen metabolism. Author(s): Price DK, Franks ME, Figg WD. Source: The Journal of Urology. 2004 February; 171(2 Pt 2): S45-9; Discussion S49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14713753&dopt=Abstract

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Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families. Author(s): Wang JT, Lin CJ, Burridge SM, Fu GK, Labuda M, Portale AA, Miller WL. Source: American Journal of Human Genetics. 1998 December; 63(6): 1694-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9837822&dopt=Abstract

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Genetics of vitamin D biosynthesis and its disorders. Author(s): Miller WL, Portale AA. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2001 March; 15(1): 95-109. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469813&dopt=Abstract

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Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth. Author(s): Rao A, Woodruff RD, Wade WN, Kute TE, Cramer SD. Source: The Journal of Nutrition. 2002 October; 132(10): 3191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368417&dopt=Abstract

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Genistein inhibits vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells. Author(s): Farhan H, Wahala K, Cross HS. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 March; 84(4): 423-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732287&dopt=Abstract

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Greater trunk muscle torque reduces postmenopausal bone loss at the spine independently of age, body size, and vitamin D receptor genotype in Japanese women. Author(s): Iki M, Saito Y, Dohi Y, Kajita E, Nishino H, Yonemasu K, Kusaka Y. Source: Calcified Tissue International. 2002 October; 71(4): 300-7. Epub 2002 August 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154394&dopt=Abstract

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Growth inhibition and differentiation in human prostate carcinoma cells induced by the vitamin D analog 1alpha,24-dihydroxyvitamin D2. Author(s): Bauer JA, Thompson TA, Church DR, Ariazi EA, Wilding G. Source: The Prostate. 2003 May 15; 55(3): 159-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692781&dopt=Abstract

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Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. Author(s): Colston KW, Perks CM, Xie SP, Holly JM. Source: Journal of Molecular Endocrinology. 1998 February; 20(1): 157-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9513092&dopt=Abstract

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Hectorol: a new vitamin D prohormone. Author(s): Peter WL. Source: Nephrology Nursing Journal : Journal of the American Nephrology Nurses' Association. 2000 February; 27(1): 67-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852695&dopt=Abstract

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Hepatocyte growth factor and vitamin D cooperatively inhibit androgenunresponsive prostate cancer cell lines. Author(s): Qadan LR, Perez-Stable CM, Schwall RH, Burnstein KL, Ostenson RC, Howard GA, Roos BA. Source: Endocrinology. 2000 July; 141(7): 2567-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875259&dopt=Abstract

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Heterogeneous nuclear ribonucleoprotein (hnRNP) binding to hormone response elements: a cause of vitamin D resistance. Author(s): Chen H, Hewison M, Hu B, Adams JS. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 May 13; 100(10): 6109-14. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716975&dopt=Abstract

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High bone turnover in Muslim women with vitamin D deficiency. Author(s): Diamond TH, Levy S, Smith A, Day P. Source: The Medical Journal of Australia. 2002 August 5; 177(3): 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149082&dopt=Abstract

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High prevalence of vitamin D deficiency in Japanese female patients with Graves' disease. Author(s): Yamashita H, Noguchi S, Takatsu K, Koike E, Murakami T, Watanabe S, Uchino S, Yamashita H, Kawamoto H. Source: Endocrine Journal. 2001 February; 48(1): 63-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403104&dopt=Abstract

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History of the development of new vitamin D analogs: studies on 22-oxacalcitriol (OCT) and 2beta-(3-hydroxypropoxy)calcitriol (ED-71). Author(s): Nishii Y, Okano T. Source: Steroids. 2001 March-May; 66(3-5): 137-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179721&dopt=Abstract

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HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. Author(s): Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. Source: Aids (London, England). 2003 March 7; 17(4): 513-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598771&dopt=Abstract

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Host genetic background at CCR5 chemokine receptor and vitamin D receptor loci and human immunodeficiency virus (HIV) type 1 disease progression among HIVseropositive injection drug users. Author(s): Barber Y, Rubio C, Fernandez E, Rubio M, Fibla J. Source: The Journal of Infectious Diseases. 2001 November 15; 184(10): 1279-88. Epub 2001 October 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679916&dopt=Abstract

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How about vitamin D receptor polymorphisms? Author(s): Pols HA, Uitterlinden AG, van Leeuwen JP. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1998; 8 Suppl 2: S20-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10197178&dopt=Abstract

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Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. Author(s): Canaff L, Hendy GN. Source: The Journal of Biological Chemistry. 2002 August 16; 277(33): 30337-50. Epub 2002 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036954&dopt=Abstract

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Human leukemic (HMC-1) mast cells are responsive to 1alpha, 25-dihydroxyvitamin D(3): selective promotion of ICAM-3 expression and constitutive presence of vitamin D(3) receptor. Author(s): Babina M, Krautheim M, Grutzkau A, Henz BM. Source: Biochemical and Biophysical Research Communications. 2000 July 14; 273(3): 1104-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10891379&dopt=Abstract

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Human neutrophils express messenger RNA of vitamin D receptor and respond to 1alpha,25-dihydroxyvitamin D3. Author(s): Takahashi K, Nakayama Y, Horiuchi H, Ohta T, Komoriya K, Ohmori H, Kamimura T. Source: Immunopharmacology and Immunotoxicology. 2002 August; 24(3): 335-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375732&dopt=Abstract

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Human TAF(II)55 interacts with the vitamin D(3) and thyroid hormone receptors and with derivatives of the retinoid X receptor that have altered transactivation properties. Author(s): Lavigne AC, Mengus G, Gangloff YG, Wurtz JM, Davidson I. Source: Molecular and Cellular Biology. 1999 August; 19(8): 5486-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10409738&dopt=Abstract

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Hurler's syndrome, West's syndrome, and vitamin D-dependent rickets. Author(s): Gudino MA, Campistol J, Chavez B, Conill J, Hernandez S, Vilaseca MA. Source: Journal of Child Neurology. 2002 February; 17(2): 149-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952079&dopt=Abstract

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Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Author(s): Omdahl JL, Morris HA, May BK. Source: Annual Review of Nutrition. 2002; 22: 139-66. Epub 2002 January 04. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055341&dopt=Abstract

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Hypercalcemia due to vitamin D intoxication with clinical features mimicking acute myocardial infarction. Author(s): Ashizawa N, Arakawa S, Koide Y, Toda G, Seto S, Yano K. Source: Intern Med. 2003 April; 42(4): 340-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729323&dopt=Abstract

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Hyperparathyroidism secondary to vitamin D deficiency. Author(s): Ahmed M, Almahfouz A, Alarifi A, Nasser T, Alkahtani N, Al Dayel F. Source: Clinical Nuclear Medicine. 2003 May; 28(5): 413-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702944&dopt=Abstract

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Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease. Author(s): Tsuchihashi K, Takizawa H, Torii T, Ikeda R, Nakahara N, Yuda S, Kobayashi N, Nakata T, Ura N, Shimamoto K. Source: Nephron. 2000 January; 84(1): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10644903&dopt=Abstract

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Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia? Author(s): McGrath J. Source: Schizophrenia Research. 1999 December 21; 40(3): 173-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638855&dopt=Abstract

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Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breastfeeding infants. Author(s): Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. Source: The Journal of Pediatrics. 2003 February; 142(2): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584539&dopt=Abstract

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Identification of a Vitamin D response element in the human insulin receptor gene promoter. Author(s): Maestro B, Davila N, Carranza MC, Calle C. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711007&dopt=Abstract

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Importance of cytochrome P450-mediated metabolism in the mechanism of action of vitamin D analogs. Author(s): Masuda S, Gao M, Zhang A, Kaufmann M, Jones G. Source: Recent Results Cancer Res. 2003; 164: 189-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899523&dopt=Abstract

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Increased 25-hydroxyvitamin D3 1alpha-hydroxylase and reduced 25-hydroxyvitamin D3 24-hydroxylase expression in parathyroid tumors--new prospects for treatment of hyperparathyroidism with vitamin d. Author(s): Correa P, Segersten U, Hellman P, Akerstrom G, Westin G. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5826-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466393&dopt=Abstract

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Indian endocrinologists warn of vitamin D deficiency. Author(s): Mudur G. Source: Bmj (Clinical Research Ed.). 2003 January 4; 326(7379): 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516610&dopt=Abstract

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Induction of apoptosis by vitamin D metabolites and analogs in a glioma cell line. Author(s): Elias J, Marian B, Edling C, Lachmann B, Noe CR, Rolf SH, Schuster I. Source: Recent Results Cancer Res. 2003; 164: 319-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899531&dopt=Abstract

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Inhibition of F-Box protein p45(SKP2) expression and stabilization of cyclindependent kinase inhibitor p27(KIP1) in vitamin D analog-treated cancer cells. Author(s): Lin R, Wang TT, Miller WH Jr, White JH. Source: Endocrinology. 2003 March; 144(3): 749-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586749&dopt=Abstract

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Inhibition of p70(S6) kinase during transforming growth factor-beta 1/vitamin D(3)induced monocyte differentiation of HL-60 cells allows tumor necrosis factor-alpha to stimulate plasminogen activator inhibitor-1 synthesis. Author(s): Peiretti F, Lopez S, Deprez-Beauclair P, Bonardo B, Juhan-Vague I, Nalbone G. Source: The Journal of Biological Chemistry. 2001 August 24; 276(34): 32214-9. Epub 2001 June 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11402043&dopt=Abstract

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Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression. Author(s): Krishnan AV, Peehl DM, Feldman D. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 363-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520538&dopt=Abstract

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Inhibitors of vitamin D hydroxylases: structure-activity relationships. Author(s): Schuster I, Egger H, Nussbaumer P, Kroemer RT. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 372-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520539&dopt=Abstract

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Intake of dairy products, calcium, and vitamin d and risk of breast cancer. Author(s): Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC. Source: Journal of the National Cancer Institute. 2002 September 4; 94(17): 1301-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208895&dopt=Abstract

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Intakes of calcium and vitamin d predict body mass index in the population of Northern Norway. Author(s): Kamycheva E, Joakimsen RM, Jorde R. Source: The Journal of Nutrition. 2003 January; 133(1): 102-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514276&dopt=Abstract

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Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk. Author(s): Colin EM, Uitterlinden AG, Meurs JB, Bergink AP, van de Klift M, Fang Y, Arp PP, Hofman A, van Leeuwen JP, Pols HA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3777-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915669&dopt=Abstract

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Interaction effects between estrogen receptor alpha gene, vitamin D receptor gene, age, and sex on bone mineral density in Chinese. Author(s): Long J, Liu P, Zhang Y, Shen H, Liu Y, Dvornyk V, Deng HW. Source: Journal of Human Genetics. 2003; 48(10): 514-9. Epub 2003 September 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505233&dopt=Abstract

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Intestinal bile acids can bind to and activate the vitamin D receptor. Author(s): Wolf G. Source: Nutrition Reviews. 2002 September; 60(9): 281-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296454&dopt=Abstract

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Intestinal calcium absorption: Molecular vitamin D mediated mechanisms. Author(s): Bouillon R, Van Cromphaut S, Carmeliet G. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 332-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520535&dopt=Abstract

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Intranuclear trafficking of transcription factors: Requirements for vitamin Dmediated biological control of gene expression. Author(s): Stein GS, Lian JB, Stein JL, Wijnen AJ, Montecino M, Javed A, Pratap J, Choi J, Zaidi SK, Gutierrez S, Harrington K, Shen J, Young D. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 340-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520536&dopt=Abstract

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Is routine supplementation therapy (calcium and vitamin D) useful after total thyroidectomy? Author(s): Bellantone R, Lombardi CP, Raffaelli M, Boscherini M, Alesina PF, De Crea C, Traini E, Princi P. Source: Surgery. 2002 December; 132(6): 1109-12; Discussion 1112-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490862&dopt=Abstract

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Is there rationale for vitamin D prescribing in the elderly population? Author(s): Fisher A, Davis M. Source: Age and Ageing. 2003 March; 32(2): 235-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615578&dopt=Abstract

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Isoflavonoids inhibit catabolism of vitamin D in prostate cancer cells. Author(s): Farhan H, Wahala K, Adlercreutz H, Cross HS. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 September 25; 777(1-2): 261-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270218&dopt=Abstract

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Isolated adrenocorticotropin deficiency presenting with impaired renin-angiotensinaldosterone system and suppressed parathyroid hormone-vitamin D axis. Author(s): Saito T, Tojo K, Yamamoto H, Hosoya T, Tajima N. Source: Intern Med. 2002 July; 41(7): 561-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132525&dopt=Abstract

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Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Author(s): Masood R, Nagpal S, Zheng T, Cai J, Tulpule A, Smith DL, Gill PS. Source: Blood. 2000 November 1; 96(9): 3188-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050002&dopt=Abstract

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Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoid arthritis. Author(s): Lee CK, Hong JS, Cho YS, Yoo B, Kim GS, Moon HB. Source: Journal of Korean Medical Science. 2001 April; 16(2): 188-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306745&dopt=Abstract

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Lack of relationship of calcium and vitamin D intake to bone mineral density in premenopausal women with inflammatory bowel disease. Author(s): Bernstein CN, Bector S, Leslie WD. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2468-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638350&dopt=Abstract

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Leukemia cell differentiation: cellular and molecular interactions of retinoids and vitamin D. Author(s): James SY, Williams MA, Newland AC, Colston KW. Source: General Pharmacology. 1999 January; 32(1): 143-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888267&dopt=Abstract

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Ligand affinity, homodimerization, and ligand-induced secondary structural change of the human vitamin d receptor. Author(s): Falsone SF, Kurkela R, Chiarandini G, Vihko P, Kungl AJ. Source: Biochemical and Biophysical Research Communications. 2001 August 3; 285(5): 1180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478779&dopt=Abstract

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Ligand recognition by the vitamin D receptor. Author(s): Choi M, Yamamoto K, Masuno H, Nakashima K, Taga T, Yamada S. Source: Bioorganic & Medicinal Chemistry. 2001 July; 9(7): 1721-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425573&dopt=Abstract

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Ligand structure-function relationships in the vitamin D endocrine system from the perspective of drug development (including cancer treatment). Author(s): Norman AW, Mizwicki MT, Okamura WH. Source: Recent Results Cancer Res. 2003; 164: 55-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899514&dopt=Abstract

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Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Author(s): Thompson PD, Jurutka PW, Whitfield GK, Myskowski SM, Eichhorst KR, Dominguez CE, Haussler CA, Haussler MR. Source: Biochemical and Biophysical Research Communications. 2002 December 20; 299(5): 730-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470639&dopt=Abstract

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Ligands for the vitamin D endocrine system: different shapes function as agonists and antagonists for genomic and rapid response receptors or as a ligand for the plasma vitamin D binding protein. Author(s): Norman AW, Ishizuka S, Okamura WH. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 JanuaryMarch; 76(1-5): 49-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384863&dopt=Abstract

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Localization of a negative vitamin D response sequence in the human growth hormone gene. Author(s): Seoane S, Alonso M, Segura C, Perez-Fernandez R. Source: Biochemical and Biophysical Research Communications. 2002 March 22; 292(1): 250-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890700&dopt=Abstract

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Longitudinal evaluation of vitamin D status in healthy subjects from southern Italy: seasonal and gender differences. Author(s): Carnevale V, Modoni S, Pileri M, Di Giorgio A, Chiodini I, Minisola S, Vieth R, Scillitani A. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12(12): 1026-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846328&dopt=Abstract

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Long-latency deficiency disease: insights from calcium and vitamin D. Author(s): Heaney RP. Source: The American Journal of Clinical Nutrition. 2003 November; 78(5): 912-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594776&dopt=Abstract

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Long-term hospitalization during pregnancy is a risk factor for vitamin D deficiency in neonates. Author(s): Nishimura K, Shima M, Tsugawa N, Matsumoto S, Hirai H, Santo Y, Nakajima S, Iwata M, Takagi T, Kanda Y, Kanzaki T, Okano T, Ozono K. Source: Journal of Bone and Mineral Metabolism. 2003; 21(2): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601575&dopt=Abstract

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Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis. Author(s): Massenkeil G, Fiene C, Rosen O, Michael R, Reisinger W, Arnold R. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 November; 15(11): 1701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681410&dopt=Abstract

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Low maternal vitamin D and schizophrenia in offspring. Author(s): Altschuler EL. Source: Lancet. 2001 October 27; 358(9291): 1464. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705539&dopt=Abstract

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Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera. Author(s): McGrath J, Eyles D, Mowry B, Yolken R, Buka S. Source: Schizophrenia Research. 2003 September 1; 63(1-2): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892860&dopt=Abstract

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Low serum vitamin d does not predict new disability or loss of muscle strength in older women. Author(s): Verreault R, Semba RD, Volpato S, Ferrucci L, Fried LP, Guralnik JM. Source: Journal of the American Geriatrics Society. 2002 May; 50(5): 912-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028180&dopt=Abstract

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Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. Author(s): Visser M, Deeg DJ, Lips P; Longitudinal Aging Study Amsterdam. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 5766-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671166&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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Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? Author(s): Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P. Source: Journal of the American College of Cardiology. 2003 January 1; 41(1): 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570952&dopt=Abstract

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Low-calcemic vitamin D analogs (deltanoids) for human cancer prevention. Author(s): Posner GH. Source: The Journal of Nutrition. 2002 December; 132(12): 3802S-3803S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468627&dopt=Abstract

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Maternal, fetal and neonatal vitamin D and calcium metabolism during pregnancy and lactation. Author(s): Weisman Y. Source: Endocr Dev. 2003; 6: 34-49. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964424&dopt=Abstract

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Measurement of vitamin D-binding protein in pleural fluids and sera by means of a turbidimetric immunoassay measuring system. Author(s): Hamashima Y, Kanazawa T, Hirata A, Yamai Y, Fujihara H, Sekine K, Nagao K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 July; 321(1-2): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031588&dopt=Abstract

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Mechanism of vitamin D action and its regulation. Author(s): Dusso AS, Brown AJ. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1998 October; 32(2 Suppl 2): S13-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808140&dopt=Abstract

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Mechanisms implicated in the growth regulatory effects of vitamin D compounds in breast cancer cells. Author(s): Lowe L, Hansen CM, Senaratne S, Colston KW. Source: Recent Results Cancer Res. 2003; 164: 99-110. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908448&dopt=Abstract

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Membrane receptors for vitamin D steroid hormones: potential new drug targets. Author(s): Farach-Carson MC, Nemere I. Source: Current Drug Targets. 2003 January; 4(1): 67-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528991&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Author(s): Papadimitropoulos E, Wells G, Shea B, Gillespie W, Weaver B, Zytaruk N, Cranney A, Adachi J, Tugwell P, Josse R, Greenwood C, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 560-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202471&dopt=Abstract

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Modulation effects of zinc on the formation of vitamin D receptor and retinoid X receptor alpha-DNA transcription complexes: analysis by microelectrospray mass spectrometry. Author(s): Craig TA, Benson LM, Naylor S, Kumar R. Source: Rapid Communications in Mass Spectrometry : Rcm. 2001; 15(12): 1011-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400211&dopt=Abstract

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Molecular basis for pseudo vitamin D-deficiency rickets in the Hannover pig. Author(s): Chavez LS, Serda R, Choe S, Davidi L, Harmeyer J, Omdahl JL. Source: The Journal of Nutritional Biochemistry. 2003 July; 14(7): 378-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915218&dopt=Abstract

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Molecular basis of the selective activity of vitamin D analogues. Author(s): Carlberg C. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 274-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520526&dopt=Abstract

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Molecular genetics of vitamin D- dependent hereditary rickets. Author(s): Kato S, Yoshizazawa T, Kitanaka S, Murayama A, Takeyama K. Source: Hormone Research. 2002; 57(3-4): 73-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006701&dopt=Abstract

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Molecular tools for study of genomic and rapid signal transduction responses initiated by 1 alpha,25(OH)(2)-vitamin D(3). Author(s): Norman AW, Bishop JE, Bula CM, Olivera CJ, Mizwicki MT, Zanello LP, Ishida H, Okamura WH. Source: Steroids. 2002 May; 67(6): 457-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960621&dopt=Abstract

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Muscle: a nontraditional 1,25-dihydroxyvitamin D target tissue exhibiting classic hormone-dependent vitamin D receptor actions. Author(s): Demay M. Source: Endocrinology. 2003 December; 144(12): 5135-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645209&dopt=Abstract

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Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. Author(s): Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, Allain TJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 May; 17(5): 891-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009020&dopt=Abstract

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New vitamin D analogs. Author(s): Lindberg JS. Source: Seminars in Dialysis. 2001 May-June; 14(3): 229-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422933&dopt=Abstract

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New vitamin D analogs. Author(s): Slatopolsky E, Finch J, Brown A. Source: Kidney International. Supplement. 2003 June; (85): S83-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753273&dopt=Abstract

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No association of vitamin D receptor gene start codon fok 1 polymorphisms in Chinese patients with systemic lupus erythematosus. Author(s): Huang CM, Wu MC, Wu JY, Tsai FJ. Source: The Journal of Rheumatology. 2002 June; 29(6): 1211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064837&dopt=Abstract

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No association of vitamin D-binding protein gene polymorphisms in Japanese patients with MS. Author(s): Niino M, Kikuchi S, Fukazawa T, Yabe I, Tashiro K. Source: Journal of Neuroimmunology. 2002 June; 127(1-2): 177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044990&dopt=Abstract

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Nodular parathyroid growth: role of vitamin D resistance. Author(s): Dusso AS. Source: Kidney International. 2002 October; 62(4): 1472-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234322&dopt=Abstract

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Normal mineral homeostasis. Interplay of parathyroid hormone and vitamin D. Author(s): Levine MA. Source: Endocr Dev. 2003; 6: 14-33. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964423&dopt=Abstract

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Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo. Author(s): Adams JS, Chen H, Chun RF, Nguyen L, Wu S, Ren SY, Barsony J, Gacad MA. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 308-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520531&dopt=Abstract

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Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing. Author(s): Zhang C, Dowd DR, Staal A, Gu C, Lian JB, van Wijnen AJ, Stein GS, MacDonald PN. Source: The Journal of Biological Chemistry. 2003 September 12; 278(37): 35325-36. Epub 2003 July 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840015&dopt=Abstract

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Nutrition. The vitamin D deficit. Author(s): Stokstad E. Source: Science. 2003 December 12; 302(5652): 1886-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671267&dopt=Abstract

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Oestrogen and vitamin D receptor (VDR) genotypes and the expression of ErbB-2 and EGF receptor in human rectal cancers. Author(s): Speer G, Cseh K, Winkler G, Takacs I, Barna I, Nagy Z, Lakatos P. Source: European Journal of Cancer (Oxford, England : 1990). 2001 August; 37(12): 14638. Erratum In: Eur J Cancer 2001 October; 37(15): 1963. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506951&dopt=Abstract

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Oral and dental manifestations of vitamin D-dependent rickets type I: report of a pediatric case. Author(s): Zambrano M, Nikitakis NG, Sanchez-Quevedo MC, Sauk JJ, Sedano H, Rivera H. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 June; 95(6): 705-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789152&dopt=Abstract

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Oral bisphosphonate therapy for vitamin D intoxication of the infant. Author(s): Bereket A, Erdogan T. Source: Pediatrics. 2003 April; 111(4 Pt 1): 899-901. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671131&dopt=Abstract

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Osteomalacia in a vitamin D-deficient woman with Graves' disease. Author(s): Nagasaka S, Shinohara Y, Kubota K, Murakami T. Source: Endocrine Journal. 2001 August; 48(4): 515-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603577&dopt=Abstract

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Osteoporosis and the role of vitamin D and calcium. Author(s): Dhesi JK, Jackson SH, Allain T. Source: Age and Ageing. 2001 January; 30(1): 88-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322684&dopt=Abstract

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Osteoporosis and vitamin D deficiency in Israel. Author(s): Weisman Y. Source: Public Health Rev. 2000; 28(1-4): 59-65. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11411278&dopt=Abstract

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Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride. Author(s): Abitbol V, Mary JY, Roux C, Soule JC, Belaiche J, Dupas JL, Gendre JP, Lerebours E, Chaussade S; Groupe D'etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID). Source: Alimentary Pharmacology & Therapeutics. 2002 May; 16(5): 919-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966500&dopt=Abstract

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Osteoporosis, vitamin D receptor gene polymorphisms and response to diet. Author(s): Ferrari SL. Source: World Review of Nutrition and Dietetics. 2001; 89: 83-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530741&dopt=Abstract

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Osteoporosis. Part III--Not just for bone loss: potential benefits of calcium and vitamin D for overall general health. Author(s): Moyad MA. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2003 February; 23(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677721&dopt=Abstract

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Osteoporosis--Part II: Dietary and/or supplemental calcium and vitamin D. Author(s): Moyad MA. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2002 December; 22(6): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593233&dopt=Abstract

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Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27. Author(s): Tokumoto M, Tsuruya K, Fukuda K, Kanai H, Kuroki S, Hirakata H, Iida M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18 Suppl 3: Iii9-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771291&dopt=Abstract

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Pathways mediating the growth-inhibitory actions of vitamin D in prostate cancer. Author(s): Peehl DM, Krishnan AV, Feldman D. Source: The Journal of Nutrition. 2003 July; 133(7 Suppl): 2461S-2469S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840225&dopt=Abstract

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Phakomatosis pigmentokeratotica associated with hypophosphataemic vitamin Dresistant rickets: improvement in phosphate homeostasis after partial laser ablation. Author(s): Saraswat A, Dogra S, Bansali A, Kumar B. Source: The British Journal of Dermatology. 2003 May; 148(5): 1074-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786855&dopt=Abstract

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Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling. Author(s): Hsieh JC, Sisk JM, Jurutka PW, Haussler CA, Slater SA, Haussler MR, Thompson CC. Source: The Journal of Biological Chemistry. 2003 October 3; 278(40): 38665-74. Epub 2003 July 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847098&dopt=Abstract

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Phytoestrogens and 17beta-estradiol influence vitamin D metabolism and receptor expression-relevance for colon cancer prevention. Author(s): Lechner D, Cross HS. Source: Recent Results Cancer Res. 2003; 164: 379-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899537&dopt=Abstract

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Polymorphic variation at the -202 locus in IGFBP3: Influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk. Author(s): Schernhammer ES, Hankinson SE, Hunter DJ, Blouin MJ, Pollak MN. Source: International Journal of Cancer. Journal International Du Cancer. 2003 October 20; 107(1): 60-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925957&dopt=Abstract

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Polymorphisms in the vitamin D receptor gene and the risk of calcium nephrolithiasis in children. Author(s): Ozkaya O, Soylemezoglu O, Misirlioglu M, Gonen S, Buyan N, Hasanoglu E. Source: European Urology. 2003 July; 44(1): 150-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814692&dopt=Abstract

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Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation. Author(s): Grados F, Brazier M, Kamel S, Mathieu M, Hurtebize N, Maamer M, Garabedian M, Sebert JL, Fardellone P. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602746&dopt=Abstract

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Prophylactic vitamin D supplementation. Author(s): Calikoglu AS, Davenport ML. Source: Endocr Dev. 2003; 6: 233-58. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964435&dopt=Abstract

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Prospects for vitamin D receptor modulators as candidate drugs for cancer and (auto)immune diseases. Author(s): Bouillon R, Verstuyf A, Verlinden L, Eelen G, Mathieu C. Source: Recent Results Cancer Res. 2003; 164: 353-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899534&dopt=Abstract

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Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. Author(s): Geusens P, Vandevyver C, Vanhoof J, Cassiman JJ, Boonen S, Raus J. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1997 December; 12(12): 2082-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9421241&dopt=Abstract

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Quantitative ultrasound of the calcaneus and falls risk in the institutionalized elderly: sex differences and relationship to vitamin D status. Author(s): Zochling J, Sitoh YY, Lau TC, Cameron ID, Cumming RG, Lord SR, Schwarz J, Trube A, March LM, Sambrook PN. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 November; 13(11): 882-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415435&dopt=Abstract

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Regulation of androgen and vitamin d receptors by 1,25-dihydroxyvitamin D3 in human prostate epithelial and stromal cells. Author(s): Leman ES, DeMiguel F, Gao AC, Getzenberg RH. Source: The Journal of Urology. 2003 July; 170(1): 235-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796696&dopt=Abstract

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Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments. Author(s): Enjuanes A, Garcia-Giralt N, Supervia A, Nogues X, Mellibovsky L, Carbonell J, Grinberg D, Balcells S, Diez-Perez A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 May; 148(5): 519-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720534&dopt=Abstract

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Regulation of extrarenal vitamin D metabolism as a tool for colon and prostate cancer prevention. Author(s): Cross HS, Kallay E, Farhan H, Weiland T, Manhardt T. Source: Recent Results Cancer Res. 2003; 164: 413-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899539&dopt=Abstract

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Regulation of renin expression and blood pressure by vitamin D(3). Author(s): Sigmund CD. Source: The Journal of Clinical Investigation. 2002 July; 110(2): 155-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122105&dopt=Abstract

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Religious/cultural causes of vitamin D deficiency in infants. Author(s): Seeler RA. Source: The Journal of Pediatrics. 2001 June; 138(6): 954. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391353&dopt=Abstract

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Rescue of the pseudo-vitamin D deficiency rickets phenotype of CYP27B1-deficient mice by treatment with 1,25-dihydroxyvitamin D3: biochemical, histomorphometric, and biomechanical analyses. Author(s): Dardenne O, Prudhomme J, Hacking SA, Glorieux FH, St-Arnaud R. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 April; 18(4): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674324&dopt=Abstract

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Research and public health implications of the intricate relationship between calcium and vitamin D in the prevention of colorectal neoplasia. Author(s): Jacobs ET, Martinez ME, Alberts DS. Source: Journal of the National Cancer Institute. 2003 December 3; 95(23): 1736-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652228&dopt=Abstract

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Response of parathyroid glands to calcitriol in culture: Is this response mediated by the genetic polymorphisms in vitamin D receptor? Author(s): Alvarez-Hernandez D, Naves M, Santamaria I, Menarguez J, Torregrosa V, Cannata J. Source: Kidney International. Supplement. 2003 June; (85): S19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753259&dopt=Abstract

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Retinoid X receptor dominates the nuclear import and export of the unliganded vitamin D receptor. Author(s): Prufer K, Barsony J. Source: Molecular Endocrinology (Baltimore, Md.). 2002 August; 16(8): 1738-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145331&dopt=Abstract

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Retinoids and vitamin D analogues: action on nuclear transcription. Author(s): Griffiths CE. Source: Hosp Med. 1998 January; 59(1): 12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9798558&dopt=Abstract

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Secondary prevention of vitamin D-deficiency rickets. Author(s): Spence JT, Serwint JR. Source: Pediatrics. 2004 January; 113(1 Pt 1): E70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14702499&dopt=Abstract

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Sensitivity to growth suppression by 1alpha,25-dihydroxyvitamin D(3) among MCF-7 clones correlates with Vitamin D receptor protein induction. Author(s): Jensen SS, Madsen MW, Lukas J, Bartek J, Binderup L. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 June; 81(2): 123-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137801&dopt=Abstract

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Sensitization to TNF-induced apoptosis by 1,25-dihydroxy vitamin D(3) involves upregulation of the TNF receptor 1 and cathepsin B. Author(s): Mathiasen IS, Hansen CM, Foghsgaard L, Jaattela M. Source: International Journal of Cancer. Journal International Du Cancer. 2001 July 15; 93(2): 224-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410870&dopt=Abstract

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Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Author(s): Zittermann A. Source: The American Journal of Clinical Nutrition. 2003 September; 78(3): 496-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936937&dopt=Abstract

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Serum vitamin D and falls in older women in residential care in Australia. Author(s): Flicker L, Mead K, MacInnis RJ, Nowson C, Scherer S, Stein MS, Thomasx J, Hopper JL, Wark JD. Source: Journal of the American Geriatrics Society. 2003 November; 51(11): 1533-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14687381&dopt=Abstract

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Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States) Author(s): Nomura AM, Stemmermann GN, Lee J, Kolonel LN, Chen TC, Turner A, Holick MF. Source: Cancer Causes & Control : Ccc. 1998 August; 9(4): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9794175&dopt=Abstract

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Short-chain fatty acids and colon cancer cells: the vitamin D receptor--butyrate connection. Author(s): Gaschott T, Stein J. Source: Recent Results Cancer Res. 2003; 164: 247-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899527&dopt=Abstract

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Structural evaluation of the agonistic action of a vitamin D analog with two side chains binding to the nuclear vitamin D receptor. Author(s): Vaisanen S, Perakyla M, Karkkainen JI, Uskokovic MR, Carlberg C. Source: Molecular Pharmacology. 2003 June; 63(6): 1230-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761332&dopt=Abstract

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Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2. Author(s): Llach F, Keshav G, Goldblat MV, Lindberg JS, Sadler R, Delmez J, Arruda J, Lau A, Slatopolsky E. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1998 October; 32(2 Suppl 2): S48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808143&dopt=Abstract

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Synergistic effect of vitamin D and calcium in preventing proximal femoral fractures in older patients. Author(s): Szulc P, Meunier PJ. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2003 June; 70(3): 157-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814757&dopt=Abstract

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The BsmI vitamin D receptor gene polymorphism in Israeli populations and in perimenopausal and osteoporotic Ashkenazi women. Author(s): Pollak RD, Blumenfeld A, Bejarano-Achache I, Idelson M, Celinke Hochner D. Source: American Journal of Nephrology. 2001 May-June; 21(3): 185-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423686&dopt=Abstract

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The effect of season and vitamin D supplementation on bone mineral density in healthy women: a double-masked crossover study. Author(s): Patel R, Collins D, Bullock S, Swaminathan R, 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. 2001; 12(4): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420782&dopt=Abstract

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The expression of vitamin D-upregulated protein 1 in skin and its interaction with sciellin in cultured keratinocytes. Author(s): Champliaud MF, Viel A, Baden HP. Source: The Journal of Investigative Dermatology. 2003 October; 121(4): 781-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14632196&dopt=Abstract

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The frequency of vitamin D deficiency in adults with Crohn's disease. Author(s): Siffledeen JS, Siminoski K, Steinhart H, Greenberg G, Fedorak RN. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 August; 17(8): 473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945007&dopt=Abstract

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The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Author(s): Agarwal KS, Mughal MZ, Upadhyay P, Berry JL, Mawer EB, Puliyel JM. Source: Archives of Disease in Childhood. 2002 August; 87(2): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138058&dopt=Abstract

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The role of reactive oxygen species in the anticancer activity of vitamin D. Author(s): Ravid A, Koren R. Source: Recent Results Cancer Res. 2003; 164: 357-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899535&dopt=Abstract

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The role of vitamin D in prostate cancer. Author(s): Krishnan AV, Peehl DM, Feldman D. Source: Recent Results Cancer Res. 2003; 164: 205-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899524&dopt=Abstract

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The Sp1 COLIA1 gene polymorphism, and not vitamin D receptor or estrogen receptor gene polymorphisms, determines bone mineral density in postmenopausal Greek women. Author(s): Efstathiadou Z, Kranas V, Ioannidis JP, Georgiou I, Tsatsoulis A. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(4): 326-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420783&dopt=Abstract

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The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects. Author(s): Souberbielle JC, Lawson-Body E, Hammadi B, Sarfati E, Kahan A, Cormier C. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3501-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915625&dopt=Abstract

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Two basic amino acids C-terminal of the proximal box specify functional binding of the vitamin D receptor to its rat osteocalcin deoxyribonucleic acid-responsive element. Author(s): Hsieh JC, Whitfield GK, Jurutka PW, Haussler CA, Thatcher ML, Thompson PD, Dang HT, Galligan MA, Oza AK, Haussler MR. Source: Endocrinology. 2003 November; 144(11): 5065-80. Epub 2003 July 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960019&dopt=Abstract

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Ultraviolet light (UV)-induced immunosuppression: is vitamin D the missing link? Author(s): Reichrath J, Rappl G. Source: Journal of Cellular Biochemistry. 2003 May 1; 89(1): 6-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682903&dopt=Abstract

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Update on vitamin D and its newer analogues. Author(s): Fournier A, Ghazali A, Presne C, Garabedian M. Source: Kidney International. 2003 April; 63(4): 1586; Author Reply 1586. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631380&dopt=Abstract

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Update on vitamin D and its newer analogues: actions and rationale for treatment in chronic renal failure. Author(s): Malluche HH, Mawad H, Koszewski NJ. Source: Kidney International. 2002 August; 62(2): 367-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109997&dopt=Abstract

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Urinary collagen crosslinks reflect further bone loss of femoral neck in osteoporotic patients undergoing vitamin D therapy. Author(s): Ohishi T, Takahashi M, Kushida K, Yamazaki K, Hoshino H, Kitazawa A, Inoue T. Source: Endocrine Research. 1998 May; 24(2): 259-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9738702&dopt=Abstract

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Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease. Author(s): Malluche HH, Monier-Faugere MC, Koszewski NJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002; 17 Suppl 10: 69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386263&dopt=Abstract

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Use of active vitamin D sterols in patients with chronic kidney disease, stages 3 and 4. Author(s): Coburn JW, Maung HM. Source: Kidney International. Supplement. 2003 June; (85): S49-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753265&dopt=Abstract

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Use of stable calcium isotopes (42Ca & 44Ca) in evaluation of calcium absorption in Beijing adolescents with low vitamin D status. Author(s): Lee WT, Jiang J, Hu P, Hu X, Roberts DC, Cheng JC. Source: Food Nutr Bull. 2002 September; 23(3 Suppl): 42-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362810&dopt=Abstract

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Use of vitamin D analogs in chronic renal failure. Author(s): Kim G, Sprague SM. Source: Adv Ren Replace Ther. 2002 July; 9(3): 175-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203199&dopt=Abstract

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Use of vitamin D and its derivatives in chronic renal failure. Author(s): Cunningham J. Source: Adv Nephrol Necker Hosp. 1999; 29: 207-19. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10561746&dopt=Abstract

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Use of vitamin D(4) analogs to investigate differences in hepatic and target cell metabolism of vitamins D(2) and D(3). Author(s): Byford V, Strugnell S, Coldwell R, Schroeder N, Makin HL, Knutson JC, Bishop CW, Jones G. Source: Biochimica Et Biophysica Acta. 2002 July 11; 1583(2): 151-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117559&dopt=Abstract

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Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India. Author(s): Balasubramanian K, Rajeswari J, Gulab, Govil YC, Agarwal AK, Kumar A, Bhatia V. Source: Journal of Tropical Pediatrics. 2003 August; 49(4): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929879&dopt=Abstract

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Vitamin D analogs and breast cancer. Author(s): O'Kelly J, Koeffler HP. Source: Recent Results Cancer Res. 2003; 164: 333-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899532&dopt=Abstract

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Vitamin D and the breastfed infant: controversies and concerns. Author(s): Heinig MJ. Source: Journal of Human Lactation : Official Journal of International Lactation Consultant Association. 2003 August; 19(3): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931774&dopt=Abstract

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Vitamin D and vitamin D analogs as cancer chemopreventive agents. Author(s): Guyton KZ, Kensler TW, Posner GH. Source: Nutrition Reviews. 2003 July; 61(7): 227-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918875&dopt=Abstract

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Vitamin D autocrine system and prostate cancer. Author(s): Wang L, Whitlatch LW, Flanagan JN, Holick MF, Chen TC. Source: Recent Results Cancer Res. 2003; 164: 223-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899525&dopt=Abstract

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Vitamin D growth inhibition of breast cancer cells: gene expression patterns assessed by cDNA microarray. Author(s): Swami S, Raghavachari N, Muller UR, Bao YP, Feldman D. Source: Breast Cancer Research and Treatment. 2003 July; 80(1): 49-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889598&dopt=Abstract

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Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm. Author(s): Yang ES, Burnstein KL. Source: The Journal of Biological Chemistry. 2003 November 21; 278(47): 46862-8. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954644&dopt=Abstract

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Vitamin D supplementation to healthy children does not affect serum osteocalcin or markers of type I collagen turnover. Author(s): Schou AJ, Heuck C, Wolthers OD. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 July; 92(7): 797-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892157&dopt=Abstract

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Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. Author(s): Rajakumar K. Source: Pediatrics. 2003 August; 112(2): E132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897318&dopt=Abstract

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Vitamin D-dependent rickets Type II with alopecia: two case reports and review of the literature. Author(s): Sultan Al-Khenaizan, Vitale P. Source: International Journal of Dermatology. 2003 September; 42(9): 682-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956677&dopt=Abstract

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Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Author(s): Arlt W, Fremerey C, Callies F, Reincke M, Schneider P, Timmermann W, Allolio B. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 February; 146(2): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834431&dopt=Abstract

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What are the dietary requirements for calcium and vitamin D? Author(s): Prentice A. Source: Calcified Tissue International. 2002 February; 70(2): 83-8. Epub 2002 January 22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870413&dopt=Abstract

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What is the optimal regimen for vitamin D? Author(s): Cunningham J. Source: Kidney International. Supplement. 1999 December; 73: S59-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633466&dopt=Abstract

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What's new in vitamin D for the nephrologist? Author(s): Schroeder NJ, Cunningham J. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 April; 15(4): 460-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727539&dopt=Abstract

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Wintertime vitamin D deficiency in male adolescents: effect on parathyroid function and response to vitamin D3 supplements. Author(s): Guillemant J, Le HT, Maria A, Allemandou A, Peres G, Guillemant S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(10): 875-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716192&dopt=Abstract

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Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Author(s): Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Source: European Journal of Clinical Nutrition. 2001 December; 55(12): 1091-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781676&dopt=Abstract

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YY1 represses vitamin D receptor-mediated 25-hydroxyvitamin D(3)24-hydroxylase transcription: relief of repression by CREB-binding protein. Author(s): Raval-Pandya M, Dhawan P, Barletta F, Christakos S. Source: Molecular Endocrinology (Baltimore, Md.). 2001 June; 15(6): 1035-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376120&dopt=Abstract

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ZK 156718, a low calcemic, antiproliferative, and prodifferentiating vitamin D analog. Author(s): Gaschott T, Steinmeyer A, Steinhilber D, Stein J. Source: Biochemical and Biophysical Research Communications. 2002 January 11; 290(1): 504-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779200&dopt=Abstract

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

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

Dietary reference intakes (DRIs) for calcium, phosphorus, magnesium, vitamin D, and fluoride. Source: Nutrition-today (USA). (October 1997). volume 32(5) page 182-188.

