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

CANDIDA 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 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Candida: 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: 0-597-83808-9 1. Candida-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 Candida. 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 CANDIDA .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Candida ......................................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 61 The National Library of Medicine: PubMed .............................................................................. 107 CHAPTER 2. NUTRITION AND CANDIDA ...................................................................................... 153 Overview.................................................................................................................................... 153 Finding Nutrition Studies on Candida...................................................................................... 153 Federal Resources on Nutrition ................................................................................................. 160 Additional Web Resources ......................................................................................................... 161 CHAPTER 3. ALTERNATIVE MEDICINE AND CANDIDA ................................................................ 163 Overview.................................................................................................................................... 163 National Center for Complementary and Alternative Medicine................................................ 163 Additional Web Resources ......................................................................................................... 180 General References ..................................................................................................................... 187 CHAPTER 4. DISSERTATIONS ON CANDIDA .................................................................................. 189 Overview.................................................................................................................................... 189 Dissertations on Candida........................................................................................................... 189 Keeping Current ........................................................................................................................ 191 CHAPTER 5. CLINICAL TRIALS AND CANDIDA ............................................................................. 193 Overview.................................................................................................................................... 193 Recent Trials on Candida........................................................................................................... 193 Keeping Current on Clinical Trials ........................................................................................... 194 CHAPTER 6. PATENTS ON CANDIDA ............................................................................................. 197 Overview.................................................................................................................................... 197 Patents on Candida .................................................................................................................... 197 Patent Applications on Candida ................................................................................................ 224 Keeping Current ........................................................................................................................ 253 CHAPTER 7. BOOKS ON CANDIDA ................................................................................................ 255 Overview.................................................................................................................................... 255 Book Summaries: Federal Agencies............................................................................................ 255 Book Summaries: Online Booksellers......................................................................................... 256 The National Library of Medicine Book Index ........................................................................... 261 Chapters on Candida.................................................................................................................. 262 CHAPTER 8. MULTIMEDIA ON CANDIDA ...................................................................................... 269 Overview.................................................................................................................................... 269 Video Recordings ....................................................................................................................... 269 Audio Recordings....................................................................................................................... 270 CHAPTER 9. PERIODICALS AND NEWS ON CANDIDA ................................................................... 273 Overview.................................................................................................................................... 273 News Services and Press Releases.............................................................................................. 273 Newsletter Articles .................................................................................................................... 276 Academic Periodicals covering Candida .................................................................................... 277 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 279 Overview.................................................................................................................................... 279 U.S. Pharmacopeia..................................................................................................................... 279 Commercial Databases ............................................................................................................... 280 Researching Orphan Drugs ....................................................................................................... 281 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 285

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Overview.................................................................................................................................... 285 NIH Guidelines.......................................................................................................................... 285 NIH Databases........................................................................................................................... 287 Other Commercial Databases..................................................................................................... 289 APPENDIX B. PATIENT RESOURCES ............................................................................................... 291 Overview.................................................................................................................................... 291 Patient Guideline Sources.......................................................................................................... 291 Finding Associations.................................................................................................................. 297 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 299 Overview.................................................................................................................................... 299 Preparation................................................................................................................................. 299 Finding a Local Medical Library................................................................................................ 299 Medical Libraries in the U.S. and Canada ................................................................................. 299 ONLINE GLOSSARIES................................................................................................................ 305 Online Dictionary Directories ................................................................................................... 305 CANDIDA DICTIONARY........................................................................................................... 307 INDEX .............................................................................................................................................. 391

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

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

Natural Defenses Against Candida Colonization Breakdown in the Oral Cavities of the Elderly Source: Journal of Dental Research. 78(4): 857-868. April 1999. Contact: Available from International Association for Dental Research. Subscription Department, 1619 Duke Street, Alexandria, VA 22314. (703) 548-0066. Fax (703) 548-1883. Summary: Candida colonization of the oral cavity increases in the elderly. A major predisposing condition is denture use. This article reports on a study undertaken to test whether the increase in colonization is age related in a fashion independent of denture use. The authors analyzed the frequency (incidence) of carriage, the intensity of carriage, the multiplicity of species, and the genetic relatedness of strains in the oral cavities of 93 test subjects separated into three age groups: 60 to 69 years, 70 to 79 years, and over 80

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years. Each age group was further subdivided into subjects with and without dentures, and into males and females. The results demonstrate that the frequency of carriage, the intensity of carriage, and multispecies carriage all increase as a function of age and differ according to gender, in both cases independent of denture use. These results suggest that the natural suppression of yeast carriage in the oral cavity breaks down in the elderly. In addition, the study demonstrates that Candida glabrata colonizes the oral cavities of elderly individuals without dentures only after 80 years of age, suggesting that there are age related compromising conditions other than denture use in this oldest age group. 5 figures. 5 tables. 42 references. (AA-M). •

Effect of Antimicrobial Mouthrinses on the In Vitro Adhesion of Candida Albicans to Human Buccal Epithelial Cells Source: Clinical Oral Investigations. 5(3): 172-176. September 2001. Contact: Available from Springer-Verlag, New York Inc. Journal Fulfillment Services Department, P.O. Box 2485, Secaucus, NJ 07096-2485. Fax (202) 348-4505. Summary: Oral candidosis (thrush, a fungal infection) is the most frequent opportunistic infection in immunocompromised patients, and Candida albicans represents its primary causative agent. Adhesion to epithelial cells is a critical step in successful oral colonization and infection by Candida albicans. This article reports on a study undertaken to compare three mouthrinse products, containing chlorhexidine 0.2 percent (CHX), cetylpyridinium chloride 0.05 percent (CPC), or triclosan 0.045 percent (TRN) for their effects on the in vitro adhesion of C. albicans to human buccal epithelial cells (BEC, the cells of the cheek lining). Candidal adhesion appeared to be significantly reduced by oral rinsing with the CHX containing mouthrinse. In vivo (in the laboratory) exposure of BEC to the CPC mouthrinse also inhibited adhesion of C. albicans. Both CHX and CPC products suppressed adhesion to the same extent. On the other hand, the TRN mouthrinse did not significantly affect epithelial adhesion of C. albicans. These findings suggest that mouthrinses containing CHX or CPC could be of value in the control of candidal colonization and infection. The authors call for clinical trials on the effectiveness of these products in reducing oral Candida infections. 3 tables. 27 references.

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Identification of Candida Dubliniensis in a Study of HIV-Seropositive Pediatric Dental Patients Source: Pediatric Dentistry. 22(3): 234-238. May-June 2000. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2616. Summary: Oral fungal colonization remains one of the most common opportunistic infections observed in both adult and pediatric HIV-infected patients. Although Candida albicans is the most frequently isolated opportunistic fungal species, a recently characterized Candida species, C. dubliniensis, has gained attention due to its almost exclusive association with HIV-seropositive individuals. This article reports on a study undertaken to prospectively screen for the presence of C. dubliniensis among pediatric HIV-positive patients. Oral samples taken from 27 children were cultured for the presence of yeast. Among the 27 patients tested, 3 patients were found to harbor C. dubliniensis, one of which also grew C. glabrata; 12 patients were colonized with C. albicans, while the remaining 12 patients were negative for yeast. All three C. dubliniensis isolates were found to be susceptible to fluconazole. These results confirm the presence of this novel species in a dental pediatric HIV-seropositive population and

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supports the need for further investigation into the prevalence and pathogenesis of C. dubliniensis. 1 figure. 30 references. •

Epidemiology of Non-Albicans Candida in Oropharyngeal Candidiasis in HIV Patients Source: SCD. Special Care in Dentistry. 20(5): 178-181. September-October 2000. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824. Summary: Oropharyngeal candidiasis (OPC) is the most common fungal infection in patients with HIV infection. The most common organism isolated in OPC is C. albicans, however, this article explores the epidemiology (causes) of non-albicans Candida in oropharyngeal candidiasis in HIV patients. Fluconazole has been proven to be very effective in treating this infection, but decreased susceptibility of Candida to this drug has emerged. Certain non-albicans species such as C. glabrata and C. krusei are commonly less susceptible to fluconazole that C. albicans and are being isolated with increased frequency in HIV patients. The authors report on a study undertaken to determine if the presence of non-albicans Candida with OPC in HIV patients had an impact on clinical presentation. The results show that late stage HIV patients have a high prevalence of Candida with decreased susceptibility to fluconazole, especially nonalbicans species. OPC episodes with non-albicans isolates were more likely to require higher doses of fluconazole to achieve clinical care. Also, the presence of non-albicans Candida was more frequently associated with severe symptoms. 4 figures. 1 table. 17 references.

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Oral Candidal Carriage and Infection in Insulin-Treated Diabetic Patients Source: Diabetic Medicine. 16(8): 675-679. August 1999. Contact: Available from Blackwell Science, Ltd. Journal Subscriptions, P.O. Box 88, Oxford OX2 0NE, UK. 44 1865 206180. Fax 44 1865 206219. E-mail: [email protected]. Summary: This article describes a study that evaluated candidal load and carriage of candidal species in insulin-treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in people who have diabetes with oral candidosis were also investigated. The candidal species were recovered from 414 insulin-treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique. The study found that 77 percent of the patients who had diabetes carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty percent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, gender, or glycemic control. However, it was significantly increased in those patients who were tobacco smokers and nonsignificantly increased in those patients who wore dentures or had clinical signs of oral candidosis. The article concludes that the epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes patients is not the result of a single entity, but rather, a combination of risk factors. 1 figure. 1 table. 25 references. (AA-M).

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Candida Infections of the Oropharynx and GI Tract: Pathogenesis, Prevention, Treatment Source: Practical Gastroenterology. 16(5): 10-11, 14-16, 18-19. May 1992. Summary: This article discusses the pathogenesis, prevention, and treatment of candida infections of the oropharynx and gastrointestinal (GI) tract. Topics include the organism itself, host defense factors and immune system diseases, diagnostic features of candidiasis, clinical studies of candidiasis therapy in four groups of patients (patients with cancer, patients for whom candida prophylaxis is appropriate, HIV-infected persons, and newborns), and resistance and invasive infection. The author considers the development of effective oral antifungal therapy (eg, ketoconazole and fluconazole), noting some of the complications that can arise with such therapy. 28 references.

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Candida Albicans Colonization of Surface-Sealed Interim Soft Liners Source: Journal of Prosthodontics. 9(4): 184-188. December 2000. Contact: Available from Harcourt Health Sciences. Subscription Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.harcourthealth.com. Summary: This article reports on an in vivo (in actual patients, not in the laboratory) investigation that evaluated the effect of 2 denture sealer agents on the microbial colonization of a newly placed soft interim denture liner during a period of 14 days. An interim soft denture liner (Coe Soft, GF America) was coated with 2 different denture surface sealants (Palaseal, Heraeus Kulzer, and MonoPoly, Plastodent). Three rectangular wells were placed in the intaglio of 10 maxillary (upper jaw) complete dentures and filled with the soft liner material. The soft liner surface was treated with Palaseal (first well) and MonoPoly (second well), and the unsealed (third well) was used as a control. These were exposed to the oral cavity for 14 days. The effect the sealant had in the prevention of Candidal colonization in vivo of the soft liner material was evaluated. Microbiological specimens were recovered from all samples and cultivated. The results showed clear differences between the sealed and unsealed soft liners. The sealed material showed significantly less colonization by yeast and bacteria. Intercomparison of the surface denture sealers, Palaseal versus MonoPoly, showed no statistically significant differences in total yeast or bacterial colonization. The authors conclude that coating of Coe Soft denture liners with either Palaseal or MonoPoly significantly decreased yeast and bacterial colonization. 1 figure. 4 tables. 27 references.

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Candida and Oral Candidosis: A Review Source: Critical Reviews in Oral Biology and Medicine. 5(2): 125-157. 1994. Summary: This lengthy review article details the current knowledge on Candida and oral candidosis together with the newer therapeutic regimes employed in treating these mycoses. Candida species are the most common fungal pathogens isolated from the oral cavity. Their oral existence both as a commensal and an opportunist pathogen has intrigued clinicians and scientists for many decades, and recent investigations have revealed many attributes of this fungus contributing to its pathogenicity. In addition, the advent of HIV and AIDS has resulted in a resurgence of oral Candida infections. Clinicians are witnessing not only classic forms of this disease, but also newer clinical variants such as erythematous candidosis, rarely described before. The review is presented in eleven sections: introduction, taxonomy and typing of Candida, Candida carriage in the oral cavity, host oral defenses against Candida infection, pathogenicity of

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Candida species, factors predisposing to oral Candida infections, classification and clinical manifestations of oral Candida infections, Candidosis and immunocompromised hosts, the possible role of Candida in oral carcinogenesis, the laboratory diagnosis of oral Candidosis, the prophylaxis of oral Candidosis, and the treatment of oral Candidosis. 6 tables. 247 references.

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

Project Title: A NOVEL ACCESSORY FOR URINARY LEGBAGS Principal Investigator & Institution: Sarangapani, Shantha; Innovative Chemical/Environmental Tech Environmental Technologies, Inc Norwood, Ma 02062 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 31-MAR-2004 Summary: The phase I effort on the testing and performance of a biocidal device (Foley Guard) placed between the catheters and urinary leg bags to prevent ascending infections from leg bags into the urinary catheters was successfully completed. An in vitro apparatus mimicking a catheterized bladder with infected leg bags was used. A multi channel pump and manifolds allowed comparison between the controls and the experimental devices under the same conditions. The addition of a biocidal device as an accessory to the leg bags resulted in the complete absence of any microorganisms near the catheter base for over 10-14 days, which was the duration of the experiment. All of the corresponding controls showed high levels of the bacteria near the catheter base within 3-9 days. These in vitro tests suggest a useful role for the device in controlling infection in patients undergoing short and long term indwelling catheterization. A continuous challenge of three pathogens in human urine medium, showed that for up to 30 days the materials inhibited all the bacteria completely. The broad-spectrum activities of the phase I biocidal material used in this Foley guard has been well established by the PI. (toward bacteria, mold, and candida-type yeast species). A two week rabbit- muscle implantation study of the biocidal material resulted in a non-toxic response. The phase II will optimize the formulation and the manufacturing protocols. A series of microbiological tests using the strains from catheterized patients will be performed to

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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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assess: the biocidal potency per unit weight of the material, the potency before and after extensive washing in synthetic urine and the bactericidal activity and the longevity of the device under in vitro conditions. The biocide release concentrations will be established firmly for our claims. Finally, human clinical trials will be conducted to establish the efficacy and performance and compared to controls. PROPOSED COMMERCIAL APPLICATIONS: In 1992 the number of urogenital devices in North America was substantial. About 1.6 billion incontinence pads and devices, 16 million catheters and 58 billion diapers were reportedly used. (Reid, 1994 J. of industrial microbiology, 13 90-96) Estimates of the cost of treating catheter-related UTI have ranged as high as $39,960 per patient per year including the increase in nursing care required. As the senior population grows this problem is becoming more common. We believe if our accessories are used by 20% of the leg bag users, a market at least million accessories exists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A NOVEL ANTIFUNGAL COMPOUND FROM CAYENNE PEPPER Principal Investigator & Institution: Selitrennikoff, Claude P.; Professor; Mycologics, Inc. 12635 E Montview Blvd Aurora, Co 80010 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 30-SEP-2001 Summary: (Adapted from the application): Deep-seated mycoses are being increasingly observed in immunocompromised patients and in patients receiving aggressive cancer chemotherapy. The use of available drugs for the treatment of these infections is limited by toxicity and the emergence of resistant fungal species. The impact of fungal infections in the clinical management of inimunocompromised patients underscores the clear need for new antifungals. Historically, microorganisms and plants have been rich sources of drugs for the treatment of human disease. We have identified a novel, broadly-active antifungal compound from the dried fruit of Capsicum spp. (cayenne pepper). CAY-1, the active agent, was purified to homogeneity and, based on chemical analysis, is a novel saponin with a molecular mass of 1243 Da. In this Phase I proposal, we plan to extend our preliminary work and characterize more fully CAY-1's potential as an antifungal therapeutic. We will accomplish this in three specific aims: A. Aim One: Purify 500 mg of CAY-1 for the work described in Aims Two through Four C. Aim Two: Characterize the antifungal activity of CAY-1. D. Aim Three. Determine the in vitro toxicity of CAY-1 and the in vivo efficacy of CAY-1 against Candida albicans PROPOSED COMMERCIAL APPLICATION: The research outlined in this Phase I SBIR proposal will lead to the evaluation of a novel antifungal compound. We estimate that the market potential for a novel and safe antifungal drug to be greater than $200,000,000 per year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ABC TRANSPORTERS AND PATHOGENECITY OF CANDIDA ALBICANS Principal Investigator & Institution: Kohler, Gerwald A.; Stomatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): ABC Transporters and Pathogenicity of Candida albicans. ABC transporters form a superfamily of ubiquitous membrane proteins involved in the energy-dependent translocation of a wide variety of substrates across cellular membranes. Multiple drug resistance and many human hereditary diseases

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have been related to ABC transporter function, however, the physiological roles of only a few of these transporters have been elucidated. One of the largest subfamilies of ABC proteins is the MRP/CFTR family (subfamily C); homologues of this group of ABC transporters are also found in the opportunistic fungal pathogen Candida albicans. In preliminary studies we have already shown that the MRP-related ABC transporter gene MLT1 of C. albicans is crucial for its invasion of parenchymal organs in a peritonitis model. This study focuses on a detailed characterization of the involvement of MRPrelated ABC transporters in fungal cell homeostasis networks during in vitro growth and in vivo interaction with the host in commensalism and opportunistic disease. Since the genome sequence of C. albicans is available, genomic expression profiling using DNA microarrays will be used to infer the functional relationships of MLT1 and two of the most closely-related transporters within the MRP/CFTR subfamily. In vitro expression studies in cell culture models will be extended to experimental infection models using innovative methods like in vivo expression technology (IVET) and realtime PCR. Specific ABC transporter gene inactivation mutants derived from wild-type C. albicans strains will be generated by gene disruption or RNA interference and phenotypically characterized. Furthermore, the functional characterization of these transporters will comprise identification of endogenous and exogenous substrates as well as determination of the subcellular localization. Our findings are likely to contribute to new approaches for treatment of fungal infections with specific compounds inhibiting ABC transporters. Since many human ABC transporters of the MRP/CFTR subfamily are involved in drug resistance or inherited disorders, our findings might help to infer their functional properties from those of their fungal homologues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALBICANS

AIDS:

COMBATTING

DRUG

RESISTANCE

OF

CANDIDA

Principal Investigator & Institution: Cannon, Richard D.; University of Otago Leith St Dunedin, Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2004 Summary: (provided by applicant): Candida albicans is a pathogenic yeast that causes serious fungal infections in the immunocompromised and opponunistic Candida infections can be the first indication of immunosuppression in HIV+ individuals. AIDS patients frequently suffer from oropharyngeal candidiasis (OPC) and require antifungal therapy. In the 1990s there was a dramatic increase in the failure of fluconazole therapy for AIDS patients with OPC due to C. albicans strains developing fluconazole resistance. The most common mechanism responsible for high level fluconazole resistance in these yeast was over-expression of drug efflux pump Cdrl p. Globally, OFC remains a major opponunistic infection in HIVIAIDS, and the widespread use of fluconazole in the third world is likely to maintain pressure on C. albicans to develop resistance. The overall objective of this research is to use a novel strategy to improve the treatment of AIDS patients with oral candidiasis by combating azoleresistance in C. albicans. Specific objectives are to: 1. Employ a novel heterologous functional hyper-expression system to determine the mechanism of pumping by Cdrl p, using both in vitro mutagenized Cdrl p and Cdrl proteins from clinical C. albicans isolates (obtained from AIDS patients) that demonstrate high and low pump activities. 2. Use the heterologous functional hyperexpression of Cdrlp to screen a unique combinatorial Doctapeptide library for peptides that inhibit the pump. This work will validate a novel approach to combating azoleresistance in C. albicana An understanding of drug pumping mechanisms may indicate

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Candida

new ways to circumvent efflux-mediated resistance. This project is expected to identify a lead compound with the potential to sensitize resistant strains to azole antifungals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF THE CANDIDA ALBICANS PROTEOME Principal Investigator & Institution: Lopez-Ribot, Jose L.; Assistant Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Candida albicans is by far the most frequently isolated human mycotic agent. In the oral cavity, oropharyngeal candidiasis (OPC) is a significant cause of morbidity in patients with HIV or AIDS. Other forms of mucosal candidiasis are also frequent in different patient populations such as infants, denture wearers, the elderly, and following antibiotic therapy. Azole derivatives, in particular fluconazole, are generally effective in the treatment of mucosal candidiasis. However, resistance has emerged as an important clinical problem. Large-scale DNA sequencing has provided an important sequence infrastructure for protein analysis. The term "Proteomics" refers to large-scale characterization of the proteins present in a cell, tissue or organism (the proteome) and involves the combined application of techniques to resolve, identify, quantitate and characterize proteins, as well as bioinformatics tools to store, communicate and interlink the resulting information. The experimental design of this proposal takes advantage of the recently completed NIDCR-funded Candida albicans genome sequencing project. The post-genomic era offers unprecedented opportunities to study host-fungal interactions. The specific aims of this proposal include: i) a pilot feasibility study of the analysis of the C. albicans proteome under a wide variety of conditions and development of a searchable proteomic map and database as a resource for the fungal community, ii) analysis of C. albicans azole resistance by proteomics and identification of proteins implicated in the regulatory networks of multidrug resistance. We will expect that these projects will establish the foundations for creating a fundamental tool for the C. albicans research community and for providing a detailed large-scale study of a biological phenomenon (drug resistance) with important clinical repercussions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADJUVANTS

ANTIFUNGALS

FROM

MARINE

INVERTEBRATES--AIDS

Principal Investigator & Institution: Molinski, Tadeusz F.; Professor; Chemistry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 01-MAR-1997; Project End 31-MAY-2005 Summary: (provided by applicant): AIDS-related fungal infections are important targets for reduction of mortality and improvement in the quality of life for people living with AIDS. Each new generation of azole drugs, such as fluconazole, have succumbed to recurrent cross resistance. Natural products are represented among clinically useful antifungal agents. Marine invertebrates, particularly Porifera (sponges) that produce chemically diverse libraries of natural products, some of which show antifungal activity. The general goal of this competitive renewal is to find and identify small molecules from marine organisms that are active against fluconazole-resistant strains of Candida albicans and inherently fluconazole-resistant non-albicans species, including Candida glabrata and Candida krusei and use these as prototypes leads for antifungal drugs. We plan to prepare and screen extracts for antifungal agents using mechanism-selective

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approach that may be useful identifying new leads for antifungal therapy. This program embodies a rational search for compounds with unique mechanisms of action, including inhibition of fungal sphingolipid biosynthesis, that complement current therapies and intervene at strategic points in fungal cell metabolism or life cycle. Active components will be isolated by a combination of solvent-partitioning, chromatography, liquid-liquid centrifugal counter current chromatography and other techniques. The in vitro antibiotic susceptibilities of pathogenic fungi will be evaluated in a panel of fluconazole-resistant fungi. Selected leads will be advanced to in vivo evaluation in murine models of C. albicans, Cryptococcus neoformans and C. glabrata. The structures of novel compounds will be determined by a combination of spectroscopic techniques including mass spectrometry, nuclear magnetic spectroscopy, circular dichroism and X-ray crystallography. Absolute stereochemistry of chiral molecules will be determined using a combination of chiroptical techniques and chemical degradation. Derivatives of existing leads, including the C. glabrata-specific dimeric sphingolipid, oceanapiside, will be synthesized de novo or by semi-synthetic modification to prepare limited libraries of analogs for structure-activity studies. Optimized leads identified from those libraries will be advanced to in vitro and in vivo evaluation. The strengths of this program include a successful track record in targeting emergent pathogenic fungi, including fIuconazole-resistant Candida species that are of importance in human health, and maximization of chemical diversity to enhance the chances of discovery of natural product antifungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIMICROBIAL COATING FOR BIOFILM INHIBITION Principal Investigator & Institution: Rawls, H R.; Professor; Biomedical Development Corporation 500 Sandau, Ste 200 San Antonio, Tx 78216 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: Description(provided by applicant): Candida is the third leading cause of catheter-related nosocomial bloodstream infections. Indwelling devices have been shown to support colonization and biofilm formulation by Candida. Intravenous lines are the most frequent indwelling device and are the single most common cause of candidemia. Once a Candida biofilm forms in vivo, removal of the substrate that is supporting the biofilm growth is almost always required to eliminate the infection. Unfortunately, in many instances removal is impossible due to deteriorated patient condition, anatomical location, or underlying disease. The goal of this project is to incorporate an antifungal agent into unique, patented formulations to create a coating for medical devices that is resistant to C. albicans. A coating and antifungal delivery system that could extend the time and/or increase the rate of delivery and achieve a higher concentration of antifungal agents to a C. albicans-susceptible site would have enormous therapeutic advantages over systemic and inefficacious topical routes of delivery. To demonstrate the feasibility of this approach, the specific aims are to optimize the coating formulation for use as short-term antifungal coatings for medical devices, evaluate the coatings for antifungal activity in vitro, and to perform an intramuscular implantation study in rabbits. PROPOSED COMMERCIAL APPLICATION: Candida albicans is by far the most frequently isolated human mycotic agent. The large number of immunosuppressed patients with indwelling devices combined with the extensive social and economic costs associated with treating C. albicans-related infections serve as justification for the pursuit of alternative therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Candida

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Project Title: AZOLE-RESISTANT CANDIDA IN MARROW TRANSPLANT PATIENTS Principal Investigator & Institution: Marr, Kieren A.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AZOLES AND CANDIDA IN AIDS - A WHOLE CELL RESPONSE Principal Investigator & Institution: White, Theodore C.; Associate Member; Seattle Biomedical Research Institute 4 Nickerson St, Ste 200 Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (provided by applicant): The use of azole antifungals, including fluconazole, for treatment and/or prophylaxis against infections caused by Candida albicans has resulted in a recent, dramatic increase in Candida strains that are resistant to antifungal drugs. This is true in oral candidiasis in AIDS patients, and has recently been documented in other immune compromised individuals including blood and marrow transplant recipients (BMT). In the past several years, the basic molecular mechanisms of azole resistance have been identified including the overexpression of the target enzyme and two types of efflux pump, and mutation in the target enzyme. Recent data from this laboratory and others has indicated that resistance is a whole cell response in which virulence determinants can have an effect on resistance, and resistance determinants can have an effect on these other virulence factors. This whole cell response includes a heterogeneous resistance (Het-R) phenotype identified in our laboratory, in which certain susceptible isolates are able to form small colonies on agar plates containing fluconazole. This Het-R phenotype may be correlated with the ability to induce true resistance in these strains, and is related to heterogeneous resistance in bacteria. The overall goal of this project is to develop an understanding of the whole cell response of C. albicans to azole antiflingals, including the Het-R phenotype. The specific aims of this proposal are: 1) to characterize the interactions between resistance and virulence factors of C. albicans, 2) to characterize the transcriptional regulation associated with the whole cell response, and 3) to characterize this Het-R phenotype as a specific whole cell response. Antifungal drug resistance and susceptibility testing has become increasingly important as invasive candidiasis has become a leading cause of nosocomial infections worldwide. The analyses outlined in this proposal will define some of the many responses of a cell to azole antifungal drugs, thus providing us with information critical to the development of effective strategies to prevent, diagnose or treat fungal infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIBODIES

BIOLOGICAL

ACTIVITIES

OF

NATURAL

ANTI-CANDIDA

Principal Investigator & Institution: Kozel, Thomas R.; Professor and Chair; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Antibodies reactive with Candida albicans mannoprotein are found in sera of most normal adults. Often referred to as "natural" antibodies, the amount of antimannan antibody found in a population of donors is normally distributed; some

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individuals have little or not antibody, other individuals have remarkably high titers. Little is known about the fine epitope specificity or biological activity of naturallyoccurring antimannan antibody. "Natural" antimannan IgG may be a first-line defenses against systemic Candida infection. The goal of the Candida: Protective Immunity MRU is to establish a knowledge base essential for development of a Candida vaccine. Naturally- occurring antimannan antibodies are a key issue that must be considered if active immunization, be it by a protein antigen (Edwards and Mitchell projects) or an epitope derived from a polysaccharide antigen (Cutler project), is to be successful. Moreover, the presence of these antimannan antibodies and the ability to affinity purify hundreds of milligrams of antibody from human plasma enables an evaluation of the function, including protective efficacy, of human antimannan antibodies. The central hypotheses is that naturally-occurring human antimannan antibodies have biological activities that influence host resistance to disseminated candidiasis. Moreover, these biological activities may be dependent on the epitope specificity of naturally occurring antimannan antibodies to activation of the classical and alternative complement pathways; iii) assess the opsonic activity of naturally-occurring antimannan antibodies; iv) determine whether naturally-occurring anti-Candida antibodies are productive in murine models of candiasis, and v) assess the effects of circulating "natural" antimannan antibodies on the efficacy of immunoprotective strategies developed by other components of the Mycology Research Unit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGICAL FUSIONS: CONJUGATION IN YEAST Principal Investigator & Institution: Fink, Gerald R.; Professor of Molecular Genetics, Mit; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-MAR-2005 Summary: (Applicant's Abstract): The goal of this proposal is to understand dimorphism, the developmental switch from the yeast to the filamentous form in fungi and to determine its role in pathogenesis. In Saccharomyces cerevisiae diploid yeast cells develop into a multicellular, pseudohyphal form under conditions of nitrogen starvation. Haploid cells undergo a related process, termed haploid-invasive growth. The analysis of filamentation in the model Saccharomyces system will guide the studies in the less tractable pathogen, Candida albicans. In both fungi the key molecules involved in dimorphism are a family of cell-surface glycoproteins called adhesins or flocculins. In Saccharomyces the MAPkinase and A kinase pathways activate the flocculin FLo1 1, which is required for filamentous growth and adhesion. In the absence of FLo1 1 other members of the flocculin family such as Fig!, and FlolO can be activated to bypass FbolI. Experiments will be carried out to identify the foil independent pathways and to determine whether they are also controlled by the MAPkinase and A kinase pathways. To this end a set of mutants that bypass the requirement for Fbo1 1 (fbp) will be analyzed. The role of an anti-sense RNA from the IME4 gene in controlling the switch between filamentation and sporulation will be determined. The discovery that Saccharomyces Like Candida can stick to plastic is the basis for experiments to uncover the genes and pathways that lead to Saccharomyces biofilm formation. The genetic and physiological requirements for this unusual behavior will be tested by mutant and whole genome array analysis. The goal is to identify the proteins involved in adherence to plastic and to uncover the molecular basis for this adherence. Candida genome arrays will be constructed and used to analyze gene expression changes when this pathogen is co-cultured with cells of the mammalian immune system, both macrophages and neutrophils. Genes identified by this analysis will be deleted and their

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Candida

role in the interaction with the immune system determined. As preliminary experiments indicate a connection between the adhesins, dimorphism, and tissue tropism special attention will be given to this family of genes. The genes uncovered in this analysis are potential targets for the development against this pathogen, which is so devastating to those afflicted with AIDS and other immunocompromised individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGY AND DRUG RESISTANCE OF CANDIDA BIOFILMS Principal Investigator & Institution: Ghannoum, Mahmoud A.; Professor; Dermatology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2005 Summary: (provided by the applicant): Candida-associated denture stomatitis (chronic atrophic candidiasis) is the most prevalent superficial oral infection and the most common form of Candida-associated disease. The etiology of denture stomatitis involves dental plaque. Dental plaque consists of a complex biofilm of bacteria and yeasts, predominantly Candida albicans. C. albicans biofilms have received much less attention than bacterial biofilms, and our present knowledge of their biology and drug resistance is at a rudimentary stage. Frequent denture stomatitis treatment failures combined with a steadily increasing population of elderly people, many of whom will be endentulous, make this area of study particularly important. The long-range goal of our work is to understand the biology and drug resistance of C. albicans biofilms. Our preliminary work in this new area resulted in the successful development of a reproducible model of C. albicans-associated biofilms (Publication #1). Since the last submission, we used this model to: 1) define the three stages of C. albicans associated biofilm development, 2) demonstrate that C. albicans biofilm is a highly heterogeneous structure, 3) show that the antifungal resistance of C. albicans biofilm increases in conjunction with biofilm development, 4) show that C. albicans has greater ability than the less pathogenic C. parapsilosis and Saccharomyces cerevisiae to form denture biofilm, and 5) show that C. albicans genes are differentially expressed under biofilm and planktonic conditions. Additionally, we initiated efforts to construct a C. albicans DNA array, and developed a bioprosthetic associated candidal biofilm model. Importantly, our studies showed that biofilm grown in our in vitro model has similar morphology as that growing in vivo on a catheter obtained from a patient with catheterassociated infection. Specific aims of the current proposal are: Specific Aim 1: Use our established biofilm model to determine the antifungal susceptibility profiles of C. albicans isolates obtained from denture stomatitis patients, and to study the effect of antifungal agents on the growth kinetics of C. albicans bioflims. Specific Aim 2: Investigate the mechanism(s) responsible for increased antifungal resistance of biofilmassociated C. albicans. Specific Aim 3: Identify genes that are involved in the formation and contribute to the development of antifungal resistance of C. albicans biofilms. By studying biofilm model systems and applying this knowledge to the patient population, we will gain a wealth of data about the biology and drug resistance of C. albicans in biofilms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPITHELIA

C.ALBICANS

REGULATION

BETA-DEFENSINS

IN

ORAL

Principal Investigator & Institution: Weinberg, Aaron; Associate Professor; Periodontics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2001; Project Start 28-SEP-2000; Project End 31-JUL-2003 Summary: (adapted from the applicant's abstract) Oropharyngeal candidiasis (OPC) is an emerging disorder owing to the prevalence of AIDS, misuse of antibiotics, and host immunosuppression in general. Candida albicans is the most common fungal species isolated from OPC lesions. Recent findings show that mucosal epithelial cells synthesize and secrete antibacterial and antifungal agents, belonging to a family of small, cationic peptides. These molecules, human beta-defensins 1 and 2 (hBD-1, hBD-2) are predicted to function as a first line of host defense against microbial pathogenesis. The PI has discovered that these peptides are expressed in normal human gingival epithelial cells and associated with differentiated epithelium of oral tissues. Moreover, they found that the non oral, yet disseminating isolate C. albicans strain SC5314 stimulates beta-defensin expression in oral epithelial cells, but a clinical OPC isolate does not. This proposal intends to test hypotheses relevant to oropharyngeal candidiasis emanating from the postulate that oral epithelial cells can be stimulated to produce beta-defensins that protect the host from candidal challenges at the oral mucosal barrier. The objectives of this proposal are (1) to determine beta-defensin expression in oral epithelial cells in response to challenge with OPC derived C. albicans isolates, (2) to characterize key virulence factors of C. albicans SC5314 and OPC isolates that lead to beta-defensin response, (3) to examine beta-defensin protection against C. albicans, and (4) to identify genes in oral epithelial cells associated with C. albicans modulation of beta-defensin expression, using microarray technology. The PI hypothesizes that peptide-based antimicrobial defense may be a way in which the gingival epithelium resists invasion of potential pathogens. In light of the frequent adjunctive use of antibiotics and antimycotics in treating oral diseases, with the threat of microbial resistance, investigations into novel eukaryotic peptides, such as beta-defensins, are highly significant and offer the potential for future clinical promise. The PI states that this research direction may be significant in leading to future studies with potential application to oral disorders, therapeutic use, and technology development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANDIDA ADHERENCE & PENETRATION OF VASCULAR ENDOTHELIUM Principal Investigator & Institution: Edwards, John E.; Professor in Residence; HarborUcla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2003; Project Start 01-SEP-1984; Project End 31-JUL-2004 Summary: (provided by applicant): Candida species are among the most common causes of hospital-acquired infections. Candidiasis is associated with substantial mortality, morbidity, and high hospitalization costs. Ongoing problems with antifungal efficacy and resistance make the development of novel immunotherapeutic approaches highly attractive. Such approaches include a Candida vaccine and passive immunotherapy with anti-Candida antibodies. We have discovered that the Candida albicans protein, agglutinin-like sequence-1 (Als1p) is a potent adhesin for human vascular endothelial cells. We have also found that four additional members of the Als protein family mediate attachment to distinct profiles of host substrates including fibronectin, gelatin, epithelial cells and endothelial cells. Our initial experiments have shown that immunization with recombinant Als1p, and antibodies to the N-terminus of the protein protect mice against lethal challenge of intravenous C. albicans. Therefore, the Als protein family provides promising targets immunotherapeutic strategies. In our proposed experiments, we will 1) define the precise domains of Als proteins that mediate substrate specific binding; 2) determine the three-dimensional structure of these

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Candida

binding domains; 3) identify the endothelial cell ligands which are bound by Als proteins, and 4) determine the in vivo expression profiles of ALS genes, and the tissue tropism they confer. Accomplishing these goals will advance the basic understanding of C. albicans interactions with the host at the receptor-ligand level. The results of these studies will enable our future development of novel immunotherapeutic approaches to block candidal adherence and enhance host defense. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANDIDA ALBICANS ORAL BIOFILM Principal Investigator & Institution: Chaffin, Welda L.; Professor; Microbiology and Immunology; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Candida albicans is a commensal that colonizes skin and mucosal surfaces including the oral cavity. The organism is also an agent of opportunistic disease of these surfaces as well as internal disseminated disease. Oral candidiasis is associated with derangements of the oral flora related with the acquisition of microbes by neonates and anti-bacterial therapy, oral prostheses, and host factors such as diabetes mellitus and HIV infection. Oral manifestations include pseudomembraneous candidiasis (thrush) and denture stomatitis. Oropharyngeal infection is virtually an inescapable consequence of AIDS (96 percent patients) and frequently reoccurs. Denture stomatitis may affect 50 percent of complete denture wearers. The organism forms biofilms on mucosa, teeth and oral devices such as dentures, generally in association with oral bacteria. Compared to planktonic cells, organisms in biofilms have characteristics such as reduced susceptibility to antifungal drugs and the presence of an extracellular matrix. This study will test the hypothesis that unique characteristics associated with C. albicans biofilms are the result of altered gene expression in general cellular metabolism as well as bioflim specific gene expression. A model of saliva-coated denture acrylic established in this laboratory will be used. About 230 alterations in general cellular metabolism have been identified in biofilm compared to planktonic cells by exploiting the high homology between Saccharomyces cerevisiae and C. albicans and the commercial availability of gene arrays for S. cerevisiae. In Aim 1 this approach will be applied to examine expression temporally during biofilm formation and to other conditions of biofilm development using C. albicans DNA chips. In Aim 2, expression in in vitro biodiverse models will also be examined to identify genes inherently associated with biofilms as differentiated from those influenced by the biofilm environment. Expression of selected genes from the inherent biofilm expression class will be determined in vivo in organisms recovered from human saliva. Aim 3 will examine the role of biofilm-regulated genes such as TUP1and EFG1 using genetically modified strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANDIDA PATHOGENESIS IN SURGERY AND TRAUMA Principal Investigator & Institution: Wells, Carol L.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: In the United States, as many as 10% of hospitalized patients develop a nosocomial infection, estimated to involve more than 2 million patients (and 58,000

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deaths), and to cost more than $4.5 billion annually. Candida species represent the 6th most common nosocomial pathogen overall, and the 4th most common cause of nosocomial bloodstream infections. Mortality from systemic candidiasis ranges from 63% to 85% in untreated patients and from 33% to 54% in those who receive appropriate antifungal therapy. Patients at highest risk include immunosuppressed patients, trauma patients, and postsurgical patients. The intestinal tract is believed to be the major colonizing habitat, and the source of most Candida infection. C. albicans accounts for 60% to 80% of all Candida isolates and C. albicans is the most virulent species. C. albicans is eucaryotic and diploid, and it is not possible to construct isogenic mutants using techniques designed for procaryotic bacteria. However, using the "Ura-blaster" method, it has recently become possible to construct isogenic strains of C. albicans that differ from a parent strain by disruption of a single gene; the gene INT1 has been associated with epithelial adhesion, morphogenesis (switching from yeast to hyphal forms), and virulence. In this proposal, well characterized wild-type and mutant strains of C. albicans (carrying two, one, or zero copies of INT1) are used to clarify the pathogenic significance of C. albicans adherence and morphogenesis, emphasizing the oral route of infection in clinically relevant mouse models of surgery and trauma, where experimental variables include antibiotic therapy, parenteral endotoxin, and hypoxia. Relevant in vitro cell culture systems (HT-29 and Caco-2 enterocytes) are also used where more defined conditions can be used to correlate the degree of C. albicans filamentation (production of germ tubes, pseudohyphae, true hyphae) with the degree of adherence, internalization, intracellular survival, and paracellular and transcellular migration. Results from in vitro cell culture systems are correlated with results from in vivo models. The working hypothesis is: Morphologic switching in C. albicans, that is conversion from yeast to hyphal forms, plays a key role in C. albicans adherence and invasion, and thus plays a key role in C. albicans pathogenesis and virulence. Thus, the overall aim is to clarify the relevance of adhesion and morphogenesis in C. albicans pathogenesis. The long term goal is to use this information to target novel treatment regimens to decrease the costly morbidity and mortality associated with systemic candidiasis in surgical patients and trauma patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CENTROMERE STRUCTURE AND FUNCTION Principal Investigator & Institution: Carbon, John A.; Professor of Biochemistry; Molecular, Cellular & Dev Biol; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2003; Project Start 01-JAN-1977; Project End 31-DEC-2007 Summary: (provided by applicant): The long-range objective of this research program is to understand in molecular terms how the centromere-kinetochore functions in eukaryotic cell division. Our previous research in this area emphasized centromere structure/function studies in the budding yeast Saccharomyces cerevisiae and fission yeast Schizo-saccharomyces pombe. Building on the valuable information gained in these groundwork studies, we will now extend the work to investigate centromerekinetochores in the two most common and clinically significant pathogenic budding yeasts, Candida albicans and Candida glabrata. All budding yeast species examined to date contain relatively small point centromeres (CEN less than 400 bp in length), whereas other organisms contain large regional centromeres characterized by the presence of long stretches of heterochromatic repeated DNA sequences. It is postulated that this fundamental difference in centromere structure could be exploited eventually to develop agents selectively toxic to the budding yeasts. Specific aims are: (1) combined

18

Candida

molecular and genetic strategies will be used to isolate and characterize CEN DNAs of C. albicans; (2) stable CEN-based plasmid and artificial chromosome vector systems will be constructed to facilitate molecular genetic research in C. albicans; and (3) inner kinetochore-associated proteins from both C. albicans and C. glabrata will be identified and characterized as potential targets for specific antifungal drug therapy. We have identified, epitope-tagged, and expressed an evolutionarily conserved, centromerespecific histone H3 protein (CaCse4p) in C. albicans. Chromatin immunoprecipitation (CHIP) with antibodies directed against this protein will be used to isolate and clone CEN DNAs. Putative CEN DNAs will be identified and characterized in terms of their nucleotide sequence and ability to mitotically stabilize plasmid and artificial chromosome vectors in actively dividing cells. Inner kinetochore proteins of Candida species will be isolated by CEN DNA affinity chromatography and the corresponding genes will be cloned and characterized. One-hybrid and two-hybrid screens currently under development for use with C. glabrata will be applied to a search for additional genes specifying CEN-associated proteins. Kinetochore association of candidate proteins will be confirmed by ChIP analysis and by studying the effects of gene deletion and/or mutagenesis on cell division and chromosome segregation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF THE S. POMBE CAMP PATHWAY Principal Investigator & Institution: Hoffman, Charles S.; Professor; Biology; Boston College 140 Commonwealth Ave Newton, Ma 02467 Timing: Fiscal Year 2001; Project Start 01-JUL-1991; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's abstract): One way cells respond to their environment is by creating internal signals that regulate gene expression. Human and yeast cells employ homologous signaling pathways to control cell growth, stress response, metabolic pathways and differentiation. Therefore, the relatively simple and genetically pliable budding and fission yeasts are valuable model organisms providing important insights to mechanisms of signal transduction in mammalian cells. My laboratory studies the glucose/cAMP signal pathway that is central to the transcriptional regulation of the fission yeast fbpl gene. Environmental glucose triggers the activation of adenylate cyclase, and the resulting cAMP signal activates protein kinase A to repress fbpI transcription. Many, but not all, of the genes we have identified in this pathway in fission yeast encode proteins whose human homologues carry out similar functions in cAMP signaling. Therefore this model system has the potential both to advance our structural understanding of conserved signaling mechanisms and to lead to novel discoveries. In addition, the catalytic domain of fission yeast adenylate cyclase enzyme closely resembles those of several pathogenic organisms including the human pathogens Trypanosoma brucei and Candida albicans. While the cAMP pathway appears to be important to growth and differentiation of these organisms, nothing is known about the regulation of their adenylate cyclase enzymes. Therefore, our studies may suggest potential targets for inhibiting the growth or invasiveness of these pathogens. We propose to continue our work on adenylate cyclase activation by conducting genetic, molecular and biochemical studies of the fission yeast glucose/cAMP pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF NOVEL ANTIFUNGAL ANTIPC NATURAL PRODUCTS Principal Investigator & Institution: Avery, Mitchell A.; Associate Professor; Medicinal Chemistry; University of Mississippi P.O. Box 907 University, Ms 386770907 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: (Adapted from Applicant's Abstract): The development of a new drug candidate for the treatment of Pneumocystis carinii pneumonia and azole-resistant Candida albicans, and the identification of one or more potential new therapeutic targets in these OI pathogens is proposed. Pseudolaric Acid B (PLAB), a diterpene acid isolated from the bark of a Chinese medicinal plant, Pseudolarix kaempferi, is proposed as a lead compound for the development of a new class of antipneumocystic and antifungal agents. PLAB appears to exert its antifungal activity and antipneumocystic activity by a novel mechanism of action involving a previously unrecognized therapeutic molecular target in these AIDS-related OI pathogens. To accomplish the objectives of new drug development and validation of the proposed new therapeutic target(s), pharmacophore-based tools for drug design by synthesis and bioassay are proposed. Parallel mechanisms of action studies are also proposed. Specifically, these goals will be met by completing ongoing studies directed towards the total synthesis of PLAB using methods that will also provide for construction of analogs not available by semi-synthesis (including carbon-14 labeled PLAB for use in mechanism of action studies); by preparing through semi-synthesis, PLAB analogs from PLAB and PLAC, both of which are in the process of being isolated from bulk quantities of Pseudolarix amabilis; by evaluating all prepared PLAB analogs for in vitro and in vivo inhibition of P. carinii and other fungal OI pathogens and for inhibition/activation of specific molecular targets; by determining the mechanism of action of PLAB and its active analogs by correlating effects on specific molecular targets with whole cell inhibitory effects; and, utilizing data derived above to design mechanism-based inhibitors/ activators of a specific therapeutic target. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DRUGS AND DELIVERY SYSTEMS FOR OPPORTUNISTIC INFECTIONS Principal Investigator & Institution: Miller, Marvin J.; George & Winifred Clark Chair Professor; Chemistry and Biochemistry; University of Notre Dame 511 Main Bldg Notre Dame, in 46556 Timing: Fiscal Year 2001; Project Start 01-FEB-1991; Project End 31-JAN-2003 Summary: (Adapted from Applicant's Abstract) The general goal of this proposed research is to develop new methods and agents for the treatment of opportunistic infections associated with AIDS and other diseases in which the immune system is compromised. Emphasis will be on the design and synthesis of new antifungal drugs and the development of new microbe selective antifungal delivery agents based on active iron transport processes that are necessary for assimilation of physiologically essential iron by pathogens. The general hypotheses to be tested are that the recently developed synthetic methods of the applicant will lead to the design of new antifungal agents (and perhaps other therapeutic agents), and that conjugates of antifungal agents with species selective microbial iron transport agents (siderophores) can be used to actively transport antifungal agents into cells of pathogenic organisms or that selective blockage of fungal iron trasport will inhibit fungal growth. Specific individual aims include: 1) Utilize methods developed by the applicant to prepare a library of

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Candida

siderophores and components to determine which can be recognized and used by opportunistic pathogens such as Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus (though many others will be included in broad screening). 2) Determine if modified forms of siderophores can block iron assimilation by select pathogens and lead to the development of new antimicrobial agents with a novel mode of action by inducing iron starvation. 3) Synthesize and study siderophore- antifungal agent conjugates, including "multiwarhead" conjugates, to determine if they can actively transport antifungal agents (drugs) into the cell or anchor the siderophore-drug conjugate in the cell membrane and, in either case, exert a lethal effect. Known and novel antifungal agents with various modes of action will be conjugated to the siderophores to determine a) optimal microbial selectivity and b) if mammalian toxicity of some drugs can be reduced by siderophore-mediated targeting of the drug to fungi. 4) Study the influence and importance of linkers [covalent (including amide, ester, hydrazone, oxime), ionic and novel "microbe triggered" release processes] between the siderophores and antifungal agents and determine if drug release is necessary. 5) Develop efficient syntheses of novel antifungal agents (and conjugates) including a) forms of potent antifungal neoenactins, b) carbocyclic nucleosides, c) peptidyl nucleosides and carbocyclic analogs, and d) novel "self delivering" antisense oligonucleotides. Detailed broad screen biological evaluation of all the antifungal agents and conjugates will help define important structure-activity relationships to demonstrate the therapeutic potential of microbially- targeted iron transport-mediated design of antifungal agents while enhancing the understanding of the essential role of iron assimilation and metabolism for virulence of opportunistic pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDODONTIC INFECTIONS IN TYPE 1 DIABETIC HOSTS Principal Investigator & Institution: Fouad, Ashraf F.; Associate Professor; Restorative Dentistry; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The causative microbial pathogens and the fundamental host responses in teeth with pulp necrosis and periapical (PA) lesions have not been adequately characterized. Much less is known about these host/pathogen interactions in patients with type 1 diabetes mellitus (DM). We hypothesize that patients with type 1 DM have more symptomatic and/or therapy-resistant PA lesions, which may or may not be related to the degree of their glycemic control. We also hypothesize that in root canals with necrotic pulp of these patients, more virulent and more numerous species of endodontopathic microorganisms are present. The aims of this research project are: (1) Determine the effects of type 1 DM on the development of symptoms in patients with pulp necrosis and apical periodontitis, and on the resolution of the periapical lesion after one year, and (2) Determine the effects of type 1 DM on the prevalence of pathogenic bacteria and Candida albicans before and after root canal preparation in these teeth, using sensitive molecular techniques. Endodontic patients who have type 1 Dm or are non-diabetic, and who have at least one tooth with pulp necrosis and a periapical lesion, will be recruited for this study. Documentation of perioperative symptoms will be done using visual analog scale measure s for pain and swelling. Endodontic treatment will be completed in a standardized manner. Microbial samples form root canals of the teeth treated will be subjected to PCR amplification of the 16SrRNA gene of selected pathogenic bacteria or 18SrRna gene Candida. Analysis will include universal eubacterial identification, followed by species-level identification

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of the selected pathogenic organisms using specific oligonucleotide PCR primers. Molecular sequencing will be performed on the PCR product generated with universal bacterial primers, in order to identify other root canal bacterial species present. Sampling and molecular identification will be repeated just before oburation of the root canals. Patients will have follow-up examinations one year post-operatively, with standardized periapical radiographs. Type 1 diabetic and non-diabetic patients will be compared as to peri-operative symptoms, treatment outcome, number of microbial species in the root canals preoperatively and following canal instrumentation, and the association of microbial species and their quantitative measures with symptoms and treatment outcome. Microbial and clinical factors will also be related to the degree of glycemic control of the diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EOSINOPHILIC INFLAMMATION IN INTRINSIC ASTHMA Principal Investigator & Institution: Kita, Hirohito; Associate Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 10-SEP-2001; Project End 31-AUG-2006 Description (provided by applicant): Toward the achievement of the overall goal of this AADRC, Project 3 "Eosinophilic Inflammation in Intrinsic Asthma" will address why eosinophilia inflammation persists in the airways of patients with asthma and what significance eosinophil degranulation has in the disease process of human asthma. Bronchial mucosal abnormalities that characterize asthma, such as persistent airway eosinophilia and increased T cells producing IL-5, strongly suggest an ongoing T helper (Th)2-like immune response of the airways. Atopy and an IgE-mediated response to extrinsic antigens are the known and identifiable predisposing factors for asthma. However, many adult patients with asthma do not seem to be particularly atopic. The objective of this project is to elucidate the causes and pathophysiologic mechanisms of asthma in patients that are not demonstrably atopic, a condition commonly referred to a non-atopic or intrinsic asthma. We will test the hypothesis that bronchial asthma in patients with non-atopic asthma is caused by a chronic immunologic reaction to intrinsic antigen, namely fungi present in the airways, resulting in persistent IL-5 production and eosinophil activation in the airways. In Specific Aim 1, we will define the enhanced immunological responses, especially IL-5 and IFN-gamma production, of patients' immune cells to non-pathologic fungal organisms present in the airways. In Specific Aim 2, we will directly test whether fungal organisms present in the airways are involved in the disease process by removing the fungi from the airways by instillation of an antifungal agent. Conversely, the effects of an increased fungal antigen burden will be investigated by segmental broncho-provocation. In Specific Aim 3, we will use novel antibodies that recognize eosinophil degranulation activities to define the clinical relevance of eosinophil activation in human asthma by testing the hypothesis that enhanced eosinophil activation and degranulation in the airway lead to exacerbation of asthma symptoms in patients with non-atopic asthma. Elucidation of the causes and mechanisms of inflammation in non-atopic asthma will likely foster a better understanding of eosinophilia inflammation in human asthma and will enhance development of specific and effective therapies for this difficult disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALBICANS

ESSENTIAL

PROTEIN

SECRETION

GENES

OF

CANDIDA

Principal Investigator & Institution: Wong, Brian; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Description (Adapted from abstract): Candida albicans causes more serious infections in humans that any other fungus. The C. albicans genome program is making steady progress and it is expected that > 6000 genes will be sequenced within the next year. The function of many of these genes can be studied by gene disruption and phenotypic analysis, but essential genes cannot be disrupted without loss of viability. The overall goals of this project are to: 1) develop new approaches for studying essential C. albicans genes using two secretion pathway genes as models and 2) use these approaches to study intracellular transport and secretion of two virulence associated C. albicans proteins. In Saccharomyces cerevisiae, SEC4 and YPT1 encode small ras-like GTPases that are required, respectively for fusion of post-Golgi secretory vesicles to the plasma membrane and for ER-to-Golgi protein transport. The SEC4 and YPT1 genes of C. albicans have been cloned and sequenced. When gene disruption experiment suggested that C. albicans SEC4 was essential, it was found that over expressing a mutant sec4 allele similar to those encoding dominant inhibitors of other ras-like GTPases inhibited growth, protein secretion and fusion of secretory vesicles to the plasma membrane in C. albicans. These results demonstrated the feasibility of using molecular approaches to study essential C. albicans genes. Aim 1 is to i) generate C. albicans strains with temperature sensitive and/or inducible dominant-negative sec4 mutations and ii) determine if double-stranded RNAs can block expression of SEC4 and other C. albicans genes. Aim 2 will define the functions of C. albicans SEC4. The C. albicans strains from Aim 1 will be tested for growth an survival, morphology and germ tube formation, ultrastructure, and the ability to transport and secrete aspartyl protease and phospholipase B. Aim 3 will generate C. albicans strains with loss-of-function ypt1 mutations and to use these mutants to define the functions of C. albicans YPT1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FOCUSED PARALLEL SYNTHESIS OF DICATION ANTIFUNGAL AGENTS Principal Investigator & Institution: Tidwell, Richard R.; Professor of Pathology and Laboratory Me; Pathology and Lab Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: The proposed studies stem from our previous research on the antifungal activity of dicationic molecules. These initial in vitro studies on over 300 dication molecules showed that leading compounds were both inhibitory and fungicidal against Candida albicans and Cryptococcus neoformans with MIC80S of <0.09 g/mg and MFCs of 0.10 g/ml against both organisms. Our studies also demonstrated that the compounds were active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans and fluconazole-resistant strains of C. albicans and C. neoformans. An outside laboratory confirmed our in vitro data and also showed that leading compounds against A. fumigatus had IC50 values that were less than 0.0050 mu g/ml and selectivity indices, when compared to HeLa cell, over 2000. More importantly, the outside laboratory demonstrated that one of the compounds was equally as active as fluconazole in a mouse survival model of candidiasis. The above findings along with