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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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Plants as a source of vitamin D3 metabolites. Source: Boland, R.L. Nutrition-reviews (USA). (January 1986). volume 44(1) page 1-8.

Additional consumer oriented references include: •

Altered receptors for 1,25-dihydroxycholecalciferol in vitamin D-dependent rickets. Source: Nutrition-reviews (USA). (June 1985). volume 43(6) page 178-180.

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By the way, doctor. Recently, you advocated taking 800 IU of vitamin D as part of osteoporosis prevention. However, during the summer, I get a lot of vitamin D from sunlight. Am I in danger of getting too much vitamin D? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 August; 6(12): 8 1070910X

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Calcium and vitamin D intakes influence the risk of bowel cancer in men. Source: Nutrition-reviews (USA). (June 1985). volume 43(6) page 170-172.

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Calcium-binding protein is induced by the active metabolite of vitamin D before intestinal calcium uptake is stimulated. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. January 1984. volume 42 (1) page 27-28. 0029-6643

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Does sunscreen block the skin's ability to make vitamin D? If so, how can I get enough of this vitamin without raising my risk of skin cancer? Source: Holick, Michael Health-News. 2002 July; 8(7): 12 1081-5880

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Enterohepatic circulation of vitamin D is negligible. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. March 1985. volume 43 (3) page 76-78. 0029-6643

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Health tips. How to make sure you get enough vitamin D. Source: Anonymous Mayo-Clin-Health-Lett. 1998 November; 16(11): 3 0741-6245

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I pay attention to how much calcium I get each day. But I recently heard that without enough vitamin D, my body can't make use of the calcium. Please explain. Source: Anonymous Mayo-Clin-Health-Lett. 2002 September; 20(9): 8 0741-6245

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Intestinal bile acids can bind to and activate the vitamin D receptor. Author(s): Department of Nutritional Sciences and Toxicology, University of California, Berkeley 94720-3104, USA. Source: Wolf, G Nutr-Revolume 2002 September; 60(9): 281-3 0029-6643

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Intracellular receptors mediate the biologic action of 1,25-dihydroxyvitamin D3. Source: Pike, J.W. Nutrition-reviews (USA). (June 1985). volume 43(6) page 161-168. vitamin d metabolism proteins models 0029-6643

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Is the RDA for vitamin D adequate for the elderly? Source: Nutrition-and-the-M.D (USA). (September 1992). volume 18(9) page 1, 3. vitamin d diet vitamin deficiencies elderly solar energy 0732-0167

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Low vitamin D linked to bone fractures. Source: Anonymous Health-News. 1999 June 1; 5(7): 5 1081-5880

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Mechanisms and functions of vitamin D. Author(s): Department of Biochemistry, University of Wisconsin-Madison 53706, USA. Source: DeLuca, H F Zierold, C Nutr-Revolume 1998 February; 56(2 Pt 2): S4-10; discussion S 54-75 0029-6643

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Metabolic bone disease and vitamin D deficiency in Crohn's disease. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. July 1983. volume 41 (7) page 213-216. 0029-6643

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Novel intracellular proteins associated with cellular vitamin D action. Author(s): Mineral Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. Source: Angelo, G Wood, R J Mayer, J Nutr-Revolume 2002 July; 60(7 Pt 1): 209-11 00296643

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Nutrition. Vitamin D update. Source: Anonymous Harv-Womens-Health-Watch. 1999 July; 6(11): 6 1070-910X

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Over 50? Chances are you need more vitamin D. Source: Tufts-Univ-Diet-Nutr-Lett. New York, N.Y. : The Letter. June 1990. volume 8 (4) page 2. 0747-4105

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Parathyroid hormone, 1,25-dihydroxyvitamin D3 and calcitonin in women breastfeeding twins. Source: Nutrition-reviews (USA). (October 1985). volume 43(10) page 300-301.

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Prevention. Vitamin D deficiency may be widespread. Source: Anonymous Harv-Health-Lett. 1998 July; 23(9): 7 1052-1577

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Too little vitamin D? Source: Anonymous Health-News. 1998 April 20; 4(5): 5 1081-5880

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Vitamin D in the elderly: an overlooked nutrient. Source: McNutt, K. Nutr-today. Baltimore, Md. : Williams & Wilkins. December 1995. volume 30 (6) page 228-233. 0029-666X

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Vitamin D keeps a form of arthritis in check. Source: Tufts-University-diet-and-nutrition-letter (USA). (December 1996).

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Vitamin D polymorphisms and calcium homeostasis: a new concept of normal gene variants and physiologic variation. Author(s): Bone and Mineral Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia. Source: Eisman, J A Nutr-Revolume 1998 February; 56(2 Pt 2): s22-9; discussion s54-75 0029-6643

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Vitamin D receptors: not just in the nucleus anymore. Author(s): University of North Carolina at Greensboro 27412-5001, USA. Source: Fleet, J C Nutr-Revolume 1999 February; 57(2): 60-2 0029-6643

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Vitamin D status of the elderly: Contributions of sunlight exposure and diet. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. March 1985. volume 43 (3) page 78-80. Ill. 0029-6643

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Vitamin D-deficient rickets: a multifactorial disease. Author(s): Department of Nutrition and Food Sciences, University of Vermont, Burlington 05401, USA. Source: Fitzpatrick, S Sheard, N F Clark, N G Ritter, M L Nutr-Revolume 2000 July; 58(7): 218-22 0029-6643

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Vitamin deficiencies in the alcoholic patient. Source: Franz, M.J. Nutr-M.D. Van Nuys, Calif. : Nutrition & the M.D. October 1987. volume 13 (10) page 1-3. 0732-0167

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

1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro. Author(s): Department of Dermatology and Allergy, Charite, Humboldt University, Berlin, Germany. Source: Heine, G Anton, K Henz, B M Worm, M Eur-J-Immunol. 2002 December; 32(12): 3395-404 0014-2980

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A novel splicing defect (IVS6+1G>T) in a patient with pseudovitamin D deficiency rickets. Author(s): Biomedical and Biotechnological Sciences Department, Cagliari University, Italy. Source: Porcu, L Meloni, A Casula, L Asunis, I Marini, M G Cao, A Moi, P J-EndocrinolInvest. 2002 June; 25(6): 557-60 0391-4097

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Calcium absorption measured by stable calcium isotopes ((42)Ca & (44)Ca) among Northern Chinese adolescents with low vitamin D status. Author(s): Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. [email protected] Source: Lee, W T Cheng, J C Jiang, J Hu, P Hu, X Roberts, D C J-Orthop-Surg-(HongKong). 2002 June; 10(1): 61-6 1022-5536

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Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? Author(s): Department of Clinical Biochemistry, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, UK. Source: Timms, P M Mannan, N Hitman, G A Noonan, K Mills, P G Syndercombe Court, D Aganna, E Price, C P Boucher, B J QJM. 2002 December; 95(12): 787-96 1460-2725

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Comparative review of the pharmacokinetics of vitamin D analogues. Author(s): Albany College of Pharmacy, Albany, New York, USA. Source: Bailie, G R Johnson, C A Semin-Dial. 2002 Sep-October; 15(5): 352-7 0894-0959

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Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Author(s): Institute of Animal Physiology, Ludwig Maximilians University, 80539 Munich, Germany. [email protected] Source: Erben, R G Soegiarto, D W Weber, K Zeitz, U Lieberherr, M Gniadecki, R Moller, G Adamski, J Balling, R Mol-Endocrinol. 2002 July; 16(7): 1524-37 0888-8809

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Discovering more roles for vitamin D. Source: Anonymous Harv-Womens-Health-Watch. 2002 November; 10(3): 5 1070-910X

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Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient. Author(s): Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA. Source: Arekat, M R And, G Lemke, S Moses, A M J-Clin-Densitom. 2002 Fall; 5(3): 26771 1094-6950

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Is routine supplementation therapy (calcium and vitamin D) useful after total thyroidectomy? Author(s): Division of Endocrine Surgery, Department of Surgery, Universita Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy. Source: Bellantone, R Lombardi, C P Raffaelli, M Boscherini, M Alesina, P F De Crea, C Traini, E Princi, P Surgery. 2002 December; 132(6): 1109-12; discussion 1112-3 0039-6060

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Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Source: Papadimitropoulos, E Wells, G Shea, B Gillespie, W Weaver, B Zytaruk, N Cranney, A Adachi, J Tugwell, P Josse, R Greenwood, C Guyatt, G Endocr-Revolume 2002 August; 23(4): 560-9 0163-769X

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Osteoporosis--Part II: Dietary and/or supplemental calcium and vitamin D. Author(s): University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA. Source: Moyad, M A Urol-Nurs. 2002 December; 22(6): 405-9 1053-816X

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Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205. Author(s): Environmental Toxicology Graduate Program, University of California, Riverside, California 92521, USA. Source: Maeda, Y Rachez, C Hawel, L 3rd Byus, C V Freedman, L P Sladek, F M MolEndocrinol. 2002 July; 16(7): 1502-10 0888-8809

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Polymorphism of vitamin D receptor gene start codon in patients with calcium kidney stones. Author(s): Division of Nephrology Dialysis and Hypertension, San Raffaele Scientific Institute, Milan, Italy. [email protected] Source: Vezzoli, G Soldati, L Proverbio, M C Adamo, D Rubinacci, A Bianchi, G Mora, S J-Nephrol. 2002 Mar-April; 15(2): 158-64 1120-3625

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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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Quantitative ultrasound of the calcaneus and falls risk in the institutionalized elderly: sex differences and relationship to vitamin D status. Author(s): Institute of Bone & Joint Research, University of Sydney, Australia. Source: Zochling, J Sitoh, Y Y Lau, T C Cameron, I D Cumming, R G Lord, S R Schwarz, J Trube, A March, L M Sambrook, P N Osteoporos-Int. 2002 November; 13(11): 882-7 0937-941X

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Regulation of the mouse Nas1 promoter by vitamin D and thyroid hormone. Author(s): School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, St. Lucia, QLD 4072, Australia. Source: Dawson, P A Markovich, D Pflugers-Arch. 2002 June; 444(3): 353-9 0031-6768

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Relationship between serum vitamin d status and clinical manifestations of primary hyperparathyroidism. Author(s): Department of Medicine, Endocrine Unit, Agamenon Magalhaes Hospital, Secretary of Health/University of Pernambuco, Recife, Brazil. Source: Bandeira, F Caldas, G Freese, E Griz, L Faria, M Bandeira, C Endocr-Pract. 2002 Jul-August; 8(4): 266-70 1530-891X

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Retinoid X receptor dominates the nuclear import and export of the unliganded vitamin D receptor. Author(s): Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Source: Prufer, K Barsony, J Mol-Endocrinol. 2002 August; 16(8): 1738-51 0888-8809

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Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese. Author(s): Department of of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan. [email protected] Source: Hamasaki, T Inatomi, H Katoh, T Ikuyama, T Matsumoto, T Urol-Int. 2002; 68(4): 226-31 0042-1138

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Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled-coil domain in complex with vitamin D(3). Author(s): Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. [email protected] Source: Ozbek, S Engel, J Stetefeld, J EMBO-J. 2002 November 15; 21(22): 5960-8 02614189

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The vitamin D response element of the involucrin gene mediates its regulation by 1,25-dihydroxyvitamin D3. Author(s): Department of Medicine, Veterans Affairs Medical Center and University of California, San Francisco, USA. [email protected] Source: Bikle, D D Ng, D Oda, Y Hanley, K Feingold, K Xie, Z J-Invest-Dermatol. 2002 November; 119(5): 1109-13 0022-202X

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Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. Author(s): Department 545, The Osteoporosis Research Clinic, Hvidovre Hospital, Denmark. Source: Tofteng, C L Jensen, J E Abrahamsen, B Odum, L Brot, C J-Bone-Miner-Res. 2002 August; 17(8): 1535-44 0884-0431

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Vitamin D and its analog EB1089 induce p27 accumulation and diminish association of p27 with Skp2 independent of PTEN in pituitary corticotroph cells. Author(s): Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Source: Liu, W Asa, S L Ezzat, S Brain-Pathol. 2002 October; 12(4): 412-9 1015-6305

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Vitamin D receptor and retinoid X receptor interactions in motion. Author(s): Laboratory of Cell Biochemistry and Biology, National Institutes of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA. [email protected]

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Source: Barsony, J Prufer, K Vitam-Horm. 2002; 65: 345-76 0083-6729

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 vitamin D; 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 Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Multiple Vitamin-Mineral Supplements Source: Healthnotes, Inc.; www.healthnotes.com Pantothenic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Alternative names: Calciferol 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 Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com

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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

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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 Channel–Blockers Source: Prima Communications, Inc.www.personalhealthzone.com Calcium/Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,937,00.html Calcium: Which Form Is Best? Source: Healthnotes, Inc.; www.healthnotes.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Sodium Fluoride Source: Healthnotes, Inc.; www.healthnotes.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 Gluten-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Macrobiotic 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

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Rice Milk Source: Healthnotes, Inc.; www.healthnotes.com Shiitake Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,308,00.html Soy Milk Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,200,00.html Vegetarian Diet Source: Healthnotes, Inc.; www.healthnotes.com

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

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to vitamin D 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 “vitamin D” (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 vitamin D: •

1,25(OH)2 vitamin D concentration in the plasma of Solanum glaucophyllum intoxicated rabbits. Author(s): Dallorso ME, Gil S, Pawlak E, Lema F, Marquez A. Source: Aust Vet J. 2001 June; 79(6): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491221&dopt=Abstract

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1,25(OH)2-vitamin D3 induces translocation of the vitamin D receptor (VDR) to the plasma membrane in skeletal muscle cells. Author(s): Capiati D, Benassati S, Boland RL. Source: Journal of Cellular Biochemistry. 2002; 86(1): 128-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112023&dopt=Abstract

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1alpha,25-dihydroxyvitamin D3 induces vascular smooth muscle cell migration via activation of phosphatidylinositol 3-kinase. Author(s): Rebsamen MC, Sun J, Norman AW, Liao JK.

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Source: Circulation Research. 2002 July 12; 91(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114317&dopt=Abstract •

1alpha,25-dihydroxyvitamin D3 inhibits uncoupling protein 2 expression in human adipocytes. Author(s): Shi H, Norman AW, Okamura WH, Sen A, Zemel MB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2002 November; 16(13): 1808-10. Epub 2002 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223452&dopt=Abstract

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A cost effectiveness analysis of calcium and vitamin D supplementation, etidronate, and alendronate in the prevention of vertebral fractures in women treated with glucocorticoids. Author(s): Buckley LM, Hillner BE. Source: The Journal of Rheumatology. 2003 January; 30(1): 132-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508402&dopt=Abstract

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A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Author(s): Harwood RH, Sahota O, Gaynor K, Masud T, Hosking DJ; The Nottingham Neck of Femur (NONOF) Study. Source: Age and Ageing. 2004 January; 33(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14695863&dopt=Abstract

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A randomized, controlled lower leg growth study of vitamin D supplementation to healthy children during the winter season. Author(s): Schou AJ, Heuck C, Wolthers OD. Source: Annals of Human Biology. 2003 March-April; 30(2): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637196&dopt=Abstract

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Active vitamin D and its analogs as drugs for the treatment of osteoporosis: advantages and problems. Author(s): Nishii Y. Source: Journal of Bone and Mineral Metabolism. 2002; 20(2): 57-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862526&dopt=Abstract

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Administration of a supplement containing both calcium and vitamin D is more effective than calcium alone to reduce secondary hyperparathyroidism in postmenopausal women with low 25(OH)vitamin D circulating levels. Author(s): Deroisy R, Collette J, Albert A, Jupsin I, Reginster JY.

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Source: Aging Clin Exp Res. 2002 February; 14(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027147&dopt=Abstract •

Alteration of cellular phosphorylation state affects vitamin D receptor-mediated CYP3A4 mRNA induction in Caco-2 cells. Author(s): Hara H, Yasunami Y, Adachi T. Source: Biochemical and Biophysical Research Communications. 2002 August 9; 296(1): 182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147248&dopt=Abstract

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Association of low bone mass with vitamin d receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis. Author(s): Masi L, Cimaz R, Simonini G, Bindi G, Stagi S, Gozzini A, Malentacchi C, Brandi ML, Falcini F. Source: The Journal of Rheumatology. 2002 October; 29(10): 2225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375338&dopt=Abstract

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Associations of renal function with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers. Author(s): Weaver VM, Schwartz BS, Ahn KD, Stewart WF, Kelsey KT, Todd AC, Wen J, Simon DJ, Lustberg ME, Parsons PJ, Silbergeld EK, Lee BK. Source: Environmental Health Perspectives. 2003 October; 111(13): 1613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527840&dopt=Abstract

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Calcium and vitamin D in osteoporosis: supplementation or treatment? Author(s): Burckhardt P. Source: Calcified Tissue International. 2002 February; 70(2): 74-7. Epub 2002 January 29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870411&dopt=Abstract

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Calcium and vitamin D nutrition and bone disease of the elderly. Author(s): Gennari C. Source: Public Health Nutrition. 2001 April; 4(2B): 547-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683549&dopt=Abstract

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Calcium and vitamin D supplementation failed to improve bone mineral density in Indo-Asians suffering from hypovitaminosis D and secondary hyperparathyroidism. Author(s): Serhan E, Holland MR. Source: Rheumatology International. 2004 January 16 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14727056&dopt=Abstract

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Calcium and vitamin D supplementation in nursing home residents. Author(s): Smith RL. Source: Journal of the American Medical Directors Association. 2001 NovemberDecember; 2(6): 289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812533&dopt=Abstract

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Calcium and vitamin D supplementation in nursing home residents. Author(s): Smith RL. Source: Journal of the American Medical Directors Association. 2003 March-April; 4(2 Suppl): S23-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807567&dopt=Abstract

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Calcium and vitamin D supplements reduce tooth loss in the elderly. Author(s): Krall EA, Wehler C, Garcia RI, Harris SS, Dawson-Hughes B. Source: The American Journal of Medicine. 2001 October 15; 111(6): 452-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11690570&dopt=Abstract

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Calcium, vitamin D, and risk of adenoma recurrence (United States). /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12020160

Author(s): Ann Intern Med. 2002 May 21;136(10):I54 Source: Cancer Causes & Control : Ccc. 2002 April; 13(3): 213-20. <Title>Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). Author(s): McCullough ML, Robertson AS, Rodriguez C, Jacobs EJ, Chao A, Carolyn J, Calle EE, Willett WC, Thun MJ. Source: Cancer Causes & Control : Ccc. 2003 February; 14(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708719&dopt=Abstract

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Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. Author(s): Feskanich D, Willett WC, Colditz GA. Source: The American Journal of Clinical Nutrition. 2003 February; 77(2): 504-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540414&dopt=Abstract

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Calcium-vitamin D3 supplementation is cost-effective in hip fractures prevention. Author(s): Lilliu H, Pamphile R, Chapuy MC, Schulten J, Arlot M, Meunier PJ. Source: Maturitas. 2003 April 25; 44(4): 299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697371&dopt=Abstract

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Can vitamin D supplementation in infancy prevent type 1 diabetes? Author(s): Harris S.

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Source: Nutrition Reviews. 2002 April; 60(4): 118-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002683&dopt=Abstract •

Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. Author(s): Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 April; 17(4): 709-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918228&dopt=Abstract

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Capsaicin potentiates 1,25-dihydoxyvitamin D3- and all-trans retinoic acid-induced differentiation of human promyelocytic leukemia HL-60 cells. Author(s): Kang SN, Chung SW, Kim TS. Source: European Journal of Pharmacology. 2001 May 25; 420(2-3): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408028&dopt=Abstract

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Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Author(s): Steiner M, Priel I, Giat J, Levy J, Sharoni Y, Danilenko M. Source: Nutrition and Cancer. 2001; 41(1-2): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094616&dopt=Abstract

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Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1alpha,25dihydroxyvitamin D3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium. Author(s): Danilenko M, Wang Q, Wang X, Levy J, Sharoni Y, Studzinski GP. Source: Cancer Research. 2003 March 15; 63(6): 1325-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649194&dopt=Abstract

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Change in plasma levels of vitamin D after consumption of cod-liver and fresh codliver oil as part of the traditional north Norwegian fish dish “Molje”. Author(s): Brustad M, Sandanger T, Wilsgaard T, Aksnes L, Lund E. Source: Int J Circumpolar Health. 2003 March; 62(1): 40-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725340&dopt=Abstract

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Characterization of mammary tumor cell lines from wild type and vitamin D3 receptor knockout mice. Author(s): Zinser GM, McEleney K, Welsh J. Source: Molecular and Cellular Endocrinology. 2003 February 28; 200(1-2): 67-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644300&dopt=Abstract

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Chronotherapy of high-dose active vitamin D3 in haemodialysis patients with secondary hyperparathyroidsm: a repeated dosing study. Author(s): Tsuruoka S, Wakaumi M, Sugimoto K, Saito T, Fujimura A. Source: British Journal of Clinical Pharmacology. 2003 June; 55(6): 531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814446&dopt=Abstract

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Chronotherapy with active vitamin D3 in aged stroke-prone spontaneously hypertensive rats, a model of osteoporosis. Author(s): Tsuruoka S, Nishiki K, Sugimoto K, Fujimura A. Source: European Journal of Pharmacology. 2001 October 5; 428(2): 287-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675047&dopt=Abstract

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Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Author(s): Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, Garnero P, Meunier PJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991447&dopt=Abstract

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Comparative effects of vitamin K and vitamin D supplementation on prevention of osteopenia in calcium-deficient young rats. Author(s): Iwamoto J, Yeh JK, Takeda T, Ichimura S, Sato Y. Source: Bone. 2003 October; 33(4): 557-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555259&dopt=Abstract

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Comparison of low and high dose of vitamin D treatment in nutritional vitamin D deficiency rickets. Author(s): Cesur Y, Caksen H, Gundem A, Kirimi E, Odabas D. Source: J Pediatr Endocrinol Metab. 2003 October-November; 16(8): 1105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594170&dopt=Abstract

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Comparisons of oral calcium, high dose vitamin D and a combination of these in the treatment of nutritional rickets in children. Author(s): Kutluk G, Cetinkaya F, Basak M. Source: Journal of Tropical Pediatrics. 2002 December; 48(6): 351-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521277&dopt=Abstract

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Consensus development for the supplementation of vitamin D in childhood and adolescence. Author(s): Hochberg Z, Bereket A, Davenport M, Delemarre-Van de Waal HA, De

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Schepper J, Levine MA, Shaw N, Schoenau E, van Coeverden SC, Weisman Y, Zadik Z; European Society for Paediatric Endocrinology (ESPE) Bone Club. Source: Hormone Research. 2002; 58(1): 39-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169780&dopt=Abstract •

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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Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. Author(s): Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT. Source: Journal of Neuroimmunology. 2003 January; 134(1-2): 128-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507780&dopt=Abstract

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Dangerous nutrition? Calcium, vitamin D, and shark cartilage nutritional supplements and cancer-related hypercalcemia. Author(s): Lagman R, Walsh D. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 April; 11(4): 232-5. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673461&dopt=Abstract

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Differential effects of 19-nor-1,25-(OH)(2)D(2) and 1alpha-hydroxyvitamin D(2) on calcium and phosphorus in normal and uremic rats. Author(s): Slatopolsky E, Cozzolino M, Finch JL. Source: Kidney International. 2002 October; 62(4): 1277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234297&dopt=Abstract

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Effect of a vitamin D3-based nutritional supplement ('Videchol') on carbohydrate metabolism of rats following chronic low dose-rate irradiation. Author(s): Starikovich LS, Aragon GA, Vernikovska YI, Vigovska TV, Veliky MM. Source: Journal of Radiological Protection : Official Journal of the Society for Radiological Protection. 2001 September; 21(3): 269-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594653&dopt=Abstract

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Effect of dietary supplementation with vitamin D metabolites in an experimental model of turkey osteomyelitis complex. Author(s): Huff GR, Huff WE, Balog JM, Rath NC, Xie H, Horst RL.

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Source: Poultry Science. 2002 July; 81(7): 958-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162356&dopt=Abstract •

Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Author(s): Trivedi DP, Doll R, Khaw KT. Source: Bmj (Clinical Research Ed.). 2003 March 1; 326(7387): 469. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609940&dopt=Abstract

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Effect of vitamin D3 supplementation level on the postmortem tenderization of beef from steers. Author(s): Montgomery JL, Carr MA, Kerth CR, Hilton GG, Price BP, Galyean ML, Horst RL, Miller MF. Source: Journal of Animal Science. 2002 April; 80(4): 971-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002334&dopt=Abstract

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Effects of boron supplementation of adequate and inadequate vitamin D3-containing diet on performance and serum biochemical characters of broiler chickens. Author(s): Kurtoglu V, Kurtoglu F, Coskun B. Source: Research in Veterinary Science. 2001 December; 71(3): 183-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798292&dopt=Abstract

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Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Author(s): Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 343-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568412&dopt=Abstract

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Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. Author(s): Kenny AM, Biskup B, Robbins B, Marcella G, Burleson JA. Source: Journal of the American Geriatrics Society. 2003 December; 51(12): 1762-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14687355&dopt=Abstract

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Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. Author(s): Latham NK, Anderson CS, Reid IR.

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Source: Journal of the American Geriatrics Society. 2003 September; 51(9): 1219-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919233&dopt=Abstract •

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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Efficacy of an oral, 10-day course of high-dose calciferol in correcting vitamin D deficiency. Author(s): Wu F, Staykova T, Horne A, Clearwater J, Ames R, Mason B, Orr-Walker B, Gamble G, Scott M, Reid I. Source: N Z Med J. 2003 August 8; 116(1179): U536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513083&dopt=Abstract

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Efficient synthesis of 1alpha-fluoro A-ring phosphine oxide, a useful building block for vitamin D analogues, from (S)-carvone via a highly selective palladium-catalyzed isomerization of dieneoxide to dieneol. Author(s): Kabat MM, Garofalo LM, Daniewski AR, Hutchings SD, Liu W, Okabe M, Radinov R, Zhou Y. Source: The Journal of Organic Chemistry. 2001 September 7; 66(18): 6141-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529743&dopt=Abstract

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Efficient synthesis of the A-ring phosphine oxide building block useful for 1 alpha,25-dihydroxy vitamin D(3) and analogues. Author(s): Daniewski AR, Garofalo LM, Hutchings SD, Kabat MM, Liu W, Okabe M, Radinov R, Yiannikouros GP. Source: The Journal of Organic Chemistry. 2002 March 8; 67(5): 1580-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871890&dopt=Abstract

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Enhancement of 1 alpha,25-dihydroxyvitamin D(3)-induced differentiation of human leukaemia HL-60 cells into monocytes by parthenolide via inhibition of NF-kappa B activity. Author(s): Kang SN, Kim SH, Chung SW, Lee MH, Kim HJ, Kim TS. Source: British Journal of Pharmacology. 2002 March; 135(5): 1235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11877332&dopt=Abstract

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Factors associated with the intention to use vitamin D supplements: quantitative study among a sample of elderly people in a medium-sized town in the Netherlands. Author(s): Engels Y, van Assema P, Dorant E, Lechner L.

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Source: Journal of Nutrition Education. 2001 May-June; 33(3): 134-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953228&dopt=Abstract •

Family screening is effective in picking up undiagnosed Asian vitamin D deficient subjects. Author(s): Iqbal SJ, Featherstone S, Kaddam IM, Mortimer J, Manning D. Source: Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association. 2001 October; 14(5): 371-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906578&dopt=Abstract

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Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth. Author(s): Rao A, Woodruff RD, Wade WN, Kute TE, Cramer SD. Source: The Journal of Nutrition. 2002 October; 132(10): 3191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368417&dopt=Abstract

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Genistein inhibits vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells. Author(s): Farhan H, Wahala K, Cross HS. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 March; 84(4): 423-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732287&dopt=Abstract

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Hypercalcemia in Langerhans' cell granulomatosis with elevated 1,25 dihydroxyvitamin D (calcitriol) level. Author(s): Al-Ali H, Yabis AA, Issa E, Salem Z, Tawil A, Khoury N, Fuleihan Gel-H. Source: Bone. 2002 January; 30(1): 331-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792606&dopt=Abstract

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Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breastfeeding infants. Author(s): Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. Source: The Journal of Pediatrics. 2003 February; 142(2): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584539&dopt=Abstract

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Impact of the Vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer. Author(s): Welsh J, Wietzke JA, Zinser GM, Smyczek S, Romu S, Tribble E, Welsh JC, Byrne B, Narvaez CJ.

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Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 85-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650704&dopt=Abstract •

Influence of daily regimen calcium and vitamin D supplementation on parathyroid hormone secretion. Author(s): Reginster JY, Zegels B, Lejeune E, Micheletti MC, Kvsaz A, Seidel L, Sarlet N. Source: Calcified Tissue International. 2002 February; 70(2): 78-82. Epub 2002 January 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870412&dopt=Abstract

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Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Author(s): Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Source: Lancet. 2001 November 3; 358(9292): 1500-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705562&dopt=Abstract

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Is routine supplementation therapy (calcium and vitamin D) useful after total thyroidectomy? Author(s): Bellantone R, Lombardi CP, Raffaelli M, Boscherini M, Alesina PF, De Crea C, Traini E, Princi P. Source: Surgery. 2002 December; 132(6): 1109-12; Discussion 1112-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490862&dopt=Abstract

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Isoflavonoids inhibit catabolism of vitamin D in prostate cancer cells. Author(s): Farhan H, Wahala K, Adlercreutz H, Cross HS. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 September 25; 777(1-2): 261-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270218&dopt=Abstract

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Lack of relationship of calcium and vitamin D intake to bone mineral density in premenopausal women with inflammatory bowel disease. Author(s): Bernstein CN, Bector S, Leslie WD. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2468-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638350&dopt=Abstract

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Maternal administration of high dose vitamin D(3) for cerebral palsy in her child. Author(s): Zimmermann B, Dorr HG, Muller W, Dotsch J. Source: European Journal of Pediatrics. 2004 February 13 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14968361&dopt=Abstract

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Maternal vitamin D deficiency and vitamin D supplementation in healthy infants. Author(s): Pehlivan I, Hatun S, Aydogan M, Babaoglu K, Gokalp AS.

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Source: Turk J Pediatr. 2003 October-December; 45(4): 315-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14768796&dopt=Abstract •

Nongenomic action of 1 alpha,25(OH)(2)-vitamin D3. Activation of muscle cell PLC gamma through the tyrosine kinase c-Src and PtdIns 3-kinase. Author(s): Buitrago C, Gonzalez Pardo V, de Boland AR. Source: European Journal of Biochemistry / Febs. 2002 May; 269(10): 2506-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027889&dopt=Abstract

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Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo. Author(s): Adams JS, Chen H, Chun RF, Nguyen L, Wu S, Ren SY, Barsony J, Gacad MA. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 308-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520531&dopt=Abstract

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Osteoporosis. Part III--Not just for bone loss: potential benefits of calcium and vitamin D for overall general health. Author(s): Moyad MA. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2003 February; 23(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677721&dopt=Abstract

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Osteoporosis--Part II: Dietary and/or supplemental calcium and vitamin D. Author(s): Moyad MA. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2002 December; 22(6): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593233&dopt=Abstract

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Phytoestrogen regulation of a Vitamin D3 receptor promoter and 1,25dihydroxyvitamin D3 actions in human breast cancer cells. Author(s): Wietzke JA, Welsh J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 149-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710998&dopt=Abstract

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Phytoestrogens and 17beta-estradiol influence vitamin D metabolism and receptor expression-relevance for colon cancer prevention. Author(s): Lechner D, Cross HS. Source: Recent Results Cancer Res. 2003; 164: 379-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899537&dopt=Abstract

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Phytoestrogens regulate vitamin D metabolism in the mouse colon: relevance for colon tumor prevention and therapy. Author(s): Kallay E, Adlercreutz H, Farhan H, Lechner D, Bajna E, Gerdenitsch W, Campbell M, Cross HS. Source: The Journal of Nutrition. 2002 November; 132(11 Suppl): 3490S-3493S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421875&dopt=Abstract

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Plasma vitamin D and 25OHD responses of young and old men to supplementation with vitamin D3. Author(s): Harris SS, Dawson-Hughes B. Source: Journal of the American College of Nutrition. 2002 August; 21(4): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166534&dopt=Abstract

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Potentiation of 1,25-dihydroxyvitamin D(3)-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone. Author(s): Kim SH, Kang SN, Kim HJ, Kim TS. Source: Biochemical Pharmacology. 2002 October 15; 64(8): 1233-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234604&dopt=Abstract

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Potentiation of the antiproliferative effect in vitro of doxorubicin, cisplatin and genistein by new analogues of vitamin D. Author(s): Siwinska A, Opolski A, Chrobak A, Wietrzyk J, Wojdat E, Kutner A, Szelejewski W, Radzikowski C. Source: Anticancer Res. 2001 May-June; 21(3B): 1925-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497279&dopt=Abstract

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Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation. Author(s): Grados F, Brazier M, Kamel S, Mathieu M, Hurtebize N, Maamer M, Garabedian M, Sebert JL, Fardellone P. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602746&dopt=Abstract

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Pregnancy in mice lacking the vitamin D receptor: normal maternal skeletal response, but fetal hypomineralization rescued by maternal calcium supplementation. Author(s): Rummens K, van Cromphaut SJ, Carmeliet G, van Herck E, van Bree R, Stockmans I, Bouillon R, Verhaeghe J. Source: Pediatric Research. 2003 October; 54(4): 466-73. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815117&dopt=Abstract

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Prevalence of vitamin D insufficiency in Canada and the United States: importance to health status and efficacy of current food fortification and dietary supplement use. Author(s): Calvo MS, Whiting SJ. Source: Nutrition Reviews. 2003 March; 61(3): 107-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723644&dopt=Abstract

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Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Author(s): Gartner LM, Greer FR; Section on Breastfeeding and Committee on Nutrition. American Academy of Pediatrics. Source: Pediatrics. 2003 April; 111(4 Pt 1): 908-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671133&dopt=Abstract

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Prophylactic vitamin D supplementation. Author(s): Calikoglu AS, Davenport ML. Source: Endocr Dev. 2003; 6: 233-58. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964435&dopt=Abstract

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Regulation of extrarenal synthesis of 1,25-dihydroxyvitamin D3--relevance for colonic cancer prevention and therapy. Author(s): Cross HS, Kallay E, Khorchide M, Lechner D. Source: Molecular Aspects of Medicine. 2003 December; 24(6): 459-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585316&dopt=Abstract

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Regulation of extrarenal vitamin D metabolism as a tool for colon and prostate cancer prevention. Author(s): Cross HS, Kallay E, Farhan H, Weiland T, Manhardt T. Source: Recent Results Cancer Res. 2003; 164: 413-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899539&dopt=Abstract

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Regulation of parathyroid vitamin D receptor expression by extracellular calcium. Author(s): Garfia B, Canadillas S, Canalejo A, Luque F, Siendones E, Quesada M, Almaden Y, Aguilera-Tejero E, Rodriguez M. Source: Journal of the American Society of Nephrology : Jasn. 2002 December; 13(12): 2945-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444213&dopt=Abstract

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Reproductive defects are corrected in vitamin d-deficient female rats fed a high calcium, phosphorus and lactose diet. Author(s): Johnson LE, DeLuca HF. Source: The Journal of Nutrition. 2002 August; 132(8): 2270-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163674&dopt=Abstract

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Research and public health implications of the intricate relationship between calcium and vitamin D in the prevention of colorectal neoplasia. Author(s): Jacobs ET, Martinez ME, Alberts DS. Source: Journal of the National Cancer Institute. 2003 December 3; 95(23): 1736-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652228&dopt=Abstract

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Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis. Author(s): Rodriguez-Martinez MA, Garcia-Cohen EC. Source: Pharmacology & Therapeutics. 2002 January; 93(1): 37-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916540&dopt=Abstract

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Secondary prevention of vitamin D-deficiency rickets. Author(s): Spence JT, Serwint JR. Source: Pediatrics. 2004 January; 113(1 Pt 1): E70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14702499&dopt=Abstract

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Short-term feeding of vitamin D3 improves color but does not change tenderness of pork-loin chops. Author(s): Wiegand BR, Sparks JC, Beitz DC, Parrish FC Jr, Horst RL, Trenkle AH, Ewan RC. Source: Journal of Animal Science. 2002 August; 80(8): 2116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211380&dopt=Abstract

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Soy protein: its effects on intestinal calcium transport, serum vitamin D, and insulinlike growth factor-I in vvariectomized rats. Author(s): Arjmandi BH, Khalil DA, Hollis BW. Source: Calcified Tissue International. 2002 June; 70(6): 483-7. Epub 2002 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11976771&dopt=Abstract

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Spinal surgery and severe vitamin D deficiency. Author(s): Plehwe WE, Carey RP. Source: The Medical Journal of Australia. 2002 May 6; 176(9): 438-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12056998&dopt=Abstract

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Synergistic induction of 1,25-dihydroxyvitamin D(3)- and all-trans-retinoic acidinduced differentiation of HL-60 leukemia cells by yomogin, a sesquiterpene lactone from Artemisia princeps. Author(s): Kim SH, Kim TS. Source: Planta Medica. 2002 October; 68(10): 886-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391550&dopt=Abstract

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The effect of conventional vitamin D(2) supplementation on serum 25(OH)D concentration is weak among peripubertal Finnish girls: a 3-y prospective study. Author(s): Lehtonen-Veromaa M, Mottonen T, Nuotio I, Irjala K, Viikari J. Source: European Journal of Clinical Nutrition. 2002 May; 56(5): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001014&dopt=Abstract

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The effect of season and vitamin D supplementation on bone mineral density in healthy women: a double-masked crossover study. Author(s): Patel R, Collins D, Bullock S, Swaminathan R, 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. 2001; 12(4): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420782&dopt=Abstract

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Towards a strategy for optimal vitamin D fortification (OPTIFORD). Author(s): Andersen R, Brot C, Ovesen L. Source: Nutr Metab Cardiovasc Dis. 2001 August; 11(4 Suppl): 74-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894759&dopt=Abstract

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Vascular influences of calcium supplementation and vitamin D-induced hypercalcemia in NaCl-hypertensive rats. Author(s): Kahonen M, Nappi S, Jolma P, Hutri-Kahonen N, Tolvanen JP, Saha H, Koivisto P, Krogerus L, Kalliovalkama J, Porsti I. Source: Journal of Cardiovascular Pharmacology. 2003 September; 42(3): 319-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960676&dopt=Abstract

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Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: a 3-y prospective study. Author(s): Lehtonen-Veromaa MK, Mottonen TT, Nuotio IO, Irjala KM, Leino AE, Viikari JS. Source: The American Journal of Clinical Nutrition. 2002 December; 76(6): 1446-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450915&dopt=Abstract

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Vitamin D and bone health in postmenopausal women. Author(s): Malabanan AO, Holick MF. Source: Journal of Women's Health (2002). 2003 March; 12(2): 151-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737713&dopt=Abstract

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Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Author(s): Gillespie WJ, Avenell A, Henry DA, O'Connell DL, Robertson J.

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Source: Cochrane Database Syst Rev. 2001; (1): Cd000227. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279685&dopt=Abstract •

Vitamin D compounds exert anti-apoptotic effects in human osteosarcoma cells in vitro. Author(s): Hansen CM, Hansen D, Holm PK, Binderup L. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 April; 77(1): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358669&dopt=Abstract

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Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)2D3 infusion or dietary calcium-phosphate supplementation. Author(s): Rummens K, van Bree R, Van Herck E, Zaman Z, Bouillon R, Van Assche FA, Verhaeghe J. Source: Calcified Tissue International. 2002 October; 71(4): 364-75. Epub 2002 August 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196905&dopt=Abstract

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Vitamin D enhances caspase-dependent and -independent TNFalpha-induced breast cancer cell death: The role of reactive oxygen species and mitochondria. Author(s): Weitsman GE, Ravid A, Liberman UA, Koren R. Source: International Journal of Cancer. Journal International Du Cancer. 2003 August 20; 106(2): 178-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800192&dopt=Abstract

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Vitamin D growth inhibition of breast cancer cells: gene expression patterns assessed by cDNA microarray. Author(s): Swami S, Raghavachari N, Muller UR, Bao YP, Feldman D. Source: Breast Cancer Research and Treatment. 2003 July; 80(1): 49-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889598&dopt=Abstract

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Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. Author(s): Vieth R, Fraser D. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 June 11; 166(12): 1541-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074121&dopt=Abstract

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Vitamin D intoxication associated with an over-the-counter supplement. Author(s): Koutkia P, Chen TC, Holick MF. Source: The New England Journal of Medicine. 2001 July 5; 345(1): 66-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439958&dopt=Abstract

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Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. Author(s): Huisman AM, White KP, Algra A, Harth M, Vieth R, Jacobs JW, Bijlsma JW, Bell DA. Source: The Journal of Rheumatology. 2001 November; 28(11): 2535-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708429&dopt=Abstract

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Vitamin D nutrition and bone disease in adults. Author(s): Mawer EB, Davies M. Source: Reviews in Endocrine & Metabolic Disorders. 2001 April; 2(2): 153-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705321&dopt=Abstract

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Vitamin D status and bone mineral density of veiled and unveiled Turkish women. Author(s): Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Source: Journal of Women's Health & Gender-Based Medicine. 2001 October; 10(8): 76570. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703889&dopt=Abstract

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Vitamin D status of women in the Geelong Osteoporosis Study: association with diet and casual exposure to sunlight. Author(s): Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz MA. Source: The Medical Journal of Australia. 2001 October 15; 175(8): 401-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700831&dopt=Abstract

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Vitamin D supplementation and bone mineral density in early postmenopausal women. Author(s): Cooper L, Clifton-Bligh PB, Nery ML, Figtree G, Twigg S, Hibbert E, Robinson BG. Source: The American Journal of Clinical Nutrition. 2003 May; 77(5): 1324-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716689&dopt=Abstract

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Vitamin D supplementation to healthy children does not affect serum osteocalcin or markers of type I collagen turnover. Author(s): Schou AJ, Heuck C, Wolthers OD. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 July; 92(7): 797-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892157&dopt=Abstract

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Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. Author(s): Grau MV, Baron JA, Sandler RS, Haile RW, Beach ML, Church TR, Heber D. Source: Journal of the National Cancer Institute. 2003 December 3; 95(23): 1765-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14652238&dopt=Abstract

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Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. Author(s): Rajakumar K. Source: Pediatrics. 2003 August; 112(2): E132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897318&dopt=Abstract

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Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. Author(s): Kumagai T, O'Kelly J, Said JW, Koeffler HP. Source: Journal of the National Cancer Institute. 2003 June 18; 95(12): 896-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813173&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/

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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/

The following is a specific Web list relating to vitamin D; 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 Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com

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Alcohol Withdrawal Source: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Anemia Source: Integrative Medicine Communications; www.drkoop.com Arthritis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis Source: Integrative Medicine Communications; www.drkoop.com Birth Defects Prevention Source: Healthnotes, Inc.; www.healthnotes.com Bone Cancer 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 Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cardiac Arrhythmia Source: Healthnotes, Inc.; www.healthnotes.com Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com

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Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Chronic Myelogenous Leukemia Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Dysmenorrhea Alternative names: Painful Menstruation Source: Prima Communications, Inc.www.personalhealthzone.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com High Triglycerides Source: Healthnotes, Inc.; www.healthnotes.com Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Hypoparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Iron-Deficiency Anemia Source: Healthnotes, Inc.; www.healthnotes.com

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Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Multiple Sclerosis Source: Integrative Medicine Communications; www.drkoop.com Myelofibrosis Source: Integrative Medicine Communications; www.drkoop.com Myeloproliferative Disorders Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteomalacia 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 Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com

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Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Polycythemia Vera Source: Integrative Medicine Communications; www.drkoop.com Premenstrual Syndrome 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 Psoriasis Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Prima Communications, Inc.www.personalhealthzone.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Rickets Source: Integrative Medicine Communications; www.drkoop.com Rickets/Osteomalacia Source: Healthnotes, Inc.; www.healthnotes.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Seasonal Affective Disorder Source: Healthnotes, Inc.; www.healthnotes.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Skin Conditions Source: Integrative Medicine Communications; www.drkoop.com

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Sunburn Source: Integrative Medicine Communications; www.drkoop.com Thrombocytosis Source: Integrative Medicine Communications; www.drkoop.com Tuberculosis Source: Integrative Medicine Communications; www.drkoop.com Vitiligo Source: Healthnotes, Inc.; www.healthnotes.com Wounds Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Allopurinol Source: Healthnotes, Inc.; www.healthnotes.com Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Bile Acid Sequestrants Source: Healthnotes, Inc.; www.healthnotes.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com Bone-Building Formula Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,838,00.html Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Cardiac Glycosides Source: Integrative Medicine Communications; www.drkoop.com

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Cholecalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Cimetidine Source: Healthnotes, Inc.; www.healthnotes.com Colestipol Source: Healthnotes, Inc.; www.healthnotes.com Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Dandelion Alternative names: Taraxacum officinale Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Erocalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc.; www.healthnotes.com Estrogens (combined) Source: Healthnotes, Inc.; www.healthnotes.com Flurbiprofen Source: Healthnotes, Inc.; www.healthnotes.com H2 Blockers Source: Prima Communications, Inc.www.personalhealthzone.com Heparin Source: Healthnotes, Inc.; www.healthnotes.com Heparin Alternative names: Hep-Lock Source: Prima Communications, Inc.www.personalhealthzone.com

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Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Hydroxychloroquine Source: Healthnotes, Inc.; www.healthnotes.com Indapamide Source: Healthnotes, Inc.; www.healthnotes.com Ipriflavone Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10039,00.html Isoniazid Source: Healthnotes, Inc.; www.healthnotes.com Isoniazid Alternative names: Laniazid, Nydrazid Source: Prima Communications, Inc.www.personalhealthzone.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Lubricant Laxatives 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 Methionine Source: Healthnotes, Inc.; www.healthnotes.com

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Miscellaneous Preparations Source: Integrative Medicine Communications; www.drkoop.com Neomycin Source: Healthnotes, Inc.; www.healthnotes.com Omeprazole Source: Healthnotes, Inc.; www.healthnotes.com Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Orlistat Source: Healthnotes, Inc.; www.healthnotes.com 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 Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Rifampin Alternative names: Rifadin, Rimactane Source: Prima Communications, Inc.www.personalhealthzone.com Risedronate Source: Healthnotes, Inc.; www.healthnotes.com Salicylates Source: Integrative Medicine Communications; www.drkoop.com Strontium Source: Healthnotes, Inc.; www.healthnotes.com Theophylline Derivatives Source: Integrative Medicine Communications; www.drkoop.com

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Thiazide Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Thiazide Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Valproic Acid Source: Prima Communications, Inc.www.personalhealthzone.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com Verapamil Source: Healthnotes, Inc.; www.healthnotes.com Warfarin Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. DISSERTATIONS ON VITAMIN D Overview In this chapter, we will give you a bibliography on recent dissertations relating to vitamin D. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “vitamin D” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on vitamin D, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Vitamin D 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 vitamin D. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Analysis of the Mechanism of 1(alpha),25-dihydroxyvitamin D(3)-mediated Repression of the Gene Expression of the Endogenous Inhibitor of Camp-Dependent Protein Kinase by Holmquist, Brett, PhD from University of California, Riverside, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3078991

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Catabolism of Vitamin D3 in Cultured Bone Cells by Lohnes, David L.; PhD from Queen's University at Kingston (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL53446

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Hplc/Mass Spectrometry-Based Studies of the Role of the Cytochrome P450, Cyp24, in Vitamin D Metabolism by Kaufmann, Martin John, MSC from Queen's University at Kingston (Canada), 2003, 170 pages http://wwwlib.umi.com/dissertations/fullcit/MQ81084

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Identification of Vitamin D Targets by Immunocytochemical Localization of D-CABP by Schreiner, Diane S; PhD from University of Ottawa (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL33251

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Molecular Characterization of Vitamin D(3) Receptor Promoter and 1,25dihydroxyvitamin D(3) Action in Breast Cancer Cells by Wietzke, Jennifer Ann, PhD from University of Notre Dame, 2003, 111 pages http://wwwlib.umi.com/dissertations/fullcit/3078486

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Part I. Conceptually New Low-Calcemic Analogs of the Hormone 1alpha,25dihydroxyvitamin D(3): Design, Synthesis and Biological Evaluation. Part II. One-pot, Multicomponent, Sequential Reactions: Synthesis of Diverse, Functionalized EOcteneolides and Nove by Halford, Bethany Anne, PhD from The Johns Hopkins University, 2003, 99 pages http://wwwlib.umi.com/dissertations/fullcit/3068162

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Physiological Importance of 1,25-dihydroxyvitamin D(3) Membrane-Initiated and Nuclear Actions As a Function of Growth, and Maturation in Male and Female Chickens by Larsson, Birgitta, PhD from Utah State University, 2003, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3083215

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Platelet Phospholipids in Relation to Thrombin, Cholesterol, and Vitamin D3 by Agwu, David Chibeze Emeraghi; PhD from University of Guelph (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65587

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Predictive Factors of Adherence in Participants in the Women's Health Initiative Calcium Vitamin D Study at the Western New York Vanguard Center by Lawrence, Shawn Amber, PhD from State University of New York at Buffalo, 2003, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3102384

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Rapid Effects of 25-hydroxyvitamin D3 on Calcium Uptake in Chick Enterocytes by Phadnis, Ruta Rajan, MS from Utah State University, 2003, 53 pages http://wwwlib.umi.com/dissertations/fullcit/1415142

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The Effect of Vitamin D3 Receptor Ablation on Mammary Gland Development and Tumorigenesis by Zinser, Glendon Michael, PhD from University of Notre Dame, 2003, 260 pages http://wwwlib.umi.com/dissertations/fullcit/3073505

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The Effects of Vitamin D Metabolites on the Renal Handling of Calcium, Magnesium and Phosphate in the Hamster by Burnatowska, Maria A; PhD from McGill University (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK50402

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The Relationship between Depression Levels and Vitamin D Status among Older Adults in Eastern South Dakota by Hogie-Lorenzen, Tami Lynn, Ms from South Dakota State University, 2003, 68 pages http://wwwlib.umi.com/dissertations/fullcit/1415391

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Toxic Interactions among Lead, Zinc and Cadmium with Varying Levels of Dietary Calcium and Vitamin D in Rats by Thawley, David G; PhD from University of Guelph (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK22726

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Vitamin A, Vitamin D#1Bb3#1Bs, and Epidermal Growth Factor Mechanisms of Interaction in Rat Bone Cells by Petkovich, Patrick Martin; PhD from University of Toronto (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29358

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Vitamin D and Genistein Inhibit Growth of Human Prostatic Epithelial Cells by Rao, Anuradha, PhD from Wake Forest University, 2003, 210 pages http://wwwlib.umi.com/dissertations/fullcit/3082972

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Vitamin D and Parotid Gland Function in the Rat by Peterfy, Charles G; PhD from McGill University (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL52334

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Vitamin D Autocrine System and Prostate Cancer by Whitlatch, Lyman William, Jr., PhD from Boston University, 2003, 174 pages http://wwwlib.umi.com/dissertations/fullcit/3051433

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Vitamin D Metabolism in the Hooded Seal (Cystophora Cristata) by Keiver, Katherine M; PhD from University of Guelph (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37553

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND VITAMIN D Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning vitamin D.

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

Resistance to Vitamin D or Parathyroid Hormone Condition(s): Hypocalcemia; Osteomalacia; Pseudopseudohypoparathyroidism; Rickets

Pseudohypoparathyroidism;

Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Patients with confirmed or suspected conditions with a resistance to vitamin D or parathyroid hormone (PTH) will be admitted for diagnosis and treatment, and inclusion in other studies pertaining to similar conditions. This study will provide information about problems relating to calcium in the blood, urine, and bones. Patients in this study will undergo a general evaluation / check-up to give researchers an idea of each person's condition or disease. Patients will receive treatment based on their diagnosis and asked to provide specimen samples for further research studies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001242 •

Role of Fat Tissue in Vitamin D Metabolism Condition(s): Vitamin D; Adipose Tissue; MedlinePlus consumer health information Study Status: This study is currently recruiting patients.

8

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Vitamin D is a fat soluble vitamin that has important effects on calcium (including absorption of calcium from the diet) and bone metabolism. Vitamin D is known to be stored in fat tissue, and it is also present in the circulation. The purpose of this study is to investigate the relationship between levels of vitamin D in fat tissue and in blood. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033826 •

Studies with Vitamin D Condition(s): Hypocalcemia; Rickets Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Vitamin D in the diet undergoes changes in the liver and kidneys to several forms. Patients suffering from disorders with Vitamin D resistance are unable to absorb calcium from food. Patients diagnosed with these disorders will be evaluated and treated with high doses of another form of Vitamin D (1,25-dihydroxyvitamin D3). Patients will be monitored and observed throughout the study to avoid experiencing side effects from the medication. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001151

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The Effect of Alendronate, Calcium, and Vitamin D on Bone Mineral Density in HIV Infected Patients Condition(s): HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Alendronate is a drug that has been shown to be effective in treating osteoporosis. The purpose of this study is to examine if alendronate in combination with calcium and vitamin D is safe and effective for treating bone loss in people with HIV. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061256

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Zoledronate, Calcium, and Vitamin D in Preventing Bone Loss in Women Receiving Adjuvant Chemotherapy for Breast Cancer Condition(s): Breast Cancer; Osteoporosis Study Status: This study is currently recruiting patients.

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Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Zoledronate plus calcium and vitamin D may prevent bone loss in patients receiving adjuvantchemotherapy for breast cancer. It is not yet known which regimen is more effective in preventing bone loss. PURPOSE: Randomizedphase III trial to compare the effectiveness of two regimens of zoledronate plus calcium and vitamin D in preventing bone loss in women who are receiving adjuvant chemotherapy for breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022087 •

Altered Calcium and Vitamin D in PMDD or Severe PMS Condition(s): Premenstrual Syndrome Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Mental Health (NIMH) Purpose - Excerpt: Osteoporosis has become one of the most widely recognized disorders of our times affecting an estimated 25 million women in this country. Recent evidence has suggested that premenstrual syndrome (PMS) is associated with a calcium deficiency state and bone loss. This may place premenopausal women at greater risk for osteoporosis. An entity such as PMS may be an important physiological marker of a calcium disturbance. The purpose of this investigation is to understand more completely the extent to which calcium balance is disturbed in severe PMS or Premenstrual Dysphoric Disorder (PMDD) by utilizing new tools to assess calcium and bone turnover. The long term objective is to elucidate the pathophysiology of PMDD or severe PMS as it relates to calcium hormones and bone markers. The experimental design involves the comparison between women witn severe PMS and asymptomatic controls. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005119

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The relationship between Vitamin D, fingernail thickness and bone density Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Vitamin D deficiency is common in the elderly and contributes to the increased incidence of falls, hip fracture and depression in this population. An unknown number of elderly have vitamin D resistance resulting in a functional vitamin D deficiency state. Because there are no simple procedures or blood tests that identify vitamin D resistance, its prevalence and contribution to disability in the elderly is unknown. Our inability to screen for this condition precludes our ability to initiate and monitor treatment. Previous studies indicate that fingernail thickness correlates with vitamin D status and may therefore provide a simple cost effective procedure to not only identify patients with vitamin D deficiency but also, those with vitamin D

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resistance. This procedure may also provide a way to monitor an individual's response to treatment. This study is designed to demonstrate the association between fingernail thickness and vitamin D status. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006196 •

Vitamin D Metabolism and the Williams Syndrome Condition(s): Williams Syndrome Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The Williams syndrome is a disease in which supravalvular aortic stenosis, an elfin facies, mental retardation and other congenital defects are sometimes associated with abnormal vitamin D and calcium metabolism. Whereas some patients have been reported to show increased sensitivity to vitamin D or an exaggerated response of serum 25-hydroxyvitamin D {25(OH)D} to administration of vitamin D and to have hypercalcemia caused by increased circulating 1,25-dihydroxyvitamin D{1,25(OH)2D} in infancy and early childhood, most patients have normal calcium metabolism and normal values for circulating 25(OH)D and 1,25(OH)2D. We propose to carry out further studies of vitamin D metabolism to elucidate the mechanism(s) for abnormal vitamin D metabolism. We will determine the response of serum 1,25(OH)2D to administration of 1,25(OH)2D3. Measurement of the 1,25(OH)2D in the patients compared to normal subjects will be the primary outcome. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013962

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 “vitamin D” (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:

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

Patents on Vitamin D By performing a patent search focusing on vitamin D, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

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

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

Combined calcium and vitamin D supplements Inventor(s): Andon; Mark Benson (Fairfield, OH), Smith; Kenneth Thomas (Cincinnati, OH) Assignee(s): The Procter & Gamble Company (cincinnati, Oh) Patent Number: 6,509,326 Date filed: March 14, 1997 Abstract: Nutritional mineral supplements comprising calcium citrate malate and vitamin D are disclosed. Estrogen can also be used with these supplements. These supplements, which provide at least 25% RDA of calcium and vitamin D are used in addition to the normal diet. These supplements are useful for increasing bone growth and for treating age-related bone loss in humans and animals. Excerpt(s): The present invention relates to nutritional and therapeutic improvements in calcium supplements containing vitamin D. These supplements are useful for increasing bone growth and treating age-related bone loss. They can be used in conjunction with foods and beverages or taken as an oral solid or liquid supplement. The invention also relates to a method of building bone or treating bone loss in osteoporotic patients, postmenopausal women and/or elderly men. Vitamin and mineral supplements for human and veterinary use are commonplace. Some diets, heavy physical exercise and disease conditions may require the intake of considerable quantities of minerals and vitamins apart from those generally obtained through what otherwise would be considered a normal diet. Calcium and vitamin supplementation is important primarily for those who have inadequate diets, including growing children. Older adults have an additional need for calcium to help prevent the bone loss which occurs as a normal consequence of the aging process. In particular, postmenopausal women need additional calcium due to hormonal changes which can accelerate the bone loss rate leading to a further diminishment in bone mass. There are well-recognized problems associated with adding both calcium and vitamin D to foods and beverages. Some of these are taste; calcium tends to be chalky in flavor. In addition, the solubility of many calcium sources prevents them from being added to many beverages. Interactions of calcium with the food or beverage affect the stability and/or the bioavailabilty of the product. This invention provides a means for making such product. Web site: http://www.delphion.com/details?pn=US06509326__

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Heterodimer complex of RXR and NURR1 or NGFI-B Inventor(s): Evans; Ronald M. (La Jolla, CA), Forman; Barry M. (La Jolla, CA), Umesono; Kazuhiko (Nara, JP) Assignee(s): The Salk Institute for Biological Studies (la Jolla, Ca) Patent Number: 6,458,926 Date filed: June 18, 1997 Abstract: Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as

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a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T.sub.3 R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T.sub.3 R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurr1 heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response. These findings establish a novel 9-cis retinoic acid response pathway and resolve the paradox as to how T.sub.3 R, RAR and VDR contribute to distinct physiologic pathways while sharing a common RXR subunit. Excerpt(s): The present invention relates to intracellular receptors, and method for the modulation thereof. In a particular aspect, th present invention relates to novel heterodimeric complexes. In another aspect, the present invention relates to methods for modulating processes mediated by retinoid X receptor and/or orphan receptor Nurr1. Heterodimerization is a common theme in eucaryotic regulatory biology. Indeed, a number of transcription factor families have been defined by their characteristic dimerization interface. These include the leucine zipper (e.g. fos, jun, CREB, C/EBP; see, for example, Lamb and McKnight, in Trends Biochem. Sci. 16:417-422 (1991)), helix-loophelix (e.g. myc, max, MyoD, E12, E47; see, for example, Amati and Land, in Curr. Opin. Genet. Dev. 4:102-108 (1994)), rel (NFkB, dorsal; see, for example, Blank et al., in Trends Biochem. Sci. 17:135-140 (1992)), ankyrin (GABP; see, for example, Brown and McKnight, in Genes Dev. 6:2502-2512 (1992)), and the nuclear receptor superfamilies (see, for example, Evans, in Science 240:889-895 (1988), and Forman and Samuels, Mol. Endocrinol. 4:1293-1301 (1990)). Detailed analyses of these proteins have shown that heterodimerization produces novel complexes that bind DNA with higher affinity or altered specificity relative to the individual members of the heterodimer (see, for example, Glass, in Endocr. Rev. 15:391-407 (1994)). Indeed, little is known about the contributions of each monomer toward the transcriptional properties of the complex. Naturally occurring HREs are composed of direct repeats (i.e., DRs; see Umesono et al., in Cell 65:1255-1266 (1991), inverted repeats (i.e., IRs; see Umesono et al., in Nature 336:262-265 (1988), and Williams et al. in J. Biol. Chem. 266:19636-19644 (1991)), and/or everted repeats (ERs; see Baniahmad et al., in Cell 61:505-514 (1990); Farsetti et al., in J. Biol. Chem. 267:15784-15788 (1992); Raisher et al., in J. Biol. Chem. 267:20264-20269 (1992); or Tini et al., in Genes Dev. 7:295-307 (1993)) of a degenerate X.sub.n -AGGTCA core-site. Web site: http://www.delphion.com/details?pn=US06458926__ •

Immune stimulating dietary supplement and method of use thereof Inventor(s): Meydani; Mohsen (Newton, MA), Meydani; Simin Nikbin (Newton, MA) Assignee(s): Trustees of Tufts College (medford, Ma) Patent Number: 6,642,259 Date filed: March 25, 2002 Abstract: The immune system of middle aged and elderly individuals is stimulated with a dietary supplement. The dietary supplement includes Vitamin E, Vitamin B6 and conjugated linoleic acid. The dietary supplement can further include glutathione alone or in combination with Vitamin C, folic acid, zinc, selenium, Vitamin D, copper and Vitamin B12. The dietary supplement is administered to middle aged and elderly

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individuals in a suitable form for consumption by the individual. Suitable forms of consumption can include a snack bar, tablet, capsule, powder, drink, or dairy products. Excerpt(s): Immune responses gradually decline with increasing age. Coincident with a decline in immune responses is a concomitant increase in the incidence of tumor development, infection and inflammatory diseases in middle aged and elderly populations of individuals. ("Fundamental Immunology" ed. W.E. Paul, Raven Press, NY (1989); Miller, R. A., Exp. Gerontol. 29:21-35 (1994). Compromised nutritional status can contribute to the impaired immunological state and, hence, declining health of aging individuals. Thus, there is a need to develop convenient and effective methods that augment the nutritional requirements of middle aged and elderly individuals, thereby stimulating the immune system to combat disease. The present invention relates to a dietary supplement. It also is directed to a method to stimulate the immune system of middle aged and elderly individuals or to stimulate proliferation of a lymphocyte by administration of the dietary supplement. In one embodiment, the dietary supplement comprises Vitamin E, Vitamin B6 and conjugated linoleic acid. In a specific embodiment, the dietary supplement includes Vitamin E in an amount in a range of between about 10 milligrams and about 267 milligrams per milligram of Vitamin B6, and conjugated linoleic acid in an amount in a range of between about 17 milligrams and about 100 milligrams per milligram of Vitamin B6. In another specific embodiment, the dietary supplement further includes glutathione Vitamin C, folic acid, zinc, selenium, Vitamin D, copper, Vitamin B12 and glutathione. Preferably, the dietary supplement includes Vitamin C in an amount in a range of between about 17 milligrams and about 200 milligrams per milligram of Vitamin B6; folic acid in an amount in a range of between about 0.05 milligrams and about 0.2 milligrams per milligram of Vitamin B6; zinc in an amount in a range of between about 1.67 milligrams and about 10 milligrams per milligram of Vitamin B6; selenium in an amount in a range of between about 0.005 milligrams and about 0.02 milligrams per milligram of Vitamin B6; Vitamin D in an amount in a range of between about 0.0008 milligrams and about 0.005 milligrams per milligram of Vitamin B6; copper in an amount in a range of between about 0.00008 milligrams and about 0.0007 milligrams per milligram of Vitamin B6; Vitamin B12 in an amount in a range of between about 0.0002 milligrams and about 0.001 milligrams per milligram of Vitamin B6; and glutathione in an amount in a range of between about 4 milligrams and about 33 milligrams per milligram of Vitamin B6. Web site: http://www.delphion.com/details?pn=US06642259__ •

Labeled vitamin D compounds and the use thereof Inventor(s): Holick; Michael F. (Sudbury, MA), Ray; Rahul (Wayland, MA) Assignee(s): A & D Bioscience, Inc. (sudbury, Ma) Patent Number: 6,455,714 Date filed: March 19, 2001 Abstract: Biotin, fluorescent and chemiluminescent labeled vitamin D compounds are disclosed as well as their use in assays for the presence of vitamin D, its metabolites and vitamin D analogs in biological fluids. Excerpt(s): The present invention relates to non-radioactive vitamin D compounds and methods to assay for the presence of vitamin D, vitamin D analogs and their metabolites which may be present in milk, blood or other biological fluids. The assay methods employed in this invention may be enzyme linked immunoassays (ELISAs)

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(with biotin containing compounds) and fluorimetric and chemiluminometric assays (with fluorescein or chemiluminiscence containing compounds). It is well-established that cutaneously synthesized vitamin D.sub.3, a seco-steroid, undergoes sequential metabolic conversions to 25-hydroxyvitamin D.sub.3 (25-OH-D.sub.3) in the liver and to 1,25(OH).sub.2 D.sub.3 in the kidney. 1,25(OH).sub.2 D.sub.3, the dihydroxylated metabolite of vitamin D.sub.3, is the most active form of vitamin D hormone which is intimately involved in calcium and phosphorous homeostasis (Holick, M. F. (1989), "Vitamin D: biosynthesis, metabolism and mode of action." In Endocrinology, vol. 2, Degroot et al. (eds.), Saunders, W. B., Philadelphia, pp. 902-926). In addition to vitamin D.sub.3 (synthesized in the skin), another chemical form of vitamin D.sub.3, called vitamin D.sub.2, exists in nature. Vitamin D.sub.2 is metabolized to 25-hydroxyvitamin D.sub.2 (25-(OH).sub.2 -D) and 1,25(OH).sub.2 D.sub.2 in a manner similar to vitamin D.sub.3. Vitamin D.sub.2 is obtained primarily from diet and vitamin D supplementation, and can be as little as 5-10%, or as high as 100% of the circulating concentration of 25-OH-D depending on the relative amounts of vitamin D.sub.2 present in the diet and cutaneously-produced vitamin D.sub.3 by exposure to sunlight (Holick, M. F. et al. (1986) "Calcium, phosphorus and bone metabolism: calcium regulating hormones," in Harrison's Principles of Internal Medicine, 13th Ed., Braunwald el aL (eds.), McGraw-Hill, New York, pp. 2137-2151). In the following discussion, it may be assumed that vitamin D, 25-OH-D and 125(OH).sub.2 D will represent the total pool of vitamin D and its metabolites, unless otherwise mentioned. Biosynthesis of 25-OH-D and 1,25(OH).sub.2 D and their metabolism are regulated by the factors that control mineral and skeletal metabolism (Holick, M. F. (1989)). As a result, the serum 1,25(OH).sub.2 D level is an important pathophysiological indicator in several diseases. For example, production of 1,25(OH).sub.2 D is strongly influenced by a number of diseases such as acquired or inherited disorders of vitamin D-metabolism, including renal osteodystrophy, certain metabolic bone diseases, sarcoidosis, hypercalcemia associated with chronic granulotomous disorders, and vitamin Ddependent rickets types I and II (Holick, M. F. et al. (1986)). Web site: http://www.delphion.com/details?pn=US06455714__ •

Method for anticipating sensitivity to medicine for osteoporosis Inventor(s): Baba; Toshiaki (Osaka, JP), Hosoi; Takayuki (Tokyo-to, JP), Kusaba; Nobutaka (Osaka, JP), Ouchi; Yasuyoshi (Tokyo-to, JP), Shiraki; Masataka (Misato-mura, JP), Yoshida; Hiroshi (Osaka, JP) Assignee(s): Nipro Corporation (osaka, Jp) Patent Number: 6,566,064 Date filed: May 18, 2000 Abstract: A method for anticipating sensitivity to a medicine for osteoporosis is provided which is characterized by analyzing respective genetic polymorphisms of a vitamin D receptor gene, an estrogen receptor gene, and an apolipoprotein E gene from a genome DNA contained in a sample obtained from a human, and anticipating, based on the analyzed combination of the genetic polymorphisms, that the sample is derived from an individual who shows a specific priority to sensitivities to a plurality of remedies for osteoporosis. A reagent for simultaneously detecting genetic polymorphisms is also provided which contains amplification primers and/or detection probes specific to respective genes of the vitamin D receptor gene, apolipoprotein E gene, and estrogen receptor gene. Further, a method for simultaneously detecting these

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genes, and a method for selecting remedies for bone disease based on the genetic polymorphisms are provided. According to the method of the present invention, a diagnosis as to which remedy, or medicine, for osteoporosis a subject patient has higher sensitivity can be made before the administration of the medicine so that selection of an appropriate medicine is possible and the QOL (quality of life) of the patient can be improved. Excerpt(s): The present invention relates to a novel method for the analysis of humanderived samples that can provide information useful in the therapy of osteoporosis. Specifically, the present invention relates to a method for the analysis of genetic polymorphism of genome DNA in human-derived samples in order to anticipate which is the most effective remedy for osteoporosis, in particular, among vitamin D, estrogen, and vitamin K2. Also, the present invention relates to a method for anticipating, based on a combination of genetic polymorphisms of genome DNA in a human-derived sample, that the sample is derived from an individual who shows specified priority in sensitivity to the above medicines. Further, the present invention relates to a kit for the analysis of genetic polymorphisms that can be used in the above method. Osteoporosis is the state of a disease in which bone mass (the amount of minerals, mainly calcium contained in bone) decreases and the fine structure of bone tissue changes so that the bone becomes brittle and tends to be broken. It occurs mostly in females after menopause and in senior males. It is said that the number of patients with osteoporosis is presumably 10,000,000 in Japan. It is anticipated that as the ratio of elderly persons in the population increases, the number of patients will henceforth inevitably increase. At present, various medicines such as bone activators, e.g., calcium preparations, vitamin D, etc., bone resorption depressants, e.g., estrogen, etc., and osteogenesis accelerators, e.g., vitamin K, etc., are used to treat osteoporosis. However, their therapeutical effects vary randomly depending on the patient and there have been made almost no study as to how to use a right medicine with a right patient. Since it has been taken as a rule that these remedies are administered singly, there is currently no way other than actually administering a single medicine to patients for several years and obtaining results before it can be judged based on the results which medicine is most effective. This is extremely inefficient. Web site: http://www.delphion.com/details?pn=US06566064__ •

Method for making hydroxy-25-ene-vitamin D compounds Inventor(s): Pouwer; Kees (Groningen, NL), Vries; Ton (Groningen, NL), Wynberg; Hans (Groningen, NL) Assignee(s): Bone Care International, Inc. (middleton, Wi) Patent Number: 6,441,207 Date filed: November 20, 2000 Abstract: The present invention provides a method for preparing a novel class of vitamin D compounds in which the C-25 or equivalent position has a double bond. In addition, the side chain is optionally extended by one or two methylene or methyne groups. The compounds prepared by the method of the present invention are of value as prodrugs for active 1.alpha., 24-dihydroxylated vitamin D compounds. Excerpt(s): This invention related generally to vitamin D compounds and in particular, to vitamin D compounds in which the C-25 or equivalent position is double bonded, and specifically to a method of making such compounds. Vitamin D has long been

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established as having an important biological role in bone and mineral metabolism. For example, vitamin D plays a critical role in stimulating calcium absorption and regulating calcium metabolism. It is also known that it is not vitamin D itself, but metabolites generated from it in vivo that are effective in regulating calcium metabolism. The discovery of active forms of vitamin D, (M. F. Holick et al., 68 Proc. Natl. Acad. Sci. USA, 803-804 (1971); G. Jones et al., 14 Biochemistry, 1250-1256 (1975), and other active vitamin D analogs (M. F. Holick et al., 180 Science 190-191 (1973); H. Y. Lam et al., 186 Science 1038-1040 (1974) caused much excitement and speculation about the usefulness of these vitamin D compounds in the treatment of bone depletive disorders. Animal studies examining the effects of these active vitamin D compounds, particularly 1.alpha.,25-dihydroxyvitamin D.sub.3, the hormonally active form of vitamin D.sub.3, suggested that such agents would be useful in restoring calcium balance. An early clinical study indicated that oral administration of 0.5.mu.g/day of 1.alpha.,25-dihydroxyvitamin D.sub.3 to a group of postmenopausal women improved intestinal calcium absorption as well as calcium balance in the women. On this basis, U.S. Pat. No. 4,225,596 ("'596 Patent") described and claimed the use of 1.alpha.,25dihydroxyvitamin D.sub.3 for increasing calcium absorption and retention, i.e., this compound is highly potent in stimulating intestinal calcium absorption as well as the resorption of calcium from bone (i.e., bone mobilization). Web site: http://www.delphion.com/details?pn=US06441207__ •

Method of locking 1.alpha.-OH of vitamin D compounds in axial orientation Inventor(s): DeLuca; Hector F. (Deerfield, WI), Sicinski; Rafal R. (Warsaw, PL) Assignee(s): Wisconsin Alumni Research Foundation (madison, Wi) Patent Number: 6,458,827 Date filed: July 20, 2001 Abstract: A method of modifying or altering the structure of a 1.alpha.-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1.alpha.hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1.alpha.-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1.alpha.-hydroxyl in the axial orientation. Excerpt(s): The present invention relates to vitamin D compounds, and more particularly, to a method of presenting the 1.alpha.-OH of vitamin D compounds in an axial orientation and the compounds made thereby. destabilization energy imparted to a monosubstituted six-membered chair by an axial substituent. Thus, for example, the A value of methyl substituent equals ca. 1.7 kcal/mol [Hirsch, Top. Stereochem. 1, 199 (1967)] that corresponds to 95% of population of equatorial conformer of methylcyclohexane at room temperature. The conformational free energies of substituents in cyclohexanes under ideal conditions are expected to be additive. It is usually assumed that all conformational effects are additive, i.e. various destabilizing interactions identified within a six-membered ring system operate independently of each other. In di-, tri- and polysubstituted cyclohexanes mutual interactions among the substituents have to be considered. Such interactions can destabilize one chair conformation raising its energy to favor an alternate inverted chair form, or even favor some other, distorted (rigid or flexible) cyclohexane geometries. The most important

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interactions that influence the equilibrium between the respective chair conformations include interaction of a pair of substituents in 1,2-trans-diequatorial and 1,3-cis-diaxial relationship. Thus, total destabilization energy (E.sub.D) can be described as a sum of the substituents' A values, representing monoaxial interactions, G values for 1,2diequatorial interactions and U values for 1,3-diaxial interactions [Corey, et al., J. Org. Chem. 45, 765 (1980)]. R.sub.1 and R.sub.2 are medium or large groups, the axial conformer is preferred over the equatorial (Malhotra et al., J. Am. Chem. Soc. 87, 5492 (1965)]. Thus, for example, when R.sub.1.dbd.R.sub.2 =Me the difference in energy between both forms is approximately 4.5 kcal/mol, in favor of the axial conformer. In the case when R.sub.1 =Me and R.sub.2 =H, a 1:3 peri interaction exists which increases by ca. 1.25 kcav/mol the destabilization energy of the system (Duraisamy et al., J. Am. Chem. Soc. 105, 3264 (1983)]. Web site: http://www.delphion.com/details?pn=US06458827__ •

Methods for treating cholesterol-containing foodstuffs using live ciliates Inventor(s): Florin-Christensen; Jorge (1430 NE. Upper Dr., Pullman, WA 99163), Harris; Joseph B. (330 SE. Camino St., Pullman, WA 99163), Itzkovici; Alejo (Bustamante 2434, 5B, RA-1425 Buenos Aires, AR), Valcarce; German A. (Bustamante 2434, 5B, RA-1425 Buenos Aires, AR) Assignee(s): None Reported Patent Number: 6,534,100 Date filed: August 17, 2000 Abstract: The present invention provides methods for changing the composition of a cholesterol-containing foodstuff. The methods comprise the step of culturing a member of the family Tetrahymenidae in a liquid, cholesterol-containing foodstuff under conditions that enable one or more (or all) of the following changes in the composition of the foodstuff: (a) reduction in the level of cholesterol in the treated foodstuff; (b) reduction in the level of saturated fatty acids in the treated foodstuff; (c) increase in the level of unsaturated fatty acids in the treated foodstuff; (d) increase in the level of at least one vitamin D precursor in the treated foodstuff and (e) reduction in the level of at least one protein in the treated foodstuff. The foodstuff can be a dairy product, such as milk or egg yolk. Excerpt(s): This application relates to the treatment of foodstuffs using live cultures of protozoa, such as Tetrahymena thermophila. One aspect of the present invention is the provision of methods for the conversion of cholesterol present in foodstuffs into provitamin D3 and other sterols containing a double bond at position 7. Animal milk is a complex mixture of different compounds, including lipids, proteins, minerals, sugars and vitamins (Russof, L. L. (1970), J. Dairy Science 53:1296-1302). The calcium, phosphate and vitamin D content of milk make it an adequate source of nutrients for bone formation (Fox, P. F. and McSweeney, P. L. H. (1998a) Salts of milk. In "Dairy Chemistry and Biochemistry", chapter 5, Blackie Academic & Professional, London). This may be a key aspect of its role in nature, allowing mammalian newborns to complete the formation of the skeleton after birth. Mineral and vitamin components of milk are also important to preserve bone structure in adulthood. Milk is also relatively economical, compared to other animal protein sources, and thus it makes a valuable contribution to the human diet (Russof, L. L. (1970), J. Dairy Science 53:1296-1302). The lipid fraction of milk includes cholesterol, however, which has been implicated as a causative agent of coronary artery disease (Artaud-Wild, S. M., Connor, S. L., Sexton, G.,

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Connor, W. E. (1993), Circulation 88:2771-2779). Other foodstuffs of animal origin such as eggs, which are commonly used in the preparation of a variety of food products, present the same problem. Because of the special organoleptic traits of milk and eggs, it is difficult to replace them by other products with less cholesterol content. Web site: http://www.delphion.com/details?pn=US06534100__ •

Nutritional composition made from conventional foods for mixing onsite in a blender and treating patients with hepatic disorders Inventor(s): Muszynska; Julia (108 Center St., Staten Island, NY 10306) Assignee(s): None Reported Patent Number: 6,524,610 Date filed: February 26, 2001 Abstract: A nutritional composition made from conventional food mixed on-site in a blender and treating patients with hepatic disorders. The composition includes a vitamin A enriched conventional food, a vitamin D enriched conventional food, a vitamin E enriched conventional food, a vitamin K enriched conventional food, a vitamin C enriched conventional food, a thiamine enriched conventional food, a riboflavin enriched conventional food, a niacin enriched conventional food; a pyridoxine enriched conventional food, a folic acid enriched conventional food, a pantothenic acid enriched conventional food, a vitamin B12 enriched conventional food, a biotin enriched conventional food, a chloine enriched conventional food, a sodium enriched conventional food, a potassium enriched conventional food, a chlorine enriched conventional food, a calcium enriched conventional food, a phosphorus enriched conventional food, a magnesium enriched conventional food, a copper enriched conventional food, an Iodine enriched conventional food, a manganese enriched conventional food, and a zinc enriched conventional food. Excerpt(s): The present invention relates to a nutritional composition. More particularly, the present invention relates to a nutritional composition made from conventional foods for mixing on site in a blender and treating patients with hepatic disorders. The liver, and its proper functioning, is of utmost importance to the survival of a patient. Because it is responsible for the metabolism of nearly all nutrients, and is the primary site for the inactivation of numerous toxins, the liver is one of the most important organs of the body. For example, the liver accounts for approximately 20% of the body's basal metabolism. The liver extracts a majority of the amino acids, carbohydrates, lipids, vitamins, and minerals from portal circulation. These nutrients, extracted by the liver, are used as substrates or cofactors in all metabolic processes carried out in the liver. Synthesis of plasma proteins and bile secretion are additionally important processes carried out by the liver. Web site: http://www.delphion.com/details?pn=US06524610__

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Ophthalmic composition containing active vitamin D Inventor(s): Ishii; Yasuo (Kawaguchi, JP), Itoh; Seiji (Mobara, JP), Kita; Kiyoshi (Tokyo, JP), Mukai; Katsuhiko (1-5-301, Matsuba-Cho 5-Chome, Kashiwa-Shi, Chiba-Ken 277, JP) Assignee(s): Mukai; Katsuhiko (kashiwa, Jp) Patent Number: 6,500,813 Date filed: October 3, 2000 Abstract: An ophthalmic composition comprises active vitamin D as an effective component and is used for preventing deterioration of the optical transparency, occurrence of high intraocular pressure diseases or defective sight, observed after an ophthalmic operation, due to hyperplasia of the anterior ocular cells in the tissues damaged by the ophthalmic operation, which are in course of a healing process, and/or excess production of cellular materials.The ophthalmic composition can be dropped in the eye after operations such as those for cataract, for transplantation of intraocular lenses and for cornea to maintain the intraocular transparency of the anterior ocular region, to control the hyperplasia of the anterior ocular cells in the tissues damaged by the ophthalmic operation, which are in course of a healing process, and/or excess production of cellular materials and to thus prevent any reduction of visual acuity. Excerpt(s): The present invention relates to an ophthalmic composition and more specifically to an ophthalmic composition for treating patients suffering from intraocular inflammation, glaucoma and corneal degeneracy and for preventing any occurrence of hyperplasia of anterior ocular cells during the damaged tissue-healing process after operations thereof and/or for preventing, for instance, any reduction in transparency, any change in refractive power and any increase in intraocular pressure. Rachitis is one of the osteopathy, and it has formerly been believed that the rachitis is closely related to the action of the sunlight. Thereafter, however, it has been found out that a certain vitamin is closely involved in the rachitis. This anti-rachitis vitamin is named vitamin D. Vitamin D.sub.2 obtained by purifying vitamin D.sub.1 which is a mixture with other isomers as well as vitamin D.sub.3 discovered through the subsequent studies have widely been used in the treatments of many patients suffering from osteopathy such as rachitis, osteomalacia, osteoporosis, ostitis fibrous and osteosclerosis, malignant tumors such as breast cancer and carcinoma of large intestine, as well as dermatosis such as psoriasis. Vitamin D is an essential vitamin for the bone modeling and it is prescribed by the Ministry of Public Welfare of Japan that the required amount of this nutrient to be taken with foods is set at 200 IU (5.mu.g)/day. However, the required amount of the nutrient differs from that prescribed in foreign countries (i.e., 400 IU/day) because of the presence of vitamin D.sub.3 which is produced in the skin by the action of ultraviolet light rays through sunbathing. In other words, it is necessary to take excess of vitamin D in case where sufficient sunbathing is not ensured. Vitamins D.sub.2 to D.sub.7 are classified as vitamins having rachitisinhibitory activity, but presently used in the treatment of this disease are vitamin D.sub.2 and vitamin D.sub.3 having high physiological activity. Vitamin D's are administered to patients per oral route or by injection. In case of skin diseases, they are also administered in the form of ointments. It has been known that the vitamin D undergoes a change in its molecular structure through the action of ultraviolet rays or in the liver and kidney and that it is thus converted into active vitamin D having high biological activities. It has been recognized that vitamin D's have not only calciumregulatory effect, but also other biological activities since the discovery of the active vitamin D.sub.3, i.e., calcitriol (1.alpha.,25-dihydroxy cholecalciferol) as a derivative of the cholecalciferol. As other derivatives or analogues of the cholecalciferol, there have

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been known, for instance, alpha-calcidol (1.alpha.-monohydroxy cholecalciferol) and calcifedol (25-monohydroxy cholecalciferol). There have recently been known about 16 kinds of cholecalciferol derivatives. In addition, there have been developed several kinds of cholecalciferol analogues such as OCT (2-oxacalcitriol) and calcipotriol. The presence of active vitamin D receptors in cells have been discovered and there have been conducted studies on inhibition of cellular activities because of the ability of the active vitamin D's to control the production of various cytokines. Web site: http://www.delphion.com/details?pn=US06500813__ •