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our studies on the toxicology and pharmacology of dicationic compounds clearly show that these molecules have great potential as antifungal agents. The current proposal will expand these initial studies by synthesizing over 2,400 related molecules per year utilizing combinatorial chemistry technology and testing these molecules in an in vitro model for activity against C. albicans and A. fumigatus and toxcity in THP-1 cell (human monocytes). Since the exact mechanism of antifungal activity is not known, and previous results indicated that more than one mode of action may contribute to their antifungal activity the compounds will be screened against the organism rather than a specific target. The antifungal data will be subjected to detailed QSAR and modeling studies and these results will be used to guide either the expansion of proposed libraries, the development of new libraries, or off resin synthesis of a small subset of related molecules. Finally, selected molecules will be tested in animal models of fungal infections. This proposal brings together a seasoned group of investigators with over seven years of successful collaboration on antimicrobial research. Utilizing the combinatorial chemistry methodology to build focused libraries coupled with highthroughput screening and data management will optimize the groups chances of achieving the goal of this project; the discovery of new antifungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION OF B-DEFENSINS IN COMMON ORAL INFECTIONS Principal Investigator & Institution: Guthmiller, Janet M.; Dows Inst for Dental Research; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-MAY-2003 Summary: (adapted from the Investigator's abstract): The most prevalent infections in the oral cavity are represented by periodontal diseases and candidal infections. Both result in an immune response represented, in part, by innate mechanisms. Antibiotic peptides are considered a key component of innate immunity. The beta-defensins are recently discovered antimicrobial peptides produced by epithelial cells whose role in protection against oral infections is as yet unknown. The hypothesis underlying the planned research is that beta-defensins function as antimicrobial agents in periodontal diseases and Candida infections. In this application, the Principal Investigator proposes studies of human beta-defensins 1 and 2 (HBD1 and 2) which they and others have recently found to be expressed in oral epithelia. The following specific aims are proposed for these studies. Aim 1 is to determine the cell-specific localization and expression of HBD-1 and HBD-2 in the oral cavity in health and disease. This aim will be addressed using both in situ hybridization and immunohistochemistry to reveal localization, and ribonuclease protection assays and RT-PCR to indicate expression. Secretion of the peptides will be assessed using Western blots. Aim 2 is to determine what the antimicrobial properties of the human beta-defensins are against periodontal bacteria and Candida. Using recombinant peptides in established antimicrobial assays, the spectrum of antimicrobial activity of the beta-defensins against oral organisms will be determined. Aim 3 is to determine what factors regulate the expression and secretion of beta-defensins in oral epithelia. To understand how beta-defensin gene expression and secretion may be regulated, cultured oral keratinocytes will be treated with candidate regulatory factors including periodontal bacteria, Candida organisms, proand anti-inflammatory cytokines and glucocorticoids. Expression of mRNA and peptide levels will be examined through the use of ribonuclease protection assays and Western blots, respectively. From these studies the Principal Investigator hopes to increase current understanding of the role beta-defensins play in the innate immunity of

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periodontal and Candida infections so as to be able to develop new therapeutic modalities against a group of prevalent oral diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION PROPERTIES OF HEMOGLOBINS AND MYOGLOBINS Principal Investigator & Institution: Olson, John S.; Professor; Biochemistry and Cell Biology; Rice University 6100 S Main Houston, Tx 77005 Timing: Fiscal Year 2003; Project Start 01-DEC-1976; Project End 31-AUG-2007 Summary: (provided by applicant): Our long range research goals are: (a) to develop stereochemical theories for ligand capture and bond formation in hemoglobins (Hb) and myoglobins (Mb); (b) to determine the mechanism of how these proteins and microbial flavohemoglobins (flavoHb) oxidize nitric oxide to nitrate without producing toxic side products; and (c) to develop strategies for inhibiting the NO dioxygenase activity of flavoHbs from pathogenic microorganisms. We have identified the roles of specific amino acids, structural motifs, and stereochemical effects in regulating O2 affinity, ligand discrimination, rates of ligand binding, and NO dioxygenation using mammalian Mb as a model system. Proof of the validity of these mechanisms and their extension to other proteins requires further testing with Mb and detailed comparisons of the functional and structural properties of four unique animal hemoglobins and three microbial flavoHbs. Three new projects are planned to achieve these goals. (1) More rigorous tests of the side path kinetic model for ligand binding in Mb will be carried out using time resolved X-ray crystallography, mutagenesis of amino acids located along the putative pathways, and measurements of the binding of alkyl isocyanides as stereochemical probes of the distal pocket. (2) The generality of the histidine gate for ligand entry and the electrostatic theory for distal regulation of O2 affinity will be tested in four different heme protein systems in which: (a) the distal histidines are exposed to solvent - alpha and beta subunits of tetrameric human HbA; (b) movement of the distal histidine is restricted by a novel dimeric interface between adjacent E-helices - lamprey Hb; (c) the distal histidine gate is completely blocked by a large polar interface Scapharca inequivalvis Hbl dimers; and (d) a well-defined internal hydrophobic channel appears to be the pathway for ligand entry and exit - Cerebratulus lacteus Hb. (3) The mechanisms and intermediates involved in NO dioxygenation by MbO2, HbO2, and microbial flavoHbO2 will be determined by rapid-mixing absorbance, freezequench EPR, and flow-flash laser photolysis techniques, and the applicability of the results will be tested in two new flavoHbs from fungal pathogens, Candida albicans and Aspergillus fumigatus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONS, TRAFFIC AND TARGETING OF FUNGAL ADHESINS Principal Investigator & Institution: Erdman, Scott E.; Biology; Syracuse University Syracuse, Ny 13210 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The fungal cell wall plays a critical role in protecting cells from osmotic stress and, in conjunction with the actin cytoskeleton, in regulating cell shape as a function of cell growth. In many fungal species growth is polarized during the formation of buds, mating projections and hyphae. Components found in the cell wall also regulate cell-cell adhesion reactions such as flocculation during vegetative growth, sexual agglutination and pathogen-host cell adhesion. These processes are crucial to the life cycles of many fungi pathogenic to humans including Candida species,

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Cryptococcus neoformans, Aspergillus fumigatus and Histoplasma capsulatum. While many key adhesion molecules responsible for cell-cell adhesion have been identified, little is presently known concerning the factors that regulate the localization, trafficking and activity within the cell wall of these glycoproteins which play key roles in pathogenesis. This proposal aims to further elucidate the structure and function of conserved WCPL and CX4C domains found in a super family of cell wall Mann proteins that are present in both S. cerevisiae and C. albicans and involved in their differentiation. The genetically tractable system of cell adhesion during mating in S. cerevisiae will be used to study the domain organization, cell wall localization and mechanisms regulating activity of a model cell wall protein, Agalp, which is a member of the super family. These studies will use biochemical and genetic methods to investigate the possibility that the WCPUCX4C domains mediate post-secretory traffic of the protein within or at the surface of the fungal cell wall. A novel approach designed to develop peptide reagents with the potential to act as specific inhibitors of the fungal adhesins Aga2p and Hwpl p and/or as structural platforms for antifungal drug development and delivery will be explored. We expect these studies to add to our understanding of fungal cell wall Mann protein modification, localization and function; such information is likely to be useful to the future design and targeting of anti-fungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC ANALYSIS OF ECHINOCANDIN SENSITIVITY Principal Investigator & Institution: Katiyar, Santosh K.; Assistant Professor; Microbiology and Immunology; Drexel University 3201 Arch Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Fungal infections are a major cause of morbidity and mortality in the immunocompromised patient. Until recently, available antifungals were limited by systemic toxicity (polyenes and imidazoles), lack of fungicidal activity (triazoles and flucytosine), or narrow spectrum (allylamines). Echinocandins (ECs) such as the recently FDA-approved caspofungin represent a new antifungal class that appears to address these limitations. ECs inhibit the fungal specific enzyme beta-1,3glucan synthase responsible for synthesizing a major cell wall polysaccharide. While common fungal pathogens such as Candida albicans and Aspergillus fumigatus are susceptible to ECs, others such as Cryptococcus neoformans are intrinsically resistant for reasons that are unclear. Also, there is an undefined potential for the selection of ECresistant or tolerant mutants of normally susceptible fungi. Using Saccharomyces cerevisiae as genetic model, initial experiments identified unique sets of "ECH" genes which, when overexpressed or deleted, conferred EC resistance or hypersensitivity. These genes encode Golgi or plasma membrane-associated proteins known to play roles in cell wall synthesis, as well as protein kinases, transcription factors, and other proteins with no previous connection to this process. But do these S. cerevisiae results have relevance to EC activity in clinically important fungi? This R03 proposal will examine this through the following Specific Aims: (1) Complete the identification of S. cerevisiae ECH genes by replica plate screening for hypersensitive deletion mutants, and test all mutants for altered antifungal sensitivities and other relevant phenotypes. (2) Construct C. albicans strains with deletions in representative ECH homologs and test for altered susceptibilities to ECs and other antifungals, and for other relevant phenotypes such as altered yeast-hyphal morphogenesis. (3) Select in vitro for C. albicans spontaneous ECresistant or tolerant mutants (initial studies revealed a high frequency of the latter) and

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Candida

examine for altered gene expression by RNA hybridization and altered gene products by DNA sequencing. Building on this foundation, future studies are likely to include: (1) testing the in vivo susceptibility and virulence of these EC-resistant or tolerant mutants, (2) identifying drugs which act synergistically or antagonistically with ECs and determining the basis for these interactions, (3) characterizing mechanisms for acquired and intrinsic EC resistance in clinical isolates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC VARIABILITY OF THE YEAST CANDIDA ALBICANS Principal Investigator & Institution: Sherman, Fred; Professor; Biochemistry and Biophysics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-MAR-1993; Project End 30-NOV-2004 Summary: (Verbatim from Applicant's Abstract): Clinical isolates of the pathogenic yeast Candida albicans exhibit extensive variation in electrophoretic karyotypes and in phenotypic polymorphism. In this connection, systematic studies conducted in our laboratory revealed that laboratory strains of C. albicans spontaneously give rise to high frequencies of many different types of mutants having altered phenotypes and karyotypes. The significance of the chromosomal alterations was established with spontaneous mutants that acquired the ability to utilize alternative carbon sources. A causal relationship was established with a series of Sou- to Sou+ to Sou- to Sou+ derivatives, in which the Sou- (L-sorbose none-utilizing) and Sou+ (L-sorbose utilizing) strains were, respectively, disomic and monosomic for chromosome 5. Furthermore, transcription of the SOU1 gene, required for L-sorbose utilization, was regulated by the copy number of chromosome 5, in spite of the fact that SOU1 resides on a different chromosome. A hypothetical negative regulator, CSU51, was postulated to reside on chromosome 5, such that transcription of SOU1 is dependent on the ratio of the CSU51 to SOU1 copy number. Other examples of negative regulation by chromosome copy number include the utilization of D-arabinose, Aru- to Aru+, and resistance to the antifungal agent, fluconazole, FluS to FluR, thus establishing a general regulatory mechanism. The major long-term goal of the proposed research is to determine mechanisms of this newly-discovered regulatory process in C. albicans, by which gene expression is controlled by chromosome copy number. Several candidates of the negative regulator residing on chromosome 5 have been isolated from a library of chromosome 5 DNA, and these are being characterized. These regulators will be investigated for their direct or indirect interaction with the SOU1 structural gene. The additional negative regulators, which were retrieved from a total genomic library, and which are located on different chromosomes, will be analyzed for their involvement in the regulatory network controlled by chromosome copy number. This work establishes for the first time a negative regulatory network for a secondary carbon source in an important pathogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENOMIC APPROACHES TO CANDIDA VIRULENCE Principal Investigator & Institution: Agabian, Nina M.; Professor; Stomatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: The long term goal of this proposal is to use post-genomics era technologies and approaches to increase our understanding of the molecular basis of pathogenesis in HIV-related oral candidiasis. Our immediate goal is to fabricate DNA micro arrays

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using the C. albicans genomic DNA sequence data generated by the Stanford DNA Sequencing and Technology Center (Stanford Center). Using this technology the patterns of C. albicans gene expression in various disease contexts will be assessed. This information will contribute to the development of specific diagnostics, drug targets and insights into the mechanism of C. albicans pathogenesis in immunocompromised individuals. The Specific Aims of this proposal are to:(1) fabricate DNA micro arrays using both PCR-product based and oligonucleotide-based technologies. Fabrication of whole genome DNA micro arrays will be completed before the termination of this grant. Fabrication will be an iterative process, beginning immediately with the construction of PCR based DNA micro arrays and using a subset of available C. albicans genomic sequences. At an early stage in these studies, protocols to make the micro arrays generally available to the Candida research community will be developed. (2) The first generation of micro arrays will be used to analyze patterns of gene expression in C. albicans obtained from a variety of environments. This will be the first approach to cataloging the function and coordinate expression of gene sequences, both known and unknown. One of the many key issues in the study of pathogenesis is the validation of animal models of infection as these will provide the basis for further analysis of genes whose functions are as yet unknown. We are therefore particularly interested in comparing the patterns of expression of C. albicans genes in the oral mucosa, with those expressed in the extant rodent models. (3) initiate the functional analysis of individual genes of interest. Comparison of the patterns of gene expression using micro arrays will identify genetic sequences which merit further study. Those of unknown function will be targeted for further genetic analysis, including the construction of specific knockout mutations and the analysis of ensuing phenotype. In this way it will be possible to begin a complete characterization of the range of gene expression which contributes to the pathogenesis of Candida in different host contexts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLYCOSYLATION IN THE YEAST GOLGI Principal Investigator & Institution: Dean, Neta; Biochemistry and Cell Biology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-SEP-1995; Project End 31-AUG-2003 Summary: Glycosylation is an essential modification that functions in a variety of biological roles ranging from the stabilization of protein structure to the regulation of cell surface properties. Despite its importance, glycosylation remains one of the most poorly understood of all the metabolic processes. The overall goal of this research is to understand how glycosylation is regulated and how carbohydrate modifications mediate their biological roles. The proposed experiments will focus on two key families of proteins that are required for terminal carbohydrate additions in the Golgi. These proteins are the nucleotide sugar transporters (NSTs), which provide the lumenal sugar substrates, and the glycosyltransferases, which catalyze sugar additions on proteins and lipids. Using the yeast S. cerevisiae as a model system, a combined genetic and biochemical approach will be used to study these enzymes. The first specific aim will be to study the mechanism by which NSTs transport nucleotide sugars into the Golgi. Using the VRG4-encoded GDP-mannose transporter as a model, novel vrg4 mutants will be isolated and assayed for defects in the binding or transport of GDP-mannose and in dimer formation. Each mutant allele will be characterized to determine the molecular basis for the defective phenotype. The in vivo function of other VRG4-homologs will also be investigated. The proposed experiments will provide important new information relating the structure of NSTs to their biological function and will contribute to our

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understanding of these proteins in other species. An understanding of the Vrg4 protein also has important implications for human disease. VRG4 is indispenable for the synthesis of cell wall mannoproteins which are key determinants in fungal pathogenicity. Although VRG4 is essential for yeast viability, it does not have a mammalian counterpart. These features make VRG4 an attractive target for anti-fungal therapies. As a first step in our long term goal of developing VRG4 as a drug target, the second specific aim is to investigate the biological role of the VRG4 gene in Candida albicans, the most frequently isolated fungal pathogen in humans. Another major aspect of this application addresses basic questions about the mannosyltransferases that function in the cis-Golgi. A subset of these proteins exists together in the membrane as a multiprotein complex. The third specific aim is to determine the requirements for complex assembly and to examine whether complex assembly and localization in the Golgi are related processes. These studies could reveal important principles for glycan synthesis in other systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GU INFECTION SELF-DIAGNOSIS FOR DEPLOYED MILITARY WOMEN Principal Investigator & Institution: Ryan-Wenger, Nancy A.; Professor; None; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-JAN-2005 Summary: Approximately 347,000 women serve in the U.S. military, and regularly deploy to austere military environments where harsh climate and terrain, primitive hygiene facilities, and unavailable or unacceptable health care resources for women increase women's risk for development of vaginitis and urinary tract infections (UTI). Untreated or inadequately treated symptoms of bacterial vaginosis, trichomonas vaginitis, candida vaginitis, and UTI are miserable, embarrassing, distracting and significantly interfere with women's quality of life, comfort, and concentration. In deployment situations, a viable solution to the problem is a field-expedient kit for selfdiagnosis and self-treatment of these symptoms. Preliminary work supports the need for such a kit and the feasibility of developing a kit that is user-friendly, sensitive and specific. In this study, 1560 Army and Navy women who seek care from a military clinic for vaginal or urinary symptoms, will conduct a self-diagnosis using a Decision-Making Guide and selected materials to measure vaginal and urinary symptoms, and vaginal pH and amines. We will test the sensitivity and specificity of military women's selfdiagnoses in comparison with laboratory reference standards (urine culture and DNA probe testing for gardnerella vaginalis, trichomonas vaginalis, and candida species). A research advanced practice nurse (APN) will enroll women in the study, conduct a protocol-driven clinical diagnostic examination, and treat the women with selected single-dose oral medications that will ultimately be included in the field-expedient selfcare kit. The women's observations on the Decision-Making Guide will be compared with the APN's clinical observations to evaluate the extent to which each item in the Guide contributes to the true diagnosis. We will also estimate the frequency with which women would have made an error in self-treatment based on their self- diagnoses if they had used this kit during deployment. The women will return to the clinic for follow-up visits with the APN in order to evaluate their satisfaction with the selfdiagnosis process and the single-dose oral treatment of their symptoms, and for their recommendations for improvement of the kit. While this proposed research focuses on a self-care intervention for military women, it has a much broader potential for use by

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civilian women who find themselves in austere environments for other reasons, i.e. missionary work, Peace Corps, humanitarian missions, expeditions, or foreign travel. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH THROUGH-PUT DETECTION OF FUNGAL PATHOGENS Principal Investigator & Institution: Fell, Jack W.; Marine Biology and Fisheries; University of Miami Coral Gables University Sta Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Diagnoses of opportunistic fungal infections constitute an increasing clinical problem. Conventional diagnostic tests are time consuming and lack specificity and sensitivity for accurate and timely prognoses. The lack of precise and prompt diagnoses has undermined the health of patients and contributed to high mortality rates in immunocompromised individuals undergoing aggressive medical treatments. This condition has led to an increase in the emergence of new antifungal resistant strains and the need for rapid non-culture based methods for the detection of pathogens at species and strain levels. In cooperation with a unique team of researchers from government (USDA, Peoria, Ill), academia (University of Miami), two clinical laboratories (John Hopkins Medical Institute and Allogen Laboratories of the Cleveland Clinic) and industry (Luminex Corp, Austin, TX) we propose to develop a sensitive, fast and reliable high throughput DNA based method aimed at detection of such important fungal pathogens as species of Aspergillus, Candida, Cryptococcus and Trichosporon. The detection method will combine the specificity and reliability of nucleic acid hybridization analysis with the speed and sensitivity of LabMap, a new flow cytometric technique by Luminex Corp. The multiplexed assay analysis will consist of a combination of fluorescent microspheres covalently bound to species-specific fungal oligonucleotide probes, with the capability to simultaneously test as many as 100 different species-specific probes per tube/well at rates 0.47 min/well probes per minute. In the preliminary stages of this research, the system will be developed with extensive in-house databases and culture collections from USDA and UM and from clinical isolates from JHMI to produce a detection technique for cultured organisms. Validation of the assay with archived clinical specimens will be in conjunction with the Allogen Lab, which will lead to a detection system directly from clinical specimens. The fungal detection system will be expanded to include all known yeasts, including medical, foodborne and industrial species as well as other filamentous pathogens. We foresee that this multiplex testing fungal platform can be expanded to other microorganisms with important applications in areas of public health, bioterrorism, food safety and the environment. Resulting data will be disseminated via GenBank, publications in leading scientific journals and as an inexpensive commercial detection system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV AND NEUTROPHIL FUNCTION IN ORAL DISEASE Principal Investigator & Institution: Thomas, Larry L.; Associate Professor; RushPresbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 03-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Neutrophils play a key and essential role in the innate immune response against candida infection, which is the most frequent oral manifestation of HIV infection. Results obtained with neutrophils isolated from blood of HIV-infected individuals have variously demonstrated that neutrophils of HIV-infected

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individuals display increased apoptosis, constitutive activation, and diminished responsiveness to inflammatory stimuli. It is not known, however, how HIV infection influences the functional status of neutrophils within the oral cavity. It is postulated that an alteration in neutrophil function contributes to the increased incidence of candidiasis and periodontal disease in HIV-infected individuals. Moreover, a second role for neutrophils in HIV infection is suggested by the findings that neutrophils bind HIV-1 and increase infection of T lymphocytes as well as increase viral replication in HIVinfected PBMC. Consistent with this postulated role, increased shedding of HIV-1 is observed with gingival linear erythema, which is frequently associated with candida infection and, thus, also an influx of neutrophils into the oral cavity. The relationship between the neutrophil functional status and the capacity of neutrophils to enhance HIV infection and replication, however, is not known. This relationship may be directly relevant to the vertical transmission of HIV infection to infants via breast-feeding by HIV+ mothers, which remains an important route of infant HIV infection in underdeveloped countries. Indeed, oral candidiasis in infants is a risk factor for the vertical transmission of HIV infection via breast milk by HIV+ mothers. Accordingly, this proposal has two specific aims. (1) Does dysregulation of neutrophil function contribute to the increased incidence of oral candidiasis and periodontal disease in HIVinfected patients? (2) Does activation or apoptosis alter the capacity of neutrophils to bind HIV and/or to enhance HIV infection and replication of macrophages or lymphocytes? It is proposed that the results of this study will provide important insight into the essential role of neutrophils in innate immunity within the oral cavity of HIVinfected patients and also into a possible role of neutrophils in the vertical transmission of HIV infection. As such, the results may provide an additional target to enhance innate immunity within the oral cavity and also to decrease the vertical transmission of HIV in breast milk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIV MODULATES ORAL MUCOSAL CALPROTECTIN AND CANDIDIASIS Principal Investigator & Institution: Ross, Karen F.; Oral Sciences; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Calprotectin is a candidacidal protein complex that is constitutively expressed by squamous mucosal epithelial cells. Epithelial cells expressing calprotectin appear to form a barrier to hyphal penetration. During HIV infection the expression and release of calprotectin into saliva is significantly reduced suggesting that expression of mucosal epithelial calprotectin is impaired. In AIDS, calprotectin is down-regulated and the risk of candidiasis increases. Cross talk between keratinocytes and infected immature dendritic and other immune cells are likely to play a significant role in the translocation of HIV, down regulation of calprotectin and the occurrence of candidiasis. We hypothesize, therefore, that HIV infection of oral mucosal epithelial cells down-regulates calprotectin to reduce resistance to Candida. To test this hypothesis, we will 1) determine the requirement of oral mucosal epithelial calprotectin in transcytosis of HIV; 2) determine if uptake of HIV into oral epithelial cells regulates expression of calprotectin-specific mRNA; 3) ascertain if dendritic or other immune cells cooperate with oral keratinocytes during HIV infection to down-regulate expression of calprotectin; 4) analyze oral epithelial cells before and after transcytosis for susceptibility to Candida infection; and 5) determine if susceptibility to Candida infection is associated with down-regulation of calprotectin. Collectively these experiments will

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suggest the basis for calprotectin protection against Candida infections, how innate immunity is thwarted in AIDS, and will set the stage to precisely define these mechanisms in a subsequent R01 application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST-RESPONSE CANDIDEMIA

RELATIONSHIPS

IN

PATIENTS

WITH

Principal Investigator & Institution: Johnson, Melissa D.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Bloodstream infections due to Candida species are encountered with an increasing frequency in clinical practice, leading to significant morbidity and mortality. This project will involve the unprecedented study of over 700 patients to systematically evaluate select factors associated with outcomes among patients with fungemia due to albicans and non-albicans Candida spp. This will result in the largest collection of data worldwide investigating host-response relationships among patients with candidemia, and involve both retrospective and prospective investigations. The project will enable the candidate, Melissa Johnson, to learn the skills necessary to become a successful clinician-scientist. She is a member of the Duke University Mycology Research Unit, which has a long and rich tradition of excellence in investigation of basic and clinical mycology. Together with her mentor, John R. Perfect, and supported by the resources of the Department of Medicine at Duke University Medical Center, she will develop a model for risk- assessment and an evidence-based treatment approach for patients with fungemia due to Candida spp. She will also evaluate the role of select pharmacodynamic, immunogenomic, and pharmacogenomic factors in associated clinical outcomes in candidemic patients. This award will enable the candidate to build upon her experiences as a clinician and researcher and obtain the skills critical for success as an independent investigator. Project activities will strengthen the candidate's technical abilities through exposure to a variety of laboratory techniques. She will also learn the various facets of epidemiologic methods, study design, mathematical modeling, and statistical analysis through interaction with her collaborators and project advisors. In addition, she will complement project activities with graduate-level coursework in pharmacokinetic and pharmacodynamic modeling at University of North Carolina and statistics, epidemiology, and clinical research as she completes the Master of Science in Clinical Research at Duke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IDENTIFYING CANDIDA GENE IN THRUSH USING IVIAT Principal Investigator & Institution: Nguyen, M H.; Medicine; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-JUL-2004 Summary: (abstract verbatim) The applicants have used a novel in vivo microbial expression technology called In Vivo Induced Antigen Technology (IVIAT) to study the pathogenesis of oropharyngeal candidiasis (OPC) in HIV-infected patients. IVIAT uses anti-Candida albicans antibodies in the sera of HIV-infected patients to identify antigens that are expressed in vivo by C. albicans but are not expressed during routine in vitro growth. In preliminary studies, they have confirmed that IVIAT can identify virulence factors for C. albicans. In this proposal, they propose to modify IVIAT to identify antigens expressed by C. albicans during OPC but not expressed during either

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Candida

colonization of the oral mucosa by C. albicans or during in vitro growth. They hypothesize that some of the antigens expressed by C. albicans exclusively during OPC are important virulence factors, and identifying these antigens will provide insight into the mechanisms by which C. albicans is transformed from a harmless commensal organism into an invasive pathogen. This application has five specific aims. In the first specific aim, two separate pooled batches of sera, one from HIV-infected patients with OPC and the other from HIV-infected patients with colonization, will be exhaustively adsorbed with in vitro grown clinical C. albicans isolates to remove all antibodies that react with antigens expressed in vitro. The adsorbed sera will be used for differential screening of a C. albicans genomic expression library. In specific aim 2, the plasmid DNA will be purified from clones that are reactive with the OPC sera but not with the colonization sera and the open reading frames (ORFs) responsible for the serum reactivity will be determined. In specific aim 3, they will confirm that the IVIAT antigens are not expressed by C. albicans in vitro. In specific aim 4, they will clone C. albicans genes encoding IVIAT antigens and purify the proteins expressed by these genes. Lastly, in specific aim 5, they will confirm that the IVIAT antigens are present within thrush samples recovered from HIV-infected patients by light microscopic immunohistochemistry using antibody raised against the purified proteins. They hope that this study will identify new C. albicans virulence factors, increase our understanding of the humoral response to OPC, and lead to potential applications for drug, vaccine or diagnostic test development. With the experience from this project, IVIAT should be readily adaptable to study other candidal infections and other fungal pathogens. Potential advantages of IVIAT over existing technologies include the use of the human immune response to identify in vivo expressed genes rather than animal models, its relative technical simplicity, and its ability to study differential gene expression in different types of C. albicans infections in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNODOMINANT STRESS PROTEINS OF P. GINGIVALIS Principal Investigator & Institution: Lopatin, Dennis E.; Professor; Biologic & Materials Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAY-2006 Summary: Studies performed in our laboratory implicate the Porphyromonas gingivalis HtpG stress protein, the prokaryotic homologue of Hsp90, in the etiology of periodontal disease. We have reported that elevated levels of anti-Hsp90 antibodies, concomitant with P. gingivalis colonization, are associated with periodontal health. Transcription of HtpG message was also found to be upregulated 7-10-fold in P. gingivalis obtained from diseased subgingival plaque. There is a precedence for Hsp90 homologues contributing to pathogenicity of other microorganisms. Immunity to a single Hsp90 epitope of Candida albicans has been demonstrated to confer protection against systemic candidiasis. Studies performed by our laboratory have revealed that P. gingivalis HtpG has a significant degree of homology with human Hsp90, but remains clearly distinct from other HtpG proteins due to its unique C-terminal region. We have found that HtpG is localized to P. gingivalis membranes and extracellular vesicles, and that it crossreacts with other prokaryotic and eukaryotic Hsp90 homologues. Our findings suggest that HtpG is readily accessible to participate in host cellular invasion processes, as well as to interfere with normal host cell functions one P. gingivalis enters the host cytoplasmic compartment. Transfection of KB cells with the P. gingivalis htpG gene stimulates IL-8 production by these cells. This application proposes to extend our

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investigations into the role that molecular mimicry by HtpG plays in the pathogenicity of P. gingivalis. Previous studies of other pathogenic microorganisms which appear to use the Hsp90 homologue as a virulence factor have been purely descriptive. Our application is unique in that while will propose to evaluate the role of HtpG in adherence and invasion mechanisms, we also propose to elucidate novel pathogenic mechanism(s) by which microorganisms such as P. gingivalis utilize molecular mimicry to disrupt normal eukaryotic cell function(s). Since the most clearly defined eukaryotic Hsp90-mediated mechanisms involved signal transduction pathways, these will be the primary foci of our investigations. The hypothesis to be tested in this study is: 1) HtpG plays a role in adherence and invasion of host cells; and 2) once internalized, signal transduction mechanisms mediated by Hsp90/TRAP1 within eukaryotic cells are disrupted by the HtpG of P. gingivalis through molecular mimicry. This leads to disruption of normal inflammatory cytokine responses to microbial invasion by P. gingivalis and other oral microorganisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFECTIONS

IMMUNOLOGICAL

REGULATION

OF

BURN-ASSOCIATED

Principal Investigator & Institution: Suzuki, Fujio; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Herpes simplex virus type 1 (HSV-1) and Candida albicans are severe pathogens in thermally injured patients (TI patients). We are attempting to regulate these infections in TI patients immunologically. A predominance of type 1 T cell responses (an essential host's defense against these infections) was not produced in patient PBL-SCID chimeras (SCID mice inoculated with peripheral blood lymphocytes from TI patients) that were manifested by burn-associated type 2 T cell responses. In previous studies, the infection-associated mortality of patient PBL-SCID chimeras was markedly reduced when they were treated with IL-12 (an inducer of type 1 T-cell responses) and sIL-4R (an inhibitor of type 2 T cell responses) in combination. However, differences in the effectiveness of the combination therapy could be related to the levels of type 1/type 2 T cell responses that affect the severity of infection with HSV-1 and C. albicans. Because a very large number of patient PBLs with high activity of type 2 T cell responses is required to explore these questions, experiments utilizing patient PBL-SCID chimeras are impractical. Therefore, in this proposal a novel model of healthy donor's PBL-SCID chimeras with experimentally enhanced type 2 T cell responses will be used. To accomplish immunological regulations of burn-associated HSV-1 and C. albicans infections, the following studies are proposed; (1) to determine a soluble initiation factor(s) (or initiation cells) for the subsequent development of burn-associated type 2 T cell responses; (2) to induce various levels of type 2 T cell responses in human SCID chimeras (type 2/human SCID chimeras); (3) to enhance optimal levels of type 1 T cell responses in type 2/human SCID chimeras; and (4) to regulate various levels of established infections with HSV-1 or C. albicans in type 2/human SCID chimeras by the combination of IL-12 +/- IL-18 and sIL-4R. Established infections with these pathogens in type 2/human chimeras would be expected to be immunologically controlled by the combination therapy. To understand if it is possible to regulate HSV-1 and C. albicans in TI patients, the information obtained by this proposal might be critical. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Candida

•

Project Title: LETHAL OROESOPHAGEAL CANDIDIASIS: IMMUNOTHERAPY Principal Investigator & Institution: Balish, Edward; Professor; Microbiology and Immunology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-JUL-2005 Summary: Candida albicans causes a variety of infectious problems for dental patients. Denture stomatitis and oroesophageal candidiasis are also major problems for AIDS patients. The applicant's recent research on cadidiasis in immunocompetent and immunodeficient gnotobiotic mice has produced new and important findings on the role of thymus-matured and non-thymus-matured T cells and phagocytic cells in resistance to lethal oroesophageal and systemic candidiasis. Their data demonstrates that immunocompetent and some immunodeficient mice manifest resistance to lethal oroesophageal candidiasis. Multiple immune defects (innate and T-cell-mediated) appear to be required for mice to show enhanced susceptibility to lethal oroesophageal candidiasis. The natural susceptibility of these gnotobiotic murine models will help elucidate the cellular basis for resistance to candidiasis at all mucosal surfaces; the model is especially good for studies on oroesophageal candidiasis that minics the disease seen in many dental and AIDS patients. The applicants have demonstrated that CD4epsilon and CD8+ (alphabeta and gammadelta T-cell receptor) T cells, as well as phagocytic cells, play unique roles in resistance to candidiasis at different mucosal sites. This research project will clarify the role that thymus-matured and non-thymusmatured T cells (and their products) and phagocytic cells play in resistance to candidiasis. The applicants will identify the lymphocytes involved in resistance, assess their capacity to restore resistance to oroesophageal candidiasis, and ascertain if therapy with cytokines, produced by immune lymphocytes, can enhance resistance to lethal oroesophageal candidiasis and systemic candidiasis of endogenous origin. This research will not only clarify the role of lymphocytes (and their products) and phagocytic cells in resistance to candidiasis, but it will also provide a rational basis for innovative immunotherapy that will enhance resistance to oroesophageal and systemic candidiasis in patients. This study is also important for the development of safe and effective vaccines that may protect immunocompetent, but not immunodeficient hosts. Restoration and enhancement of immune function may be critical for the effectiveness of anti-Candida vaccines that are now under development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: LEUKOCYTE INTEGRIN ALPHA M BETA 2 Principal Investigator & Institution: Plow, Edward F.; Professor & Chairman; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 15-DEC-2000; Project End 30-NOV-2004 Summary: (Investigator's abstract) The beta2 subfamily of integrins, which includes alphaMbeta2, controls the participation of leukocytes in biological settings. A number of specific leukocyte responses are regulated by alphaMbeta2, including the respiratory burst, homotypic aggregation, phagocytosis, migration, apoptosis, tumor surveillance, and ischemia-reperfusion injury. These responses depend upon the capacity of alphaMbeta2, to function as a receptor for an extremely broad spectrum of ligands. The mechanism by which alphaMbeta2 interacts with structurally diverse ligands to mediate the cellular responses of adhesion, migration and activation is the central focus of this application. Preliminary data developed in this application indicate that four representative ligands, iC3b, NIF, the P2 peptide of fibrinogen and C. albicans, not only

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interact with the I-domain in the alphaM subunit but also utilized the same five small segments on the cation-binding MIDAS face for ligand engagement. The hypothesis to be tested in Aim I is that different contact residues within these five segments contact these structurally-unrelated ligands. This mosaic model of ligand binding to alphaMbeta2 will be tested by systematic mutagenesis involving not only loss but also gain-in-function strategies. Preliminary data in the application indicate that P2, a 19 amino acid peptide corresponding to residues 377-395 of the gamma-chain of fibrinogen, contains all the information needed to support alphaMbeta2 -dependent cell adhesion, migration and activation. In Aim 2, the role of the individual amino acids within P2 and within alphaMbeta2 in eliciting these responses will be dissected. The hypothesis to be tested is that, in order to generate the differential intracellular signals required to elicit these alphaMbeta2 -dependent cellular responses, different contact residues in the peptide and in the receptor must interact. Aim 3focuses upon the interaction of the major opportunistic pathogen C. albicans with alphaMbeta2. Evidence for release of a soluble ligand, CASL, from the fungus, which interacts with alphaMbeta2 to induce cell adhesion and migration, has been developed. CASL will be isolated, its sequence determined, and its role in controlling the virulence of C. albicans will be established in vitro and in vivo. Overall, the proposed studies have the potential to provide fundamental insights into the functioning of a receptor, alphaMbeta2, which plays a major role in controlling leukocyte responses. The insights gained from these studies are likely to extend to other leukocyte integrins as well. Specific therapeutic targets for controlling the pathogenesis associated with insufficient or overly exuberant alphaMbeta2 -mediated responses, ranging from inflammatory responses to fungal infections, will also be identified through these studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MANNOSYLATION IN C ALBICANS HYDROPHOBICITY Principal Investigator & Institution: Hazen, Kevin C.; Professor; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: ( Adapted from applicants abstract): Pathogenesis of Candida albicans (CA) and other Candida species involves direct contact of the organism's cell surface with host tissues. Little is known about how Candida species surface macromolecules are modified during initiation of pathogenesis and establishment of infection. However, it has been shown that the cell surface of C. albicans varies in surface hydrophobicity status and that cell surface hydrophobicity (CSH) enhances pathogenicity of C. albicans. Recent studies suggest that CSH status of C. albicans is determined by cell wall protein mannosylation. Biochemical, biophysical, and immunologic studies lead us to propose that modification of the beta-1,2-phosphomannosyl group critically influences exposure of surface hydrophobic proteins (and therefore pathogenesis). In this project, the group will firmly establish the importance of the beta-1,2-phosphomannosyl group in conferring cell surface hydrophobicity. To do so, they will perform the following: 1) test by biochemical means the hypothesis that alteration of the beta-1,2-phosphomannosyl (beta-1,2ManP) group, not necessarily other mannosyl regions, determines CSH; 2) identify and clone the initial synthetic genes for beta-1,2ManP. At least two critical enzymatic steps are involved in synthesis of the beta-1,2ManP group. The first is a phosphomannosyl transferase and the second is a beta-1,2-mannosyltransferase (beta1,2-ManTase); 3) determine the role of the genes in conferring hydrophilicity by phenotypic characterization of the phosphomannosyl transferase and beta-1,2mannosyltransferase; and 4) establish the general regulation of expression during

36

Candida

growth and morphogenesis. From these experiments the PI will demonstrate the critical role of phosphomannosyl transferase and beta1,2-ManTase in determining CSH of C. albicans and influencing cell adhesion. The long-term goal of this research is to dissect the mechanisms of mannosylation of C. albicans cell wall proteins during pathogenesis and determine which ones provide the best targets for anti-Candida species therapy. Regardless of whether expression of the genes is involved in CSH status, elucidation of the genetic mechanism of expression of the beta1,-2ManP group will influence vaccine studies and contribute to the understanding of cell wall protein mannosylation events in pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM ADJUVANTICITY

OF

CHOLERA

TOXIN

AND

E

COLI

LT

Principal Investigator & Institution: Clements, John D.; Professor & Chairman; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: The WHO report of Infectious Disease deaths for 1995 indicated that there were more than 13 million deaths world-wide during that year. The majority of those deaths were caused by organisms that first make contact with and then either colonize or cross mucosal surfaces to infect the host. A number of strategies have been developed to facilitate mucosal immunization to prevent these diseases, including addition of bacterial products with known adjuvant properties. The two bacterial products with the greatest potential to function as mucosal adjuvants are cholera toxin (T), produced by various strains of Vibrio cholerae, and the heat-labile enterotoxin (LT) produced by some enterotoxigenic strains of Escherichia coli. A number of mutants of CT and LT have been developed in an attempt to dissociate the desirable adjuvant properties of these molecules from their toxic effects. Both active-site and protease-site mutants have been constructed and evaluated in a variety of animal models with different antigens. Important questions regarding the adjuvanticity of CT and CT and mutants of these toxins remain to be answered. Some of these questions are practical and the answers will impact the immediate and short term use of these molecules in human vaccines. Other questions address the underlying mechanisms associated with adjuvanticity and the answers will have their greatest impact in the design of future adjuvants and vaccine strategies and in the development of a better understanding of vaccine induced immunity. The proposal includes a series of Specific Aims designed to directly address these issues. One of the most important aspects of the proposed study is a side-by-side comparison of CT, LT, active-site mutants, protease-site mutants, and recombinant Bsubunits for the ability to induce specific, targeted immunologic outcomes as a function of route of immunization and nature of the co-administered antigen. With the information obtained in the proposed studies, future vaccine strategies can be designed employing the optimum adjuvant/antigen formulation and route of administration for a variety of bacterial and viral pathogens. This proposal also examines the underlying cellular and intracellular signaling pathways activated by these different molecules to better understand the mechanisms of adjuvanticity at the cellular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORING CANDIDIASIS

PATIENT-ORIENTED

RESEARCH

ON

ORAL

Principal Investigator & Institution: Macphail, Laurie A.; Oral & Maxfacial Path/Med/Sur; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122

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Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2005 Summary: The candidate's immediate and long-term career objectives are to pursue a career that combines clinical research, mentoring of new clinical researchers, and patient care. The mid-career award would (1) ensure the candidate the time and funding to participate in clinical research projects and mentor new researchers, and (2) provide funds for the candidate and these new researchers for such purposes as obtaining the preliminary data for successful grant applications. The candidate has substantial experience in patient-oriented research over 11 years at University of California, San Francisco (UCSF). Her current research project, "Self-care intervention to prevent oral candidiasis" (NIH-NINR, R01 NR04396), targets the nutrient supplies for the ubiquitous commensal organism and opportunistic pathogen, Candida albicans. The specific aims are: 1) to determine, through a controlled, single-blind randomized clinical trial, whether the PRO-SELF: CANDIDIASIS (P-S:C) program of dietary and oral hygiene instruction is effective in increasing inter-episode time for recurrences of oral candidiasis in susceptible HIV-infected persons; and 2) to determine whether HIVinfected persons in the P-S:C study arm self-report the recurrence of their oral candidiasis more accurately than do HIV-infected persons in the control arm. Participants will be cleared of oral candidiasis, randomized to the P-S:C arm or the control arm, and followed for 26 weeks to determine recurrence frequency. Each participant's self-diagnosis will be compared for accuracy with the investigators' clinical diagnosis. If successful, the P-S:C Program could be widely employed by medical and dental health-care workers dealing with HIV-infected persons in all risk groups to reduce the morbidity associated with oral candidiasis by reducing the number and severity of recurrences through earlier detection and prompt treatment. These benefits would substantially increase quality of life for people with HIV. The candidate's mentoring plans will be tailored to the experience and needs of new or prospective researchers. Opportunities to be made available to them include: 1) research experience to be gained by participating in ongoing research projects and planning sessions for new projects; 2) pertinent course work; 3) attendance at national and international research meetings and seminars, and 4) encouragement and support for development of new research projects or sub-projects. The training in patient-oriented research will occur at UCSF, which offers a wealth of training and educational experiences for those desiring an advanced degree and those seeking experience in clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROBICIDAL SALIVARY HISTIDINE-RICH PROTEINS Principal Investigator & Institution: Oppenheim, Frank G.; Professor and Chair; Periodontology & Oral Biology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-APR-1986; Project End 31-DEC-2006 Summary: Histatins constitute a distinct family of low molecular weight, histidine-rich, cationic salivary proteins which exhibit a broad range of antimicrobial activities. Unlike several other cationic antimicrobial peptides which act in local environments and in close proximity to their site of synthesis, histatins are secreted by both parotid and submandibular glands and are subsequently transported to the oral cavity protecting oral, pharyngeal and esophageal tissues. The long term objective of this project is to understand how histatins, representing an important part of the oral innate host defense system, protect against the multiple potentially adverse effects of microorganisms entering and residing in the oral cavity. The mechanism by which histatins kill Candida albicans, a pathogenic yeast, has not been fully elucidated. It has been shown that

38

Candida

histatins, by virtue of their weakly amphipathic nature and reluctance to form helical structures in hydrophobic environments, do not form pore structures in cell membranes. Since histatins are taken up only by metabolically active cells, target mitochondria, inhibit cellular respiration and form reactive oxygen species (ROS), it is likely that the candidacidal activity of the histatins is related to the deleterious effects of ROS on cellular membranes. Aim 1 focuses on the mechanism of action of histatins by identification of: a) the site of inhibition within the respiratory chain, b) the mechanism of ROS formation triggered by histatins and c) ROS induced destabilization of cell membranes by the characterization of nucleotides and proteins/peptides released into the extracellular environment. Another unique feature of histatins is their effect against bacterial virulence factors such as host tissue destroying enzymes and bacterial toxins. Aim 2 is to characterize these "second generation type antibiotic" effects of histatins by investigating the inhibition of several bacterial enzymes, such as the gingipains from Porphyromonas gingivalis, host-derived proteases such as metalloproteinases and the process of neutralization of the leukotoxin released from the periodontal pathogen Actinobacillus actinomycetemcomitans. Aim 3 will assess the structure/function relationships between histatins and their antimicrobial activity using recombinant technologies to construct artificial histatins containing naturally occurring sequences of functional importance, and to generate hybrid molecules exhibiting bi-functional activities. Aim 4 is planned to investigate the functional consequences of the propensity of histatins to form heterotypic complexes employing the molecular approach of the yeast two-hybrid system and the direct biochemical characterization of complexes formed in saliva. Aim 5 will establish the in vivo relationship between histatin levels in whole saliva and the oral microbial profile using the DNA-DNA checkerboard assay providing quantitative information on C. albicans and 80 species of oral bacteria ranging from harmless commensal organisms to periodontal pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODELS OF GENOMIC SYSTEMS: THEORY AND EXPERIMENT Principal Investigator & Institution: Milac, Thomas I.; Applied Mathematics; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002 Summary: This proposal outlines a three-year continuation and extension of work initiated by the candidate with the support of a Sloan Foundation and Department of Energy postdoctoral fellowship in Computational Molecular Biology. The objective of the candidate in submitting this proposal is to complete a research career transition to computational molecular biology. Three research projects are described. A Markov model of telomeric silencing in yeast A model for the development of a unique colony morphology in yeast A study of natural variation in yeast by analysis of mRNA expression data for glycolysis genes and modeling of the glycolytic pathway The first project, a study of telomeric silencing in yeast, is undertaken in collaboration with the laboratory of Daniel Gottschling at the Fred Hutchinson Cancer Research Center. The second, examining a unique colony morpholoy in yeast, is conducted under the auspices of the Gottschling laboratory and incorporates a significant laboratory training component for the candidate. The last project, a study of yeast natural variation, is an outgrowth of the candidate's collaboration with Maynard Olson and his laboratory at the University of Washington; this study will be conducted in collaboration with the laboratory of Leland Hartwell at the Fred Hutchinson Cancer Research Center. The proposal incorporates a career development plan for the candidate which includes formal coursework in genetics and biochemistry, training in laboratory techniques,

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participation in a short course on genomics, and attendance at conferences. Thomas Milac, the candidate, received the B.S. in physics and mathematics from Syracuse University in 1982, and the Ph.D. in applied mathematics (theoretical mechanics) from the University of Washington in 1995. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PHAGOCYTES

BASIS

FOR

MICROBICIDAL

ACTION

IN

Principal Investigator & Institution: Hurst, James K.; Professor; Chemistry; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2001; Project Start 01-APR-1979; Project End 31-JAN-2006 Summary: (Verbatim from Applicant's Abstract): The long-term objectives of this research are to identify the oxidative toxins generated by phagocytic cells (neutrophils, macrophages) and to determine their microbicidal mechanisms. This knowledge is expected to lead to improved/new methods of pharmacological intervention in combating infection, as well as provide insights into the causes and progression of human diseases associated with oxidative stress. Oxidative reactions within stimulated phagocytes will be probed by using unique fluorescein-conjugated polyacrylamide microspheres that, when opsonized, are avidly phagocytosed by these cells. Fluorescence changes of the engulfed particles will be used to monitor in real time the intracellular oxidation processes; recovery of the dye and subsequent chemical analyses will identify the oxidant(s) generated by the cells. These studies will resolve major issues concerning the function of the neutrophil enzyme, myeloperoxidase, and the microbicidal competence of the putative macrophage-generated toxin, peroxynitrous acid (ONOOH). In other studies, radiobiological methods will be used to examine the microbial toxicity of short-lived oxidants that can be formed from peroxynitrite decomposition in physiological environments, namely the radicals 0H, C03-, N02, and the nitrosating agent N203. For C03-, ONOOH, and other reactive nitrogen species (RNS) that are found to be toxic to selected microbes, the metabolic dysfunctions associated with cellular death will be identified by various biophysical and biochemical analyses. The membrane permeabilities of the RNS will be determined using model liposomal systems containing entrapped reductants; this information will be used along with the extensive kinetic data available on oxidation rates by the RNS to mathematically simulate the fate of the short-lived oxidants within the phagosome. Finally, the molecular sites leading to oxidative inactivation will be investigated using advanced mass spectral analyses for a P-type H+-ATPase whose functional loss is implicated in the fungicidal mechanisms of these oxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF BIOFILM FORMATION Principal Investigator & Institution: Kolter, Roberto G.; Professor; Microbiol & Molecular Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2006 Summary: (provided by applicant): Populations of surface-attached microorganisms are commonly referred to as biofilms. In most natural settings bacteria are found predominantly in biofilms, yet for many years studies of bacterial physiology focused on the planktonic state of bacterial cells. The widespread recognition that biofilms impact a myriad of environments has led to concerted efforts to gain a better

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understanding of the molecular mechanisms that underlie the development of these communities. Recent results have revealed that biofilm formation is a complex developmental process that occurs in response to environmental cues. Working models for how planktonic bacteria proceed from environmental sensing to the formation of mature biofilms are now guiding many investigators in their research. However, most of the attention has been placed on biofilms that form on abiotic solid surfaces such as plastics and glass. The formation of biofilms on living surfaces is also widespread and has important impacts in environmental and clinical settings. In our first experimental approach we propose to extend the studies we have carried out with a model bacterium, Pseudomonas aeruginosa, to investigate how it forms a biofilm on living fungal filaments. To this end we will: 1) Characterize the bacterial-fungal interactions through physiological, biochemical and microscopic analyses, 2) Select specific genes in which to generate mutations and test their effects on bacterial-fungal interactions and 3) Carry out a mutant screen and perform transcriptional profiling using microarrays to identify additional genes involved in the bacterial-fungal interactions. It is generally accepted that there is cellular differentiation within biofilms. Yet, relatively little is known about the molecular mechanisms that underlie differentiation processes in bioflims. In a second experimental approach that follows a path analogous to our first approach, we will address the question of cellular differentiation in biofilms through the study of a well-characterized sporulation process in Bacillus subtilis. We will: 1) Analyze the spatial and temporal patterns of transcription of a spore-specific gene using reporter fusions and light, electron and confocal scanning laser microscopic techniques, 2) Generate additional reporter gene fusions to selected genes and analyze their spatial and temporal patterns of expression in order to develop a more complete functional anatomy of the biofilm and 3) Test the effects of mutations involved in cell-cell signaling and environmental sensing on cellular differentiation within the biofilm. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MORPHOGENESIS AND CELL CYCLE REGULATION IN C. ALBICANS Principal Investigator & Institution: Berman, Judith G.; Associate Professor; Plant Biology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Opportunistic infections remain the most important complication of infection with the Human Immunodeficiency Virus (HIV) and the principal cause of death in patients with the Acquired Immune Deficiency Syndrome (AIDS). A large proportion of patients infected with HIV develop severe oropharyngeal and esophageal candidiasis. The predominant infecting species, Candida albicans, can grow as yeast, pseudohyphae and hyphae and the ability to transition between these different cell types is important for virulence. Cell cycle progression, which is controlled by cyclin-dependent kinases, is often intimately connected to the regulation of morphogenesis. Our preliminary data indicate that the two C. albicans B-cyclins (Cyblp and Cyb99p) and a putative transcriptional regulator of cell cycle genes (Fkh2p) are important for distinct aspects of morphogenesis and that Fkh2p regulates the levels of Cyb99 mRNA. We will test four hypotheses: First, that the two C. albicans B-cyclins have distinct roles in cell cycle progression; second, that Fkh2p is a transcriptional regulator of B-cyclin and other cell cycle-regulated genes; third, that C. albicans hyphae have cell cycle dynamics more similar to filamentous fungi than to budding yeast; and fourth, that C. albicans morphogenesis involves specific, fundamental changes in cell

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cycle dynamics that are also important for virulence. We propose to identify and characterize C. albicans gene products that regulate both cell cycle progression and morphogenesis in order to reveal the molecular mechanisms that underlie the coordination of these processes. Specifically, we will determine the mechanisms by which the B-cyclins and Fkh2p contribute to morphogenesis, cell cycle regulation, and virulence. We will compare wild-type strains and strains lacking Fkh2p or B-cyclins using time-lapse microscopy of fluorescent proteins to follow the dynamics of cell cycle progression. We will use DNA microarrays to follow transcriptional regulation and in vitro aasays of interactions between the pathogen and epithelial tissue or macrophages to study aspects of virulence. Ultimately, fungal-specific gene products that execute essential cell cycle processes may be important new targets for the development of antifungal therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCOSAL CANDIDIASIS

IMMUNIZATION--PREVENTION

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SYSTEMIC

Principal Investigator & Institution: Freytag, Lucia C.; Research Assistant Professor; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Candida albicans is a ubiquitous fungus which may be found as part of the normal flora of humans. In healthy hosts, serious disease seldom occurs unless some factor alters the balance in favor of the fungus. Unfortunately, precipitating factors such as immunosuppressive therapies and diseases which down-regulate the immune system are becoming more prevalent. Currently, there are no vaccines against human mycoses, and a vaccine capable of stimulating immunity in selected patients prior to immunosuppression would be of considerable value. A novel approach for the development of antifungal vaccines is the use of mucosal immunization. We have recently demonstrated the ability of a novel mucosal adjuvant, developed in our laboratory, to enhance the humoral and cellular immune responses against C. albicans and to induce protection against colonization and lethal i.v. challenge with wild-type C. albicans. Solid protection was achieved following intranasal immunization with heatkilled whole organisms in conjunction with this adjuvant. Both humoral and cellular immune responses against C. albicans were enhanced. A strong DTH response to mannan was observed in animals vaccinated with the killed yeast and adjuvant mixture. Moreover, isotype analysis of anti-Candida antibodies in protected animals revealed a predominance of antibodies of the IgG2a isotype, suggesting a strong Th1 type cytokine response. This proposal seeks to examine the underlying immunological correlates of protection against disseminated candidiasis following mucosal immunization, whether the protection conferred by this vaccine strategy can be passively transferred to naive mice, and whether immunological protection transcends the induction of immunosuppression in experimental animals. Concomitantly, our studies will determine if protection can be achieved in animals that are colonized with Candida prior to vaccination and if cross-protection against other Candida species can be achieved using this mucosal immunization strategy. With the information obtained in the proposed studies, future vaccine strategies can be designed employing similar vaccination protocols for a variety of fungal pathogens. These are important issues because they take us beyond the phenomenological observations of "enhanced immunity" to a more clear understanding of the mechanisms of protection against Candida and the practical implications for the development of antifungal vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW METHODS FOR USING GENE DISRUPTION LIBRARIES Principal Investigator & Institution: Rothstein, Rodney J.; Professor; Genetics and Development; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The complete gene disruption library of the yeast Saccharomyces cerevisiae has recently become available. In many ways, this resource will facilitate genome-wide analysis and the main aim of this proposal is the development of methods to enhance the utility of this resource. For one specific aim, we will develop a novel donor yeast strain to permit mating-based plasmid transfer for rapid screening of the disruption library with any plasmid-based reporter assay. Such an approach will facilitate the identification of all genes that affect any particular process for which a reporter assay can be designed. The second specific aim is to develop reagents to allow in vivo excision of a plasmid based gene disruption for integration into the genome of any laboratory strain background. The disruption construct is designed to permit recycling of the selectable marker via direct repeat recombination to allow additional rounds of gene disruptions using the same approach. In conjunction with the mating-based plasmid transfer, this will allow rapid construction of new deletion strain libraries. The proposal can be divided into the following two specific aims: (1) Create a universal donor strain to be used in conjunction with the current (or any future) yeast gene disruption library to permit the facile introduction of any reporter plasmid into the set of disruptions via kar-mediated plasmid transfer. (2) Develop methods to permit the transfer of gene disruptions into any yeast genetic background by activating a plasmidbased gene disruption cassette in vivo. The methods outlined here are not specific to the yeast genome; they can be applied to any sequenced genome. For example, gene disruptions can be constructed in any transformable species for which a sequenced genome is available (e.g., Candida or one of many bacterial strains). Successful completion of these aims will greatly expand the methods available in the molecular geneticist's tool kit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NICHE SPECIFIC PATHOBIOLOGY OF CANDIDA ALBICANS Principal Investigator & Institution: Fonzi, William A.; Associate Professor; Microbiology and Immunology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (Adapted from Applicant's Abstract) Candida albicans is an opportunistic pathogen of AIDS patients. These individuals typically develop oral and esophageal infections due to this fungus. More recently, candidemia has been recognized as a nosocomial complication in AIDS patients with significant associated mortality. Longterm and prophylactic antifungal treatment of AIDS patients has resulted in the emergence of clinically resistant C. albicans strains. This situation is exacerbated by the limited arsenal of efficacious drugs. Much of the biology of C. albicans is unknown due, in part, to the past difficulties in the genetic manipulation of this fungus. However, a substantial amount of data implicate the dimorphic ability of C. albicans in the development of disease. In the case of C. albicans, dimorphism refers to the ability of this organism to adopt either a yeast (single-celled) or hyphal (multicellular filamentous) morphology. The relatively recent development of methods to overcome many of the technical problems in the genetic dissection of C. albicans now permits a closer mechanistic examination of the role of dimorphism in disease. The aim of the present proposal is the investigation of a particular genetic determinant of dimorphism