Pharmaceutical composition Inventor(s): Morris; David (Lugarno, AU) Assignee(s): Mrc Holdings Pty Limited (sydney, Au) Patent Number: 6,664,246 Date filed: May 22, 2001 Abstract: The present invention is concerned with a pharmaceutical composition suitable for the treatment of cancer and in particular with a pharmaceutical composition containing vitamin D or a precursor, analogue or metabolite thereof and the use of these compositions in the treatment of a tumor in a subject. Excerpt(s): The present invention is concerned with pharmaceutical compositions suitable for the treatment of cancer, and in particular, with pharmaceutical compositions containing vitamin D or a precursor, analogue or metabolite thereof and the use of these compositions in the treatment of a tumor in a subject. Vitamin D is an isoprenoid compound made up of activated 5-carbon units. The most abundant form of vitamin D is vitamin D.sub.3, or cholecalciferol. Vitamin D.sub.3 arises from biosynthesis of 7dehydrocholesterol, an intermediate in cholesterol biosynthesis. Vitamin D.sub.3 is metabolised in the liver to 25-hydroxycholecalciferol [25(OH)D.sub.3 ] which is a major form of Vitamin D circulating in the blood compartment 25(OH)D.sub.3 is converted by the kidney to produce two principal dihydroxylated metabolites, namely, 1,25dihydroxycholecalciferol [1,25(OH).sub.2 D.sub.3 ] and 24,25-dihydroxycholecalciferol [24R,25(OH).sub.2 D.sub.3 ]. 1,25(OH).sub.2 D.sub.3 is the most biologically active naturally occurring form of vitamin D.sub.3 and is transported in the bloodstream to its major site of action in the mucosal cells of the intestine, where calcium absorption is stimulated. Thus vitamin D.sub.3 may be regarded as a prohormone because it is converted to a metabolite that acts analogously to a steroid hormone. It regulates calcium and phosphorous metabolism particularly in the synthesis of the inorganic matrix of bones. Web site: http://www.delphion.com/details?pn=US06664246__

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Pharmaceuticals for modulating hormone responsiveness Inventor(s): Dedhar; Shoukat (#1-219 East 8th St., North Vancouver B.C., CA V7L 1Y9) Assignee(s): None Reported Patent Number: 6,518,397 Date filed: July 24, 1997

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Abstract: This invention relates to isolated and purified proteins, such as calreticulin and mimetics and inhibitors of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including cancer, osteoporosis and chronic inflammatory disease. The proteins include or bind to an amino acid sequence [SEQ ID NO: 1] KXFFX.sup.1 R, wherein X is either G, A or V and Y is either K or R. This sequence is present in the DNA-binding domain, and is critical for the DNA binding activity, of a variety of hormone receptors, including glucocorticoid receptor, minerolcorticoid receptor, androgen receptor, progesterone receptor, estrogen receptor, retinoic acid receptor, thyroid hormone receptor and vitamin D receptor. Proteins which bind to this sequence may inhibit hormone receptor induced gene transcription. Proteins which include this sequence may promote hormone receptor induced gene transcription. Excerpt(s): The physiology of many organs in mammals is regulated by hormones. These hormones include steroid hormones, thyroid hormones, metabolites of vitamins, such as all trans retinoic acid, 9-cis retinoic acid, vitamin D and its metabolite 1,25 dihydroxyvitamin D3. These hormones bind to intracellular receptors which regulate expression of genes (O'Malley, 1990). There are a variety of receptors which respond to hormones. Osteoblasts and osteoclasts respond to steroid hormones, vitamin D and retinoic acid. Mammary epithelial cells and breast carcinoma cells respond to estrogens, progesterone, retinoic acid and glucocorticoids. Lymphocytes respond to glucocorticoids. The response of receptors to hormones is particularly important in the development of a number of diseases, including cancer, osteoporosis and chronic inflammatory disease. For example, the vitamin D receptor is strongly implicated in the evolution of osteoporosis (Morrison, 1994). Web site: http://www.delphion.com/details?pn=US06518397__ •

Prevention of ovarian cancer by administration of a vitamin D compound Inventor(s): Rodriguez; Gustavo C. (Durham, NC), Whitaker; Regina Salas (Hillsborough, NC) Assignee(s): New Life Pharmaceuticals Inc. (chicago, Il) Patent Number: 6,444,658 Date filed: January 7, 2000 Abstract: The present invention relates to methods for preventing the development of epithelial ovarian cancer by administering a Vitamin D compound in an amount capable of increasing apoptosis in non-neoplastic ovarian epithelial cells of the female subject. Excerpt(s): Ovarian cancer is the fourth leading cause of cancer deaths among women in the United States and causes more deaths than all other gynecologic malignancies combined. In the United States, a woman's lifetime risk of developing ovarian cancer is 1 in 70. In 1992, about 21,000 cases of ovarian cancer were reported, and about 13,000 women died from the disease. Chapter 321, Ovarian Cancer, Harrison's Principles of Internal Medicine, 13th ed., Isselbacher et al., eds., McGraw-Hill, N.Y. (1994), pages 1853-1858; American Cancer Society Statistics, Cancer J. Clinicians, 45:30 (1995). Epithelial ovarian cancer, the most common ovarian cancer, has a distinctive pattern of spread: cancer cells may migrate through the peritoneum to produce multiple metastatic nodules in the visceral and parietal peritoneum and the hemidiaphragms. In addition

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cancer cells metastasize through the lymphatic and blood vessels to areas such as the liver, lung and brain. Early stage ovarian cancer is often asymptomatic and is detected coincidentally by palpating an ovarian mass on pelvic examination. In premenopausal patients, about 95% of these masses are benign. Even after menopause, 70% of masses are benign but detection of any enlargement requires exploratory surgery. In postmenopausal women with a pelvic mass, a markedly elevated serum CA-125 level of greater than 65 U/ml indicates malignancy with a 96% positive predictive value. Chapter 321, Ovarian Cancer, Harrison's Principles of Internal Medicine, supra. Epithelial ovarian cancer is seldom encountered in women less than 35 years of age. Its incidence increases sharply with advancing age and peaks at ages 75 to 80, with the median age being 60 years. The single most important risk factor for this cancer is a strong family history of breast or ovarian cancer. In families in which ovarian, breast, endometrial or colon cancer can be tracked as an apparent autosomal dominant trait, the risk of this cancer can be as high as 50%. Having a single first-degree relative with ovarian cancer increases a woman's risk by at least three-fold, and having a personal history of breast or colorectal cancer increases the risk of subsequently developing ovarian cancer by two-fold. Chapter 321, Ovarian Cancer, Harrison's Principles of Internal Medicine, supra. In addition, those with identifiable genetic mutations in genes such as BRCA1 also have an increased risk. Baker et al., Etiology, Biology, and Epidemiology of Ovarian Cancer, Seminars in Surgical Oncology 10: 242-248, 1994; Amus et al., Genetic Epidemiology of Epithelial Ovarian Cancer, Cancer 71: 566-72, 1993; Whitmore, Characteristics Relating To Ovarian Cancer Risk: Implications for Preventing and Detection, Gynecologie Oncology 55, 515-19, 1994. Oncogenes associated with ovarian cancers include the HER-2/neu (c-erbB-2) gene, which is overexpressed in a third of ovarian cancers, the fins oncogene, and abnormalities in the p53 gene, which are seen in about half of ovarian cancers. A number of environmental factors have also been associated with a higher risk of epithelial ovarian cancer, including a high fat diet and intake of lactose in subjects with relatively low tissue levels of galactose-1phosphate uridyl transferase. Previously, there has existed no established pharmaceutical approach to the prevention of ovarian cancer. For all women, especially those at high risk of developing this disease, the only available option has been surgical removal of the ovaries, with all of the attendant risks and subsequent adverse health consequences due to resulting estrogen deficiency. Web site: http://www.delphion.com/details?pn=US06444658__ •

Stereoselective synthesis of 24-hydroxylated compounds useful for the preparation of aminosterols, vitamin D analogs, and other compounds Inventor(s): Bulliard; Michel (Angers, FR), Jones; Steven (West Chester, PA), Kinney; William A. (Richboro, PA), Lee; Nancy (Foxboro, MA), Meckler; Harold (Delmar, NY), Rao; Meena N. (Lansdale, PA), Zhang; Xuehai (E. Norriton, PA) Assignee(s): Magainin Pharmaceuticals, Inc. (plymouth, Pa) Patent Number: 6,610,866 Date filed: April 12, 2001 Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The

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fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds. Excerpt(s): Since the discovery of squalamine, however, several other interesting properties of this compound have been discovered. For example, as described in U.S. patent application Ser. Nos. 08/416,883 (filed Apr. 20, 1995) and 08/478,763 (filed Jun. 7, 1995), squalamine may function as an antiangiogenic agent. These patent applications are entirely incorporated herein by reference. Additional uses of squalamine (e.g., as an agent for inhibiting NHE3 and as an agent for inhibiting endothelial cell growth) are disclosed in U.S. patent application Ser. No. 08/474,799 (filed Jun. 7, 1995) and U.S. patent application Ser. No. 08/840,706 (filed Apr. 25, 1997). These patent applications also are entirely incorporated herein by reference. Methods for synthesizing squalamine have been devised, such as the methods described in WO 94/19366 (published Sep. 1, 1994). This PCT publication is entirely incorporated herein by reference. This PCT application relates to U.S. patent application Ser. No. 08/023,347, which application also is entirely incorporated herein by reference. Additionally, U.S. patent application Ser. No. 08/474,799 also discloses squalamine isolation and synthesis techniques. Compound 1436 previously has been described in U.S. patent application Ser. Nos. 08/483,057 and 08/487,443, each filed Jun. 7, 1995. Each of these U.S. patent applications is entirely incorporated herein by reference. As further described in these patent applications, compound 1436 has a variety of interesting properties. For example, compound 1436 inhibits human T-lymphocyte proliferation, as well as the proliferation of a wide variety of other cells and tissues. Additional uses of compound 1436 are disclosed in U.S. Provisional Patent Appl. No. 60/017,627 (filed May 17, 1996) and the subsequently filed U.S. patent application Ser. Nos. 08/857,288 filed May 16, 1997 and 08/962,290 filed Oct. 31, 1997. These patent applications also are entirely incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06610866__ •

Treatment of systemic lupus erythematosis Inventor(s): Cantorna; Margherita T. (State College, PA), DeLuca; Hector F. (Deerfield, WI), Humpal-Winter; Jean (Poynett, WI) Assignee(s): Wisconsin Alumni Research Foundation (madison, Wi) Patent Number: 6,673,782 Date filed: October 21, 1999 Abstract: A method of treating SLE symptoms of an SLE patient comprising administering to an SLE patient an amount of vitamin D compound effective to reduce symptoms and observing a reduction in symptoms is disclosed. Excerpt(s): Systemic lupus erythematosis (SLE) is a systemic autoimmune disease with the potential to be directly involved in multiple organ systems. (See review by Kotzin, B. L., Cell 85:303-306, 1996.) The clinical manifestations of SLE include skin rash and joint pain, and severe and progressive kidney involvement. SLE patients typically present elevated serum levels of antibodies to nuclear constituents (i.e., antinuclear antibodies). In order to study the disease, workers have employed several animal models, including the F1 hybrid of New Zealand Black (NZB) and New Zealand White (NZW) mice, MRL

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mice homozygous for the lymphoproliferation (lpr) gene and BXSB mice, which carry the disease accelerating Yaa gene on the Y chromosome. Principal targets of the autoantibodies produced in SLE patients include protein-nucleic acid complexes, such as chromatin, the U1 and Sm small nuclear ribonucleoprotein (snRNP) particles and the Ro/SSA and La/SSB RNP complexes (Tan, 1989; Cotson and Odell, 1995). Autoantibodies to phospholipids and cell surface molecules are also detected. Current treatments have addressed lupus nephritis, although commonly used therapeutic regimes are potentially toxic and may be ineffective for some high risk patients. Typically, intensive immunosuppressive regimes are prescribed. For severe SLE, immunosuppressives such as chemotherapies and cyclosporin are used. Other treatments include treatment with corticosteroids and cytotoxic drugs. Alternative therapies include treatment with cyclophosphamide and prednisone. Side effects of long term use of prednisone include development of high blood pressure, diabetes and osteoporosis. Web site: http://www.delphion.com/details?pn=US06673782__ •

Vitamin D analogues and their pharmaceutical use Inventor(s): Hansen; Kai Holst (Herlev, DK) Assignee(s): Leo Pharmaceutical Products Ltd. (ballerup, Dk) Patent Number: 6,537,980 Date filed: October 23, 2001 Abstract: The present invention relates to compounds of general formula (I) wherein R.sup.1 and R.sup.2, which may be the same or different, represent (C.sub.1 C.sub.4)alkyl, and R.sup.3 represents hydrogen, halogen, (C.sub.1 -C.sub.4)alkyl, or O-(C.sub.1 -C.sub.4)alkyl, and in-vivo hydrolysable esters there with pharmaceutically acceptable acids. The present compounds are of value in the human and veterinary practice. Excerpt(s): This invention relates to hitherto unknown vitamin D compounds which shows strong activity in inducing differentiation and inhibiting undesirable proliferation of certain cells, including skin cells and cancer cells, as well as antiinflammatory and immunomodulating effects, to pharmaceutical preparations containing these compounds, to dosage units of such preparations, and to their use in the treatment and prophylaxis of diseases characterised by abnormal cell differentiation and/or cell proliferation such as cancer, leukemia, myelofibrosis, and psoriasis, of a number of disease states including hyperparathyroidism, particularly secondary hyperparathyroidism associated with renal failure, diabetes mellitus, hypertension, acne, alopecia, skin ageing, AIDS, neurodegenerative disorders such as Alzheimer's disease, host versus graft reactions, rejection of transplants, inflammatory diseases such as rheumatoid arthritis and asthma, for prevention and/or treatment of steroid induced skin atrophy, and for promoting osteogenesis and treating osteoporosis. It has been shown that 1.alpha.,25-dihydroxy-vitamin D.sub.3 (1,25(OH).sub.2 D.sub.3) influences the effects and/or production of interleukins (Muller, K. et al., Immunol. Lett., 17, 361366 (1988)), indicating the potential use of this compound in the treatment of diseases characterised by a dysfunction of the immune system, e.g. autoimmune diseases, AIDS, host versus graft reactions, and rejection of transplants or other conditions characterised by an abnormal interleukin-1 production, e.g. inflammatory diseases such as rheumatoid arthritis and asthma. It has also been shown that 1,25(OH).sub.2 D.sub.3 is able to stimulate the differentiation of cells and inhibit excessive cell proliferation (Abe,

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E. et al., Proc. Natl. Acad. Sci., U.S.A., 78, 4990-4994 (1981)), and it has been suggested that this compound might be useful in the treatment of diseases characterised by abnormal cell proliferation and/or cell differentiation such as leukemia, myelofibrosis and psoriasis. Web site: http://www.delphion.com/details?pn=US06537980__ •

Vitamin D derivatives with phosphorus atoms in the side chains Inventor(s): Fahnrich; Marianne (Berlin, DE), Haberey; Martin (Berlin, DE), Kirsch; Gerald (Berlin, DE), Langer; Gernot (Berlin, DE), Neef; Gunter (Berlin, DE), Schwarz; Katica (Berlin, DE), Steinmeyer; Andreas (Berlin, DE), Wiesinger; Herbert (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (berlin, De) Patent Number: 6,531,459 Date filed: August 4, 2000 Abstract: Described are new vitamin D derivatives such as of the formula (I) detailed in this disclosure. Also described are methods for preparing these derivatives, inter mediates used to prepare the derivatives and use of the derivatives as pharmaceutical agents. Excerpt(s): process for their production, intermediate products of the process as well as the use for the production of pharmaceutical agents. In addition to their pronounced effect on the calcium and phosphate metabolism, the active metabolites of vitamins D.sub.2 and D.sub.3 and their synthetic derivatives have a proliferation-inhibiting and differentiation-stimulating action on tumor cells and normal cells, such as, for example, skin cells. In addition, a pronounced effect on cells of the immune system (inhibiting of proliferation and interleukin 2-synthesis of lymphocytes, increase of cytotoxicity and phagocytosis in vitro of monocytes) has been found, which manifests itself in an immunomodulatory action, and finally, because of a stimulating action on bone-forming cells, an increased formation of bone in normal and osteoporotic rats is found [R. Bouillon et al. "Short Term Course of 1,25-(OH).sub.2 D.sub.3 Stimulates Osteoblasts But Not Osteoclasts," Calc. Tissue Int. 49, 168 (1991)]. All actions are mediated by bonding to the vitamin D receptor. Because of the bonding, the activity of specific genes is regulated. Web site: http://www.delphion.com/details?pn=US06531459__

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Vitamin d solution holder and containers for transfusions Inventor(s): Kaga; Junji (Tokushima, JP JPN), Kobatake; Hideki (Naruto, JP), Sekimoto; Shigehito (Tokushima, JP), Tani; Seiji (Tokushima, JP) Assignee(s): Otsuka Pharmaceutical Factory, Inc. (tokushima, Jp) Patent Number: 6,572,603 Date filed: August 2, 2000 Abstract: The present invention relates to a polyolefin-made holder for solutions containing vitamin D or derivatives thereof, in which the volume of polyolefin constituting a solution-holding portion of the holder is 30 cm.sup.3 or less per.mu.mol of the vitamin D or derivatives thereof contained therein; and to a transfusion fluid

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container comprising the vitamin D solution holder. Use of the holder or container can minimize reduction in vitamin D content. Excerpt(s): The present invention relates to a polyolefin-made holder for a vitamin D solution, which minimizes reduction in vitamin D content, and to a transfusion fluid container that accommodates the holder. In many cases, patients who have undergone surgery on the digestive tract cannot ingest nutrition orally. Therefore, in order to provide nutrition to such patients, intravenous hyperalimentation (IVH) is generally carried out. IVH facilitates an improvement in the nutritional status of the aforementioned patients and maintenance of the improved nutritional status, and thus promotes recovery and healing in these patients. Therefore, IVH is considered to be very effective, and at present IVH is widely employed in the field of surgical treatment. In IVH, carbohydrates and amino acids, serving as nutritional sources, and electrolytes are usually administered. Transfusion products containing all of these sources have been developed for IVH, and generally, commercially available products are of the type in which two containers, one containing glucose and the other containing amino acids (here the glucose and amino acids are known to induce the Maillard reaction). Web site: http://www.delphion.com/details?pn=US06572603__ •

Wildlife nutritional supplement Inventor(s): Fuhr; David R. (Winigan, MO), Hauser; David (Winigan, MO) Assignee(s): 4 Seasons Wildlife Nutrition, Llc (winigan, Mo) Patent Number: 6,572,903 Date filed: May 8, 2002 Abstract: The present invention is a wildlife nutritional supplement for free ranging ruminants including about 7.5-8.5% calcium, about 3.5% phosphorus, about 32-37% salt, at least one "B" series vitamin is selected from a group consisting of pantothenic acid, folic acid, riboflavin, niacin, thiamine, cobalamin, and pyridoxine hydrocholoride, about 16-19% sodium, about 0.15% magnesium, about 0.15% potassium, about 2.5% sulfur, about 1,200 PPM iron, about 20 PPM copper, about 105 PPM manganese, about 45 PPM zinc, about 5 PPM cobalt, about 1 PPM selenium, about 1 PPM iodine, about 50,000 IU/LB Vitamin A, about 20,000 IU/LB Vitamin D, about 50 IU/LB Vitamin E, about 134 MG/LB biotin, about 60 MG/LB ascorbic acid, oxytetracycline and fenbendazole. Excerpt(s): This invention relates to wildlife nutritional supplements, and more particularly to a ruminant feed supplement having enhanced palatability and immunesystem bolstering effects. The reduction of habitat due to human development has left a noticeable impact on the health and vitality of wild ruminant animals. Ruminant animals such as deer, elk and the like, suffer diminished reproduction, decreased weight, smaller antlers, and susceptibility to disease and parasites. There are seven major minerals that have an important effect on wildlife: (1) calcium aids in the growth of bones, teeth and antlers and is important in the function of muscles and nerves; (2) phosphorus aids in the growth of bones, teeth and antlers, enhances energy metabolism and enzymation as well as proper protein utilization; (3) potassium is integral in the function of nerves, enzyme processes, as well as mineral and water balance; (4) sulfur is an essential component of some proteins; (5) sodium is vital to the function of muscles and nerves and also maintains water balance; (6) chloride of sodium forms hydrochloric acid in the abomasums which aids in protein breakdown; and (7) magnesium is an important component is almost all body processes.

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Web site: http://www.delphion.com/details?pn=US06572903__

Patent Applications on Vitamin D 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 vitamin D: •

5,6-Trans-2-alkylvitamin d derivatives Inventor(s): Fujishima, Toshie; (Tokyo, JP), Takayama, Hiroaki; (Tokyo, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030092687 Date filed: November 4, 2002 Abstract: Object of the present invention is to synthesize novel vitamin D derivatives.The present invention provides 5,6-trans-2-alkyl-substituted vitamin D derivatives of Formula (1): 1whereinR.sub.1 is straight or branched-chain alkyl; andR.sub.2 is straight or branched-chain alkyl optionally substituted with hydroxy. Excerpt(s): The present invention relates to novel vitamin D derivatives, more particularly, relates to 5,6-trans-2-alkyl-substituted vitamin D derivatives. Activated vitamin D.sub.3 derivatives including 1.alpha.,25-dihydroxyvitamin D.sub.3 are known to have many physiological activities such as calcium metabolism regulatory activities, growth inhibitory, and differentiation inducing activities for tumor cells, and immunoregulatory activities. However, some activated vitamin D.sub.3 derivatives may cause hypercalcemia during long-term and continuous administration, therefore they are not suitable for use as antitumor agents, antirheumatic agents, and the like. Thus, a number of studies have been conducted to synthesize vitamin D derivatives for the purpose of separating those activities. The studies conducted by the inventors of the present invention clarified that introduction of a 2.alpha.-methyl group into an A ring part of active vitamin D.sub.3, that is 1.alpha.,25-dihydroxyvitamin D.sub.3, increases the vitamin D receptor (VDR) binding property (Bioorg. Med. Chem. Lett., 1998, 8, 151; K. Konno et al.). Furthermore, a combination of the introduction of a 2.alpha.-methyl group and the epimerization of the side chain at 20-position has been reported to enhance the VDR binding property (Bioorg. Med. Chem. Lett., 1998, 8, 2145; T. Fujishima et al.). However, no work has beet done to synthesize a vitamin D derivative in which the 2-position is substituted, the steric configuration at the 20-position is native or epimerized, and the double bond at the 5-position is in E configuration; further, the physiologically activities of such a vitamin D derivative have not been studied. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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

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Agents and methods for promoting bone growth Inventor(s): Popoff, Steven N.; (Warrington, PA), Safadi, Fayez; (Philadelphia, PA), Schneider, Gary B.; (Hudson, OH) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20030229014 Date filed: November 9, 2001 Abstract: Agents for promoting bone deposition and growth in a mammalian subject. The agents are O-glycosylated and non-glycosylated peptides that are derived from vitamin D binding protein, collectively referred to hereinafter as "DBP" peptides. The DBP peptides are from 3 to 18, preferably from 4 to 14 amino acids in length and comprise a sequence which is at least 80% identical, preferably at least 90% identical to the amino acid sequence of a fragment contained within domain III of DBP. Methods for promoting bone deposition in a subject in need of the same are also provided. The methods comprise administering to the subject a therapeutically effective quantity of an agent selected from the group consisting of an activated form of vitamin D binding protein referred to hereinafter as "ADBP", one or more DBP peptides, and combinations thereof. The agents may be administered locally or systemically. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/247,464 filed on Nov. 9, 2000. The inventions relate to agents and methods for promoting bone deposition and growth in a mammalian subject. These agents and methods are particularly suited for use in mammals with diseases or disorders involving bone loss, such as osteoporosis, osteopenias, fractures, and bone necrosis. There are a variety of diseases which have an adverse impact on bone, including osteoporosis, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, Paget's disease, immobilization-induced osteopenia, loosening of bone prostheses and glucocorticoid treatment. A characteristic feature shared by each of these diseases is bone loss. In some cases, this bone loss is thought to result from an imbalance between bone resorption (breakdown) and bone formation. Bone loss occurs in a wide range of subjects including aging men and women, post-menopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing's syndrome, and patients having gonadal dysgenesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Allosteric control of nuclear hormone receptors Inventor(s): Evans, Ronald M.; (La Jolla, CA), Forman, Barry M.; (La Jolla, CA), Umesono, Kazuhiko; (Nara, JP) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030083469 Date filed: September 6, 2002 Abstract: Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as

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a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T.sub.3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T.sub.3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurrl heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response. These findings establish a novel 9-cis retinoic acid response pathway and resolve the paradox as to how T.sub.3R, RAR and VDR contribute to distinct physiologic pathways while sharing a common RXR subunit. Excerpt(s): The present invention relates to intracellular receptors, and methods for the modulation thereof. In a particular aspect, the present invention relates to novel heterodimeric complexes. In another aspect, the present invention relates to methods for modulating processes mediated by retinoid X receptor and/or orphan receptor Nurrl. Heterodimerization is a common theme in eucaryotic regulatory biology. Indeed, a number of transcription factor families have been defined by their characteristic dimerization interface. These include the leucine zipper (e.g. fos, jun, CREB, C/EBP; see, for example, Lamb and McKnight, in Trends Biochem. Sci. 16:417-422 (1991)), helix-loophelix (e.g. myc, max, MyoD, E12, E47; see, for example, Amati and Land, in Curr. Opin. Genet. Dev. 4:102-108 (1994)), rel (NF.kappa.B, dorsal; see, for example, Blank et al., in Trends Biochem. Sci. 17:135-140 (1992)), ankyrin (GABP; see, for example, Brown and McKnight, in Genes Dev. 6:2502-2512 (1992)), and the nuclear receptor superfamilies (see, for example, Evans, in Science 240:889-895 (1988), and Forman and Samuels, Mol. Endocrinol. 4:1293-1301 (1990)). Detailed analyses of these proteins have shown that heterodimerization produces novel complexes that bind DNA with higher affinity or altered specificity relative to the individual members of the heterodimer (see, for example, Glass, in Endocr. Rev. 15:391-407 (1994)). Indeed, little is known about the contributions of each monomer toward the transcriptional properties of the complex. Naturally occurring HREs are composed of direct repeats (i.e., DRs; see Umesono et al., in Cell 65:1255-1266 (1991), inverted repeats (i.e., IRs; see Umesono et al., in Nature 336:262-265 (1988), and Williams et al. in J. Biol. Chem. 266:19636-19644 (1991)), and/or everted repeats (ERs; see Baniahmad et al., in Cell 61:505-514 (1990); Farsetti et al., in J. Biol. Chem. 267:15784-15788 (1992); Raisher et al., in J. Biol. Chem. 267:20264-20269 (1992); or Tini et al., in Genes Dev. 7:295-307 (1993)) of a degenerate X.sub.n-AGGTCA core-site. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antisense modulation of vitamin D nuclear receptor expression Inventor(s): Baker, Brenda F.; (Carlsbad, CA), Dobie, Kenneth; (Del Mar, CA), Roach, Mark P.; (Carlsbad, CA) Correspondence: Jane Massey Licata; Licata & Tyrrell, P.C.; 66 East Main Street; Marlton; NJ; 08053; US Patent Application Number: 20030125271 Date filed: November 14, 2001 Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of vitamin D nuclear receptor. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding vitamin D nuclear receptor. Methods are provided for using these compounds

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for modulation of vitamin D nuclear receptor expression, including examples of modulation of specific variants of vitamin D nuclear receptor relative to other variants. Methods for treatment of diseases associated with expression of vitamin D nuclear receptor are provided. Excerpt(s): The present invention provides compositions and methods for modulating the expression of vitamin D nuclear receptor. In particular, this invention relates to compounds, particularly oligonucleotides, specifically hybridizable with nucleic acids encoding vitamin D nuclear receptor. Such compounds have been shown to modulate the expression of vitamin D nuclear receptor. Steroid, thyroid and retinoid hormones produce a diverse array of physiologic effects through the regulation of gene expression. Upon entering the cell, these hormones bind to a unique group of intracellular nuclear receptors which have been characterized as ligand-dependent transcription factors. This complex then moves into the nucleus where the receptor and its cognate ligand interact with the transcription preinitiation complex affecting its stability and ultimately, the rate of transcription of the target genes. Members of the nuclear receptor family share several structural features including a central, highly conserved DNA-binding domain which targets the receptor to specific DNA sequences known as hormone response elements (Kliewer et al., Science, 1999, 284, 757-760). The vitamin D nuclear receptor was cloned and mapped to chromosome 12q12-q14, a region implicated in pseudovitamin D deficiency rickets (Baker et al., Proc. Natl. Acad. Sci. U. S. A., 1988, 85, 32943298; Labuda et al., J. Bone Miner. Res., 1992, 7, 1447-1453). Nucleic acid sequences encoding vitamin D nuclear receptor are disclosed in PCT publication WO 01/38393 (Moras et al., 2001). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combination chemotherapy Inventor(s): Johnson, Candace S.; (Pittsburgh, PA), Trump, Donald L.; (Pittsburgh, PA) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20030216359 Date filed: May 5, 2003 Abstract: This invention relates to combination chemotherapy, particularly involving vitamin D or a derivative thereof. In one aspect, the invention provides a method of killing a cell by first administering to the cell vitamin D (or a derivative) and subsequently administering to the cell a cytotoxic agent. Where this strategy is applied to an intact tumor, the present invention provides a method of retarding the growth of the tumor by first administering vitamin D (or a derivative) to the tumor and subsequently administering the cytotoxic agent. A further aspect of the invention concerns a method of treating prostate cancer within a patient by co-administration of vitamin D (or a derivative) and a glucocorticoid to the patient. In yet a further aspect, the invention provides an improved method of treating a patient with vitamin-D involving the adjunctive administration of zoledronate. Excerpt(s): This patent application is a continuation of co-pending U.S. patent application Ser. No. 09/544,724, filed Apr. 6, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 08/921,170, filed Aug. 29, 1997, now U.S. Pat. No. 6,087,350. Combating the growth of neoplastic cells and tumors has been a major focus of biological and medical research. Such research has led to the discovery of novel

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cytotoxic agents potentially useful in the treatment of neoplastic disease. Examples of cytotoxic agents commonly employed in chemotherapy include anti-metabolic agents interfering with microtubule formation, alkylating agents, platinum-based agents, anthracyclines, antibiotic agents, topoisomerase inhibitors, and other agents. Aside from merely identifying potential chemotherapeutic agents, cancer research has led to an increased understanding of the mechanisms by which these agents act upon neoplastic cells, as well as on other cells. For example, cholecalciferol (vitamin D) can effect differentiation and reduce proliferation of several cell types cells both in vitro and in vivo. The active metabolite of vitamin D (1,25-dihydroxycholecalciferol (hereinafter "1,25D.sub.3")) and analogs (e.g., 1,25-dihydroxy-16-ene-23-yne-cholecalciferol (Ro237553), 1,25-dihydroxy-16-ene-23-yne-26, 27-hexafluoro-19-nor-cholecalciferol (Ro256760), etc.) mediate significant in vitro and in vivo anti-tumor activity by retarding the growth of established tumors and preventing tumor induction (Colston et al., Lancet, 1, 188 (1989); Belleli et al., Carcinogenesis, 13, 2293 (1992); McElwain et al., Mol. Cell. Diff., 3, 31-50 (1995); Clark et al., J. Cancer Res. Clin. Oncol., 118, 190 (1992); Zhou et al., Blood, 74, 82-93 (1989)). In addition to retarding neoplastic growth, 1,25D.sub.3 induces a G.sub.0/G.sub.1-S phase block in the cell cycle (Godyn et al, Cell Proliferation, 27, 37-46 (1994); Rigby et al., J. Immunol., 135, 2279-86 (1985); Elstner et al., Cancer Res., 55, 282230 (1995); Wang et al., Cancer Res., 56, 264-67 (1996)). These properties have led to the successful use of 1,25D.sub.3 to treat neoplastic tumors (see Cunningham et al., Br. J. Cancer, 63, 4673 (1991); Mackie et al., Lancet, 342, 172 (1993), Bower et al., Proc. Am. Assoc. Cancer. Res., 32, 1257 (1991)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition for promoting healthy bone structure Inventor(s): Johnson, Holly A.; (San Clemente, CA), Krumhar, Kim C.; (Carlsbad, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030059481 Date filed: September 9, 2002 Abstract: A dietary supplement for benefitting human bone health includes a calcium source, a source of vitamin D activity, and an osteoblast stimulant. A preferred calcium source is microcrystalline hydroxyapatite, which also contains protein (mostly collagen), phosphorus, fat, and other minerals. A preferred source of vitamin D activity is cholecalciferol, and a preferred osteoblast stimulant is ipriflavone. In addition to these basic ingredients, the composition can further include various other minerals known to occur in bone, vitamin C, and glucosamine sulfate, all of which exert beneficial effects on growth and maintenance of healthy bone. A method for benefitting human bone health involves administering a daily regimen of the dietary supplement. Excerpt(s): This application is a continuation of application Ser. No. 09/568,903, filed May 11, 2000, which claims the benefit of U.S. Provisional Application No. 60/133,603, filed May 11, 1999, which is hereby incorporated herein by reference. This invention relates to dietary supplements. More particularly, this invention relates to compositions and methods for promoting healthy bone structure. Osteoporosis is a common metabolic bone disease that leads to the gradual loss of mineralized bone from the skeletal mass. This is due in part to an imbalance in the rates of cell-mediated bone deposition and resorption due to the actions of osteoblasts and osteoclasts in the bone matrix. Bone mineral is in a constant state of destruction and repair referred to as

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"remodeling," and maintenance of bone density over time is believed to require a precise balance after menopause or during the course of certain disease states. Bone resorption, when exceeding bone formation, can lead to bone fractures resulting from minimal trauma. Unfortunately, there are no symptoms preceding fractures. A common cause of osteoporosis is the decrease in estrogen production following menopause that leads to an increase in bone resorption. Conventional methods to counter bone resorption in women include estrogen therapy and calcium supplementation. Long-term treatment with estrogen has been the only method correlated to significant protection from bone loss in postmenopausal women. See Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcified Tissue International 1997;61:S23-S27. The isoflavone, ipriflavone, is now successfully used in many countries to treat and prevent osteoporosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for treatment of vitamin D deficiency Inventor(s): Blacher, Russell W.; (Castro Valley, CA), Kumagai, Yoshinari; (Alameda, CA), Nakagawa, Kimie; (Kobe, JP), Okano, Toshio; (Kobe, JP), Tsugawa, Naoko; (Kobe, JP) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030186891 Date filed: February 7, 2003 Abstract: The present invention provides peptides which are characterized by having a biological activity that increases 25-hydroxyvitamin D3 1.alpha.-hydroxylase activity in a cell, thereby increasing calcitriol (active vitamin D) levels. The peptides have a sequence related to the contiguous sequence defined by residues 242 to 264 in the naturally occurring matrix extracellular phosphoglycoprotein (PHEX). Methods of modulating 25-hydroxyvitamin 1.alpha.-hydroxylase gene expression and calcitriol levels using the subject peptides are also provided. Also provided are kits for practicing the subject methods. The subject compositions and methods find use in a variety of application, including the treatment of vitamin D-related disorders, such as Paget's Disease, rickets, osteoporosis, renal osteodystrophy, and psoriasis. Excerpt(s): This application claims priority to U.S. Provisional Patent Application Serial No. 60/355,548 filed Feb. 8, 2002; the disclosures of which application is herein incorporated by reference. The present invention relates to peptides that may be used to manipulate vitamin D metabolism. More specifically, the present invention relates to dentonin peptides that stimulate increase 25-hydroxyvitamin D3 1.alpha.-hydroxylase activity to produce calcitriol, the active form of vitamin D. Vitamin D is a hormone that plays an active role in the maintenance of calcium and phosphate balance and bone mineralization. Vitamin D deficiency causes rickets and osteomalacia in both adults and children. Both conditions are characterized by failure of calcification of osteoid, which is the matrix of bone, leading to weak and malformed bones. The active form of vitamin D, 1.alpha.,25-dihydroxyvitamin D3 (otherwise known as calcitriol), is made from inactive 25-monohydroxyvitamin D3 through a hydroxylation reaction performed by a 1.alpha.-hydroxylase (1.alpha.-OHase), which places a hydroxyl group on the 1.alpha. position of the carbon chain of the molecule. Hydroxylation of the precursor 25monohydroxyvitamin D3 by a 24-hydroxylase (24-OHase) causes the pathway to

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"bypass" the active form of the compound. Hydroxylation of calcitriol by the 24hydroxylase inactivates calcitriol, and initiates its further metabolism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods of treating abnormal cell proliferation Inventor(s): Achkar, Charles C.; (North Bergen, NJ) Correspondence: Charles C. Achkar; 7855 Boulevard East, #26g; North Bergen; NJ; 07047; US Patent Application Number: 20030207848 Date filed: April 17, 2003 Abstract: A composition is described comprising a vitamin D analog and a retinoid wherein: (a) the vitamin D analog is capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor; and (b) the retinoid is selected from the group consisting of retinol in a concentration of at least about 1.0%, a compound in a concentration of at least about 1.0% capable of being converted in vivo into retinol, and a retinoid characterized by having a substitution at the 4-position. Further, methods of treating disorders characterized by abnormal cellproliferation and/or cell-differentiation are also described. Excerpt(s): This application is a division of U.S. Ser. No. 09/872,662, filed Jun. 1, 2001, now allowed, which is a continuation-in-part of U.S. Ser. No. 09/351,020, filed Jul. 12, 1999, now U.S. Pat. No. 6,242,435, which is a continuation-in-part of U.S. Ser. No. 09/116,632, filed Jul. 16, 1998. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. The present invention relates to compositions comprising certain retinoids and vitamin D analogs useful in inducing differentiation and inhibiting undesirable proliferation of cells, such as cancer cells and skin cells. The present invention also relates to methods of using the above compositions in the treatment of diseases and conditions characterized by abnormal cell differentiation and/or cell proliferation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compositions for providing vitamin D year round and uses thereof Inventor(s): Holick, Michael F.; (Sudbury, MA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W.; Washington; DC; 20005; US Patent Application Number: 20030220308 Date filed: May 22, 2003 Abstract: Methods for enhancing the ability of an individual, exposed to sunlight, to produce vitamin D via the skin. Pharmaceutical compositions comprising provitamin D and at least one of lumisterol and tachysterol and analogs and derivatives thereof are also disclosed.