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in C. albicans, the gene HWP1. HWP1 was isolated in a screen for genes expressed only in the filamentous form. HWP1 is required for filamentation and virulence in a mouse model of systemic disease, but is not required for gastrointestinal infection in mice nor for filament formation in the gut. This is the first demonstration that the pathogenic attribute of dimorphism has biological facets unique to mucosal vs. systemic disease. The investigators propose a series of molecular genetic studies to define the mechanism(s) governing the development-specific expression of HWP1 in vitro and in vivo and the function of the encoded protein in hyphal development. These studies are set forth with the long-term objective of understanding the molecular basis of pathogenesis by C. albicans and that this knowledge may contribute to better approaches to disease prevention and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL ANTIFUNGAL DRUG TARGETS IN CRYPTOCOCCUS NEOFORMANS Principal Investigator & Institution: Heitman, Joseph B.; Professor; Molecular Genetics and Microbiology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: Fungal infections are increasingly common as a result of AIDS, transplantation, high dose chemotherapy, steroid treatment, antibiotic treatment, and invasive procedures. However, existing antifungal agents are limited to amphotericin B, flucytosine, and azoles, and drug resistant strains are emerging. We propose to elucidate signal transduction cascades regulating fungal growth and virulence as targets for antifungal drug development. We propose studies on both Candida albicans, the most common human fungal pathogen, and Cryptococcus neoformans, the leading cause of fungal meningitis and an important opportunistic fungal pathogen. We have discovered that the immunosuppressive drugs rapamycin, cyclosporin A, and FK506 have potent antifungal activity. In studies supported by this award, we have identified the fungal drug target proteins, including FKBP12, the Tor1 kinase, and two cyclophilin A homologs. Our studies demonstrate that the antifungal effects of rapamycin are mediated via a complex with FKBP12 that inhibits the fungal Tor1 kinase homolog. We have identified nonimmunosuppressive analogs of each of these drugs that retain antifungal activity. By genetic and biochemical approaches, we show that these analogs take advantage of structural differences between host and fungal enzymes, sparing immune function while impairing fungal cell growth. Finally, we have identified examples of potent synergistic drug interactions. For example, the calcineurin inhibitors cyclosporin A and FK506 are potently synergistic with azoles in Candida albicans. Here we propose to establish the cellular functions and targets of the rapamycin target protein Tor1. The TOR1 gene will be disrupted in diploid strains of C. neoformans to test if it is essential. Targets of the Tor kinase will be identified by genetic and two hybrid screens, and by analyzing gene expression with genome arrays. We will also identify the targets of the C. neoformans cyclosporin A target proteins, the Cpa1 and Cpa2 cyclophilins, which are important for cell growth and virulence. We will determine the molecular basis of synergistic drug interactions. First, we will identify a novel target of the FKBP12-FK506 complex that is synergistic with proton pump inhibitors in C. neoformans. Second, we will focus on the roles of FKBP12 and calcineurin in azole action in C. albicans, testing the hypothesis that calcineurin is either essential or becomes essential during cell membrane stress as a result of azole treatment. Finally, we will test rapamycin and nonimmunosuppressive rapamycin analogs, and the synergistic combination of calcineurin inhibitors and azoles, in animal models of

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cryptococcosis and candidiasis. Our long term goal is to identify unique targets and develop novel antifungal drug therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL BIFUNCTIONAL MOLECULES FOR INTRAORAL DRUG DELIVERY Principal Investigator & Institution: Periathamby, Antony R.; Periodontics; Marquette University P.O. Box 1881 Milwaukee, Wi 532011881 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: The goal of this innovative research project is to develop simple bifunctional molecules for intraoral delivery of antimicrobial agents. The bifunctional hybrid molecules will each be composed of a carrier sequence possessing high affinity for tooth and pellicle surfaces, and a natural antimicrobial peptide. These two sequences will be linked to each other with a biodegradable bond. With this linkage, antimicrobial sequences inherently linked to the carrier will be released efficiently from the tooth surface and in saliva through the oral physiological and microbial environment for a controlled and sustained release of the antimicrobial agent, thereby providing a novel and efficient method for intraoral drug delivery. This research project involves: 1) Synthesis of hybrid molecules by rationally selecting carrier sequences from salivary statherin, and antimicrobial sequences from bactenecins and defensins; 2) Determination of toxicity of hybrid molecules to ensure that they are cytotoxic only to microbes; 3) Delineation of the effect of whole saliva on the stability of hybrid molecules; 4) Assessment of the adsorption and desorption characteristics of hybrid molecules onto hydroxyapatite surfaces; 5) Determination of the extent of adherence of Candida albicans, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Streptococcus mutans, Streptococcus gordonii and Streptococcus sanguis onto the hybrid adsorbed hydroxyapatite surfaces. This proposed research will identify new, safe, and affordable hybrid molecules for the prevention and treatment of plaquerelated oral diseases. The hybrid molecules can be directly used as a topical rinse, or irrigant or they may be applied professionally to sub-gingival areas. The oral physiological and microbial environment will naturally induce the dissociation and the release of the antimicrobial peptide from the tooth surface into the site of oral infection. The hybrid molecules will serve as an efficient local drug delivery system and eliminate the discomfort and retention problems associated with the existing local delivery devices. The hybrid molecules will have a high potential for clinical and commercial application as anti-plaque agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL INHIBITORS OF FUNGAL ASPARTIC PROTEINASES Principal Investigator & Institution: Dunn, Ben M.; Distinguished Professor; Biochem and Molecular Biology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2003 Summary: Immunocompromised patients are susceptible to infection by organisms that are typically cleared by the normal host immune system. Candida albicans (CA) infection leads to several moderate to life threatening or disseminated clinical diseases. Agents that could prevent this infection would help relieve suffering in patients undergoing transplantation, chemotherapy, and fighting AIDS. Proteases secreted by CA aid in penetration through the extracellular matrix to spread infection. These proteases are believed to be virulence factors, and are members of the aspartic

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proteinase family. It is known that pepstatin, a general inhibitor of aspartic proteinases, will suppress growth of CA. We have recently determined the three-dimensional structure of a related fungal enzyme, yeast proteinase A (YprA) in complex with its natural protein inhibitor, IA-3. This new complex reveals novel features of the inhibition that we proposed to explore further in this project. IA-3 is completely unfolded in solution, as we have established by NMR analysis. By understanding the interactions between YprA and IA-3, we plan to design new inhibitors targeted to the closely related protease from CA. We will achieve this objective through four specific aims. In Aim 1, we will create mutants of the IA-3 to aid in studies of the helix-coil transition and the physical interaction with enzyme through fluorescence energy transfer and continuousflow micro-mixing procedures. In Aim 2, mutants will be designed to determine critical points of interaction, which could result in simplification of the inhibitor structure. Based on the interactions of the mutants with YprA, we will select some for studies by NMR in both Aims 1 and 2 to determine the dynamics of the unbound state and changes in structure upon binding. In Aim 3 we will make changes in the structure to permit binding to and inhibition of the Candida albicans protease of similar structure and function. In Specific Aim 4 we will exploit the new information provided by the IA3/YprA complex to aid in design of small molecule inhibitors that achieve specificity through a new mechanism of binding. Compounds developed through this program will be tested against Candida albicans in culture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORAL AMB FOR THE TREATMENT OF FUNGAL INFECTION Principal Investigator & Institution: Gould-Fogerite, Susan; Biodelivery Sciences International, Inc. C/O Umdnj New Jersey Med School Newark, Nj 071032757 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-AUG-2004 Summary: (provided by applicant): The long term goals of our research are to develop new formulations of therapeutically important drugs using cochleates as the delivery vehicle. Such formulations would have an improved route of delivery (oral rather than injectable to improve ease of administration and to reduce adverse effects of parenteral therapy), and lower toxicity, thereby improving the safety profile of drugs. The SBIR Phase I advanced the development of a new formulation of amphotericin B (AmB) that has low toxicity and allows the oral delivery of AmB. Oral amphotericin B cochleates showed excellent activity in murine models of clinically relevant invasive fungal infections: Disseminated candidiasis, disseminated aspergillosis, and central nervous system cryptococcosis. The overall objective of this SBIR Phase II is to further develop this new AmB cochleate formulation for the following target indications: 1) Treatment of azole-susceptible and azole-resistant oropharyngeal and esophageal candidiasis in immunosuppressed patients, 2) empiric therapy for presumed fungal infection in febrile, neutropenic patients, 3) treatment of selected patients with proven or probable invasive infections due to Aspergillus species, Candida species, and other life-threatening invasive fungal infections. To this end the following specific aims will be investigated: 1. To optimize cochleate AMB formulations (CAMB) as a commercially viable human therapeutic by testing CAMB prepared with less expensive raw materials (mainly phosphatidylserine) and simplified protocols. 2. To perform preclinical studies in a higher animal model. 3. To determine the mechanism of drug delivery mediated by cochleate 4. To initiate Phase I trials with CAMB in humans PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL CANDIDASIS: ANTIGEN STRUCTURE AND VACCINE DESIGN Principal Investigator & Institution: Woods, Robert J.; None; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-JUL-2004 Summary: The goal of this proposal is to develop and evaluate the efficacy of antiCandida vaccines for use in the treatment of oropharyngeal Candidiasis (OPC). To achieve optimal design, the applicants will take a purely synthetic approach to vaccine synthesis. The immunogenic core of the vaccine is based on recently discovered peptides that are able to elicit protective anti-Candida responses in mice. These peptides were found by screening antibodies, raised against the cell surface polysaccharides of C. albicans, against a phage-displayed peptide library. To enhance the immunogenicity of the peptides, they will be covalently linked to a branched dendrimer, which will also contain a linked lipid adjuvant. This approach will enable the applicants to precisely vary the valency of the vaccine molecules and thereby optimize their immunogenicity. The details of the mechanism through which the immunogenic peptides are able to mimic the endogenous carbohydrate epitope are unknown. This mimicry is not an isolated example. Several peptides have now been reported that are capable of mimicking carbohydrates from a variety of sources. In general, this mimicry can be both immunological and structural. To date, however, very little is known about the physical nature of this mimicry. In order to exploit fully the peptide mimetics in the design of a vaccine, it is essential to better understand the structures of the peptides and the mechanism of the molecular mimicry. Therefore, concurrent with the chemical synthesis and immunological evaluations, they will attempt to determine the 3-dimensional structures of the free and antibody-bound forms of the carbohydrate epitope and the peptide mimetics. The structural information will be provided by three complementary techniques, namely, nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction analysis, and molecular modeling. Insight into the antigenic conformations of the peptides and endogenous antigens will provide a model for the further design and optimization of anti-Candida vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL EPITHELIAL CELL CYTOKINES CANDIDA & PMN ACTIVATION Principal Investigator & Institution: Dongari-Bagtzoglou, Anna I.; None; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-JUL-2002 Summary: (abstract verbatim) Oropharyngeal candidiasis is particularly prevalent in patients who are immunocompromised by disease or immunosuppressive treatment. Interestingly, even in immunocompromised patients invasive oral candidiasis is rare and seems to be associated with additional risk factors such as extreme neutropenia. One strategy for improving resistance to opportunistic pathogens is to define host cellular responses during the invasion process and enhance those responses that are relevant to defense mechanisms. Compelling experimental evidence suggests that the primary effector cell responsible for Candida clearance is the neutrophil. Neutrophils accumulate rapidly at the site of infection in the oral cavity and participate in the local control of Candida growth and invasion, yet very little is known about the host signals responsible for regulating these events. Several cytokines provide signals for neutrophil activation of antifungal functions, including interleukin-1 beta (IL-1b) and granulocyte

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macrophage colony stimulating factor (GM-CSF). In cases of T-helper cell depletion or inactivation, such as HIV disease or Cyclosporin A treatment, PMN are most likely potentiated in their anti-fungal function by stimulating cytokines derived from nonimmune cell. Epithelial cells are capable of synthesizing IL-1b and GM-CSF and maybe one of the few defenses remaining under CD+ T cell-deficient conditions. The central hypothesis of this project is that cytokines such as IL-1b and GM-CSF are released by oral epithelial cells upon interaction with Candida and act as local stimulators of neutrophil anti-fungal functions. Using a human oral epithelial cell Candida albicans coculture model system the applicants will first determine whether this microorganism can trigger secretion of these potent neutrophil activating cytokines by oral epithelial cells. Once this goal is accomplished, mechanisms eliciting Candida-mediated cytokine responses will be explored. Finally, they will perform functional assays for these epithelial cell-derived cytokines as they relate to neutrophil activation of Candida phagocytosis and killing, using isolated neutrophils from healthy, HIV+ and Cyclosporine A-treated individuals. Given the fact that most fungal infections take place in an immunocompromised host, neutrophil priming by non-immune cell derived cytokines may be of paramount importance, not just in the initiation of a protective inflammatory response, but also in the prevention of fungal invasion into the deeper connective tissues of the oral mucosa. The studies proposed herein will be crucial in identifying oral epithelial cell-derived cytokines with the potential to prime neutrophil antifungal function in vitro. Identification of such cytokines may have future therapeutic applications in the treatment of oral candidiasis in the severely immunocompromised host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOBIOLOGY OF GI INFECTION AND INFLAMATION Principal Investigator & Institution: Gershon, Michael D.; Professor and Chairman; Anatomy and Cell Biology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (adapted from the application) A multidisciplinary group of senior investigators at Columbia, with a common interest in the mechanisms that protect the bowel from microbial infection, have designed a GI Infection and Inflammation training program and request support. Funds are requested for 2 pre-doctoral fellows in the year 1, 3 pre-doctoral fellows in year 2 and 4 pre-doctoral fellows in years 3-5. Historically, at Columbia, basic research on infection was centered in the Dept. of Microbiology. Study of pathogenesis, however, has increasingly involved the study of cell biology, because of the ability of invading organisms to exploit host cell machinery to carry out their nefarious life cycles. Similarly, microbiologists are now just as concerned about cell biology as members of the department that bears that name. It is thus both realistic and important to expose trainees broadly to many disciplines. Bacterial and viral pathogenesis provides a great multidisciplinary training opportunity of which we now propose to take full advantage. In addition, the best pre-doctoral applicants are interested in the mechanisms of disease and want it included in their predoctoral training. Accordingly, 18 faculty from 4 basic and 3 clinical science departments have joined together to develop a thematic, interdepartmental pre-doctoral training program in GI infection and inflammation. Participating faculty include: Q. Al-Awqati (differentiation & membrane trafficking of gut epithelium); J. Bulinski (microtubule function in intracellular transport); M. Field (ion transport across intestinal epithelial membranes); M. Gershon (development & function of the enteric nervous system); A. Gershon (Herpes virus and HIV infection); S. Goff (retrovirus infection & replication); G.

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Gundersen (microtubule control of membrane trafficking); R. Kessin (mechanisms of phagocytosis); R. Liem (cytoskeleton of the enteric nervous system); J. Luan (HIV-1 replication & pathogenesis); A. Mitchell (infection by the fungus, Candida albicans); L. Pon (actin cytoskeletal control of membrane trafficking & enterobacterial infection); A. Prince (bacteria-host interactions); V. Racaniello (enterovirus pathogenesis); H. Shuman (pathogenesis of enterobacteria); S. Silverstein (membrane transport & leukocytes); and H. Worman (inflammatory bowel, and hepatobiliary diseases and hepatitis C). The multidisciplinary nature of this program is congruent with an evolution of graduate education at Columbia University. It also provides, for the first time in years, an institutional focus on research and research training in GI disease. The inception of this program has already led to the development of new graduate courses, expansion of existing courses and establishment of new collaborations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACODYNAMICS IN ANTIFUNGAL RESISTANCE Principal Investigator & Institution: Andes, David R.; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): The research performed in the context of the K08 follows work as a fellow and by combining pharmocodynamics (PD) and molecular biology will open the development of an entirely untapped field of study. C. albicans is the most common opportunistic pathogen in HIV infected patients. Azoles are frontline agents for treatment of Candida infections, however therapy remains suboptimal and several mechanisms of azole resistance have recently emerged. There is a need for improved therapy and an understanding of drug exposure factors that lead to and prevent of the emergence of resistance. The proposed research is divided into two phases. (l) In phase one, azole PDs will be studied in a murine model. The findings obtained in the PD studies will be used to optimize dosing of azoles and investigate the relationship between the emergence of specific resistance mechanisms and azole dosing using (a) reconstruction experiments with a susceptible parent strain, doped with a fixed level of the genetically related resistant mutant strain and (b) a strain which has demonstrated temporary phenotypic resistance. (2) In phase two, basic studies of gene expression in C. albicans will be undertaken and correlated with results of phase I PD studies. Serial analysis of gene expression (SAGE) will be used to study mRNA abundance in C. albicans on a genome-wide basis. The biologic variables will include: the adaptive response of C. albicans to azole antibiotics (a) during the initial exposure, (b) following exposure during period of inhibition and regrowth, or the postantifungal effect (PAFE), and (c) the effect of specific known resistance mutations on these responses. The candidate's goal is to integrate knowledge of antifungal PD and the acquisition of approaches and skills in molecular biology through the completion of this grant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHOSPHOLIPASE B: A VIRULENCE FACTOR FOR CANDIDA GLABRATA Principal Investigator & Institution: Clancy, Cornelius J.; Medicine; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003

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Summary: (adapted from application abstract): In this K08 application, Cornelius Clancy requests 3 years of support to learn the skills necessary to achieve his career goal of becoming a successful clinician-scientist. The applicant's long-term research interest is in identifying and studying virulence factors for the yeast pathogen Candida glabrata, now a leading bloodstream fungal infection in the United States. C. glabrata is a model organism for studying molecular genetics because it has a haploid genome and is closely related to Saccharomyces cerevisiae. The applicant s laboratory has correlated levels of extracellular phospholipase B (PLB) activity with the severity of C. glabrata invasive infections in humans. He hypothesizes that the gene cgPLB2 is responsible for much of C. glabrata s PLB activity, and that disruption of cgPLB2 will significantly reduce the virulence of the organism. The applicant s short-term goal is to conclusively prove that cgPLB2 is important in virulence by fulfilling the molecular form of Koch's postulates. Specifically, he will finish cloning cgPLB2, demonstrate that the reduction of PLB activity caused by disruption of cgPLB2 attenuates virulence in a murine model of disseminated infection, and demonstrate that restoration of PLB activity by reinsertion of cgPLB2 restores virulence. In completing this project, he will learn a wide range of techniques in molecular biology, biochemistry, and animal models of disseminated infections. In addition he will learn to formulate hypotheses, design appropriate experiments, apply statistical tools, and interpret data. These skills will be complemented by an educational plan including courses and advanced seminars in basic sciences and statistics. He will receive this training in a multidisciplinary environment supported by the resources of the Dept of Medicine and the Dept of Molecular Genetics and Microbiology at the University of Florida, guided closely by his mentor, Alfred Lewin (a yeast geneticist) and his co-mentor, Frederick Southwick (Chief of Infectious Diseases and an expert in microbial pathogenesis and cell biology). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOSPHOMANNAN AS A VACCINE CANDIDATE Principal Investigator & Institution: Cutler, Jim E.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: During the current MRU funding period, we established that a vaccine comprised of Candida albicans phosphomannan complex (PMC) material encapsulated into liposomes induced a protective response in mice against disseminated candidiasis. The protection appeared due to serum antibodies and a monoclonal antibody specific for a beta-1,2-mannotriose in the PMC was protective. We will aggressive pursue these observations by testing two working hypotheses. 1. The liposomal vaccine can be improved by utilizing a stabilized form of liposomes and/or eliminating the liposomal part of the vaccine by making mannan-protein conjugates. 2. A DNA vaccine that encodes peptides that mimic the critical or "protective" mannan epitopes ("peptide mimetics" or "mimotopes"), can be constructed. These new approaches give great potential for vast improvements in the vaccine effectiveness because additional components, such as Candida cell wall proteins (provided by the Edwards and Mitchell labs) may be incorporated. The hypotheses will be tested by the following specific aims: 1. Utilize stabilized liposomal constructs to improve the liposomal vaccine formulation. Protective epitopes will be covalently linked to the surface of polymerized liposomes that are stable for years. This is a novel approach, but the chemistry expertise of Dr. Jon Nagy ensures that the liposomes may be quickly and appropriately modified as needed. 2. Construct protein conjugates of the critical mannan epitopes. The mannans will be coupled to an appropriate carrier protein. This approach will allow us to exploit the use

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of a wide selection of Candida cell wall protein that will be supplied though the Edwards and Mitchell labs. 3. Construct a DNA vaccine based on peptide mimotopes. Candidate peptides that mimic protective mannan epitopes are being identified in our laboratory. We will clone genes the encode mimotopes into an appropriate eukaryotic expression vector and determine if vaccinated mice taking antibodies to the mimotopes and are protected against candidiasis. Additionally, peptide mimotopes fused to candida cell wall protein that will be supplied through the work of the Edwards and Mitchell laboratories will be made part of a mouse major lysosomal glycoprotein (lgp-A or LAMP-1) for diversion into an MHC class II antigen processing compartment. The expertise of Dr. Bruce Granger ensures the expeditious making of variations of DNA constructs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PMN ENHANCEMENT OF ENDOTHELIAL RESPONSE TO CANDIDA Principal Investigator & Institution: Filler, Scott G.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2002 Summary: (Adapted from the applicant's abstract): The incidence of bloodstream infections caused by Candida species has increased dramatically, so that these organisms now account for 10% of all bloodstream isolates. During the process of hematogenous dissemination, it is likely that blood-borne organisms must adhere to and penetrate the endothelial lining of the vasculature to invade the tissue parenchyma. Thus, a potential method to prevent or treat hematogenously disseminated candidal infections is to augment the combined response of neutrophils and endothelial cells against this organism while it is within the intravascular compartment. We have shown that adding neutrophils to Candida-infected endothelium prevents endothelial cell injury in vitro. Also, we have found that Candida albicans by itself can stimulate endothelial cells to express leukocyte adhesion molecules and proinflammatory cytokines. The expression of these factors is greatly increased when neutrophils are added to endothelium infected with C. albicans. Together, these results suggest that there is a two-way exchange of signals between endothelial cells and neutrophils during their response to intravascular infection. The experiments outlined in this proposal are designed to elucidate the mechanisms that mediate this neutrophil amplification of the endothelial cell proinflammatory response to C. albicans. The influence of the microbial target (C. albicans) on the neutrophil enhancement of the endothelial cell response will be evaluated first. Based on these results, the immunomodulatory substances that mediate this neutrophil amplification will be identified. The expression of the leukocyte adhesion molecules, E-selectin and VCAM-1, will be used as a marker of endothelial cell activation in these experiments. Next, the activities of the immunomodulatory substances identified by the above experiments will be inhibited to determine if theses substances also influence the ability of neutrophils to kill C. albicans and protect endothelial cells from candidal injury. Finally, the results of these in vitro experiments will be evaluated in vivo. Both immunocompetent and neutropenic mice will be infected with C. albicans and immunohistochemistry will be used to detect the local expression of leukocyte adhesion molecules and cytokines at sites of candidal infection. Investigating the interactions between endothelial cells, neutrophils and C. albicans will enable us to determine the mechanism by which endothelial cells are activated in response to infection. The long-range goal of these studies is to devise endothelial cell-

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based strategies to enhance the host inflammatory response to blood-borne microbial pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF CANDIDIASIS IN CRITICALLY III PATIENTS Principal Investigator & Institution: Sylvester, Shelley L.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The Candidate, Dr. Sylvester, is a post-doctoral fellow in Infectious Diseases and a doctoral candidate in the Graduate Training Program in Clinical Investigation at Johns Hopkins University. Through this award she seeks to become an independent investigator in patient-oriented research, with expertise in the area of Candida and candidiasis in compromised patient populations. Experts in clinical investigation, critical care, medical mycology, and biostatistics will mentor her. She will supplement her research activities and her knowledge of introductory biostatistics and epidemiology with advanced courses in clinical investigation, biostatistics and research ethics at the Bloomberg School of Public Health. To prepare for translational aspects of her future research, she will take courses in immunology, microbiology and molecular biology. Background - Candida is a deadly and increasingly common pathogen in critically ill patients. In certain patient populations, including critically ill surgical patients at Johns Hopkins, antifungal prophylaxis has been shown to prevent Candida infections. Antifungal prophylaxis has not been well studied in critically ill medical patients. The emergence of antimicrobial resistance among Candida species presents a major concern with regard to the widespread use of prophylaxis. Dr. Sylvester proposes to explore the ecology of Candida and the impact of antifungal prophylaxis in critically ill patients. Specific Aims. 1 ). To determine Candida species distribution and fluconazole susceptibilities in high-risk SICU patients and compare current species distribution and susceptibility data to data collected during a 1998-1999 randomized, double blind placebo-controlled trial of fluconazole prophylaxis in critically ill surgical patients at Johns Hopkins. 2). To determine Candida species distribution and fluconazole susceptibilities in high-risk MICU patients, to whom fluconazole prophylaxis is not given, and compare these data to data collected concurrently from high-risk SICU patients, to whom antifungal prophylaxis is routinely administered. 3). To evaluate, in a randomized, double blind, placebo-controlled trial, the effect of antifungal prophylaxis on the prevention of invasive Candida infection in high-risk, critically ill medical patients. Significance. The overall goals of this research are to define the ecology of Candida in critically ill patients, to define the impact of antifungal prophylaxis on this ecology, to assess differences in ecology and predictors of invasive infection in critically ill medical and surgical patients, and to develop a safe, effective strategy to prevent these often-fatal infections in critically ill medical patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTITIVE MICRBIOLOGIC MODEL FOR PRETERM DELIVERY Principal Investigator & Institution: Onderdonk, Andrew B.; Associate Professor of Pathology; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2001 Summary: Preterm delivery (PTD) is the leading cause of infant morbidity and mortality in the United States, and prevention of PTD is a primary goal in perinatal health care. Recent data indicates a strong association a strong association between maternal genital

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tract infection, including bacterial vaginosis, and PTD, with compelling evidence that micro- organisms are a cause of PTD. However, the relationship between concentrations of vaginal microorganisms and PTD, the identification of key microbial populations that are significant risk factors for PTD, and the pathophysiologic mechanisms by which bacteria contribute to PTD remain to be determined. In addition, the interactions between microbial populations of significance to PTD are unknown. Preterm labor may be initiated by bacterial phospholipases A2 and which release arachidonic acid-the primary substance for prostaglandins which are considered fundamental to the initiation of labor. It has been hypothesized that the combined activities of lipase and phospholipases also account for a variety of effects associated with membrane damage. However, the relationship between these combined enzyme activities in the vagina and pregnancy outcome has not been determined. The objective of the proposed project is to prospectively collect quantitative data on microbiologic populations and enzyme activities and to receptor the presence or absence of bacterial vaginosis in two cohorts at high risk for PTD and one to record the presence or absence of bacterial vaginosis in two cohorts at high risk for PTD and one cohort at low risk. Generalized estimating equation regression will be used to analyze repeat measurement data and to formulate quantitative models to predict PTD. The following Specific Aims will be addressed: (1) quantitatively identify key microbial population as risk factors for PTD, (2) identify interactions between microbial populations that contribute to PTD, (3) determine whether there is an association between vaginal enzyme (lipase, phospholipase) activities and PTD, and (4) document any relationship between the presence or absence of bacterial vaginosis and PTD, and (4) document any relationship between the presence of absence of bacterial vaginosis and PTD. Recognition of predictive pathway(s) for PTD may permit the identification of individuals at risk for PTD may permit the identification of individuals at risk for PTD and, ultimately, the implementation of noel strategies for its prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAPID EVALUATION OF DRUG RESISTANCE IN PATHOGENIC FUNGI Principal Investigator & Institution: Perlin, David S.; Scientific Director; Public Health Research Institute 225 Warren St Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Fungal infections caused by Candida spp. represent a significant cause of morbidity and mortality for severely ill patients. The widespread use of antifungal agents has resulted in the selection of naturally resistant Candida species, as well as expression of resistance from previously susceptible species resulting from genetic mutations and/or selection of resistant subpopulations. Several mechanisms have been linked to antifungal resistance, including mutations that alter drug-target interactions and reduced drug accumulation by overexpression of drug efflux pumps. The care of critically-ill patients requires a rapid identification of fungal pathogens with an assessment of antifungal susceptibility. Nucleic acid-based amplification assays provide an optimal approach to this problem because they are more rapid and sensitive than current culture-based and biochemical methods. A series of Molecular Beacon-based diagnostic panels will be constructed that allow sensitive identification of fungal pathogens with a rapid assessment of antifungal drug resistance by examining prominent mechanisms. The panel will be constructed for Candida albicans, which accounts for a majority of fungal infections, and will target resistance mechanisms for azole-based drugs and the new echinocandin class of antifungal agents.

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An important feature of the test panels will be allele discrimination, which will enable mutations resulting in drug resistance to be easily detected in the diploid (multiploid) Candida albicans. The major impact of the test panel will be rapid detection of drug resistance that can speed diagnosis and guide treatment decisions for life-threatening illnesses. Although our emphasis is on fungal infections, this approach should serve as a paradigm for applications to other pathogens with established resistance mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF MORPHOGENESIS IN C. ALBICANS Principal Investigator & Institution: Konopka, James B.; Associate Professor; Molecular Genetics & Microbiol; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: The goal of this proposal is to determine the molecular mechanisms of morphogenesis for Candida albicans. C. albicans is the most common fungal pathogen in humans and causes particularly severe life-threatening infections in immunocompromised individuals. The significance of C. albicans as a health risk is increasing as better medical techniques make long-term care of organ transplant, cancer, and HIV patients more common. A better understanding of the mechanisms of pathogenesis is needed to formulate new therapeutic strategies to combat Candidiasis because the drugs currently used against C. albicans are not very effective, especially after it has invaded into tissues. One virulence factor that has been strongly implicated in the pathogenesis of C. albicans is the ability of this yeast to undergo morphological transitions between round budding cells and filamentous hyphae. Therefore, the specific aims of this grant are designed to identify the proteins that regulate morphogenesis of C. albicans. In particular, the septin family of cytoskeletal proteins will be examined because the septins play important roles in morphological transitions in the yeast S. cerevisiae and other organisms. Genetic strategies will be used to determine which members of the septin family function in hyphal morphogenesis. Biochemical approaches will then be used to study the mechanisms that regulate C. albicans septin proteins, and targeted mutagenesis will be used to determine their role in controlling hyphal morphogenesis. Septins act by recruiting key regulatory proteins. Therefore, Septin function in C. albicans will be defined further by identifying septin-binding proteins and analyzing their function. The experimental procedures are designed to take full advantage of recently improved strategies for the genetic analysis of C. albicans and the data being made available from the C. albicans genome sequencing project. Altogether, these studies are expected to identify key regulators of morphological transitions that promote the pathogenesis of C. albicans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RNA INTERFERENCE IN THE FUNGAL PATHOGEN CANDIDA ALBICANS Principal Investigator & Institution: Staab, Janet F.; Seattle Biomedical Research Institute 4 Nickerson St, Ste 200 Seattle, Wa 98109 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2005 Summary: (provided by applicant): Candida albicans is the most common etiologic agent of oropharyngeal candidiasis (OPC), an opportunistic infection in HIV v patients occurring in as many as 90% of AIDS patients at some point during the course of HIV disease. OPC is also seen at an appreciable rate in head and neck cancer patients due to impaired salivary function resulting from radiation therapy. A salient characteristic of

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C. albicans is the ability to grow in different morphological forms, from ovoid yeasts to filamentous hyphae. The expression of several virulence factors is intimately associated with morphology, and strains impaired in morphological transitions have reduced virulence in animal models. The molecular mechanism of how C. albicans coordinates expression of virulence genes with morphological forms is unclear. The recently described phenomenon of gene silencing termed posttranscriptional gene silencing (PTGS) triggered by double-stranded RNA (dsRNA) appears to be a conserved mechanism involved in resistance to viruses, protection of the genome from repetitive elements, developmental timing, and heterochromatin silencing. The PTGS effect is achieved by the degradation of mRNA termed RNA interference (RNAi). Genetic studies across many species have identified several homologous genes involved in RNAi, and in every organism where a PTGS function has been described, a member of the Argonaute protein family has been found. The finding of an ARGONAUTE gene homolog in C. albicans suggests that the fungus is capable of PTGS. This novel gene regulatory system may prove to be important in C. albicans for the regulation of virulence genes indirectly by affecting morphological transitions. The goals of this exploratory/developmental proposal are: (1) to uncover evidence in C. albicans of gene regulation by PTGS through RNAi; and (2) to determine the role of PTGS in control of virulence attributes through morphological transitions, and in maintenance of centromeric heterochromatic structure. The proposed initial studies will take genetic and molecular approaches to determine the capability of C. albicans to perform PTGS through analyses of RNAi constructs and gene knock out strains. Although the role of RNAi in the biology of C. albicans is unknown, the probability is high that novel gene regulatory mechanisms will be found that are common to other fungal pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING COMPLEXES AND THE 14-3-3 PROTEIN IN CANDIDA Principal Investigator & Institution: Sturtevant, Joy E.; Assistant Professor; Microbiology and Immunology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 15-JUN-1999; Project End 31-MAY-2004 Summary: (Adapted from Applicant's Abstract) Fungal infections have increased dramatically in recent years due to the onset of AIDS and improved treatment of immunosuppressed individuals. Among AIDS patients, the most prevalent mycotic disease is mucosal infection due to Candida albicans. However, the molecular events which occur during the pathogenesis of C. albicans are not well defined. For example, upon contact with mammalian tissue and initiation of infection, C. albicans switches between growth forms. Therefore, genes involved in environmental response, cell morphology, and cell cycle must be coordinately regulated when the fungus interacts with the host. Using differential display reverse transcription technology in conjunction with a novel adherence assay, the P.I. identified BMH1. This gene is differentially regulated after adherence to a human esophageal cell line grown in an extracellular matrix. BMH1 exists as a single copy gene in C. albicans and encodes a 14-3-3 protein motif that is highly homologous to other 14-3-3 genes of the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The expression of the C. albicans homolog significantly decreases after exposure to the extracellular matrix. Because 14-3-3 proteins are important for the activation of signaling genes in mammals as well as pseudohyphal induction, normal bud development, and cell cycle control in yeasts, investigations are proposed to examine the role of C. albicans BMH1 in signaling, morphogenesis, and cell cycle control. The present proposal intends to construct null mutants and reconstituted strains to functionally characterize the BMH1 gene and its role in these events. The yeast

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two-hybrid system and gene fusion constructs will be created to detect protein interactions with BMH1. Finally, the P.I. proposes to assess if Bmh1p is involved in pathogenesis using an oral candidiasis model. It is hoped that the results of this study will lead to the identification of potential antifungal targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF THE MRNA CAPPING APPARATUS Principal Investigator & Institution: Lima, Christopher D.; Associate Professor; Biochemistry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: The 5' cap structure (m7GpppN) of eukaryotic messenger RNA modulates the function and metabolism of RNA in the cell. The cap structure is directly involved in RNA function through recognition of mature mRNA by the translation machinery. The cap structure also protects mRNA from degradation. Capping occurs through a series of three chemical reactions. The first reaction is catalyzed by RNA triphosphatase, which removes the terminal gamma phosphate from the nascent 5' triphosphate terminated mRNA chain. This reaction leaves a 5' diphosphate RNA end that is subsequently capped with GMT in a second reaction catalyzed by RNA guanylyltransferase. The third reaction in the capping process is mediated by RNA (guanine-7) methyltransferase, which methylates the N7 position of the terminal guanine. Disruption of any of these catalytic steps blocks cell growth. The main objectives of this proposal are to illuminate the structural basis for eukaryotic mRNA capping by determining crystal structures for several cap forming enzymes in complex with one another, and in complex with key nucleotide and RNA catalytic intermediates. A focus of this research will be to devise methods for determining crystal structures of unique RNA catalytic intermediates that will provide insights into RNA recognition and catalytic mechanism. Another focus will be to structurally characterize the multimeric macromolecular complexes necessary for RNA capping in the cell. We are specifically targeting structure determinations in two fungal systems because these organisms utilize specific mechanisms unique to both viral and fungal pathogens, thus making them ideal targets for structure-based drug design. Structure-based approaches to disrupting the capping process in these organisms will further the development of therapeutic intervention against them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND FUNCTION OF FUNGAL CELL ADHESION PROTEINS Principal Investigator & Institution: Lipke, Peter N.; Professor; Hunter College 695 Park Ave New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Fungal infections remain a serious cause of morbidity and mortality, especially in immunocompromised patients. Candida albicans is among the most common agents, perhaps because of its normally commensal status. While candidiasis is often superficial in AIDS patients, deeper infections are becoming increasingly common, and are often difficult to treat. In C. albicans, the ALS genes (alpha-Agglutinin Like Sequences) are a large family that mediates substrate adhesion to mammalian cells and self-aggregation. The sequence similarity of Als proteins to the S. cerevisiae sexual cell adhesion protein alpha-agglutinin means that alpha- agglutinin, which is well studied, can serve as a structural and functional prototype for the Als proteins. Additional regions in the Als proteins, but not in alpha-agglutinin, have sequence similarity to S.

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cerevisiae flocculins, which mediate Ca++-dependent aggregation. We propose that the structure and activities of the S. cerevisiae sexual agglutinins and flocculins can be used as models for the pathogenesis-related ALS proteins from C. albicans. Three dimensional models of the Als protein structure and binding will predict differences in structure and function, and that these differences will relate to the roles of the Als proteins in host-pathogen interaction. In collaboration with Dr. Stephen Klotz: 1. We will determine the binding properties and physical characteristics of three regions of C. albicans Als99p that are predicted to mediate adhesive interactions. 2. We will test the idea that sequences rich in Thr and other beta-branched amino acids are common to the C. albicans ALS gene family model for Als proteins we will determine if the tight binding of the S. cerevisiae agglutinins is mediated by conformational shift in alphaagglutinin. 4. The binding characteristics of Als99p to its ligands will be investigated following the model resulting from Aim 3. These studies will generate a molecular picture of the structure and function of the Als family of proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGET-BASED ANTIFUNGAL DRUG DISCOVERY Principal Investigator & Institution: Trawick, John D.; Elitra Pharmaceuticals, Inc. 3510 Dunhill St San Diego, Ca 921211212 Timing: Fiscal Year 2003; Project Start 15-AUG-2000; Project End 31-JAN-2005 Summary: (provided by applicant): The incidence of serious fungal infections has increased markedly in the last two decades and effective treatment options are increasingly compromised by the emergence of drug-resistant strains. The goal of the proposed work is to develop novel antifungal drugs that are safer and more effective than those currently available. The work will focus primarily on the dimorphic yeast, C. albicans, which is by far the leading cause of both life-threatening systemic fungal infections and more commonly occurring topical infections. A distinguishing feature of the drug-discovery strategy the applicants are pursuing is that it is based on target discovery, target prioritization and screening, all conducted with the pathogen itself, rather than with a surrogate model system. This strategy has been enabled by geneidentification and screen-configuration technologies developed at Elitra Pharmaceuticals, including important technologies developed under Phase I funding for this program. Under Phase I, an expression vector system was constructed that will allow screening for dominant-negative phenotypes. No such tools existed previously for C. albicans. Screens for dominant-negatives will identify new drug targets in C. albicans and help annotate essential physiological pathways in this important fungal pathogen. Critical functional features of the expression vector system have already been validated, a C. albicans complementary deoxyribonucleic acid (cDNA) library has been constructed in the vector, and pilot screening for dominant-negatives is in progress. Under Phase II funding, the investigators propose to implement the screen more broadly, characterize and prioritize the targets that are identified and conduct screening for drug leads. The dominant-negative phenotypes of the newly identified targets will be used to develop primary or secondary cell-based assays to screen chemical libraries for potential antifungal drugs and to facilitate the characterization of hits identified through other screening strategies. The proposed Phase II work will complement and enhance the value of internally funded target-identification and screening efforts at Elitra and will help promote the discovery of badly needed therapeutic agents in a medical area that generally receives insufficient attention from the pharmaceutical industry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ALS GENE FAMILY OF CANDIDA ALBICANS Principal Investigator & Institution: Hoyer, Lois L.; Associate Professor; Animal Sciences and Veterinary Pathobiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-JUL-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF THE CCAAT-BINDING FACTOR IN CANDIDA ALBICANS Principal Investigator & Institution: Mcnabb, David S.; Biological Sciences; University of Arkansas at Fayetteville Fayetteville, Ar 72701 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Candida albicans is the most frequently encountered fungal pathogen in humans, and is responsible for a variety of rnucocutaneous and systemic infections. There are a number of predisposing factors that contribute to Candida infections; however, the increasing number of immunocompromised patients (due primarily to imrnunosuppressive therapies and AIDS) has led to a sharp increase in the incidence of candidiasis. This fact, coupled with the limited arsenal of therapeutic agents, dictates that current research efforts focus on elucidating pathways that contribute to Candida virulence and on identifying novel targets for drug development. The long-term goal of this research program is to investigate whether a unique structural feature of fungal CCAAT-binding factors could serve as a target for antifungal compounds. The CCAAT-binding factor is a heterooligomeric transcriptional activator that is highly conserved evolutionarily in all eukaryotes; however, in fungi this transcription factor contains a novel subunit (termed Hap4p) that is not found in other eukaryotes. It is the unique interaction of this fungalspecific subunit with other components of the heteromeric complex that represents a potential target for drug development. The failure of Hap4p to interact with the DNAbinding components of the complex results in the loss of target gene expression. Thus, development of peptides or small molecules that inhibit this fungal-specific proteinprotein interaction could offer a viable approach to combating fungal infections. The goal of the studies described in this proposal is to determine the regulatory function of the CCAAT-binding factor in C. albicans, and to examine whether it is important in the regulation of genes involved in virulence and pathogenesis, as the initial step toward exploring its potential as a therapeutic drug target. The proposed studies will address the following specific aims: 1) to generate mutants in the genes encoding the various subunits of the CCAAT-binding factor and evaluate their phenotypes; 2) to determine whether the CCAAT-binding factor is important for C. albicans virulence; and 3) to dissect the regulatory function of the CCAAT-binding factor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE SIGNIFICANCE OF FUNGURIA IN HOSPITALIZED PATIENTS Principal Investigator & Institution: Miller, Loren G.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from applicant's abstract): The incidence of fungal urinary tract infections, largely caused by Candida species, is rapidly increasing in hospitalized

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patients. In just one decade, the proportion of fungal urinary isolates from medical intensive care units has increased from 22% to 39%. The significance of isolated fungi from the urinary tract remains a subject of considerable debate. Nevertheless, many patients with funguria receive antifungal drugs, which is expensive and may be contribute to selection of drug resistant fungi. Since there is an urgent need to understand the significance of fungal urinary tract isolates, the applicant plans to perform a series of 5 patient-oriented research projects. Project 1 is a prospective observational study of >600 patients with funguria from 2 centers over 24 months. The patients will be followed longitudinally for persistence of infection and complications, and they will be compared to similar numbers of control patients without funguria (to be identified in Project 2, a hospital-based prospective surveillance project) to create models to address whether funguria is independently associated with mortality and whether funguria is associated with or predicts fungemia. The robust size of these models will allow the applicant to control for known risks of mortality and fungemia and to ask whether subpopulations (e.g., critically ill patients) are at higher risk for morbidity or mortality from fungemia. Project 3 will be to follow patients with funguria up to 1 year after hospital discharge to define long-term outcomes and complications. Project 4 will employ molecular typing methods to investigate strain relatedness between blood and urine fungal isolates in patients who have both funguria and fungemia. Project 5 will estimate the incidence of funguria among hospitalized patients and the impact of funguria on resource utilization nationwide using various health care databases. From the above studies, the applicant expects to generate information that will help clinicians employ focused strategies toward the patient with funguria and may result in cost savings while contributing to the effort to avoid a shift towards azoleresistant fungi. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE SYNTHESIS OF LEUCASCANDROLIDE A Principal Investigator & Institution: Kozmin, Sergey A.; Chemistry; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 04-JAN-2002; Project End 31-DEC-2005 Summary: The primary objective of this research program is to develop a practical synthesis of leucascandrolide A (1), a novel marine macrolide isolated by Pietra in 1996. In preliminary in vitro studies, leucascandrolide A deisplayed a potent cytotoxicity, and strong inhibition of the pathogenic yeast Candida albicans. Due to the difficulty of isolation of leucascandrolide A, combined with the presently unknown biogenetic origin, an efficient chemical synthesis represents the only viable approach to this rare natural product. Having completed the synthesis of the C(1)-C(15) fragment of this natural product, we propose a convergent, fully stereocontrolled synthetic approach to leucascandrolide A, suitable for the production of sufficient amount of this natural product for a comprehensive biological evaluation. In addition, we will develop the new synthetic methods including asymmetric Prins desymmetrization, tandem and catalytic asymmetric hydrosilylations, designed to provide an access to a variety of valuable synthetic intermediates. Starting at the level of basic research in organic and organometallic synthesis, it is our ultimate objective to provide new directions for the development of new anticancer therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TOLL-LIKE RECEPTORS IN CANDIDIASIS Principal Investigator & Institution: Hong, Soon-Cheol; Microbiology and Immunology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-JUL-2005 Summary: (abstract verbatim) Oropharyngeal candidiasis (OPC) is a major problem in patients with AIDS, diabetes, and a number of other predisposing conditions. The predominant species, Candida albicans, may be found in small numbers in healthy persons but the numbers increase dramatically when OPC is found. The nature of host resistance to Candida is poorly understood in that it is not at all clear why the numbers of yeast remain low in healthy persons. The PI proposes that the interactions of C albicans with toll-like receptors play a role in the induction of protective defenses. In our preliminary experiments, the PI has found that C. albicans mannan, as well as lipopolysaccharide from Gram-negative bacteria, regulates several different TLRs in murine macrophages. The PI plans to analyze the kinetics of TLR gene expression after macrophage exposure to mannan. In addition to assaying mRNA, production of TLR proteins will be monitored by use of antibodies generated as part of the research. In addition, they will investigate the role of mannan as a regulator of expression of the costimulatory molecules B7-1 and B7-2, and of the proinflammatory cytokine TNF-alpha as these can be induced as a result of TLR-mediated signaling. They will determine whether whole cells and a variety of extracts of C. albicans and other yeast species invoke the same sort of immune response via interactions involving TLRs. Successful understanding of the interactions of pathogenic yeasts with TLRs should lay a foundation for development of immunological strategies that may augment defense responses in OPC and other infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OF FUNGAL INFECTIONS WITH ATAK CELLS Principal Investigator & Institution: Ibrahim, Ashraf S.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Hematogenously disseminated fungal infections are increasing in number and have unacceptably high mortality rates despite current treatment options. New therapeutic modalities are therefore critically needed and immuno-based strategies may hold tremendous promise in the treatment of disseminated fungal infections. To treat invasive fungal infections, we propose to construct an immortal phagocytic cell-line that will specifically target leukocytes to attack fungal pathogens. We will create a genetic construct coding for a chimeric receptor formed by fusing the signal-transducing component of the Fc/gamma receptor to the antigen-binding portion of a monoclonal antibody (MAb) recognizing a fungal cell surface adhesin. By transforming a phagocytic cell-line with this chimeric receptor, we predict that the effector cells would have an enhanced ability to recognize, phagocytize, and kill fungi in vivo. Such technology is already being used to develop immunotherapies for cancer patients. We have initially targeted Candida albicans by raising a MAb (3A5) against a cell surface glycoprotein which is expressed on both the yeast and the hyphal forms. We also identified a macrophage cell-line (HL-60) that has the ability to kill C. albicans in vitro. Our specific aims are: 1) To generate a line of Antibody Targeted Activated Killer (ATAK) cells by transforming HL-60 cells with the chimeric receptor construct. In addition, several safety controls will be incorporated into

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the ATAK system to ensure that the cells can be eliminated from the host once the infection has resolved. 2) To characterize the binding specificity of the chimeric receptor to C. albicans in vitro, and assess the effect of the receptor on improving HL-60mediated fungal killing. 3) To demonstrate the efficacy and safety of ATAK cells in a neutropenic mouse model of hematogenously disseminated candidiasis. Construction of ATAK cells that can be safely infused into humans will revolutionize therapy of infections in immunocompromised patients. Furthermore, the genetic construct targeting ATAK cells to Candida can easily be adapted to any other pathogen against which a MAb has been raised. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALBICANS

TWO-COMPONENT

HISTIDINE

KINASES

OF

CANDIDA

Principal Investigator & Institution: Calderone, Richard A.; Professor of Microbiology; Microbiology and Immunology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2003 Summary: Candida albicans is the leading cause of fungal infections in the US and, Candida spp. now rank fourth among all pathogens in causing nosocomial infections. Virulence in this organism is probably multi-factorial and tissue-specific, since C. albicans is capable of infecting a number of diverse environmental sites (for example, the acid vaginal canal vs. the neutral pH of blood and tissues). Two-component, histidine kinases (HK) are environmental sensor, phosphorelay proteins of prokaryotes and lower eukaryotes whose activity results in transcriptional activation of genes associated with an adaptive response to stress. Among the HK genes of pathogenic fungi, recently, we isolated a C. albicans hybrid HK (CaHK1), which is unique structurally and functionally among all HK genes thus far described. A cahk1 null strain has been constructed and compared phenotypically in vitro and in vivo to parental and gene-reconstituted strains. In vitro, hyphae of null strains flocculate at pH 7.5, indicating that cell surface changes in hyphae are associated with a mutation in caHK1 The null is also avirulent in a systemic murine model but virulent in a rat vaginal mucosal model when compared to parental and gene- reconstituted strains. While Northern analyses indicate that CaHK1 is expressed in both acid and neutral pH media, we hypothesize that activity of Cahk1p may depend upon its state of phosphorylation. There are 3 specific aims in this proposal. 1. The influence of environmental factors (temp, pH, osmolarity) on the expression of CaHK1 will be measured in vitro using Northern analyses; post-translational modifications of Cahk1p will be determined. 2. We will evaluate the virulence of CaHK1 strain constructs in oral and vaginal models in order to extend our knowledge on the role of Cahk1p in virulence. 3. Cahk1p interactions with other proteins including down-stream effector proteins are to be identified. In summary, these studies will partially define the Cahk1p phosphorelay pathway and function of CaHK1 in the pathogenesis of candidiasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENS

WANGIELLA:

A

MODEL

FOR

DEMATIACEOUS

FUNGAL

Principal Investigator & Institution: Szaniszlo, Paul J.; Molecular Genetics & Microbiol0gy; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2003; Project Start 01-DEC-1992; Project End 31-DEC-2007

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Summary: (provided by applicant): Our research has shown that the polymorphic fungal pathogen of humans Wangiella dermatitidis has at least five chitin synthases (WdChsp), each of which is representative of a different class. Of these, newly discovered WdChs5p, a class V isozyme, requires considerable additional in-depth study, because it is the only single chitin synthase of this dematiaceous (melanized) agent of phaeohyphomycosis required for survival at 37degrees C and for full virulence in murine models of acute infection. These striking characteristics make the pathways leading to WdChs5p production and function exceptionally suitable targets for the design of antifungal drugs that are effective against dematiaceous fungi, and perhaps other pathogens with class V chitin synthases. Our rapid development of W. dermatitidis into a molecularly tractable model for studies of chitin biosynthesis, and our numerous new and novel findings about this essential fungal process, suggest that my proposed studies of WdChs5p will provide additional important insights about chitin synthases that are wide spread in molds, but have no orthologs in Saccharomyces cerevisiae or Candida albicans. These proposed new studies will mechanistically probe how WdChs5p production is regulated by stress conditions associated with infection, why its lack of function leads to cell death at 37 degrees C but not at 25 degrees C, and whether its unique myosin motor-like domain contributes directly to the positional insertions of a specific cell wall chitin in stressed yeasts, hyphae or sclerotic bodies of W. dermatitidis. My proposal's revised Specific Aims are to 1) determine if the elevated transcript levels of the WdCHS5 gene detected at temperature of infection are affected by post-transcriptional modifications; 2) confirm that one or more cis-acting elements in the 5' URS of WdCHS5 interact with trans-acting factors to up-regulate its transcription under stress conditions associated with infections; 3) establish how the product of WdCHS5 protects against lysis and death at 37 degrees C, and document that the pathways leading to the production and function of WdChs5p and other class V chitin synthases are particularly vulnerable targets for antifungal drug design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Candida” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for Candida in the PubMed Central database:

3 4

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

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

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[beta]-1,2-Mannosylation of Candida albicans Mannoproteins and Glycolipids Differs with Growth Temperature and Serotype. by Trinel PA, Jouault T, Cutler JE, Poulain D.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128217

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A Forkhead Transcription Factor Is Important for True Hyphal as well as Yeast Morphogenesis in Candida albicans. by Bensen ES, Filler SG, Berman J.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=126749

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A G1 Cyclin Is Necessary for Maintenance of Filamentous Growth in Candida albicans. by Loeb JD, Sepulveda-Becerra M, Hazan I, Liu H.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104361

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A Hyphal-Specific Chitin Synthase Gene (CHS2) is not Essential for Growth, Dimorphism, or Virulence of Candida albicans. by Gow NA, Robbins PW, Lester JW, Brown AJ, Fonzi WA, Chapman T, Kinsman OS.; 1994 Jun 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44169

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A Methylotrophic Pathway Participates in Pectin Utilization by Candida boidinii. by Nakagawa T, Miyaji T, Yurimoto H, Sakai Y, Kato N, Tomizuka N.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=92293

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A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei. by Sanati H, Belanger P, Fratti R, Ghannoum M.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164150

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A single strain of Candida albicans associated with separate episodes of fungemia and meningitis. by Porter SD, Noble MA, Rennie R.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229123

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A Single-Transformation Gene Function Test in Diploid Candida albicans. by Enloe B, Diamond A, Mitchell AP.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94694

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A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence. by Sanglard D, Hube B, Monod M, Odds FC, Gow NA.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175504

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Accumulation of 3-Ketosteroids Induced by Itraconazole in Azole-Resistant Clinical Candida albicans Isolates. by Marichal P, Gorrens J, Laurijssens L, Vermuyten K, Van Hove C, Le Jeune L, Verhasselt P, Sanglard D, Borgers M, Ramaekers FC, Odds F, Vanden Bossche H.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89540

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Acetate-Mediated Growth Inhibition in Sterol 14[alpha]-Demethylation-Deficient Cells of Candida albicans. by Shimokawa O, Nakayama H.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89028

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Action of Chlorhexidine Digluconate against Yeast and Filamentous Forms in an Early-Stage Candida albicans Biofilm. by Suci PA, Tyler BJ.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128749

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Activities of Fluconazole and Voriconazole against 1,586 Recent Clinical Isolates of Candida Species Determined by Broth Microdilution, Disk Diffusion, and Etest Methods: Report from The ARTEMIS Global Antifungal Susceptibility Program, 2001. by Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153922

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Activity of a new triazole, Sch 56592, compared with those of four other antifungal agents tested against clinical isolates of Candida spp. and Saccharomyces cerevisiae. by Pfaller MA, Messer S, Jones RN.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163694

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Activity of Protegrins against Yeast-Phase Candida albicans. by Cho Y, Turner JS, Dinh NN, Lehrer RI.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108228

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Activity of Voriconazole, a New Triazole, Combined with Neutrophils or Monocytes against Candida albicans: Effect of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor. by Vora S, Purimetla N, Brummer E, Stevens DA.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105565

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Altered Expression of Selectable Marker URA3 in Gene-Disrupted Candida albicans Strains Complicates Interpretation of Virulence Studies. by Lay J, Henry LK, Clifford J, Koltin Y, Bulawa CE, Becker JM.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108662

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Alternative Identification Test Relying upon Sexual Reproductive Abilities of Candida lusitaniae Strains Isolated from Hospitalized Patients. by Francois F, Noel T, Pepin R, Brulfert A, Chastin C, Favel A, Villard J.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88463

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Amino Acid Substitutions in the Cytochrome P-450 Lanosterol 14[alpha]Demethylase (CYP51A1) from Azole-Resistant Candida albicans Clinical Isolates Contribute to Resistance to Azole Antifungal Agents. by Sanglard D, Ischer F, Koymans L, Bille J.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105395

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Amphotericin B- and Fluconazole-Resistant Candida spp., Aspergillus fumigatus, and Other Newly Emerging Pathogenic Fungi Are Susceptible to Basic Antifungal

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Peptides. by Helmerhorst EJ, Reijnders IM, van 't Hof W, Simoons-Smit I, Veerman EC, Amerongen AV.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89188 •

An n-Alkane-Responsive Promoter Element Found in the Gene Encoding the Peroxisomal Protein of Candida tropicalis Does Not Contain a C6 Zinc Cluster DNABinding Motif. by Kanai T, Hara A, Kanayama N, Ueda M, Tanaka A.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111312

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Analysis of Microsatellite Markers of Candida albicans Used for Rapid Typing. by Botterel F, Desterke C, Costa C, Bretagne S.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88489

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Analysis of Phase-Specific Gene Expression at the Single-Cell Level in the WhiteOpaque Switching System of Candida albicans. by Strauss A, Michel S, Morschhauser J.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95254

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Analysis of the Gene Family Encoding Lipases in Candida rugosa by Competitive Reverse Transcription-PCR. by Lee GC, Tang SJ, Sun KH, Shaw JF.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99716

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Antagonism of Azole Activity against Candida albicans following Induction of Multidrug Resistance Genes by Selected Antimicrobial Agents. by Henry KW, Cruz MC, Katiyar SK, Edlind TD.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89399

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Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro. by Moran GP, Sullivan DJ, Henman MC, McCreary CE, Harrington BJ, Shanley DB, Coleman DC.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163761