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Excerpt(s): The invention is in the field of cosmetics and medicinal chemistry. In particular, the present invention relates to topical compositions which provide vitamin D and derivatives thereof throughout the year. The topical compositions of the invention allow a user in the high northern and southern latitudes to produce previtamin D on their skin even when exposed to low energy sunlight in the winter as well as in the morning and evening throughout the year. The compositions comprise provitamin D and at least one of tachysterol and lumisterol, and derivatives and analogs thereof, which photoisomerize to previtamin D, and analogs and derivatives thereof. Vitamin D.sub.3 is a derivative of provitamin D.sub.3 (7-dehydrocholesterol), the immediate biological precursor of cholesterol. With adequate exposure to sunlight, dietary supplements are not normally required. Holick et al. in Braunwald et al., Harrison's Principles of Internal Medicine, 11th ed. McGraw-Hill (1987), pp. 1857-69. However, not all individuals are exposed to the adequate levels of sunlight, especially in the winter. When skin is exposed to sunlight or artificial sources of ultraviolet (UV) radiation, the UV radiation penetrates the epidermis and causes a variety of biochemical reactions. Included in these reactions include the transformation of provitamin D.sub.3 to previtamin D.sub.3. The solar electromagnetic energy having wave-lengths between 290 and 315 nm is absorbed by provitamin D.sub.3 resulting in its fragmentation to previtamin D.sub.3. Although previtamin D.sub.3 is biologically inert, it is thermally labile and spontaneously undergoes a temperature-dependent rearrangement to form the thermally stable vitamin D.sub.3. After biosynthesis, vitamin D.sub.3 is translocated from the epidermis into the circulation via a vitamin-D binding protein. Holick et al., Science 211:590-593 (1981); Holick et al. in Braunwald et al., Harrison's Principles of Internal Medicine, 11th ed., McGraw-Hill (1987), pp. 1857-69. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Dietary calcium as a supplement to vitamin D compound treatment of multiple sclerosis Inventor(s): Cantorna, Margheritea T.; (State College, PA), DeLuca, Hector F.; (Deerfield, WI), Humpal-Winter, Jean; (Poynette, WI) Correspondence: Quarles & Brady Llp; 411 E. Wisconsin Avenue, Suite 2040; Milwaukee; WI; 53202-4497; US Patent Application Number: 20030207847 Date filed: April 2, 2003 Abstract: A method of and composition for diminishing multiple sclerosis symptoms are disclosed. In one embodiment, the method comprises the step of administrating an amount of calcium and a vitamin D compound effect to diminish multiple sclerosis symptoms. In another embodiment, the invention is a pharmaceutical composition comprising an amount of calcium and vitamin D compound effective to diminish multiple sclerosis symptoms. Excerpt(s): Vitamin D is a recent arrival in the roster of agents that are known to regulate the immune system. Vitamin D is converted in a two-step process to the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH).sub.2D.sub.3).sup.1 that is a key factor in regulating serum calcium, phosphorus and bone (DeLuca, 1997). This hormone acts in a steroid hormone-like mechanism through a nuclear receptor, the vitamin D receptor (VDR), which is a member of the steroid hormone receptor superfamily (Pike, 1991; Ross, et al., 1993). The discovery of VDR in peripheral blood lymphocytes (Bhalla, et al., 1983; Provvedini, et al., 1983) is a factor that led to the realization that 1,25-

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(OH).sub.2D.sub.3 is a significant regulator of the immune system. The most striking evidence of a role for 1,25-(OH).sub.2D.sub.3as an immune system regulator comes from in vivo experiments. 1,25-(OH).sub.2D.sub.3 can prevent the development of EAE (Cantorna, et al., 1996 and U.S. Pat. No. 5,716,946; Lemire and Archer, 1991), experimental arthritis (Cantorna, et al., 1998a), and 1,25-(OH).sub.2D.sub.3can markedly inhibit transplant rejection (Bouillon, et al., 1995; Hullett, et al., 1998). Abbreviations: central nervous system, CNS; 1,25-dihydroxycholecalciferol, 1,25-(OH).sub.2D.sub.3; experimental autoimmune encephalomyelitis, EAE; glyceraldehyde-3-phosphate dehydrogenase, lymph node, LN; multiple sclerosis, MS; interferon.gamma., IFN.gamma.; interleukin-4, IL-4; transforming growth factor.beta.1, TGF-.beta.1; tumor necrosis factor-.alpha., TNF-.alpha.; type-1 helper, Th1; type-2 helper, Th2; vitamin D receptor, VDR. EAE is mediated by CD4+ T cells, which mount an inappropriate immune-mediated attack on the central nervous system (CNS). Type-1 helper (Th1) cells specific for CNS antigens induce the disease and the Th1 cytokines interferon (IFN).gamma. and tumor necrosis factor (TNF)-.alpha. are associated with EAE in mice (Holda and Swanborg, 1982; Powell, et al., 1990). Conversely, type-2 helper (Th2) cells and other cell types which produce interleukin (IL)-4 and transforming growth factor (TGF)-.beta.1 in response to CNS antigens are known to ameliorate EAE. In vivo 1,25(OH).sub.2D.sub.3 treatments result in a net loss in the total number of lymphocytes and a net increase in the expression of IL-4 and TGF-.beta.1 (Cantorna, et al., 1998b). Conversely the in vivo 1,25-treatments had no effect on IFN-.gamma. or TNF-.alpha. expression (Cantorna, et al., 1998b). The role, if any, for calcium in the regulation of the immune response remains unclear. The present invention is a method of more effectively treating multiple sclerosis patients. The method comprises the step of administration of an amount of calcium that renders a vitamin D compound effective in preventing or markedly reducing MS symptoms. Preferably, this amount of calcium is 0.5-2 g per patient per day. Most preferably, the amount is between 1 and 2 g of calcium as a salt with a variety of anions, e.g. CO.sub.3.sup.=, PO.sub.4.sup.=, Cl.sub.2.sup.acetate, gluconate, citrate, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Dosage forms for immediate gastric release of a calcium transport stimulator coupled with delayed gastric release of a bis-phosphonate Inventor(s): Fleshner-Barak, Moshe; (Petach Tikva, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030158154 Date filed: July 17, 2002 Abstract: The present invention provides a gastric retention dosage form for immediate or uncontrolled release of a vitamin D derivative that stimulates calcium absorption from the intestine, like calcitriol, alphacalcidol and calcifediol, combined with delayed release of a bis-phosphonate calcium resorption inhibitor such as alendronic acid and its pharmaceutically acceptable salts and hydrates. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/306,383, filed Jul. 18, 2001 which is incorporated herein by reference. The present invention relates to a gastric retention system for immediate release of a vitamin D derivative that stimulates calcium absorption from the intestine, like calcitriol, combined with delayed release of a bis-phosphonate calcium resorption inhibitor such as alendronic acid and its pharmaceutically acceptable salts and hydrates. Treatment of

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osteoporosis, metastatic bone disease, and Paget's disease can benefit from improvements in controlled gastric release and multiple dose delivery technology. Bisphosphonates such as alendronate, risedronate, etidronate and tiludronate are commonly prescribed drugs for treatment of these diseases. Despite their benefits, bisphosphonates suffer from very poor oral bioavailability. Alendronate has less than 1% bioavailability. Gert, B. J.; Holland, S. D.; Kline, W. F.; Matuszewski, B. K.; Freeman, A.; Quan, H.; Lasseter, K. C.; Mucklow, J. C.; Porras, A. G. "Studies of The Oral Bioavailablity of Alendronate," Clinical Pharmacology & Therapeutics 1995, 58, 288-298. Its absorption is inhibited by foods and beverages other than water. Id. Side effects experienced by patients who have taken alendronate include irritation of the upper gastrointestinal mucosa. Liberman, U. A.; Hirsch, L. J.; "Esophagitis and Alendronate" N. Engl. J. Med., 1996, 335, 1069-70. This irritation can lead to more serious conditions. Physicians' Desk Reference, Fosamax, Warnings. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Healthy bone formulation Inventor(s): Gorsek, Wayne F.; (Boynton Beach, FL) Correspondence: Hoffman, Wasson & Gitler, P.C.; Suite 522; 2361 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20040005366 Date filed: July 3, 2002 Abstract: The key to the unique formulation is a combination of specific vitamins, minerals, herbs and nutrients. These essential components in the amounts provided uniquely contribute to improved blood sugar levels and insulin delivery to the cells. The formulation contains essential amounts of Calcium, magnesium Vitamin D, Vitamin K1, Folic Acid and Soy Isoflavones, as well as other ingredients and healthy filler components. Excerpt(s): The invention relates to a composition that contains the most potent combination of nutrients with clinical studies proven to assist in the maintenance of normal bone density and development. The advanced formulation is designed to reduce bone loss and reduce bone fracture rates by significant amounts. It helps in the treatment and prevention of osteoporosis and osteoarthritis. It is estimated that between 37 to 50 million people in this country suffer with some degree of bone loss. An unique and effective combination of minerals and supplements are required to prevent such loss and deterioration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for inhibiting bone resorption with an alendronate and vitamin D formulation Inventor(s): Daifotis, Anastasia G.; (Westfield, NJ), Mazel, Sidney; (Basking Ridge, NJ), Yates, John; (Lansdale, PA) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030195171 Date filed: April 1, 2003

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Abstract: Composition and method for preventing or treating abnormal bone resorption in mammals, the composition characterized as containing, a supplementary effective amount of a non-activated metabolite of vitamin D.sub.2 and/or D.sub.3 and a pharmaceutically effective amount of bisphosphonate to provide vitamin D nutrition during treatment to facilitate normal bone formation and mineralization, while minimizing the occurrence of or potential for the complications associated with vitamin D insufficiency, such as hypocalcemia and osteomalacia. The method of preventing or treating may be further characterized by concomitantly administering the components simultaneously or alternately at dosing intervals selected from once-weekly, twiceweekly, bi-weekly, monthly, and bi-monthly. Excerpt(s): The present invention relates to methods for inhibiting bone resorption in a mammal in need thereof by providing supplemental vitamin D nutrition to facilitate normal bone mineralization and formation while minimizing the occurrence of or potential for the complications associated with vitamin D insufficiency and the administration of bisphosphonate resulting from bone resorption. The method of the invention provides adequate vitamin D nutrition, while minimizing the occurrence of or potential for complications of hypocalcemia and osteomalacia associated with excessive amounts of activated vitamin D. The method may be characterized by orally administering, to a mammal, a pharmaceutical composition containing, in combination, a supplementary amount of a non-activated metabolite of vitamin D.sub.2 and/or D.sub.3, and a pharmaceutically effective amount of a bisphosphonate, as a unit dosage, according to a continuous schedule having a dosing interval of once-weekly, twiceweekly, biweekly, monthly, and bimonthly. The present invention also relates to pharmaceutical compositions containing various amounts of the combination of supplemental vitamin D nutrition and bisphosphonates, medicaments and kits useful for carrying out these methods. A variety of disorders in humans and other mammals are associated with abnormal bone resorption. Such disorders include, but are not limited to, osteoporosis, Paget's disease, periprosthetic bone loss or osteolysis, metastatic bone disease, hypercalcemia of malignancy, and arthritides (including but not limited to osteoarthritis and rheumatoid arthritis). One of the most common of these disorders is osteoporosis, which in its most frequent manifestation occurs in postmenopausal women. Osteoporosis is a systemic skeletal disease characterized by a low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Because osteoporosis, as well as other disorders associated with bone loss, are chronic conditions, it is believed that appropriate therapy will generally require chronic treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for stimulating hair growth by administering vitamin D analogs Inventor(s): Koeffler, H. Philip; (Los Angeles, CA), Vegesna, Vijay; (Los Angeles, CA) Correspondence: Pillsbury Winthrop Llp; Suite 2800; 725 South Figueroa Street; Los Angeles; CA; 90017-5406; US Patent Application Number: 20030095937 Date filed: October 2, 2001 Abstract: Disclosed herein is a method for stimulating the growth of hair by administering to a subject analogs of vitamin D.sub.3 or prodrugs of these analogs. Disclosed are doses and routes for such analogs, as well as experimental data that show

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the analogs of the invention are effective in stimulating hair growth even in nude mice (BNX nu/nu mice). Excerpt(s): Embodiments of the present invention are directed to a method for promoting the growth of hair in mammals. Those seeking a cure for hair loss have applied to their scalp compounds such as ascorbic acid, benzoic acid, retinoic acid, estradiol, wheat germ oil, earth metals, and sulfur. One inventor, DiTucci (U.S. Pat. No. 5,674,510) for example, teaches that a mixture of garlic powder, brewer's yeast, grapefruit juice, acetic acid, and kelp can "eliminate" hair loss. Despite such efforts, however, a basic medical text still teaches that "[t]herapeutic options for male-pattern alopecia are limited." M. H. Beers and R. Berkow, eds., Merck Manual of Diagnosis and Therapy,.sctn.10, Ch. 116 (Centennial Edition, 1999). The U.S. Food and Drug Administration has yet to approve the sale of any non-prescription drug that claims it prevents hair loss or promotes the growth of new hair. The FDA has gone to court to stop the sale of such drugs, arguing (and always winning) that there is no scientific evidence that supports these claims. The FDA has approved only two drugs for treating hair loss, minoxidil and finasteride, and these drugs have only limited effectiveness. Only about half of men and women respond positively to these drugs; of those individuals who report a positive responsive, the response tends to be a modest one, with most individuals reporting only moderate hair growth. These drugs are moreover expensive, require several months (typically 6 to 9 months or more) to produce any observable effect, and exclude large categories of potential users (minoxidil is recommended only for use in healthy individuals without any scalp abrasions; finasteride is contraindicated in women who are or may be pregnant because it may cause abnormalities of the external genitalia of the male fetus). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of determining the initial dose of vitamin D compounds Inventor(s): Amdahl, Michael J.; (Wauconda, IL) Correspondence: Steven F. Weinstock; Abbott Laboratories; D-377/ Ap6d-2; 100 Abbott Park Road; Abbott Park; IL; 60064-6050; US Patent Application Number: 20030092686 Date filed: October 12, 2001 Abstract: A method is provided for determining the initial or starting dose of vitamin D compounds when used for the treatment of renal osteodystrophy or secondary hyperparathyroidism. The starting dose is based in part on the patient's baseline PTH. The invention also provides for the administration of an initial dose of a vitamin D compound wherein the dose is determined following the method of the invention. Excerpt(s): This application claims priority to U.S. provisional application Serial No. 60/240,126, filed Oct. 13, 2001. The present invention is directed to a method for determining the initial dose of vitamin D compounds when used for the treatment of secondary hyperparathyroidism and renal osteodystrophy. The present invention also is directed to the administration of an initial dose of a vitamin D compound wherein the dose is determined following the method of the invention. Renal osteodystrophy, which encompasses a host of metabolic and morphologic abnormalities of the bone, is an early complication of kidney disease. Elevation of intact parathyroid hormone (iPTH; used interchangeably with "PTH") secondary to renal failure (also referred to as secondary hyperparathyroidism) is a major contributor to high-turnover renal osteodystrophy. The

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various disorders of bone formation with high-turnover renal osteodystrophy may be accompanied by such conditions as fractures and bone deformities, bone cysts, osteopenia, resistance to erythropoietin caused by marrow fibrosis, intractable pruritus, spontaneous tendon rupture, periarthritis and joint pain, myopathy, growth failure in children, and extraskeletal calcification. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of locking 1alpha-OH of vitatmin D compounds in axial orientation Inventor(s): DeLuca, Hector F.; (Deerfield, WI), Sicinski, Rafal R.; (Warsaw, PL) Correspondence: Andrus, Sceales, Starke & Sawall, Llp; 100 East Wisconsin Avenue, Suite 1100; Milwaukee; WI; 53202; US Patent Application Number: 20030040508 Date filed: September 11, 2002 Abstract: A method of modifying or altering the structure of a 1.alpha.-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1.alpha.hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1.alpha.-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1.alpha.-hydroxyl in the axial orientation. Excerpt(s): The present invention relates to vitamin D compounds, and more particularly, to a method of presenting the 1.alpha.-OH of vitamin D compounds in an axial orientation and the compounds made thereby. destabilization energy imparted to a monosubstituted six-membered chair by an axial substituent. Thus, for example, the A value of methyl substituent equals ca. 1.7 kcal/mol [Hirsch, Top. Stereochem. 1, 199 (1967)] that corresponds to 95% of population of equatorial conformer of methylcyclohexane at room temperature. The conformational free energies of substituents in cyclohexanes under ideal conditions are expected to be additive. It is usually assumed that all conformational effects are additive, i.e. various destabilizing interactions identified within a six-membered ring system operate independently of each other. In di-, tri- and polysubstituted cyclohexanes mutual interactions among the substituents have to be considered. Such interactions can destabilize one chair conformation raising its energy to favor an alternate inverted chair form, or even favor some other, distorted (rigid or flexible) cyclohexane geometries. The most important interactions that influence the equilibrium between the respective chair conformations include interaction of a pair of substituents in 1,2-trans-diequatorial and 1,3-cis-diaxial relationship. Thus, total destabilization energy (ED) can be described as a sum of the substituents' A values, representing monoaxial interactions, G values for 1,2diequatorial interactions and U values for 1,3-diaxial interactions [Corey, et al., J. Org. Chem. 45, 765 (1980)]. R.sub.1 and R.sub.2 are medium or large groups, the axial conformer is preferred over the equatorial (Malhotra et al., J. Am. Chem. Soc. 87, 5492 (1965)]. Thus, for example, when R.sub.1=R.sub.2=Me the difference in energy between both forms is approximately 4.5 kcal/mol, in favor of the axial conformer. In the case when R.sub.1=Me and R.sub.2=H, a 1:3 peri interaction exists which increases by ca. 1.25 kcal/mol the destabilization energy of the system (Duraisamy et al., J. Am. Chem. Soc. 105, 3264 (1983)].

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

Method of synthesizing 1alpha-hydroxy-2-methylene-19-nor-homopregnacalcife- rol Inventor(s): DeLuca, Hector F.; (Deerfield, WI), Gowlugari, Sumithra; (Fremont, CA), Sicinski, Rafal R.; (Warsaw, PL) Correspondence: Andrus, Sceales, Starke & Sawall, Llp; 100 East Wisconsin Avenue, Suite 1100; Milwaukee; WI; 53202; US Patent Application Number: 20030191095 Date filed: March 26, 2003 Abstract: A method of making 1.alpha.-hydroxy-2-methylene-19-norhomopregnacalcifero- l. The method includes the steps of condensing a bicyclic ketone with an allylic phosphine oxide to produce a protected 19-nor-pregnacalciferol analog, thereafter cleaving the protecting group to form 22-alcohol, converting the alcohol to an ester, reducing the ester to 17.beta.-isopropyl-19-nor-vitamin D analog, and finally deprotecting the 17.beta.-isopropyl derivative to form the desired compound. Excerpt(s): This application is based on and claims priority from provisional patent Application No. 60/369,159 filed on Mar. 29, 2002. The natural hormone, 1.alpha.,25dihydroxyvitamin D.sub.3 and its analog in the ergosterol series, i.e. 1.alpha.,25dihydroxyvitamin D.sub.2 are known to be highly potent regulators of calcium homeostasis in animals and humans, and more recently their activity in cellular differentiation has been established, Ostrem et al., Proc. Natl. Acad. Sci. USA, 84, 2610 (1987). Many structural analogs of these metabolites have been prepared and tested, including 1.alpha.-hydroxyvitamin D.sub.3, 1.alpha.-hydroxyvitamin D.sub.2, various side chain homologated vitamins and fluorinated analogs. Some of these compounds exhibit an interesting separation of activities in cell differentiation and calcium regulation. This difference in activity may be useful in the treatment of a variety of diseases such as renal osteodystrophy, vitamin D-resistant rickets, osteoporosis, psoriasis, and certain malignancies. Recently, a new class of vitamin D analogs has been discovered, i.e. the so called 19-nor-vitamin D compounds, which are characterized by the replacement of the A-ring exocyclic methylene group (carbon 19), typical of the vitamin D system, by two hydrogen atoms. Biological testing of such 19-nor-analogs (e.g., 1.alpha.,25-dihydroxy-19-nor-vitami- n D.sub.3) revealed a selective activity profile with high potency in inducing cellular differentiation, and very low calcium mobilizing activity. Thus, these compounds are potentially useful as therapeutic agents for the treatment of malignancies, or the treatment of various skin disorders. Two different methods of synthesis of such 19-nor-vitamin D analogs have been described [Perlman et al., Tetrahedron Lett. 31, 1823 (1990); Perlman et al., Tetrahedron Lett. 32, 7663 (1991), and DeLuca et al., U.S. Pat. No. 5,086,191)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating malignancy associated hypercalcemia using active vitamin D analogues Inventor(s): Bishop, Charles W.; (Madison, WI), Mazess, Richard B.; (Madison, WI) Correspondence: Michael Best & Friedrich, Llp; One South Pinckney Street; P O Box 1806; Madison; WI; 53701 Patent Application Number: 20030207810 Date filed: May 20, 2003 Abstract: Methods utilizing active vitamin D analogs for the treatment of malignancyassociated hypercalcemia. Methods comprise the application of an effective amount of a hypocalcemic vitamin D compound to alleviate hypercalcemia, lower serum parathyroid hormone related protein (PTHrP) levels. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/596,149 filed Feb. 23, 1998, which is a continuation-in-part of U.S. application Ser. No. 08/781,910, filed Dec. 20, 1996, now U.S. Pat. No. 5,763,429, all of which are incorporated herein by reference. This invention relates generally to a method of treating malignancy-associated hypercalcemia (MAH), and in particular, to the use of active forms of vitamin D to reduce hypercalcemia associated with inhibit the hyperproliferative diseases. Extensive research during the past two decades has established important biologic roles for vitamin D apart from its classic role in bone and mineral metabolism. Specific nuclear receptors for 1.alpha.,25-dihydroxyvitamin D.sub.3, the hormonally active form of vitamin D, are present in cells from diverse organs not involved in calcium homeostasis. For example, specific, biologically active vitamin D receptors have been demonstrated in the human prostatic carcinoma cell line, LNCaP, (Miller et al., 52 Cancer Res. (1992) 515-520); Vitamin D receptors have also been described for many other neoplastic cells, e.g., carcinomas of the breast and carcinomas of the colon. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating prostatic diseases using active vitamin D analogues Inventor(s): Bishop, Charles W.; (Madison, WI), Knutson, Joyce C.; (Madison, WI), Mazess, Richard B.; (Madison, WI) Correspondence: Michael Best & Friedrich, Llp; One South Pinckney Street; P O Box 1806; Madison; WI; 53701 Patent Application Number: 20040023934 Date filed: March 25, 2003 Abstract: The invention provides therapeutic methods for inhibiting, ameliorating or alleviating the hyperproliferative cellular activity of diseases of the prostate, e.g., prostatic cancer and prostatic hyperplasia, which includes administering to a patient in need thereof an active vitamin D analogue. Cell differentiation is promoted, induced or enhanced without causing to the patient dose-limiting hypercalcemia and hypercalciuria. Excerpt(s): This application is a continuation-in-part of Ser. No. 08/415,488. Apr. 3, 1995, which is a continuation-in-part of Ser. No. 08/119,895, Sep. 10, 1993, now U.S. Pat. No. 5,403,831, and is also a continuation-in-part of Ser. No. 08/486,387, Jun. 7, 1995, which is a continuation-in-part of Ser. No. 08/265,438, Jun. 24, 1994, all of which are incorporated

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herein by reference. This invention relates generally to a method of treating hyperproliferative prostatic diseases, and in particular, to the use of active forms of vitamin D to inhibit the hyperproliferative cellular activity of these diseases and to promote differentiation of the cells. The prostate gland is found exclusively in male mammals and is subject to certain hyperproliferative diseases. A proliferation of basal and stroma cells of the prostate gland gives rise to benign prostatic hyperplasia which is one common prostate disease. Another common prostate disease is prostate cancer, especially prostatic adenocarcinoma. Adenocarcinoma of the prostate is the most common of the fatal pathophysiological prostate cancers, and typically involves a malignant transformation of epithelial cells in the peripheral region of the prostate gland. Both prostatic hyperplasia and prostate cancer have a high rate of incidence in the aging human male population. Approximately one out of every four males above the age of 55 suffers from a prostate disease of some form or another. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods employing XOR-6, a vitamin D-like receptor from xenopus Inventor(s): Blumberg, Bruce; (San Diego, CA), Evans, Ronald M.; (La Jolla, CA), Umesono, Kazuhiko; (Nara, JP) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030044914 Date filed: May 21, 2002 Abstract: In accordance with the present invention, there are provided new members of the steroid receptor superfamily of receptors, a representative member of which has been designated XOR-6. Invention receptors are responsive to hydroxy, mercapto or amino benzoates, and are expressed, for example, in Xenopus laevis embryos. XOR-6 is most closely, although distantly, related to the vitamin D3 receptor (VDR). The proteins are about 73% identical in amino acid sequence in the DNA-binding domains and about 42% identical in the ligand binding domain. Like VDR, XOR-6 has an extended D region between the DNA and ligand binding domains. Notably, the region amino-terminal to the XOR-6 DNA-binding domain is extremely acidic. This may influence its ability to activate target genes. XOR-6 is not restricted to Xenopus because southern blots show the presence of XOR-6-related sequences in a variety of other vertebrates. Indeed, a human genomic clone for an XOR-6 related gene has recently been isolated. In accordance with a particular aspect of the present invention, there are also provided nucleic acid sequences encoding the above-identified receptor, as well as constructs and cells containing same, and probes derived therefrom. Furthermore, we have also discovered that hydroxy, mercapto or amino benzoates modulate the transcription activating effects of invention receptors. Excerpt(s): The present invention relates to intracellular receptors, and ligands therefor. In a particular aspect, the present invention relates to methods for the modulation of processes mediated by invention receptors, as well as methods for the identification of compounds which effect such modulation. Nuclear receptors constitute a large superfamily of ligand-activated transcription factors. Members of this family influence transcription either directly, through specific binding to the promoters of target genes (see Evans, in Science 240:889-895 (1988), or indirectly, via protein-protein interactions with other transcription factors (see, for example, Jonat et al., in Cell 62:1189-1204 (1990), Schuele et al., in Cell 62:1217-1226 (1990), and Yang-Yen et al., in Cell 62:1205-1215 (1990)). The steroid/thyroid receptor superfamily includes receptors, for a variety of

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hydrophobic ligands including cortisol, aldosterone, estrogen, progesterone, testosterone, vitamin D.sub.3, thyroid hormone and retinoic acid, as well as a number of receptor-like molecules, termed "orphan receptors" for which the ligands remain unknown (see Evans, 1988, supra). These receptors all share a common structure indicative of divergence from an ancestral archetype. Identification of ligands for orphan receptors presents a significant challenge for the future since the number of orphan receptors which have been identified far exceeds the number of receptors with known ligands. Indeed, at least 40 genes, both vertebrate and invertebrate, have been identified which are structurally related to the steroid/thyroid receptor superfamily, but whose ligands are unidentified. Among these are Drosophila genes of known developmental significance including: the gap gene, knirps (Nauber et al., in Nature 336:489-492 (1988), the terminal gene tailless, involved in patterning the head and tail regions (Pignoni et al., in Cell 62:151-163 (1990), seven-up, which influences photoreceptor cell-fate (Mlodzik et al., in Cell 60: 211-224 (1990), and ultraspiracle, a gene required both maternally and zygotically for pattern formation (Oro et al., in Nature 347: 298-301 (1990)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Multiple antioxidant micronutrients Inventor(s): Haase, Gerald M.; (Greenwood Village, CO), Prasad, Kedar N.; (Denver, CO) Correspondence: Ostrolenk, Faber, Gerb & Soffen, Llp; 1180 Avenue OF The Americas; New York; NY; 10036-8403; US Patent Application Number: 20030147996 Date filed: August 28, 2002 Abstract: A method for optimizing the health of humans according to their age and sex is disclosed wherein the method comprises administering to said humans a daily dose of a multiple antioxidant micronutrient composition comprising vitamin A (palmitate), beta-carotene (from natural d. salina), vitamin C (calcium ascorbate), vitamin D-3 (cholecalciferol), natural source vitamin E including both d-alpha tocopherol and dalpha tocopheryl acid succinate, thiamine mononitrate, riboflavin, niacinamide ascorbate, d-calcium pantothenate, pyridoxine hydrochloride, cyanocobalamin, folic acid (folacin), d-biotin, selenium (l-seleno methionine), chromium picolinate, zinc glycinate, calcium citrate, and magnesium citrate.For persons over the age of about 51, the composition preferably further comprises one or more of co-enzyme Q.sub.10, Nacetyl cysteine, and alpha lipoic acid. Preferably, also, vitamin D is added for women over the age of about 36. Excerpt(s): We claim the benefit under Title 35, United States Code,.sctn.120 of U.S. Provisional Application No. 60/315,523, filed Aug. 29, 2001, entitled MULTIPLE ANTIOXIDANT MICRONUTRIENTS FOR OPTIMAL HEALTH. In the beginning, the earth's atmosphere had no oxygen. Anaerobic organisms, which can live without oxygen, were thriving. About 2.5 billion years ago, blue-green algae in the ocean acquired the ability to split water into hydrogen and oxygen and this chemical reaction initiated the release of oxygen into the atmosphere. The increased levels of atmospheric oxygen caused extinction of many anaerobic organisms owing to oxygen's toxicity. This important biological event also led to the evolution of multicellular organisms, including humans, who utilize oxygen for survival. The content of oxygen in the air gradually increased to the current amounts of about 21 percent in dry air and about 34

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percent in water. The use of oxygen by any organism generates free radicals that are toxic. Therefore, during this period of atmospheric oxygenation, organisms must have struggled to survive the sudden exposure to oxygen toxicity. There must have been enormous rearranging of nucleotides in genes to produce specific proteins that could protect organisms against the damage produced by free radicals. This process eventually led to the production of three antioxidant enzymes. Superoxide dismutase (SOD) requires manganese, copper, or zinc for its biological activity. Mn-SOD is present in mitochondria, whereas Cu-SOD and Zn-SOD are present in the cytoplasm and nucleus of the cell. All three can destroy free radicals and hydrogen peroxide. Another enzyme, catalase, requires iron for its biological activity and it destroys H.sub.2O.sub.2 in cells. Human tissue also contains glutathione peroxidase which requires selenium for its biological activity. It is also responsible for removing hydrogen peroxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Multi-vitamin and hormone replacement supplement Inventor(s): Fox, Dorothy Jean; (Chesapeake, VA), Schloss, Caroline Maxine; (Knotts Island, NC) Correspondence: Kimberly A Chasteen; Williams Mullen Clark & Dobbins; One Iod Oyster Point Road; Suite 210; Newport News; VA; 23602 Patent Application Number: 20030096018 Date filed: September 23, 2002 Abstract: A supplement is disclosed for use by naturally or surgically menopausal women. The supplement includes: Estrogen, Selenium, Zinc, Chromium, Calcium, Copper, Phosphorus, Magnesium, Molybdenum, Iodine, Beta Carotene, Ascorbic Acid, Vitamin D, Vitamin E, Vitamin K, Thiamin, Riboflavin, Vitamin B6, Vitamin B12, Folic Acid, Iron, Pantothenic Acid, and Biotin. The supplement provides hormone replacement therapy along with nutritional supplements. Excerpt(s): The present invention relates generally to a pharmaceutical supplement for menopausal women and more specifically to a pharmaceutical supplement which combines the hormone estrogen with daily supplemental vitamins to treat menopausal women and women who have undergone complete hysterectomies as more fully set forth in the below specifications, drawings and claims. It is well known that estrogen is critical to a woman's health in that it helps to protect the cardiovascular system, helps protect against bone loss and aids mental sharpness. At menopause or subsequent to a complete hysterectomy, the estrogen levels decline significantly thus, the protective aspects of estrogen are significantly reduced for these women. Because heart disease is a major cause of death in women, this creates an increased risk for menopausal and posthysterectomy women. Further, loss of the protection against bone loss can lead to osteoporosis, another major problem for these women. The impairment of cognitive abilities can be another side effect of the significant estrogen loss suffered in menopause or post-hysterectomy. Additional side effects have been linked to reduced estrogen levels such as urinary incontinence and weight gain. Many women are treated with hormone replacement therapy to help reduce these symptoms. The treatment generally consists of supplemental estrogen. This reduces the problems noted above, heart disease, bone loss, loss of cognitive ability, urinary incontinence, weight gain, as well as other well-known symptoms such as hot flashes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nanometer grade hydroxyapatite composition for replenishing calcium Inventor(s): Li, Jinghong; (Changchun, CN) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040009235 Date filed: June 12, 2003 Abstract: The invention provides a hydroxyapatite composition for replenishing calcium, comprising 5 to 80 wt % hydroxyapatite with particle size of 5-800 nm and pharmaceutically acceptable excipient. The composition may comprise organic acid, such as citric acid, malic acid, starch, dextrin, sugar, Vitamin D, Vitamin A, Vitamin B, Vitamin C, and Vitamin E, and trace clement(s) selected from the group consisting of Sr, F, Fe, Zn, and Mn. The composition may be in solid preparation form such as powder, tablet, including coated tablet, capsule, and infusion (medicinal granules), and liquid preparation form such as oral liquid, injection solution, and beverage; and ion introduction type transdermal-preparation- , etc. Furthermore the composition can be incorporated into any other foods. The composition of the invention can be made into different type of products including general type, children type, pregnant women type, liver and kidney type and climacteric type to meet the need of different people. Excerpt(s): The present Application claims the benefit of priority of the Chinese application 02123918.5 filed Jul. 9, 2002, which is expressly incorporated herein by reference in its entirety. The present invention relates to a composition for replenishing calcium containing nanometer grade hydroxyapatite as active agent. Calcium is one of the largest amount and the most important element contained in the body of human beings, which is important to maintain normal function of respiratory, nervous, digestive, endocrine, urinary, and immune system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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New vitamin D derivatives with cyclic substructures in the side chains, process and intermediate products for their production, and the use for the production of pharmaceutical agents Inventor(s): Fahnrich, Marianne; (Berlin, DE), Giesen, Claudia; (Berlin, DE), Haberey, Martin; (Berlin, DE), Schwarz, Katica; (Berlin, DE), Steinmeyer, Andreas; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030149006 Date filed: November 26, 2002 Abstract: The invention relates to vitamin D derivatives of general formula I, 1process for their production, intermediate products of the process as well as the use for the production of pharmaceutical agents. Excerpt(s): process for their production, intermediate products of the process as well as the use for the production of pharmaceutical agents. In addition to their pronounced effect on the calcium-and phosphate metabolism, the active metabolites of vitamin D.sub.2 and vitamin D.sub.3 and their synthetic derivatives have a proliferationinhibiting and differentiation-stimulating action on tumor cells and normal cells, such as, for example, skin cells. In addition, a pronounced effect on cells of the immune

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system (inhibiting of proliferation-and interleukin-2-synthesis of lymphocytes, increase of cytotoxicity and phagocytosis in vitro of monocytes) has been found, which manifests itself in an immunomodulatory action. Finally, because of a stimulating action on boneforming cells, an increased formation of bone in normal and osteoporotic rats is found [R. Bouillon et al. "Short Term Course of 1,25(OH).sub.2D.sub.3 Stimulates Osteoblasts But Not Osteoclasts," Calc. Tissue Int. 49, 168 (1991)]. All actions are mediated by binding to the vitamin D receptor. Because of the binding, the activity of specific genes is regulated. When using biologically active metabolites of vitamins D.sub.2 and D.sub.3, a toxic effect on the calcium metabolism is produced (hypercalcemia). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel use of calreticulin in modulating hormone responsiveness and new pharmaceuticals for treating cancer, osteoporosis and chronic inflammatory disease Inventor(s): Dedhar, Shoukat; (Ontario, CA) Correspondence: T. Gene Dillahunty; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030060613 Date filed: November 29, 2001 Excerpt(s): This invention relates to isolated and purified proteins, such as calreticulin and mimetics of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including cancer, osteoporosis and chronic inflammatory disease. The proteins include or bind to an amino acid sequence KXFFYR, wherein X is either G, A or V and Y is either K or R. This sequence is present in the DNA-binding domain, and is critical for the DNA binding activity, of a variety of hormone receptors, including glucocorticoid receptor, minerolcorticoid receptor, androgen receptor, progesterone receptor, estrogen receptor, retinoic acid receptor, thyroid hormone receptor and vitamin D receptor. Proteins which bind to this sequence may inhibit hormone receptor induced gene transcription. Proteins which include this sequence may promote hormone receptor induced gene transcription. The invention includes isolated DNA molecules for these proteins, methods of treating diseases using these proteins, synthetic peptides and their mimetics, and kits containing these proteins, synthetic peptides or their mimetics. The physiology of many organs in mammals is regulated by hormones. These hormones include steroid hormones, thyroid hormones, metabolites of vitamins, such as all trans retinoic acid, 9-cis retinoic acid, vitamin D and its metabolite 1,25 dihydroxyvitamin D3. These hormones are proteins and bind to intracellular receptors which regulate expression of genes (O'Malley, 1990). There are a variety of receptors which respond to hormones. Osteoblasts and osteoclasts respond to steroid hormones, vitamin D and retinoic acid. Mammary epithelial cells and breast carcinoma cells respond to estrogens, progesterone, retinoic acid and glucocorticoids. Lymphocytes respond to glucocorticoids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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NOVEL VITAMIN D RECEPTOR RELATED POLYPEPTIDES, NUCLEIC ACID SEQUENCE ENCODING THE SAME AND USES THEREOF Inventor(s): BERKENSTAM, ANDERS; (STOCKHOLM, SE), DAHLBERG, MATS; (STOCKHOLM, SE) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030032790 Date filed: August 31, 1998 Abstract: The present invention relates to novel vitamin D receptor related (VDRR) polypeptides, and formulations containing the same. Nucleic acid sequences encoding the VDRR polypeptides, expression vectors containing such sequences and host cells transformed with such expression vectors are also disclosed, as are methods for the expression of the novel VDRR polypeptides of the invention. The invention further relates to VDRR polypeptides for use as medicaments, and use of substances affecting VDRR signal transduction for the manufacture of medicaments for treating metabolic, proliferative or inflammatory conditions. The present invention also relates to methods for identifying clones encoding a VDRR polypeptide, methods for identifing ligands to a VDRR and methods for identifying substances for treatment of conditions affected by a VDRR polypeptide. More specifically, the novel VDRR polypeptide can be the polypeptide designated VDRR.gamma., which may be regulated by any small chemical molecule similar in structure to known ligands for nuclear receptors. Excerpt(s): The present invention relates to novel vitamin D receptor related (VDRR) polypeptides. Nucleic acid sequences encoding the same, expression vectors containing such sequences and host cells transformed with such expression vectors are also disclosed, as are methods for the expression of the novel VDRR polypeptides of the invention, and uses thereof. Nuclear hormone receptors is a large group of conditionally regulated transcription factors. These receptors are activated and regulate target gene expression in response to binding a variety of small chemical molecules (ligands) including steroids, vitamin D3, retinoids, eicosanoides (prostanoids), thyroid hormone and cholesterol derivatives. A growing number of structurally related receptors have been identified for which no ligands yet have been identified. This group of receptors is referred to as orphan nuclear receptors (ONRs). A review of the ONRs can be found in Enmark et al, Mol. Endo., vol. 10, No. 11 (1996) pp. 1293-1307, which is hereby incorporated by reference. The pivotal importance of a number of ONRs for processes such as metabolic homeostasis, cell differentiation and development have been demonstrated both by biochemical and genetic techniques. In addition, several ONRs have also been implicated as key factors in a variety of common diseases and disorders such as diabetes, obesity, inflammatory conditions and proliferative diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Ointment composition for treating decubitus ulcers and methods for its making and its use Inventor(s): Goulbourne, Mary J.; (St. Albans, NY) Correspondence: Richard L. Miller; 12 Parkside Drive; Dix Hills; NY; 11746-4879; US Patent Application Number: 20040013744 Date filed: July 17, 2002

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Abstract: An ointment composition for treating decubitus ulcers and methods for its making and its use. The composition includes a skin protestant ointment, a rash cream, an antibiotic ointment, virgin olive oil, and boric acid powder. The skin protestant ointment includes active ingredients petroleum 53.4%, lanolin 15.5%, and inactive ingredients cod liver oil containing vitamin A & vitamin D, a fragrance, light mineral oil, microcrystalline wax, and paraffin. The rash cream includes active ingredients dimethicone 1% and zinc oxide 10%, and inactive ingredients aloe barbadensis extract, benzyl alcohol, coconut oil, cod liver oil containing vitamin A & vitamin D, a fragrance, glycerol oleate, light mineral oil, ozokerite, paraffin, propylene glycol, sorbitol, synthetic beeswax, and water. The antibiotic ointment includes active ingredients polymyxin B sulfate 5,000 units, bacitracin zinc 400 units, and neomycin base (as sulfate) 3.5 mg., and an inactive ingredient white petroleum. Excerpt(s): The present invention relates to an ointment composition. More particularly, the present invention relates to an ointment composition for treating decubitus ulcers and methods for its making and its use. Numerous innovations for compositions for treating skin irritations have been provided in the prior art that will be described. Even though these innovations may be suitable for the specific individual purposes to which they address, however, they differ from the present invention. A FIRST EXAMPLE, U.S. Pat. No. 3,943,248 to Shulman teaches chemotherapeutic compositions and methods for topically traumatic, diseased and degenerative skin disorders. One of the invention compositions comprises abietic acid and a-tocopherol contained in a pharmaceutically acceptable carrier. One or more of the invention compositions are suitable for the alleviation of severe burn injuries, and in the treatment of other skin disorders such as diabetic ulcers, decubitus ulcers, gangrene, abrasions, lacerations, puncture wounds, localized infections, and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical compositions comprising active vitamin D compounds Inventor(s): Chen, Andrew X.; (San Diego, CA), Fan, Jun; (San Diego, CA), Whitehouse, Martha J.; (San Francisco, CA), Yu, Xi-Yun; (San Diego, CA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W.; Washington; DC; 20005; US Patent Application Number: 20030191093 Date filed: December 3, 2002 Abstract: Disclosed are pharmaceutical compositions comprising an active vitamin D compound in emulsion pre-concentrate formulations, as well as emulsions and submicron droplet emulsions produced therefrom. The compositions comprise a lipophilic phase component, one or more surfactants, and an active vitamin D compound. The compositions may optionally further comprise a hydrophilic phase component. Excerpt(s): The present invention relates to novel pharmaceutical compositions comprising an active vitamin D compound, wherein the pharmaceutical compositions are emulsion pre-concentrates. The invention also relates to emulsions and sub-micron droplet emulsions produced upon dilution of the emulsion pre-concentrates with an aqueous solution. Vitamin D is a fat soluble vitamin which is essential as a positive regulator of calcium homeostasis. (See Harrison's Principles of Internal Medicine: Part Eleven, "Disorders of Bone and Mineral Metabolism," Chapter 335, pp. 1860-1865, E. Braunwald et al., (eds.), McGraw-Hill, New York (1987)). The active form of vitamin D

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is 1.alpha.,25-dihydroxyvitami- n D.sub.3, also known as calcitriol. Specific nuclear receptors for active vitamin D compounds have been discovered in cells from diverse organs not involved in calcium homeostasis. (Miller et al., Cancer Res. 52:515-520 (1992)). In addition to influencing calcium homeostasis, active vitamin D compounds have been implicated in osteogenesis, modulation of immune response, modulation of the process of insulin secretion by the pancreatic B cell, muscle cell function, and the differentiation and growth of epidermal and hematopoictic tissues. Moreover, there have been many reports demonstrating the utility of active vitamin D compounds in the treatment of cancer. For example, it has been shown that certain vitamin D compounds and analogues possess potent antileukemic activity by virtue of inducing the differentiation of malignant cells (specifically, leukemic cells) to non-malignant macrophages (monocytes) and are useful in the treatment of leukemia. (Suda et al., U.S. Pat. No. 4,391,802; Partridge et al., U.S. Pat. No. 4,594,340). Antiproliferative and differentiating actions of calcitriol and other vitamin D.sub.3 analogues have also been reported with respect to the treatment of prostate cancer. (Bishop et al., U.S. Pat. No. 5,795,882). Active vitamin D compounds have also been implicated in the treatment of skin cancer (Chida et al., Cancer Research 45:5426-5430 (1985)), colon cancer(Disman et al., Cancer Research 47:21-25 (1987)), and lung cancer (Sato et al., Tohoku J. Exp. Med. 138:445-446 (1982)). Other reports suggesting important therapeutic uses of active vitamin D compounds are summarized in Rodriguez et al., U.S. Pat. No. 6,034,079. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Selective enzymatic esterification and solvolysis of epimeric vitamin D analog and separation of the epimers Inventor(s): Effenberger, Reinhard; (Haifa, IL), Fishman, Ayelet; (Haifa, IL), Maymon, Asher; (Petach Tikva, IL), Schwartz, Anchel; (Rehovot, IL), Shapiro, Evgeny; (Haifa, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030166226 Date filed: January 9, 2003 Abstract: Provided is a method of selectively enzymatically esterifying or selectively enzymatically solvolyzing epimers of analogs of vitamin D having a stereogenic center at C-24 that has a free or esterified OH group. The metod can be used, for example, for separating mixed epimers of the vitamin D analog. Excerpt(s): The present application claims the benefit of the filing date of U.S. Provisional Patent Applications No. 60/348,082, filed Jan. 10, 2002, and No. 60/349,977, filed Jan. 18, 2002. The present invention relates to methods of selectively enzymatically esterifying and selectively enzymatically solvolyzing epimers at C-24 of analogs of vitamin D and esters thereof. The present invention further relates to methods of separating mixed epimers of analogs of vitamin D including a selective enzymatic esterification step or a selective enzymatic solvolysis step. Since the discovery of 1.alpha., 25-dihydroxyvitamin D.sub.3 (1,25-(OH).sub.2D.sub.3), the hormonally active metabolite form of vitamin D.sub.3, many analogs have been prepared in order to obtain active compounds with low calcemic affect. Much effort has been expended on modification of the vitamin D side chain. While the 1.alpha. hydroxyl group is essential for the hormonal activity, the C-25 hydroxyl group can be replaced with the C-24 hydroxyl group: see, for example, MC 903, (Structure 1) or 1, 24--(OH).sub.2 D.sub.3 (Structure II).

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

Synthesis intermediate products for producing vitamin d derivatives Inventor(s): Boidol, Werner; (Berlin, DE), Steinmeyer, Andreas; (Berlin, DE), Zorn, Ludwig; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030187287 Date filed: May 27, 2003 Abstract: The invention relates to a new synthesis intermediate product of formula I 1its microbiological production and use for synthesis of vitamin D derivatives. Excerpt(s): Vitamin D derivatives have recently gained considerable importance since in addition to the known therapeutic uses (e.g., vitamin D-deficiency diseases, rickets), new types of indications are distinguished. The discovery of the "non-classic" vitamin D activities, e.g., influence of the cell growth of cancer cells, cells of the skin or cells of the immune system, points to the therapeutic potential of vitamin D derivatives in the treatment of tumor diseases, skin diseases as well as disorders of the immune system. In nature, vitamin D derivatives occur only in extremely small amounts, so that for each pharmaceutical preparation, synthetic material must be obtained. In addition, structural variations of the active metabolite of vitamin D.sub.3, 1.alpha.,25-dihydroxy vitamin D.sub.3, allow the production of derivatives with altered profiles of action. The most prominent synthesis of vitamin D derivatives with modifications in the side chain is the Barton-Hesse synthesis [D. R. Andrews, D. H. R. Barton, R. H. Hesse, M. M. Pechet, Synthesis of 25-Hydroxy Vitamin D.sub.3 and 1.alpha.,25-Dihydroxy Vitamin D.sub.3 from Vitamin D.sub.2 (Calciferol). J. Org. Chem. 51: 4819-4828 (1986), EP 0010992, EP 078704, EP 078705]. The drawback of this synthesis is the use of the expensive starting material vitamin D.sub.2, which, moreover, greatly limits the flexibility of the structural variations. Thus, for example, it is not possible to establish structural manipulations on the vitamin D skeleton in this way. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Topical urea composition Inventor(s): Perlmutter, Alan Lorne; (London, CA), Singh, Parashu Ram; (North York, CA) Correspondence: Blake, Cassels & Graydon Llp; Box 25, Commerce Court West; 199 Bay Street; Toronto; ON; M5l 1a9; CA Patent Application Number: 20030104080 Date filed: March 5, 2002 Abstract: Topical composition that contains about 10 to about 50% by weight urea with respect to the total composition weight of the composition; and a topically effective amount of an anti-oxidant compatible with skin. Compositions containing vitamin E, vitamin C, vitamin D and green tea are described. Also described is a method of enhancing delivery of an anti-oxidant to the viable epidermis, including topically applying a composition of the invention to a skin surface of a mammal.

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Excerpt(s): This application is a continuation-in-part application of PCT/CA 00/01031 filed Sep. 7, 2000 designating the United States, which application claims priority from U.S. Provisional Patent Application Serial No. 60/152,637 filed Sep. 7, 1999. Both of these prior applications are incorporated herein by reference. International patent application No. PCT/CA 00/01031 was published in English under Article 21 of the Patent Cooperation Treaty under No. WO 01/17484 on Mar. 15, 2001. This invention relates to a topical skin composition containing an active ingredient and urea for enhancing delivery of the ingredient. The active ingredient can be, alone, or in combination with another active ingredient, one or more of an antioxidant, vitamin, a.beta.-glucan, or other active ingredient. Particularly useful is a composition containing vitamin E and urea, or a composition containing urea, vitamins A, C and E, and green tea extract. Topical compositions are widely used in the cosmetics and pharmaceutical industries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of inflammatory bowel disease with vitamin d compounds Inventor(s): Cantorna, Margherita T; (State College, PA) Correspondence: Andrus Sceales Starke & Sawall; Suite 1100; 100 East Wisconsin Avenue; Milwaukee; WI; 53202-4178; US Patent Application Number: 20030188756 Date filed: August 19, 2002 Abstract: A method of treating inflammatory bowel disease, particularly ulcerative colitis and Crohn's disease, is disclosed. The method involves administering a vitamin D compound in an amount effective to treat the disease. The administration of a vitamin D compound also prevents the development of or delays the onset of inflammatory bowel disease in susceptible individuals. Excerpt(s): This invention relates to vitamin D compounds, and more particularly to the use of vitamin D compounds to treat inflammatory bowel disease. The natural hormone, 1.alpha.,25-dihydroxyvitamin D.sub.3 and its analog 1.alpha.,25dihydroxyvitamin D.sub.2 are known to be highly potent regulators of calcium homeostasis in animals and humans, and their activity in cellular differentiation has also been established, Ostrem et al., Proc. Natl. Acad. Sci. USA, 84, 2610 (1987). Many structural analogs of these metabolites have been prepared and tested, including 1.alpha.-hydroxyvitamin D.sub.3, 1.alpha.-hydroxyvitamin D.sub.2, various side chain homologated vitamins and fluorinated analogs. Some of these compounds exhibit an interesting separation of activities in cell differentiation and calcium regulation. This difference in activity may be useful in the treatment of a variety of diseases such as renal osteodystrophy, vitamin D-resistant rickets, osteoporosis, psoriasis, and certain malignancies. Inflammatory bowel diseases (IBD) are immune mediated diseases of unknown etiology affecting the gastrointestinal (GI) tract. There are at least two distinct forms of IBD, ulcerative colitis and Crohn's disease. IBD are chronic recurring illnesses most commonly involving inflammation of the terminal ileum and colon, although these diseases can also affect many sites throughout the alimentary tract. Clearly, genetic factors predispose individuals to development of IBD (Podolosky 1991). In addition, the environment contributes to IBD development, and there is reason to believe that vitamin D may be an environmental factor which affects IBD. Vitamin D from sunlight exposure is less in areas where IBD occurs most often, as IBD is most prevalent in northern climates such as North America and Northern Europe (Podolosky 1991,

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Sonnenberg et al. 1991). A major source of vitamin D results from its manufacture via a photolysis reaction in the skin, and vitamin D available from sunlight exposure is significantly less in northern climates, and especially low during the winter (Clemens et al. 1982, DeLuca 1993). Dietary intake of vitamin D is problematic since there are few foods which are naturally rich in vitamin D. Weight loss occurs in 65-75% of patients diagnosed with Crohn's disease and 1862% of patients with ulcerative colitis (Fleming 1995, Geerling et al. 1998). Vitamin deficiencies in general and vitamin D deficiency in particular have been shown to occur in IBD patients (Andreassen et al. 1998, Kuroki et al. 1993). To date the possible association between vitamin D status and the incidence and severity of IBD in humans or animals has not been studied. The anecdotal information suggests that vitamin D status could be an environmental factor affecting the prevalence rate for IBD and that the correlation warrants investigation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Triaromatic vitamin D analogues Inventor(s): Bernardon, Jean-Michel; (Nice, FR), Biadatti, Thibaud; (Opio, FR) Correspondence: Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030195259 Date filed: December 10, 2002 Abstract: The invention relates, as novel and useful industrial products, to triaromatic compounds, which are vitamin D analogues, of general formula (I): 1and also to a method for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119 of FR-01/15924, filed Dec. 10, 2001, and of provisional application Ser. No. 60/351,433, filed Jan. 28, 2002, both hereby expressly incorporated by reference. This application is also a continuation of said '433 provisional. The invention relates, as novel and useful industrial products, to triaromatic compounds which are vitamin D analogues. The invention also relates to a process for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of carbon-2-modified-vitamin D analogs to induce the formation of new bone Inventor(s): DeLuca, Hector F.; (Deerfield, WI), Pike, J. Wesley; (Madison, WI), Shevde, Nirupama K.; (Madison, WI) Correspondence: Andrus, Sceales, Starke & Sawall, Llp; 100 East Wisconsin Avenue, Suite 1100; Milwaukee; WI; 53202; US Patent Application Number: 20030195175 Date filed: March 25, 2002 Abstract: It has been discovered that the 2-carbon-modified derivatives of 1.alpha.,25dihydroxyvitamin D.sub.3 specifically stimulate osteoblasts to form new bone. The ability of the 2-carbon-modified vitamin D analogs to stimulate new bone formation suggest that these compounds can be used where synthesis of new bone is required.

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Thus, these compounds can be used either systemically or locally to stimulate the growth of bone transplants, to increase the rate of fracture healing and thereby reduce the time required for the healing of fractures, the stimulation of bone growth when required for replacement surgery, and also for the growth of bone to implants or other devices required to maintain the skeleton or teeth in the proper positions. Excerpt(s): The present invention relates to vitamin D compounds, and more particularly to 19-nor vitamin D compounds substituted at the carbon 2 position which are useful for stimulating growth of new bone. The ability of vitamin D to bring about normal bone formation is well recognized and has been for well over 75 years. Thus, vitamin D will heal rickets and osteomalacia. In the case of these two diseases, it is envisioned that the osteoblasts of bone are able to synthesize the organic matrix of the skeleton even in the absence of vitamin D but that vitamin D is required for the deposit of mineral in the newly-layed down matrix. In this capacity, it is generally believed that vitamin D heals rickets and osteomalacia by the elevation of plasma calcium and phosphorus to levels required for the mineralization process to proceed (DeLuca.sup.1, 1981). Thus, early work (Shipley, Kramer, and Howland,.sup.2,3 1925; 1926) suggested that serum taken from normal rats could heal rachitic lesions in culture, whereas serum taken from rachitic rats was unable to bring about the same healing process. Later, it was discovered that this was because vitamin D by virtue of its ability to elevate the absorption of calcium and phosphorus in the small intestine, is able to raise the plasma calcium and phosphorus to supersaturation levels required for the mineralization of the skeleton. Furthermore, it was envisioned that vitamin D also could cause the mobilization of calcium from bone to elevate plasma calcium concentration (DeLuca.sup.1, 1981) or could stimulate the kidney to reabsorb calcium from the formed urine (Yamamoto et al.sup.4, 1984) raising the plasma calcium and phosphorus product needed for the mineralization process. Final proof that this is the case was provided when calcium and phosphorus infusion into the blood stream of vitamin D-deficient rats brought about normal mineralization of organic matrix of bone and that vitamin D contributed little beyond that if any (Underwood and DeLuca.sup.5, 1984). In the intervening time between the work of Shipley, Kramer, and Howland,.sup.2,3 (1925; 1925) and the work carried out by Underwood and DeLuca.sup.5 (1984), a great deal of information was derived regarding how vitamin D carries out its functions. It is now abundantly clear that vitamin D must first be 25-hydroxylated in the liver and subsequently 1.alpha.-hydroxylated in the kidney before it can function (DeLuca.sup.6, 1974). These two reactions produce the final active form of vitamin D, namely 1,25(OH).sub.2D.sub.3 (DeLuca & Schnoes.sup.7, 1983). This compound then stimulates the intestine to absorb calcium, the kidney to reabsorb calcium, the intestine to absorb phosphate, and it stimulates bone to mobilize calcium when signaled by high parathyroid hormone levels. These actions result in a rise in plasma calcium and phosphorus levels that bring about the healing of bone lesions such as rickets and osteomalacia and prevent the neurological disorder of hypocalcemic tetany. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of vitamin d compounds to prevent transplants rejection Inventor(s): Becker, Bryan N.; (Verona, WI), Deluca, Hector F.; (Deerfield, WI), Hullett, Debra A.; (Oregon, WI), Sollinger, Hans W.; (Madison, WI) Correspondence: Quarles & Brady Llp; 411 E. Wisconsin Avenue; Suite 2040; Milwaukee; WI; 53202-4497; US Patent Application Number: 20030225045 Date filed: March 13, 2003 Abstract: A method of stabilizing kidney function in transplant patients is disclosed. In one embodiment, the method comprises the steps of kidney transplant patient, wherein the transplant patient is undergoing immunosuppressive therapy, with a sufficient amount of vitamin D compound whereby the kidney function stabilizes. Excerpt(s): Chronic rejection is the major cause of failure of kidney transplants, other than patient death. Chronic allograft nephropathy (CAN) is characterized by functional impairment of the kidney and has a pathology including tubular atrophy, interstitial fibrosis, and fibrous intimal thickening. Factors involved may include pre-existing chronic conditions in the donor, acute injury related to the transplant process, and immune stress. One indication of CAN is a changing serum creatinine level. Up to 40% percent of kidney grafts develop progressive dysfunction, despite the use of immunosuppressive drugs (L.C. Paul, Kidney International 56:783-793, 1999). Standard immunosuppressive drug therapy includes cyclosporine A, tacrolimus and corticosteroids. Additional immunosuppressive therapies include azathioprine, mycophenolate mofetil, sirolimus, rapamycin, rapamycin analogs and prednisone. One focus of transplant research today is to reduce the amount of immunosuppressive drug usage after kidney transplantation. Cyclosporine-treated patients are known to develop nephrotoxicity and hypertension. Diabetes mellitus occurs in approximately 15% of renal transplant patients. Additionally, immunosuppressive drugs have negative cosmetic side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of vitamin d derivatives as bone resorption inhibitors Inventor(s): Imaizumi, Atsushi; (Tokyo, JP), Ishizuka, Seiichi; (Tokyo, JP), Kurihara, Noriyoshi; (Pittsburgh, PA), Oue, Yasuhiro; (Tokyo, JP), Reddy, Sakamuri V; (Pittsburgh, PA), Roodman, G. David; (Pittsburgh, PA), Takenouchi, Kazuya; (Tokyo, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20040019024 Date filed: August 4, 2003 Abstract: To obtain a bone resorption inhibitor or a treating agent for Paget's disease of bone, there are provided a method of inhibiting bone resorption, comprising administering to a patient a vitamin D antagonist; and a method for treating Paget's disease of bone, comprising administering to a patient a vitamin D antagonist. Excerpt(s): The present invention relates to a group of therapeutic agents containing vitamin D antagonists as their active moiety that inhibits bone resorption. Specifically, the present invention relates to the use of these agents as therapeutic modalities for

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Paget's disease of bone. Bone is a dynamic tissue that undergoes cycles of resorption followed by new bone formation. This process is continued throughout the skeleton in discreet multi-cellular units called the bone remodeling unit. In the adult bone resorption followed by bone formation is called bone remodeling, and through the remodeling process, bone mass is either maintained or it decreases or increases during life. The relative bone mass depends on the balance between the levels of bone resorption and bone formation. In metabolic bone diseases, this balance between bone resorption and bone formation is changed. Examples include osteoporosis and Paget's disease of bone. Osteoporosis is a disease in which both the organic components and mineral of bone decrease. In osteoporosis, bone mass decreases, and fractures of bone are more likely to occur. Osteoporosis has been classified into two types; type I, which is, found in postmenopausal women, and type II, which is found in aged persons. In postmenopausal osteoporosis, also called Type I osteoporosis, estrogen deficiency results in increased local levels of cytokines such as interleukin-6, interleukin-11 and interleukin-1. Treatments for postmenopausal osteoporosis include, for example, administration of estrogen or its derivatives, bisphosphonates and calcitonin to block-off osteoclastic bone resorption. Similarly, bone metabolism turnover activators such as 1.alpha.-hydroxyvitamin D.sub.3 and 1.alpha.,25-hydroxyvitamin D.sub.3 preparations derivatives, and bone formation enhancers such as vitamin K.sub.2 preparations, have all been used to treat this disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vitamin and zinc monomethionine compositions Inventor(s): Dahl, Eva Marie; (Sausalito, CA) Correspondence: Gavin J. Milczarek-desai; Durando Birdwell & Janke Plc; 2929 E. Broadway BLVD.; Tucson; AZ; 85716; US Patent Application Number: 20030170327 Date filed: March 5, 2002 Abstract: A dietary supplement composition that contains zinc monomethionine in combination with vitamin A, vitamin C, vitamin D, and a bioflavonoid that is formulated to be optimally absorbed and to help maintain normal human system functions. Excerpt(s): The invention relates in general to the field of dietary supplements and more particularly to compositions containing a combination of zinc monomethionine, vitamin A, vitamin C, vitamin D, and a bioflavonoid. The fast pace and resultant stress of modern society increasingly raises dietary health and wellness issues. Chief among these issues is that this lifestyle tends to compromise several normal functions of the healthy human immune system. One aspect of these health issues relates to vitamin and mineral intake. As processed, instant, and fast food become more the mainstay of our national diet, so too have the health concerns stemming from vitamin and mineral deficiencies. Hence, a number of vitamin and mineral supplements have been developed to address deficiencies in persons who do not receive sufficient amounts of these nutrients through their "normal" diet. It has only recently come to be recognized that vitamin and mineral intake can have a pronounced effect on the body's general ability to protect itself against certain conditions. For instance, such "immune-system enhancing" effects for vitamin C have been well documented in clinical studies (Hemill H. Does Vitamin C Alleviate the Symptoms of the Common Cold, A Review of Current Evidence. Scand J Infect Dis 1994;26:1-6). Thus, vitamin and mineral preparations are

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commonly administered not only as general nutritional supplements but also to help maintain normal healthy functioning of the Body's defense systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vitamin D and its analogs in the treatment of tumors and other hyperproliferative disorders Inventor(s): Beer, Tomasz M.; (Portland, OR), Henner, William D.; (Portland, OR) Correspondence: Klarquist Sparkman, Llp; One World Trade Center; Suite 1600; 121 S.W. Salmon Street; Portland; OR; 97204; US Patent Application Number: 20030119795 Date filed: November 21, 2002 Abstract: Treatment of hyperproliferative disorders (including tumors and psoriasis) by pulse administration of a drug (such as Vitamin D or an analog) that increases blood or tissue levels of Vitamin D. The drug is administered at a sufficient dose to have an antiproliferative effect, but the pulsed administration of the drug avoids the development of severe symptomatic or life-threatening hypercalcemia. In particular embodiments, avoidance of hypercalcemia (as measured by serum levels of calcium above normal range) is avoided altogether. In a particular example, the drug is calcitriol administered at an oral dose of about 0.5 mcg/kg once a week. Excerpt(s): This invention concerns the use of Vitamin D and its analogs in the treatment of tumors and hyperproliferative disorders. Vitamin D is a generic term for a family of secosteroids that have affinity for the Vitamin D receptor, and are involved in the physiologic regulation of calcium and phosphate metabolism. Exposure to the sun and dietary intake are common sources of Vitamin D, but deficiencies of this vitamin can cause rickets and osteomalacia. Supplementation of dairy and other food products has reduced the incidence of Vitamin D deficiency conditions in modem society, and medical research concerning this vitamin has turned to its therapeutic effects in a variety of pathological conditions. Vitamin D.sub.3 is synthesized in human skin from 7dehydrocholesterol and ultraviolet light. Vitamin D.sub.3, or its analog Vitamin D.sub.2, can be ingested from the diet, for example in fortified milk products. Vitamin D.sub.2 and D.sub.3 undergo hydroxylation first in the liver to 25-hydroxyvitamin D, then in the kidney to 1.alpha.,25-dihydroxycholecalciferol (also known as 1,25dihydroxyvitamin D or calcitriol), which is the principal biologically active form of Vitamin D. The biological production of this active form of the vitamin is tightly physiologically regulated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Vitamin d derivatives Inventor(s): Emura, Takashi; (Shizuoka, JP), Kawase, Akira; (Shizuoka, JP), Kinoshita, Kazutomo; (Shizuoka, JP), Shimizu, Hitoshi; (Tokyo, JP), Shimizu, Kazuki; (Shizuoka, JP) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20030195176 Date filed: October 17, 2002 Abstract: The object of the present invention is to provide a vitamin D derivative exhibiting excellent physiological activity as medicines, in particular as therapeutic agents for skin disease including psoriasis, and having decreased hypercalcemic activity.The present invention provides vitamin D derivatives represented by the general Formula (1): 1whereinin Formula (1), X is oxygen or sulfur;R.sub.1 is hydrogen or Formula (2) 2R.sub.2 is hydrogen or alkyl;R.sub.3 and R.sub.4 are hydrogen or alkyl or R.sub.3 and R.sub.4 together form a double bond between the 16- and 17positions;R.sub.5 is hydrogen or -OR.sub.13 in which R.sub.13 is hydrogen or a protecting group; andR.sub.6 is hydrogen or a protecting group. Excerpt(s): The present invention relates to novel vitamin D derivatives, and more particularly, relates to vitamin D derivatives useful as medicines (such as therapeutic agents for skin diseases including psoriasis). In vivo, vitamin D.sub.3 is led to 25hydroxyvitamin D.sub.3 in liver by the hydroxylation of the 25-position and then led to 1.alpha., 25-dihydroxyvitamin D.sub.3 or 24R, 25-dihydroxyvitamin D.sub.3 by the hydroxylation of the 1.alpha.- or 24-position, respectively. Among those metabolites, for example, 1.alpha., 25-dihydroxyvitamin D.sub.3 and its synthetic analogues are known to have various physiological activities such as calcium metabolism regulatory activities, growth inhibitory and differentiation inducing activities for tumor cells, and immunoregulatory activities. Long-term and continuous administration of vitamin D.sub.3 has tended to have a disadvantageous effect of causing hypercalcemia. To solve this problem, synthesis of various vitamin D derivatives is discussed and vitamin D derivatives having a reduced hypercalcemic effect have been proposed (e.g., JP No. 7330714 A and JP No. 10-231284 A). 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 vitamin D, 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 “vitamin D” (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 vitamin D. You can also use this procedure to view pending patent applications concerning vitamin D. 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 7. BOOKS ON VITAMIN D Overview This chapter provides bibliographic book references relating to vitamin D. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on vitamin D 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 “vitamin D” (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 vitamin D: •

Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride Source: Washington, DC: National Academy Press. 1998. 432 pp. Contact: Available from National Academy Press, 2101 Constitution Avenue, N.W., Lockbox 285, Washington, DC 20002 / Web site: http://www.nap.edu. $24.95; $19.96 (paperback) when ordered through the publisher's Web bookstore, plus shipping and handling. Summary: This book is the first in a series about the Dietary Reference Intakes that replace the Recommended Dietary Allowances. It evaluates calcium, phosphorus, magnesium, vitamin D, and fluoride. For each nutrient, the book presents what is known about how the nutrient functions in the human body, what is the best method to determine its requirement, which factors may affect how it works, and how the nutrient may be related to chronic disease or developmental abnormalities. The book also

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identifies the Tolerable Upper Level Intake (UL) which may result in adverse effects if consumed consistently and provides a model for determining the UL. Recommended intakes are proposed for age groups from infancy to midlife and later years.

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: Online booksellers typically produce search results for medical and non-medical books. When searching for “vitamin D” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “vitamin D” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “vitamin D” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Calcium Regulating Hormones, Vitamin D Metabolites, and Cyclic AMP Assays and Their Clinical Application; ISBN: 3540522298; http://www.amazon.com/exec/obidos/ASIN/3540522298/icongroupinterna

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Calcium Regulating Hormones, Vitamin d Metabolites, and Cyclic Amp Assays and Their Clinical Application by H. Schmidt-Gayk, et al; ISBN: 0387522298; http://www.amazon.com/exec/obidos/ASIN/0387522298/icongroupinterna

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Dietary Reference Intakes: For Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride (Dietary Reference Series) by Institute of Medicine; ISBN: 0309064031; http://www.amazon.com/exec/obidos/ASIN/0309064031/icongroupinterna

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DK Pocket Healers: Vitamin D (DK Pocket Healers Healers) by Stephanie Pederson; ISBN: 0751331961; http://www.amazon.com/exec/obidos/ASIN/0751331961/icongroupinterna

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Natural Care Library Vitamin D: Safe and Effective Self-Care for Improving Circulation and Growth by Stephanie Pedersen; ISBN: 0789451972; http://www.amazon.com/exec/obidos/ASIN/0789451972/icongroupinterna

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Nutritional Imbalances in Infant and Adult Disease: Mineral, Vitamin D, and Cholesterol: Proceedings of the Sixteenth Annual Meeting of the American C by American College Of Nutrition; ISBN: 0893350079; http://www.amazon.com/exec/obidos/ASIN/0893350079/icongroupinterna

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Rickets and osteomalacia : report of the Working Party on Fortification of Food with Vitamin D, Committee on Medical Aspects of Food Policy; ISBN: 0113207476; http://www.amazon.com/exec/obidos/ASIN/0113207476/icongroupinterna

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Round 1 progress report anabolic vitamin D analogs as countermeasures to bone loss (SuDoc NAS 1.26:113066) by Norman J. Karin; ISBN: B00010YUUU; http://www.amazon.com/exec/obidos/ASIN/B00010YUUU/icongroupinterna

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The Metabolism and function of vitamin D : proceedings of a colloquium organized by the Lipid Group of the Biochemical Society and held at King's College, London, February 1973; ISBN: 0950197270; http://www.amazon.com/exec/obidos/ASIN/0950197270/icongroupinterna

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The Role of 1a,25-Dihydroxyvitamin D3 and the Vitamin D Receptor in the Control of Proliferation and Differentiation of the Epidermal Keratinocyte (Acta Biomedica

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Lovaniensia 196) by Siegfried Segaert; ISBN: 9061869609; http://www.amazon.com/exec/obidos/ASIN/9061869609/icongroupinterna •

Uses and actions of 1,25-dihydroxyvitamin D b3 s in uremia; ISBN: 3805530641; http://www.amazon.com/exec/obidos/ASIN/3805530641/icongroupinterna

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Vitamin D by Francis Glorieux (Author), et al; ISBN: 0122526856; http://www.amazon.com/exec/obidos/ASIN/0122526856/icongroupinterna

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Vitamin D by Norman; ISBN: 3110114771; http://www.amazon.com/exec/obidos/ASIN/3110114771/icongroupinterna

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Vitamin D by D Lawson; ISBN: 0124398502; http://www.amazon.com/exec/obidos/ASIN/0124398502/icongroupinterna

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Vitamin D : basic research and its clinical application : proceedings of the Fourth Workshop on Vitamin D, Berlin, West Germany, February 1979; ISBN: 3110077124; http://www.amazon.com/exec/obidos/ASIN/3110077124/icongroupinterna

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Vitamin D : biochemical, chemical, and clinical aspects related to calcium metabolism : proceedings of the Third Workshop on Vitamin D, Asilomar, Pacific Grove, California, USA, January 1977; ISBN: 3110069180; http://www.amazon.com/exec/obidos/ASIN/3110069180/icongroupinterna

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Vitamin D : chemical, biochemical, and clinical update : proceedings of the Sixth Workshop on Vitamin D, Merano, Italy, March 1985; ISBN: 0899250661; http://www.amazon.com/exec/obidos/ASIN/0899250661/icongroupinterna

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Vitamin D : chemistry, biology and clinical applications of the steroid hormone : proceedings of the Tenth Workshop on Vitamin D, Strasbourg, France, May 24-29, 1997 by Roger Bouillon, A. W. Norman; ISBN: 1891168002; http://www.amazon.com/exec/obidos/ASIN/1891168002/icongroupinterna

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Vitamin D : gene regulation, structure-function analysis, and clinical application : proceedings of the Eighth Workshop on Vitamin D, Paris, France, July 5-10, 1991; ISBN: 0899257445; http://www.amazon.com/exec/obidos/ASIN/0899257445/icongroupinterna

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Vitamin D : metabolism and function by Hector F. DeLuca; ISBN: 0387091823; http://www.amazon.com/exec/obidos/ASIN/0387091823/icongroupinterna

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Vitamin D Analogs in Cancer Prevention and Therapy (Recent Results in Cancer Research, 164) by W. Tilgen (Editor), et al; ISBN: 3540002901; http://www.amazon.com/exec/obidos/ASIN/3540002901/icongroupinterna

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Vitamin D and Calcium Metabolism in Renal Diseases: Contributions from Japan by K. Kobayashi; ISBN: 380550389X; http://www.amazon.com/exec/obidos/ASIN/380550389X/icongroupinterna

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Vitamin D and problems related to uremic bone disease : proceedings of the Second Workshop on Vitamin D, Wiesbaden, West Germany, October 1974; ISBN: 3110057751; http://www.amazon.com/exec/obidos/ASIN/3110057751/icongroupinterna

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Vitamin D and Rickets (Endocrine Development, 6) by Z. Hochberg (Editor); ISBN: 3805575823; http://www.amazon.com/exec/obidos/ASIN/3805575823/icongroupinterna

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Vitamin D deficiency and osteomalacia by S. J. Darke; ISBN: 0113202407; http://www.amazon.com/exec/obidos/ASIN/0113202407/icongroupinterna

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Vitamin D in Dermatology by Knud Kragballe (Editor); ISBN: 0824777042; http://www.amazon.com/exec/obidos/ASIN/0824777042/icongroupinterna

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Vitamin D status of submariners during patrol (SuDoc D 206.10:1129) by C. L. Schlichting; ISBN: B00010IZL0; http://www.amazon.com/exec/obidos/ASIN/B00010IZL0/icongroupinterna

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Vitamin D, chemical, biochemical, and clinical endocrinology of calcium metabolism : proceedings of the Fifth Workshop on Vitamin D, Williamsburg, VA, USA, February 1982; ISBN: 3110088649; http://www.amazon.com/exec/obidos/ASIN/3110088649/icongroupinterna

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Vitamin D, Molecular Biology and Clinical Nutrition (Basic and Clinical Nutrition, Vol 2) by Anthony W. Norman (Editor); ISBN: 0824768914; http://www.amazon.com/exec/obidos/ASIN/0824768914/icongroupinterna

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Vitamin D, Slide Set by Francis Glorieux (Author), et al; ISBN: 0122526864; http://www.amazon.com/exec/obidos/ASIN/0122526864/icongroupinterna

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Vitamin D: A Pluripotent Steroid Hormone: Structional Studies, Molecular Endocrinology and Clinical Applications: Proceedings of the Ninth Workshop on Vitamin by A. W. Norman (Editor), et al; ISBN: 3110141574; http://www.amazon.com/exec/obidos/ASIN/3110141574/icongroupinterna

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Vitamin D: Basic and Clinical Aspects by Rajiv Kumar (Editor); ISBN: 0898386209; http://www.amazon.com/exec/obidos/ASIN/0898386209/icongroupinterna

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Vitamin D: Chemical , Biochemical and Clinical Update: Proceedings of the Sixth Workshop on Vitamin d Merano, Italy, March 1985 by A.W. Norman, et al; ISBN: 3110101815; http://www.amazon.com/exec/obidos/ASIN/3110101815/icongroupinterna

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Vitamin D: Gene Regulation, Structure Function Analysis and Clinical Application: Proceedings of the Eighth Workshop on Vitamin d Paris, France Jul by A.W. Norman, et al; ISBN: 3110126389; http://www.amazon.com/exec/obidos/ASIN/3110126389/icongroupinterna

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Vitamin D: Molecular Cellular and Clinical Endocrinology: Proceedings by A.W. Norman (Editor); ISBN: 0899253938; http://www.amazon.com/exec/obidos/ASIN/0899253938/icongroupinterna

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Vitamin D: Physiology, Molecular Biology, and Clinical Applications by M. F. Holick (Editor); ISBN: 0896034674; http://www.amazon.com/exec/obidos/ASIN/0896034674/icongroupinterna

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Vitamin D: The Calcium Homeostatic Steroid Hormone by Anthony W. Norman; ISBN: 0125210507; http://www.amazon.com/exec/obidos/ASIN/0125210507/icongroupinterna

Chapters on Vitamin D In order to find chapters that specifically relate to vitamin D, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and vitamin D 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 “vitamin D” (or

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synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on vitamin D: •

Calcium, Phosphorus, and Vitamin D Metabolism in Renal Disease and Chronic Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 341-369. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors discuss calcium, phosphorus, and vitamin D metabolism in renal disease and chronic renal failure (CRF). The authors begin with a brief review of normal physiologic control of calcium and phosphorus homeostasis and normal vitamin D and parathyroid hormone metabolism. Next, they discuss the effects of the failing kidney on mineral metabolism, secondary hyperparathyroidism, hyperphosphatemia, therapeutic interventions in predialysis patients, and control of phosphate retention and secondary hyperparathyroidism in dialysis patients. The authors conclude that dietary restriction of phosphorus intake and adequate dialysis therapy form the basis for management, but are usually insufficient to bring about adequate control. Calcium-based phosphate binders and hormonal vitamin D replacement are powerful adjuncts in regulating mineral pathophysiology. Despite these maneuvers, parathyroidectomy is still occasionally required. The authors provide an algorithm for the management of hyperphosphatemia and secondary hyperparathyroidism. Additional sections discuss the implications for bone disease (renal osteodystrophy), one of the more serious complications of disordered mineral metabolism in renal failure; implications for other complications; disturbances of mineral metabolism following renal transplantation; and disturbances of mineral and vitamin D metabolism in nephrotic syndrome. 5 figures. 124 references. (AA-M).

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CHAPTER 8. MULTIMEDIA ON VITAMIN D Overview In this chapter, we show you how to keep current on multimedia sources of information on vitamin D. 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 vitamin D is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “vitamin D” 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 “vitamin D” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on vitamin D: •

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;

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hypo-and hyperparathyroidism). Vitamin D deficiency results in rickets (soft, weak 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.

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CHAPTER 9. PERIODICALS AND NEWS ON VITAMIN D Overview In this chapter, we suggest a number of news sources and present various periodicals that cover vitamin D.

News Services and Press Releases One of the simplest ways of tracking press releases on vitamin D 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 “vitamin D” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to vitamin D. 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 “vitamin D” (or synonyms). The following was recently listed in this archive for vitamin D: •

Vitamin D supplements tied to reduced risk of multiple sclerosis in women Source: Reuters Industry Breifing Date: January 12, 2004

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Vitamin D may protect against rheumatoid arthritis Source: Reuters Industry Breifing Date: January 09, 2004

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Vitamin D deficiency common in patients with musculoskeletal pain Source: Reuters Medical News Date: December 29, 2003

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Maternal vitamin D intake in food decreases risk of autoimmune diabetes in offspring Source: Reuters Medical News Date: December 15, 2003

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Calcium and vitamin D work together to prevent colorectal neoplasia Source: Reuters Medical News Date: December 08, 2003

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Vitamin D mimic may improve prostate cancer therapy Source: Reuters Health eLine Date: August 27, 2003

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Vitamin D analog enhances radiation's ability to kill prostate cancer cells Source: Reuters Industry Breifing Date: August 27, 2003

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Dialysis patients live longer with newer vitamin D Source: Reuters Health eLine Date: July 30, 2003

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Vitamin D receptor polymorphism linked to acute-onset type 1 diabetes Source: Reuters Medical News Date: July 28, 2003

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Vitamin D analog enhances radiation's effects on experimental breast tumors Source: Reuters Medical News Date: June 10, 2003

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Vitamin D supplements recommended for infants Source: Reuters Medical News Date: April 07, 2003

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Experts: Babies should get vitamin D supplement Source: Reuters Health eLine Date: April 07, 2003

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Vitamin D receptor polymorphism influences alendronate's effect on osteoporosis Source: Reuters Industry Breifing Date: March 21, 2003

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Resistance training, vitamin D supplementation no help in rehab of frail elderly Source: Reuters Medical News Date: March 14, 2003

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High-dose vitamin D prevents bone breaks in elderly Source: Reuters Health eLine Date: February 28, 2003

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Low-cost vitamin D supplementation reduces fractures in elderly Source: Reuters Medical News Date: February 27, 2003

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Vitamin D status may contribute to pathogenesis of heart failure Source: Reuters Medical News Date: January 29, 2003

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Calcium and vitamin D supplements may benefit women at risk of osteoporosis Source: Reuters Medical News Date: January 13, 2003

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Vitamin D deficiency common among pregnant women from ethnic minorities Source: Reuters Medical News Date: September 20, 2002

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Vitamin D analogues might be useful antihypertensive agents Source: Reuters Industry Breifing Date: August 09, 2002

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Vitamin D protects against colon cancer by inducing bile acid breakdown Source: Reuters Medical News Date: May 16, 2002

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Vitamin D analog shows promise in treatment of experimental diabetes model Source: Reuters Medical News Date: May 16, 2002

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Vitamin D cuts risk of cardiovascular death in women Source: Reuters Medical News Date: April 23, 2002

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Intravesical vitamin D a prospect for bladder cancer treatment Source: Reuters Industry Breifing Date: January 19, 2001

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Air pollution linked to vitamin D deficiency in children Source: Reuters Medical News Date: September 29, 2000

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Vitamin D supplementation advised for breast-fed infants Source: Reuters Medical News Date: August 31, 2000

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Vitamin D analogue inhibits mouse skin tumorigenesis Source: Reuters Industry Breifing Date: August 24, 2000

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Vitamin D deficiency a risk factor for severe bone loss in hyperparathyroidism Source: Reuters Medical News Date: July 03, 2000

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Vitamin D urged for breast-fed, dark-skinned infants Source: Reuters Health eLine Date: June 19, 2000

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Vitamin D supplementation urged for breast-fed, dark-skinned infants Source: Reuters Medical News Date: June 19, 2000

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Vitamin D does not benefit patients with relapsing-remitting MS Source: Reuters Medical News Date: May 08, 2000

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Vitamin D depletion contributes to osteopenia in child survivors of severe burns Source: Reuters Medical News Date: March 15, 2002

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Ultraviolet B radiation treats vitamin D deficiency due to Crohn's disease Source: Reuters Medical News Date: January 03, 2002

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Vitamin D guidelines in Canada may be too low for women Source: Reuters Medical News Date: December 12, 2001

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Vitamin D receptor genotype affects disease progression in HIV-infected IDUs Source: Reuters Medical News Date: December 05, 2001

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Vitamin D intake in early childhood linked to reduced diabetes risk Source: Reuters Medical News Date: November 01, 2001

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Vitamin D gene variant linked to breast cancer Source: Reuters Medical News Date: October 04, 2001

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Vitamin D status influences serum PTH values in the elderly Source: Reuters Medical News Date: August 17, 2001

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Vitamin D and calcium keep blood pressure down Source: Reuters Health eLine Date: May 03, 2001

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Vitamin D may help MS patients Source: Reuters Health eLine Date: April 10, 2001

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Breast-fed babies may risk vitamin D deficiency Source: Reuters Health eLine Date: March 30, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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

Newsletters on Vitamin D Find newsletters on vitamin D 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 “vitamin D.” 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 “vitamin D” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Rheumatic Manifestations of Gastrointestinal Diseases Source: Bulletin on the Rheumatic Diseases. 51(2): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on the rheumatic manifestations of gastrointestinal diseases. Pathologic changes in the gastrointestinal tract may have a role in the pathogenesis of arthropathies. Impairment of the gastrointestinal barrier function and altered gut permeability may have a role in various diseases, including inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis (UC), celiac sprue, Whipple's disease, and enteric reactive arthritis.

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Crohn's disease and UC are associated with various extraintestinal chronic inflammatory diseases, including arthritis. The type of arthritis associated with IBDs may be either axial or peripheral. Management of arthritis in patients with IBD requires good control of the underlying gastrointestinal pathology with drugs such as sulfasalazine, azathioprine, glucocorticords, and methotrexate. Low bone mineral density is a complication of IBD, so patients with IBD should be advised to consume adequate vitamin D and calcium and to participate in a regular weight bearing exercise program. Celiac sprue, or gluten enteropathy, is characterized by diffuse damage to the proximal small intestinal mucosa that results in villous atrophy and altered gut permeability. Arthritis is a complication in children and adults. Whipple's disease is a rare multisystemic illness caused by infection with Tropheryma whippelii. Diagnosis is based on duodenal or lymph node biopsy. Recommended treatment is trimethoprim combined with sulfamethoxazole. Reactive arthritis, a common arthritide affecting young adults, usually follows urogenital or intestinal bacterial infection. The mainstays of treatment are analgesics and nonsteroidal antiinflammatory drugs. 2 tables and 37 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 “vitamin D” (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 vitamin D: •

Overweight People More Prone to Vitamin D Shortfall Source: Tufts University Health and Nutrition Letter. 18(9):6. November 2000. Contact: 10 High Street, Suite 706, Boston, MA 02110. [email protected]. www.healthletter.tufts.edu. Summary: The more overweight someone is, the lower the level of vitamin D in the bloodstream. Less vitamin D means the body is less capable of absorbing calcium. Researchers have found that the vitamin D that overweight people produce, as well as the vitamin D they eat in food, is less likely to make it to their blood. When exposed to sunlight, overweight men produce the same amount as thinner men, but rather than flowing from tiny capillaries in the skin into the main pathways of the bloodstream, the vitamin moves to the fat cells beneath the skin's surface. The researchers also believe that when vitamin D is eaten in foods, and after it is absorbed into the bloodstream from the gastrointestinal tract, it ends up "sequestered" in the large pool of body fat. The chance of a vitamin D deficiency is not high in an overweight person not attempting to lose weight. However, once an overweight person, especially a very overweight person, starts a weight-loss diet, then a marginal deficiency can become a definite vitamin D deficiency. Many low-fat, low-calorie diets are low in vitamin D. Researchers recommend a supplement containing vitamin D for overweight people attempting to lose weight. The more a person weighs, the more important a supplement becomes because more fat cells mean less vitamin D ends up in the bloodstream.

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

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CHAPTER 10. 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 vitamin D. 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 nonprofit 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 vitamin D. 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 vitamin D: Alendronate •

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

Calcitonin •

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

Etidronate •

Systemic - U.S. Brands: Didronel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202233.html

Risedronate •

Systemic - U.S. Brands: Actonel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203554.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

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/.

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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

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/

11

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/

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

•

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

•

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

•

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

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

•

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.12 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:13 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

12

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

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•

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

•

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

The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “vitamin D” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 34656 198 801 29 116 35800

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “vitamin D” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 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.20 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.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

The Genome Project and Vitamin D In the following section, we will discuss databases and references which relate to the Genome Project and vitamin D. 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).22 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. 19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 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. 22 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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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “vitamin D” (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 vitamin D: •

Pseudovitamin D Deficiency Rickets Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?264700

•

Vitamin D 25-hydroxylation, Rickets due to Defect in Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600081

•

Vitamin D Receptor Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601769

•

Vitamin D Receptor-interacting Protein, 36-kd Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605718

•

Vitamin D-dependent Rickets, Receptor-positive Type Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600785

•

Vitamin D-dependent Rickets, Type Ii Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?277420

•

Vitamin D-resistant Rickets with End-organ Unresponsiveness to dihydroxycholecalciferol Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?277440

1,25-

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

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

•

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

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity,

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paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html •

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “vitamin D” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 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. 23

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “vitamin D” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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

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Other guides Antioxidants http://www.nlm.nih.gov/medlineplus/antioxidants.html Macular Degeneration http://www.nlm.nih.gov/medlineplus/maculardegeneration.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Vitamins and Minerals http://www.nlm.nih.gov/medlineplus/vitaminsandminerals.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on vitamin D. 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: •

Diet, Vitamin D and Men Source: Abbott Park, IL: Abbott Laboratories. 1991. 2 p. Contact: Available from Abbott Laboratories. Renal Care, Abbott Park, IL 60064. (800) 323-9100 or (708) 937-3933. PRICE: Single copy free; contact local Abbott representative for copies. Order Number 90-1641/R1-40-Sep.,91. Summary: This booklet was written to help kidney patients understand the importance of vitamin D in kidney disease. Using a question and answer format, the authors discuss how vitamin D affects the way calcium and phosphorus are used by the body; what happens when calcium and phosphorus levels are out of balance in the blood; renal bone disease; calcitriol supplements; dietary limitations of phosphorus and calcium; and the role of phosphorus binders.