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Antifungal Effects of Lysozyme and Lactoferrin against Genetically Similar, Sequential Candida albicans Isolates from a Human Immunodeficiency VirusInfected Southern Chinese Cohort. by Samaranayake YH, Samaranayake LP, Pow EH, Beena VT, Yeung KW.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88334

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Antifungal Susceptibility of Candida Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins. by Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127206

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Application of CHROMagar Candida for rapid screening of clinical specimens for Candida albicans, Candida tropicalis, Candida krusei, and Candida (Torulopsis) glabrata. by Pfaller MA, Houston A, Coffmann S.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228730

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Ash1 Protein, an Asymmetrically Localized Transcriptional Regulator, Controls Filamentous Growth and Virulence of Candida albicans. by Inglis DO, Johnson AD.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139894

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Assessment of Antifungal Activities of Fluconazole and Amphotericin B Administered Alone and in Combination against Candida albicans by Using a Dynamic In Vitro Mycotic Infection Model. by Lewis RE, Lund BC, Klepser ME, Ernst EJ, Pfaller MA.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105608

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Assessment of the Effect of Amphotericin B on the Vitality of Candida albicans. by Liao RS, Rennie RP, Talbot JA.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89108

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Attenuated Virulence of Chitin-Deficient Mutants of Candida albicans. by Bulawa CE, Miller DW, Henry LK, Becker JM.; 1995 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40653

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Attenuation of Virulence and Changes in Morphology in Candida albicans by Disruption of the N-Acetylglucosamine Catabolic Pathway. by Singh P, Ghosh S, Datta A.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98888

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Autoactivation by a Candida glabrata copper metalloregulatory transcription factor requires critical minor groove interactions. by Koch KA, Thiele DJ.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231052

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Avirulence of Candida albicans CaHK1 Mutants in a Murine Model of Hematogenously Disseminated Candidiasis. by Calera JA, Zhao XJ, De Bernardis F, Sheridan M, Calderone R.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96739

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Avirulence of Candida albicans FAS2 mutants in a mouse model of systemic candidiasis. by Zhao XJ, McElhaney-Feser GE, Sheridan MJ, Broedel SE Jr, Cihlar RL.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176135

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Azasordarins: Susceptibility of Fluconazole-Susceptible and Fluconazole-Resistant Clinical Isolates of Candida spp. to GW 471558. by Cuenca-Estrella M, Mellado E, Diaz-Guerra TM, Monzon A, Rodriguez-Tudela JL.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90570

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Biofilm Formation by Candida dubliniensis. by Ramage G, Vande Walle K, Wickes BL, Lopez-Ribot JL.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88324

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Biofilm Formation by the Fungal Pathogen Candida albicans: Development, Architecture, and Drug Resistance. by Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95423

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Biofilm Production by Isolates of Candida Species Recovered from Nonneutropenic Patients: Comparison of Bloodstream Isolates with Isolates from Other Sources. by Shin JH, Kee SJ, Shin MG, Kim SH, Shin DH, Lee SK, Suh SP, Ryang DW.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140345

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Biotyping and Virulence Properties of Skin Isolates of Candida parapsilosis. by De Bernardis F, Mondello F, San Millan R, Ponton J, Cassone A.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85673

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Bloodstream Infections Due to Candida Species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, 1997-1998. by Pfaller MA, Jones RN, Doern GV, Sader HS, Messer SA, Houston A, Coffman S, Hollis RJ.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89757

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Calcineurin is essential for survival during membrane stress in Candida albicans. by Cruz MC, Goldstein AL, Blankenship JR, Del Poeta M, Davis D, Cardenas ME, Perfect JR, McCusker JH, Heitman J.; 2002 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=125859

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Candida albicans and Candida krusei Differentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production. by Xiong J, Kang K, Liu L, Yoshida Y, Cooper KD, Ghannoum MA.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97447

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Candida albicans Estrogen-Binding Protein Gene Encodes an Oxidoreductase that is Inhibited by Estradiol. by Madani ND, Malloy PJ, Rodriguez-Pombo P, Krishnan AV, Feldman D.; 1994 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43065

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Candida albicans Expresses a Focal Adhesion Kinase-Like Protein That Undergoes Increased Tyrosine Phosphorylation upon Yeast Cell Adhesion to Vitronectin and the EA.hy 926 Human Endothelial Cell Line. by Santoni G, Lucciarini R, Amantini C, Jacobelli J, Spreghini E, Ballarini P, Piccoli M, Gismondi A.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128043

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Candida albicans Hyphal Formation and the Expression of the Efg1-Regulated Proteinases Sap4 to Sap6 Are Required for the Invasion of Parenchymal Organs. by Felk A, Kretschmar M, Albrecht A, Schaller M, Beinhauer S, Nichterlein T, Sanglard D, Korting HC, Schafer W, Hube B.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128044

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Candida albicans INT1-Induced Filamentation in Saccharomyces cerevisiae Depends on Sla2p. by Asleson CM, Bensen ES, Gale CA, Melms AS, Kurischko C, Berman J.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99580

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Candida albicans Int1p Interacts with the Septin Ring in Yeast and Hyphal Cells. by Gale C, Gerami-Nejad M, McClellan M, Vandoninck S, Longtine MS, Berman J.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60274

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Candida albicans Killing by RAW 264.7 Mouse Macrophage Cells: Effects of Candida Genotype, Infection Ratios, and Gamma Interferon Treatment. by Marcil A, Harcus D, Thomas DY, Whiteway M.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=130362

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Candida albicans Mutants Deficient in Respiration Are Resistant to the Small Cationic Salivary Antimicrobial Peptide Histatin 5. by Gyurko C, Lendenmann U, Troxler RF, Oppenheim FG.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89682

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Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions. by Davis D, Edwards JE Jr, Mitchell AP, Ibrahim AS.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=101559

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Candida albicans secreted aspartyl proteinases: isoenzyme pattern is determined by cell type, and levels are determined by environmental factors. by White TC, Agabian N.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177311

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Candida albicans Sterol C-14 Reductase, Encoded by the ERG24 Gene, as a Potential Antifungal Target Site. by Jia N, Arthington-Skaggs B, Lee W, Pierson CA, Lees ND, Eckstein J, Barbuch R, Bard M.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127109

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Candida albicans stimulates cytokine production and leukocyte adhesion molecule expression by endothelial cells. by Filler SG, Pfunder AS, Spellberg BJ, Spellberg JP, Edwards JE Jr.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174117

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Candida albicans strains heterozygous and homozygous for mutations in mitogenactivated protein kinase signaling components have defects in hyphal development. by Kohler JR, Fink GR.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24074

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Candida and Torulopsis: a blinded evaluation of use of pseudohypha formation as basis for identification of medically important yeasts. by Odds FC, Rinaldi MG, Cooper CR Jr, Fothergill A, Pasarell L, McGinnis MR.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229568

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Candida dubliniensis at a University Hospital in Saudi Arabia. by Fotedar R, Al Hedaithy SS.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154754

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Candida dubliniensis: Characteristics and Identification. by Sullivan D, Coleman D.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104537

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Candida glabrata Oropharyngeal Candidiasis in Patients Receiving Radiation Treatment for Head and Neck Cancer. by Redding SW, Kirkpatrick WR, Coco BJ, Sadkowski L, Fothergill AW, Rinaldi MG, Eng TY, Patterson TF.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130928

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Candida glabrata: Review of Epidemiology, Pathogenesis, and Clinical Disease with Comparison to C. albicans. by Fidel PL Jr, Vazquez JA, Sobel JD.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88907

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Candida Isolates from Neonates: Frequency of Misidentification and Reduced Fluconazole Susceptibility. by Rowen JL, Tate JM, Nordoff N, Passarell L, McGinnis MR.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85744

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Candida Species Exhibit Differential In Vitro Hemolytic Activities. by Luo G, Samaranayake LP, Yau JY.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88272

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Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026p (Mrf1[prime prime or minute]p), 2-Enoyl Thioester Reductases Essential for Mitochondrial Respiratory Competence. by Torkko JM, Koivuranta KT, Miinalainen IJ, Yagi AI, Schmitz W, Kastaniotis AJ, Airenne TT, Gurvitz A, Hiltunen KJ.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87346

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Candida tropicalis in a Neonatal Intensive Care Unit: Epidemiologic and Molecular Analysis of an Outbreak of Infection with an Uncommon Neonatal Pathogen. by Roilides E, Farmaki E, Evdoridou J, Francesconi A, Kasai M, Filioti J, Tsivitanidou M, Sofianou D, Kremenopoulos G, Walsh TJ.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149715

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Candidacidal Activities of Human Lactoferrin Peptides Derived from the N Terminus. by Lupetti A, Paulusma-Annema A, Welling MM, Senesi S, van Dissel JT, Nibbering PH.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90189

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CAP1, an Adenylate Cyclase-Associated Protein Gene, Regulates Bud-Hypha Transitions, Filamentous Growth, and Cyclic AMP Levels and Is Required for Virulence of Candida albicans. by Bahn YS, Sundstrom P.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95223

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Catheter-Related Candidemia Caused by Candida lipolytica in a Patient Receiving Allogeneic Bone Marrow Transplantation. by D'Antonio D, Romano F, Pontieri E, Fioritoni G, Caracciolo C, Bianchini S, Olioso P, Staniscia T, Sferra R, Boccia S, Vetuschi A, Federico G, Gaudio E, Carruba G.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140330

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Cdc24, the GDP-GTP Exchange Factor for Cdc42, Is Required for Invasive Hyphal Growth of Candida albicans. by Bassilana M, Blyth J, Arkowitz RA.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=141177

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CDC42 Is Required for Polarized Growth in Human Pathogen Candida albicans. by Ushinsky SC, Harcus D, Ash J, Dignard D, Marcil A, Morchhauser J, Thomas DY, Whiteway M, Leberer E.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=118047

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Cell Biology of Mating in Candida albicans. by Lockhart SR, Daniels KJ, Zhao R, Wessels D, Soll DR.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=141171

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Cell Wall and Secreted Proteins of Candida albicans: Identification, Function, and Expression. by Chaffin WL, Lopez-Ribot JL, Casanova M, Gozalbo D, Martinez JP.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98909

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Change in Colony Morphology of Candida lusitaniae in Association with Development of Amphotericin B Resistance. by McClenny NB, Fei H, Baron EJ, Gales AC, Houston A, Hollis RJ, Pfaller MA.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127144

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Characterization of Candida albicans RNA triphosphatase and mutational analysis of its active site. by Pei Y, Lehman K, Tian L, Shuman S.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103306

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Characterization of genetically distinct subgroup of Candida albicans strains isolated from oral cavities of patients infected with human immunodeficiency virus. by McCullough M, Ross B, Reade P.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228016

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Chronic Urinary Tract Infection Due to Candida utilis. by Hazen KC, Theisz GW, Howell SA.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84571

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Clonal and Spontaneous Origins of Fluconazole Resistance in Candida albicans. by Xu J, Ramos AR, Vilgalys R, Mitchell TG.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86380

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Cloning and Analysis of a Candida albicans Gene That Affects Cell Surface Hydrophobicity. by Singleton DR, Masuoka J, Hazen KC.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95234

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Cloning and Characterization of a Complex DNA Fingerprinting Probe for Candida parapsilosis. by Enger L, Joly S, Pujol C, Simonson P, Pfaller M, Soll DR.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87794

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Cloning and Sequencing of a Candida albicans Catalase Gene and Effects of Disruption of This Gene. by Wysong DR, Christin L, Sugar AM, Robbins PW, Diamond RD.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108149

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Cluster of oral atypical Candida albicans isolates in a group of human immunodeficiency virus-positive drug users. by Boerlin P, Boerlin-Petzold F, Durussel C, Addo M, Pagani JL, Chave JP, Bille J.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228117

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Comparative analysis of genetic variability among Candida albicans isolates from different geographic locales by three genotypic methods. by Clemons KV, Feroze F, Holmberg K, Stevens DA.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229744

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Comparative Genotyping of Candida albicans Bloodstream and Nonbloodstream Isolates at a Polymorphic Microsatellite Locus. by Dalle F, Franco N, Lopez J, Vagner O, Caillot D, Chavanet P, Cuisenier B, Aho S, Lizard S, Bonnin A.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87636

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Comparative resistance of Candida albicans clinical isolates to fluconazole and itraconazole in vitro and in vivo in a murine model. by Valentin A, Le Guennec R, Rodriguez E, Reynes J, Mallie M, Bastide JM.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163328

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Comparison of Biofilms Formed by Candida albicans and Candida parapsilosis on Bioprosthetic Surfaces. by Kuhn DM, Chandra J, Mukherjee PK, Ghannoum MA.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127692

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Comparison of four DNA-based methods for strain delineation of Candida lusitaniae. by King D, Rhine-Chalberg J, Pfaller MA, Moser SA, Merz WG.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228197

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Comparison of Pathogenesis and Host Immune Responses to Candida glabrata and Candida albicans in Systemically Infected Immunocompetent Mice. by Brieland J, Essig D, Jackson C, Frank D, Loebenberg D, Menzel F, Arnold B, DiDomenico B, Hare R.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98599

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Comparison of rapid testing methods for enzyme production with the germ tube method for presumptive identification of Candida albicans. by Heelan JS, Siliezar D, Coon K.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229419

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Comparison of the API Candida System with the AUXACOLOR System for Identification of Common Yeast Pathogens. by Campbell CK, Davey KG, Holmes AD, Szekely A, Warnock DW.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84570

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Comparison of the Hydrophobic Properties of Candida albicans and Candida dubliniensis. by Hazen KC, Wu JG, Masuoka J.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97952

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Comparison of the MUREX C. albicans, Albicans-Sure, and BactiCard Candida test kits with the germ tube test for presumptive identification of Candida albicans. by Crist AE Jr, Dietz TJ, Kampschroer K.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229336

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Comparison of the Rapid Yeast Plus Panel with the API20C Yeast System for Identification of Clinically Significant Isolates of Candida Species. by Heelan JS, Sotomayor E, Coon K, D'Arezzo JB.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104850

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Comparison of Three Methods for Testing Azole Susceptibilities of Candida albicans Strains Isolated Sequentially from Oral Cavities of AIDS Patients. by Tortorano AM, Viviani MA, Barchiesi F, Arzeni D, Rigoni AL, Cogliati M, Compagnucci P, Scalise G.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104880

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Comparison of use of phenotypic and genotypic characteristics for identification of species of the anamorph genus Candida and related teleomorph yeast species. by Latouche GN, Daniel HM, Lee OC, Mitchell TG, Sorrell TC, Meyer W.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230143

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Confirmation of the Distinct Genotype Groups within the Form Species Candida parapsilosis. by Roy B, Meyer SA.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=124837

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Control of Filament Formation in Candida albicans by Polyamine Levels. by Herrero AB, Lopez MC, Garcia S, Schmidt A, Spaltmann F, Ruiz-Herrera J, Dominguez A.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96821

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Control of White-Opaque Phenotypic Switching in Candida albicans by the Efg1p Morphogenetic Regulator. by Sonneborn A, Tebarth B, Ernst JF.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96790

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Correlation between rhodamine 123 accumulation and azole sensitivity in Candida species: possible role for drug efflux in drug resistance. by Clark FS, Parkinson T, Hitchcock CA, Gow NA.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163126

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Crk1, a Novel Cdc2-Related Protein Kinase, Is Required for Hyphal Development and Virulence in Candida albicans. by Chen J, Zhou S, Wang Q, Chen X, Pan T, Liu H.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86484

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Decreased Accumulation or Increased Isoleucyl-tRNA Synthetase Activity Confers Resistance to the Cyclic [beta]-Amino Acid BAY 10-8888 in Candida albicans and Candida tropicalis. by Ziegelbauer K.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105649

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Defective Hyphal Development and Avirulence Caused by a Deletion of the SSK1 Response Regulator Gene in Candida albicans. by Calera JA, Zhao XJ, Calderone R.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97171

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Defective Hyphal Induction of a Candida albicans Phosphatidylinositol 3-Phosphate 5-Kinase Null Mutant on Solid Media Does Not Lead to Decreased Virulence. by Augsten M, Hubner C, Nguyen M, Kunkel W, Hartl A, Eck R.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128189

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Defective Induction of Interleukin-12 in Human Monocytes by Germ-Tube Forms of Candida albicans. by Chiani P, Bromuro C, Torosantucci A.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=101515

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Defects in Assembly of the Extracellular Matrix Are Responsible for Altered Morphogenesis of a Candida albicans phr1 Mutant. by Popolo L, Vai M.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106863

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Deficiency of d-Erythroascorbic Acid Attenuates Hyphal Growth and Virulence of Candida albicans. by Huh WK, Kim ST, Kim H, Jeong G, Kang SO.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98429

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Degradation of humoral host defense by Candida albicans proteinase. by Kaminishi H, Miyaguchi H, Tamaki T, Suenaga N, Hisamatsu M, Mihashi I, Matsumoto H, Maeda H, Hagihara Y.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173099

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Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility. by Geber A, Hitchcock CA, Swartz JE, Pullen FS, Marsden KE, Kwon-Chung KJ, Bennett JE.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163017

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Depletion of the Squalene Synthase (ERG9) Gene Does Not Impair Growth of Candida glabrata in Mice. by Nakayama H, Izuta M, Nakayama N, Arisawa M, Aoki Y.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90078

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Derepressed Hyphal Growth and Reduced Virulence in a VH1 Family-related Protein Phosphatase Mutant of the Human Pathogen Candida albicans. by Csank C, Makris C, Meloche S, Schroppel K, Rollinghoff M, Dignard D, Thomas DY, Whiteway M.; 1997 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25726

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Detection and identification of Candida species in experimentally infected tissue and human blood by rRNA-specific fluorescent in situ hybridization. by Lischewski A, Kretschmar M, Hof H, Amann R, Hacker J, Morschhauser J.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230092

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Detection of Antibodies to Candida albicans Germ Tubes during Experimental Infections by Different Candida Species. by Bikandi J, San Millan R, Regulez P, Moragues MD, Quindos G, Ponton J.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104526

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Detection of antibodies to Candida albicans germ tubes for diagnosis and therapeutic monitoring of invasive candidiasis in patients with hematologic malignancies. by Garcia-Ruiz JC, del Carmen Arilla M, Regulez P, Quindos G, Alvarez A, Ponton J.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230163

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Detection of Candida dubliniensis in Oropharyngeal Samples from Human Immunodeficiency Virus-Infected Patients in North America by Primary CHROMagar Candida Screening and Susceptibility Testing of Isolates. by Kirkpatrick WR, Revankar SG, Mcatee RK, Lopez-Ribot JL, Fothergill AW, McCarthy DI, Sanche SE, Cantu RA, Rinaldi MG, Patterson TF.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105102

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Detection of Fluconazole-Resistant Candida Strains by a Disc Diffusion Screening Test. by Sandven P.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85829

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Detection of Resistance to Amphotericin B in Candida Isolates by Using Iso-Sensitest Broth. by Cuenca-Estrella M, Diaz-Guerra TM, Mellado E, Rodriguez-Tudela JL.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90602

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Development and Characterization of Complex DNA Fingerprinting Probes for the Infectious Yeast Candida dubliniensis. by Joly S, Pujol C, Rysz M, Vargas K, Soll DR.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88646

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Development of two species-specific fingerprinting probes for broad computerassisted epidemiological studies of Candida tropicalis. by Joly S, Pujol C, Schroppel K, Soll DR.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229460

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Differential activation of a Candida albicans virulence gene family during infection. by Staib P, Kretschmar M, Nichterlein T, Hof H, Morschhauser J.; 2000 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18565

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Differential humoral response against alpha- and beta-linked mannose residues associated with tissue invasion by Candida albicans. by Jouault T, Delaunoy C, Sendid B, Ajana F, Poulain D.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170527

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Differential susceptibility of yeast and hyphal forms of Candida albicans to macrophage-derived nitrogen-containing compounds. by Blasi E, Pitzurra L, Puliti M, Chimienti AR, Mazzolla R, Barluzzi R, Bistoni F.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173228

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Differential susceptibility of yeast and hyphal forms of Candida albicans to proteolytic activity of macrophages. by Blasi E, Pitzurra L, Chimienti AR, Mazzolla R, Puliti M, Barluzzi R, Bistoni F.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173143

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Differentiation between Candida dubliniensis and Candida albicans by Fatty Acid Methyl Ester Analysis Using Gas-Liquid Chromatography. by Peltroche-Llacsahuanga H, Schmidt S, Seibold M, Lutticken R, Haase G.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87459

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Differentiation of Candida albicans and Candida dubliniensis by Fluorescent In Situ Hybridization with Peptide Nucleic Acid Probes. by Oliveira K, Haase G, Kurtzman C, Hyldig-Nielsen JJ, Stender H.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88499

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Differentiation of Candida albicans and Candida dubliniensis by Using Recombinant Human Antibody Single-Chain Variable Fragments Specific for Hyphae. by Bliss JM, Sullivan MA, Malone J, Haidaris CG.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150300

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Differentiation of Candida dubliniensis from Candida albicans on Staib Agar and Caffeic Acid-Ferric Citrate Agar. by Al Mosaid A, Sullivan D, Salkin IF, Shanley D, Coleman DC.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87722

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Direct identification and recognition of yeast species from clinical material by using albicans ID and CHROMagar Candida plates. by Baumgartner C, Freydiere AM, Gille Y.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228820

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Discrimination between Candida albicans and Other Pathogenic Species of the Genus Candida by Their Differential Sensitivities to Toxins of a Panel of Killer Yeasts. by Buzzini P, Martini A.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88347

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Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. by Hube B, Sanglard D, Odds FC, Hess D, Monod M, Schafer W, Brown AJ, Gow NA.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175503

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Disruption of the Candida albicans TPS1 Gene Encoding Trehalose-6-Phosphate Synthase Impairs Formation of Hyphae and Decreases Infectivity. by Zaragoza O, Blazquez MA, Gancedo C.; 1998 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=107363

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Disruption of the Candida albicans TPS2 Gene Encoding Trehalose-6-Phosphate Phosphatase Decreases Infectivity without Affecting Hypha Formation. by Van Dijck P, De Rop L, Szlufcik K, Van Ael E, Thevelein JM.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127825

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Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial Candida albicans Isolates from Human Immunodeficiency VirusInfected Patients with Oropharyngeal Candidiasis. by Lopez-Ribot JL, McAtee RK, Lee LN, Kirkpatrick WR, White TC, Sanglard D, Patterson TF.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105968

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Distinctive Carbohydrate Assimilation Profiles Used To Identify the First Clinical Isolates of Candida dubliniensis Recovered in the United States. by Salkin IF.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104861

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Distinguishing Candida Species by [beta]-N-Acetylhexosaminidase Activity. by Niimi K, Shepherd MG, Cannon RD.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88094

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Divergence in Fitness and Evolution of Drug Resistance in Experimental Populations of Candida albicans. by Cowen LE, Kohn LM, Anderson JB.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95195

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Divergence of Eukaryotic Secretory Components: the Candida albicans Homolog of the Saccharomyces cerevisiae Sec20 Protein Is N Terminally Truncated, and Its Levels Determine Antifungal Drug Resistance and Growth. by Weber Y, Santore UJ, Ernst JF, Swoboda RK.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94848

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DNA fingerprinting of Candida rugosa via repetitive sequence-based PCR. by Redkar RJ, Dube MP, McCleskey FK, Rinaldi MG, Del Vecchio VG.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229093

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Effect of Environmental pH on Morphological Development of Candida albicans Is Mediated via the PacC-Related Transcription Factor Encoded by PRR2. by Ramon AM, Porta A, Fonzi WA.; 1999 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94210

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Effect of Growth Rate on Resistance of Candida albicans Biofilms to Antifungal Agents. by Baillie GS, Douglas LJ.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105707

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Effect of the Echinocandin Caspofungin on Expression of Candida albicans Secretory Aspartyl Proteinases and Phospholipase In Vitro. by Ripeau JS, Aumont F, Belhumeur P, Ostrosky-Zeichner L, Rex JH, de Repentigny L.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127410

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Effects of Azole Antifungal Drugs on the Transition from Yeast Cells to Hyphae in Susceptible and Resistant Isolates of the Pathogenic Yeast Candida albicans. by Ha KC, White TC.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89204

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Effects of the Human Immunodeficiency Virus (HIV) Proteinase Inhibitors Saquinavir and Indinavir on In Vitro Activities of Secreted Aspartyl Proteinases of Candida albicans Isolates from HIV-Infected Patients. by Korting HC, Schaller M, Eder G, Hamm G, Bohmer U, Hube B.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89410

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Effects of Two Different Growth Media on the Postantifungal Effect Induced by Polyenes on Candida Species. by Shu M, Ellepola AN, Samaranayake LP.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88225

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Efficacies of Fluconazole, Caspofungin, and Amphotericin B in Candida glabrataInfected p47phox[minus sign]/[minus sign] Knockout Mice. by Ju JY, Polhamus C, Marr KA, Holland SM, Bennett JE.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127175

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EFG1 Null Mutants of Candida albicans Switch but Cannot Express the Complete Phenotype of White-Phase Budding Cells. by Srikantha T, Tsai LK, Daniels K, Soll DR.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94455

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Efg1, a Morphogenetic Regulator in Candida albicans, Is a Sequence-Specific DNA Binding Protein. by Leng P, Lee PR, Wu H, Brown AJ.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95293

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Electrophoretic Karyotype Analysis of Sequential Candida parapsilosis Isolates from Patients with Persistent or Recurrent Fungemia. by Shin JH, Shin DH, Song JW, Kee SJ, Suh SP, Ryang DW.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87921

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Elevated Phenotypic Switching and Drug Resistance of Candida albicans from Human Immunodeficiency Virus-Positive Individuals prior to First Thrush Episode. by Vargas K, Messer SA, Pfaller M, Lockhart SR, Stapleton JT, Hellstein J, Soll DR.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87443

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Endothelial Cell Injury Caused by Candida albicans Is Dependent on Iron. by Fratti RA, Belanger PH, Ghannoum MA, Edwards JE Jr, Filler SG.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=107876

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Enhanced Extracellular Production of Aspartyl Proteinase, a Virulence Factor, by Candida albicans Isolates following Growth in Subinhibitory Concentrations of Fluconazole. by Wu T, Wright K, Hurst SF, Morrison CJ.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89845

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Enhanced oxidative killing of azole-resistant Candida glabrata strains with ERG11 deletion. by Kan VL, Geber A, Bennett JE.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163402

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Epidemiology of Oropharyngeal Candida Colonization and Infection in Patients Receiving Radiation for Head and Neck Cancer. by Redding SW, Zellars RC, Kirkpatrick WR, McAtee RK, Caceres MA, Fothergill AW, Lopez-Ribot JL, Bailey CW, Rinaldi MG, Patterson TF.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85839

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Ergosterol Biosynthesis Inhibitors Become Fungicidal when Combined with Calcineurin Inhibitors against Candida albicans, Candida glabrata, and Candida krusei. by Onyewu C, Blankenship JR, Del Poeta M, Heitman J.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149324

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Estimation of Minimum Sterol 14[alpha]-Demethylation-Inhibitory Concentration of Azoles in Candida Yeasts Using Acetate-Mediated Growth Inhibition: Potential Utility in Susceptibility Testing. by Shimokawa O, Nakayama H.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87139

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Evaluation of a Rapid, Quantitative Real-Time PCR Method for Enumeration of Pathogenic Candida Cells in Water. by Brinkman NE, Haugland RA, Wymer LJ, Byappanahalli M, Whitman RL, Vesper SJ.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150045

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Evaluation of a Reformulated CHROMagar Candida. by Jabra-Rizk MA, Brenner TM, Romagnoli M, Baqui AA, Merz WG, Falkler WA Jr, Meiller TF.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88073

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Evaluation of Etest Method for Determining Caspofungin (MK-0991) Susceptibilities of 726 Clinical Isolates of Candida Species. by Pfaller MA, Messer SA, Mills K, Bolmstrom A, Jones RN.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88553

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Evaluation of latex reagents for rapid identification of Candida albicans and C. krusei colonies. by Freydiere AM, Buchaille L, Guinet R, Gille Y.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229694

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Evaluation of Phenotypic Markers for Selection and Identification of Candida dubliniensis. by Tintelnot K, Haase G, Seibold M, Bergmann F, Staemmler M, Franz T, Naumann D.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86499

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Evaluation of pulsed-field gel electrophoresis as a typing system for Candida rugosa: comparison of karyotype and restriction fragment length polymorphisms. by Dib JC, Dube M, Kelly C, Rinaldi MG, Patterson JE.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229048

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Evaluation of the Etest Method for Determining Voriconazole Susceptibilities of 312 Clinical Isolates of Candida Species by Using Three Different Agar Media. by Pfaller MA, Messer SA, Houston A, Mills K, Bolmstrom A, Jones RN.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87462

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Evidence for nosocomial transmission of Candida albicans obtained by Ca3 fingerprinting. by Schmid J, Tay YP, Wan L, Carr M, Parr D, McKinney W.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228135

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Evidence for presence in the cell wall of Candida albicans of a protein related to the hsp70 family. by Lopez-Ribot JL, Alloush HM, Masten BJ, Chaffin WL.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174226

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Evidence from comparative genomics for a complete sexual cycle in the 'asexual' pathogenic yeast Candida glabrata. by Wong S, Fares MA, Zimmermann W, Butler G, Wolfe KH.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151300

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Evolution of Drug Resistance in Experimental Populations of Candida albicans. by Cowen LE, Sanglard D, Calabrese D, Sirjusingh C, Anderson JB, Kohn LM.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94447

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Experimental Induction of Fluconazole Resistance in Candida tropicalis ATCC 750. by Barchiesi F, Calabrese D, Sanglard D, Falconi Di Francesco L, Caselli F, Giannini D, Giacometti A, Gavaudan S, Scalise G.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89916

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Expressed Sequence Tag Analysis of the Human Pathogen Paracoccidioides brasiliensis Yeast Phase: Identification of Putative Homologues of Candida albicans Virulence and Pathogenicity Genes. by Goldman GH, dos Reis Marques E, Custodio Duarte Ribeiro D, Angelo de Souza Bernardes L, Quiapin AC, Vitorelli PM, Savoldi M, Semighini CP, de Oliveira RC, Nunes LR, Travassos LR, Puccia R, Batista WL, Ferreira LE, Moreira JC, Bogossian AP, Tekaia F, Nobrega MP, Nobrega FG, Goldman MH.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=141168

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Expression of surface hydrophobic proteins by Candida albicans in vivo. by Glee PM, Sundstrom P, Hazen KC.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173161

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First Isolation of Reddish-Pigmented Candida (Torulopsis) glabrata from a Clinical Specimen. by Peltroche-Llacsahuanga H, von Oy S, Haase G.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120294

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Fluconazole- and itraconazole-resistant Candida albicans strains from AIDS patients: multilocus enzyme electrophoresis analysis and antifungal susceptibilities. by Le Guennec R, Reynes J, Mallie M, Pujol C, Janbon F, Bastide JM.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228565

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Fluconazole and Voriconazole Multidisk Testing of Candida Species for Disk Test Calibration and MIC Estimation. by Kronvall G, Karlsson I.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87949

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Fluconazole Disk Diffusion Susceptibility Testing of Candida Species. by Kirkpatrick WR, Turner TM, Fothergill AW, McCarthy DI, Redding SW, Rinaldi MG, Patterson TF.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105351

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Fluconazole Resistance Associated with Drug Efflux and Increased Transcription of a Drug Transporter Gene, PDH1, in Candida glabrata. by Miyazaki H, Miyazaki Y, Geber A, Parkinson T, Hitchcock C, Falconer DJ, Ward DJ, Marsden K, Bennett JE.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105668

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Fluconazole resistance due to energy-dependent drug efflux in Candida glabrata. by Parkinson T, Falconer DJ, Hitchcock CA.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162810

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Fluconazole Susceptibilities of Bloodstream Candida sp. Isolates as Determined by National Committee for Clinical Laboratory Standards Method M27-A and Two Other Methods. by Canton E, Peman J, Carrillo-Munoz A, Orero A, Ubeda P, Viudes A, Gobernado M.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85117

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Fluconazole Susceptibility of Vaginal Isolates Obtained from Women with Complicated Candida Vaginitis: Clinical Implications. by Sobel JD, Zervos M, Reed BD, Hooton T, Soper D, Nyirjesy P, Heine MW, Willems J, Panzer H.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=148960

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Fluconazole versus Candida albicans: A Complex Relationship. by Graybill JR, Montalbo E, Kirkpatrick WR, Luther MF, Revankar SG, Patterson TF.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105969

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Fluorescence In Situ Hybridization with Peptide Nucleic Acid Probes for Rapid Identification of Candida albicans Directly from Blood Culture Bottles. by Rigby S, Procop GW, Haase G, Wilson D, Hall G, Kurtzman C, Oliveira K, Von Oy S, HyldigNielsen JJ, Coull J, Stender H.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130801

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Folding of the group I intron ribozyme from the 26S rRNA gene of Candida albicans. by Zhang Y, Leibowitz MJ.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=55740

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Formation of Azole-Resistant Candida albicans by Mutation of Sterol 14Demethylase P450. by Asai K, Tsuchimori N, Okonogi K, Perfect JR, Gotoh O, Yoshida Y.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89127

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Functional analysis of the promoter of the phase-specific WH11 gene of Candida albicans. by Srikantha T, Chandrasekhar A, Soll DR.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230404

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Functional characterization of the MKC1 gene of Candida albicans, which encodes a mitogen-activated protein kinase homolog related to cell integrity. by Navarro-Garcia F, Sanchez M, Pla J, Nombela C.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230448

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Further Characterization of Human Salivary Anticandidal Activities in a Human Immunodeficiency Virus-Positive Cohort by Use of Microassays. by Lin AL, Shi Q, Johnson DA, Patterson TF, Rinaldi MG, Yeh CK.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95787

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Gastrointestinal Colonization by Candida albicans Mutant Strains in AntibioticTreated Mice. by Wiesner SM, Jechorek RP, Garni RM, Bendel CM, Wells CL.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96034

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Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans. by Tripathi G, Wiltshire C, Macaskill S, Tournu H, Budge S, Brown AJ.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=129063

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Genetic Analysis of Azole Resistance in the Darlington Strain of Candida albicans. by Kakeya H, Miyazaki Y, Miyazaki H, Nyswaner K, Grimberg B, Bennett JE.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=101590

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Genetic Basis for Differential Activities of Fluconazole and Voriconazole against Candida krusei. by Fukuoka T, Johnston DA, Winslow CA, de Groot MJ, Burt C, Hitchcock CA, Filler SG.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152512

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Genetic dissimilarity of two fluconazole-resistant Candida albicans strains causing meningitis and oral candidiasis in the same AIDS patient. by Berenguer J, DiazGuerra TM, Ruiz-Diez B, Bernaldo de Quiros JC, Rodriguez-Tudela JL, Martinez-Suarez JV.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229058

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Genetic Evaluation of Physiological Functions of Thiolase Isozymes in the n-AlkaneAssimilating Yeast Candida tropicalis. by Kanayama N, Ueda M, Atomi H, Tanaka A.; 1998 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106940

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Genetic organization and mRNA expression of enolase genes of Candida albicans. by Postlethwait P, Sundstrom P.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176805

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Genetic Structure of Candida glabrata Populations in AIDS and Non-AIDS Patients. by de Meeus T, Renaud F, Mouveroux E, Reynes J, Galeazzi G, Mallie M, Bastide JM.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130676

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Genomic evidence for a complete sexual cycle in Candida albicans. by Tzung KW, Williams RM, Scherer S, Federspiel N, Jones T, Hansen N, Bivolarevic V, Huizar L, Komp C, Surzycki R, Tamse R, Davis RW, Agabian N.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30639

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Genomic Profiling of the Response of Candida albicans to Itraconazole Treatment Using a DNA Microarray. by De Backer MD, Ilyina T, Ma XJ, Vandoninck S, Luyten WH, Vanden Bossche H.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90529

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Genotyping of Candida albicans Oral Strains from Healthy Individuals by Polymorphic Microsatellite Locus Analysis. by Dalle F, Dumont L, Franco N, Mesmacque D, Caillot D, Bonnin P, Moiroux C, Vagner O, Cuisenier B, Lizard S, Bonnin A.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154696

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Geranylgeranyltransferase I of Candida albicans: Null Mutants or Enzyme Inhibitors Produce Unexpected Phenotypes. by Kelly R, Card D, Register E, Mazur P, Kelly T, Tanaka KI, Onishi J, Williamson JM, Fan H, Satoh T, Kurtz M.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94333

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Germ Tubes and Proteinase Activity Contribute to Virulence of Candida albicans in Murine Peritonitis. by Kretschmar M, Hube B, Bertsch T, Sanglard D, Merker R, Schroder M, Hof H, Nichterlein T.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97077

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Growth Competition between Candida dubliniensis and Candida albicans under Broth and Biofilm Growing Conditions. by Kirkpatrick WR, Lopez-Ribot JL, Mcatee RK, Patterson TF.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86241

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Hemin induces germ tube formation in Candida albicans. by Casanova M, Cervera AM, Gozalbo D, Martinez JP.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175626

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High Oral Prevalence of Candida krusei in Leprosy Patients in Northern Thailand. by Reichart PA, Samaranayake LP, Samaranayake YH, Grote M, Pow E, Cheung B.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154582

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High-Frequency, In Vitro Reversible Switching of Candida lusitaniae Clinical Isolates from Amphotericin B Susceptibility to Resistance. by Yoon SA, Vazquez JA, Steffan PE, Sobel JD, Akins RA.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89214

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Highly Polymorphic Microsatellite for Identification of Candida albicans Strains. by Sampaio P, Gusmao L, Alves C, Pina-Vaz C, Amorim A, Pais C.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149659

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Histatin 3-Mediated Killing of Candida albicans: Effect of Extracellular Salt Concentration on Binding and Internalization. by Xu Y, Ambudkar I, Yamagishi H, Swaim W, Walsh TJ, O'Connell BC.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89457

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Histone Deacetylase Inhibitors Enhance Candida albicans Sensitivity to Azoles and Related Antifungals: Correlation with Reduction in CDR and ERG Upregulation. by Smith WL, Edlind TD.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128736

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Hospital Specificity, Region Specificity, and Fluconazole Resistance of Candida albicans Bloodstream Isolates. by Pfaller MA, Lockhart SR, Pujol C, Swails-Wenger JA, Messer SA, Edmond MB, Jones RN, Wenzel RP, Soll DR.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104870

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Human Salivary Histatin 5 Causes Disordered Volume Regulation and Cell Cycle Arrest in Candida albicans. by Baev D, Li XS, Dong J, Keng P, Edgerton M.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128240

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HWP1 Functions in the Morphological Development of Candida albicans Downstream of EFG1, TUP1, and RBF1. by Sharkey LL, McNemar MD, Saporito-Irwin SM, Sypherd PS, Fonzi WA.; 1999 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94032

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Hyphae and Yeasts of Candida albicans Differentially Regulate Interleukin-12 Production by Human Blood Monocytes: Inhibitory Role of C. albicans Germination. by Liu L, Kang K, Takahara M, Cooper KD, Ghannoum MA.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98552

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Hyphal Elongation Is Regulated Independently of Cell Cycle in Candida albicans. by Hazan I, Sepulveda-Becerra M, Liu H.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65078

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Identification and Expression of Multidrug Transporters Responsible for Fluconazole Resistance in Candida dubliniensis. by Moran GP, Sanglard D, Donnelly SM, Shanley DB, Sullivan DJ, Coleman DC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105690

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Identification and Phylogenetic Relationship of the Most Common Pathogenic Candida Species Inferred from Mitochondrial Cytochrome b Gene Sequences. by Yokoyama K, Biswas SK, Miyaji M, Nishimura K.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87628

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Identification of Candida dubliniensis Based on Temperature and Utilization of Xylose and [alpha]-Methyl-d-Glucoside as Determined with the API 20C AUX and Vitek YBC Systems. by Gales AC, Pfaller MA, Houston AK, Joly S, Sullivan DJ, Coleman DC, Soll DR.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85818

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Identification of Candida dubliniensis in a Prospective Study of Patients in the United States. by Jabra-Rizk MA, Baqui AA, Kelley JI, Falkler WA Jr, Merz WG, Meiller TF.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84296

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Identification of Candida species by PCR and restriction fragment length polymorphism analysis of intergenic spacer regions of ribosomal DNA. by Williams DW, Wilson MJ, Lewis MA, Potts AJ.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228446

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Identification of Candida species by randomly amplified polymorphic DNA fingerprinting of colony lysates. by Steffan P, Vazquez JA, Boikov D, Xu C, Sobel JD, Akins RA.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229897

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Identification of Candida spp. by Randomly Amplified Polymorphic DNA Analysis and Differentiation between Candida albicans and Candida dubliniensis by Direct PCR Methods. by Bautista-Munoz C, Boldo XM, Villa-Tanaca L, Hernandez-Rodriguez C.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149553

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Identification of Four Distinct Genotypes of Candida dubliniensis and Detection of Microevolution In Vitro and In Vivo. by Gee SF, Joly S, Soll DR, Meis JF, Verweij PE, Polacheck I, Sullivan DJ, Coleman DC.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153410

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Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase I from Candida albicans. by Fostel J, Montgomery D.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162588

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Identification of various medically important Candida species in clinical specimens by PCR-restriction enzyme analysis. by Morace G, Sanguinetti M, Posteraro B, Lo Cascio G, Fadda G.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229647

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Impact of N-Chlorotaurine on Viability and Production of Secreted Aspartyl Proteinases of Candida spp. by Nagl M, Gruber A, Fuchs A, Lell CP, Lemberger EM, Borg-von Zepelin M, Wurzner R.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127226

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Improved Detection of Amphotericin B-Resistant Isolates of Candida lusitaniae by Etest. by Peyron F, Favel A, Michel-Nguyen A, Gilly M, Regli P, Bolmstrom A.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87726

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Improved detection of Candida albicans by PCR in blood of neutropenic mice with systemic candidiasis. by van Deventer AJ, Goessens WH, van Belkum A, van Vliet HJ, van Etten EW, Verbrugh HA.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228002

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Improved Immunodiagnosis of Human Candidiasis by an Enzyme-Linked Immunosorbent Assay Using a Candida albicans 52-Kilodalton Metallopeptidase. by El Moudni B, Rodier MH, Daniault G, Jacquemin JL.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96209

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In Vitro Activities of BMS-207147 against Over 600 Contemporary Clinical Bloodstream Isolates of Candida Species from the SENTRY Antimicrobial Surveillance Program in North America and Latin America. by Diekema DJ, Pfaller MA, Messer SA, Houston A, Hollis RJ, Doern GV, Jones RN.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89453

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In Vitro Activities of Terbinafine against Cutaneous Isolates of Candida albicans and Other Pathogenic Yeasts. by Ryder NS, Wagner S, Leitner I.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105744

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In Vitro Activities of Terbinafine in Combination with Fluconazole, Itraconazole, Voriconazole, and Posaconazole against Clinical Isolates of Candida glabrata with Decreased Susceptibility to Azoles. by Perea S, Gonzalez G, Fothergill AW, Sutton DA, Rinaldi MG.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130943

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In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates of Candida spp. by Marco F, Pfaller MA, Messer S, Jones RN.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105473

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In Vitro Activity of Caspofungin against Candida albicans Biofilms. by Bachmann SP, VandeWalle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, Lopez-Ribot JL.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128731

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In Vitro and In Vivo Effects of 14[alpha]-Demethylase (ERG11) Depletion in Candida glabrata. by Nakayama H, Nakayama N, Arisawa M, Aoki Y.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90779

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In vitro kill curves of a new semisynthetic echinocandin, LY-303366, against fluconazole-sensitive and -resistant Candida species. by Karlowsky JA, Harding GA, Zelenitsky SA, Hoban DJ, Kabani A, Balko TV, Turik M, Zhanel GG.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164168

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In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species. by Barry AL, Brown SD.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163448

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In Vitro Susceptibilities of Candida Bloodstream Isolates to the New Triazole Antifungal Agents BMS-207147, Sch 56592, and Voriconazole. by Pfaller MA, Messer SA, Hollis RJ, Jones RN, Doern GV, Brandt ME, Hajjeh RA.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106028

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In Vitro Susceptibilities of Candida dubliniensis Isolates Tested against the New Triazole and Echinocandin Antifungal Agents. by Pfaller MA, Messer SA, Gee S, Joly S, Pujol C, Sullivan DJ, Coleman DC, Soll DR.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84591

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Increased expression of Candida albicans secretory proteinase, a putative virulence factor, in isolates from human immunodeficiency virus-positive patients. by Ollert MW, Wende C, Gorlich M, McMullan-Vogel CG, Borg-von Zepelin M, Vogel CW, Korting HC.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228525

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Inducible Azole Resistance Associated with a Heterogeneous Phenotype in Candida albicans. by Marr KA, Lyons CN, Ha K, Rustad TR, White TC.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90239

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Influence of Glucose Supplementation and Inoculum Size on Growth Kinetics and Antifungal Susceptibility Testing of Candida spp. by Cuenca-Estrella M, Diaz-Guerra TM, Mellado E, Rodriguez-Tudela JL.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87770

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Influence of Human Serum on Antifungal Pharmacodynamics with Candida albicans. by Zhanel GG, Saunders DG, Hoban DJ, Karlowsky JA.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90594

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Infrequent Genetic Exchange and Recombination in the Mitochondrial Genome of Candida albicans. by Anderson JB, Wickens C, Khan M, Cowen LE, Federspiel N, Jones T, Kohn LM.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94952

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Inhibition of Candida albicans Biofilm Formation by Farnesol, a Quorum-Sensing Molecule. by Ramage G, Saville SP, Wickes BL, Lopez-Ribot JL.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=129887

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Inhibition of Inositol Phosphorylceramide Synthase by Aureobasidin A in Candida and Aspergillus Species. by Zhong W, Jeffries MW, Georgopapadakou NH.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89741

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Inhibition of sterol 4-demethylation in Candida albicans by 6-amino-2-npentylthiobenzothiazole, a novel mechanism of action for an antifungal agent. by Kuchta T, Leka C, Farkas P, Bujdakova H, Belajova E, Russell NJ.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162777

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Interleukin-18 and Gamma Interferon Production by Oral Epithelial Cells in Response to Exposure to Candida albicans or Lipopolysaccharide Stimulation. by Rouabhia M, Ross G, Page N, Chakir J.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=133048

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International Surveillance of Bloodstream Infections Due to Candida Species: Frequency of Occurrence and Antifungal Susceptibilities of Isolates Collected in 1997 in the United States, Canada, and South America for the SENTRY Program. by Pfaller MA, Jones RN, Doern GV, Sader HS, Hollis RJ, Messer SA, Group FT.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104946

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International Surveillance of Bloodstream Infections Due to Candida Species: Frequency of Occurrence and In Vitro Susceptibilities to Fluconazole, Ravuconazole, and Voriconazole of Isolates Collected from 1997 through 1999 in the SENTRY Antimicrobial Surveillance Program. by Pfaller MA, Diekema DJ, Jones RN, Sader HS, Fluit AC, Hollis RJ, Messer SA.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88327

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Interplay between Protective and Inhibitory Antibodies Dictates the Outcome of Experimentally Disseminated Candidiasis in Recipients of a Candida albicans Vaccine. by Bromuro C, Torosantucci A, Chiani P, Conti S, Polonelli L, Cassone A.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128316

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Intracellular Accumulation of Polyphosphate by the Yeast Candida humicola G-1 in Response to Acid pH. by McGrath JW, Quinn JP.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=92260

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Invasive Lesions Containing Filamentous Forms Produced by a Candida albicans Mutant That Is Defective in Filamentous Growth in Culture. by Riggle PJ, Andrutis KA, Chen X, Tzipori SR, Kumamoto CA.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116558

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Iron-Limited Biofilms of Candida albicans and Their Susceptibility to Amphotericin B. by Baillie GS, Douglas LJ.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105891

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Isogenic Strain Construction and Gene Targeting in Candida dubliniensis. by Staib P, Moran GP, Sullivan DJ, Coleman DC, Morschhauser J.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99503

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Isolation and Characterization of a Species-Specific DNA Fragment for Identification of Candida (Torulopsis) glabrata by PCR. by Becker K, Badehorn D, Keller B, Schulte M, Bohm KH, Peters G, Fegeler W.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88345

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Isolation and Characterization of EPD1, an Essential Gene for Pseudohyphal Growth of a Dimorphic Yeast, Candida maltosa. by Nakazawa T, Horiuchi H, Ohta A, Takagi M.; 1998 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=107133

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Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. by Nolte FS, Parkinson T, Falconer DJ, Dix S, Williams J, Gilmore C, Geller R, Wingard JR.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163686

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Isolation and characterization of the GFA1 gene encoding the glutamine:fructose-6phosphate amidotransferase of Candida albicans. by Smith RJ, Milewski S, Brown AJ, Gooday GW.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177940

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Isolation of a Putative Candida albicans Transcriptional Regulator Involved in Pleiotropic Drug Resistance by Functional Complementation of a pdr1 pdr3 Mutation in Saccharomyces cerevisiae. by Talibi D, Raymond M.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103554

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Isolation of Candida glabrata Homologs of the Saccharomyces cerevisiae KRE9 and KNH1 Genes and Their Involvement in Cell Wall [beta]-1,6-Glucan Synthesis. by Nagahashi S, Lussier M, Bussey H.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=107535

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Isolation of Candida species on media with and without added fluconazole reveals high variability in relative growth susceptibility phenotypes. by Schoofs A, Odds FC, Colebunders R, Ieven M, Wouters L, Goossens H.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163976

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Lack of Catheter Infection by the efg1/efg1 cph1/cph1 Double-Null Mutant, a Candida albicans Strain That Is Defective in Filamentous Growth. by Lewis RE, Lo HJ, Raad II, Kontoyiannis DP.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127119

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Lack of Consistent Short Sequence Repeat Polymorphisms in Genetically Homologous Colonizing and Invasive Candida albicans Strains. by Lunel FV, Licciardello L, Stefani S, Verbrugh HA, Melchers WJ, Meis JF, Scherer S, van Belkum A.; 1998 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=107357

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Lactoferrin Peptide Increases the Survival of Candida albicans- Inoculated Mice by Upregulating Neutrophil and Macrophage Functions, Especially in Combination with Amphotericin B and Granulocyte-Macrophage Colony-Stimulating Factor. by Tanida T, Rao F, Hamada T, Ueta E, Osaki T.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98415

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Large-Scale Identification of Putative Exported Proteins in Candida albicans by Genetic Selection. by Monteoliva L, Lopez Matas M, Gil C, Nombela C, Pla J.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=117995

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Low Levels of Antigenic Variability in Fluconazole-Susceptible and -Resistant Candida albicans Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis. by Lopez-Ribot JL, McAtee RK, Kirkpatrick WR, La Valle R, Patterson TF.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95751

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MDR1-Mediated Drug Resistance in Candida dubliniensis. by Wirsching S, Moran GP, Sullivan DJ, Coleman DC, Morschhauser J.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90846

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Mechanism of Fluconazole Resistance in Candida krusei. by Orozco AS, Higginbotham LM, Hitchcock CA, Parkinson T, Falconer D, Ibrahim AS, Ghannoum MA, Filler SG.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105912

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Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. by Sanglard D, Kuchler K, Ischer F, Pagani JL, Monod M, Bille J.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162951

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Membrane Filtration Test for Rapid Presumptive Differentiation of Four Candida Species. by Bauters TG, Peleman R, Moerman M, Vermeersch H, de Looze D, Noens L, Nelis HJ.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84813

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Minimum Chemical Requirements for Adhesin Activity of the Acid-Stable Part of Candida albicans Cell Wall Phosphomannoprotein Complex. by Kanbe T, Cutler JE.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108735

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Misexpression of the Opaque-Phase-Specific Gene PEP1 (SAP1) in the White Phase of Candida albicans Confers Increased Virulence in a Mouse Model of Cutaneous Infection. by Kvaal C, Lachke SA, Srikantha T, Daniels K, McCoy J, Soll DR.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97079

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Mitochondrial Telomeres as Molecular Markers for Identification of the Opportunistic Yeast Pathogen Candida parapsilosis. by Nosek J, Tomaska L', Rycovska A, Fukuhara H.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140342

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Molecular Analysis of the Candida albicans Homolog of Saccharomyces cerevisiae MNN9, Required for Glycosylation of Cell Wall Mannoproteins. by Southard SB, Specht CA, Mishra C, Chen-Weiner J, Robbins PW.; 1999 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94199

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Molecular and Phenotypic Characterization of Genotypic Candida albicans Subgroups and Comparison with Candida dubliniensis and Candida stellatoidea. by McCullough MJ, Clemons KV, Stevens DA.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84325

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Molecular biological characterization of an azole-resistant Candida glabrata isolate. by Marichal P, Vanden Bossche H, Odds FC, Nobels G, Warnock DW, Timmerman V, Van Broeckhoven C, Fay S, Mose-Larsen P.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164098

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Molecular Characterization of New Clinical Isolates of Candida albicans and C. dubliniensis in Japan: Analysis Reveals a New Genotype of C. albicans with Group I Intron. by Tamura M, Watanabe K, Mikami Y, Yazawa K, Nishimura K.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88541

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Molecular Characterization of Yarrowia lipolytica and Candida zeylanoides Isolated from Poultry. by Deak T, Chen J, Beuchat LR.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=92305

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Molecular Cloning and Characterization of Chitinase Genes from Candida albicans. by McCreath KJ, Specht CA, Robbins PW.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42254

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Molecular Cloning and Functional Expression of Alternative Oxidase from Candida albicans. by Huh WK, Kang SO.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=93902

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Molecular epidemiology of Candida isolates from AIDS patients showing different fluconazole resistance profiles. by Lischewski A, Ruhnke M, Tennagen I, Schonian G, Morschhauser J, Hacker J.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228034

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Molecular Epidemiology of Candida. by Stevens DA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120568

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Molecular probe for typing strains of Candida albicans. by Postlethwait P, Bell B, Oberle WT, Sundstrom P.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228826

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Molecular tracking of Candida albicans in a neonatal intensive care unit: long-term colonizations versus catheter-related infections. by Ruiz-Diez B, Martinez V, Alvarez M, Rodriguez-Tudela JL, Martinez-Suarez JV.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230117

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Molecular typing of Candida albicans in oral candidiasis: karyotype epidemiology with human immunodeficiency virus-seropositive patients in comparison with that with healthy carriers. by Lupetti A, Guzzi G, Paladini A, Swart K, Campa M, Senesi S.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228137

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Morphogenesis, Adhesive Properties, and Antifungal Resistance Depend on the Pmt6 Protein Mannosyltransferase in the Fungal Pathogen Candida albicans. by Timpel C, Zink S, Strahl-Bolsinger S, Schroppel K, Ernst J.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94490

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Most frequent scenario for recurrent Candida vaginitis is strain maintenance with "substrain shuffling": demonstration by sequential DNA fingerprinting with probes Ca3, C1, and CARE2. by Lockhart SR, Reed BD, Pierson CL, Soll DR.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228891

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Multicenter Comparison of the Sensititre YeastOne Colorimetric Antifungal Panel with the National Committee for Clinical Laboratory Standards M27-A Reference Method for Testing Clinical Isolates of Common and Emerging Candida spp., Cryptococcus spp., and Other Yeasts and Yeast-Like Organisms. by Espinel-Ingroff A, Pfaller M, Messer SA, Knapp CC, Killian S, Norris HA, Ghannoum MA.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84481

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Multifunctional Centromere Binding Factor 1 Is Essential for Chromosome Segregation in the Human Pathogenic Yeast Candida glabrata. by Stoyan T, Gloeckner G, Diekmann S, Carbon J.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87199

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Multilocus Genotypes and DNA Fingerprints Do Not Predict Variation in Azole Resistance among Clinical Isolates of Candida albicans. by Cowen LE, Sirjusingh C, Summerbell RC, Walmsley S, Richardson S, Kohn LM, Anderson JB.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89590

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Multilocus Genotyping Indicates that the Ability To Invade the Bloodstream Is Widespread among Candida albicans Isolates. by Luu LN, Cowen LE, Sirjusingh C, Kohn LM, Anderson JB.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87994

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Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. by Albertson GD, Niimi M, Cannon RD, Jenkinson HF.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163632

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Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical Candida albicans Strains. by Franz R, Kelly SL, Lamb DC, Kelly DE, Ruhnke M, Morschhauser J.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106000

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Myosin I Is Required for Hypha Formation in Candida albicans. by Oberholzer U, Marcil A, Leberer E, Thomas DY, Whiteway M.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=118025

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New Assay for Measuring Cell Surface Hydrophobicities of Candida dubliniensis and Candida albicans. by Jabra-Rizk MA, Falkler WA Jr, Merz WG, Meiller TF.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96105

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New Monoclonal Antibody Specific for Candida albicans Germ Tube. by MarotLeblond A, Grimaud L, Nail S, Bouterige S, Apaire-Marchais V, Sullivan DJ, Robert R.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86019

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Noninhibitory binding of human interleukin-2-activated natural killer cells to the germ tube forms of Candida albicans. by Arancia G, Molinari A, Crateri P, Stringaro A, Ramoni C, Dupuis ML, Gomez MJ, Torosantucci A, Cassone A.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172989

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Nonperinatal Nosocomial Transmission of Candida albicans in a Neonatal Intensive Care Unit: Prospective Study. by Reef SE, Lasker BA, Butcher DS, McNeil MM, Pruitt R, Keyserling H, Jarvis WR.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104810

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Nosocomial Candida glabrata Colonization: an Epidemiologic Study. by Vazquez JA, Dembry LM, Sanchez V, Vazquez MA, Sobel JD, Dmuchowski C, Zervos MJ.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104553

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Novel Posttranslational Activation of the LYS2-Encoded [alpha]-Aminoadipate Reductase for Biosynthesis of Lysine and Site-Directed Mutational Analysis of Conserved Amino Acid Residues in the Activation Domain of Candida albicans. by Guo S, Evans SA, Wilkes MB, Bhattacharjee JK.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95560

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NRG1 represses yeast --hypha morphogenesis and hypha-specific gene expression in Candida albicans. by Murad AM, Leng P, Straffon M, Wishart J, Macaskill S, MacCallum D, Schnell N, Talibi D, Marechal D, Tekaia F, d'Enfert C, Gaillardin C, Odds FC, Brown AJ.; 2001 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=125592

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Oral Colonization, Phenotypic, and Genotypic Profiles of Candida Species in Irradiated, Dentate, Xerostomic Nasopharyngeal Carcinoma Survivors. by Leung WK, Dassanayake RS, Yau JY, Jin LJ, Yam WC, Samaranayake LP.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86768

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Overexpression of a Dominant-Negative Allele of SEC4 Inhibits Growth and Protein Secretion in Candida albicans. by Mao Y, Kalb VF, Wong B.; 1999 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103685

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Overexpression of the Candida albicans ALA1 Gene in Saccharomyces cerevisiae Results in Aggregation following Attachment of Yeast Cells to Extracellular Matrix Proteins, Adherence Properties Similar to Those of Candida albicans. by Gaur NK, Klotz SA, Henderson RL.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96991

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Parity among the randomly amplified polymorphic DNA method, multilocus enzyme electrophoresis, and Southern blot hybridization with the moderately repetitive DNA probe Ca3 for fingerprinting Candida albicans. by Pujol C, Joly S, Lockhart SR, Noel S, Tibayrenc M, Soll DR.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229967

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Pathogenic Yeasts Cryptococcus neoformans and Candida albicans Produce Immunomodulatory Prostaglandins. by Noverr MC, Phare SM, Toews GB, Coffey MJ, Huffnagle GB.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98248

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PCR Fingerprinting of Candida albicans Associated with Chronic Hyperplastic Candidosis and Other Oral Conditions. by Bartie KL, Williams DW, Wilson MJ, Potts AJ, Lewis MA.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88488

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PCR-Restriction Enzyme Analysis for Detection of Candida DNA in Blood from Febrile Patients with Hematological Malignancies. by Morace G, Pagano L, Sanguinetti M, Posteraro B, Mele L, Equitani F, D'Amore G, Leone G, Fadda G.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84973

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Penetration and damage of endothelial cells by Candida albicans. by Filler SG, Swerdloff JN, Hobbs C, Luckett PM.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173098

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Pentamidine Inhibition of Group I Intron Splicing in Candida albicans Correlates with Growth Inhibition. by Miletti KE, Leibowitz MJ.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89798

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Performance of Candida ID, a New Chromogenic Medium for Presumptive Identification of Candida Species, in Comparison to CHROMagar Candida. by Willinger B, Hillowoth C, Selitsch B, Manafi M.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88437

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Peroxisomal Catalase in the Methylotrophic Yeast Candida boidinii: Transport Efficiency and Metabolic Significance. by Horiguchi H, Yurimoto H, Goh TK, Nakagawa T, Kato N, Sakai Y.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=100133

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Persistence of Oropharyngeal Candida albicans Strains with Reduced Susceptibilities to Fluconazole among Human Immunodeficiency Virus-Seropositive Children and Adults in a Long-Term Care Facility. by Makarova NU, Pokrowsky VV, Kravchenko AV, Serebrovskaya LV, James MJ, McNeil MM, Lasker BA, Warnock DW, Reiss E.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154751

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Persistence of Pigment Production by Yeast Isolates Grown on CHROMagar Candida Medium. by Hospenthal DR, Murray CK, Beckius ML, Green JA, Dooley DP.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154593

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Phenotypic Analysis and Virulence of Candida albicans LIG4 Mutants. by Andaluz E, Calderone R, Reyes G, Larriba G.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97865

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Photoaffinity Analog of the Semisynthetic Echinocandin LY303366: Identification of Echinocandin Targets in Candida albicans. by Radding JA, Heidler SA, Turner WW.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105773

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PHR1 and PHR2 of Candida albicans Encode Putative Glycosidases Required for Proper Cross-Linking of [beta]-1,3- and [beta]-1,6-Glucans. by Fonzi WA.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94183

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PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis. by Saporito-Irwin SM, Birse CE, Sypherd PS, Fonzi WA.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231914

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Physiological traits associated with success of Candida albicans strains as commensal colonizers and pathogens. by Schmid J, Hunter PR, White GC, Nand AK, Cannon RD.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228607

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Population genomics of drug resistance in Candida albicans. by Cowen LE, Nantel A, Whiteway MS, Thomas DY, Tessier DC, Kohn LM, Anderson JB.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123132

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Postantifungal Effects of Echinocandin, Azole, and Polyene Antifungal Agents against Candida albicans and Cryptococcus neoformans. by Ernst EJ, Klepser ME, Pfaller MA.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89826

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Presumptive Identification of Candida kefyr on Levine Formulation of Eosin Methylene Blue Agar. by Munson EL, Troy DR, Weber JK, Messer SA, Pfaller MA.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139658

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Prevalence and Antifungal Susceptibility of 442 Candida Isolates from Blood and Other Normally Sterile Sites: Results of a 2-Year (1996 to 1998) Multicenter Surveillance Study in Quebec, Canada. by St-Germain G, Laverdiere M, Pelletier R, Bourgault AM, Libman M, Lemieux C, Noel G.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87855

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Prevalence of Candida dubliniensis Isolates in a Yeast Stock Collection. by Odds FC, Van Nuffel L, Dams G.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105079

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Prevalence of Candida Species, Including Candida dubliniensis, in Singapore. by Yang CW, Barkham TM, Chan FY, Wang Y.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149596

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Prevalence of Molecular Mechanisms of Resistance to Azole Antifungal Agents in Candida albicans Strains Displaying High-Level Fluconazole Resistance Isolated from Human Immunodeficiency Virus-Infected Patients. by Perea S, Lopez-Ribot JL, Kirkpatrick WR, McAtee RK, Santillan RA, Martinez M, Calabrese D, Sanglard D, Patterson TF.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90716

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Production of the Carotenoids Lycopene, [beta]-Carotene, and Astaxanthin in the Food Yeast Candida utilis. by Miura Y, Kondo K, Saito T, Shimada H, Fraser PD, Misawa N.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106133

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Production, Characterization, and Epitope Mapping of a Monoclonal Antibody against Aspartic Proteinase of Candida albicans. by Na BK, Chung GT, Song CY.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103737

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Prospective Evaluation of the New Chromogenic Medium Candida ID, in Comparison with Candiselect, for Isolation of Molds and Isolation and Presumptive Identification of Yeast Species. by Letscher-Bru V, Meyer MH, Galoisy AC, Waller J, Candolfi E.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140398

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Prospective Study of Candida Species in Patients at a Comprehensive Cancer Center. by Safdar A, Chaturvedi V, Cross EW, Park S, Bernard EM, Armstrong D, Perlin DS.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90613

96

Candida

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Prospective, Multicenter Surveillance Study of Candida glabrata: Fluconazole and Itraconazole Susceptibility Profiles in Bloodstream, Invasive, and Colonizing Strains and Differences between Isolates from Three Urban Teaching Hospitals in New York City (Candida Susceptibility Trends Study, 1998 to 1999). by Safdar A, Chaturvedi V, Koll BS, Larone DH, Perlin DS, Armstrong D.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128796

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PRR1, a Homolog of Aspergillus nidulans palF, Controls pH-Dependent Gene Expression and Filamentation in Candida albicans. by Porta A, Ramon AM, Fonzi WA.; 1999 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=94209

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Purification and biochemical characterization of a 65-kilodalton mannoprotein (MP65), a main target of anti-Candida cell-mediated immune responses in humans. by Gomez MJ, Torosantucci A, Arancia S, Maras B, Parisi L, Cassone A.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174113

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Quantification of Candida albicans Actin mRNA by the LightCycler System as a Means of Assessing Viability in a Model of Cutaneous Candidiasis. by Okeke CN, Tsuboi R, Ogawa H.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88377

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Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis. by ArthingtonSkaggs BA, Warnock DW, Morrison CJ.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90017

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Quorum Sensing in the Dimorphic Fungus Candida albicans Is Mediated by Farnesol. by Hornby JM, Jensen EC, Lisec AD, Tasto JJ, Jahnke B, Shoemaker R, Dussault P, Nickerson KW.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=92970

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Racial Distribution of Candida dubliniensis Colonization among South Africans. by Blignaut E, Pujol C, Joly S, Soll DR.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154709

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Random Amplification of Polymorphic DNA and Microsatellite Genotyping of Preand Posttreatment Isolates of Candida spp. from Human Immunodeficiency VirusInfected Patients on Different Fluconazole Regimens. by Metzgar D, van Belkum A, Field D, Haubrich R, Wills C.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105037

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Rapamycin and Less Immunosuppressive Analogs Are Toxic to Candida albicans and Cryptococcus neoformans via FKBP12-Dependent Inhibition of TOR. by Cruz MC, Goldstein AL, Blankenship J, Del Poeta M, Perfect JR, McCusker JH, Bennani YL, Cardenas ME, Heitman J.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90798

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Rapid Detection and Identification of Candida, Aspergillus, and Fusarium Species in Ocular Samples Using Nested PCR. by Jaeger EE, Carroll NM, Choudhury S, Dunlop AA, Towler HM, Matheson MM, Adamson P, Okhravi N, Lightman S.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87142

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Rapid Differentiation of Closely Related Candida Species and Strains by PyrolysisMass Spectrometry and Fourier Transform-Infrared Spectroscopy. by Timmins EM, Howell SA, Alsberg BK, Noble WC, Goodacre R.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104544

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Rapid flow cytometric susceptibility testing of Candida albicans. by Ramani R, Ramani A, Wong SJ.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229962

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Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions. by Wilson RB, Davis D, Mitchell AP.; 1999 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=93587

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Rapid Identification and Differentiation of Candida albicans and Candida dubliniensis by Capillary-Based Amplification and Fluorescent Probe Hybridization. by Selvarangan R, Limaye AP, Cookson BT.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139684

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Rapid Identification of Candida albicans and Other Human Pathogenic Yeasts by Using Short Oligonucleotides in a PCR. by Mannarelli BM, Kurtzman CP.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104892

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Rapid Identification of Candida dubliniensis by Indirect Immunofluorescence Based on Differential Localization of Antigens on C. dubliniensis Blastospores and Candida albicans Germ Tubes. by Bikandi J, Millan RS, Moragues MD, Cebas G, Clarke M, Coleman DC, Sullivan DJ, Quindos G, Ponton J.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105138

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Rapid Identification of Candida dubliniensis Using a Species-Specific Molecular Beacon. by Park S, Wong M, Marras SA, Cross EW, Kiehn TE, Chaturvedi V, Tyagi S, Perlin DS.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87122

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Rapid Identification of Candida dubliniensis with Commercial Yeast Identification Systems. by Pincus DH, Coleman DC, Pruitt WR, Padhye AA, Salkin IF, Geimer M, Bassel A, Sullivan DJ, Clarke M, Hearn V.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85686

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Rapid Identification of Candida glabrata Based on Trehalose and Sucrose Assimilation Using Rosco Diagnostic Tablets. by Lopez J, Dalle F, Mantelin P, Moiroux P, Nierlich AC, Pacot A, Cuisenier B, Vagner O, Bonnin A.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87898

98

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Rapid Identification of Candida glabrata by Using a Dipstick To Detect TrehalaseGenerated Glucose. by Peltroche-Llacsahuanga H, Schnitzler N, Lutticken R, Haase G.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84207

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Rapid Identification of Candida Species by Confocal Raman Microspectroscopy. by Maquelin K, Choo-Smith LP, Endtz HP, Bruining HA, Puppels GJ.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153356

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Rapid identification of Candida species in blood cultures by a clinically useful PCR method. by Shin JH, Nolte FS, Morrison CJ.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229766

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Rapid Identification of Candida Species with Species-Specific DNA Probes. by Elie CM, Lott TJ, Reiss E, Morrison CJ.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105312

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Rapid Identification of up to Three Candida Species in a Single Reaction Tube by a 5[prime prime or minute] Exonuclease Assay Using Fluorescent DNA Probes. by Shin JH, Nolte FS, Holloway BP, Morrison CJ.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84197

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Rapid PCR Test for Discriminating between Candida albicans and Candida dubliniensis Isolates Using Primers Derived from the pH-Regulated PHR1 and PHR2 Genes of C. albicans. by Kurzai O, Heinz WJ, Sullivan DJ, Coleman DC, Frosch M, Muhlschlegel FA.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84840

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Rapid, Transient Fluconazole Resistance in Candida albicans Is Associated with Increased mRNA Levels of CDR. by Marr KA, Lyons CN, Rustad T, Bowden RA, White TC.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105901

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Ras Signaling Is Required for Serum-Induced Hyphal Differentiation in Candida albicans. by Feng Q, Summers E, Guo B, Fink G.; 1999 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103768

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Recovery of Candida dubliniensis and Other Yeasts from Human Immunodeficiency Virus-Associated Periodontal Lesions. by Jabra-Rizk MA, Ferreira SM, Sabet M, Falkler WA, Merz WG, Meiller TF.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88577

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Recovery of Candida dubliniensis from Non-Human Immunodeficiency VirusInfected Patients in Israel. by Polacheck I, Strahilevitz J, Sullivan D, Donnelly S, Salkin IF, Coleman DC.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86047

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Red-Pigmented Candida albicans in Patients with Cystic Fibrosis. by Kerkmann ML, Schuppler M, Paul KD.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84240

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Reduced accumulation of drug in Candida krusei accounts for itraconazole resistance. by Venkateswarlu K, Denning DW, Manning NJ, Kelly SL.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163554

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Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy. by Umazume M, Ueta E, Osaki T.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227962

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Reduced virulence of Candida albicans MKC1 mutants: a role for mitogen-activated protein kinase in pathogenesis. by Diez-Orejas R, Molero G, Navarro-Garcia F, Pla J, Nombela C, Sanchez-Perez M.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176136

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Reduced Virulence of HWP1-Deficient Mutants of Candida albicans and Their Interactions with Host Cells. by Tsuchimori N, Sharkey LL, Fonzi WA, French SW, Edwards JE Jr, Filler SG.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97378

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Regulation and Physiological Role of the DAS1 Gene, Encoding Dihydroxyacetone Synthase, in the Methylotrophic Yeast Candida boidinii. by Sakai Y, Nakagawa T, Shimase M, Kato N.; 1998 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=107661

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Regulation of the formate dehydrogenase gene, FDH1, in the methylotrophic yeast Candida boidinii and growth characteristics of an FDH1-disrupted strain on methanol, methylamine, and choline. by Sakai Y, Murdanoto AP, Konishi T, Iwamatsu A, Kato N.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179282

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Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata. by Brun S, Aubry C, Lima O, Filmon R, Berges T, Chabasse D, Bouchara JP.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149308

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Relative Abundance of Oligosaccharides in Candida Species as Determined by Fluorophore-Assisted Carbohydrate Electrophoresis. by Goins TL, Cutler JE.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87130

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Replacement of Candida albicans with C. dubliniensis in Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis Treated with Fluconazole. by Martinez M, Lopez-Ribot JL, Kirkpatrick WR, Coco BJ, Bachmann SP, Patterson TF.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130753

100 Candida

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Repression of Hyphal Proteinase Expression by the Mitogen-Activated Protein (MAP) Kinase Phosphatase Cpp1p of Candida albicans Is Independent of the MAP Kinase Cek1p. by Schroppel K, Sprosser K, Whiteway M, Thomas DY, Rollinghoff M, Csank C.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97832

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Retrospective Identification and Characterization of Candida dubliniensis Isolates among Candida albicans Clinical Laboratory Isolates from Human Immunodeficiency Virus (HIV)-Infected and Non-HIV-Infected Individuals. by Jabra-Rizk MA, Falkler WA Jr, Merz WG, Baqui AA, Kelley JI, Meiller TF.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86831

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Reverse Cross Blot Hybridization Assay for Rapid Detection of PCR-Amplified DNA from Candida Species, Cryptococcus neoformans, and Saccharomyces cerevisiae in Clinical Samples. by Posteraro B, Sanguinetti M, Masucci L, Romano L, Morace G, Fadda G.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86500

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Rfg1, a Protein Related to the Saccharomyces cerevisiae Hypoxic Regulator Rox1, Controls Filamentous Growth and Virulence in Candida albicans. by Kadosh D, Johnson AD.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86882

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RIM101-Dependent and -Independent Pathways Govern pH Responses in Candida albicans. by Davis D, Wilson RB, Mitchell AP.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85214

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RNA triphosphatase is essential in Schizosaccharomyces pombe and Candida albicans. by Pei Y, Schwer B, Saiz J, Fisher RP, Shuman S.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60989

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Role of a Candida albicans P1-Type ATPase in Resistance to Copper and Silver Ion Toxicity. by Riggle PJ, Kumamoto CA.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111370

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Role of aspartic proteases in disseminated Candida albicans infection in mice. by Fallon K, Bausch K, Noonan J, Huguenel E, Tamburini P.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176095

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Role of ATP-Binding-Cassette Transporter Genes in High-Frequency Acquisition of Resistance to Azole Antifungals in Candida glabrata. by Sanglard D, Ischer F, Bille J.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90441

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Role of Hyphal Formation in Interactions of Candida albicans with Endothelial Cells. by Phan QT, Belanger PH, Filler SG.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97632

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Role of the Mitogen-Activated Protein Kinase Hog1p in Morphogenesis and Virulence of Candida albicans. by Alonso-Monge R, Navarro-Garcia F, Molero G, DiezOrejas R, Gustin M, Pla J, Sanchez M, Nombela C.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=93760

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Role of three chitin synthase genes in the growth of Candida albicans. by Mio T, Yabe T, Sudoh M, Satoh Y, Nakajima T, Arisawa M, Yamada-Okabe H.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177954

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Roles of the Candida albicans Mitogen-Activated Protein Kinase Homolog, Cek1p, in Hyphal Development and Systemic Candidiasis. by Csank C, Schroppel K, Leberer E, Harcus D, Mohamed O, Meloche S, Thomas DY, Whiteway M.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108260

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Roles of Three Histidine Kinase Genes in Hyphal Development and Virulence of the Pathogenic Fungus Candida albicans. by Yamada-Okabe T, Mio T, Ono N, Kashima Y, Matsui M, Arisawa M, Yamada-Okabe H.; 1999 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103686

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Roles of TUP1 in Switching, Phase Maintenance, and Phase-Specific Gene Expression in Candida albicans. by Zhao R, Lockhart SR, Daniels K, Soll DR.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=118011

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Secreted Aspartic Proteinase Family of Candida tropicalis. by Zaugg C, Borg-von Zepelin M, Reichard U, Sanglard D, Monod M.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97897

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Secreted Aspartyl Proteinases and Interactions of Candida albicans with Human Endothelial Cells. by Ibrahim AS, Filler SG, Sanglard D, Edwards JE Jr, Hube B.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108304

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Sensitive Bioassay for Determination of Fluconazole Concentrations in Plasma Using a Candida albicans Mutant Hypersusceptible to Azoles. by Marchetti O, Majcherczyk PA, Glauser MP, Bille J, Moreillon P, Sanglard D.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90358

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Septin Function in Candida albicans Morphogenesis. by Warenda AJ, Konopka JB.; 2002 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117938

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Sequencing, Disruption, and Characterization of the Candida albicans Sterol Methyltransferase (ERG6) Gene: Drug Susceptibility Studies in erg6 Mutants. by Jensen-Pergakes KL, Kennedy MA, Lees ND, Barbuch R, Koegel C, Bard M.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105764

102 Candida

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Serological Differentiation of Experimentally Induced Candida dubliniensis and Candida albicans Infections. by Moragues MD, Omaetxebarria MJ, Elguezabal N, Bikandi J, Quindos G, Coleman DC, Ponton J.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88280

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Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. by Leberer E, Harcus D, Broadbent ID, Clark KL, Dignard D, Ziegelbauer K, Schmidt A, Gow NA, Brown AJ, Thomas DY.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24073

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Signaling through Adenylyl Cyclase Is Essential for Hyphal Growth and Virulence in the Pathogenic Fungus Candida albicans. by Rocha CR, Schroppel K, Harcus D, Marcil A, Dignard D, Taylor BN, Thomas DY, Whiteway M, Leberer E.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60281

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Simple and Rapid Detection of Candida albicans DNA in Serum by PCR for Diagnosis of Invasive Candidiasis. by Wahyuningsih R, Freisleben HJ, Sonntag HG, Schnitzler P.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87175

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Simple, Inexpensive, Reliable Method for Differentiation of Candida dubliniensis from Candida albicans. by Pinjon E, Sullivan D, Salkin I, Shanley D, Coleman D.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104987

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Single-Copy IMH3 Allele Is Sufficient To Confer Resistance to Mycophenolic Acid in Candida albicans and To Mediate Transformation of Clinical Candida Species. by Beckerman J, Chibana H, Turner J, Magee PT.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97861

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Species differentiation by internally transcribed spacer PCR and HhaI digestion of fluconazole-resistant Candida krusei, Candida inconspicua, and Candida norvegensis strains. by Nho S, Anderson MJ, Moore CB, Denning DW.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229734

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Species-specific identification of Candida krusei by hybridization with the CkF1,2 DNA probe. by Carlotti A, Couble A, Domingo J, Miroy K, Villard J.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229103

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Specific Chromosome Alterations in Fluconazole-Resistant Mutants of Candida albicans. by Perepnikhatka V, Fischer FJ, Niimi M, Baker RA, Cannon RD, Wang YK, Sherman F, Rustchenko E.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=93895

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Stable Phenotypic Resistance of Candida Species to Amphotericin B Conferred by Preexposure to Subinhibitory Levels of Azoles. by Vazquez JA, Arganoza MT, Boikov D, Yoon S, Sobel JD, Akins RA.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105185

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Sterol and Fatty Acid Composition of Candida lusitaniae Clinical Isolates. by Peyron F, Favel A, Calaf R, Michel-Nguyen A, Bonaly R, Coulon J.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127033

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Strain variation among and antifungal susceptibilities of isolates of Candida krusei. by Berrouane YF, Hollis RJ, Pfaller MA.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229137

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Streptococcus thermophilus and its biosurfactants inhibit adhesion by Candida spp. on silicone rubber. by Busscher HJ, van Hoogmoed CG, Geertsema-Doornbusch GI, van der Kuijl-Booij M, van der Mei HC.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168689

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Stress-induced Gene Expression in Candida albicans: Absence of a General Stress Response. by Enjalbert B, Nantel A, Whiteway M.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153114

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Structure and regulation of a Candida albicans RP10 gene which encodes an immunogenic protein homologous to Saccharomyces cerevisiae ribosomal protein 10. by Swoboda RK, Broadbent ID, Bertram G, Budge S, Gooday GW, Gow NA, Brown AJ.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176729

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Structure and regulation of the HSP90 gene from the pathogenic fungus Candida albicans. by Swoboda RK, Bertram G, Budge S, Gooday GW, Gow NA, Brown AJ.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173642

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Studies of the mechanism of human salivary histatin-5 candidacidal activity with histatin-5 variants and azole-sensitive and -resistant Candida species. by Tsai H, Bobek LA.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164097

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Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. by Sanglard D, Ischer F, Monod M, Bille J.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163524

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Susceptibility of Candida dubliniensis to Salivary Histatin 3. by Fitzgerald DH, Coleman DC, O'Connell BC.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149010

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Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against Clinical Candida Isolates. by Kuipers ME, de Vries HG, Eikelboom MC, Meijer DK, Swart PJ.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89536

104 Candida

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Synthetic Analogues of [beta]-1,2 Oligomannosides Prevent Intestinal Colonization by the Pathogenic Yeast Candida albicans. by Dromer F, Chevalier R, Sendid B, Improvisi L, Jouault T, Robert R, Mallet JM, Poulain D.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=132753

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Techniques for investigation of an apparent outbreak of infections with Candida glabrata. by Arif S, Barkham T, Power EG, Howell SA.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229218

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The ATP Binding Cassette Transporter Gene CgCDR1 from Candida glabrata Is Involved in the Resistance of Clinical Isolates to Azole Antifungal Agents. by Sanglard D, Ischer F, Calabrese D, Majcherczyk PA, Bille J.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89555

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The Basic Helix-Loop-Helix Transcription Factor Cph2 Regulates Hyphal Development in Candida albicans Partly via Tec1. by Lane S, Zhou S, Pan T, Dai Q, Liu H.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99789

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The bZip Transcription Factor Cap1p Is Involved in Multidrug Resistance and Oxidative Stress Response in Candida albicans. by Alarco AM, Raymond M.; 1999 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=93433

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The Candida albicans CDR3 gene codes for an opaque-phase ABC transporter. by Balan I, Alarco AM, Raymond M.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179668

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The Candida albicans KRE9 gene is required for cell wall [beta]-1,6-glucan synthesis and is essential for growth on glucose. by Lussier M, Sdicu AM, Shahinian S, Bussey H.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21421

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The Candida boidinii peroxisomal membrane protein Pmp30 has a role in peroxisomal proliferation and is functionally homologous to Pmp27 from Saccharomyces cerevisiae. by Sakai Y, Marshall PA, Saiganji A, Takabe K, Saiki H, Kato N, Goodman JM.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177542

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The Candida dubliniensis CdCDR1 Gene Is Not Essential for Fluconazole Resistance. by Moran G, Sullivan D, Morschhauser J, Coleman D.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127416

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The Cell Wall-Associated Glyceraldehyde-3-Phosphate Dehydrogenase of Candida albicans Is Also a Fibronectin and Laminin Binding Protein. by Gozalbo D, GilNavarro I, Azorin I, Renau-Piqueras J, Martinez JP, Gil ML.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108162

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The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is a surface antigen. by Gil-Navarro I, Gil ML, Casanova M, O'Connor JE, Martinez JP, Gozalbo D.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179354

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The Golgi GDPase of the Fungal Pathogen Candida albicans Affects Morphogenesis, Glycosylation, and Cell Wall Properties. by Herrero AB, Uccelletti D, Hirschberg CB, Dominguez A, Abeijon C.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=118022

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The high copper tolerance of Candida albicans is mediated by a P-type ATPase. by Weissman Z, Berdicevsky I, Cavari BZ, Kornitzer D.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16272

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The Histone Deacetylase Genes HDA1 and RPD3 Play Distinct Roles in Regulation of High-Frequency Phenotypic Switching in Candida albicans. by Srikantha T, Tsai L, Daniels K, Klar AJ, Soll DR.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95357

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The pH of the Host Niche Controls Gene Expression in and Virulence of Candida albicans. by De Bernardis F, Muhlschlegel FA, Cassone A, Fonzi WA.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108348

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The R467K Amino Acid Substitution in Candida albicans Sterol 14[alpha]Demethylase Causes Drug Resistance through Reduced Affinity. by Lamb DC, Kelly DE, White TC, Kelly SL.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89629

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The Siderophore Iron Transporter of Candida albicans (Sit1p/Arn1p) Mediates Uptake of Ferrichrome-Type Siderophores and Is Required for Epithelial Invasion. by Heymann P, Gerads M, Schaller M, Dromer F, Winkelmann G, Ernst JF.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128288

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The Yeast Candida albicans Binds Complement Regulators Factor H and FHL-1. by Meri T, Hartmann A, Lenk D, Eck R, Wurzner R, Hellwage J, Meri S, Zipfel PF.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128257

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The Yeast Candida albicans has a Clonal Mode of Reproduction in a Population of Infected Human Immunodeficiency Virus-Positive Patients. by Pujol C, Reynes J, Renaud F, Raymond M, Tibayrenc M, Ayala FJ, Janbon F, Mallie M, Bastide J.; 1993 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47587

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Three distinct genotypes within Candida parapsilosis from clinical sources. by Lin D, Wu LC, Rinaldi MG, Lehmann PF.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228276

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Toxic Effects of Ag(I) and Hg(II) on Candida albicans and C. maltosa: a Flow Cytometric Evaluation. by Zhang S, Crow SA Jr.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=93125

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Transcription Profiling of Candida albicans Cells Undergoing the Yeast-to-Hyphal Transition. by Nantel A, Dignard D, Bachewich C, Harcus D, Marcil A, Bouin AP, Sensen CW, Hogues H, van het Hoog M, Gordon P, Rigby T, Benoit F, Tessier DC, Thomas DY, Whiteway M.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129958

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Transcriptional Analyses of Antifungal Drug Resistance in Candida albicans. by Lyons CN, White TC.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90061

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Transient Fungemia Caused by an Amphotericin B-Resistant Isolate of Candida haemulonii. by Rodero L, Cuenca-Estrella M, Cordoba S, Cahn P, Davel G, Kaufman S, Guelfand L, Rodriguez-Tudela JL.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130759

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Trends in Antifungal Susceptibility among Candida sp. Urinary Isolates from 1994 and 1998. by Baran J Jr, Klauber E, Barczak J, Riederer K, Khatib R.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86229

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Typing Candida albicans oral isolates from human immunodeficiency virus-infected patients by multilocus enzyme electrophoresis and DNA fingerprinting. by Boerlin P, Boerlin-Petzold F, Goudet J, Durussel C, Pagani JL, Chave JP, Bille J.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228989

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Typing of Candida albicans Isolates by Sequence Analysis of the Cytochrome b Gene and Differentiation from Candida stellatoidea. by Biswas SK, Yokoyama K, Wang L, Nishimura K, Miyaji M.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87978

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Typing of Candida glabrata in Clinical Isolates by Comparative Sequence Analysis of the Cytochrome c Oxidase Subunit 2 Gene Distinguishes Two Clusters of Strains Associated with Geographical Sequence Polymorphisms. by Sanson GF, Briones MR.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88700

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Unanticipated Heterogeneity in Growth Rate and Virulence among Candida albicans AAF1 Null Mutants. by Rieg G, Fu Y, Ibrahim AS, Zhou X, Filler SG, Edwards JE Jr.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116495

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Undecylenic Acid Inhibits Morphogenesis of Candida albicans. by McLain N, Ascanio R, Baker C, Strohaver RA, Dolan JW.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90168

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Upregulation of ERG Genes in Candida Species by Azoles and Other Sterol Biosynthesis Inhibitors. by Henry KW, Nickels JT, Edlind TD.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90137

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Use of Amplified Fragment Length Polymorphism Analysis To Identify Medically Important Candida spp., Including C. dubliniensis. by Borst A, Theelen B, Reinders E, Boekhout T, Fluit AC, Savelkoul PH.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153876

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Usefulness of Multilocus Sequence Typing for Characterization of Clinical Isolates of Candida albicans. by Bougnoux ME, Morand S, d'Enfert C.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140389

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Vaginal and Oral Epithelial Cell Anti-Candida Activity. by Nomanbhoy F, Steele C, Yano J, Fidel, Jr. PL.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=133056

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Variations in fluconazole susceptibility and DNA subtyping of multiple Candida albicans colonies from patients with AIDS and oral candidiasis suffering one or more episodes of infection. by Redding SW, Pfaller MA, Messer SA, Smith JA, Prows J, Bradley LL, Fothergill AW, Rinaldi MG.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229836

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Virulence of a Phosphoribosylaminoimidazole Carboxylase-Deficient Candida albicans Strain in an Immunosuppressed Murine Model of Systemic Candidiasis. by Donovan M, Schumuke JJ, Fonzi WA, Bonar SL, Gheesling-Mullis K, Jacob GS, Davisson VJ, Dotson SB.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98190

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Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals. by Sullivan D, Haynes K, Bille J, Boerlin P, Rodero L, Lloyd S, Henman M, Coleman D.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229710

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to

6

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

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sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Candida, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Candida” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Candida (hyperlinks lead to article summaries): •

A comparison of the specificity and sensitivity of two Candida antigen assay systems for the diagnosis of deep candidiasis in patients with hematologic diseases. Author(s): Misaki H, Iwasaki H, Ueda T. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 February; 9(2): Mt1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601299&dopt=Abstract

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A forkhead transcription factor is important for true hyphal as well as yeast morphogenesis in Candida albicans. Author(s): Bensen ES, Filler SG, Berman J. Source: Eukaryotic Cell. 2002 October; 1(5): 787-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455696&dopt=Abstract

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A monoclonal antibody directed against a Candida albicans cell wall mannoprotein exerts three anti-C. albicans activities. Author(s): Moragues MD, Omaetxebarria MJ, Elguezabal N, Sevilla MJ, Conti S, Polonelli L, Ponton J. Source: Infection and Immunity. 2003 September; 71(9): 5273-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933874&dopt=Abstract

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A new method for studying the adhesion of Candida albicans to dentin in the presence or absence of smear layer. Author(s): Sen BH, Chugal NM, Liu H, Fleischmann J. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 August; 96(2): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931094&dopt=Abstract

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A randomized trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis. Author(s): Rigopoulos D, Katoulis AC, Ioannides D, Georgala S, Kalogeromitros D, Bolbasis I, Karistinou A, Christofidou E, Polydorou D, Balkou P, Fragouli E, Katsambas AD. Source: The British Journal of Dermatology. 2003 July; 149(1): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890209&dopt=Abstract

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A study on Candida carriage and cytological evaluation of oral mucosa in human immunodeficiency virus (HIV) patients. Author(s): Sainis R, Aithal D. Source: Indian J Dent Res. 2003 January-March; 14(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800757&dopt=Abstract

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A system for studying genetic changes in Candida albicans during infection. Author(s): Forche A, May G, Beckerman J, Kauffman S, Becker J, Magee PT. Source: Fungal Genetics and Biology : Fg & B. 2003 June; 39(1): 38-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742062&dopt=Abstract

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Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by Broth microdilution, disk diffusion, and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001. Author(s): Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ. Source: Journal of Clinical Microbiology. 2003 April; 41(4): 1440-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682127&dopt=Abstract

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Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hosts. Author(s): Romani L, Bistoni F, Puccetti P. Source: Current Opinion in Microbiology. 2003 August; 6(4): 338-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941401&dopt=Abstract

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Adding 2% glucose to culture media does not influence the activity of caspofungin against Candida species. Author(s): Laverdiere M, Restieri C, Habel F. Source: The Journal of Antimicrobial Chemotherapy. 2003 January; 51(1): 183-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493809&dopt=Abstract

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Adherence of Candida strains isolated from the human gastrointestinal tract. Author(s): Biasoli MS, Tosello ME, Magaro HM. Source: Mycoses. 2002 December; 45(11-12): 465-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472722&dopt=Abstract

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Adherence to polystyrene of clinically relevant isolates of Candida species. Author(s): Sanchez-Sousa A, Tarrago D, Velasco J, Alvarez ME, Baquero F. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2001 July; 7(7): 379-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531986&dopt=Abstract

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An unusual cause of vertebral osteomyelitis: Candida species. Author(s): Garbino J, Schnyder I, Lew D, Bouchuiguir-Wafa K, Rohner P. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(4): 288-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839165&dopt=Abstract

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An unusual native tricuspid valve endocarditis caused by Candida colliculosa. Author(s): Kaygusuz I, Mulazimoglu L, Cerikcioglu N, Toprak A, Oktay A, Korten V. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 April; 9(4): 319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667244&dopt=Abstract

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Anti-Candida antibodies in serum and saliva of patients with denture stomatitis. Author(s): Kantardjiev TV, Popova EV. Source: Folia Med (Plovdiv). 2002; 44(4): 39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751686&dopt=Abstract

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Antifungal drug susceptibilities of commensal Candida isolates. Author(s): Holmes AR, Niimi M, Girgis JM, Boyd DH, Cannon RD. Source: N Z Dent J. 2002 June; 98(432): 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125327&dopt=Abstract

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Antifungal drug susceptibility of Candida albicans. Author(s): Bii CC, Ouko TT, Amukoye E, Githinji LW. Source: East Afr Med J. 2002 March; 79(3): 143-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389961&dopt=Abstract

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Antifungal properties of 5-hydroxytryptamine (serotonin) against Candida species in vitro. Author(s): Lass-Florl C, Fuchs D, Ledochowski M, Speth C, Dierich MP, Wurzner R. Source: Journal of Medical Microbiology. 2003 February; 52(Pt 2): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543924&dopt=Abstract

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Azole susceptibility patterns and genetic relationship among oral Candida strains isolated in the era of highly active antiretroviral therapy. Author(s): Tacconelli E, Bertagnolio S, Posteraro B, Tumbarello M, Boccia S, Fadda G, Cauda R. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2002 September 1; 31(1): 38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352148&dopt=Abstract

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Betel quid-associated oral lesions and oral Candida species in a female Cambodian cohort. Author(s): Reichart PA, Schmidtberg W, Samaranayake LP, Scheifele C. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2002 September; 31(8): 468-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220354&dopt=Abstract

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Bilateral endogenous Candida endophthalmitis after induced abortion. Author(s): Sikic J, Vukojevic N, Katusic D, Saric B. Source: Croatian Medical Journal. 2001 December; 42(6): 676-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740854&dopt=Abstract

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Bilateral presumed endogenous candida endophthalmitis and stage 3 retinopathy of prematurity. Author(s): Shah GK, Vander J. Source: American Journal of Ophthalmology. 2003 May; 135(5): 747-8; Author Reply 748. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719106&dopt=Abstract

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Bilateral presumed endogenous candida endophthalmitis and stage 3 retinopathy of prematurity. Author(s): Gago LC, Capone A Jr, Trese MT. Source: American Journal of Ophthalmology. 2002 October; 134(4): 611-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383825&dopt=Abstract

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Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells. Author(s): Jong AY, Chen SH, Stins MF, Kim KS, Tuan TL, Huang SH. Source: Journal of Medical Microbiology. 2003 August; 52(Pt 8): 615-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867553&dopt=Abstract

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Biofilm formation by Candida dubliniensis. Author(s): Ramage G, Vande Walle K, Wickes BL, Lopez-Ribot JL. Source: Journal of Clinical Microbiology. 2001 September; 39(9): 3234-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11526156&dopt=Abstract

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Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. Author(s): Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. Source: Journal of Bacteriology. 2001 September; 183(18): 5385-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11514524&dopt=Abstract

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Biofilm formation of Candida albicans on the surfaces of deteriorated soft denture lining materials caused by denture cleansers in vitro. Author(s): Nikawa H, Jin C, Makihira S, Egusa H, Hamada T, Kumagai H. Source: Journal of Oral Rehabilitation. 2003 March; 30(3): 243-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588495&dopt=Abstract

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Biofilm production by isolates of Candida species recovered from nonneutropenic patients: comparison of bloodstream isolates with isolates from other sources. Author(s): Shin JH, Kee SJ, Shin MG, Kim SH, Shin DH, Lee SK, Suh SP, Ryang DW. Source: Journal of Clinical Microbiology. 2002 April; 40(4): 1244-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923339&dopt=Abstract

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Biofilm-forming ability of Candida albicans is unlikely to contribute to high levels of oral yeast carriage in cases of human immunodeficiency virus infection. Author(s): Jin Y, Yip HK, Samaranayake YH, Yau JY, Samaranayake LP. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 2961-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843027&dopt=Abstract

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Boric acid susceptibility testing of non-C. albicans Candida and Saccharomyces cerevisiae: comparison of three methods. Author(s): Otero L, Palacio V, Mendez FJ, Vazquez F. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2002 June; 40(3): 319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12146764&dopt=Abstract

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Breakthrough candidaemias during empirical therapy with fluconazole in non-cancer and non-HIV adults caused by in vitro-susceptible Candida spp.: report of 33 cases. Author(s): Kovacicova G, Mateicka F, Hanzen J, Liskova A, Sabo A, Szovenyova Z, Chmelik B, Huttova M, Krcmery V. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(10): 749-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728041&dopt=Abstract

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Breakthrough candidemia in patients with cancer differs from de novo candidemia in host factors and Candida species but not intensity. Author(s): Kontoyiannis DP, Reddy BT, Hanna H, Bodey GP, Tarrand J, Raad II. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 September; 23(9): 542-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269454&dopt=Abstract

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Breakthrough fungaemia in neonates and infants caused by Candida albicans and Candida parapsilosis susceptible to fluconazole in vitro. Author(s): Krcmery V, Huttova M, Mateicka F, Laho L, Jurga L, Ondrusova A, Tarekova Z, Kralinsky K, Hanzen J, Liskova A, Mrazova M, Sabo A, Pisarcikova M, Kovacicova G, Chovancova D, Szovenyiova Z. Source: The Journal of Antimicrobial Chemotherapy. 2001 October; 48(4): 521-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11581231&dopt=Abstract

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Breakthrough fungemia caused by azole-resistant Candida albicans in neutropenic patients with acute leukemia. Author(s): Myoken Y, Kyo T, Kohara T, Fujihara M, Sugata T, Mikami Y. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 1; 36(11): 1496-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766847&dopt=Abstract

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Calcineurin is essential for virulence in Candida albicans. Author(s): Bader T, Bodendorfer B, Schroppel K, Morschhauser J. Source: Infection and Immunity. 2003 September; 71(9): 5344-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933882&dopt=Abstract

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Calcium blocks fungicidal activity of human salivary histatin 5 through disruption of binding with Candida albicans. Author(s): Dong J, Vylkova S, Li XS, Edgerton M. Source: Journal of Dental Research. 2003 September; 82(9): 748-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939362&dopt=Abstract

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Candida albicans adherence to resin-composite restorative dental material: influence of whole human saliva. Author(s): Maza JL, Elguezabal N, Prado C, Ellacuria J, Soler I, Ponton J. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002 November; 94(5): 589-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424453&dopt=Abstract

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Candida albicans sternal wound infections: a chronic and recurrent complication of median sternotomy. Author(s): Malani PN, McNeil SA, Bradley SF, Kauffman CA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 December 1; 35(11): 1316-20. Epub 2002 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439793&dopt=Abstract

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Candida dubliniensis identification in Brazilian yeast stock collection. Author(s): Mariano Pde L, Milan EP, da Matta DA, Colombo AL. Source: Memorias Do Instituto Oswaldo Cruz. 2003 June; 98(4): 533-8. Epub 2003 August 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937769&dopt=Abstract

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Candida famata central nervous system infection. Author(s): Prinsloo B, Weldhagen GF, Blaine RW. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 August; 93(8): 601-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531119&dopt=Abstract

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Candida infections today--how big is the problem? Author(s): Nola I, Kostovic K, Oremovic L, Soldo-Belic A, Lugovic L. Source: Acta Dermatovenerol Croat. 2003; 11(3): 171-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967510&dopt=Abstract

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Candida krusei renal cyst infection and measurement of amphotericin B levels in cystic fluid in a patient receiving AmBisome. Author(s): Hepburn MJ, Pennick GJ, Sutton DA, Crawford GE, Jorgensen JH. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2003 April; 41(2): 163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964849&dopt=Abstract

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Candida parapsilosis on peripheral blood smear. Author(s): Bakshi S, Abella E. Source: Indian Pediatrics. 2003 September; 40(9): 903-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530556&dopt=Abstract

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Candida septic arthritis of the hip in a young patient without predisposing factors. Author(s): Kawanabe K, Hayashi H, Miyamoto M, Tamura J, Shimizu M, Nakamura T. Source: The Journal of Bone and Joint Surgery. British Volume. 2003 July; 85(5): 734-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892201&dopt=Abstract

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Candida--agent of the diaper dermatitis? Author(s): Dorko E, Viragova S, Pilipcinec E, Tkacikova L. Source: Folia Microbiol (Praha). 2003; 48(3): 385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879751&dopt=Abstract

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Candida-induced stomatopyrosis. Author(s): Atkin PA. Source: British Dental Journal. 2003 July 26; 195(2): 65; Author Reply 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881730&dopt=Abstract

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Candidal abscess of the parotid gland associated with facial nerve paralysis. Author(s): Marioni G, Rinaldi R, de Filippis C, Gaio E, Staffieri A. Source: Acta Oto-Laryngologica. 2003 June; 123(5): 661-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875591&dopt=Abstract

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CDC42 is required for polarized growth in human pathogen Candida albicans. Author(s): Ushinsky SC, Harcus D, Ash J, Dignard D, Marcil A, Morchhauser J, Thomas DY, Whiteway M, Leberer E. Source: Eukaryotic Cell. 2002 February; 1(1): 95-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455975&dopt=Abstract

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Chemistry and biology of angiitis inducer, Candida albicans water-soluble mannoprotein-beta-glucan complex (CAWS). Author(s): Ohno N. Source: Microbiology and Immunology. 2003; 47(7): 479-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953841&dopt=Abstract

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Chronic hyperplastic candidosis/candidiasis (candidal leukoplakia). Author(s): Sitheeque MA, Samaranayake LP. Source: Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 2003; 14(4): 253-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907694&dopt=Abstract

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Cloning and characterization of PRB1, a Candida albicans gene encoding a putative novel endoprotease B and factors affecting its expression. Author(s): Orozco I, Ortiz L, Elorza MV, Ruiz-Herrera J, Sentandreu R. Source: Research in Microbiology. 2002 November; 153(9): 611-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455710&dopt=Abstract

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Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature. Author(s): Favel A, Michel-Nguyen A, Peyron F, Martin C, Thomachot L, Datry A, Bouchara JP, Challier S, Noel T, Chastin C, Regli P. Source: Diagnostic Microbiology and Infectious Disease. 2003 September; 47(1): 331-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967746&dopt=Abstract

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Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence. Author(s): Hwang CS, Rhie GE, Oh JH, Huh WK, Yim HS, Kang SO. Source: Microbiology (Reading, England). 2002 November; 148(Pt 11): 3705-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427960&dopt=Abstract

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Defective Hyphal induction of a Candida albicans phosphatidylinositol 3-phosphate 5-kinase null mutant on solid media does not lead to decreased virulence. Author(s): Augsten M, Hubner C, Nguyen M, Kunkel W, Hartl A, Eck R. Source: Infection and Immunity. 2002 August; 70(8): 4462-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117957&dopt=Abstract

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Denture stomatitis and salivary Candida in Brazilian edentulous patients. Author(s): Pires FR, Santos EB, Bonan PR, De Almeida OP, Lopes MA. Source: Journal of Oral Rehabilitation. 2002 November; 29(11): 1115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453267&dopt=Abstract

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Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis. Author(s): Lilic D, Gravenor I, Robson N, Lammas DA, Drysdale P, Calvert JE, Cant AJ, Abinun M. Source: Infection and Immunity. 2003 October; 71(10): 5690-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500490&dopt=Abstract

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Detecting Candida albicans in human milk. Author(s): Morrill JF, Pappagianis D, Heinig MJ, Lonnerdal B, Dewey KG. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 475-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517899&dopt=Abstract

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Detection of anti-Candida antibodies by the indirect immunofluorescence assay in patients with cancer in the orofacial region. Author(s): Dorko E, Jenca A, Pilipcinec E, Tkacikova L. Source: Folia Microbiol (Praha). 2002; 47(6): 732-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630328&dopt=Abstract

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Detection of anti-Candida antibodies in neonates from a Neonatal Intensive Care Unit. Author(s): Dorko E, Viragova S, Pilipcinec E, Tkacikova L. Source: Folia Microbiol (Praha). 2002; 47(3): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094742&dopt=Abstract

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Detection of fluconazole-resistant isolates of Candida glabrata by using an agar screen assay. Author(s): Nelson SM, Cartwright CP. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2141-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734262&dopt=Abstract

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Detection of human P-glycoprotein-like molecule in azole-resistant Candida albicans from HIV+ patients. Author(s): Stringaro A, Molinari A, Calcabrini A, Arancia G, Ceddia PG, Cianfriglia M, Poloni F, Mondello F, Angiolella L, De Bernardis F, Cassone A. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Fall; 8(3): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363014&dopt=Abstract

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Development and evaluation of the nuclisens basic kit NASBA for the detection of RNA from Candida species frequently resistant to antifungal drugs. Author(s): Loeffler J, Dorn C, Hebart H, Cox P, Magga S, Einsele H. Source: Diagnostic Microbiology and Infectious Disease. 2003 March; 45(3): 217-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663165&dopt=Abstract

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Differential expression of Candida albicans phospholipase B (PLB1) under various environmental and physiological conditions. Author(s): Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA. Source: Microbiology (Reading, England). 2003 January; 149(Pt 1): 261-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576599&dopt=Abstract

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Differential expression of Candida albicans secreted aspartyl proteinase and phospholipase B genes in humans correlates with active oral and vaginal infections. Author(s): Naglik JR, Rodgers CA, Shirlaw PJ, Dobbie JL, Fernandes-Naglik LL, Greenspan D, Agabian N, Challacombe SJ. Source: The Journal of Infectious Diseases. 2003 August 1; 188(3): 469-79. Epub 2003 July 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870130&dopt=Abstract

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Differentiation of Candida albicans and Candida dubliniensis by using recombinant human antibody single-chain variable fragments specific for hyphae. Author(s): Bliss JM, Sullivan MA, Malone J, Haidaris CG. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1152-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624045&dopt=Abstract

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Direct isolation of Candida spp. from blood cultures on the chromogenic medium CHROMagar Candida. Author(s): Horvath LL, Hospenthal DR, Murray CK, Dooley DP. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791890&dopt=Abstract

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Disseminated fungemia due to Candida krusei with cutaneous lesions and successful treatment by amphotericin B lipid complex and catheter removal: a case report. Author(s): Hourez R, Gillard PH, Mariat P, Aoun M. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2002 December; 6(4): 326-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725216&dopt=Abstract

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Distribution and susceptibility of Candida species isolated in the Medical University of Debrecen. Author(s): Majoros L, Kardos G, Pocsi I, Szabo B. Source: Acta Microbiol Immunol Hung. 2002; 49(2-3): 351-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109169&dopt=Abstract

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Donor-to-host transmission of Candida albicans after corneal transplantation. Author(s): Sutphin JE, Pfaller MA, Hollis RJ, Wagoner MD. Source: American Journal of Ophthalmology. 2002 July; 134(1): 120-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095820&dopt=Abstract

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Down syndrome: lip lesions (angular stomatitis and fissures) and Candida albicans. Author(s): Scully C, van Bruggen W, Diz Dios P, Casal B, Porter S, Davison MF. Source: The British Journal of Dermatology. 2002 July; 147(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100182&dopt=Abstract

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Drug resistant neonatal Candida tropicalis septicemia. Did it cause diaphragmatic hernia? Author(s): Dutta S, Narang A. Source: Indian Pediatrics. 2003 March; 40(3): 261-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657764&dopt=Abstract

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Drug sensitivity of Candida yeast isolated from patients with allergic diseases. Author(s): Arzumanyan VG, Semenov BF. Source: Bulletin of Experimental Biology and Medicine. 2001 April; 131(4): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550023&dopt=Abstract

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Dual Candida albicans and Cryptococcus neoformans fungaemia in an AIDS presenter: a unique disease association in the highly active antiretroviral therapy (HAART) era. Author(s): Manfredi R, Calza L, Chiodo F. Source: Journal of Medical Microbiology. 2002 December; 51(12): 1135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466414&dopt=Abstract

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Early membrane exposure of phosphatidylserine followed by late necrosis in murine macrophages induced by Candida albicans from an HIV-infected individual. Author(s): Panagio LA, Felipe I, Vidotto MC, Gaziri LC. Source: Journal of Medical Microbiology. 2002 November; 51(11): 929-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448676&dopt=Abstract

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Effect of Candida albicans metabolite(s) on cellular actin. Author(s): Sandovsky-Losica H, Berdicevsky I, Tsarfaty I, Segal E. Source: Fems Microbiology Letters. 2002 September 24; 215(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393201&dopt=Abstract

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Effect of CAWS, a mannoprotein-beta-glucan complex of Candida albicans, on leukocyte, endothelial cell, and platelet functions in vitro. Author(s): Kurihara K, Shingo Y, Miura NN, Horie S, Usui Y, Adachi Y, Yadomae T, Ohno N. Source: Biological & Pharmaceutical Bulletin. 2003 February; 26(2): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576686&dopt=Abstract

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Effects of carbohydrate polymers applicable in saliva substitutes on the anti-Candida activity of a histatin-derived peptide. Author(s): Ruissen AL, Groenink J, Lommerse CH, Van 't Hof W, Veerman EC, Nieuw Amerongen AV. Source: Archives of Oral Biology. 2002 November; 47(11): 749-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446181&dopt=Abstract

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Effects of tongue and oral mucosa cleaning on oral Candida species and production of volatile sulfur compounds in the elderly in a nursing home. Author(s): Yonezawa H, Takasaki K, Teraoka K, Asaka T, Sato C, Tsuchiya K. Source: J Med Dent Sci. 2003 March; 50(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715913&dopt=Abstract

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Elevated fecal Candida counts in patients with antibiotic-associated diarrhea: role of soluble fecal substances. Author(s): Krause R, Krejs GJ, Wenisch C, Reisinger EC. Source: Clinical and Diagnostic Laboratory Immunology. 2003 January; 10(1): 167-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522055&dopt=Abstract

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Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to 2000: increased susceptibility of Candida species to fluconazole. Author(s): Hsueh PR, Teng LJ, Yang PC, Ho SW, Luh KT. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Winter; 8(4): 311-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523628&dopt=Abstract

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Endogenous Candida endophthalmitis after two consecutive procedures of suction dilatation and curettage. Author(s): Chang TS, Chen WC, Chen HS, Lee HW. Source: Chang Gung Med J. 2002 November; 25(11): 778-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553368&dopt=Abstract

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Enzymatic differentiation of Candida parapsilosis from other Candida spp. in a membrane filtration test. Author(s): Bauters TG, Peleman R, Dhont M, Vanhaesebrouck P, Nelis HJ. Source: Journal of Microbiological Methods. 2003 April; 53(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609718&dopt=Abstract

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Epidemiology of clinical isolates of Candida albicans and their susceptibility to triazoles. Author(s): Wroblewska MM, Swoboda-Kopec E, Rokosz A, Krawczyk E, Marchel H, Luczak M. Source: International Journal of Antimicrobial Agents. 2002 December; 20(6): 472-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458145&dopt=Abstract

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Evaluation of a method for identification of Candida dubliniensis bloodstream isolates. Author(s): Sancak B, Rex JH, Paetznick V, Chen E, Rodriguez J. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 489-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517903&dopt=Abstract

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Evaluation of Etest method for determining fluconazole and voriconazole MICs for 279 clinical isolates of Candida species infrequently isolated from blood. Author(s): Maxwell MJ, Messer SA, Hollis RJ, Boyken L, Tendolkar S, Diekema DJ, Pfaller MA. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1087-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624034&dopt=Abstract

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Evaluation of internal transcribed spacer region of ribosomal DNA sequence analysis for molecular characterization of Candida albicans and Candida dubliniensis isolates from HIV-infected patients. Author(s): Millon L, Piarroux R, Drobacheff C, Monod M, Grenouillet F, Bulle B, Bole J, Blancard A, Meillet D. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2002 December; 40(6): 535-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521117&dopt=Abstract

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Evaluation of the Etest and disk diffusion methods for determining susceptibilities of 235 bloodstream isolates of Candida glabrata to fluconazole and voriconazole. Author(s): Pfaller MA, Diekema DJ, Boyken L, Messer SA, Tendolkar S, Hollis RJ. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1875-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734220&dopt=Abstract

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Evaluation of the in vitro activity of caspofungin against bloodstream isolates of Candida species from cancer patients: comparison of Etest and NCCLS reference methods. Author(s): Laverdiere M, Restieri C, Habel F. Source: International Journal of Antimicrobial Agents. 2002 December; 20(6): 468-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458144&dopt=Abstract

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Evaluation of the roles of four Candida albicans genes in virulence by using gene disruption strains that express URA3 from the native locus. Author(s): Cheng S, Nguyen MH, Zhang Z, Jia H, Handfield M, Clancy CJ. Source: Infection and Immunity. 2003 October; 71(10): 6101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500538&dopt=Abstract

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Evolution of antifungal susceptibility among Candida species isolates recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis. Author(s): Vazquez JA, Peng G, Sobel JD, Steele-Moore L, Schuman P, Holloway W, Neaton JD. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 October 1; 33(7): 1069-75. Epub 2001 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528582&dopt=Abstract

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Expressed sequence tag analysis of the human pathogen Paracoccidioides brasiliensis yeast phase: identification of putative homologues of Candida albicans virulence and pathogenicity genes. Author(s): Goldman GH, dos Reis Marques E, Duarte Ribeiro DC, de Souza Bernardes LA, Quiapin AC, Vitorelli PM, Savoldi M, Semighini CP, de Oliveira RC, Nunes LR, Travassos LR, Puccia R, Batista WL, Ferreira LE, Moreira JC, Bogossian AP, Tekaia F, Nobrega MP, Nobrega FG, Goldman MH. Source: Eukaryotic Cell. 2003 February; 2(1): 34-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582121&dopt=Abstract