•

Dietary Supplement Fact Sheet: Vitamin D Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2000. 11 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D020.

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Summary: This fact sheet is designed to provide basic information about the role of vitamin D in health and disease and to guide decisions about the use of a vitamin D supplement. First, it explains what vitamin D is and how it is used by the body, what the sources of vitamin D are, what an adequate daily intake of vitamin D for adults is, when a vitamin D deficiency can occur, and who may need extra vitamin D. Then, it discusses current issues and controversies related to vitamin D and osteoporosis, cancer, steroids, and Alzheimer's disease. Finally, it examines the health risk of too much vitamin D. The fact sheet includes a table listing selected food sources of vitamin D and 37 references. 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: •

Facts About Dietary Supplements: Vitamin D Summary: Answers basic questions about vitamin D, such as what it is, what foods provide it, and what intake is needed to provide the recommended dietary allowance. Source: Warren Grant Magnuson Clinical Center, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6472 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 vitamin D. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

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•

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

•

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

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

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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 “vitamin D” (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.25

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

25

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)26: •

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

•

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

•

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

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

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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/

•

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

26

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

•

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

•

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

•

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

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

•

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

•

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

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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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

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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

•

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

•

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

•

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

•

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

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

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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/

•

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

•

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

•

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

•

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

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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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Vitamin D Vitamin D Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002405.htm

•

Nutrition for Vitamin D Balanced diet Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002449.htm Vitamins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002399.htm

•

Background Topics for Vitamin D Food guide pyramid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002093.htm

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

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

•

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

•

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

•

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

267

VITAMIN D DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [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] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [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] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH]

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Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [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] 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] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [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] 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] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] 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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions

Dictionary

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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] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] 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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] 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] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Aloe: A genus of the family Liliaceae containing anthraquinone glycosides such as aloinemodin or aloe-emodin (emodin). [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] 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] 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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH]

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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 Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [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] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [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] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] 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] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [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] 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] 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] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anthracyclines: Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] 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 lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood

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thinner. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU] 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] 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]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antirheumatic Agents: Drugs that are used to treat rheumatoid arthritis. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell pathological process of necrosis). Apoptosis is the physiological deletion of cells and appears to be characterized by distinctive morphologic changes in the

death occurs (the other being the mechanism responsible for the intrinsically programmed. It is nucleus and cytoplasm, chromatin

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cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] 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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [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] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU]

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Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [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] 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] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] 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] Basal Metabolism: Heat production, or its measurement, of an organism at the lowest level of cell chemistry in an inactive, awake, fasting state. It may be determined directly by means of a calorimeter or indirectly by calculating the heat production from an analysis of the end products of oxidation within the organism or from the amount of oxygen utilized. [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]

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Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzoates: Salts and esters of benzoic acid that possess antibacterial and antifungal properties. They are used as preservatives in pharmaceutical formulations including oral preparations, cosmetics, and food. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response

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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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [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 pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically

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separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [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] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [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 metastases: Cancer that has spread from the original (primary) tumor to the 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] 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 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

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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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] 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 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] 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 Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx

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through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Citrate Malate: It transmits extracellular signals within cells. [NIH] Calcium Isotopes: Stable calcium atoms that have the same atomic number as the element calcium, but differ in atomic weight. Ca-42-44, 46, and 48 are stable calcium isotopes. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calorimeter: Measures the amounts of heat absorbed or given off by a solid, a liquid, or a gas. [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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] 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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular 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] Cardiovascular System: The heart and the blood vessels by which blood is pumped and

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circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] 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]

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Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell 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 Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central fat distribution: The waist circumference is an index of body fat distribution. Increasing waist circumference is accompanied by increasing frequencies of overt type 2 diabetes, dyslipidemia, hypertension, coronary heart disease, stroke, and early mortality. In the body fat patterns called android type (apple shaped) fat is deposited around the waist and upper abdominal area and appears most often in men. Abdominal body fat is thought to be associated with a rapid mobilization of fatty acids rather than resulting from other fat depots, although it remains a point of contention. If abdominal fat is indeed more active than other fat depots, it would then provide a mechanism by which we could explain (in part) the increase in blood lipid and glucose levels. The latter have been clearly associated with an increased risk for cardiovascular disease, hypertension, and type 2 diabetes. The gynoid type (pear-shaped) of body fat is usually seen in women. The fat is deposited around the hips, thighs, and buttocks, and presumably is used as energy reserve during pregnancy and lactation. [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

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gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Check-up: A general physical examination. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [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] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU]

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Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] 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] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] 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] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [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] 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]

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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] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] 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] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [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.

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Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [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] 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] 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]

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Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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

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represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [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] 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 clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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] Coproporphyrinogen Oxidase: One of the enzymes active in heme biosynthesis. It catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen III by the conversion of two propionic acid groups to two vinyl groups. It can act under both aerobic and anaerobic conditions. EC 1.3.3.3. [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] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [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

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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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Illness: A disease or state in which death is possible or imminent. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]

Cyclohexanes: A group of alicyclic hydrocarbons with the general formula R-C6H11. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] 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] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [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

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contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] 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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

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Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Deoxycytidine: A drug that protects healthy tissues from the toxic effects of anticancer drugs. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [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] Dermal: Pertaining to or coming from the skin. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] 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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] 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]

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Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] 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] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] 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] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme

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class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Dose-rate: The strength of a treatment given over a period of time. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [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] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysgenesis: Defective development. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [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] 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] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service

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produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [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] Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Emollient: Softening or soothing; called also malactic. [EU] 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] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [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] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune

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and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] 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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [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] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] 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] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH]

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Enhancer: Transcriptional element in the virus genome. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [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] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [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] Epigastric: Having to do with the upper middle area of the abdomen. [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] 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] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH]

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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] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [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 receptor negative: ER-. Breast cancer cells that do not have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER- do not need the hormone estrogen to grow and usually do not respond to hormone (antiestrogen) therapy that blocks these receptor sites. [NIH] Estrogen receptor positive: ER+. Breast cancer cells that have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER+ need the hormone estrogen to grow and will usually respond to hormone (antiestrogen) therapy that blocks these receptor sites. [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]

Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]

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Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] 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] 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] Extrarenal: Outside of the kidney. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] 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] Febrile: Pertaining to or characterized by fever. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Fractures: Fractures of the femur. [NIH] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fenbendazole: Antinematodal benzimidazole used in veterinary medicine. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical

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vessels at the time of delivery. [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] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [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] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] 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] 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] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [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] Follicles: Shafts through which hair grows. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes bony callus formation and normal replacement of bone tissue. [NIH] Frail Elderly: Older adults or aged individuals who are lacking in general strength and are unusually susceptible to disease or to other infirmity. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH]

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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] Fungistatic: Inhibiting the growth of fungi. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [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] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic 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 Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH]

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Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] 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] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] 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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid

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(glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] 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] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [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] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH]

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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] 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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [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] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] 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 Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to

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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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [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] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] 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 Antagonists: Chemical substances which inhibit the function of the endocrine

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glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. [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] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] 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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] 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 replacement of hydrogen. [EU]

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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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [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] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypervitaminosis: A condition due to ingestion of an excess of one or more vitamins; called also supervitaminosis. [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] Hypovitaminosis: A condition due to a deficiency of one or more essential vitamins. [EU] 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] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immaturity: The state or quality of being unripe or not fully developed. [EU] 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]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH]

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Immunogenic: Producing immunity; evoking an immune response. [EU] 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] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [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] 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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [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] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, 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

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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] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [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] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] 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

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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-11: Lymphohematopoietic cytokine that has the ability to modulate antigenspecific antibody responses, potentiate megakaryocytes, and regulate bone marrow adipogenesis. [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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] 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, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [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]

Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]

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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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [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] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isoprenoid: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH]

Isopropyl: A gene mutation inducer. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [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

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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] Kinetic: Pertaining to or producing motion. [EU] Knee Injuries: Injuries to the knee or the knee joint. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacerations: Torn, ragged, mangled wounds. [NIH] 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 indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Lanolin: A yellow fat obtained from sheep's wool. It is used as an emollient, cosmetic, and pharmaceutic aid. [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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

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] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from

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fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] 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] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows

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strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [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 Extracts: Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [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] 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] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Low-calorie diet: Caloric restriction of about 800 to 1,500 calories (approximately 12 to 15 kcal/kg of body weight) per day. [NIH] Lubricants: Oily or slippery substances. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU]

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Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] 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] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH]

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Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [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] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH]

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Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some 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 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] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [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] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] 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 viruses. [NIH]

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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] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] 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] Mineral Oil: A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient. [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] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH]

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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 Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [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, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] 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] 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]

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Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephrolithiasis: Kidney stones. [NIH]

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Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [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]

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Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear 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 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] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclease Protection Assays: Techniques for measuring specific nucleic acid interaction with another nucleic acid or with a protein by digestion of the non-interacting nucleic acid by various nucleases. After all non-interacting regions are eliminated by nuclease digestion, the protected nucleic acid that remains is analyzed. DNA footprinting utilizes this technique to analyze the DNA contact sites of DNA-binding proteins. [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] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [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] 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] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU]

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Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] 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] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [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] Ophthalmic: Pertaining to the eye. [EU] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Organoleptic: Of, relating to, or involving the employment of the sense organs; used especially of subjective testing (as of flavor, odor, appearance) of food and drug products. [NIH]

Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmoles: The standard unit of osmotic pressure. [NIH]

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Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] 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] 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] 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] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH]

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Osteosclerosis: An abnormal hardening or increased density of bone tissue. [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] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [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]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [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] Parathyroidectomy: Excision of one or both of the parathyroid glands. [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] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic fracture: A broken bone caused by disease, often by the spread of cancer to the bone. [NIH] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] 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]

Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be

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used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] 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] Periarthritis: Inflammation of the tissues around a joint. [EU] 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] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [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] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by

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phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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] Phosphorous: Having to do with or containing the element phosphorus. [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] Photobiology: The branch of biology dealing with the effect of light on organisms. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] 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]

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Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Placental tissue: The tissue intervening between fetal blood and maternal blood in the placenta; it acts as a selective membrane regulating the passage of substances from the maternal to the fetal blood. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [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]

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Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [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] Polyarthritis: An inflammation of several joints together. [EU] Polycyclic Hydrocarbons: Hydrocarbons consisting of two or more fused ring structures. [NIH]

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] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [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] Population Characteristics: Qualities and characterization of various types of populations within a social or geographic group, with emphasis on demography, health status, and socioeconomic factors. [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]

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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] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] Potentiate: 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] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] 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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [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] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [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]

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Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [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] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [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

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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 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] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [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] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [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

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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] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [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.

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Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] 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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] 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]

Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [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] Rachitis: A disturbance of the calcium/phosphorus metabolism which occurs in the

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growing child as a result of vitamin-D deficiency. [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 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] Radioactive: Giving off radiation. [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] 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] 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] Radius: The lateral bone of the forearm. [NIH] 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] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU]

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Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [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] 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] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and

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relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [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 failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [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] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [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] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH]

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Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] 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] 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] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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

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sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [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] 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] Secosteroids: Steroids in which fission of one or more ring structures and concomitant addition of a hydrogen atom at each terminal group has occurred. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and

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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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex 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 or male. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [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] Sigmoidal: S-shaped; shaped like the letter sigma. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an

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activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solar Energy: Energy transmitted from the sun in the form of electromagnetic radiation. [NIH]

Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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]

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Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [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] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Stabilization: The creation of a stable state. [EU] 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 Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the

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ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by

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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]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Subtrochanteric: Below a trochanter. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] 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] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH]

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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]

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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] 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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]

hydroxyethyl)-4-

Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [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] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and

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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] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue 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] Tonicity: The normal state of muscular tension. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [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

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microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [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 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]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [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] Transurethral: Performed through the urethra. [EU]

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Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [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] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor 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] Tumor model: A type of animal model which can be 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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10

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megahertz. [NIH] Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. [NIH]

Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] 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] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] 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] 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] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together

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to form veins. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viremia: The presence of viruses in the blood. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [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] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH]

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Vitamin D

Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xenopus: An aquatic genus of the family Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes. [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] Zinc Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock. [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]

351

INDEX 1 1-phosphate, 185, 267 A Abdomen, 267, 276, 277, 295, 308, 312, 324, 341, 342, 344, 349 Abdominal, 11, 153, 267, 281, 290, 313, 315, 323, 325, 329, 347 Abdominal fat, 267, 281 Abdominal Pain, 267, 313, 347 Aberrant, 42, 58, 267 Ablation, 74, 113, 164, 267 Acatalasia, 267, 280 Acceptor, 267, 323 Acetylcholine, 267, 282, 319 Acne, 187, 267 Actin, 68, 81, 86, 267 Acute myeloid leukemia, 267, 330 Acyl, 267, 296 Adaptability, 267, 281 Adenocarcinoma, 48, 205, 267, 303, 331 Adenoma, 20, 83, 138, 267 Adenosine, 267, 273, 326 Adipocytes, 136, 267, 310 Adipose Tissue, 50, 167, 267 Adjunctive Therapy, 19, 268 Adjuvant, 168, 169, 268, 299 Adolescence, 12, 22, 25, 140, 268 Adrenal Cortex, 268, 269, 287, 288, 296, 330, 336 Adrenergic, 268, 272, 295 Adrenergic beta-Antagonists, 268, 272 Adverse Effect, 46, 222, 268, 339 Aerobic, 268, 287, 316 Afferent, 268, 310, 326 Affinity, 35, 39, 40, 48, 53, 55, 105, 175, 192, 219, 268, 312, 315, 340 Affinity Chromatography, 39, 268 Age Groups, 222, 268 Aged, 80 and Over, 268 Ageing, 78, 104, 112, 136, 187, 268 Aggressiveness, 30, 268 Agonist, 41, 105, 268, 334, 343 Albumin, 73, 268, 327 Aldosterone, 105, 206, 269 Alendronate, 90, 136, 168, 199, 230, 238, 269 Algorithms, 269, 276 Alimentary, 78, 112, 214, 269

Alkaline, 4, 269, 270, 278, 326, 344 Alkaline Phosphatase, 4, 269 Alkalosis, 269, 344 Alkylating Agents, 194, 269 Alleles, 67, 97, 269, 312 Allogeneic, 58, 269, 302 Allograft, 217, 269 Aloe, 211, 269 Alopecia, 57, 74, 122, 187, 201, 269, 288 Alpha Particles, 269, 334 Alternative medicine, 14, 233, 269 Alveolar Process, 269, 336 Alveoli, 269, 290 Ameliorating, 204, 269 Amino Acid Motifs, 270, 286 Amino Acid Sequence, 72, 184, 191, 205, 209, 270, 271, 286, 297, 299 Aminolevulinic Acid, 78, 80, 137, 270 Amino-terminal, 55, 205, 270 Ammonia, 270, 348 Amniotic Fluid, 270, 300 Amplification, 58, 177, 270 Anabolic, 41, 222, 270, 291 Anaerobic, 206, 270, 287 Anaesthesia, 270, 306 Anal, 29, 270, 295, 312 Analgesics, 234, 270 Analogous, 270, 346 Anaphylatoxins, 270, 285 Anaplasia, 270, 331 Anatomical, 270, 273, 293, 306, 338 Androgens, 10, 45, 51, 268, 270, 287 Anemia, 154, 155, 249, 271, 278, 284, 298, 322, 325 Anesthesia, 270, 271 Angiogenesis, 59, 60, 271, 314 Angiotensin-Converting Enzyme Inhibitors, 271, 272 Angiotensinogen, 271, 336 Animal model, 32, 49, 62, 74, 186, 271, 347 Anions, 198, 269, 271, 309 Annealing, 271, 328 Anode, 271 Anorexia, 14, 271, 322 Anthracyclines, 194, 271 Antiallergic, 271, 288 Antiangiogenic, 186, 271 Antibacterial, 271, 275, 309, 341

352

Vitamin D

Antibiotic, 194, 211, 271, 289, 292, 296, 318, 323, 328, 341, 342 Antibodies, 36, 186, 271, 274, 302, 304, 306, 313, 317, 327 Antibody, 268, 271, 272, 277, 285, 302, 303, 305, 306, 308, 309, 314, 317, 334, 341, 350 Anticoagulant, 271, 332 Antidote, 272, 311 Antifungal, 272, 275 Antigen, 36, 60, 268, 271, 272, 285, 289, 300, 303, 305, 306, 308, 314 Antigen-Antibody Complex, 272, 285 Antigen-presenting cell, 272, 289 Antihypertensive, 231, 272 Antihypertensive Agents, 231, 272 Anti-infective, 272, 304, 308 Anti-inflammatory, 19, 187, 272, 273, 288, 290, 300, 324, 329 Anti-Inflammatory Agents, 272, 273, 288 Antimetabolite, 272, 290, 298 Antineoplastic, 269, 272, 279, 288, 292, 298, 299, 300, 323 Antineoplastic Agents, 269, 272 Antioxidant, 10, 44, 139, 206, 207, 214, 272, 273 Antiproliferative, 47, 60, 123, 147, 212, 272 Antirheumatic Agents, 190, 272 Antiseptic, 272, 280, 350 Antiviral, 272, 299, 307, 325 Anuria, 272, 309 Anus, 270, 272, 277, 335 Apoptosis, 7, 8, 22, 27, 32, 48, 58, 59, 60, 73, 78, 85, 102, 117, 184, 272, 280 Aqueous, 211, 273, 274, 289, 293, 304, 310 Arachidonic Acid, 36, 273, 311, 331 Arginine, 270, 273, 319, 321, 333 Aromatic, 273, 315, 326 Arrestin, 41, 273 Arterial, 273, 305, 332, 343 Arteries, 273, 276, 287, 315, 318, 345 Arteriolar, 273, 277, 336 Arterioles, 273, 276, 279 Articular, 77, 273, 322 Ascorbic Acid, 189, 201, 207, 273, 305, 323 Aspirin, 31, 273 Assay, 4, 9, 32, 41, 50, 176, 273, 305 Astringent, 273, 280, 350 Asymptomatic, 169, 185, 267, 273 Ataxia, 249, 273, 344 ATP, 57, 273, 291, 300, 312, 326, 332 Atrial, 48, 65, 273 Atrium, 273, 348

Atrophy, 187, 217, 234, 248, 249, 274 Attenuated, 274, 291 Autoantibodies, 187, 274 Autoantigens, 274 Autoimmune disease, 62, 186, 187, 274, 317 Autoimmune Hepatitis, 96, 274 Autologous, 274, 302 Autologous bone marrow transplantation, 274, 302 Autopsy, 44, 274 Avian, 39, 65, 66, 74, 274 B Bactericidal, 274, 348 Bacteriophage, 274, 346, 349 Bacteriostatic, 274, 296 Basal Ganglia, 273, 274, 333 Basal Ganglia Diseases, 273, 274 Basal Metabolism, 181, 274 Base, 14, 52, 185, 211, 269, 274, 288, 289, 290, 299, 309, 310, 316, 320, 325, 326, 328, 344 Basement Membrane, 274, 297 Bed Rest, 11, 275 Benign, 130, 185, 205, 267, 275, 277, 298, 302, 318, 334 Benign prostatic hyperplasia, 130, 205, 275, 298 Benzoates, 205, 275 Benzoic Acid, 201, 275 Benzyl Alcohol, 211, 275 Bile, 21, 104, 126, 158, 181, 231, 275, 299, 304, 312, 330, 342 Bile Acids, 21, 104, 126, 275, 342 Bile Acids and Salts, 275 Bile Ducts, 275, 330 Bilirubin, 269, 275 Binding Sites, 95, 275 Bioassay, 81, 275 Bioavailability, 16, 81, 127, 199, 275 Bioavailable, 44, 275 Biochemical reactions, 197, 275 Biological response modifier, 275, 276, 307 Biological therapy, 275, 302 Biomarkers, 7, 10, 37, 276 Biopsy, 35, 234, 276 Biosynthesis, 51, 81, 97, 98, 177, 183, 197, 273, 276, 287, 304, 321, 331 Biotechnology, 64, 77, 233, 245, 247, 248, 249, 250, 276 Biotic, 276, 348 Biotin, 176, 177, 181, 189, 206, 207, 276

Index 353

Biotransformation, 44, 276 Bivalent, 276, 315 Bladder, 231, 275, 276, 306, 317, 331, 336, 337, 348 Blastocyst, 276, 286, 323, 327, 347 Bloating, 276, 306, 313 Blood Coagulation, 276, 278, 345 Blood Glucose, 276, 303, 307 Blood pressure, 48, 73, 82, 115, 187, 232, 272, 276, 279, 299, 305, 317, 340 Blot, 17, 276, 305 Blotting, Western, 276, 305 Body Composition, 50, 277 Body Fluids, 269, 276, 277, 278, 292, 340, 347 Body Mass Index, 13, 45, 103, 277, 323 Bone Cysts, 202, 277 Bone Density, 5, 10, 15, 38, 46, 62, 97, 169, 195, 199, 277 Bone Development, 25, 277 Bone metastases, 191, 277, 296 Bone Remodeling, 49, 114, 147, 218, 277 Bone Resorption, 7, 32, 33, 178, 191, 195, 199, 200, 217, 277, 278 Boron, 132, 142, 277 Boron Neutron Capture Therapy, 277 Bowel, 20, 126, 214, 270, 277, 291, 307, 308, 310, 325, 342, 347 Bowel Movement, 277, 291, 342 Brachytherapy, 277, 308, 309, 334, 350 Bradykinin, 277, 319, 327 Branch, 263, 278, 313, 324, 326, 333, 341, 344 Breakdown, 189, 191, 231, 278, 291, 299, 321 Buccal, 278, 313 Burns, 231, 278 Burns, Electric, 278 Bypass, 196, 278 C Cadmium, 29, 164, 278 Cadmium Poisoning, 278 Calcaneus, 115, 129, 278, 344 Calcifediol, 198, 278 Calcification, 195, 202, 278 Calcitriol, 6, 39, 59, 60, 99, 116, 144, 182, 195, 198, 212, 219, 254, 278 Calcium Carbonate, 19, 20, 90, 278 Calcium channel blocker, 272, 278 Calcium Channel Blockers, 272, 278 Calcium Channels, 16, 279 Calcium Citrate Malate, 174, 279

Calcium Isotopes, 120, 128, 279 Calcium Oxalate, 18, 279, 323 Calculi, 279 Callus, 279, 293, 298 Calorimeter, 274, 279 Capillary, 16, 277, 279, 348 Capsules, 279, 298, 299 Carbohydrate, 141, 279, 287, 301, 328 Carboplatin, 60, 279 Carcinogen, 7, 51, 279 Carcinogenesis, 8, 29, 30, 46, 59, 63, 85, 194, 279, 282 Carcinogenic, 269, 279, 307, 321, 330, 342, 348 Carcinoma, 51, 98, 182, 184, 204, 209, 279 Cardiac, 48, 65, 154, 158, 268, 279, 295, 311, 318, 342, 343 Cardiomyopathy, 154, 279 Cardiovascular, 48, 101, 150, 207, 231, 279, 281, 311 Cardiovascular disease, 279, 281 Cardiovascular System, 207, 279 Carotene, 44, 206, 207, 280, 337 Carotenoids, 44, 280 Carrier Proteins, 280, 327 Case report, 122, 280, 283 Case series, 280, 283 Caspase, 151, 280 Catabolism, 104, 145, 163, 280 Catalase, 207, 267, 280 Cataract, 182, 280 Catechol, 10, 280 Causal, 42, 280, 295 Cause of Death, 207, 280 Caveolae, 35, 280 Caveolins, 280, 284 Cecum, 280, 310 Celiac Disease, 14, 154, 280 Cell Cycle, 22, 37, 40, 48, 57, 58, 60, 63, 194, 281, 283, 288, 302, 332 Cell Death, 7, 51, 151, 272, 281, 300, 318 Cell Differentiation, 58, 62, 85, 105, 187, 196, 203, 210, 214, 281, 340 Cell Division, 248, 274, 281, 302, 314, 315, 316, 327, 330, 338 Cell membrane, 279, 280, 281, 282, 290, 309, 326, 328, 349 Cell Membrane Structures, 280, 281 Cell Physiology, 58, 281 Cell proliferation, 9, 22, 32, 41, 42, 48, 187, 196, 281, 308, 340 Cell Respiration, 281, 316, 336

354

Vitamin D

Cell Survival, 281, 302 Cell Transplantation, 58, 281, 302 Cellulose, 281, 327 Central fat distribution, 36, 281 Central Nervous System, 198, 267, 279, 281, 299, 301, 302, 311, 317 Centrifugation, 281, 316 Cerebellar, 273, 282, 335 Cerebral, 145, 273, 274, 282, 295, 324, 333 Cerebral Palsy, 145, 282 Cerebrum, 282, 347 Cervical, 79, 282 Cervix, 282, 336 Character, 282, 289, 301 Check-up, 167, 282 Chemoprevention, 14, 20, 63, 85, 282 Chemopreventive, 7, 47, 56, 59, 63, 121, 282 Chemotactic Factors, 282, 285 Chemotherapy, 7, 45, 51, 58, 168, 169, 194, 282 Chloride Channels, 16, 282 Chlorine, 181, 282 Cholecalciferol, 9, 69, 142, 159, 182, 183, 194, 206, 282 Cholesterol, 164, 180, 183, 197, 210, 222, 275, 280, 282, 287, 292, 305, 334, 338, 342, 343 Choline, 7, 22, 37, 282 Chromaffin System, 282, 294 Chromatin, 17, 72, 187, 272, 282, 319, 320 Chromium, 206, 207, 282 Chromosomal, 20, 71, 270, 282, 299, 327 Chromosome, 20, 187, 193, 283, 286, 302, 311, 312, 338, 346 Chronic Disease, 221, 283, 311 Chronic renal, 4, 11, 36, 120, 121, 225, 283, 328 Circulatory system, 283, 294 CIS, 37, 42, 47, 49, 174, 180, 184, 191, 202, 209, 283, 337 Cisplatin, 60, 147, 283 Citric Acid, 208, 283 Citrus, 273, 283 Clamp, 16, 283 Clathrin, 283, 284, 294 Clear cell carcinoma, 283, 290 Cleave, 60, 283 Climacteric, 208, 283 Clinical Medicine, 283, 329 Clinical study, 179, 283, 287

Clinical trial, 6, 13, 14, 19, 20, 24, 58, 59, 60, 167, 170, 245, 283, 287, 288, 332, 334 Clone, 16, 20, 36, 205, 283 Cloning, 20, 30, 35, 42, 43, 67, 71, 85, 276, 284 Cluster Analysis, 56, 284 Coagulation, 276, 284, 327, 345 Coated Vesicles, 283, 284, 294 Cobalt, 189, 284 Cod Liver Oil, 211, 284, 293 Codon, 75, 76, 110, 129, 284, 299 Coenzyme, 273, 284, 319 Cofactor, 284, 332, 345 Cognition, 14, 29, 284 Cohort Studies, 31, 284, 295 Colitis, 215, 284 Collagen, 79, 97, 120, 122, 152, 194, 274, 284, 297, 298, 299, 314, 327, 330 Collapse, 278, 284 Colloidal, 269, 285, 325 Colorectal, 7, 20, 30, 84, 88, 116, 138, 149, 152, 155, 185, 230, 285 Colorectal Cancer, 7, 30, 84, 88, 138, 155, 185, 285 Combination chemotherapy, 193, 285 Combination Therapy, 285, 296 Complement, 42, 270, 285, 299, 313, 327 Complementary and alternative medicine, 135, 162, 285 Complementary medicine, 135, 285 Complete remission, 285, 336 Computational Biology, 245, 247, 285 Computed tomography, 25, 277, 286 Computerized axial tomography, 286 Computerized tomography, 286 Conception, 286, 298, 342 Concomitant, 176, 286, 338 Cone, 286, 326 Confusion, 286, 348 Congestive heart failure, 82, 108, 286 Conjugated, 7, 175, 176, 275, 286, 289, 320, 337 Conjugation, 276, 286 Connective Tissue, 273, 277, 284, 286, 298, 299, 313, 315, 337, 338, 342, 343 Consciousness, 270, 286, 291 Consensus Sequence, 58, 270, 286, 287 Conserved Sequence, 270, 286 Consumption, 84, 138, 139, 176, 287, 320, 336 Continuum, 26, 27, 53, 287 Contraindications, ii, 287

Index 355

Control group, 11, 15, 19, 287, 330, 334 Controlled clinical trial, 23, 287 Controlled study, 46, 287 Coordination, 19, 287, 317 Coproporphyrinogen Oxidase, 51, 287 Cornea, 182, 287, 342, 348 Corneum, 287, 295 Coronary, 180, 279, 281, 287, 315, 318 Coronary heart disease, 279, 281, 287 Coronary Thrombosis, 287, 315, 318 Corpus, 287, 300, 313, 318, 330 Corpus Luteum, 287, 313, 330 Cortex, 273, 287, 322, 335 Corticosteroid, 84, 287, 329, 342 Cortisol, 17, 206, 269, 288 Cortisone, 288, 290, 329 Creatinine, 4, 20, 217, 288, 310 Critical Illness, 83, 288 Crossing-over, 288, 335 Cross-Sectional Studies, 288, 295 Cultured cells, 73, 288 Curative, 288, 319, 338, 344 Cutaneous, 79, 87, 288, 313 Cyclic, 73, 208, 222, 288, 302, 319, 326, 331 Cyclin, 22, 37, 52, 58, 102, 113, 288 Cyclin-Dependent Kinases, 58, 288 Cyclohexanes, 179, 202, 288 Cyclophosphamide, 19, 187, 288 Cyclosporine, 4, 217, 288 Cyst, 277, 288 Cysteine, 58, 206, 288, 294, 343 Cystine, 288 Cytidine, 8, 288 Cytochrome, 16, 19, 36, 70, 71, 75, 87, 102, 163, 288 Cytokine, 57, 141, 289, 308 Cytoplasm, 40, 122, 207, 272, 281, 289, 293, 301, 315, 319, 337 Cytosine, 288, 289 Cytotoxic, 187, 193, 194, 289, 334, 340 Cytotoxicity, 188, 209, 283, 289 D Dairy Products, 84, 103, 138, 176, 289, 338 Databases, Bibliographic, 245, 289 Daunorubicin, 289, 292 Deamination, 289, 348 Decarboxylation, 287, 289, 321, 333 Decubitus, 210, 211, 289 Decubitus Ulcer, 210, 211, 289 Degenerative, 211, 289, 303, 322, 337 Deletion, 47, 128, 272, 289, 312 Denaturation, 289, 328

Dendrites, 289 Dendritic, 68, 88, 289, 314 Dendritic cell, 68, 88, 289 Density, 3, 5, 6, 10, 19, 24, 28, 36, 45, 46, 69, 78, 79, 80, 82, 86, 91, 92, 94, 104, 105, 114, 118, 119, 137, 143, 145, 147, 150, 152, 168, 234, 277, 281, 290, 292, 321, 323 Dental Caries, 290, 298 Dentition, 5, 290 Deoxycytidine, 8, 290 Deoxyribonucleic, 119, 128, 290 Deoxyribonucleic acid, 119, 128, 290 Deoxyribonucleotides, 290 Deoxyuridine, 7, 290 Depolarization, 290, 340 Deprivation, 33, 290 Dermal, 27, 86, 290 Dermatosis, 182, 290 DES, 112, 270, 290 Deuterium, 290, 304 Dexamethasone, 42, 60, 290 Diabetes Mellitus, 76, 96, 187, 290, 300, 303 Diagnostic procedure, 173, 233, 290, 339 Dialyzer, 290, 302 Diaphragm, 290, 328 Diarrhea, 14, 290, 310, 313 Diastolic, 291, 305 Diffusion, 291, 302 Digestion, 269, 275, 277, 291, 306, 308, 312, 320, 342 Digestive system, 171, 291 Digestive tract, 189, 291, 340 Dihydrotestosterone, 291, 335 Dihydroxy, 61, 64, 89, 117, 143, 182, 187, 194, 203, 213, 269, 291 Dilatation, 291, 330 Dilated cardiomyopathy, 77, 291 Dilution, 211, 291 Dimerization, 76, 175, 192, 291 Diploid, 291, 327 Direct, iii, 12, 41, 52, 62, 72, 73, 75, 175, 192, 237, 283, 291, 335 Disease Progression, 100, 232, 291 Dissociation, 42, 268, 291 Dissociative Disorders, 291 Distal, 15, 291, 309, 332 Diuretic, 291, 341 Diuretics, Thiazide, 272, 291 DNA Topoisomerase, 291, 300 Docetaxel, 60, 292 Domesticated, 292, 302

356

Vitamin D

Dorsal, 175, 192, 292, 328 Dorsum, 292 Dose-limiting, 204, 292 Dose-rate, 141, 292 Dosimetry, 81, 292 Doxorubicin, 147, 292 Drug Interactions, 17, 238, 239, 292 Duct, 292, 296, 323, 338 Duodenum, 275, 292, 342 Dyes, 292, 319 Dysgenesis, 191, 292 Dyslipidemia, 281, 292 Dyspareunia, 292, 296 Dysplasia, 249, 292 Dystrophy, 249, 292 E Edema, 292, 319 Effector, 39, 62, 267, 285, 292 Effector cell, 62, 292 Efficacy, 7, 16, 19, 20, 24, 45, 46, 51, 56, 63, 91, 109, 129, 143, 148, 195, 292 Egg Yolk, 180, 293 Elastin, 284, 293, 297 Elective, 11, 73, 293 Electrolysis, 271, 293 Electrolyte, 269, 287, 293, 310, 316, 329, 340 Electrons, 272, 274, 293, 309, 323, 334 Electroplating, 280, 293 Embolus, 293, 306 Embryo, 276, 277, 281, 293, 298, 300, 306, 315, 322 Embryogenesis, 42, 44, 293 Emodin, 269, 293 Emollient, 293, 301, 310, 316, 321 Emulsion, 211, 293 Enamel, 5, 290, 293, 309 Encapsulated, 293, 312 Encephalitis, 293, 294 Encephalomyelitis, 62, 64, 67, 198, 293 Endemic, 31, 294, 341 Endocrine Glands, 294, 304, 324 Endocrine System, 61, 63, 106, 294 Endocytosis, 280, 294 Endometrial, 25, 26, 53, 185, 294, 323 Endometrium, 294, 315, 347 Endopeptidases, 294, 331 Endosomes, 18, 294 Endothelial cell, 16, 40, 60, 186, 294, 344 Endothelium, 48, 294, 319, 327 Endothelium, Lymphatic, 294 Endothelium, Vascular, 294

Endothelium-derived, 294, 319 Endotoxic, 294, 312 Endotoxin, 294, 347 End-stage renal, 101, 283, 294, 328 Energy balance, 294, 310 Enhancer, 39, 72, 295, 336 Enterocytes, 16, 164, 295 Environmental Exposure, 49, 295, 321 Environmental Health, 78, 80, 130, 137, 244, 246, 295 Enzymatic, 32, 44, 212, 278, 280, 285, 288, 290, 295, 296, 328, 337 Enzyme Inhibitors, 295, 327 Epidemic, 295, 341 Epidemiologic Studies, 38, 295 Epidemiological, 10, 20, 47, 56, 295 Epidermal, 41, 51, 164, 212, 222, 295, 309, 314 Epidermal Growth Factor, 41, 164, 295 Epidermis, 9, 197, 213, 287, 295, 304, 309, 330 Epigastric, 295, 323 Epinephrine, 268, 295, 347 Epithelial Cells, 8, 9, 15, 63, 165, 184, 205, 209, 295, 303 Epithelial ovarian cancer, 23, 184, 295 Epithelium, 50, 274, 294, 295, 309, 331 Erythrocytes, 271, 277, 295 Erythromycin, 71, 296 Erythropoietin, 202, 296 Esophagus, 291, 296, 342 Essential Tremor, 249, 296 Esterification, 212, 296 Estradiol, 16, 51, 113, 146, 159, 201, 296 Estrogen receptor, 45, 52, 79, 82, 91, 92, 97, 103, 104, 119, 177, 184, 209, 296 Estrogen receptor negative, 91, 296 Estrogen receptor positive, 45, 296 Estrogen Replacement Therapy, 11, 296 Ethnic Groups, 46, 296 Etidronate, 84, 136, 199, 238, 296 Eukaryotic Cells, 296, 306, 320, 321 Excipient, 208, 296 Excrete, 272, 296, 309, 336 Exocrine, 296, 323 Exogenous, 10, 23, 29, 47, 276, 296, 331, 347 Exon, 92, 297 Extensor, 297, 332 External-beam radiation, 297, 309, 334, 350

Index 357

Extracellular, 7, 11, 21, 41, 43, 48, 49, 96, 148, 195, 279, 286, 294, 297, 298, 314, 322, 340, 344 Extracellular Matrix, 7, 43, 286, 297, 298, 314, 322 Extracellular Matrix Proteins, 297, 314 Extracellular Space, 48, 297 Extrarenal, 115, 148, 297 F Facial, 86, 297, 324 Family Planning, 245, 297 Fat, 7, 22, 37, 50, 167, 168, 185, 194, 211, 234, 267, 273, 275, 277, 280, 281, 287, 289, 293, 297, 310, 311, 312, 317, 323, 328, 337, 338, 340 Fatigue, 14, 155, 297, 302 Fatty acids, 21, 117, 180, 269, 281, 297, 301, 331 Febrile, 297, 341 Femoral, 4, 5, 118, 120, 297, 303 Femoral Fractures, 118, 297 Femoral Neck Fractures, 297, 303 Femur, 4, 46, 62, 95, 136, 297, 303 Fenbendazole, 189, 297 Fermentation, 297, 298 Fetal Blood, 297, 327 Fetal Development, 44, 298 Fetus, 24, 44, 201, 277, 296, 297, 298, 327, 329, 348 Fibrinogen, 298, 327, 344 Fibroblasts, 298, 308 Fibrosis, 155, 202, 217, 249, 298, 338 Filler, 199, 298 Finasteride, 201, 298 Fluorescence, 16, 298 Fluorine, 298 Fluorouracil, 7, 298 Folate, 7, 22, 30, 37, 85, 94, 133, 290, 298 Fold, 8, 25, 26, 53, 185, 298 Folic Acid, 132, 175, 176, 181, 189, 199, 206, 207, 298, 311 Follicles, 298 Food Preservatives, 58, 298 Forearm, 45, 276, 298, 334 Fracture Healing, 216, 298 Frail Elderly, 230, 298 Fructose, 66, 298 Fungi, 272, 286, 299, 301, 315, 316, 350 Fungistatic, 275, 299 G Gallbladder, 267, 275, 291, 299 Gamma-interferon, 64, 299

Ganglia, 267, 274, 299, 319, 325 Ganglionic Blockers, 272, 299 Gangrene, 211, 267, 299 Gas, 270, 279, 282, 291, 298, 299, 304, 306, 313, 319, 320, 348 Gastrectomy, 91, 299 Gastric, 96, 198, 295, 299, 304 Gastrin, 96, 299, 303 Gastrointestinal, 199, 214, 233, 234, 278, 295, 299, 310, 311, 341, 343, 347 Gastrointestinal tract, 233, 234, 299, 310, 311, 341, 347 Gelatin, 299, 301, 344 Gene Expression, 21, 22, 32, 37, 44, 47, 49, 51, 54, 56, 58, 69, 70, 73, 74, 75, 76, 77, 103, 104, 115, 122, 151, 163, 193, 195, 210, 250, 299 Genetic Code, 299, 320 Genetic Engineering, 276, 284, 299 Genetic Markers, 12, 299 Genetic Techniques, 210, 299 Genetic testing, 300, 328 Genetics, 13, 34, 57, 94, 98, 104, 109, 286, 299, 300 Genistein, 51, 98, 144, 147, 165, 300 Genital, 283, 300, 348 Genitourinary, 300, 348 Genomics, 21, 22, 32, 37, 95, 300 Genotype, 12, 20, 25, 81, 82, 97, 98, 103, 114, 128, 232, 300, 326 Germ Cells, 300, 314, 321, 323, 340, 344 Germ Layers, 277, 300 Gestation, 24, 300, 327 Gestational, 44, 300 Gestational Age, 44, 300 Giant Cells, 277, 300, 338 Gland, 4, 9, 12, 56, 144, 164, 165, 205, 268, 282, 288, 300, 313, 323, 324, 327, 331, 334, 338, 342, 343, 345 Glioma, 102, 300 Globus Pallidus, 274, 300, 333 Glomerular, 300, 310, 336 Glucocorticoid, 44, 46, 184, 191, 193, 209, 290, 300, 329 Glucose, 75, 189, 248, 273, 276, 281, 282, 290, 300, 302, 307, 334, 338, 341 Glucose Intolerance, 290, 300 Glutamic Acid, 298, 300, 330 Glutathione Peroxidase, 207, 301, 339 Gluten, 15, 133, 234, 280, 301 Glycerol, 211, 301, 326 Glycerophospholipids, 301, 326