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Extracellular proteinase and phospholipase activity of three genotypic strains of a human pathogenic yeast, Candida albicans. Author(s): Sugita T, Kurosaka S, Yajitate M, Sato H, Nishikawa A. Source: Microbiology and Immunology. 2002; 46(12): 881-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597363&dopt=Abstract

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Factors accounting for misidentification of Candida species. Author(s): Lo HJ, Ho YA, Ho M. Source: J Microbiol Immunol Infect. 2001 September; 34(3): 171-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605807&dopt=Abstract

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Fatal disseminated Candida lusitaniae infection in an infant with chronic granulomatous disease. Author(s): Levy O, Bourquin JP, McQueen A, Cantor AB, Lachenauer C, Malley R. Source: The Pediatric Infectious Disease Journal. 2002 March; 21(3): 262-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005097&dopt=Abstract

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First characterization of Candida albicans by random amplified polymorphic DNA method in Nicaragua and comparison of the diagnosis methods for vaginal candidiasis in Nicaraguan women. Author(s): Darce Bello M, Gonzalez A, Barnabe C, Larrouy G. Source: Memorias Do Instituto Oswaldo Cruz. 2002 October; 97(7): 985-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471425&dopt=Abstract

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First isolation of reddish-pigmented Candida (Torulopsis) glabrata from a clinical specimen. Author(s): Peltroche-Llacsahuanga H, von Oy S, Haase G. Source: Journal of Clinical Microbiology. 2002 March; 40(3): 1116-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880457&dopt=Abstract

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Fluconazole and Candida krusei fungemia. Author(s): Girmenia C, Pagano L, Leone G, Martino P. Source: Archives of Internal Medicine. 2001 October 8; 161(18): 2267-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575996&dopt=Abstract

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Fluconazole in combination with flucytosine in the treatment of fluconazole-resistant Candida infections. Author(s): Girmenia C, Venditti M, Martino P. Source: Diagnostic Microbiology and Infectious Disease. 2003 July; 46(3): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867100&dopt=Abstract

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Fluconazole susceptibility of Brazilian Candida isolates assessed by a disk diffusion method. Author(s): Colombo AL, Da Matta D, De Almeida LP, Rosas R. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2002 June; 6(3): 118-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144747&dopt=Abstract

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Fluconazole susceptibility of Candida species in Singapore by disc diffusion test. Author(s): Oon LL, Yeo MG. Source: Ann Acad Med Singapore. 2002 July; 31(4): 497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161887&dopt=Abstract

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Fluconazole susceptibility of Italian Candida dubliniensis clinical isolates determined by reference and simplified tests. Author(s): Giammanco GM, Pecorella S, Distefano S, Pecoraro V, Milici ME, Pizzo G. Source: New Microbiol. 2001 October; 24(4): 397-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718378&dopt=Abstract

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Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications. Author(s): Sobel JD, Zervos M, Reed BD, Hooton T, Soper D, Nyirjesy P, Heine MW, Willems J, Panzer H. Source: Antimicrobial Agents and Chemotherapy. 2003 January; 47(1): 34-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499165&dopt=Abstract

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Fluconazole therapy for Candida albicans urinary tract infections in infants. Author(s): Triolo V, Gari-Toussaint M, Casagrande F, Garraffo R, Dageville C, Boutte P, Berard E. Source: Pediatric Nephrology (Berlin, Germany). 2002 July; 17(7): 550-3. Epub 2002 June 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172774&dopt=Abstract

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Flucytosine-fluconazole cross-resistance in purine-cytosine permease-deficient Candida lusitaniae clinical isolates: indirect evidence of a fluconazole uptake transporter. Author(s): Noel T, Francois F, Paumard P, Chastin C, Brethes D, Villard J. Source: Antimicrobial Agents and Chemotherapy. 2003 April; 47(4): 1275-84. Erratum In: Antimicrob Agents Chemother. 2003 June; 47(6): 2062. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654658&dopt=Abstract

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Fluorescence in situ hybridization with peptide nucleic acid probes for rapid identification of Candida albicans directly from blood culture bottles. Author(s): Rigby S, Procop GW, Haase G, Wilson D, Hall G, Kurtzman C, Oliveira K, Von Oy S, Hyldig-Nielsen JJ, Coull J, Stender H. Source: Journal of Clinical Microbiology. 2002 June; 40(6): 2182-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037084&dopt=Abstract

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Frequency of Trichomonas vaginalis, Candida sp and Gardnerella vaginalis in cervical-vaginal smears in four different decades. Author(s): Adad SJ, de Lima RV, Sawan ZT, Silva ML, de Souza MA, Saldanha JC, Falco VA, da Cunha AH, Murta EF. Source: Sao Paulo Medical Journal = Revista Paulista De Medicina. 2001 November 1; 119(6): 200-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723534&dopt=Abstract

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Function of Candida glabrata ABC transporter gene, PDH1. Author(s): Izumikawa K, Kakeya H, Tsai HF, Grimberg B, Bennett JE. Source: Yeast (Chichester, England). 2003 February; 20(3): 249-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557277&dopt=Abstract

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Functional characterization of a H+/nucleoside co-transporter (CaCNT) from Candida albicans, a fungal member of the concentrative nucleoside transporter (CNT) family of membrane proteins. Author(s): Loewen SK, Ng AM, Mohabir NN, Baldwin SA, Cass CE, Young JD. Source: Yeast (Chichester, England). 2003 June; 20(8): 661-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794928&dopt=Abstract

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Fungal mating: Candida albicans flips a switch to get in the mood. Author(s): Hull CM, Heitman J. Source: Current Biology : Cb. 2002 November 19; 12(22): R782-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445405&dopt=Abstract

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Fungicidal activities of commonly used disinfectants and antifungal pharmaceutical spray preparations against clinical strains of Aspergillus and Candida species. Author(s): Gupta AK, Ahmad I, Summerbell RC. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2002 April; 40(2): 201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058733&dopt=Abstract

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Genes involved in beta-oxidation, energy metabolism and glyoxylate cycle are induced by Candida albicans during macrophage infection. Author(s): Prigneau O, Porta A, Poudrier JA, Colonna-Romano S, Noel T, Maresca B. Source: Yeast (Chichester, England). 2003 June; 20(8): 723-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794933&dopt=Abstract

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Genetic relatedness of Candida strains isolated from women with vaginal candidiasis in Malaysia. Author(s): Chong PP, Lee YL, Tan BC, Ng KP. Source: Journal of Medical Microbiology. 2003 August; 52(Pt 8): 657-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867559&dopt=Abstract

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Genetic structure of Candida glabrata populations in AIDS and non-AIDS patients. Author(s): de Meeus T, Renaud F, Mouveroux E, Reynes J, Galeazzi G, Mallie M, Bastide JM. Source: Journal of Clinical Microbiology. 2002 June; 40(6): 2199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037087&dopt=Abstract

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Genetically engineered human salivary histatin genes are functional in Candida albicans: development of a new system for studying histatin candidacidal activity. Author(s): Baev D, Li X, Edgerton M. Source: Microbiology (Reading, England). 2001 December; 147(Pt 12): 3323-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739764&dopt=Abstract

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Genome-wide expression profile analysis reveals coordinately regulated genes associated with stepwise acquisition of azole resistance in Candida albicans clinical isolates. Author(s): Rogers PD, Barker KS. Source: Antimicrobial Agents and Chemotherapy. 2003 April; 47(4): 1220-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654650&dopt=Abstract

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Genomic differences between Candida glabrata and Saccharomyces cerevisiae around the MRPL28 and GCN3 loci. Author(s): Walsh DW, Wolfe KH, Butler G. Source: Yeast (Chichester, England). 2002 August; 19(11): 991-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125055&dopt=Abstract

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Genotypic analysis by 27A DNA fingerprinting of Candida albicans strains isolated during an outbreak in a neonatal intensive care unit. Author(s): Boccia S, Posteraro B, La Sorda M, Vento G, Matassa PG, Tempera A, Petrucci S, Fadda G. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 May; 23(5): 281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026157&dopt=Abstract

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Genotypic subgrouping of clinical isolates of Candida albicans and Candida dubliniensis by 25S intron analysis. Author(s): Millar BC, Moore JE, Xu J, Walker MJ, Hedderwick S, McMullan R. Source: Letters in Applied Microbiology. 2002; 35(2): 102-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100582&dopt=Abstract

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Genotyping and antifungal susceptibility of human subgingival Candida albicans isolates. Author(s): Pizzo G, Barchiesi F, Falconi Di Francesco L, Giuliana G, Arzeni D, Milici ME, D'Angelo M, Scalise G. Source: Archives of Oral Biology. 2002 March; 47(3): 189-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839354&dopt=Abstract

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Genotyping of Candida albicans oral strains from healthy individuals by polymorphic microsatellite locus analysis. Author(s): Dalle F, Dumont L, Franco N, Mesmacque D, Caillot D, Bonnin P, Moiroux C, Vagner O, Cuisenier B, Lizard S, Bonnin A. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2203-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734280&dopt=Abstract

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Giant blastoconidia of Candida albicans. A case report and review of the literature. Author(s): Alasio TM, Lento PA, Bottone EJ. Source: Archives of Pathology & Laboratory Medicine. 2003 July; 127(7): 868-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823045&dopt=Abstract

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Global distribution and outcomes for Candida species causing invasive candidiasis: results from an international randomized double-blind study of caspofungin versus amphotericin B for the treatment of invasive candidiasis. Author(s): Colombo AL, Perfect J, DiNubile M, Bartizal K, Motyl M, Hicks P, Lupinacci R, Sable C, Kartsonis N. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 August; 22(8): 470-4. Epub 2003 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884068&dopt=Abstract

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Granulocyte-macrophage colony-stimulating factor responses of oral epithelial cells to Candida albicans. Author(s): Dongari-Bagtzoglou A, Kashleva H. Source: Oral Microbiology and Immunology. 2003 June; 18(3): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753468&dopt=Abstract

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Growth inhibition of Candida albicans by human vaginal epithelial cells. Author(s): Barousse MM, Steele C, Dunlap K, Espinosa T, Boikov D, Sobel JD, Fidel PL Jr. Source: The Journal of Infectious Diseases. 2001 December 1; 184(11): 1489-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709796&dopt=Abstract

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Growth of Candida species on commercial denture adhesives in vitro. Author(s): Makihira S, Nikawa H, Satonobu SV, Jin C, Hamada T. Source: Int J Prosthodont. 2001 January-February; 14(1): 48-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842904&dopt=Abstract

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Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1encoded haem oxygenase. Author(s): Santos R, Buisson N, Knight S, Dancis A, Camadro JM, Lesuisse E. Source: Microbiology (Reading, England). 2003 March; 149(Pt 3): 579-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634327&dopt=Abstract

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Hematogenous infections due to Candida parapsilosis: changing trends in fungemic patients at a comprehensive cancer center during the last four decades. Author(s): Safdar A, Perlin DS, Armstrong D. Source: Diagnostic Microbiology and Infectious Disease. 2002 September; 44(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376025&dopt=Abstract

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Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis. Author(s): Martinez M, Lopez-Ribot JL, Kirkpatrick WR, Bachmann SP, Perea S, Ruesga MT, Patterson TF. Source: The Journal of Antimicrobial Chemotherapy. 2002 March; 49(3): 515-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11864952&dopt=Abstract

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High oral prevalence of Candida krusei in leprosy patients in northern Thailand. Author(s): Reichart PA, Samaranayake LP, Samaranayake YH, Grote M, Pow E, Cheung B. Source: Journal of Clinical Microbiology. 2002 December; 40(12): 4479-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454139&dopt=Abstract

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High rate of vaginal infections caused by non-C. albicans Candida species among asymptomatic women. Author(s): Dan M, Poch F, Levin D. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2002 August; 40(4): 383-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230217&dopt=Abstract

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Highly polymorphic microsatellite for identification of Candida albicans strains. Author(s): Sampaio P, Gusmao L, Alves C, Pina-Vaz C, Amorim A, Pais C. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 552-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574245&dopt=Abstract

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HIV proteinase inhibitors: do they really work against Candida in a clinical setting? Author(s): Cassone A, Cauda R. Source: Trends in Microbiology. 2002 April; 10(4): 177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912024&dopt=Abstract

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HIV-1 and its transmembrane protein gp41 bind to different Candida species modulating adhesion. Author(s): Gruber A, Lell CP, Spruth M, Lass-Florl C, Speth C, Stoiber H, Hube B, Coleman D, Polonelli L, Dierich MP, Wurzner R. Source: Fems Immunology and Medical Microbiology. 2003 June 10; 37(1): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770763&dopt=Abstract

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Horizontal transmission of Candida parapsilosis candidemia in a neonatal intensive care unit. Author(s): Lupetti A, Tavanti A, Davini P, Ghelardi E, Corsini V, Merusi I, Boldrini A, Campa M, Senesi S. Source: Journal of Clinical Microbiology. 2002 July; 40(7): 2363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089249&dopt=Abstract

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Host versus in vitro signals and intrastrain allelic differences in the expression of a Candida albicans virulence gene. Author(s): Staib P, Kretschmar M, Nichterlein T, Hof H, Morschhauser J. Source: Molecular Microbiology. 2002 June; 44(5): 1351-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028383&dopt=Abstract

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HP (2-20) derived from the amino terminal region of helicobacterpylori ribosomal protein L1 exerts its antifungal effects by damaging the plasma membranes of Candida albicans. Author(s): Lee DG, Kim PI, Park Y, Jang SH, Park SC, Woo ER, Hahm KS. Source: Journal of Peptide Science : an Official Publication of the European Peptide Society. 2002 August; 8(8): 453-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212808&dopt=Abstract

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Human immunodeficiency virus type 1 Tat binds to Candida albicans, inducing hyphae but augmenting phagocytosis in vitro. Author(s): Gruber A, Lell CP, Speth C, Stoiber H, Lass-Florl C, Sonneborn A, Ernst JF, Dierich MP, Wurzner R. Source: Immunology. 2001 December; 104(4): 455-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899432&dopt=Abstract

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Human salivary histatin 5 causes disordered volume regulation and cell cycle arrest in Candida albicans. Author(s): Baev D, Li XS, Dong J, Keng P, Edgerton M. Source: Infection and Immunity. 2002 September; 70(9): 4777-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183519&dopt=Abstract

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Hypertonic sabouraud broth as a simple and powerful test for Candida dubliniensis screening. Author(s): Alves SH, Milan EP, de Laet Sant'Ana P, Oliveira LO, Santurio JM, Colombo AL. Source: Diagnostic Microbiology and Infectious Disease. 2002 May; 43(1): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052633&dopt=Abstract

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Hypoxia and extraintestinal dissemination of Candida albicans yeast forms. Author(s): Kim AS, Garni RM, Henry-Stanley MJ, Bendel CM, Erlandsen SL, Wells CL. Source: Shock (Augusta, Ga.). 2003 March; 19(3): 257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630526&dopt=Abstract

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Identification and antifungal susceptibility of Candida isolated from intensive care unit patients. Author(s): Zer Y, Balci I, Meric G. Source: New Microbiol. 2002 October; 25(4): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437230&dopt=Abstract

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Identification of chlamydospore-negative Candida albicans using CHROMagar Candida medium. Author(s): Fotedar R, al-Hedaithy SS. Source: Mycoses. 2003 April; 46(3-4): 96-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870197&dopt=Abstract

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Immunoglobulins G could prevent adherence of Candida albicans to polystyrene and extracellular matrix components. Author(s): Rodier MH, Imbert C, Kauffmann-Lacroix C, Daniault G, Jacquemin JL. Source: Journal of Medical Microbiology. 2003 May; 52(Pt 5): 373-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721311&dopt=Abstract

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Immunotherapy for recalcitrant warts in children using intralesional mumps or Candida antigens. Author(s): Clifton MM, Johnson SM, Roberson PK, Kincannon J, Horn TD. Source: Pediatric Dermatology. 2003 May-June; 20(3): 268-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787281&dopt=Abstract

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Impact of components of denture acrylic resin on gingival cell growth and sensitivity to Candida albicans adhesion. Author(s): Makihira S, Nikawa H, Nishimura M, Egusa H, Sadamori S, Rahayu RP, Nishimura H, Hamada T. Source: Mycoses. 2002 October; 45(8): 300-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572719&dopt=Abstract

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Importance of the terminal complement components for immune defence against Candida. Author(s): Triebel T, Grillhosl B, Kacani L, Lell CP, Fuchs A, Speth C, Lass-Florl C, Steinmann J, Dierich MP, Wurzner R. Source: International Journal of Medical Microbiology : Ijmm. 2003 February; 292(7-8): 527-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635935&dopt=Abstract

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In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazoleresistant isolates. Author(s): Pfaller MA, Diekema DJ, Messer SA, Hollis RJ, Jones RN. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 1068-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604543&dopt=Abstract

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In vitro activities of voriconazole, posaconazole, and four licensed systemic antifungal agents against Candida species infrequently isolated from blood. Author(s): Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN; International Fungal Surveillance Participant Group. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 78-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517829&dopt=Abstract

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In vitro activity of a new polyene SPK-843 against Candida spp, Cryptococcus neoformans and Aspergillus spp clinical isolates. Author(s): Kantarcioglu AS, Yucel A, Vidotto V. Source: Journal of Chemotherapy (Florence, Italy). 2003 June; 15(3): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868560&dopt=Abstract

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In vitro activity of micafungin (FK-463) against Candida spp.: microdilution, timekill, and postantifungal-effect studies. Author(s): Ernst EJ, Roling EE, Petzold CR, Keele DJ, Klepser ME. Source: Antimicrobial Agents and Chemotherapy. 2002 December; 46(12): 3846-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435687&dopt=Abstract

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Increased incidence of vulvovaginal candidiasis caused by Candida glabrata in Jordan. Author(s): Abu-Elteen KH. Source: Japanese Journal of Infectious Diseases. 2001 June; 54(3): 103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11544399&dopt=Abstract

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Indocyanine green angiographic features in endogenous Candida chorioretinis. Author(s): Baglivo E, Seghelmeble C, Bagnoud M, Leuenberger PM, Safran AB. Source: Klinische Monatsblatter Fur Augenheilkunde. 2003 March; 220(3): 179-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728921&dopt=Abstract

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Interaction of sertraline with Candida species selectively attenuates fungal virulence in vitro. Author(s): Lass-Florl C, Ledochowski M, Fuchs D, Speth C, Kacani L, Dierich MP, Fuchs A, Wurzner R. Source: Fems Immunology and Medical Microbiology. 2003 January 21; 35(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589952&dopt=Abstract

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Interleukin-18 and gamma interferon production by oral epithelial cells in response to exposure to Candida albicans or lipopolysaccharide stimulation. Author(s): Rouabhia M, Ross G, Page N, Chakir J. Source: Infection and Immunity. 2002 December; 70(12): 7073-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438388&dopt=Abstract

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Intestinal Candida phospholipase is not elevated in patients with antibioticassociated diarrhea. Author(s): Krause R, Haberl R, Strempfl C, Daxbock F, Krejs GJ, Reisinger EC, Wenisch C. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(11): 815-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578149&dopt=Abstract

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Investigation of Candida dubliniensis in Candida spp.-positive hemocultures. Author(s): Dolapci I, Tekeli A, Gocmen JS, Aysev D, Guriz H. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2002 May; 110(5): 391-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076256&dopt=Abstract

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Is Candida albicans a trigger in the onset of coeliac disease? Author(s): Nieuwenhuizen WF, Pieters RH, Knippels LM, Jansen MC, Koppelman SJ. Source: Lancet. 2003 June 21; 361(9375): 2152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826451&dopt=Abstract

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Isolation and partial characterisation of a new antiproliferative substance from human leucocytes inhibiting growth of Candida albicans. Author(s): Naess-Andresen CF, Ekeberg D, Fagerhol MK, Sandvik K, Staahl L. Source: Molecular Pathology : Mp. 2003 August; 56(4): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890745&dopt=Abstract

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Isolation of Candida dubliniensis in an aboriginal community in Ontario, Canada. Author(s): Montour L, Tey R, Xu J. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843110&dopt=Abstract

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Karyotyping of Candida albicans and Candida glabrata isolates from recurrent vaginal infections by pulsed-field gel electrophoresis. Author(s): Fodor E, Dosa E, Nagy A, Nagy E, Ferenczy L. Source: Acta Microbiol Immunol Hung. 2002; 49(1): 59-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073826&dopt=Abstract

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Keratitis caused by Candida glabrata in a patient with chronic granulomatous disease. Author(s): Djalilian AR, Smith JA, Walsh TJ, Malech HL, Robinson MR. Source: American Journal of Ophthalmology. 2001 November; 132(5): 782-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704043&dopt=Abstract

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Killing of Candida albicans by histatin 5: cellular uptake and energy requirement. Author(s): Gyurko C, Lendenmann U, Helmerhorst EJ, Troxler RF, Oppenheim FG. Source: Antonie Van Leeuwenhoek. 2001 September; 79(3-4): 297-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11816973&dopt=Abstract

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Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1. Author(s): Baev D, Rivetta A, Li XS, Vylkova S, Bashi E, Slayman CL, Edgerton M. Source: Infection and Immunity. 2003 June; 71(6): 3251-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761106&dopt=Abstract

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Large-scale identification of putative exported proteins in Candida albicans by genetic selection. Author(s): Monteoliva L, Matas ML, Gil C, Nombela C, Pla J. Source: Eukaryotic Cell. 2002 August; 1(4): 514-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456000&dopt=Abstract

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Late complications of Candida (Torulopsis) glabrata fungemia: description of a phenomenon. Author(s): Gumbo T, Chemaly RF, Isada CM, Hall GS, Gordon SM. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(11): 817-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578150&dopt=Abstract

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Lectin typing of five medically important Candida species. Author(s): Munoz A, Alonso B, Alvarez O, Llovo J. Source: Mycoses. 2003 April; 46(3-4): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870195&dopt=Abstract

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Limited genetic diversity of Candida albicans in fecal flora of healthy volunteers and inpatients: a proposed basis for strain homogeneity in clinical isolates. Author(s): Khatib R, Ramanathan J, Riederer KM, DePoister D Jr, Baran J Jr. Source: Mycoses. 2002 November; 45(9-10): 393-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421288&dopt=Abstract

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Local immune responsiveness following intravaginal challenge with Candida antigen in adult women at different stages of the menstrual cycle. Author(s): Fidel PL Jr, Barousse M, Lounev V, Espinosa T, Chesson RR, Dunlap K. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2003 April; 41(2): 97-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964841&dopt=Abstract

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Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. Author(s): Ohmit SE, Sobel JD, Schuman P, Duerr A, Mayer K, Rompalo A, Klein RS; HIV Epidemiology Research Study (HERS) Group. Source: The Journal of Infectious Diseases. 2003 July 1; 188(1): 118-27. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825180&dopt=Abstract

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Lymphocyte adhesion to Candida albicans. Author(s): Forsyth CB, Mathews HL. Source: Infection and Immunity. 2002 February; 70(2): 517-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796578&dopt=Abstract

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Management and outcome of bloodstream infections due to Candida species in England and Wales. Author(s): Kibbler CC, Seaton S, Barnes RA, Gransden WR, Holliman RE, Johnson EM, Perry JD, Sullivan DJ, Wilson JA. Source: The Journal of Hospital Infection. 2003 May; 54(1): 18-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767842&dopt=Abstract

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Mannose receptor contribution to Candida albicans phagocytosis by murine E-clone J774 macrophages. Author(s): Porcaro I, Vidal M, Jouvert S, Stahl PD, Giaimis J. Source: Journal of Leukocyte Biology. 2003 August; 74(2): 206-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885937&dopt=Abstract

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Massive septic thrombus formation on a superior vena cava indwelling catheter following Torulopsis (Candida) glabrata fungemia. Author(s): Gressianu MT, Dhruva VN, Arora RR, Patel S, Lopez S, Jihayel AK, Saric M. Source: Intensive Care Medicine. 2002 March; 28(3): 379-80. Epub 2001 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904673&dopt=Abstract

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Maternal sepsis and intrauterine fetal death resulting from Candida tropicalis chorioamnionitis in a woman with a retained intrauterine contraceptive device. Author(s): Barth T, Broscheit J, Bussen S, Dietl J. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 October; 81(10): 981-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366491&dopt=Abstract

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Methaemoglobinaemia with concurrent blood isolation of Saccharomyces and Candida. Author(s): Lungarotti MS, Mezzetti D, Radicioni M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 September; 88(5): F446. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937065&dopt=Abstract

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Microevolutionary changes and chromosomal translocations are more frequent at RPS loci in Candida dubliniensis than in Candida albicans. Author(s): Joly S, Pujol C, Soll DR. Source: Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2002 October; 2(1): 19-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797998&dopt=Abstract

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Microorganisms in intertriginous psoriasis: no evidence of Candida. Author(s): Flytstrom I, Bergbrant IM, Brared J, Brandberg LL. Source: Acta Dermato-Venereologica. 2003; 83(2): 121-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735640&dopt=Abstract

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Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species. Author(s): Canton E, Peman J, Viudes A, Quindos G, Gobernado M, Espinel-Ingroff A. Source: Diagnostic Microbiology and Infectious Disease. 2003 March; 45(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663162&dopt=Abstract

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Mitochondrial telomeres as molecular markers for identification of the opportunistic yeast pathogen Candida parapsilosis. Author(s): Nosek J, Tomaska L, Rycovska A, Fukuhara H. Source: Journal of Clinical Microbiology. 2002 April; 40(4): 1283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923346&dopt=Abstract

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Mixed species biofilms of Candida albicans and Staphylococcus epidermidis. Author(s): Adam B, Baillie GS, Douglas LJ. Source: Journal of Medical Microbiology. 2002 April; 51(4): 344-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926741&dopt=Abstract

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Modular domain structure in the Candida glabrata adhesin Epa1p, a beta1,6 glucancross-linked cell wall protein. Author(s): Frieman MB, McCaffery JM, Cormack BP. Source: Molecular Microbiology. 2002 October; 46(2): 479-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406223&dopt=Abstract

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Molecular characterization of Candida spp. isolated from the oral cavities of patients from diverse clinical settings. Author(s): Al-Karaawi ZM, Manfredi M, Waugh AC, McCullough MJ, Jorge J, Scully C, Porter SR. Source: Oral Microbiology and Immunology. 2002 February; 17(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860555&dopt=Abstract

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Molecular diversity and routes of colonization of Candida albicans in a surgical intensive care unit, as studied using microsatellite markers. Author(s): Stephan F, Bah MS, Desterke C, Rezaiguia-Delclaux S, Foulet F, Duvaldestin P, Bretagne S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 December 15; 35(12): 1477-83. Epub 2002 Dec 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471566&dopt=Abstract

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Molecular epidemiology of Candida. Author(s): Stevens DA. Source: Journal of Clinical Microbiology. 2002 July; 40(7): 2710. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089319&dopt=Abstract

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Molecular heterogeneity of fluconazole-resistant and -susceptible oral Candida albicans isolates within a single geographic locale. Author(s): Cochrane Database Syst Rev. 2002;(4):CD002033 Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2002 April; 110(4): 315-24. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519566

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Molecular mechanisms of fluconazole resistance in Candida dubliniensis isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Author(s): Perea S, Lopez-Ribot JL, Wickes BL, Kirkpatrick WR, Dib OP, Bachmann SP, Keller SM, Martinez M, Patterson TF. Source: Antimicrobial Agents and Chemotherapy. 2002 June; 46(6): 1695-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019078&dopt=Abstract

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Multicenter comparative evaluation of six commercial systems and the national committee for clinical laboratory standards m27-a broth microdilution method for fluconazole susceptibility testing of Candida species. Author(s): Morace G, Amato G, Bistoni F, Fadda G, Marone P, Montagna MT, Oliveri S, Polonelli L, Rigoli R, Mancuso I, La Face S, Masucci L, Romano L, Napoli C, Tato D, Buscema MG, Belli CM, Piccirillo MM, Conti S, Covan S, Fanti F, Cavanna C, D'Alo F, Pitzurra L. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2953-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149358&dopt=Abstract

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Multicenter comparison of Fungitest for susceptibility testing of Candida species. Author(s): Willinger B, Engelmann E, Hofmann H, Metzger S, Apfalter P, Hirschl AM, Makristathis A, Rotter M, Raddatz B, Seibold M. Source: Diagnostic Microbiology and Infectious Disease. 2002 November; 44(3): 253-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493172&dopt=Abstract

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Multiple patterns of resistance to fluconazole in Candida glabrata isolates from a patient with oropharyngeal candidiasis receiving head and neck radiation. Author(s): Redding SW, Kirkpatrick WR, Saville S, Coco BJ, White W, Fothergill A, Rinaldi M, Eng T, Patterson TF, Lopez-Ribot J. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 619-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574256&dopt=Abstract

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Mycological and cytological examination of oral candidal carriage in diabetic patients and non-diabetic control subjects: thorough analysis of local aetiologic and systemic factors. Author(s): Kadir T, Pisiriciler R, Akyuz S, Yarat A, Emekli N, Ipbuker A. Source: Journal of Oral Rehabilitation. 2002 May; 29(5): 452-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028493&dopt=Abstract

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Nasal vaccination induces the ability to eliminate Candida colonization without influencing the pre-existing antigen-specific IgE Abs: a possibility for the control of Candida-related atopic dermatitis. Author(s): Suenobu N, Kweon MN, Kiyono H. Source: Vaccine. 2002 July 26; 20(23-24): 2972-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126910&dopt=Abstract

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Neonatal Candida glabrata sepsis: clinical and laboratory features compared with other Candida species. Author(s): Fairchild KD, Tomkoria S, Sharp EC, Mena FV. Source: The Pediatric Infectious Disease Journal. 2002 January; 21(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791097&dopt=Abstract

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Neonatal Candida meningitis. Author(s): Moylett EH. Source: Seminars in Pediatric Infectious Diseases. 2003 April; 14(2): 115-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881799&dopt=Abstract

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Neutrophil hypochlorous acid production is impaired in multiple organ failure patients with candidaemia; reversal with antifungal agents. Author(s): Hussien M, Delecata RJ, Carey PD. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 April; 51(4): 213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058960&dopt=Abstract

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New molecular methods to study gene functions in Candida infections. Author(s): Theiss S, Kohler GA, Kretschmar M, Nichterlein T, Hacker J. Source: Mycoses. 2002 November; 45(9-10): 345-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421279&dopt=Abstract

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Non Candida albicans fungal peritonitis in continuous ambulatory peritoneal dialysis patients. Author(s): Kleinpeter MA, Butt AA. Source: Adv Perit Dial. 2001; 17: 176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510270&dopt=Abstract

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Non-albicans Candida infections in patients with hematologic malignancies. Author(s): Moosa MY, Sobel JD. Source: Seminars in Respiratory Infections. 2002 June; 17(2): 91-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070827&dopt=Abstract

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Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients. Author(s): Mullen CA, Abd El-Baki H, Samir H, Tarrand JJ, Rolston KV. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 May; 11(5): 321-5. Epub 2003 March 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720076&dopt=Abstract

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Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. Author(s): Krcmery V, Barnes AJ. Source: The Journal of Hospital Infection. 2002 April; 50(4): 243-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014897&dopt=Abstract

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NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. Author(s): Murad AM, Leng P, Straffon M, Wishart J, Macaskill S, MacCallum D, Schnell N, Talibi D, Marechal D, Tekaia F, d'Enfert C, Gaillardin C, Odds FC, Brown AJ. Source: The Embo Journal. 2001 September 3; 20(17): 4742-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532938&dopt=Abstract

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Olecranon bursitis due to Candida parapsilosis in an immunocompetent adult. Author(s): Jimenez-Palop M, Corteguera M, Ibanez R, Serrano-Heranz R. Source: Annals of the Rheumatic Diseases. 2002 March; 61(3): 279-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830444&dopt=Abstract

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Optimization and validation of multilocus sequence typing for Candida albicans. Author(s): Tavanti A, Gow NA, Senesi S, Maiden MC, Odds FC. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3765-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904388&dopt=Abstract

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Oral Candida albicans and Candida dubliniensis differentiation by multilocus enzyme electrophoresis and sodium dodecylsulphate-polyacrylamide gel electrophoresis. Author(s): Rosa EA, Rosa RT, Boriollo MF, Bernardo WL, Hofling JF. Source: Rev Argent Microbiol. 2003 January-March; 35(1): 24-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833677&dopt=Abstract

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Oral Candida and nasal Aspergillus flora in a group of Saudi healthy dentate subjects. Author(s): Darwazeh AM, Al-Dosari A, Al-bagieh NH. Source: Int Dent J. 2002 August; 52(4): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212815&dopt=Abstract

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Oral candidal infections and antimycotics. Author(s): Ellepola AN, Samaranayake LP. Source: Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 2000; 11(2): 172-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002814&dopt=Abstract

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Oral colonization by Candida spp. among AIDS household contacts. Author(s): Milan EP, Kallas EG, Costa PR, da Matta DA, Lopes Colombo A. Source: Mycoses. 2001; 44(7-8): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714061&dopt=Abstract

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Oral mucosal lesions caused by Candida albicans. Author(s): de Waal H. Source: Sadj. 2003 March; 58(2): 76. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800271&dopt=Abstract

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Outbreak of Candida rugosa candidemia: an emerging pathogen that may be refractory to amphotericin B therapy. Author(s): Colombo AL, Melo AS, Crespo Rosas RF, Salomao R, Briones M, Hollis RJ, Messer SA, Pfaller MA. Source: Diagnostic Microbiology and Infectious Disease. 2003 August; 46(4): 253-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944016&dopt=Abstract

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Outbreak of nosocomial fungemia caused by Candida glabrata. Author(s): Nedret Koc A, Kocagoz S, Erdem F, Gunduz Z. Source: Mycoses. 2002 December; 45(11-12): 470-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472723&dopt=Abstract

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Parenteral administration of medium- but not long-chain lipid emulsions may increase the risk for infections by Candida albicans. Author(s): Wanten GJ, Netea MG, Naber TH, Curfs JH, Jacobs LE, Verver-Jansen TJ, Kullberg BJ. Source: Infection and Immunity. 2002 November; 70(11): 6471-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379731&dopt=Abstract

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Peritoneal infection with multiple species of Candida: a case report. Author(s): Islam S, Zaidi AK, Wilson J. Source: Surgical Infections. 2002 Spring; 3(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593698&dopt=Abstract

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Persistence of oral Candida albicans carriage in healthy Portuguese schoolchildren followed for 3 years. Author(s): Starr JR, White TC, Leroux BG, Luis HS, Bernardo M, Leitao J, Roberts MC. Source: Oral Microbiology and Immunology. 2002 October; 17(5): 304-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354212&dopt=Abstract

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Persistence of oropharyngeal Candida albicans strains with reduced susceptibilities to fluconazole among human immunodeficiency virus-seropositive children and adults in a long-term care facility. Author(s): Makarova NU, Pokrowsky VV, Kravchenko AV, Serebrovskaya LV, James MJ, McNeil MM, Lasker BA, Warnock DW, Reiss E. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1833-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734213&dopt=Abstract

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Physical parameters of hydroxyapatite adsorption and effect on candidacidal activity of histatins. Author(s): Yin A, Margolis HC, Grogan J, Yao Y, Troxler RF, Oppenheim FG. Source: Archives of Oral Biology. 2003 May; 48(5): 361-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711380&dopt=Abstract

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Physiological role of S-formylglutathione hydrolase in C(1) metabolism of the methylotrophic yeast Candida boidinii. Author(s): Yurimoto H, Lee B, Yano T, Sakai Y, Kato N. Source: Microbiology (Reading, England). 2003 August; 149(Pt 8): 1971-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904537&dopt=Abstract

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Pneumonia due to Candida krusei. Author(s): Petrocheilou-Paschou V, Georgilis K, Kontoyannis D, Nanas J, Prifti H, Costopoulos H, Stamatelopoulos S. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 December; 8(12): 806-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519355&dopt=Abstract

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Population structure of Candida albicans, a member of the human flora, as determined by microsatellite loci. Author(s): Fundyga RE, Lott TJ, Arnold J. Source: Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2002 October; 2(1): 57-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798001&dopt=Abstract

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Post-antifungal effect of polyene, azole and DNA-analogue agents against oral Candida albicans and Candida tropicalis isolates in HIV disease. Author(s): Anil S, Ellepola AN, Samaranayake LP. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 September; 30(8): 481-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545239&dopt=Abstract

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Predictive factors of mortality due to polymicrobial peritonitis with Candida isolation in peritoneal fluid in critically ill patients. Author(s): Dupont H, Paugam-Burtz C, Muller-Serieys C, Fierobe L, Chosidow D, Marmuse JP, Mantz J, Desmonts JM. Source: Archives of Surgery (Chicago, Ill. : 1960). 2002 December; 137(12): 1341-6; Discussion 1347. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470095&dopt=Abstract

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Presumptive identification of Candida kefyr on levine formulation of eosin methylene blue agar. Author(s): Munson EL, Troy DR, Weber JK, Messer SA, Pfaller MA. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4281-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409410&dopt=Abstract

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Prevalence of Candida albicans in oral cavities and root canals of children. Author(s): Akdeniz BG, Koparal E, Sen BH, Ates M, Denizci AA. Source: Asdc J Dent Child. 2002 September-December; 69(3): 289-92, 235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613314&dopt=Abstract

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Prevalence of Candida species, including Candida dubliniensis, in Singapore. Author(s): Yang CW, Barkham TM, Chan FY, Wang Y. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 472-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517898&dopt=Abstract

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Prevalence of Candida spp. in hospitalized patients and their risk factors. Author(s): Resende JC, de Resende MA, Saliba JL. Source: Mycoses. 2002 October; 45(8): 306-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572720&dopt=Abstract

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Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Author(s): Garbino J, Lew DP, Romand JA, Hugonnet S, Auckenthaler R, Pittet D. Source: Intensive Care Medicine. 2002 December; 28(12): 1708-17. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447512&dopt=Abstract

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Propranolol inhibits hyphal development in Candida albicans. Author(s): Baker CA, Desrosiers K, Dolan JW. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3617-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384374&dopt=Abstract

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Prospective epidemiologic analysis of triazole-resistant nosocomial Candida glabrata isolated from patients at a comprehensive cancer center. Author(s): Safdar A, Armstrong D, Cross EW, Perlin DS. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2002 September; 6(3): 198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718835&dopt=Abstract

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Prospective evaluation of Candida species colonization in hospitalized cancer patients: impact on short-term survival in recipients of marrow transplantation and patients with hematological malignancies. Author(s): Safdar A, Armstrong D. Source: Bone Marrow Transplantation. 2002 December; 30(12): 931-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476287&dopt=Abstract

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Pseudooutbreak of Candida versatilitis fungemia in a microbiology laboratory. Author(s): Brandt ME, Benjamin LE, Steinkraus GE. Source: Diagnostic Microbiology and Infectious Disease. 2003 May; 46(1): 73-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742323&dopt=Abstract

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Quantification of Candida albicans actin mRNA by the LightCycler system as a means of assessing viability in a model of cutaneous candidiasis. Author(s): Okeke CN, Tsuboi R, Ogawa H. Source: Journal of Clinical Microbiology. 2001 October; 39(10): 3491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574561&dopt=Abstract

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Quantitative relationship between salivary level of Streptococcus mutans and Candida albicans in children with Down's syndrome. Author(s): Linossier A, Vargas A, Villegas R, Chimenos E. Source: Medicina Oral : Organo Oficial De La Sociedad Espanola De Medicina Oral Y De La Academia Iberoamericana De Patologia Y Medicina Bucal. 2002 July-October; 7(4): 284-92. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134129&dopt=Abstract

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Quantitative variation of biofilms among strains in natural populations of Candida albicans. Author(s): Li X, Yan Z, Xu J. Source: Microbiology (Reading, England). 2003 February; 149(Pt 2): 353-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624197&dopt=Abstract

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Race, Candida sepsis, and retinopathy of prematurity. Author(s): Tadesse M, Dhanireddy R, Mittal M, Higgins RD. Source: Biology of the Neonate. 2002; 81(2): 86-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844875&dopt=Abstract

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Racial distribution of Candida dubliniensis colonization among South Africans. Author(s): Blignaut E, Pujol C, Joly S, Soll DR. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1838-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734214&dopt=Abstract

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Rapid and cost-effective identification of Candida species using multipoint inoculation of CHROMagar Candida media, cycloheximide sensitivity and carbohydrate assimilation tests. Author(s): Tambosis E, Atkins BL, Capizzi T, Gottlieb T. Source: Pathology. 2003 April; 35(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745454&dopt=Abstract

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Rapid detection of Candida albicans in clinical blood samples by using a TaqManbased PCR assay. Author(s): Maaroufi Y, Heymans C, De Bruyne JM, Duchateau V, Rodriguez-Villalobos H, Aoun M, Crokaert F. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843077&dopt=Abstract

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Rapid differentiation of Candida albicans from other Candida species using its unique germ tube formation at 39 degrees C. Author(s): Kim D, Shin WS, Lee KH, Kim K, Young Park J, Koh CM. Source: Yeast (Chichester, England). 2002 August; 19(11): 957-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125052&dopt=Abstract

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Rapid identification and differentiation of Candida albicans and Candida dubliniensis by capillary-based amplification and fluorescent probe hybridization. Author(s): Selvarangan R, Limaye AP, Cookson BT. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409417&dopt=Abstract

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Rapid identification of Candida glabrata with a new commercial test, GLABRATA RTT. Author(s): Freydiere AM, Robert R, Ploton C, Marot-Leblond A, Monerau F, Vandenesch F. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3861-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904403&dopt=Abstract

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Rapid identification of Candida species by using nuclear magnetic resonance spectroscopy and a statistical classification strategy. Author(s): Himmelreich U, Somorjai RL, Dolenko B, Lee OC, Daniel HM, Murray R, Mountford CE, Sorrell TC. Source: Applied and Environmental Microbiology. 2003 August; 69(8): 4566-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902244&dopt=Abstract

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Rapid identification of fluconazole resistance using Chrom agar Candida. Author(s): Verghese SL, Padmaja P, Sutha P, Mathew T, Johni ES. Source: Indian J Pathol Microbiol. 2001 July; 44(3): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024918&dopt=Abstract

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Reassessing the presence of Candida albicans in denture-related stomatitis. Author(s): Barbeau J, Seguin J, Goulet JP, de Koninck L, Avon SL, Lalonde B, Rompre P, Deslauriers N. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 January; 95(1): 51-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539027&dopt=Abstract

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Recovery and studies on chlamydospore-negative Candida albicans isolated from clinical specimens. Author(s): Al-Hedaithy SS, Fotedar R. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2002 June; 40(3): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12146760&dopt=Abstract

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Reduced expression of the hyphal-independent Candida albicans proteinase genes SAP1 and SAP3 in the efg1 mutant is associated with attenuated virulence during infection of oral epithelium. Author(s): Korting HC, Hube B, Oberbauer S, Januschke E, Hamm G, Albrecht A, Borelli C, Schaller M. Source: Journal of Medical Microbiology. 2003 August; 52(Pt 8): 623-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867554&dopt=Abstract

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Reintroduction of the PLB1 gene into Candida albicans restores virulence in vivo. Author(s): Mukherjee PK, Seshan KR, Leidich SD, Chandra J, Cole GT, Ghannoum MA. Source: Microbiology (Reading, England). 2001 September; 147(Pt 9): 2585-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535799&dopt=Abstract

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Relationship between the physical properties of Candida albicans cell well betaglucan and activation of leukocytes in vitro. Author(s): Ishibashi K, Miura NN, Adachi Y, Ogura N, Tamura H, Tanaka S, Ohno N. Source: International Immunopharmacology. 2002 July; 2(8): 1109-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12349948&dopt=Abstract

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Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole. Author(s): Martinez M, Lopez-Ribot JL, Kirkpatrick WR, Coco BJ, Bachmann SP, Patterson TF. Source: Journal of Clinical Microbiology. 2002 September; 40(9): 3135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202543&dopt=Abstract

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Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin. Author(s): Dinubile MJ, Lupinacci RJ, Berman RS, Sable CA. Source: Aids Research and Human Retroviruses. 2002 September 1; 18(13): 903-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230933&dopt=Abstract

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Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology. Author(s): Rodriguez-Adrian LJ, King RT, Tamayo-Derat LG, Miller JW, Garcia CA, Rex JH. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2003 May; 82(3): 187-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792305&dopt=Abstract

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Risk factors for nosocomial candidaemia: a case-control study in children. Author(s): Paganini H, Rodriguez Brieshcke T, Santos P, Seu S, Rosanova MT. Source: The Journal of Hospital Infection. 2002 April; 50(4): 304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014905&dopt=Abstract

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Role of pH response in Candida albicans virulence. Author(s): Fonzi WA. Source: Mycoses. 2002; 45 Suppl 1: 16-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073557&dopt=Abstract

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Role of the toll-like receptor 4 Asp299Gly polymorphism in susceptibility to Candida albicans infection. Author(s): Morre SA, Murillo LS, Spaargaren J, Fennema HS, Pena AS. Source: The Journal of Infectious Diseases. 2002 November 1; 186(9): 1377-9; Author Reply 1379. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402214&dopt=Abstract

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Secreted aspartic proteases as virulence factors of Candida species. Author(s): Monod M, Borg-von ZM. Source: Biological Chemistry. 2002 July-August; 383(7-8): 1087-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437091&dopt=Abstract

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Shifting patterns in the epidemiology of nosocomial Candida infections. Author(s): Snydman DR. Source: Chest. 2003 May; 123(5 Suppl): 500S-3S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740235&dopt=Abstract

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Species distribution and antifungal susceptibility profile of Candida spp. bloodstream isolates from Latin American hospitals. Author(s): Godoy P, Tiraboschi IN, Severo LC, Bustamante B, Calvo B, Almeida LP, da Matta DA, Colombo AL. Source: Memorias Do Instituto Oswaldo Cruz. 2003 April; 98(3): 401-5. Epub 2003 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886424&dopt=Abstract

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Sperm and oocyte donor selection and management: experience of a 10 year follow-up of more than 2100 candidates. Author(s): Garrido N, Zuzuarregui JL, Meseguer M, Simon C, Remohi J, Pellicer A. Source: Human Reproduction (Oxford, England). 2002 December; 17(12): 3142-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456614&dopt=Abstract

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Spontaneous intestinal perforation and Candida peritonitis presenting as extensive necrotizing enterocolitis. Author(s): Robertson NJ, Kuna J, Cox PM, Lakhoo K. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003; 92(2): 258-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710658&dopt=Abstract

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Stable susceptibility of Candida blood isolates to fluconazole despite increasing use during the past 10 years. Author(s): Chen YC, Chang SC, Luh KT, Hsieh WC. Source: The Journal of Antimicrobial Chemotherapy. 2003 July; 52(1): 71-7. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775680&dopt=Abstract

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Stensen's duct obstruction by foreign body and subsequent candidal infection of the parotid gland. Author(s): Stefanopoulos PK, Karakassis DT, Triantafyllidou A. Source: The Journal of Laryngology and Otology. 2003 August; 117(8): 662-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956927&dopt=Abstract

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Successful medical treatment of Candida albicans in mechanical prosthetic valve endocarditis. Author(s): Aaron L, Therby A, Viard JP, Lahoulou R, Dupont B. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(5): 351-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875529&dopt=Abstract

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Successful treatment of Candida krusei infection with caspofungin acetate: a new antifungal agent. Author(s): McGee WT, Tereso GJ. Source: Critical Care Medicine. 2003 May; 31(5): 1577-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771636&dopt=Abstract

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Successful treatment of flat warts using intralesional Candida antigen. Author(s): Ritter SE, Meffert J. Source: Archives of Dermatology. 2003 April; 139(4): 541-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707109&dopt=Abstract

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Susceptibility of Candida albicans isolates from the oral cavities of HIV-positive patients to histatin-5. Author(s): Nikawa H, Jin C, Makihira S, Hamada T, Samaranayake LP. Source: The Journal of Prosthetic Dentistry. 2002 September; 88(3): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426495&dopt=Abstract

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Susceptibility profile of 200 bloodstream isolates of Candida spp. collected from Brazilian tertiary care hospitals. Author(s): Colombo AL, Nakagawa Z, Valdetaro F, Branchini ML, Kussano EJ, Nucci M. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2003 June; 41(3): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964715&dopt=Abstract

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Systemic Candida infections in patients with leukemia: an overview of drug therapy. Author(s): Blash JL. Source: Clinical Journal of Oncology Nursing. 2002 November-December; 6(6): 323-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434463&dopt=Abstract

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The ability of Candida spp. strains to induce production of tumor necrosis factor and interleukin-6 by whole blood cells. Author(s): Nawrot U, Grzybek-Hryncewicz K, Czarny A. Source: Acta Microbiol Pol. 2003; 52(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916731&dopt=Abstract

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The Golgi GDPase of the fungal pathogen Candida albicans affects morphogenesis, glycosylation, and cell wall properties. Author(s): Herrero AB, Uccelletti D, Hirschberg CB, Dominguez A, Abeijon C. Source: Eukaryotic Cell. 2002 June; 1(3): 420-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455990&dopt=Abstract

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The relationship between oral Candida carriage and the secretor status of blood group antigens in saliva. Author(s): Shin ES, Chung SC, Kim YK, Lee SW, Kho HS. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 July; 96(1): 48-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847444&dopt=Abstract

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The sixth ASM Candida and candidiasis conference. Author(s): Sullivan D. Source: Fems Yeast Research. 2002 May; 2(2): 249-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702313&dopt=Abstract

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The use of Niger seed agar to screen for Candida dubliniensis in the clinical microbiology laboratory. Author(s): Lees E, Barton RC. Source: Diagnostic Microbiology and Infectious Disease. 2003 May; 46(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742313&dopt=Abstract

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Time to positive culture results in neonatal Candida septicemia. Author(s): Schelonka RL, Moser SA. Source: The Journal of Pediatrics. 2003 May; 142(5): 564-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756391&dopt=Abstract

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Treatment of Candida glabrata using topical amphotericin B and flucytosine. Author(s): Shann S, Wilson J. Source: Sexually Transmitted Infections. 2003 June; 79(3): 265-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794227&dopt=Abstract

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Treatment of nondermatophyte mold and Candida onychomycosis. Author(s): Tosti A, Piraccini BM, Lorenzi S, Iorizzo M. Source: Dermatologic Clinics. 2003 July; 21(3): 491-7, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956201&dopt=Abstract

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Trends in frequency and in vitro susceptibilities to antifungal agents, including voriconazole and anidulafungin, of Candida bloodstream isolates. Results from a sixyear study (1996-2001). Author(s): Marco F, Danes C, Almela M, Jurado A, Mensa J, de la Bellacasa JP, Espasa M, Martinez JA, Jimenez de Anta MT. Source: Diagnostic Microbiology and Infectious Disease. 2003 August; 46(4): 259-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944017&dopt=Abstract

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Ty3/gypsy-like retrotransposons in Candida albicans and Candida dubliniensis: Tca3 and Tcd3. Author(s): Goodwin TJ, Dalle Nogare DE, Butler MI, Poulter RT. Source: Yeast (Chichester, England). 2003 April 30; 20(6): 493-508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722183&dopt=Abstract

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Ura-status-dependent adhesion of Candida albicans mutants. Author(s): Bain JM, Stubberfield C, Gow NA. Source: Fems Microbiology Letters. 2001 November 13; 204(2): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731143&dopt=Abstract

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Urbanization and baseline prevalence of genital infections including Candida, Trichomonas, and human papillomavirus and of a disturbed vaginal ecology as established in the Dutch Cervical Screening Program. Author(s): Boon ME, van Ravenswaay Claasen HH, Kok LP. Source: American Journal of Obstetrics and Gynecology. 2002 August; 187(2): 365-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193926&dopt=Abstract

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Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection. Author(s): Eisen DP, Bartley PB, Hope W, Sigmundsdottir G, Pehrson C, Larsson L, Christensson B. Source: Diagnostic Microbiology and Infectious Disease. 2002 January; 42(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821170&dopt=Abstract

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Use of amplified fragment length polymorphism analysis to identify medically important Candida spp., including C. dubliniensis. Author(s): Borst A, Theelen B, Reinders E, Boekhout T, Fluit AC, Savelkoul PH. Source: Journal of Clinical Microbiology. 2003 April; 41(4): 1357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682114&dopt=Abstract

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Use of Fourier-transform infrared spectroscopy for typing of Candida albicans strains isolated in intensive care units. Author(s): Sandt C, Sockalingum GD, Aubert D, Lepan H, Lepouse C, Jaussaud M, Leon A, Pinon JM, Manfait M, Toubas D. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 954-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624015&dopt=Abstract

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Usefulness of multilocus sequence typing for characterization of clinical isolates of Candida albicans. Author(s): Bougnoux ME, Morand S, d'Enfert C. Source: Journal of Clinical Microbiology. 2002 April; 40(4): 1290-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923347&dopt=Abstract

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Uses and limitations of the XTT assay in studies of Candida growth and metabolism. Author(s): Kuhn DM, Balkis M, Chandra J, Mukherjee PK, Ghannoum MA. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 506-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517908&dopt=Abstract

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Vaginal and oral epithelial cell anti-Candida activity. Author(s): Nomanbhoy F, Steele C, Yano J, Fidel PL Jr. Source: Infection and Immunity. 2002 December; 70(12): 7081-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438389&dopt=Abstract

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Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy. Author(s): Singh S, Sobel JD, Bhargava P, Boikov D, Vazquez JA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 November 1; 35(9): 1066-70. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384840&dopt=Abstract

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Variation in random amplified polymorphic DNA (RAPD) profiles specific to fluconazole-resistant and -sensitive strains of Candida albicans. Author(s): Jain P, Khan ZK, Bhattacharya E, Ranade SA. Source: Diagnostic Microbiology and Infectious Disease. 2001 November; 41(3): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750163&dopt=Abstract

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Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location. Author(s): Pfaller MA, Messer SA, Boyken L, Tendolkar S, Hollis RJ, Diekema DJ. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734273&dopt=Abstract

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Virulence in Candida species. Author(s): Haynes K. Source: Trends in Microbiology. 2001 December; 9(12): 591-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728872&dopt=Abstract

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Visual and anatomical outcome following submacular surgery for choroidal neovascularization secondary to Candida endophthalmitis. Author(s): Recchia FM, Shah GK, Eagle RC, Sivalingam A, Fischer DH. Source: Retina (Philadelphia, Pa.). 2002 June; 22(3): 323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055466&dopt=Abstract

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Voriconazole and fluconazole susceptibility of Candida isolates. Author(s): Pelletier R, Loranger L, Marcotte H, De Carolis E. Source: Journal of Medical Microbiology. 2002 June; 51(6): 479-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018654&dopt=Abstract

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Vulvovaginal carriage of yeasts other than Candida albicans. Author(s): Holland J, Young ML, Lee O, C-A Chen S. Source: Sexually Transmitted Infections. 2003 June; 79(3): 249-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794215&dopt=Abstract

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Vulvovaginitis due to fluconazole resistant Candida albicans following self treatment with non-prescribed triazoles. Author(s): Dorrell L, Edwards A. Source: Sexually Transmitted Infections. 2002 August; 78(4): 308-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181480&dopt=Abstract

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What's your assessment? Candida balanitis. Author(s): Bielan B. Source: Dermatology Nursing / Dermatology Nurses' Association. 2003 April; 15(2): 134, 170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751348&dopt=Abstract

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When candida turns deadly. Author(s): Randolph S. Source: Rn. 2002 March; 65(3): 41-4; Quiz 45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961868&dopt=Abstract

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White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Author(s): Miller MG, Johnson AD. Source: Cell. 2002 August 9; 110(3): 293-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176317&dopt=Abstract

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Yeasts of the genus Candida are the dominant cause of onychomycosis in Libyan women but not men: results of a 2-year surveillance study. Author(s): Ellabib MS, Agaj M, Khalifa Z, Kavanagh K. Source: The British Journal of Dermatology. 2002 June; 146(6): 1038-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072073&dopt=Abstract

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

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

7

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

154 Candida

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

A yeast for all reasons or is candidiasis the hidden enemy? Source: Palmer, C.A. Dwyer, J.T. Nutrition-today (USA). (June 1993). volume 28(3) page 24-29.

Additional consumer oriented references include: •

A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-gamma- and interleukin-13-treated murine peritoneal macrophages. Author(s): Laboratoire des Macrophages, Mediateurs de l'Inflammation et Interactions Cellulaires, UPRES-EA 2405, INSERM IFR 31, C.H.U., Rangueil, 1 avenue Jean Poulhes, Tolouse, France. Source: Coste, A Linas, M D Cassaing, S Bernad, J Chalmeton, S Seguela, J P Pipy, B JAntimicrob-Chemother. 2002 May; 49(5): 731-40 0305-7453

•

Acidic polysaccharides from rhizomes of Atractylodes lancea as protective principle in Candida-lnfected mice. Author(s): Kampo & Pharmacognosy Laboratory, Tsumura & Co., Ibaraki, Japan. [email protected] Source: Inagaki, N Komatsu, Y Sasaki, H Kiyohara, H Yamada, H Ishibashi, H Tansho, S Yamaguchi, H Abe, S Planta-Med. 2001 July; 67(5): 428-31 0032-0943

•

Antifungal activity of propolis on different species of Candida. Author(s): Dental School, UNESP, Sao Jose dos Campos, SP, Brasil. Source: Ota, C Unterkircher, C Fantinato, V Shimizu, M T Mycoses. 2001 November; 44(9-10): 375-8 0933-7407

•

Application of Candida solubilized cell wall beta-glucan in antitumor immunotherapy against P815 mastocytoma in mice. Author(s): Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. Source: Tokunaka, Kazuhiro Ohno, Naohito Adachi, Yoshiyuki Miura, Noriko N Yadomae, Toshiro Int-Immunopharmacol. 2002 January; 2(1): 59-67 1567-5769

•

Arbortristosides modulate murine peritoneal macrophages for phagocytosis and intracellular killing of Candida albicans. Source: Gyanchandani, A. Khan, Z.K. Maitra, S.C. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. December 2000. volume 38 (5) page 340-352. 1388-0209

•

Bioavailability and ecological effects of cadmium on Folsomia candida (Willem) in an artificial soil substrate as influenced by pH and organic matter. Source: Crommentuijn, T. Doornekamp, A. Gestel, C.A.M. van. Agric,-ecosyst-environ,Appl-soil-ecol. Amsterdam : Elsevier Science B. V., c1994-. June 1997. volume 5 (3) page 261-271. 0929-1393

•

Blocking the tunnel: engineering of Candida rugosa lipase mutants with short chain length specificity. Author(s): Institute of Technical Biology, University of Stuttgart, Allmandring 31, D70569 Stuttgart, Germany. Source: Schmitt, J Brocca, S Schmid, R D Pleiss, J Protein-Eng. 2002 July; 15(7): 595-601 0269-2139

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•

Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine, serine, or alanine patches. Author(s): Research Service, VA Medical Center, Kansas City, MO, University of Kansas School of Medicine, Kansas City, KS, USA. Source: Gaur, N K Smith, R L Klotz, S A Cell-Commun-Adhes. 2002 Jan-February; 9(1): 45-57

•

Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Author(s): University of Hacettepe, School of Health Services, Department of Microbiology and Clinical Microbiology, Ankara, Turkey. Source: Ergin, A Arikan, S J-Chemother. 2002 October; 14(5): 465-72 1120-009X

•

Does gastrointestinal Candida albicans prevent ubiquinone absorption? Author(s): Applied Research Institute, Palmerston North, New Zealand Source: Krone, C A Elmer, G W Ely, J T Fudenberg, H H Thoreson, J Med-Hypotheses. 2001 November; 57(5): 570-2 0306-9877

•

Effect of commercial ethanol propolis extract on the in vitro growth of Candida albicans collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis. Author(s): Department of Clinical Pathology and Surgery, School of Dentistry, Minas Gerais Federal University, Belo Horizonte, Brazil. Source: Martins, Rachel S Pereira, Erika S J Jr Lima, Sergio M Senna, Maria I B Mesquita, Ricardo A Santos, Vagner R J-Oral-Sci. 2002 Mar; 44(1): 41-8 1343-4934

•

Effect of sodium hypochlorite and five intracanal medications on Candida albicans in root canals. Author(s): Department of Endodontics, School of Dentistry, Paulista State University (UNESP), SP, Brazil. Source: Valera, M C de Moraes Rego, J Jorge, A O J-Endod. 2001 June; 27(6): 401-3 00992399

•

Endocytosis of Candida albicans by vascular endothelial cells is associated with tyrosine phosphorylation of specific host cell proteins. Author(s): St John's Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA. Source: Belanger, P H Johnston, D A Fratti, R A Zhang, M Filler, S G Cell-Microbiol. 2002 December; 4(12): 805-12 1462-5814

•

Glycerol production by a novel osmotolerant yeast Candida glycerinogenes. Author(s): Research Center of Industrial Microorganisms and Research and Design Center of Glycerol Fermentation, School of Biotechnology, South-Yangtze University, Wuxi, China. [email protected] Source: Zhuge, J Fang, H Y Wang, Z X Chen, D Z Jin, H R Gu, H L Appl-MicrobiolBiotechnol. 2001 June; 55(6): 686-92 0175-7598

•

Growth inhibition effect of Brazilian cerrado plant extracts on Candida species. Source: Silva, M.V. Costa, T.R. Costa, M.R. Ferreira, E.C. Fernandes, O.F.L. Santos, S.C. Liao, L.M. Ferri, P.H. Paula, J.R. Ferreira, H.D. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. April 2001. volume39 (2) page 138-141. 1388-0209

156 Candida

•

Growth of Albugo candida infected mustard callus in culture. Author(s): Pathology and Tissue Culture Laboratory, Department of Botany, University of Rajasthan, Jaipur, India. [email protected] Source: Nath, M D Sharma, S L Kant, U Mycopathologia. 2001; 152(3): 147-53 0301-486X

•

Impact of lysozyme and lactoferrin on oral Candida isolates exposed to polyene antimycotics and fluconazole. Author(s): Oral Bio-Sciences, Faculty of Dentistry, University of Hong Kong. Source: Anil, S Samaranayake, L P Oral-Dis. 2002 July; 8(4): 199-206 1354-523X

•

In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. Author(s): Institute of Microbiology, University La Sapienza, Rome, Italy. Source: D'Auria, F D Laino, L Strippoli, V Tecca, M Salvatore, G Battinelli, L Mazzanti, G J-Chemother. 2001 August; 13(4): 377-83 1120-009X

•

In vitro activity of three new triazoles and one echinocandin against Candida bloodstream isolates from cancer patients. Author(s): Department of Microbiology-Infectious Diseases, Hopital MaisonneuveRosemont, 5415 Boulevard l'Assomption, Montreal, Quebec H1T 2M4. [email protected] Source: Laverdiere, M Hoban, D Restieri, C Habel, F J-Antimicrob-Chemother. 2002 July; 50(1): 119-23 0305-7453

•

Indian medicinal plants: a potential source for anticandidal drugs. Source: Mehmood, Z. Ahmad, I. Mohammad, F. Ahmad, S. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. July 1999. volume 37 (3) page 237-242. 13880209

•

Influence of methylfenpropidine on growth, sterol content and fatty acid composition of Candida albicans. Author(s): Department of Biochemical Technology, Slovak University of Technology, 812 37 Bratislava. [email protected] Source: Sajbidor, J Breierova, E Lamacka, M Bohov, P Folia-Microbiol-(Praha). 2000; 45(4): 313-9 0015-5632

•

Involvement of alpha(v)beta3 integrin-like receptor and glycosaminoglycans in Candida albicans germ tube adhesion to vitronectin and to a human endothelial cell line. Author(s): Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Camerino, Italy. [email protected] Source: Santoni, G Spreghini, E Lucciarini, R Amantini, C Piccoli, M Microb-Pathog. 2001 October; 31(4): 159-72 0882-4010

•

Mycological and cytological examination of oral candidal carriage in diabetic patients and non-diabetic control subjects: thorough analysis of local aetiologic and systemic factors. Author(s): Department of Microbiology, Marmara University, Istanbul, Turkey. [email protected] Source: Kadir, T Pisiriciler, R Akyuz, S Yarat, A Emekli, N Ipbuker, A J-Oral-Rehabil. 2002 May; 29(5): 452-7 0305-182X

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•

Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii. Author(s): National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, Thad Cochran Research Center, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA. Source: Zhang, Zhizhen ElSohly, Hala N Jacob, Melissa R Pasco, David S Walker, Larry A Clark, Alice M Planta-Med. 2002 January; 68(1): 49-54 0032-0943

•

Respiratory chain network in mitochondria of Candida parapsilosis: ADP/O appraisal of the multiple electron pathways. Author(s): Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, SP, Brazil. Source: Milani, G Jarmuszkiewicz, W Sluse Goffart, C M Schreiber, A Z Vercesi, A E Sluse, F E FEBS-Lett. 2001 November 16; 508(2): 231-5 0014-5793

•

The non-steroidal anti-inflammatory drug niflumic acid inhibits Candida albicans growth. Author(s): Department of Plant Sciences, University of Cambridge, United Kingdom. Source: Baker, A Northrop, F D Miedema, H Devine, G R Davies, J M Mycopathologia. 2002; 153(1): 25-8 0301-486X

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

Copper complexes with bioactive ligands, 1: Antimicrobial activity. Author(s): Slovenska Technicka Univ., Bratislava (Slovak Republic). Fakulta Chemickej a Potravinarskej Technologie Source: Dudova, B. Hudecova, D. Pokorny, R. Mikulasova, M. Palicova, M. Segla, P. Melnik, M. Folia-Microbiologica (Czech Republic). (October 2001). volume 46(5) page 379-384.

•

Mycoses part-1: Antimycotic effect of Azadirachta indica on Candida albicans. Author(s): Hamdard Univ., Karachi (Pakistan). Bait-al-Hikmah Research Inst. Source: Khan, M. Zubairy, H.N. Hamdard-Medicus (Pakistan). (Oct-December 1998). volume 41(4) page 33-34.

Additional physician-oriented references include: •

A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-gamma- and interleukin-13-treated murine peritoneal macrophages. Author(s): Laboratoire des Macrophages, Mediateurs de l'Inflammation et Interactions Cellulaires, UPRES-EA 2405, INSERM IFR 31, C.H.U., Rangueil, 1 avenue Jean Poulhes, Tolouse, France. Source: Coste, A Linas, M D Cassaing, S Bernad, J Chalmeton, S Seguela, J P Pipy, B JAntimicrob-Chemother. 2002 May; 49(5): 731-40 0305-7453

•

Acidic polysaccharides from rhizomes of Atractylodes lancea as protective principle in Candida-lnfected mice. Author(s): Kampo & Pharmacognosy Laboratory, Tsumura & Co., Ibaraki, Japan. [email protected] Source: Inagaki, N Komatsu, Y Sasaki, H Kiyohara, H Yamada, H Ishibashi, H Tansho, S Yamaguchi, H Abe, S Planta-Med. 2001 July; 67(5): 428-31 0032-0943

•

Antifungal activity of propolis on different species of Candida. Author(s): Dental School, UNESP, Sao Jose dos Campos, SP, Brasil.

158 Candida

Source: Ota, C Unterkircher, C Fantinato, V Shimizu, M T Mycoses. 2001 November; 44(9-10): 375-8 0933-7407 •

Application of Candida solubilized cell wall beta-glucan in antitumor immunotherapy against P815 mastocytoma in mice. Author(s): Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. Source: Tokunaka, Kazuhiro Ohno, Naohito Adachi, Yoshiyuki Miura, Noriko N Yadomae, Toshiro Int-Immunopharmacol. 2002 January; 2(1): 59-67 1567-5769

•

Arbortristosides modulate murine peritoneal macrophages for phagocytosis and intracellular killing of Candida albicans. Source: Gyanchandani, A. Khan, Z.K. Maitra, S.C. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. December 2000. volume 38 (5) page 340-352. 1388-0209

•

Bioavailability and ecological effects of cadmium on Folsomia candida (Willem) in an artificial soil substrate as influenced by pH and organic matter. Source: Crommentuijn, T. Doornekamp, A. Gestel, C.A.M. van. Agric,-ecosyst-environ,Appl-soil-ecol. Amsterdam : Elsevier Science B. V., c1994-. June 1997. volume 5 (3) page 261-271. 0929-1393

•

Blocking the tunnel: engineering of Candida rugosa lipase mutants with short chain length specificity. Author(s): Institute of Technical Biology, University of Stuttgart, Allmandring 31, D70569 Stuttgart, Germany. Source: Schmitt, J Brocca, S Schmid, R D Pleiss, J Protein-Eng. 2002 July; 15(7): 595-601 0269-2139

•

Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine, serine, or alanine patches. Author(s): Research Service, VA Medical Center, Kansas City, MO, University of Kansas School of Medicine, Kansas City, KS, USA. Source: Gaur, N K Smith, R L Klotz, S A Cell-Commun-Adhes. 2002 Jan-February; 9(1): 45-57

•

Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Author(s): University of Hacettepe, School of Health Services, Department of Microbiology and Clinical Microbiology, Ankara, Turkey. Source: Ergin, A Arikan, S J-Chemother. 2002 October; 14(5): 465-72 1120-009X

•

Does gastrointestinal Candida albicans prevent ubiquinone absorption? Author(s): Applied Research Institute, Palmerston North, New Zealand Source: Krone, C A Elmer, G W Ely, J T Fudenberg, H H Thoreson, J Med-Hypotheses. 2001 November; 57(5): 570-2 0306-9877

•

Effect of commercial ethanol propolis extract on the in vitro growth of Candida albicans collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis. Author(s): Department of Clinical Pathology and Surgery, School of Dentistry, Minas Gerais Federal University, Belo Horizonte, Brazil. Source: Martins, Rachel S Pereira, Erika S J Jr Lima, Sergio M Senna, Maria I B Mesquita, Ricardo A Santos, Vagner R J-Oral-Sci. 2002 Mar; 44(1): 41-8 1343-4934

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•

Effect of sodium hypochlorite and five intracanal medications on Candida albicans in root canals. Author(s): Department of Endodontics, School of Dentistry, Paulista State University (UNESP), SP, Brazil. Source: Valera, M C de Moraes Rego, J Jorge, A O J-Endod. 2001 June; 27(6): 401-3 00992399

•

Endocytosis of Candida albicans by vascular endothelial cells is associated with tyrosine phosphorylation of specific host cell proteins. Author(s): St John's Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA. Source: Belanger, P H Johnston, D A Fratti, R A Zhang, M Filler, S G Cell-Microbiol. 2002 December; 4(12): 805-12 1462-5814

•

Glycerol production by a novel osmotolerant yeast Candida glycerinogenes. Author(s): Research Center of Industrial Microorganisms and Research and Design Center of Glycerol Fermentation, School of Biotechnology, South-Yangtze University, Wuxi, China. [email protected] Source: Zhuge, J Fang, H Y Wang, Z X Chen, D Z Jin, H R Gu, H L Appl-MicrobiolBiotechnol. 2001 June; 55(6): 686-92 0175-7598

•

Growth inhibition effect of Brazilian cerrado plant extracts on Candida species. Source: Silva, M.V. Costa, T.R. Costa, M.R. Ferreira, E.C. Fernandes, O.F.L. Santos, S.C. Liao, L.M. Ferri, P.H. Paula, J.R. Ferreira, H.D. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. April 2001. volume39 (2) page 138-141. 1388-0209

•

Growth of Albugo candida infected mustard callus in culture. Author(s): Pathology and Tissue Culture Laboratory, Department of Botany, University of Rajasthan, Jaipur, India. [email protected] Source: Nath, M D Sharma, S L Kant, U Mycopathologia. 2001; 152(3): 147-53 0301-486X

•

Impact of lysozyme and lactoferrin on oral Candida isolates exposed to polyene antimycotics and fluconazole. Author(s): Oral Bio-Sciences, Faculty of Dentistry, University of Hong Kong. Source: Anil, S Samaranayake, L P Oral-Dis. 2002 July; 8(4): 199-206 1354-523X

•

In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. Author(s): Institute of Microbiology, University La Sapienza, Rome, Italy. Source: D'Auria, F D Laino, L Strippoli, V Tecca, M Salvatore, G Battinelli, L Mazzanti, G J-Chemother. 2001 August; 13(4): 377-83 1120-009X

•

Indian medicinal plants: a potential source for anticandidal drugs. Source: Mehmood, Z. Ahmad, I. Mohammad, F. Ahmad, S. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. July 1999. volume 37 (3) page 237-242. 13880209

•

Influence of methylfenpropidine on growth, sterol content and fatty acid composition of Candida albicans. Author(s): Department of Biochemical Technology, Slovak University of Technology, 812 37 Bratislava. [email protected] Source: Sajbidor, J Breierova, E Lamacka, M Bohov, P Folia-Microbiol-(Praha). 2000; 45(4): 313-9 0015-5632

160 Candida

•

Involvement of alpha(v)beta3 integrin-like receptor and glycosaminoglycans in Candida albicans germ tube adhesion to vitronectin and to a human endothelial cell line. Author(s): Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Camerino, Italy. [email protected] Source: Santoni, G Spreghini, E Lucciarini, R Amantini, C Piccoli, M Microb-Pathog. 2001 October; 31(4): 159-72 0882-4010

•

Mycological and cytological examination of oral candidal carriage in diabetic patients and non-diabetic control subjects: thorough analysis of local aetiologic and systemic factors. Author(s): Department of Microbiology, Marmara University, Istanbul, Turkey. [email protected] Source: Kadir, T Pisiriciler, R Akyuz, S Yarat, A Emekli, N Ipbuker, A J-Oral-Rehabil. 2002 May; 29(5): 452-7 0305-182X

•

Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii. Author(s): National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, Thad Cochran Research Center, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA. Source: Zhang, Zhizhen ElSohly, Hala N Jacob, Melissa R Pasco, David S Walker, Larry A Clark, Alice M Planta-Med. 2002 January; 68(1): 49-54 0032-0943

•

Respiratory chain network in mitochondria of Candida parapsilosis: ADP/O appraisal of the multiple electron pathways. Author(s): Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, SP, Brazil. Source: Milani, G Jarmuszkiewicz, W Sluse Goffart, C M Schreiber, A Z Vercesi, A E Sluse, F E FEBS-Lett. 2001 November 16; 508(2): 231-5 0014-5793

•

The non-steroidal anti-inflammatory drug niflumic acid inhibits Candida albicans growth. Author(s): Department of Plant Sciences, University of Cambridge, United Kingdom. Source: Baker, A Northrop, F D Miedema, H Devine, G R Davies, J M Mycopathologia. 2002; 153(1): 25-8 0301-486X

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

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

•

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

•

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

•

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

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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/

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to Candida; 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: •

Minerals Betaine Hydrochloride Source: Prima Communications, Inc.www.personalhealthzone.com Iodine Source: Integrative Medicine Communications; www.drkoop.com

•

Food and Diet Bluefish Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,164,00.html Chicken Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

162 Candida

Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,86,00.html Cinnamon Alternative names: Cinnamomum zeylanicum Source: Healthnotes, Inc.; www.healthnotes.com Crème Fraîche Source: Healthnotes, Inc.; www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Garlic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html Honey Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,283,00.html Juices Source: Healthnotes, Inc.; www.healthnotes.com Kefir Source: Healthnotes, Inc.; www.healthnotes.com Lhassi Source: Healthnotes, Inc.; www.healthnotes.com Milk Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Cheese Source: Healthnotes, Inc.; www.healthnotes.com

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

5-Fluorocytosine antagonizes the action of sterol biosynthesis inhibitors in Candida glabrata. Author(s): Siau H, Kerridge D. Source: The Journal of Antimicrobial Chemotherapy. 1999 June; 43(6): 767-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404315&dopt=Abstract

•

A bioactive seco-rosane diterpenoid from Vellozia candida. Author(s): Valente LM, Gunatilaka AA, Kingston DG, Patitucci ML, Pinto AC. Source: Journal of Natural Products. 1997 May; 60(5): 478-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9170291&dopt=Abstract

•

A novel mechanism of fluconazole resistance associated with fluconazole sequestration in Candida albicans isolates from a myelofibrosis patient. Author(s): Maebashi K, Kudoh M, Nishiyama Y, Makimura K, Uchida K, Mori T, Yamaguchi H.

164 Candida

Source: Microbiology and Immunology. 2002; 46(5): 317-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139391&dopt=Abstract •

Accumulation of 3-ketosteroids induced by itraconazole in azole-resistant clinical Candida albicans isolates. Author(s): Marichal P, Gorrens J, Laurijssens L, Vermuyten K, Van Hove C, Le Jeune L, Verhasselt P, Sanglard D, Borgers M, Ramaekers FC, Odds F, Vanden Bossche H. Source: Antimicrobial Agents and Chemotherapy. 1999 November; 43(11): 2663-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10543744&dopt=Abstract

•

Acidic polysaccharides from rhizomes of Atractylodes lancea as protective principle in Candida-lnfected mice. Author(s): Inagaki N, Komatsu Y, Sasaki H, Kiyohara H, Yamada H, Ishibashi H, Tansho S, Yamaguchi H, Abe S. Source: Planta Medica. 2001 July; 67(5): 428-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488456&dopt=Abstract

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Adherence of platelets to Candida species in vivo. Author(s): Robert R, Nail S, Marot-Leblond A, Cottin J, Miegeville M, Quenouillere S, Mahaza C, Senet JM. Source: Infection and Immunity. 2000 February; 68(2): 570-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639419&dopt=Abstract

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Anticandidal activity of certain South Indian medicinal plants. Author(s): Vaijayanthimala J, Anandi C, Udhaya V, Pugalendi KV. Source: Phytotherapy Research : Ptr. 2000 May; 14(3): 207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815017&dopt=Abstract

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Anticandidal activity of Santolina chamaecyparissus volatile oil. Author(s): Suresh B, Sriram S, Dhanaraj SA, Elango K, Chinnaswamy K. Source: Journal of Ethnopharmacology. 1997 January; 55(2): 151-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9032628&dopt=Abstract

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Anticandidal and antidermatophytic activity of Cinnamomum species essential oils. Author(s): Mastura M, Nor Azah MA, Khozirah S, Mawardi R, Manaf AA. Source: Cytobios. 1999; 98(387): 17-23. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10490360&dopt=Abstract

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Anticholinergic poisoning due to Datura candida. Author(s): Finlay P.

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Source: Trop Doct. 1998 July; 28(3): 183-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700295&dopt=Abstract •

Antifungal activity of plant extracts against Candida albicans. Author(s): Perez C, Suarez C. Source: The American Journal of Chinese Medicine. 1997; 25(2): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288365&dopt=Abstract

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Antifungal activity of propolis on different species of Candida. Author(s): Ota C, Unterkircher C, Fantinato V, Shimizu MT. Source: Mycoses. 2001 November; 44(9-10): 375-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766101&dopt=Abstract

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Bioactivity of nickel(II) complex containing N-glycosides derived from Dglucosamine and ethylenediamine against pathogenic yeast, Candida albicans. Author(s): Yano S, Inoue S, Nouchi R, Kato M, Suzuki T. Source: Biological & Pharmaceutical Bulletin. 1995 June; 18(6): 923-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7550136&dopt=Abstract

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Biological behavior of plasmid in Rhizobium sp. strain S25 from Tephrosia candida. Author(s): Zou X, Feng XL, Chen WX, Li FD. Source: Plasmid. 1998 September; 40(2): 158-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9735317&dopt=Abstract

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Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line. Author(s): Santoni G, Lucciarini R, Amantini C, Jacobelli J, Spreghini E, Ballarini P, Piccoli M, Gismondi A. Source: Infection and Immunity. 2002 July; 70(7): 3804-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065524&dopt=Abstract

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Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. Author(s): Sanglard D, Ischer F, Parkinson T, Falconer D, Bille J. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2404-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878497&dopt=Abstract

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Candida famata fungemia in a cancer patient: case report. Author(s): Krcmery V, Kunova A.

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Source: Journal of Chemotherapy (Florence, Italy). 2000 April; 12(2): 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789561&dopt=Abstract •

Carvone and perillaldehyde interfere with the serum-induced formation of filamentous structures in Candida albicans at substantially lower concentrations than those causing significant inhibition of growth. Author(s): McGeady P, Wansley DL, Logan DA. Source: Journal of Natural Products. 2002 July; 65(7): 953-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141851&dopt=Abstract

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Cell-associated collagenolytic activity by Candida albicans. Author(s): Nishimura M, Nikawa H, Yamashiro H, Nishimura H, Hamada T, Embery G. Source: Mycopathologia. 2002; 153(3): 125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998872&dopt=Abstract

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Characterization and optimization of in vitro assay conditions for (1,3)beta-glucan synthase activity from Aspergillus fumigatus and Candida albicans for enzyme inhibition screening. Author(s): Wood RL, Miller TK, Wright A, McCarthy P, Taft CS, Pomponi S, Selitrennikoff CP. Source: J Antibiot (Tokyo). 1998 July; 51(7): 665-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9727393&dopt=Abstract

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Chemical composition and antifungal activity of the essential oil of Origanum virens on Candida species. Author(s): Salgueiro LR, Cavaleiro C, Pinto E, Pina-Vaz C, Rodrigues AG, Palmeira A, Tavares C, Costa-de-Oliveira S, Goncalves MJ, Martinez-de-Oliveira J. Source: Planta Medica. 2003 September; 69(9): 871-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598221&dopt=Abstract

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Chronic episodic diarrhoea associated with apparent intestinal colonisation by the yeasts Saccharomyces cerevisiae and Candida famata in a German shepherd dog. Author(s): Milner RJ, Picard J, Tustin R. Source: J S Afr Vet Assoc. 1997 December; 68(4): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9561501&dopt=Abstract

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Coaggregation of Candida albicans with oral Actinomyces species. Author(s): Grimaudo NJ, Nesbitt WE, Clark WB. Source: Oral Microbiology and Immunology. 1996 February; 11(1): 59-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8604256&dopt=Abstract

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Coaggregation of Candida dubliniensis with Fusobacterium nucleatum. Author(s): Jabra-Rizk MA, Falkler WA Jr, Merz WG, Kelley JI, Baqui AA, Meiller TF.

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Source: Journal of Clinical Microbiology. 1999 May; 37(5): 1464-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203506&dopt=Abstract •

Comparison of D0870, a new triazole antifungal agent, to fluconazole for inhibition of Candida albicans cytochrome P-450 by using in vitro assays. Author(s): Venkateswarlu K, Denning DW, Manning NJ, Kelly SL. Source: Antimicrobial Agents and Chemotherapy. 1996 June; 40(6): 1382-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8726005&dopt=Abstract

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Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Author(s): Ergin A, Arikan S. Source: Journal of Chemotherapy (Florence, Italy). 2002 October; 14(5): 465-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462426&dopt=Abstract

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Comparison of responses of DNA topoisomerase I from Candida albicans and human cells to four new agents which stimulate topoisomerase-dependent DNA nicking. Author(s): Fostel J, Montgomery D, Lartey P. Source: Fems Microbiology Letters. 1996 May 1; 138(2-3): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9026436&dopt=Abstract

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Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Author(s): Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, Harrison LH, Sofair AN, Warnock DW; Candidemia Active Surveillance Group. Source: Antimicrobial Agents and Chemotherapy. 2002 August; 46(8): 2477-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121921&dopt=Abstract

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Composition and antibacterial activity of the essential oils of Stachys candida and S. chrysantha from southern Greece. Author(s): Skaltsa HD, Lazari DM, Chinou IB, Loukis AE. Source: Planta Medica. 1999 April; 65(3): 255-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10232072&dopt=Abstract

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Cytotoxicity of triterpenoid saponins. Part 2: Relationships between the structures of glycosides of polygalacic acid and their activities against pathogenic Candida species. Author(s): Bader G, Seibold M, Tintelnot K, Hiller K. Source: Pharmazie. 2000 January; 55(1): 72-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10683877&dopt=Abstract

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Detection of beta-1,2-mannosyltransferase in Candida albicans cells. Author(s): Suzuki A, Takata Y, Oshie A, Tezuka A, Shibata N, Kobayashi H, Okawa Y, Suzuki S. Source: Febs Letters. 1995 October 16; 373(3): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7589482&dopt=Abstract

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Dietary vitamin E supplementation does not inhibit Candida albicans intestinal translocation in rats. Author(s): Morandi MV, Martinez R, Vannucchi H. Source: J Nutr Sci Vitaminol (Tokyo). 1999 April; 45(2): 153-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10450556&dopt=Abstract

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Different adhesins for type IV collagen on Candida albicans: identification of a lectin-like adhesin recognizing the 7S(IV) domain. Author(s): Alonso R, Llopis I, Flores C, Murgui A, Timoneda J. Source: Microbiology (Reading, England). 2001 July; 147(Pt 7): 1971-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429474&dopt=Abstract

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Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans. Author(s): Park KS, Kang KC, Kim JH, Adams DJ, Johng TN, Paik YK. Source: The Journal of Antimicrobial Chemotherapy. 1999 May; 43(5): 667-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382888&dopt=Abstract

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Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae. Author(s): Young LY, Hull CM, Heitman J. Source: Antimicrobial Agents and Chemotherapy. 2003 September; 47(9): 2717-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936965&dopt=Abstract

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Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of amphotericin B. Author(s): Geraghty P, Kavanagh K. Source: Archives of Microbiology. 2003 April; 179(4): 295-300. Epub 2003 March 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640519&dopt=Abstract

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DNA-dependent RNA polymerase II from Candida species is a multiple zinccontaining metalloenzyme. Author(s): Patturajan M, Sevugan M, Chatterji D. Source: Iubmb Life. 1999 August; 48(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10794592&dopt=Abstract

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Effect of commercial ethanol propolis extract on the in vitro growth of Candida albicans collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis. Author(s): Martins RS, Pereira ES Jr, Lima SM, Senna MI, Mesquita RA, Santos VR. Source: J Oral Sci. 2002 March; 44(1): 41-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058869&dopt=Abstract

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Effect of fluconazole on the growth and adhesion of Candida albicans in the presence of antineoplastic agents. Author(s): Fekete-Forgacs K, Kis B, Nagy G, Lenkey B. Source: Journal of Basic Microbiology. 1999; 39(5-6): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629971&dopt=Abstract

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Effect of Inula viscosa extract on chitin synthesis in dermatophytes and Candida albicans. Author(s): Maoz M, Neeman I. Source: Journal of Ethnopharmacology. 2000 August; 71(3): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10940586&dopt=Abstract

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Effect of peroxisomicine A2 and T 544 of the genus Karwinskia on peroxisomes of Candida boidinii. Author(s): Salazar-Aranda R, Sepulveda-Saavedra J, Waksman de Torres N, PineyroLopez A, Moreno-Sepulveda M. Source: Fems Microbiology Letters. 1998 January 15; 158(2): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9465396&dopt=Abstract

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Effects of glycyrrhizin, an active component of licorice roots, on Candida albicans infection in thermally injured mice. Author(s): Utsunomiya T, Kobayashi M, Herndon DN, Pollard RB, Suzuki F. Source: Clinical and Experimental Immunology. 1999 May; 116(2): 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10337021&dopt=Abstract

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Efficacy of parenteral itraconazole against disseminated Candida albicans infection in two mouse strains. Author(s): MacCallum DM, Odds FC. Source: The Journal of Antimicrobial Chemotherapy. 2002 August; 50(2): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161403&dopt=Abstract

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Endocytosis of Candida albicans by vascular endothelial cells is associated with tyrosine phosphorylation of specific host cell proteins. Author(s): Belanger PH, Johnston DA, Fratti RA, Zhang M, Filler SG.

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Source: Cellular Microbiology. 2002 December; 4(12): 805-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464011&dopt=Abstract •

Enhanced antifungal activity of ketoconazole by Euphorbia characias latex against Candida albicans. Author(s): Giordani R, Trebaux J, Masi M, Regli P. Source: Journal of Ethnopharmacology. 2001 November; 78(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585681&dopt=Abstract

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Enzymatic hydrolysis of carotenoid fatty acid esters of red pepper (Capsicum annuum L.) by a lipase from Candida rugosa. Author(s): Breithaupt DE. Source: Z Naturforsch [c]. 2000 November-December; 55(11-12): 971-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204204&dopt=Abstract

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Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Author(s): Onyewu C, Blankenship JR, Del Poeta M, Heitman J. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 956-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604527&dopt=Abstract

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Evaluation of differential gene expression in fluconazole-susceptible and -resistant isolates of Candida albicans by cDNA microarray analysis. Author(s): Rogers PD, Barker KS. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3412-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384344&dopt=Abstract

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Expression of CDR1, a multidrug resistance gene of Candida albicans: transcriptional activation by heat shock, drugs and human steroid hormones. Author(s): Krishnamurthy S, Gupta V, Prasad R, Panwar SL, Prasad R. Source: Fems Microbiology Letters. 1998 March 15; 160(2): 191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9532737&dopt=Abstract

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Expression of the CIP1 gene induced under cadmium stress in Candida sp. Author(s): Hong YM, Park SW, Choi SY. Source: Molecules and Cells. 1998 February 28; 8(1): 84-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9571636&dopt=Abstract

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Fatty acid steryl, stanyl, and steroid esters by esterification and transesterification in vacuo using Candida rugosa lipase as catalyst. Author(s): Weber N, Weitkamp P, Mukherjee KD.

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Source: Journal of Agricultural and Food Chemistry. 2001 January; 49(1): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11170561&dopt=Abstract •

Flocculation of the yeast Candida famata (Debaryomyces hansenii): an essential role for peptone. Author(s): Cubells Martinez XC, Narbad A, Carter AT, Stratford M. Source: Yeast (Chichester, England). 1996 April; 12(5): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8740415&dopt=Abstract

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Garlic (Allium sativum) as an anti-Candida agent: a comparison of the efficacy of fresh garlic and freeze-dried extracts. Author(s): Lemar KM, Turner MP, Lloyd D. Source: Journal of Applied Microbiology. 2002; 93(3): 398-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174037&dopt=Abstract

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Genistein effects on growth and cell cycle of Candida albicans. Author(s): Yazdanyar A, Essmann M, Larsen B. Source: Journal of Biomedical Science. 2001 March-April; 8(2): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11287745&dopt=Abstract

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Glycyrrhizin improves the resistance of MAIDS mice to opportunistic infection of Candida albicans through the modulation of MAIDS-associated type 2 T cell responses. Author(s): Utsunomiya T, Kobayashi M, Ito M, Pollard RB, Suzuki F. Source: Clinical Immunology (Orlando, Fla.). 2000 May; 95(2): 145-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10779408&dopt=Abstract

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Ground red hot pepper agar in the isolation of yeasts of Candida spp. Author(s): Stepanovic S, Djukic S, Vukovic D, Mitrovic S, Babic D. Source: Journal of Medical Microbiology. 1998 November; 47(11): 1027-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9822304&dopt=Abstract

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Hydrolysis of menhaden oil by a Candida cylindracea lipase immobilized in a hollow-fiber reactor. Author(s): Rice KE, Watkins J, Hill CG Jr. Source: Biotechnology and Bioengineering. 1999 April 5; 63(1): 33-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10099579&dopt=Abstract

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Hydrolysis of steryl esters by a lipase (Lip 3) from Candida rugosa. Author(s): Tenkanen M, Kontkanen H, Isoniemi R, Spetz P, Holmbom B.

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Source: Applied Microbiology and Biotechnology. 2002 October; 60(1-2): 120-7. Epub 2002 August 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382052&dopt=Abstract •

In vitro activity of Cinnamomum zeylanicum against azole resistant and sensitive Candida species and a pilot study of cinnamon for oral candidiasis. Author(s): Quale JM, Landman D, Zaman MM, Burney S, Sathe SS. Source: The American Journal of Chinese Medicine. 1996; 24(2): 103-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8874667&dopt=Abstract

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In vitro activity of fluconazole on Candida albicans. Author(s): Abecia LC, Arevalo JM, Lopez MJ. Source: Microbiologia. 1996 December; 12(4): 613-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9018696&dopt=Abstract

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In vitro activity of Melaleuca alternifolia (tea tree) oil against bacterial and Candida spp. isolates from clinical specimens. Author(s): Banes-Marshall L, Cawley P, Phillips CA. Source: British Journal of Biomedical Science. 2001; 58(3): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575735&dopt=Abstract

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In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. Author(s): D'Auria FD, Laino L, Strippoli V, Tecca M, Salvatore G, Battinelli L, Mazzanti G. Source: Journal of Chemotherapy (Florence, Italy). 2001 August; 13(4): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589479&dopt=Abstract

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In vitro antifungal susceptibilities of Candida albicans and other fungal pathogens to polygodial, a sesquiterpene dialdehyde. Author(s): Lee SH, Lee JR, Lunde CS, Kubo I. Source: Planta Medica. 1999 April; 65(3): 204-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10232062&dopt=Abstract

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In vitro studies on colonization resistance of the human gut microbiota to Candida albicans and the effects of tetracycline and Lactobacillus plantarum LPK. Author(s): Payne S, Gibson G, Wynne A, Hudspith B, Brostoff J, Tuohy K. Source: Curr Issues Intest Microbiol. 2003 March; 4(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691257&dopt=Abstract

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In vitro synergism between nyasol, an active compound isolated from Anemarrhena asphodeloides, and azole agents against Candida albicans. Author(s): Iida Y, Oh KB, Saito M, Matsuoka H, Kurata H.

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Source: Planta Medica. 2000 June; 66(5): 435-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10909263&dopt=Abstract •

Influence of methylfenpropidine on growth, sterol content and fatty acid composition of Candida albicans. Author(s): Sajbidor J, Breierova E, Lamacka M, Bohov P. Source: Folia Microbiol (Praha). 2000; 45(4): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347252&dopt=Abstract

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Inhibition of 2,3-oxidosqualene-lanosterol cyclase in Candida albicans by pyridinium ion-based inhibitors. Author(s): Goldman RC, Zakula D, Capobianco JO, Sharpe BA, Griffin JH. Source: Antimicrobial Agents and Chemotherapy. 1996 April; 40(4): 1044-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8849227&dopt=Abstract

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Inhibition of Candida rugosa lipase by berberine and structurally related alkaloids, evaluated by high-performance liquid chromatography. Author(s): Grippa E, Valla R, Battinelli L, Mazzanti G, Saso L, Silvestrini B. Source: Bioscience, Biotechnology, and Biochemistry. 1999 September; 63(9): 1557-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10540743&dopt=Abstract

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Inhibition of germ tube formation, filamentation and ergosterol biosynthesis in Candida albicans treated with 6-amino-2-n-pentylthiobenzothiazole. Author(s): Fabry S, Gaborova S, Bujdakova H, Klobusicky M, Vollekova A, Kuchta T. Source: Folia Microbiol (Praha). 1999; 44(5): 523-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997135&dopt=Abstract

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Inhibition of sterol 14 alpha-demethylation of Candida albicans with NND-502, a novel optically active imidazole antimycotic agent. Author(s): Niwano Y, Koga H, Kodama H, Kanai K, Miyazaki T, Yamaguchi H. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 1999 October; 37(5): 351-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10520160&dopt=Abstract

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Inhibition of sterol 4-demethylation in Candida albicans by 6-amino-2-npentylthiobenzothiazole, a novel mechanism of action for an antifungal agent. Author(s): Kuchta T, Leka C, Farkas P, Bujdakova H, Belajova E, Russell NJ. Source: Antimicrobial Agents and Chemotherapy. 1995 July; 39(7): 1538-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7492100&dopt=Abstract

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Interactions between Candida species and platelets. Author(s): Willcox MD, Webb BC, Thakur A, Harty DW.

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Source: Journal of Medical Microbiology. 1998 February; 47(2): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9879951&dopt=Abstract •

In-vitro activity of D0870, a new triazole antifungal drug, in comparison with fluconazole and itraconazole against Aspergillus fumigatus and Candida krusei. Author(s): Venkateswarlu K, Denning DW, Kelly SL. Source: The Journal of Antimicrobial Chemotherapy. 1997 June; 39(6): 731-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9222042&dopt=Abstract

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In-vitro activity of essential oils, in particular Melaleuca alternifolia (tea tree) oil and tea tree oil products, against Candida spp. Author(s): Hammer KA, Carson CF, Riley TV. Source: The Journal of Antimicrobial Chemotherapy. 1998 November; 42(5): 591-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9848442&dopt=Abstract

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Mechanism of fluconazole resistance in Candida krusei. Author(s): Orozco AS, Higginbotham LM, Hitchcock CA, Parkinson T, Falconer D, Ibrahim AS, Ghannoum MA, Filler SG. Source: Antimicrobial Agents and Chemotherapy. 1998 October; 42(10): 2645-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9756770&dopt=Abstract

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Melaleuca alternifolia (tea tree) oil inhibits germ tube formation by Candida albicans. Author(s): Hammer KA, Carson CF, Riley TV. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2000 October; 38(5): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092382&dopt=Abstract

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Membrane fluidity affects functions of Cdr1p, a multidrug ABC transporter of Candida albicans. Author(s): Smriti, Krishnamurthy SS, Prasad R. Source: Fems Microbiology Letters. 1999 April 15; 173(2): 475-81. Erratum In: Fems Microbiol Lett 1999 July 1; 176(1): 263. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227177&dopt=Abstract

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Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum. Author(s): Zhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM. Source: Journal of Natural Products. 2002 July; 65(7): 979-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141856&dopt=Abstract

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Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii. Author(s): Zhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM.

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Source: Planta Medica. 2002 January; 68(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842327&dopt=Abstract •

Optimisation of Candida albicans typing by pulsed-field gel electrophoresis. Author(s): Hong E, Leung P. Source: British Journal of Biomedical Science. 1998 December; 55(4): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436536&dopt=Abstract

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Phenolic compounds from Miconia myriantha inhibiting Candida aspartic proteases. Author(s): Li XC, Jacob MR, Pasco DS, ElSohly HN, Nimrod AC, Walker LA, Clark AM. Source: Journal of Natural Products. 2001 October; 64(10): 1282-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678651&dopt=Abstract

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Phospholipid and sterol analysis of plasma membranes of azole-resistant Candida albicans strains. Author(s): Loffler J, Einsele H, Hebart H, Schumacher U, Hrastnik C, Daum G. Source: Fems Microbiology Letters. 2000 April 1; 185(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10731607&dopt=Abstract

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Probiotic effects of feeding heat-killed Lactobacillus acidophilus and Lactobacillus casei to Candida albicans-colonized immunodeficient mice. Author(s): Wagner RD, Pierson C, Warner T, Dohnalek M, Hilty M, Balish E. Source: J Food Prot. 2000 May; 63(5): 638-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10826722&dopt=Abstract

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Production of the carotenoids lycopene, beta-carotene, and astaxanthin in the food yeast Candida utilis. Author(s): Miura Y, Kondo K, Saito T, Shimada H, Fraser PD, Misawa N. Source: Applied and Environmental Microbiology. 1998 April; 64(4): 1226-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9546156&dopt=Abstract

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Production, purification, and characterization of a highly glucose-tolerant novel betaglucosidase from Candida peltata. Author(s): Saha BC, Bothast RJ. Source: Applied and Environmental Microbiology. 1996 September; 62(9): 3165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8795205&dopt=Abstract

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Proliferation of intracellular structure corresponding to reduced affinity of fluconazole for cytochrome P-450 in two low-susceptibility strains of Candida albicans isolated from a Japanese AIDS patient. Author(s): Maebashi K, Kudoh M, Nishiyama Y, Makimura K, Kamai Y, Uchida K, Yamaguchi H.

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Source: Microbiology and Immunology. 2003; 47(2): 117-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680714&dopt=Abstract •

Protection of C3H/HE J mice from development of Candida albicans infection by oral administration of Juzen-taiho-to and its component, Ginseng radix: possible roles of macrophages in the host defense mechanisms. Author(s): Akagawa G, Abe S, Tansho S, Uchida K, Yamaguchi H. Source: Immunopharmacology and Immunotoxicology. 1996 February; 18(1): 73-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8683040&dopt=Abstract

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Protection of immunosuppressed mice from lethal Candida infection by oral administration of a kampo medicine, hochu-ekki-to. Author(s): Abe S, Tansho S, Ishibashi H, Akagawa G, Komatsu Y, Yamaguchi H. Source: Immunopharmacology and Immunotoxicology. 1999 May; 21(2): 331-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10319284&dopt=Abstract

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Protective effect of iridals from saponin injury in Candida albicans cells. Author(s): Leconte O, Bonfils JP, Sauvaire Y. Source: Phytochemistry. 1997 February; 44(4): 575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9041715&dopt=Abstract

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Protective effect of oral administration of a traditional medicine, Juzen-Taiho-To, and its components on lethal Candida albicans infection in immunosuppressed mice. Author(s): Abe S, Tansho S, Ishibashi H, Inagaki N, Komatsu Y, Yamaguchi H. Source: Immunopharmacology and Immunotoxicology. 1998 August; 20(3): 421-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9736446&dopt=Abstract

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Purification and characterisation of a metallopeptidase of Candida albicans. Author(s): el Moudni B, Rodier MH, Barrault C, Ghazali M, Jacquemin JL. Source: Journal of Medical Microbiology. 1995 October; 43(4): 282-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7562990&dopt=Abstract

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Purification and characterization of lysophospholipase-transacylase (h-LPTA) from a highly virulent strain of Candida albicans. Author(s): Mirbod F, Banno Y, Ghannoum MA, Ibrahim AS, Nakashima S, Kitajima Y, Cole GT, Nozawa Y. Source: Biochimica Et Biophysica Acta. 1995 July 13; 1257(2): 181-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7619859&dopt=Abstract

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Purification and characterization of NADPH-dependent carbonyl reductase, involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate, from Candida magnoliae.

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Author(s): Wada M, Kataoka M, Kawabata H, Yasohara Y, Kizaki N, Hasegawa J, Shimizu S. Source: Bioscience, Biotechnology, and Biochemistry. 1998 February; 62(2): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9532783&dopt=Abstract •

Quantitation of Candida albicans ergosterol content improves the correlation between in vitro antifungal susceptibility test results and in vivo outcome after fluconazole treatment in a murine model of invasive candidiasis. Author(s): Arthington-Skaggs BA, Warnock DW, Morrison CJ. Source: Antimicrobial Agents and Chemotherapy. 2000 August; 44(8): 2081-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10898679&dopt=Abstract

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Quantitation of ergosterol content: novel method for determination of fluconazole susceptibility of Candida albicans. Author(s): Arthington-Skaggs BA, Jradi H, Desai T, Morrison CJ. Source: Journal of Clinical Microbiology. 1999 October; 37(10): 3332-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10488201&dopt=Abstract

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Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Author(s): Marr KA, Lyons CN, Rustad TR, Bowden RA, White TC, Rustad T. Source: Antimicrobial Agents and Chemotherapy. 1998 October; 42(10): 2584-9. Erratum In: Antimicrob Agents Chemother 1999 February; 43(2): 438. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9756759&dopt=Abstract

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Relation between cell wall chitin content and susceptibility to amphotericin B in Kluyveromyces, Candida and Schizosaccharomyces species. Author(s): Bahmed K, Bonaly R, Coulon J. Source: Research in Microbiology. 2003 April; 154(3): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706511&dopt=Abstract

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Resistance to fluconazole in Candida albicans from AIDS patients correlated with reduced intracellular accumulation of drug. Author(s): Venkateswarlu K, Denning DW, Manning NJ, Kelly SL. Source: Fems Microbiology Letters. 1995 September 15; 131(3): 337-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7557345&dopt=Abstract

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Screening of traditionally used South African plants for antifungal activity against Candida albicans. Author(s): Motsei ML, Lindsey KL, van Staden J, Jager AK. Source: Journal of Ethnopharmacology. 2003 June; 86(2-3): 235-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738093&dopt=Abstract

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Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp. Author(s): Santos MA, Cheesman C, Costa V, Moradas-Ferreira P, Tuite MF. Source: Molecular Microbiology. 1999 February; 31(3): 937-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10048036&dopt=Abstract

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Serum-mediated enhancement of TNF-alpha release by human monocytes stimulated with the yeast form of Candida albicans. Author(s): Ghezzi MC, Raponi G, Angeletti S, Mancini C. Source: The Journal of Infectious Diseases. 1998 December; 178(6): 1743-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9815228&dopt=Abstract

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Stable phenotypic resistance of Candida species to amphotericin B conferred by preexposure to subinhibitory levels of azoles. Author(s): Vazquez JA, Arganoza MT, Boikov D, Yoon S, Sobel JD, Akins RA. Source: Journal of Clinical Microbiology. 1998 September; 36(9): 2690-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9705415&dopt=Abstract

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Streptococcus thermophilus and its biosurfactants inhibit adhesion by Candida spp. on silicone rubber. Author(s): Busscher HJ, van Hoogmoed CG, Geertsema-Doornbusch GI, van der KuijlBooij M, van der Mei HC. Source: Applied and Environmental Microbiology. 1997 October; 63(10): 3810-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9327543&dopt=Abstract

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Structural characterization of (1-->3)-beta-D-glucans isolated from blastospore and hyphal forms of Candida albicans. Author(s): Lowman DW, Ferguson DA, Williams DL. Source: Carbohydrate Research. 2003 July 4; 338(14): 1491-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829394&dopt=Abstract

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Susceptibility of Helicobacter pylori and Candida spp. to the east African plant Terminalia spinosa. Author(s): Fabry W, Okemo P, Mwatha WE, Chhabra SC, Ansorg R. Source: Arzneimittel-Forschung. 1996 May; 46(5): 539-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8737643&dopt=Abstract

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Synergy between 6-amino-2-n-pentylthiobenzothiazole and ergosterol biosynthesisinhibiting antimycotics against Candida albicans in vitro. Author(s): Muckova M, Bujdakova H, Kuchta T. Source: International Journal of Antimicrobial Agents. 2000 July; 15(2): 153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854813&dopt=Abstract

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The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Author(s): Sanglard D, Ischer F, Calabrese D, Majcherczyk PA, Bille J. Source: Antimicrobial Agents and Chemotherapy. 1999 November; 43(11): 2753-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10543759&dopt=Abstract

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The complete amino acid sequence of a trypsin inhibitor from Bauhinia variegata var. candida seeds. Author(s): Di Ciero L, Oliva ML, Torquato R, Kohler P, Weder JK, Camillo Novello J, Sampaio CA, Oliveira B, Marangoni S. Source: Journal of Protein Chemistry. 1998 November; 17(8): 827-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9988529&dopt=Abstract

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The effect of cryptolepine on the morphology and survival of Escherichia coli, Candida albicans and Saccharomyces cerevisiae. Author(s): Sawer IK, Berry MI, Brown MW, Ford JL. Source: The Journal of Applied Bacteriology. 1995 September; 79(3): 314-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7592125&dopt=Abstract

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The effect of ethylenediamine-tetraacetic acid on Candida albicans. Author(s): Sen BH, Akdeniz BG, Denizci AA. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2000 November; 90(5): 651-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11077392&dopt=Abstract

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The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity. Author(s): Kelly SL, Lamb DC, Loeffler J, Einsele H, Kelly DE. Source: Biochemical and Biophysical Research Communications. 1999 August 19; 262(1): 174-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448088&dopt=Abstract

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Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Author(s): Henry KW, Nickels JT, Edlind TD. Source: Antimicrobial Agents and Chemotherapy. 2000 October; 44(10): 2693-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991846&dopt=Abstract

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YM-170320, a novel lipopeptide antibiotic inducing morphological change of colonies in a mutant of Candida tropicalis pK233. Author(s): Sugawara T, Tanaka A, Tanaka K, Nagai K, Suzuki K, Suzuki T.

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Source: J Antibiot (Tokyo). 1998 April; 51(4): 435-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9630867&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 Candida; 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 AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Appendicitis Source: Integrative Medicine Communications; www.drkoop.com Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Candidiasis Source: Integrative Medicine Communications; www.drkoop.com

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Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Chronic Candidiasis Source: Healthnotes, Inc.; www.healthnotes.com Genital Herpes Source: Healthnotes, Inc.; www.healthnotes.com Hiv and Aids Source: Integrative Medicine Communications; www.drkoop.com Hives Source: Healthnotes, Inc.; www.healthnotes.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Sexually Transmitted Diseases Source: Integrative Medicine Communications; www.drkoop.com Stds Source: Integrative Medicine Communications; www.drkoop.com Vaginal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Healthnotes, Inc.; www.healthnotes.com Vaginitis Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Healthnotes, Inc.; www.healthnotes.com Yeast Infection Source: Integrative Medicine Communications; www.drkoop.com •

Homeopathy Candida Albicans Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Achillea Alternative names: Yarrow; Achillea millefolium L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Acidophilus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,748,00.html Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aminoglycoside Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Amoxicillin Source: Healthnotes, Inc.; www.healthnotes.com Ampicillin Source: Healthnotes, Inc.; www.healthnotes.com Antibiotics Source: Healthnotes, Inc.; www.healthnotes.com Azithromycin Source: Healthnotes, Inc.; www.healthnotes.com Azt Source: Healthnotes, Inc.; www.healthnotes.com Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com Brewer’s Yeast Source: Healthnotes, Inc.; www.healthnotes.com Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Caprylic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10111,00.html Capsaicin Source: Integrative Medicine Communications; www.drkoop.com Capsicum Frutescens Source: Integrative Medicine Communications; www.drkoop.com

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Cayenne Alternative names: Capsicum frutescens, Capsicum spp., Capsaicin, Chili Pepper, Red Pepper Source: Integrative Medicine Communications; www.drkoop.com Cephalosporins Source: Healthnotes, Inc.; www.healthnotes.com Chili Pepper Source: Integrative Medicine Communications; www.drkoop.com Chlorhexidine Source: Healthnotes, Inc.; www.healthnotes.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ciprofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Clarithromycin Source: Healthnotes, Inc.; www.healthnotes.com Clindamycin Oral Source: Healthnotes, Inc.; www.healthnotes.com Clindamycin Topical Source: Healthnotes, Inc.; www.healthnotes.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Dapsone Source: Healthnotes, Inc.; www.healthnotes.com Dicloxacillin Source: Healthnotes, Inc.; www.healthnotes.com Doxycycline Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Echinacea Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Econazole Source: Healthnotes, Inc.; www.healthnotes.com

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Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Erythromycin Source: Healthnotes, Inc.; www.healthnotes.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Fluconazole Source: Healthnotes, Inc.; www.healthnotes.com Gentamicin Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Glabra Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Grapefruit Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,985,00.html Gymnema Alternative names: Gymnema sylvestre Source: Healthnotes, Inc.; www.healthnotes.com Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ketoconazole Source: Healthnotes, Inc.; www.healthnotes.com L. Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Lactobacillus Acidophilus Source: Integrative Medicine Communications; www.drkoop.com

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Lapacho Source: Integrative Medicine Communications; www.drkoop.com Lapacho Source: Prima Communications, Inc.www.personalhealthzone.com Levofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Loracarbef Source: Healthnotes, Inc.; www.healthnotes.com Macrolides Source: Healthnotes, Inc.; www.healthnotes.com Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Minocycline Source: Healthnotes, Inc.; www.healthnotes.com Neomycin Source: Healthnotes, Inc.; www.healthnotes.com Nitrofurantoin Source: Healthnotes, Inc.; www.healthnotes.com Nitrous Oxide Source: Healthnotes, Inc.; www.healthnotes.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Oregano/wild Marjoram Alternative names: Origanum vulgare Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Pau d'Arco Alternative names: Tabebuia avellanedae, Lapacho Source: Integrative Medicine Communications; www.drkoop.com Penicillin V Source: Healthnotes, Inc.; www.healthnotes.com Penicillins Source: Healthnotes, Inc.; www.healthnotes.com Peppermint Source: Prima Communications, Inc.www.personalhealthzone.com Probiotics Source: Healthnotes, Inc.; www.healthnotes.com Quinolones Source: Healthnotes, Inc.; www.healthnotes.com Red Pepper Source: Integrative Medicine Communications; www.drkoop.com Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Spirulina Alternative names: Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com Stevia Alternative names: Sweetleaf; Stevia rebaudiana Bertoni Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Sulfasalazine Source: Healthnotes, Inc.; www.healthnotes.com Sulfonamides Source: Healthnotes, Inc.; www.healthnotes.com Swertia Alternative names: Swertia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tabebuia Avellanedae Source: Integrative Medicine Communications; www.drkoop.com Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Tanacetum V Alternative names: Tansy; Tanacetum vulgare (L.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tea Tree Source: Prima Communications, Inc.www.personalhealthzone.com Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Source: Healthnotes, Inc.; www.healthnotes.com Tetracyclines Source: Healthnotes, Inc.; www.healthnotes.com Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tobramycin Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim/sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Valerian Source: Prima Communications, Inc.www.personalhealthzone.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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 CANDIDA Overview In this chapter, we will give you a bibliography on recent dissertations relating to Candida. 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 “Candida” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Candida, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Candida 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 Candida. 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: •

A Study of the Growth Inhibition of Candida Lipolytica at Elevated Partial Pressures of Oxygen by Wein, Edward; Phd from University of Toronto (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK13084

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Adhesion and Subsequent Biofilm Formation of Candida Albicans on Chemically Different Surfaces As Investigated Using Confocal Scanning Laser Microscopy by Wesenberg, Karen Emma; Phd from Montana State University, 2002, 250 pages http://wwwlib.umi.com/dissertations/fullcit/3069288

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Analysis of Septin Contribution to Candida Albicans Morphogenesis by Warenda, Amy Jean; Phd from State University of New York at Stony Brook, 2002, 100 pages http://wwwlib.umi.com/dissertations/fullcit/3067593

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Biotechnological Production of Xylitol with Candida Yeasts by Granstrom, Tom Birger; Phd from Teknillinen Korkeakoulu (helsinki) (finland), 2002, 160 pages http://wwwlib.umi.com/dissertations/fullcit/f336225

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Development, Characterization, and Application of a Candida Parapsilosis Dna Fingerprinting Method by Enger, Lee Randolph; Phd from The University of Iowa, 2002, 217 pages http://wwwlib.umi.com/dissertations/fullcit/3073363

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Molecular Analysis of Ergosterol and Prenylation Pathways in Candida Albicans by Song, Jia Ling; Phd from University of Washington, 2002 http://wwwlib.umi.com/dissertations/fullcit/f342145

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Molecular and Antigenic Characterization of Two Unique Epitopes from the Phospholipase B1 Molecule to Candida Albicans by Tarcha, Eric J.; Ms from Michigan State University, 2002, 65 pages http://wwwlib.umi.com/dissertations/fullcit/1409562

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Population Genomics of Drug Resistance in the Pathogenic Yeast Candida Albicans by Cowen, Leah Elizabeth; Phd from University of Toronto (canada), 2002, 247 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74578

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Preparation and Characterization of Chitosan-containing Hydrogel Beads for Immobilization of Candida Rugosa Lipase with High Retention of Its Hydrolytic Activity by Alsarra, Ibrahim A.; Phd from University of Missouri - Kansas City, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3043433

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Quorum Sensing and the Regulation of Morphology in the Dimorphic Fungus Candida Albicans by Hornby, Jacob Michael; Phd from The University of Nebraska Lincoln, 2003, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3085737

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Regulation of Hyphal Morphogenesis in Candida Albicans by Hazan, Idit; Phd from University of California, Irvine, 2002, 177 pages http://wwwlib.umi.com/dissertations/fullcit/3039202

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Selective Production of Ethyl Acetate and Acetaldehyde by Candida Utilis by Armstrong, David W; Phd from Carleton University (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65737

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Studies on the Morphology and Growth Patterns of Candida Albicans by Hendry, A. T; Advdeg from The University of Western Ontario (canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK09869

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The Candida Albicans Ess1 Prolyl-isomerase Gene Is Required for Growth, Morphogenesis and Virulence by Devasahayam, Gina; Phd from State University of New York at Albany, 2002, 197 pages http://wwwlib.umi.com/dissertations/fullcit/3065113

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The Measurement and Effect of Dissolved Oxygen on Candida Lipolytica by Kok, Robert; Phd from The University of Western Ontario (canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20518

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Utilization of Alkanes by Candida Lipolytica (atcc 8661) by Whitworth, Derek A; Advdeg from University of Waterloo (canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK08634

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

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

Anidulafungin versus Fluconazole in the Treatment of Candidemia Condition(s): Candida; Candidiasis Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Fluconazole is an FDA-approved drug that is widely used to treat fungal infections due to candida. The experimental drug anidulafungin has been found to be active in treating life-threatening fungal infections. The purpose of this study is to determine whether anidulafungin is as effective as fluconazole in treating candidemia, an invasive form of candidiasis. Three hundred patients 16 years of age or older will participate in this study. Participants will be randomly assigned to one of two groups: one-half will receive anidulafungin; the other half will receive fluconazole. They will receive the drug for as few as 10 days or for up to 42 days, depending on the seriousness of the infection. The drug will be given over a four-hour period on the first day, and over two hours on the remaining days. While taking the study medication, participants will be required to give blood samples every week until the end of treatment. At two weeks and six weeks following the end of therapy, participants will return for evaluation. Prior to their participation in this study, patients will undergo the following evaluations: a physical exam, an eye exam, an electrocardiogram, and possibly blood work. Phase(s): Phase III Study Type: Interventional

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These are listed at www.ClinicalTrials.gov.