358

Vitamin D

Glycine, 58, 270, 275, 301 Glycoprotein, 16, 296, 298, 300, 301, 344, 347 Glycosidic, 271, 301, 321 Goats, 289, 301 Goblet Cells, 295, 301 Gonad, 36, 301 Gonadal, 191, 301, 342 Gonadotropin, 23, 301 Governing Board, 301, 329 Gp120, 301, 325 Grade, 208, 301, 331 Graft, 187, 301, 304, 318 Graft-versus-host disease, 301, 318 Granulocytes, 301, 311, 340, 350 Grasses, 298, 301 Growth, 7, 9, 10, 17, 24, 25, 26, 27, 30, 33, 36, 41, 44, 46, 47, 48, 49, 52, 53, 54, 57, 59, 62, 64, 74, 76, 77, 78, 91, 98, 99, 103, 108, 110, 113, 114, 117, 122, 136, 144, 149, 151, 164, 165, 174, 186, 189, 190, 191, 193, 194, 198, 200, 201, 202, 212, 213, 216, 220, 222, 249, 268, 271, 272, 273, 274, 276, 281, 295, 298, 299, 301, 302, 304, 307, 308, 313, 318, 321, 322, 323, 327, 332, 336, 338, 345, 346, 347, 349 Growth factors, 30, 47, 59, 114, 302 Guanylate Cyclase, 302, 319 Guinea Pigs, 68, 151, 302 H Habitat, 189, 302 Haemodialysis, 140, 302 Hair follicles, 58, 302 Haploid, 302, 327 Haplotypes, 79, 302 Haptens, 268, 302 Headache, 302, 329 Health Status, 11, 148, 302, 328 Heart failure, 230, 271, 302 Heartbeat, 302, 343 Helix-loop-helix, 175, 192, 302 Hematopoietic Stem Cell Transplantation, 107, 302 Heme, 51, 270, 275, 287, 288, 302 Hemodialysis, 81, 118, 278, 290, 302, 310 Hemoglobin, 26, 27, 53, 271, 295, 302, 303, 311 Hemoglobinuria, 249, 303 Hemorrhage, 302, 303, 342 Hepatic, 65, 121, 181, 269, 303 Hepatitis, 31, 303 Hepatocellular, 31, 78, 303

Hepatocellular carcinoma, 31, 78, 303 Hepatocytes, 17, 303 Hereditary, 18, 66, 109, 303, 337 Heredity, 299, 300, 303 Heterodimer, 72, 174, 175, 192, 303 Heterogeneity, 10, 268, 303 Hip Fractures, 62, 138, 297, 303 Histology, 33, 303, 324 Homodimer, 303, 346 Homogeneous, 287, 303 Homologous, 41, 269, 276, 288, 303, 338, 343, 346 Hormonal, 10, 11, 12, 16, 36, 44, 47, 49, 57, 62, 73, 174, 212, 225, 274, 287, 296, 303, 349 Hormonal therapy, 11, 303 Hormone Antagonists, 55, 303 Hormone Replacement Therapy, 4, 23, 35, 45, 207, 304 Hormone therapy, 303, 304 Horny layer, 295, 304 Host, 31, 100, 187, 201, 210, 274, 304, 311, 349 Human Development, 189, 244, 304 Human growth hormone, 106, 304, 341 Humoral, 48, 304 Humour, 304 Hybrid, 20, 29, 39, 186, 283, 304 Hybridization, 30, 304 Hybridomas, 304, 308 Hydrochloric Acid, 189, 304 Hydrogen Peroxide, 207, 280, 301, 304 Hydrolysis, 276, 283, 304, 326, 328, 332 Hydrophilic, 211, 304 Hydrophobic, 206, 301, 304, 309 Hydroxylation, 18, 19, 36, 71, 195, 219, 220, 248, 278, 304 Hydroxylysine, 284, 305 Hydroxyproline, 284, 305 Hypercalciuria, 6, 18, 204, 305 Hypercholesterolemia, 55, 90, 292, 305 Hyperplasia, 12, 182, 305 Hypersensitivity, 68, 305, 311, 337 Hypertension, 21, 129, 187, 217, 268, 271, 272, 279, 281, 302, 305, 319 Hyperthyroidism, 55, 305 Hypertrophy, 275, 305 Hypervitaminosis, 72, 305 Hypothalamus, 305, 327, 341 Hypovitaminosis, 4, 24, 101, 137, 144, 305 Hysterectomy, 191, 207, 305

Index 359

I Id, 69, 131, 153, 199, 255, 262, 264, 305 Idiopathic, 137, 305, 338 Ileum, 214, 280, 305, 349 Imaging procedures, 305, 346 Imidazole, 276, 305 Immaturity, 68, 305 Immune function, 305, 346 Immune response, 31, 176, 198, 212, 268, 272, 274, 288, 302, 305, 306, 313, 343, 347, 349 Immunoassay, 108, 305 Immunoblotting, 9, 58, 305 Immunodeficiency, 64, 70, 100, 248, 305 Immunogenic, 306, 312 Immunoglobulin, 271, 306, 317, 339 Immunohistochemistry, 9, 306 Immunologic, 68, 282, 300, 305, 306, 334 Immunology, 88, 176, 268, 306 Immunosuppressant, 269, 298, 306 Immunosuppressive, 4, 187, 217, 288, 300, 306, 343 Immunosuppressive therapy, 4, 217, 306 Impairment, 207, 217, 233, 273, 306, 315 Implant radiation, 306, 308, 309, 334, 350 In situ, 22, 30, 32, 38, 41, 45, 306 In Situ Hybridization, 30, 306 Incision, 306, 308, 331 Incontinence, 207, 306 Indicative, 206, 222, 306, 324, 348 Indigestion, 306, 310 Induction, 8, 60, 62, 65, 74, 78, 102, 117, 137, 149, 194, 270, 299, 306, 330 Infancy, 138, 170, 222, 306, 337 Infant, Newborn, 268, 306 Infarction, 10, 306 Infection, 5, 23, 31, 176, 234, 274, 275, 282, 293, 305, 306, 313, 337, 342, 350 Infertility, 228, 307 Inflammation, 7, 21, 73, 153, 182, 214, 267, 269, 272, 273, 284, 290, 293, 298, 303, 307, 311, 322, 325, 328, 333, 337, 342, 343, 347, 348 Inflammatory bowel disease, 105, 112, 145, 214, 233, 307 Infusion, 151, 208, 216, 307, 346 Ingestion, 278, 305, 307, 344 Initiation, 7, 45, 58, 75, 76, 94, 307, 330, 342, 346 Inoperable, 78, 307 Inorganic, 183, 283, 307, 317 Inositol, 60, 307

Insight, 7, 31, 33, 50, 58, 307 Insomnia, 307, 329 Insulator, 307, 317 Insulin, 10, 25, 26, 28, 30, 53, 57, 75, 98, 102, 114, 149, 199, 212, 307, 347 Insulin-dependent diabetes mellitus, 307 Insulin-like, 10, 25, 26, 30, 53, 57, 98, 114, 149, 307 Interferon, 70, 198, 299, 307 Interferon-alpha, 307 Interleukin-1, 187, 218, 307, 308 Interleukin-11, 218, 308 Interleukin-2, 75, 209, 308 Interleukin-4, 198, 308 Interleukin-6, 79, 218, 308 Interleukins, 187, 308 Internal Medicine, 13, 39, 44, 53, 177, 184, 197, 211, 294, 308, 337 Internal radiation, 308, 309, 334, 350 Interstitial, 217, 277, 297, 308, 309, 336, 350 Intestine, 28, 71, 183, 198, 216, 275, 277, 285, 308, 310 Intoxication, 101, 112, 151, 308 Intraocular, 182, 308 Intraocular pressure, 182, 308 Intravenous, 19, 78, 85, 189, 307, 308 Intrinsic, 43, 73, 175, 192, 268, 274, 308 Invasive, 308, 331 Invertebrates, 21, 308 Involuntary, 274, 296, 308, 318, 340, 341 Iodine, 181, 189, 207, 308 Ionizing, 269, 295, 309, 314, 334, 348 Ions, 274, 279, 282, 291, 293, 304, 309, 317 Iris, 287, 309, 333 Irradiation, 141, 277, 309, 350 Ischemia, 274, 289, 309 Isoniazid, 71, 160, 309 Isoprenoid, 183, 309 Isopropyl, 203, 309 J Joint, 29, 91, 118, 129, 143, 186, 202, 273, 309, 310, 322, 325, 343 K Kb, 49, 244, 309 Keratin, 309 Keratinocytes, 51, 54, 60, 61, 118, 309 Kidney Cortex, 309, 315 Kidney Disease, 108, 118, 120, 130, 167, 168, 169, 171, 201, 227, 244, 249, 254, 309, 336 Kidney Failure, 228, 294, 309, 310 Kidney Failure, Acute, 309, 310

360

Vitamin D

Kidney Failure, Chronic, 310 Kidney stone, 129, 310, 318, 323, 336 Kidney Transplantation, 4, 217, 310 Kinetic, 13, 61, 309, 310 Knee Injuries, 38, 310 L Labile, 197, 285, 310 Lacerations, 211, 310 Lactation, 108, 121, 281, 310, 330 Lactose Intolerance, 82, 310 Lanolin, 211, 310 Large Intestine, 182, 280, 285, 291, 308, 310, 335, 340 Latency, 106, 310 Latent, 44, 310, 329 Laxative, 293, 310, 316, 341 Least-Squares Analysis, 310, 335 Lens, 280, 310 Leptin, 12, 310 Lesion, 75, 311, 312, 339, 347 Leucine, 175, 192, 311 Leucocyte, 311 Leucovorin, 7, 311 Leukaemia, 143, 311 Leukemia, 58, 65, 85, 89, 105, 107, 139, 149, 153, 155, 156, 169, 187, 212, 248, 267, 292, 311 Leukocytes, 277, 282, 301, 307, 308, 311, 319, 347 Leukotrienes, 273, 311 Libido, 270, 311 Library Services, 262, 311 Lidocaine, 275, 311 Ligament, 311, 331 Ligands, 21, 35, 41, 49, 55, 68, 73, 86, 106, 175, 192, 205, 210, 311 Likelihood Functions, 311, 335 Linear Models, 29, 311, 335 Linkage, 20, 30, 271, 299, 311 Lipid, 57, 180, 222, 280, 281, 282, 301, 307, 311, 312, 317 Lipid A, 57, 281, 311 Lipophilic, 21, 211, 312 Lipopolysaccharides, 311, 312 Liposomal, 54, 312 Liver Extracts, 20, 181, 312 Lobe, 304, 312 Localization, 61, 65, 106, 164, 306, 312 Localized, 9, 27, 30, 59, 61, 211, 290, 293, 306, 312, 322, 327, 347 Locomotion, 312, 327 Logistic Models, 312, 335

Longitudinal study, 19, 25, 50, 88, 95, 312 Loop, 91, 160, 312 Loss of Heterozygosity, 30, 312 Low-calorie diet, 234, 312 Lubricants, 312, 325 Luciferase, 58, 312 Lumbar, 4, 29, 46, 312 Lupus, 186, 313, 343 Lupus Nephritis, 187, 313 Lutein Cells, 313, 330 Lymph, 198, 234, 282, 283, 294, 304, 313, 338, 343 Lymph node, 198, 234, 282, 313, 338 Lymphatic, 185, 294, 307, 313, 315, 340, 341, 345 Lymphatic system, 313, 340, 341, 345 Lymphocyte, 72, 176, 186, 272, 313, 314 Lymphoid, 271, 311, 313 Lymphoma, 248, 313 Lytic, 277, 313, 339, 349 M Macrophage, 32, 64, 66, 80, 308, 313 Major Histocompatibility Complex, 302, 308, 313 Malabsorption, 6, 14, 28, 33, 248, 280, 313 Malabsorption syndrome, 33, 313 Malignancy, 16, 48, 56, 185, 191, 200, 204, 313 Malignant, 8, 20, 52, 182, 205, 212, 248, 267, 272, 313, 318, 322, 334, 338 Malignant tumor, 182, 313, 322 Malnutrition, 269, 274, 313, 317 Mammary, 8, 9, 51, 56, 63, 85, 139, 144, 164, 184, 209, 313, 334, 343 Mammogram, 278, 313, 316 Mandible, 269, 314, 336 Man-made, 280, 314 Matrix metalloproteinase, 75, 314 Meat, 314, 338 Mediate, 39, 40, 52, 55, 74, 88, 126, 194, 314 Mediator, 40, 41, 308, 314 MEDLINE, 245, 247, 249, 314 Medullary, 314, 333 Megakaryocytes, 308, 314 Megaloblastic, 290, 298, 314 Meiosis, 40, 276, 314, 343 Melanin, 309, 314, 326, 347 Melanocytes, 314 Melanoma, 248, 277, 314 Membrane Glycoproteins, 314 Membrane Proteins, 280, 314 Memory, 271, 314

Index 361

Meninges, 281, 314 Menopause, 45, 62, 156, 178, 185, 195, 207, 314, 325, 329 Menstrual Cycle, 315, 329, 330 Menstruation, 155, 314, 315, 329 Mental Disorders, 171, 315 Mental Health, iv, 6, 169, 171, 244, 246, 315, 333 Mental Processes, 291, 315, 333 Mental Retardation, 170, 250, 315 Mesenchymal, 295, 315 Mesentery, 315, 325 Mesoderm, 315, 347 Metabolic disorder, 21, 315 Metallothionein, 29, 73, 315 Metaphase, 40, 276, 315 Metastasis, 314, 315 Metastasize, 185, 315, 338 Metastatic, 59, 184, 199, 200, 315, 338 Methionine, 7, 22, 30, 37, 160, 206, 315, 343 MI, 45, 129, 266, 315 Microbe, 315, 346 Microbiological, 213, 315 Microbiology, 315 Microcalcifications, 278, 316 Microgram, 6, 316 Micronutrients, 206, 316 Microorganism, 284, 316, 349 Microsomal, 19, 87, 316 Microtubules, 316, 323 Migration, 22, 44, 135, 316 Milligram, 176, 316 Milliliter, 277, 316 Mineral Oil, 211, 316 Mineralization, 19, 41, 42, 43, 141, 151, 195, 200, 216, 316, 322 Mineralocorticoids, 268, 287, 316 Mitochondria, 65, 151, 207, 316, 321 Mitochondrial Swelling, 316, 318 Mitosis, 273, 316 Mitotic, 292, 316 Mitotic inhibitors, 292, 316 Mobility, 39, 316 Mobilization, 40, 179, 216, 281, 316 Modeling, 75, 93, 182, 316 Modification, 7, 35, 50, 212, 299, 317, 333 Modulator, 28, 317 Molecular Structure, 20, 182, 317 Monitor, 83, 169, 288, 317, 320 Monoclonal, 304, 305, 309, 317, 334, 350 Monoclonal antibodies, 305, 317 Monocyte, 70, 88, 103, 317

Mononuclear, 71, 317, 347 Morphological, 268, 293, 314, 317 Morphology, 58, 280, 317 Motility, 60, 317 Mucins, 295, 301, 317 Mucosa, 20, 199, 234, 280, 295, 313, 317, 330, 342 Mucus, 317, 347 Multiple sclerosis, 62, 96, 141, 197, 198, 229, 317 Muscle Fibers, 317 Muscular Atrophy, 249, 317 Muscular Dystrophies, 292, 317 Mutagenesis, 21, 318 Mutagenic, 269, 318, 348 Mutagens, 318 Mycophenolate mofetil, 4, 217, 318 Myelin, 317, 318 Myelofibrosis, 156, 187, 318 Myeloma, 153, 318 Myocardial infarction, 10, 101, 287, 315, 318 Myocardium, 315, 318 Myopathy, 202, 318 Myotonic Dystrophy, 249, 318 N Naive, 59, 318 Nausea, 306, 318, 329, 348 NCI, 1, 38, 169, 171, 243, 283, 318 Necrosis, 191, 198, 272, 306, 315, 318, 338 Neomycin, 161, 211, 318 Neonatal, 44, 108, 318 Neoplasia, 116, 149, 230, 248, 318, 331 Neoplasm, 318, 338 Neoplastic, 9, 20, 51, 58, 63, 184, 193, 204, 270, 304, 312, 313, 318 Neostriatum, 318, 333 Nephrolithiasis, 18, 114, 318 Nephrologist, 123, 319 Nephron, 37, 90, 101, 319 Nephropathy, 217, 309, 319 Nephrosis, 319 Nephrotic, 225, 319 Nephrotic Syndrome, 225, 319 Nerve, 67, 268, 271, 273, 289, 314, 317, 319, 324, 326, 329, 337, 338, 342, 346 Nervous System, 48, 198, 249, 268, 271, 281, 314, 319, 325 Networks, 21, 319 Neural, 268, 299, 304, 319 Neuromuscular, 110, 267, 319, 328 Neuronal, 279, 319

362

Vitamin D

Neurosecretory Systems, 294, 319 Neutrons, 269, 277, 309, 319, 334 Neutrophils, 100, 301, 311, 319 Niacin, 181, 189, 319, 347 Niacinamide, 206, 319 Nitric Oxide, 40, 64, 80, 137, 319 Nitrogen, 9, 270, 288, 297, 310, 320, 347 Nuclear Matrix, 27, 111, 320 Nuclear Pore, 320 Nuclear Proteins, 39, 47, 320 Nuclease Protection Assays, 47, 320 Nucleic acid, 187, 192, 193, 205, 210, 289, 299, 304, 306, 318, 320, 341 Nucleic Acid Hybridization, 304, 320 Nucleolus, 320, 337 Nucleoproteins, 320 Nucleosomes, 18, 320 Nutritional Status, 176, 189, 320 O Observational study, 35, 320 Occult, 49, 320 Ocular, 182, 320 Odds Ratio, 321, 335 Ointments, 182, 321, 324, 350 Oligosaccharides, 12, 321 Oliguria, 309, 310, 321 Oncogene, 66, 185, 248, 321 Oncogenic, 56, 321, 332 Oocytes, 40, 321 Opacity, 280, 290, 321 Operon, 321, 330, 336 Ophthalmic, 182, 321 Opsin, 321, 337 Organ Culture, 321, 345 Organelles, 281, 283, 289, 314, 321 Organoleptic, 181, 321 Ornithine, 27, 321, 333 Ornithine Decarboxylase, 27, 321 Osmolarity, 96, 321 Osmoles, 321 Osmotic, 269, 316, 321, 322 Osseointegration, 277, 322 Ossification, 322, 337 Osteoarthritis, 38, 92, 156, 199, 200, 322 Osteoblasts, 41, 42, 43, 49, 54, 115, 184, 188, 194, 209, 215, 216, 322 Osteocalcin, 17, 25, 43, 67, 68, 70, 72, 73, 74, 76, 77, 79, 119, 122, 152, 322 Osteoclasts, 7, 32, 73, 80, 184, 188, 194, 209, 322 Osteocytes, 42, 322 Osteodystrophy, 201, 322

Osteogenesis, 178, 187, 212, 277, 322 Osteogenic sarcoma, 322 Osteolysis, 200, 322 Osteomalacia, 112, 156, 157, 167, 182, 195, 200, 216, 219, 222, 223, 228, 278, 322 Osteomyelitis, 141, 322 Osteopetrosis, 32, 322 Osteosarcoma, 40, 69, 70, 151, 322 Osteosclerosis, 182, 323 Ovaries, 185, 295, 323, 336, 339 Ovary, 287, 296, 301, 323, 342 Overexpress, 43, 323 Overweight, 38, 131, 234, 323 Ovulation, 23, 323 Ovum, 287, 300, 323, 330, 347 Ovum Implantation, 323, 347 Oxalate, 18, 323 Oxalic Acid, 279, 323 Oxidation, 61, 267, 272, 274, 276, 288, 301, 323 Oxidation-Reduction, 276, 323 Oxygenation, 207, 323 Oxytetracycline, 189, 323 P P53 gene, 185, 323 Paclitaxel, 60, 323 Palladium, 143, 323 Palliative, 323, 344 Pamidronate, 46, 78, 323 Pancreas, 14, 267, 276, 291, 307, 323, 324, 341, 347 Pancreatic, 212, 248, 324 Pancreatic cancer, 248, 324 Paneth Cells, 295, 324 Papilla, 27, 324 Paraffin, 211, 324 Parathyroid, 4, 5, 7, 11, 15, 29, 33, 39, 41, 47, 62, 72, 74, 83, 87, 89, 93, 96, 97, 102, 105, 107, 110, 111, 113, 116, 118, 119, 123, 127, 145, 148, 167, 201, 204, 216, 225, 227, 278, 324, 338, 344 Parathyroid Glands, 116, 324, 338 Parathyroidectomy, 81, 85, 225, 324 Parietal, 184, 324, 325, 328 Parietal Lobe, 324 Parotid, 165, 324, 338 Paroxysmal, 249, 324 Partial remission, 324, 336 Particle, 208, 314, 324, 346 Parturition, 324, 330 Patch, 16, 324, 346

Index 363

Pathogenesis, 5, 6, 42, 43, 55, 83, 108, 230, 233, 324 Pathologic, 87, 233, 273, 276, 287, 305, 324, 333, 336 Pathologic fracture, 87, 324 Pathologic Processes, 273, 324 Pathophysiology, 169, 225, 324 Patient Education, 254, 260, 262, 266, 324 Pedigree, 34, 324 Pelvic, 11, 185, 325, 331 Peptide, 26, 27, 41, 43, 47, 48, 52, 53, 55, 294, 309, 310, 325, 328, 331, 332 Peptide T, 41, 325 Perception, 91, 142, 286, 325 Perfusion, 325, 345 Periarthritis, 202, 325 Pericardium, 325, 343 Perimenopausal, 118, 325 Periodontal disease, 80, 191, 325 Peripheral blood, 60, 64, 70, 197, 302, 307, 325 Peripheral Nervous System, 325, 341, 343 Peritoneum, 184, 315, 325 Pernicious, 312, 314, 325 Pernicious anemia, 312, 325 Peroxide, 207, 325 Petrolatum, 293, 325 Petroleum, 211, 316, 324, 325 PH, 81, 277, 325 Phagocytosis, 188, 209, 325 Pharmaceutical Preparations, 187, 281, 299, 326, 330 Pharmacokinetic, 4, 61, 326 Pharmacologic, 16, 19, 20, 271, 326, 345, 346 Phenolphthalein, 293, 326 Phenotype, 16, 20, 42, 43, 58, 59, 67, 70, 116, 151, 326 Phenylalanine, 326, 347 Phospholipases, 16, 326, 340 Phospholipids, 164, 187, 297, 307, 326 Phosphorous, 177, 183, 326 Phosphorylated, 60, 69, 273, 284, 326 Phosphorylation, 40, 54, 69, 78, 137, 288, 326, 332 Photobiology, 54, 86, 326 Photodynamic therapy, 51, 326 Photoreceptor, 206, 326 Phototransduction, 273, 326 Physical Examination, 282, 300, 326 Physiology, 6, 40, 44, 49, 50, 90, 128, 129, 130, 184, 209, 224, 294, 326

Pigment, 275, 314, 327 Pilot study, 88, 107, 327 Pituitary Gland, 287, 327 Placenta, 296, 297, 327, 330 Placental tissue, 44, 327 Plants, 126, 282, 283, 293, 300, 317, 323, 327, 328, 338, 346 Plasma, 10, 15, 35, 49, 68, 75, 84, 89, 106, 114, 135, 139, 147, 181, 216, 269, 271, 281, 294, 298, 299, 300, 303, 309, 316, 318, 327, 336, 339, 345 Plasma cells, 271, 318, 327 Plasma protein, 181, 269, 294, 327 Plasmid, 58, 327, 348 Plasmin, 327 Plasminogen, 103, 327 Plasminogen Activators, 327 Platelet Activation, 327, 340 Platelet Aggregation, 270, 319, 327, 345 Platelets, 314, 319, 327, 345 Platinum, 194, 283, 312, 323, 328 Pleura, 328 Pleural, 108, 328 Point Mutation, 37, 58, 328 Polyarthritis, 19, 328 Polycyclic Hydrocarbons, 29, 328 Polycystic, 249, 328 Polymerase, 9, 81, 328, 330, 336 Polymerase Chain Reaction, 9, 328 Polymorphism, 10, 75, 76, 80, 81, 83, 88, 93, 94, 95, 96, 105, 118, 119, 129, 130, 178, 230, 328 Polymyxin, 211, 328 Polypeptide, 210, 270, 284, 286, 295, 298, 304, 327, 328, 330, 332, 341, 350 Polyposis, 285, 328 Polysaccharide, 272, 281, 328 Polyunsaturated fat, 51, 328, 345 Population Characteristics, 13, 328 Posterior, 270, 273, 292, 309, 323, 328 Postmenopausal, 6, 10, 33, 35, 62, 79, 80, 84, 87, 89, 90, 92, 94, 98, 109, 114, 119, 129, 130, 136, 138, 141, 147, 150, 152, 174, 179, 185, 195, 200, 218, 228, 269, 296, 322, 329, 334 Postnatal, 21, 329, 342 Postsynaptic, 329, 340 Potassium, 181, 189, 269, 291, 316, 329 Potentiate, 7, 308, 329 Potentiation, 147, 329, 340 Practice Guidelines, 246, 329 Precancerous, 282, 329

364

Vitamin D

Preclinical, 45, 59, 329 Precursor, 36, 44, 51, 180, 183, 195, 197, 271, 273, 282, 288, 292, 295, 326, 327, 329, 330, 331, 341, 346, 347, 349 Predisposition, 34, 47, 329 Prednisolone, 329 Prednisone, 4, 19, 187, 217, 329 Pregnancy Tests, 300, 329 Premalignant, 22, 52, 329, 331 Premenopausal, 97, 105, 145, 169, 185, 329 Premenstrual, 157, 169, 329 Premenstrual Syndrome, 157, 169, 329 Prenatal, 101, 293, 329 Prevalence, 10, 14, 23, 24, 99, 148, 169, 215, 321, 329 Prickle, 309, 330 Primary Biliary Cirrhosis, 96, 330 Primary endpoint, 22, 46, 330 Probe, 94, 330 Prodrug, 330 Progesterone, 9, 23, 40, 184, 206, 209, 330, 342 Progression, 7, 9, 38, 45, 49, 59, 64, 122, 271, 288, 330, 347 Progressive, 186, 217, 281, 283, 296, 301, 310, 317, 318, 322, 327, 330, 336 Prolactin, 10, 57, 330 Proline, 284, 305, 330 Promoter, 8, 18, 31, 37, 43, 47, 48, 58, 65, 67, 70, 71, 72, 76, 95, 102, 130, 146, 164, 330 Promotor, 330, 336 Promyelocytic leukemia, 139, 147, 330 Prone, 140, 234, 330 Prophase, 40, 276, 321, 330, 343 Prophylaxis, 187, 330 Proportional, 13, 330 Propylene Glycol, 211, 330 Prospective study, 11, 138, 150, 312, 330 Prostaglandin, 41, 75, 271, 331, 345 Prostaglandins A, 331 Prostate gland, 9, 205, 331 Prostatectomy, 59, 61, 331 Prostatic Hyperplasia, 204, 205, 331 Prostatic Intraepithelial Neoplasia, 44, 61, 331 Protease, 16, 39, 99, 285, 331 Protease Inhibitors, 16, 99, 331 Protein Binding, 17, 331, 345 Protein C, 49, 57, 81, 269, 270, 274, 284, 309, 320, 322, 332, 348 Protein Conformation, 270, 309, 332

Protein Kinases, 16, 57, 332 Protein S, 180, 249, 250, 276, 286, 296, 299, 304, 318, 322, 332, 337, 342 Protein-Tyrosine Kinase, 300, 332 Proteinuria, 18, 319, 332 Proteolytic, 285, 298, 327, 332 Protocol, 63, 332 Protons, 269, 304, 309, 332, 334 Proto-Oncogene Proteins, 323, 332 Proto-Oncogene Proteins c-mos, 323, 332 Protozoa, 180, 286, 315, 316, 332 Proximal, 4, 15, 18, 36, 42, 46, 48, 95, 118, 119, 234, 277, 291, 309, 332 Pruritus, 202, 332 Psoriasis, 157, 182, 187, 195, 203, 214, 219, 220, 228, 332 Psychic, 283, 311, 333, 339 Psychology, 291, 333 Psychomotor, 110, 333 Puberty, 12, 25, 333 Public Health, 10, 15, 23, 24, 38, 44, 112, 116, 137, 149, 246, 333 Public Policy, 245, 333 Publishing, 64, 333 Pulmonary, 17, 68, 276, 282, 287, 309, 311, 333, 348 Pulmonary Artery, 276, 333, 348 Pulmonary Edema, 282, 309, 333 Pulse, 19, 219, 317, 333 Pupil, 287, 333 Purifying, 182, 333 Putamen, 72, 274, 318, 333 Putrefaction, 299, 333 Putrescine, 321, 333, 341 Pyogenic, 322, 333 Pyrazinamide, 71, 333 Pyridoxal, 321, 333 Q Quality of Life, 10, 14, 29, 178, 333 R Race, 10, 29, 45, 47, 316, 333 Rachitis, 182, 333 Radiation, 14, 20, 29, 51, 54, 81, 197, 230, 232, 295, 297, 298, 308, 309, 314, 334, 340, 350 Radiation therapy, 297, 308, 309, 334, 350 Radioactive, 176, 304, 306, 308, 309, 314, 317, 320, 321, 334, 350 Radiography, 300, 334 Radioisotope, 334, 346 Radiolabeled, 277, 309, 334, 350 Radiotherapy, 277, 309, 334, 350

Index 365

Radius, 45, 334 Raloxifene, 141, 334, 339 Random Allocation, 334 Randomization, 21, 334 Randomized, 3, 4, 13, 19, 20, 23, 24, 50, 63, 78, 90, 136, 139, 142, 152, 293, 334 Randomized clinical trial, 63, 334 Reabsorption, 18, 334 Reactive Oxygen Species, 119, 151, 335 Reagent, 177, 185, 282, 304, 312, 323, 335 Recombinant, 43, 47, 71, 335, 348 Recombination, 41, 286, 299, 335 Rectal, 36, 111, 335 Rectum, 272, 277, 285, 291, 299, 306, 307, 310, 331, 335 Recurrence, 20, 138, 282, 335 Red Nucleus, 273, 335 Reductase, 30, 47, 298, 335 Refer, 1, 12, 278, 285, 299, 312, 318, 319, 335 Refraction, 335, 341 Refractive Power, 182, 335 Refractory, 60, 335 Regimen, 19, 123, 145, 169, 194, 292, 335 Registries, 32, 335 Regression Analysis, 35, 335 Relative risk, 22, 335 Reliability, 35, 336 Remission, 19, 58, 335, 336 Renal failure, 12, 16, 18, 187, 201, 225, 336 Renal Osteodystrophy, 177, 195, 201, 203, 214, 225, 336 Renal pelvis, 310, 336 Renal tubular, 15, 43, 336 Renin, 64, 73, 105, 115, 271, 336 Renin-Angiotensin System, 64, 271, 336 Repressor, 8, 39, 41, 321, 336 Reproductive system, 331, 336 Research Design, 8, 336 Resorption, 32, 33, 179, 194, 198, 200, 217, 218, 277, 322, 334, 336 Respiration, 317, 336 Response Elements, 39, 40, 52, 54, 65, 69, 72, 75, 99, 100, 193, 336 Response rate, 7, 336 Restoration, 298, 337, 350 Retina, 310, 326, 337, 338, 348 Retinal, 44, 273, 286, 326, 337, 349 Retinoblastoma, 248, 337 Retinol, 44, 114, 196, 337 Retropubic, 331, 337 Rheumatic Diseases, 84, 233, 337

Rheumatism, 337 Rheumatoid, 19, 75, 105, 157, 187, 191, 200, 229, 272, 337 Rheumatoid arthritis, 19, 105, 187, 191, 200, 229, 272, 337 Rheumatology, 5, 19, 92, 110, 136, 137, 152, 337 Riboflavin, 181, 189, 206, 207, 337 Ribonucleoproteins, 320, 337 Ribose, 267, 288, 337 Ribosome, 337, 346 Rigidity, 327, 338 Risk factor, 18, 25, 26, 28, 29, 30, 37, 38, 47, 49, 53, 75, 107, 185, 231, 295, 312, 330, 335, 338 Risk patient, 187, 338 Rod, 283, 326, 338 S Salivary, 291, 324, 338, 343 Salivary glands, 291, 338 Saponins, 338, 342 Sarcoidosis, 157, 177, 338 Sarcoma, 105, 338 Saturated fat, 180, 338 Schizophrenia, 101, 107, 338 Sclerosis, 62, 64, 78, 156, 197, 198, 249, 317, 338 Screening, 15, 17, 35, 43, 93, 144, 283, 338 Secondary tumor, 315, 338 Secosteroids, 48, 219, 338 Secretion, 47, 118, 145, 181, 212, 288, 295, 304, 307, 308, 310, 316, 317, 338, 339, 346 Secretory, 331, 338 Segregation, 335, 338 Seizures, 324, 339 Selective estrogen receptor modulator, 334, 339, 343 Selenium, 175, 176, 189, 206, 207, 339 Semen, 331, 339 Senile, 322, 339 Sequence Homology, 325, 339 Sequencing, 328, 339 Serologic, 15, 305, 339 Serologic Tests, 15, 339 Serous, 294, 328, 339 Sex Characteristics, 268, 270, 333, 339, 344 Sex Determination, 249, 339 Sharpness, 207, 339, 349 Shedding, 41, 339 Shock, 339, 347 Side effect, 168, 187, 199, 207, 217, 237, 268, 275, 288, 292, 339, 345

366

Vitamin D

Sigmoidal, 11, 339 Signal Transduction, 34, 48, 56, 67, 109, 210, 280, 307, 339 Signs and Symptoms, 336, 340 Skeletal, 6, 17, 22, 24, 25, 32, 33, 46, 74, 135, 147, 177, 194, 200, 271, 283, 317, 340, 341, 344 Skeleton, 82, 85, 180, 213, 216, 218, 267, 277, 297, 309, 331, 340 Skull, 340, 344 Small intestine, 216, 275, 280, 292, 303, 305, 308, 340, 349 Smooth muscle, 135, 270, 279, 336, 340, 341, 343 Sneezing, 339, 340 Social Environment, 333, 340 Socioeconomic Factors, 328, 340 Sodium, 48, 133, 181, 189, 269, 291, 316, 326, 334, 340 Soft tissue, 277, 340 Solar Energy, 127, 340 Solid tumor, 271, 292, 340 Solvent, 301, 322, 330, 340 Soma, 340 Somatic, 21, 268, 283, 293, 304, 314, 316, 325, 340, 341 Somatic cells, 314, 316, 341 Somatostatin, 57, 341 Sorbitol, 211, 341 Soybean Oil, 328, 341 Spasm, 341, 344 Specialist, 256, 341 Specificity, 17, 61, 175, 192, 268, 279, 294, 341, 345 Spectrum, 14, 341, 348 Sperm, 270, 283, 341 Spermidine, 321, 341 Spinal cord, 281, 282, 293, 314, 319, 325, 341 Spinous, 295, 309, 341 Spleen, 313, 338, 341 Splenomegaly, 322, 341 Sporadic, 52, 80, 337, 341 Sprue, 233, 341 Stabilization, 67, 102, 122, 341 Steel, 283, 341 Stem Cells, 296, 301, 302, 341 Sterile, 324, 342 Sterility, 288, 307, 342 Steroid therapy, 46, 342 Stimulant, 194, 342 Stimulus, 292, 310, 342, 344

Stomach, 267, 291, 296, 299, 303, 318, 340, 341, 342 Stool, 306, 310, 342 Strand, 328, 342 Streptomycin, 71, 342 Stress, 7, 217, 218, 288, 318, 329, 337, 342 Stridor, 342, 344 Stroke, 140, 171, 244, 279, 281, 342 Stroma, 205, 309, 342 Stromal, 115, 342 Stromal Cells, 115, 342 Structure-Activity Relationship, 103, 342 Subacute, 306, 342 Subclinical, 306, 339, 342 Subcutaneous, 267, 292, 343, 349 Submaxillary, 295, 343 Subspecies, 341, 343 Substance P, 296, 315, 338, 342, 343 Substrate, 16, 31, 43, 295, 343 Substrate Specificity, 16, 343 Subtrochanteric, 303, 343 Sudden death, 44, 343 Sulfur, 189, 201, 220, 297, 315, 343 Supplementation, 5, 13, 19, 20, 23, 24, 35, 62, 69, 83, 84, 90, 91, 101, 104, 114, 118, 122, 129, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 147, 148, 150, 151, 152, 174, 177, 195, 219, 230, 231, 343 Suppression, 49, 67, 69, 117, 118, 288, 290, 343 Symphysis, 331, 343 Symptomatic, 38, 219, 343 Synaptic, 340, 343 Synergistic, 20, 118, 149, 330, 343 Systemic lupus erythematosus, 110, 152, 313, 343 Systolic, 305, 343 T Tacrolimus, 217, 343 Tamoxifen, 45, 63, 339, 343 Tarsal Bones, 278, 344 Telangiectasia, 249, 344 Temporal, 10, 12, 16, 41, 344 Teratogenic, 269, 344 Terminator, 284, 344 Testis, 296, 344 Testosterone, 28, 40, 45, 206, 298, 335, 344 Tetany, 216, 324, 344 Thalamic, 273, 344 Thalamic Diseases, 273, 344 Therapeutics, 78, 112, 149, 199, 239, 344 Thermal, 277, 291, 319, 328, 344

Index 367

Thiamine, 181, 189, 206, 344 Thigh, 4, 297, 344 Thoracic, 29, 290, 328, 344, 350 Thorax, 267, 312, 344 Threonine, 325, 332, 344 Threshold, 305, 344 Thrombin, 164, 298, 327, 332, 344 Thrombolytic, 327, 344 Thrombomodulin, 332, 344 Thrombosis, 332, 342, 345 Thromboxanes, 273, 345 Thrombus, 287, 306, 327, 344, 345 Thymus, 313, 345 Thyroid, 21, 40, 55, 69, 76, 100, 130, 175, 184, 192, 193, 205, 209, 210, 305, 308, 324, 345, 347 Thyroid Gland, 305, 324, 345 Thyroid Hormones, 21, 184, 209, 345, 347 Thyroxine, 269, 326, 345 Tin, 175, 192, 328, 345 Tissue Culture, 43, 345 Tissue Distribution, 37, 345 Tomography, 345 Tonicity, 48, 345 Tooth Loss, 138, 345 Topical, 197, 213, 214, 273, 304, 324, 325, 345, 350 Topoisomerase inhibitors, 194, 345 Torsion, 306, 345 Toxic, iv, 36, 58, 59, 164, 187, 207, 209, 269, 286, 289, 290, 294, 295, 301, 333, 339, 345, 346 Toxicity, 59, 206, 292, 293, 345 Toxicology, 47, 126, 129, 246, 346 Toxins, 181, 272, 279, 293, 306, 317, 346 Trace element, 277, 282, 284, 298, 345, 346 Tracer, 13, 16, 346 Trachea, 342, 345, 346 Traction, 283, 346 Transcription Factors, 18, 40, 51, 65, 104, 174, 191, 193, 205, 210, 336, 346 Transdermal, 208, 346 Transduction, 48, 57, 339, 346 Transfection, 8, 39, 47, 276, 346 Transforming Growth Factor beta, 54, 346 Transfusion, 188, 189, 346 Translation, 40, 42, 66, 75, 88, 94, 296, 318, 346 Translational, 18, 58, 346 Translocating, 49, 346 Translocation, 135, 296, 346 Transmitter, 267, 314, 346

Transplantation, 3, 4, 85, 113, 120, 123, 182, 225, 283, 313, 346 Transurethral, 331, 346, 347 Transurethral Resection of Prostate, 331, 347 Trauma, 195, 274, 302, 318, 344, 347 Trophoblast, 44, 276, 347 Tryptophan, 284, 347 Tubercle, 70, 71, 347 Tuberculosis, 64, 68, 158, 287, 309, 313, 347 Tuberculostatic, 309, 347 Tuberous Sclerosis, 249, 347 Tumor marker, 276, 347 Tumor model, 60, 347 Tumor Necrosis Factor, 31, 70, 103, 198, 347 Tumor suppressor gene, 52, 312, 323, 347 Tumor-derived, 59, 60, 347 Type 2 diabetes, 281, 347 Tyrosine, 41, 146, 332, 347 U Ulcer, 289, 347 Ulceration, 289, 347 Ulcerative colitis, 214, 233, 307, 347 Ultrasonography, 300, 347 Ultraviolet Rays, 182, 348 Unconscious, 305, 348 Urea, 213, 214, 310, 321, 348 Uremia, 82, 223, 309, 336, 348 Ureters, 310, 348 Urethra, 275, 331, 346, 347, 348 Urinary, 120, 207, 208, 279, 300, 306, 321, 331, 337, 348 Urogenital, 234, 300, 348 Uterus, 282, 287, 294, 305, 315, 323, 330, 336, 348 Uveitis, 273, 348 V Vaccine, 268, 332, 347, 348 Vagina, 282, 290, 315, 336, 348 Vascular, 135, 150, 279, 294, 306, 307, 319, 327, 345, 348 Vasodilator, 272, 278, 348 Vasomotor, 296, 348 VE, 65, 70, 76, 83, 348 Vector, 346, 348 Vein, 308, 320, 324, 348 Venous, 332, 348 Ventricle, 305, 333, 343, 348 Venules, 276, 279, 294, 348 Vertebral, 6, 28, 94, 103, 136, 349 Vesicular, 18, 316, 349

368

Vitamin D

Veterinary Medicine, 215, 245, 297, 349 Villi, 349 Villous, 234, 280, 349 Viral, 31, 64, 293, 300, 321, 346, 349 Viremia, 31, 349 Virulence, 274, 345, 349 Virulent, 70, 349 Virus, 31, 64, 70, 100, 274, 295, 299, 300, 301, 307, 346, 349 Viscera, 315, 340, 349 Visceral, 184, 325, 349 Visual Acuity, 182, 349 Vitamin A, 44, 164, 189, 207, 208, 218, 307, 337, 349 Vitro, 9, 11, 17, 18, 30, 36, 40, 41, 42, 43, 51, 55, 60, 62, 65, 66, 68, 70, 128, 147, 151, 188, 194, 209, 306, 328, 343, 345, 349 Vivo, 12, 17, 30, 32, 36, 41, 42, 51, 54, 58, 59, 60, 62, 65, 68, 70, 73, 74, 90, 179, 187, 194, 196, 198, 220, 306, 343, 345, 349

Voltage-gated, 18, 349 W Waist circumference, 281, 349 Weight Gain, 207, 350 White blood cell, 267, 271, 311, 313, 317, 318, 327, 350 Windpipe, 345, 350 Wound Healing, 314, 350 X Xenograft, 271, 347, 350 Xenopus, 40, 65, 205, 350 X-ray, 13, 25, 28, 52, 55, 277, 286, 298, 309, 313, 314, 320, 334, 348, 350 X-ray therapy, 309, 350 Y Yeasts, 299, 326, 350 Z Zinc Oxide, 211, 350 Zoledronate, 168, 169, 193, 350 Zymogen, 332, 350

Index 369

370

Vitamin D

Index 371

372

Vitamin D