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058682 •

Evaluation of Amphotericin B in the Treatment of Biopsy Proven Candida Esophagitis in Immunocompromised Patients Condition(s): Candidiasis, esophageal; HIV Infections Study Status: This study is no longer recruiting patients. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: To determine the appropriate duration of amphotericin B therapy for Candida esophagitis. To compare the effectiveness of two different amphotericin B doses in the treatment of biopsy-proven Candida esophagitis. To determine if low-dose amphotericin B is less toxic than standard dose therapy during a limited treatment period. To evaluate pharmacokinetic and pharmacodynamic parameters of the two different dosing regimens. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002041

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A Study of the Side Effects of L-743,872 in Men with Candidal Esophagitis Condition(s): Candidiasis, esophageal; HIV Infections Study Status: This study is completed. Sponsor(s): Merck Research Laboratories Purpose - Excerpt: The purpose of this study is to see if it is safe to give L-743,872 to men with candidal esophagitis, an AIDS-related yeast infection in the esophagus. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005921

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

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

9Adapted

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

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

Acetyl-COA-carboxylase from Candida albicans Inventor(s): Chavda; Suberna J (Macclesfield, CA), Dixon; Graham K (Macclesfield, GB), Schnell; Norbert F (Macclesfield, GB), Thain; John L (Macclesfield, GB), Vincent; John P (Macclesfield, GB) Assignee(s): Syngenta Limited (London, GB) Patent Number: 6,566,048 Date filed: June 19, 2000 Abstract: The Acetyl-COA-carboxylase (ACCase) gene from Candida albicans. Excerpt(s): The present invention relates to Acetyl-COA-carboxylase (ACCase) genes from Candida Albicans (C. albicans) and methods for its expression. The invention also relates to novel hybrid organisms for use in such expression methods. C. albicans is an important fungal pathogen and the most prominent target organism for antifungal research. ACCase is an enzyme of fatty acid biosynthesis and essential for fungal growth and viability. Inhibitors of the ACCase enzyme should therefore be potent antifungals. The ACCase proteins in all organisms are homologous to each other but they also differ significantly in the amino acid sequence. Because selectivity problems (for example fungal versus human) it is extremely important to optimise potential inhibitor leads directly against the target enzyme (C. albicans) and not against a homologous but nonidentical model protein, for example from Saccharomyces cerevisiae (S. Cerevisiae). We have now successfully cloned the ACCase gene from C. albicans (hereinafter referred to as the C. Albicans ACC1 gene) and elucidated its full length DNA sequence and corresponding polypeptide sequence, as set out in FIGS. 4 and 5 of this application respectively. The coding DNA sequence of the C. Albicans ACC1 gene is 6810 nucleotides in length and the corresponding protein sequence is 2270 amino acids in length. As will be explained below there are two forms of the C. Albicans ACC1 gene, the above numbers relate to the longer version, Met1. Web site: http://www.delphion.com/details?pn=US06566048__

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Active carbon electro-deposited with Ag-I system having sterilizing effect Inventor(s): Jung; Woo Young (Chung-Ju, KR) Assignee(s): Sol Nanochem Ltd. (KR) Patent Number: 6,413,405 Date filed: December 14, 2000 Abstract: An environmentally functional active carbon and its method of manufacturing is provided. The active carbon has improved adsorption capability against diseasesource bacteria and microbes with prominent anti-bacterial and sterilizing effect as well as against organic and inorganic contaminants due to the process of electro-depositing Ag--I to the surface of active carbon and active carbon fiber. This invention creates functional active carbon having outstanding sterilizing effect for disease-source bacteria from known bacteria such as Gram positive bacteria including Staphylococcus, Bacillus subtillis and Gram negative bacteria including Escherichia coli, Pseudomonas

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Aeruginosa, Klebsiella Pneumonie, Candida Albicans causing albicans as yeast fungus, Trichophyton interdigital causing athlete's foot as a kind of mold. Excerpt(s): This invention relates to active carbon electro-deposited with Ag--I compositions having a sterilizing effect and a method of preparing such compositions. Plating a metal element on an adsorbent increase the selective adsorption capability of the adsorbent owing to the surface polarity of the metal ion while maintaining a high level of adsorption capability. It is applied to remove polar contaminants from polluted water and wastewater. Known methods of metal impregnation for solid substrates are dipping, chemical vapor deposition and admixing during the manufacture process. Recently, much of research and development is being done concerning the anti-bacterial effect of active carbon electro-deposited with Ag. However, so far there has been no report about the anti-bacterial and sterilizing effect of active carbon electro-deposited with Ag--I against disease-source bacteria. The purpose of this invention is to provide functional active carbon having improved adsorption capability against disease-source bacteria and microbes with prominent anti-bacterial and sterilizing effect as well as against organic and inorganic contaminants and preparing method thereof. As used herein, the term "active carbon" is meant to include activated carbon. Web site: http://www.delphion.com/details?pn=US06413405__ •

Antifungal activity of dicationic molecules Inventor(s): Boykin; David W. (Atlanta, GA), Perfect; John R. (Durham, NC), Tidwell; Richard R. (Pittsboro, NC) Assignee(s): Duke University (Durham, NC), Georgia State University Research Found, Inc. (Atlanta, GA), University of North Carolina-Chapel Hill (Chapel Hill, NC) Patent Number: 6,326,395 Date filed: September 15, 1999 Abstract: Methods of treating fungal infections comprise administering a therapeutically effective amount of a compound described by Formulas [(I)-(VI)]. Examples of fungal infections include Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Fusarium solani, and combinations thereof. Excerpt(s): The invention generally relates to methods for treating fungal infections. The incidence of fungal infections in the immunocompromised population has significantly increased over the past several years. In particular, Candida species, especially Candida albicans, are often significant pathogens in patients infected with human immunodeficinecy virus (HIV). As an example, infections can range from somewhat mild oropharyngeal or vulvovaginal candidiasis to severe debilitating mucocutaneous candidiasis. Moreover, AIDS patients suffering from oral candidiasis may also experience esophageal candidiasis which has been known to lead to gastrointestinal bleeding and perforation. Candida albicans is a species which is commonly isolated from patients with the above-mentioned infections. Treatment of candidiasis has typically involved two classes of drugs: (1) polyenes such as amphotericin B and nystatin; and (2) azoles such as clotrimazole, ketoconozole, fluconozole, and itraconazole. Since immunosuppression in AIDS-infected patients often occurs over an extended period of time, fungal reinfection may be common. Accordingly, these patients commonly receive prolonged antifungal therapy. Widespread antifungal therapy, however, has raised issues regarding the increased level of resistance among isolates of the Candida species, especially with respect to fluconozole. See Pfaller, M. A., et al.,

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Journal of Clinical Microbiology, January 1994, pp. 59-64; and Cameron, M. L., et al., Antimicrobial Agents and Chemotherapy, November 1993, pp. 2449-2453. Web site: http://www.delphion.com/details?pn=US06326395__ •

Antimicrobial denture cleansing compositions Inventor(s): Watkins; C. Douglas (Keizer, OR) Assignee(s): Denture Dynamic Inc. (Keizer, OR), Protech Professional Products, Inc. (Boca Raton, FL) Patent Number: 6,309,622 Date filed: March 26, 1999 Abstract: A denture cleansing composition includes a monoperoxysulfate compound, an effective amount a sequestering agent, such as a citrate compound, for removal of calculus and to provide a pH to the composition in solution (water) of about 3 to 5, and an effective amount of an antimicrobial agent, such as a benzoate compound, to provide antimicrobial activity to the composition to effectively kill bacteria, or other microorganisms found on the dentures. Tests conducted show that the composition is particularly effective in killing microbial strains of Streptococcus mutans, Streptococcus pyogenes, Candida albicans and Actinomyces viscosus within 20 minutes of contact. Excerpt(s): This invention relates to a denture cleansing composition and, more particularly, to a denture cleansing composition having improved antimicrobial activity as compared to other denture cleansing compositions. Specifically, the invention relates to a composition suitable for use as a safe and effective cleanser for dentures containing a monopersulfate compound, a sequestering agent, and an antimicrobial agent, such as a benzoate compound, which, together, effectively kill bacteria, and other microorganisms commonly found on dentures. In order to avoid denture buildup or otherwise rid the dentures of such buildup and stains, the dentures must be cleansed from time to time. Denture cleansing is generally carried out either by brushing dentures with a paste or by soaking dentures, typically overnight, in an aqueous cleansing solution. Aqueous denture cleanser solutions are known and generally compose tablets, granules, or powders that are dissolved in water to form a cleansing bath or cleansing system in water. Numerous denture cleansing compositions, typically provided in tablet or powder form, are well known in the art for this purpose. Traditionally, these compositions have contained a variety of sulfate salts, such as bisulfates, monopersulfates, and sulfates as detergents, oxidizers and the like, and have also utilized alkali metal and alkaline earth metal halides as bleaches. Such compositions have also included perborate, carbonate and phosphate salts in various amounts to provide effervescence and cleaning activation. Web site: http://www.delphion.com/details?pn=US06309622__

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ARO1 multifunctional polypeptide of Candida albicans Inventor(s): Greenwood; Rebecca (Berwyn, PA), Nicholas; Richard (Collegeville, PA) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,346,405 Date filed: October 10, 2000

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Abstract: The invention provides ARO1 polypeptides and DNA (RNA) encoding such ARO1 and a procedure for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing such ARO1 for the treatment of infection, particularly fungal infections. Antagonists against such ARO1 and their use as a therapeutic to treat infections, particularly fungal infections are also provided. Further provided are diagnostic assays for detecting diseases related to the presence of ARO1 nucleic acid sequences and the polypeptides in a host. Also provided are diagnostic assays for detecting polynucleotides encoding arom and for detecting the polypeptide in a host. Excerpt(s): This invention relates, in part, to newly identified polynucleotides and polypeptides; variants of these polynucleotides and polypeptides; processes for making these polynucleotides and these polypeptides, and their variants; agonists and antagonists of the polypeptides; and uses of these polynucleotides, polypeptides, variants, agonists and antagonists. In particular, in these and in other regards, the invention relates to polynucleotides and polypeptides of arom, hereinafter referred to as "ARO1" and "ARO1". The frequency of Candida albicans infections has risen dramatically in the past 20 years. This has been attributed to an increasing population of people with weakened immune systems and the use of broad spectrum antibacterials and more interventional surgical practices. The amoury of good antifingal agents is small and resistance to existing agents is an emerging problem. This has created a demand for both new antifingal agents and diagnostic tests for this organism. Fungi like bacteria and plants, but unlike mammals, are able to synthesize the aromatic amino acids phenylalanine, tyrosine and tryptophan. In fungi, a single polypeptide, the arom multifunctional enzyme, catalyses five consecutive reactions of the central aromatic biosynthetic pathway (Lambert et al. (1985). The 3-dehydroquinate synthase activity of the pentafunctional arom enzyme complex of Neurospora crassa is Zn.sup.2+ dependent. Biochemical Journal 226:817-29. Duncan et al. (1987). The pentafunctional arom enzyme of Saccharomyces cerevisiae is a mosaic of monofinctional domains. Biochemical Journal 246:375-86.). Inhibition of any step catalyzed by this enzyme will prevent the synthesis of aromatic amino acids, p-aminobenzoic acid (precursor for folate) and ubiquinone. These essential metabolites are in limiting concentrations in mammalian tissues and thus inhibition of this enzyme is a valid antifingal strategy. Web site: http://www.delphion.com/details?pn=US06346405__ •

CaESS1: a Candida albicans gene, methods for making and using, and targeting it and its expression products for antifungal applications Inventor(s): Chaturvedi; Vishnu (Slingerlands, NY), Devasahayam; Gina (Madras, IN), Hanes; Steven D. (Albany, NY) Assignee(s): Health Research Incorporated (Rensselaer, NY) Patent Number: 6,537,753 Date filed: February 18, 2000 Abstract: Disclosed and claimed is the CaESS1 gene, portions thereof such as primers or probes, expression products therefrom, and methods for using the gene, and expression products; for instance, for diagnostic, therapeutic or preventive compositions. Excerpt(s): The present invention relates to compositions and methods for diagnosing and/or detecting and/or preventing and/or treating Candida albicans or conditions or symptoms associated therewith, as well as to process and products for preparing such

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compositions and methods. The present invention further relates to CaESS1, an important Candida albicans gene, e.g., nucleic acid molecules therefor, and/or fragments or portions thereof, expression products therefrom, e.g., the protein CaEss1 or fragments or portions thereof, methods for making and using the gene, portions thereof and expression products therefrom, and to targeting the gene or portions thereof and/or the expression products therefrom for antifungal applications. The identification of the CaESS1 gene allows for identifying compounds or agents that specifically bind to and/or inhibit the gene, or portions thereof and/or expression products therefrom, and methods for preventing and/or treating Candida albicans and/or symptoms or conditions associated therewith, as well as generally for making and using such compounds or agents. Thus, the invention relates to antifungal preparations and/or compositions and methods for making and using them. Web site: http://www.delphion.com/details?pn=US06537753__ •

Candida albicans gene (CSA1) encoding a mycelial surface antigen, and uses thereof Inventor(s): Bourbonnais; Yves (Cap-Rouge, CA), Deslauriers; Noella (St-Ferreol-lesNeiges, CA) Assignee(s): Universite Laval (Quebec, CA) Patent Number: 6,320,033 Date filed: July 9, 1999 Abstract: The present invention relates to a Candida albicans gene (CSA1) encoding a surface protein. The present invention also relates to the surface protein and methods for using the protein or the gene for the detection, prophylaxis or treatment of candidal infection. The protein encoded is a surface antigen of Candida albicans yeast and mycelial forms, respectively. The mycelial surface antigen was shown to be present predominantly in the terminal third of the hyphal structures. CSA1 is a gene coding for a unique surface antigen. Excerpt(s): The invention relates to Candida albicans gene (CSA1) encoding a mycelial surface antigen, and uses thereof for the treatment or prophylaxis of candidal infections. Candida albicans is of major medical importance, being the most commonly isolated fungal species from various mucosal surfaces in healthy individuals and from infectious sites in patients with candidiasis. Most frequently, it causes superficial, irritating infections of the oral and urogenital tracts. However, serious deep-seated or systemic infections can develop, particularly in immunocompromised subjects. The performance of Candida albicans as an opportunistic pathogen is associated with a number of factors that include the morphological and functional modifications resulting from switching between the yeast and the hyphal forms. Mycelium formation is believed to contribute to fungal adhesion to host cell surfaces and to facilitate invasion of a variety of host tissues through the expression of specialized surface proteins and enzymes (Staab, J. F., et al., Science 283: 1535-1538, 1999). On the basis that the dimorphic process is likely to be associated with differential expression of mycelial cell-specific molecules, biochemical and immunological approaches have been used for their identification. Web site: http://www.delphion.com/details?pn=US06320033__

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Candida albicans KRE9 and uses thereof Inventor(s): Bussey; Howard (Westmount, CA), Lussier; Marc (Montreal, CA), Sdicu; Anne-Marie (Pierrefonds, CA), Shahinian; Sarkis Serge (Montreal, CA) Assignee(s): McGill University (Montreal, CA) Patent Number: 6,582,911 Date filed: August 10, 2000 Abstract: The present invention to an isolated DNA which codes for a gene essential for cell wall glucan synthesis of Candida albicans, wherein the gene is referred to as CaKRE9, wherein the sequence of the DNA is as set forth in FIG. 1. The present invention relates to antifungal in vitro and in vivo screening assays for identifying compounds which inhabit the synthesis, assembly and/or regulation of.beta.1,6-glucan. There is also disclosed an in vitro method for the diagnosis of disease caused by fungal infection in a patient. Excerpt(s): The invention relates to a novel gene, CaKRE9, isolated in the yeast pathogen, Candida albicans, that is a functional homolog of the S. cerevisiae KRE9 gene and which is essential for cell wall glucan synthesis, and to novel antifungal screening assays. Fungi constitute a vital part of our ecosystem but once they penetrate the human body and start spreading they cause infections or "mycosis" and they can pose a serious threat to human health. Fungal is infections have dramatically increased in the last 2 decades with the development of more sophisticated medical interventions and are becoming a significant cause of morbidity and mortality. Infections due to pathogenic fungi are frequently acquired by debilitated patients with depressed cell-mediated immunity such as those with human immunodeficiency virus (HIV) and now also constitute a common complication of many medical and surgical therapies. Risk factors that predispose individuals to the development of mycosis include neutropenia, use of immunosuppressive agents at the time of organ transplants, intensive chemotherapy and irradiation for hematopoietic malignancies or solid tumors, use of corticosteroids, extensive surgery and prosthetic devices, indwelling venous catheters, hyperalimentation and intravenous drug use, and when the delicate balance of the normal flora is altered through antimicrobial therapy. The yeast genus Candida constitutes one of the major groups that cause systemic fungal infections and the five medically relevant species which are most often recovered from patients are C. albicans, C. tropicalis, C. glabrata, C. parapsilosis and C. krusei. Web site: http://www.delphion.com/details?pn=US06582911__

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Candida albicans SRB-7 Inventor(s): Thompson; Craig M. (Arlington, MA) Assignee(s): Anadys Pharmaceuticals, Inc. (Waltham, MA) Patent Number: 6,358,708 Date filed: January 31, 2000 Abstract: Disclosed herein is a purified isolated nucleic acid encoding Candida Albicans SRB-7 (CaSRB-7) and an isolated polypeptide encoded by said nucleic acid. Also disclosed herein are vectors comprising the nucleic acid sequences, cells comprising the vectors, methods for producing the polypeptides and methods of use thereof.

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Excerpt(s): This invention pertains to proteins required for activated transcription in fungi, nucleic acids encoding these proteins, and methods for using these proteins. Most fungi are opportunistic pathogens, producing serious disease only in compromised individuals. As the result of an aging population as well as an increase in the number of immunocompromised patients, e.g., patients with acquired immunodeficiency syndrome (AIDS), patients undergoing cancer chemotherapy, or immunosuppressive therapy, e.g., treatment with corticosteroids, and patients undergoing organ transplantation, fungal infections are increasing rapidly. Most infections begin by colonization of either the skin, a mucosal membrane, or the respiratory epithelium. Passage through the initial surface barrier is accomplished through a mechanical break in the epithelium. Although most fungi are readily killed by neutrophils, some species are resistant to phagocytic killing and can infect otherwise healthy individuals. Web site: http://www.delphion.com/details?pn=US06358708__ •

Candida boidini dihydroxyacetone synthase promoter Inventor(s): Kato; Nobuo (Kyoto, JP), Komeda; Toshihiro (Kanagawa, JP), Kondo; Keiji (Kanagawa, JP), Sakai; Yasuyoshi (Kyoto, JP) Assignee(s): Kirin Beer Kabushiki Kaisha (Tokyo, JP) Patent Number: 6,423,510 Date filed: August 18, 2000 Abstract: This invention relates to a promoter for dihydroxyacetone synthase gene from Candida boidinii; an expression cassette or vector comprising the promoter and a heterologous gene; a transformant transformed with this vector; and a method for producing an expression product of the heterologous gene which comprises culturing the transformant to express the heterologous gene. Excerpt(s): The present invention relates to a promoter for dihydroxyacetone synthase gene (also referred to as DAS) from Candida boidinii; a gene expression cassette containing said promoter, a heterologous gene and a terminator; an expression vector containing said gene expression cassette; a transformant transformed with said vector; and a method for producing a heterologous gene product using said transformant. Methanol-assimilating yeasts are those capable of growing on a medium containing methanol as a sole carbon source. The methanol metabolism in the methanolassimilating yeasts is performed as follows. In the first reaction formaldehyde and hydrogen peroxide are produced from methanol and oxygen by alcohol oxidase. The hydrogen peroxide produced is decomposed by catalase into water and oxygen. The formaldehyde, on the other hand, is oxidized eventually into carbon dioxide via actions of formaldehyde dehydrogenase, S-formylglutathione hydrolase and formate dehydrogenase, and NADH produced in these reactions is utilized as an energy source for cells. Simultaneously, the formaldehyde is condensed with xylulose-5-phosphate by dihydroxyacetone synthase to be converted into glyceraldehyde-3-phosphate and dihydroxyacetone which are then converted to cell constituents via the pentose phosphate pathway. When the methanol-assimilating yeasts are cultured in the presence of methanol, the above-mentioned alcohol oxidase, dihydroxyacetone synthase and formate dehydrogenase are produced in significant amounts and their contents reach about 40% of the intracellular soluble proteins. Because a large scale cultivation of the methanol-assimilating yeasts can be done with inexpensive methanol as described above and because they possess methanol inducible promoters with a strong

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transcriptional activity not observed in other yeasts, the methanol-assimilating yeasts can be considered to be yeasts suitable for a heterologous gene expression system. Web site: http://www.delphion.com/details?pn=US06423510__ •

Candida magnoliae producing mannitol and fermentation method for producing mannitol Inventor(s): Baek; Hong (Junranam-Do, KR), Hyun; Hyung Hwan (Kyunggi-Do, KR), Jung; Soo Ryun (Seoul, KR), Kim; Sang Yong (Kyunggi-Do, KR), Lee; Jung Kul (Kyunggi-Do, KR), Park; Song Mi (Choongchungnam-Do, KR), Song; Ji Yoon (Seoul, KR), Song; Kyung Hwa (Kyunggi-Do, KR) Assignee(s): BioNgene Co., Ltd. (Seoul, KR), Bolak Co., Ltd. (Kyunggi-Do, KR) Patent Number: 6,528,290 Date filed: October 18, 2001 Abstract: The present Invention is to provide a novel strain, Candida magnoliae (KCCM-10252) producing mannitol isolated from the fermentation sludge collected from a xylitol manufacturing company, and further a method for manufacturing mannitol with high yield and high productivity by optimizing various culture conditions and medium composition using the new strain, Candida magnoliae. Excerpt(s): The present invention relates to a fermentation process for producing mannitol from fructose using a novel strain, Candida magnoliae (KCCM-10252) producing mannitol in high yield and high productivity, and a novel strain of Candida magnoliae (KCCM-10252) which is isolated from a natural substance. Mannitol is a six carbon sugar alcohol, and it is contained in natural substances, such as, brown algae, mushrooms, fungi and the like in nature. Since it has 30.about.40% of sugar's sweetness, not only it can be used as an alternative sweetening agent in the food processing industry where the use of sugar is limited, but also it can be mostly used as an additive for confectionary, a filler for medicine, a surfactant, a waterproof agent and the like, because it has superior properties, such as, a cool taste, low hygroscopic property, fluidity and the like. Further, it has been widely used in the food and pharmaceutical industry, for example, as a therapeutic intermediate of hypotension and a coating agent for reducing a bitter taste during the manufacturing various drugs. Mannitol exists in many kinds of fruits or vegetables as a natural product in a very small amount. Therefore, it is industrially of little economical value to extract mannitol from fruits or vegetables. Web site: http://www.delphion.com/details?pn=US06528290__

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Candida maltosa used for the bio-degradation of petroleum product pollutants Inventor(s): Avchieva; Penker Babaevna (117593, Litovsky bulvar, 3-2-543, Moscow, RU), Kuznetsov; Petr Alexandrovich (350000, u1. Pervomaiskay, d.21, Krasnodar, RU) Assignee(s): none reported Patent Number: 6,444,204 Date filed: June 21, 1999 Abstract: The present invention relates to the field of bio-technologies and environmental protection, and refers the cleaning of water, soil and other media

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polluted with petroleum products. The cleaning method of the present invention is carried out with a biological preparation that comprises a pool of yeast of the Candida maltosa genus from the strains deposited under No. VKPM Y-2256 and No. VKPM Y2257. These strains may be present in the pool in any ratio but preferably in the ratio of 1:1. The biological preparation may be used for removing pollution caused by a wide range of hydrocarbons contained in crude oil and petroleum products, for example fuel oil, oils, etc. The biological preparation affords recovery of oil pollution at temperatures up to +41.degree. C. and pH 3.0-9.0, and may be used in saline ecosystems. The process for producing the biological preparation comprises simultaneously cultivating the above-mentioned yeast strains on a liquid medium followed by separation and removal of the biomass thus grown. To obtain a powdered preparation, the biomass is subjected to drying. When cleaning the above-cited media from oil pollution, an aqueous suspension of the biological preparation with a nitrogen-phosphate additive is used. Excerpt(s): The present invention relates generally to the field of bio-technologies and, more particularly, to microbiology and environmental protection, refers to the creation of a novel pool for cleaning oil-polluted soil, water and equipment, to the manufacture of a new biological preparation based on this pool designed to be used for the purification of water, industrial sewage, soil and other media from a wide range of petroleum products and directly from crude oil, and to the use of the obtained biological preparation for the efficient recovery of the above said oil-polluted media. The evergrowing volumes of oil output, transportation, refining and utilization result in the wide-spread pollution of water and soil areas with crude oil and oil products. Despite safety precautions taken, accidents intermittently occur at petroleum-extracting and oilrefining enterprises, pipelines, oil tankers, resulting in an environmentally hazardous oil and oil-product spillage. It is common knowledge that Nature itself possesses an efficient system for the recovery of oil-polluted areas by means of microorganisms capable of assimilating the hydrocarbons of oil. However, the microflora of Nature is no longer capable of effectively recovering million tons of oil finding every year its way into the environment. As a result, the mankind has found itself under the real threat of ecological disaster (see, L. R. Brown. Chemical Engineering Progress. (1987) Vol. 83, No. 10, pp. 35-40; "Oil-degrading microorganisms"). Such traditional methods of recovery as mechanical, chemical and physical fail to provide a sufficient degree of recovery of oilpolluted water and soil. Besides, in many cases the application of these methods inflicts a more pronounced damage on the environment than oil spillage itself. Web site: http://www.delphion.com/details?pn=US06444204__ •

Candida saitoana compositions for biocontrol of plant postharvest decay Inventor(s): El Ghaouth; Ahmed (Frederick, MD), Wilson; Charles (Martinsburg, WV) Assignee(s): Biotechnology Research and Development Corporation (Peoria, IL), The United States of America as represented by the Secretary of Agriculture (Washington, DC) Patent Number: 6,419,922 Date filed: June 2, 1999 Abstract: Novel methods and compositions are provided for the biocontrol of plant diseases, in particular diseases causing plant postharvest decay. The novel compositions are "biocontrol cocktails" that are combinations of antagonistic microorganisms and antifungal agents. Suitable microorganisms include yeasts such as Candida spp. Suitable antifungal agents include enzymes or combinations of enzymes such as

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lysozyme or lyticase. The compositions are applied to the plants either to prevent or cure infections caused by microorganisms such as fungi. Synergistic effects occur. The methods and compositions are comparable to or better than synthetic fungicides or to either agent alone. Excerpt(s): Novel methods and compositions are provided for the biocontrol of plant diseases, in particular diseases causing postharvest decay. The methods and compositions are both protective and curative. Combinations of antagonistic microorganisms and antifungal agents are used. The U.S. market for biocontrol of tree fruit postharvest diseases could exceed $100 million by the year 2000 (Industrial Bioprocessing, September 1992). In Postharvest News and Information (1991) it was estimated that approximately 25% of harvested fruit and vegetables are lost because of postharvest diseases. Synthetic fingicides have been the primary means for controlling postharvest diseases of fruit and vegetables. However, increased concern of the public over the carcinogenicity of synthetic fungicides, has led to the withdrawal of some fungicides from the market. The development of fungicide-resistance in pathogens has limited chemical fingicides as a means of controlling them. Control of plant diseases is not a problem confined to the U.S. The European Parliament has voted in favor of a total ban on postharvest treatment of fruit and vegetables with pesticides as soon as this ban becomes feasible. The withdrawal of current fungicides from use in the United States and other parts of the world is creating a large, new market for biological control agents ("biocontrol"). Baker (1987) has defined biological control as "the decrease of inoculum or the disease-producing activity of a pathogen accomplished through one or more organisms, including the host plant but excluding man." The cost of commercializing a biological control agent is much less expensive than the cost of commercializing a synthetic pesticide because only Tier 1 toxicology tests (Hofstein et al 1994.) are required. Also, if a biological control agent is properly selected, fewer new environmental impact studies are required. Web site: http://www.delphion.com/details?pn=US06419922__ •

Cyclic lipopeptide from Cryptosporiopsis quercina possessing antifungal activity Inventor(s): Strobel; Gary A. (Bozeman, MT) Assignee(s): HMV Corporation (Alpine, UT) Patent Number: 6,613,738 Date filed: May 30, 2001 Abstract: A unique lipopeptide antimycotic, termed Cryptocandin, is described from Cryptosporiopsis cf quercina, an endophytic fungus. Cryptocandin with a molecular mass of 1079 contains equimolar amounts of 1,2-dihydroxy-homotyrosine, 4-hydroxy proline, threonine, glutamine, 3-hydroxy-4-hydroxy methyl proline, 4,5 dihydroxy ornithine, and palmitic acid. Cryptocandin is chemically related to well-known antimycotics, the echinocandins, and pneumocandins which are produced by such fungi as Zalerion arboricola, Pezicula spp., and Aspergillus spp. Cryptocandin has minimum inhibitory concentration values less than 0.03.mu.g ml.sup.-1 against isolates of Candida albicans, Trichophyton mentagrophytes and Trichophyton rubrum. Cryptocandin is also active against a number of plant pathogenic fungi including Sclerotinia sclerotiorum and Botrytis cinerea. Excerpt(s): The present invention is related to the isolation of an antimycotic compound. The present invention is also related to an antimycotic composition comprising the

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compound, and a method for controlling or treating fungal infection, particularly in humans and plants. Human and plant infections caused by pathogenic fungi are a continuing and serious problem. Thus, the discovery and characterization of novel, effective antimycotics is especially important. In the case of humans, the increase in fungal infections has resulted, in part, from the frequent use of antibacterial compounds, which enhances opportunities for fungal infections. Furthermore, there is a worldwide increase in the number of immunocompromised patients who are susceptible to fungal infections. This patient population has resulted from the AIDS epidemic, chemotherapy of cancer patients, and the profusion of organ transplant patients (Miller et al., 1998). Cryptosporiopsis cf. quercina is the imperfect stage of Pezicula cinnamomea, a fungus commonly associated with hardwood species in Europe (Sutton, 1980). This fungus and related species occur as endophytes and plant pathogens in many parts of the world (Sutton, 1980). Certain Pezicula spp. and Zalerion arboricola produce one or more members of a family of antimycotics, (lipopeptides) known as the pneumocandins. Related lipopeptides, the echinocandins, are also produced by Aspergillus species. Web site: http://www.delphion.com/details?pn=US06613738__ •

Cytochrome b5 gene and protein of Candida tropicalis and methods relating thereto Inventor(s): Craft; David L. (Fort Thomas, KY), Loper; John C. (Cincinnati, OH), Madduri; Krishna M. (Westfield, IN) Assignee(s): Cognis Corporation (Gulph Mills, PA) Patent Number: 6,503,734 Date filed: July 24, 2001 Abstract: A novel gene has been isolated which encodes cytochrome b5 (CYTb5) protein of the.omega.-hydroxylase complex of C. tropicalis 20336. Vectors including this gene, and transformed host cells are provided. Methods of increasing the production of a CYTb5 protein are also provided which involve transforming a host cell with a gene encoding this protein and culturing the cells. Methods of increasing the production of a dicarboxylic acid are also provided which involve increasing in the host cell the number of genes encoding this protein. Excerpt(s): This invention relates to processes and compositions involved in dicarboxylic acid production in yeast. More particularly, the invention relates to a novel gene which encodes a cytochrome b5 protein in Candida tropicalis. Aliphatic dioic acids are versatile chemical intermediates useful as raw materials for the preparation of perfumes, polymers, adhesives and macrolid antibiotics. While several chemical routes to the synthesis of long-chain.alpha.,.omega.-dicarboxylic acids are available, the synthesis is not easy and most methods result in mixtures containing shorter chain lengths. As a result, extensive purification steps are necessary. While it is known that long-chain dioic acids can also be produced by microbial transformation of alkanes, fatty acids or esters thereof, chemical synthesis has remained the most commercially viable route, due to limitations with the current biological approaches. Several strains of yeast are known to excrete.alpha.,.omega.-dicarboxylic acids as a byproduct when cultured on alkanes or fatty acids as the carbon source. In particular, yeast belonging to the Genus Candida, such as C. albicans, C. cloacae, C. guillermondii, C. intermedia, C. lipolytica, C. maltosa, C. parapsilosis and C. zeylenoides are known to produce such dicarboxylic acids (Agr. Biol. Chem. 35: 2033-2042 (1971)). Also, various strains of C. tropicalis are known to produce dicarboxylic acids ranging in chain lengths from C.sub.11 through C.sub.18 (Okino et al., B M Lawrence, B D Mookherjee and B J Willis (eds), in Flavors and

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Fragrances: A World Perspective. Proceedings of the 10.sup.th International Conference of Essential Oils, Flavors and Fragrances, Elsevier Science Publishers BV Amsterdam (1988)), and are the basis of several patents as reviewed by Buhler and Schindler, in Aliphatic Hydrocarbons in Biotechnology, H. J. Rehm and G. Reed (eds), Vol. 169, Verlag Chemie, Weinheim (1984). Web site: http://www.delphion.com/details?pn=US06503734__ •

DNA encoding--candida albicans integrin-like protein Inventor(s): Bendel; Catherine M. (Hopkins, MN), Gale; Cheryl A. (Minneapolis, MN), Hostetter; Margaret K. (Minneapolis, MN), Tao; Nian-jun (Malden, MA) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN) Patent Number: 6,346,411 Date filed: March 8, 1999 Abstract: An isolated and purified DNA molecule encoding Candida albicans protein with integrin-like motifs, the protein itself, antibodies thereto, and methods of use, are provided. Excerpt(s): Candida albicans is the leading fungal pathogen in normal hosts and in patients with damaged immune systems. In normal hosts, disease caused by C. albicans ranges from mild, easily treated, superficial disease (e.g., thrush in newborn infants; paronychia in workers whose hands are immersed in water) to more severe, chronic or recurrent infections (e.g., candidal vaginitis). It is estimated that 5% of women of childbearing age will suffer from recurrent candidal vaginitis (Hurley, "Trends in candidal vaginitis." Proc. R. Soc. Med. 70 (Suppl. 4), 1-8 (1970), and that virtually every woman will experience at least one episode during her reproductive years. Vaginitis is particularly frequent in otherwise normal females with diabetes or a history of prolonged antibiotic or oral contraceptive use. While short-term topical therapy is effective in treating individual episodes of vaginitis, such agents do not prevent recurrences. Thus, even in the normal host, infection with C. albicans can occur at epithelial surfaces, and recurrences are not prevented by presently available therapies. In immunocompromised hosts such as cancer patients, transplant patients, postoperative surgical patients, premature newborns, or HIV-infected people, C. albicans ranks as the leading fungal pathogen. In this population, disease ranges from aggressive local infections such as periodontitis, oral ulceration, or esophagitis in HIV-infected patients, to complex and potentially lethal infections of the bloodstream with subsequent dissemination to brain, eye, heart, liver, spleen, kidneys, or bone. Such grave prognoses require more toxic therapy, with attendant consequences from both the underlying infection and the treatment. Here again, the infection typically begins at an epithelial site, evades local defenses, and invades the bloodstream in the face of immunosuppression. Strategies to interrupt candidal adhesion therefore have broad applicability to the prevention of mild but recurrent disease in the normal host and to the reduction of substantial morbidity and mortality in the immunocompromised. Vertebrate integrins are composed of two subunits: an.alpha.-subunit and a.beta.subunit. There are approximately 14.alpha. and 8.beta. subunits described to date in vertebrate cells. Using monoclonal or polyclonal antibodies to vertebrate integrins, several investigators have obtained evidence for integrin-like proteins in C. albicans: an.alpha.M analog, an.alpha. 5/.beta.1 complex, or a.beta.1 analog. Neither the.alpha. 5/.beta.1 complex nor the.beta.1 analog has been isolated from C. albicans or from any

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other candidal species, and the responsible genes encoding these "integrin-like proteins" have not been identified. Web site: http://www.delphion.com/details?pn=US06346411__ •

Dominant selectable marker for gene transformation and disruption in yeasts Inventor(s): Bussey; Howard (Westmount, CA), Davison; John (Montreal, CA), Roemer; Terry (Montreal, CA) Assignee(s): McGill University (Montreal, CA) Patent Number: 6,562,595 Date filed: February 16, 2001 Abstract: The present invention provides a novel dominant selectable marker system in yeast that is based on an aminoglycoside, nourseothricin (NST). This compound possesses a powerful antifungal activity against Candida albicans and S. cerevisiae. The invention provides a cognate drug resistance marker for use in gene transformation and disruption experimentation in Candida albicans and Saccharomyces cerevisiae. In particular, the invention presents: 1) direct utility for gene manipulations in both clinically and experimentally relevant strains regardless of genotype and without affecting growth rate, or hyphal formation; and 2) applicability to antifungal drug discovery, including target validation and various forms of drug screening assays. Excerpt(s): This invention relates to the discovery of nourseothricin (NST) drug sensitivity in the pathogenic yeast, Candida albicans and in Saccharomyces cerevisiae. In particular, the present invention relates to a cognate drug resistance marker system for use in gene transformation and disruption experimentation. Specifically, the present invention provides a modified nourseothricin/streptothricin resistance gene, SAT, for expression in C. albicans. The present invention also provides a cell, nucleic acid molecule, and vector comprising the modified SAT1 nucleic acid sequence. The present invention further provides a SAT expression module for gene knock-outs. Opportunistic fungi are a rapidly emerging class of microbial pathogens causing systemic fungal infection or "mycosis" in patients immunocompromised either by illness (e.g., AIDS) or standard medical treatment (e.g., organ transplants, chemotherapy, radiation therapy). Candida spp. rank as the predominant genus of such fungal pathogens. In recent years, rapid and reliable diagnosis of fungal infection has advanced primarily through the application of molecular biological techniques. Understanding the pathogenesis of this organism, from which novel treatment strategies will develop, is also dependent on improved techniques in molecular genetics. The recent commitment by the Stanford Sequence Center to sequence the entire C. albicans yeast genome will accelerate our understanding in both the biology and eventual treatment of candidiasis. The DNA sequence resulting from this enterprise however offers only a prediction towards potential pathogenesis pathway(s) and antifungal targets. Maximum information gained from this effort requires experimentation. The ability to study the role of any particular gene, both by abolishing its function through gene disruption experiments, as well as overproducing its gene product through transformation experiments, directly tests the predictions made by bioinformatic analysis. As C. albicans is an imperfect fungus which lacks a sexual cycle and is fixed in the diploid state, gene disruption experiments are more cumbersome, requiring replacement of both alleles of the target gene before an examination of its null phenotype be determined. To this end, improved DNA methodologies are required for experimentation in C. albicans.

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Web site: http://www.delphion.com/details?pn=US06562595__ •

Fungicidal saponin, CAY-1, and isolation thereof from Capsium species fruit Inventor(s): Bland; John M. (Slidell, LA), De Lucca, II; Anthony J. (Metairie, LA), Selitrennikoff; Claude P. (Denver, CO), Vigo; Craig B. (Metairie, LA) Assignee(s): Mycologics, Inc. (Denver, CO), The United States of America as represented by the Secretary of Agriculture (Washington, DC) Patent Number: 6,310,091 Date filed: September 14, 2000 Abstract: A novel antifungal compound, "CAY-1", was isolated from the dried fruit of Capsicum frutescens (cayenne pepper), purified to homogeneity, and characterized as a novel sterol glycoside (a saponin) with a molecular mass of 1243.35 Da. CAY-1 demonstrates antifungal activity against a large variety of fungal organisms associated with diseases in plants, animals and humans including, but not limited to, Aspergillus flavus, A. fumigatus, A. parasiticus, A. niger, Pneumocystis carnii and Candida albicans, but has minimal toxic effects on mammalian cells. Excerpt(s): This invention relates to a novel fungicidal saponin and its isolation from cayenne pepper or other capsicum species fruit. This compound shows potential for improving crop resistance to a variety of aflatoxin-producing fungi and also as a pharmaceutical against human and animal fungal-induced diseases. The identification of novel antifungal agents has been a continuing challenge. Due to the occurrence of new disease epidemics in agricultural crops and as a result of the growing resistance to antimicrobial drugs, there is an ongoing search for new antifungal compounds having unique structures. The need for novel antifungal agents is significant, and is especially critical in the medical field. Immunocompromised patients provide perhaps the greatest challenge to modern health care delivery. During the last three decades there has been a dramatic increase in the frequency of fungal infections in these patients (Herbrecht, R., Eur. J. Haematol., 1996, 56:12-17; Cox, G. et al., Curr. Opin. Infect. Dis., 1993, 6:422-426; Fox, J. L., ASM News, 1993, 59:515-518). Deep-seated mycoses are increasingly observed in patients undergoing organ transplants and in patients receiving aggressive cancer chemotherapy (Alexander, B. D. et al., Drugs, 1997, 54:657-678). The most common pathogens associated with invasive fungal infections are the opportunistic yeast, Candida albicans, and the filamentous fungus, Aspergillus fumigatus (Bow, E. J., Br. J. Haematol., 1998, 101:1-4; Wamock, D. W., J. Antimicrob. Chemother., 1998, 41:95-105). There are an estimated 200,000 patients per year who acquire nosocomial fungal infections (Beck-Sague, C. M. et al., J. Infect. Dis., 1993, 167:1247-1251); bloodstream fungal infections have a mean mortality rate of 55 w. Also adding to the increase in the numbers of fungal infections is the emergence of Acquired Immunodeficiency Syndrom (AIDS) where virtually all patients become affected with some form of mycoses (Alexander, B. D. et al., Drugs, 1997, 54:657-678; HIV/AIDS Surveillance Report, 1996, 7(2), Year-End Edition; Hood, S. et al., J. Antimicrob. Chemother., 1996, 37:71-85). The most common organisms encountered in these patients are Cryptococcus neoformans, Pneumocystis carinii, and C. albicans (HIV/AIDS Surveillance Report, 1996, 7(2), YearEnd Edition; Polis, M. A. et al., AIDS: Biology, Diagnosis, Treatment and Prevention, fourth edition, 1997). New opportunistic fungal pathogens such as Penicillium marneffei, C. krusei, C. glabrata, Histoplasma capsulatum, and Coccidioides immitis (HIV/AIDS Surveillance Report, 1996, 7(2), Year-End Edition; Ampel, N. M., Emerging

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Infectious Diseases, 1996, 2:109-116) are also being reported with regularity in immunocompromised patients throughout the world. Web site: http://www.delphion.com/details?pn=US06310091__ •

Isolated Candida albicans oligopeptide transporter gene Inventor(s): Becker; Jeffrey M. (Knoxville, TN), Lubkowitz; Mark A. (Berkeley, CA) Assignee(s): The University of Tennessee Research Corporation (TN) Patent Number: 6,441,134 Date filed: October 2, 1998 Abstract: A Candida albicans oligopeptide transport gene, OPT1, was cloned from a C. albicans genomic library through heterologous expression in the Saccharomyces cerevisiae di-/tripeptide transport mutant PB1X-9B. When transformed with a plasmid harboring OPT1, S. cerevisiae PB1X-9B, which did not express tetra-/pentapeptide transport activity under the conditions used, was conferred with an oligopeptide transport phenotype as indicated by growth on the tetrapeptide Lysyl-Leucyl-LeucylGlycine, sensitivivity to toxic tetra- and pentapeptides, and an increase in the initial uptake rate of the radiolabeled tetrapeptide Lysyl-Leucyl-Glycyl-[.sup.3 H]Leucine. The entire 3.8 kb fragment containing the oligopeptide transport activity was sequenced and an open reading frame of 2349 nucleotides containing a 58 nucleotide intron was identified. The deduced protein product of 783 amino acid residues contained twelve hydrophobic regions suggestive of a membrane transport protein. The oligopeptide transporter facilitates targeting of antifungal, especially anticandidal drugs. Excerpt(s): The invention relates to novel nucleic acid sequences encoding peptide transporters, to novel polypeptides and drug delivery systems. Peptide transport, a phenomenon defined as the translocation of peptides across the plasma membrane in an energy-dependent manner, has been well documented in bacteria, plants, fungi, and mammals (for reviews see Becker & Naider, 1995; Payne and Smith, 1994). Upon internalization, peptides are quickly hydrolyzed into their amino acid components to serve as sources of amino acids or nitrogen. In addition to acquiring nutrients from the environment, peptide transport has been shown to play a role in recycling cell wall peptides and in transducing signals for group behaviors such as sporulation and competency in B. subtilis and chemotaxis in E. coli. Recently it has been proposed that in Salmonella typhimurium peptide transporters aid the bacteria in evading the host immune response by transporting membrane disrupting peptides away from the plasma membrane (Parra-Lopez et al., 1993). Similarly, in Streptococcus pneumoniae the peptide transporters encoded by plpA and the amiA loci play a role in virulence by modulating adherence to epithelial and endothelial cells (Cundel et al., 1995). A family of di-/tripeptide transporters named the PTR (Peptide TRansport) Family has recently been identified. This family is characterized by several conserved motifs, has twelve putative transmembrane domains, and is driven by the proton motive force. Members of the PTR family have been identified in a broad variety of eukaryotes and one prokaryote as well (Steiner et al, 1995). Well characterized members of the PTR family are the diand tripeptide transporters from S. cerevisiae (ScPTR2, Perry et al., 1994) and from C. albicans (CaPTR2, Basrai et al., 1995). Both CaPTR2 and ScPTR2 have been shown to be regulated by nitrogen source and inducible by micromolar amounts of amino acids; their encoded proteins have broad substrate specificities with a preference for peptides containing hydrophobic residues (Basrai et al., 1992; Island et al., 1987). Prior to the establishment of the PTR family, all peptide transporters cloned were from prokaryotes

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and were members of the ATP Binding Cassette (ABC) Superfamily (Higgins, 1992). Recently, transporters from the PTR family have been identified in the prokaryote Lactococcus lactis (Hagting et al., 1995). However, in eukaryotes all peptide transporters thus far identified are members of the PTR family. Web site: http://www.delphion.com/details?pn=US06441134__ •

Mammalian-derived peptides for the treatment of microbial infections Inventor(s): Dubnick; Bernard (Old Tappan, NJ), Hoffman; Brian F. (Key Biscayne, FL) Assignee(s): Theragem, Inc. (OldTappan, NJ) Patent Number: 6,337,314 Date filed: July 14, 1999 Abstract: The present invention provides compositions useful as antimicrobial agents which include mammalian hemoglobin, the.alpha. and.beta. chains of hemoglobin free of heme, fragments of the.alpha. and.beta. chains that result from cyanogen bromide cleavage of the.alpha. and.beta. chains, and synthetic peptides derived therefrom. The compositions exert antimicrobial activity against both bacteria and fungi that is comparable to known antimicrobial peptides from human neutrophils, cathepsin G and azurocidin. Sensitive organisms include Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, Gram-positive bacteria such as Staphylococcus aureus and Streptococcus faecalis, and the fungus Candida albicans. Methods for preparing the compositions also are provided. Excerpt(s): The present invention relates to a method for treating microbial infections of mammals, including humans and other primates; a method for killing bacteria and fungi; and a method for treating material subject to microbial contamination by administration of an effective antimicrobial amount of hemoglobin, or of the.alpha. or.beta. chains of this molecule, free of heme, or polypeptide fragments of the.alpha. and.beta. chains resulting from cleavage by cyanogen bromide or synthetic fragments thereof. The invention also relates to compositions comprising such proteins, polypeptides or fragments. Many bacteria produce antimicrobial peptides (bacteriocins) and proteins; those released from Gram-negative bacteria are the more potent and have the wider spectrum of activity (2). The defensins are small antimicrobial peptides found in neutrophils, non-human macrophages and Paneth cells (3). Amphibian skin is a rich source of antimicrobial peptides, one of these, magainin, isolated from Xenopus laevis, currently is undergoing clinical trial (4,5). Plants form a variety of gene-encoded antimicrobial peptides including the phytoalexins, the PR proteins and the AMPs (6,7). Insects have been shown to synthesize bacteriocidal peptides and proteins such as cecropin obtained from the moth Cecropia (8,9,10) and the sarcotoxins obtained from the larvae of the flesh fly Sarcocphaga perigrina (11). The hemocytes of the horse-shoe crab Limulus are the source of the tachyplesins and squalamine, an aminosteroid with antimicrobial activity, has been isolated from the shark, Squalus acanthias (12). Thus, many antimicrobial substances lie within the families of "natural" antibiotics such as the cecropins, magainins, defensins, serprocidins and others. These substances are widely distributed in nature and provide an innate defense mechanism against infection in species ranging from insects to amphibians to mammals. Generally these substances are stored in cells, to be induced and secreted within the animal when challenged. Many act by disrupting the bacterial cell membrane selectively; many would be toxic to host cells as well, were they not sequestered (13). A number of these compounds have been proposed as being useful as antimicrobial agents (14,15).

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Web site: http://www.delphion.com/details?pn=US06337314__ •

Method for detecting candida infection Inventor(s): Miyada; Charles Garrett (Mountain View, CA), Quong; Melanie W (La Jolla, CA), Switchenko; Arthur C. (Palo Alto, CA), Wong; Man-Ying Laurie (Fremont, CA) Assignee(s): Dade Behring Marburg GmbH (Marburg, DE) Patent Number: 6,426,204 Date filed: June 7, 1995 Abstract: A D-arabinitol dehydrogenase enzyme is disclosed. The enzyme is capable of catalyzing the oxidation of D-arabinitol and substantially incapable of catalyzing the oxidation of D-mannitol and is substantially free of other enzymes capable of oxidizing D-mannitol. Also disclosed are methods for determining D-arabinitol. In one embodiment the method comprises the steps of providing in combination (1) a medium suspected of containing D-arabinitol and (2) a D-arabinitol dehydrogenase enzyme and examining the medium for the product of the oxidation of the D-arabinitol. The enzyme utilized is capable of catalyzing the oxidation of D-arabinitol and substantially incapable of catalyzing the oxidation of D-mannitol. Kits for conducting the present method are also disclosed. Excerpt(s): At present the laboratory tools available to clinicians for the diagnosis of invasive candidiasis are limited. Surveillance cultures of peripheral sites have little predictive value, with the possible exception of Candida tropicalis infection in neutropenic patients. Blood cultures, even when they are tailored for optimal growth of fungi, are slow, insensitive, and nonspecific. Measurement of antibodies to Candida is not helpful in immunosuppressed patients who comprise the very group that is most vulnerable to invasive infections. Detection of circulating fungal products, particularly mannan, provides the desired level of specificity, but the clinical sensitivity of current assays is disappointing, and the technology for performing them is not readily portable to clinical laboratories. Commercially available latex agglutination kits detect uncharacterized antigen(s) and lack sensitivity and specificity. Most medically important species of Candida produce micromolar amounts of the pentitol D-arabinitol in vitro and there is considerable evidence that patients with invasive candidiasis have higher serum D-arabinitol levels and higher serum D-arabinitol/creatinine ratios than uninfected patients. Therefore, D-arabinitol is potentially useful as a diagnostic marker for invasive candidiasis, a disease that often is difficult to diagnose antemortem by traditional methods. Enantioselective measurements of D-arabinitol in human serum were originally made by combined microbiologic-gas chromatographic (GC) and enzymatic-GC techniques. These approaches were, however, time consuming and cumbersome. Recently, two GC methods have been developed that employ columns with a chiral stationary phase capable of separating enantiomers of arabinitol. Although these methods are highly specific for D-arabinitol and do not require serum pretreatment by enzymatic or microbiologic techniques, they are too cumbersome for routine use in the clinical laboratory. A more practical enzymatic fluorometric method has been developed that uses an Enterobacter aerogenes (Klebsiella pneumoniae) Darabinitol dehydrogenase. Unfortunately, cross reactivity of the dehydrogenase with Dmannitol, a hexitol normally present in human serum, reduces the specificity of this assay. Web site: http://www.delphion.com/details?pn=US06426204__

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Method for eliminating ethanol in exhaust gas Inventor(s): Matsumoto; Nobuya (Osaka, JP), Saeki; Takeshi (Hyogo, JP), Shiba; Hirotaka (Osaka, JP), Tada; Chieko (Hyogo, JP) Assignee(s): Suntory Limited (Osaka, JP) Patent Number: 6,423,534 Date filed: October 22, 1999 Abstract: A method and an apparatus for decomposing and eliminating ethanol in an exhaust gas by bringing the ethanol in the exhaust gas into contact with an ethanolutilizing microorganism held in a filter bed are provided. A microorganism selected from the genus Candida, the genus Pichia and/or the genus Hansenula is used as the ethanol-utilizing microorganism, whereby a method and an apparatus having a high removal efficiency of ethanol in the exhaust gas, and being capable of long-term, stable decomposition and elimination of ethanol under high concentration, high load capacity, can be provided. Excerpt(s): This invention relates to a novel method for eliminating ethanol in an exhaust gas by use of a microorganism. More specifically, the invention relates to a method for eliminating ethanol, comprising passing an exhaust gas, which contains ethanol, etc., through a filter bed holding an ethanol-utilizing microorganism, to bring the ethanol, etc. into contact with the microorganism, thereby decomposing the ethanol, etc. so that the ethanol, etc. may be directly eliminated from the exhaust gas. The invention also relates to an apparatus used in performing this method. Ethanol is one of the volatile organic compounds which contributes to the destruction of the ozone layer, although not to such a high degree as methane. Thus, it is necessary to suppress the emission of ethanol-containing exhaust gases formed during the manufacturing process for fermentation products, for example, at bakery, soy sauce plants, alcohol production plants, and breweries or distilleries; or those generated, for example, at laundry factories using ethanol as a solvent. This is a crucial task for the protection of the earth's environment. Exhaust gas containing ethanol have often been eliminated by methods, such as flame incineration using a boiler or the like, catalytic combustion, adsorption to activated carbon or resin, and dissolution into water by mans of a scrubber or by cooling condensation. Treating methods other than burning have required that ethanol be recovered, and then further subjected to combustion or microbial treatment as a postrecovery step. Web site: http://www.delphion.com/details?pn=US06423534__

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Nucleic acids for identifying anti-fungal agents, and uses related thereto Inventor(s): Berlin; Vivian (Dunstable, MA), Damagnez; Veronique (Cambridge, MA), Smith; Susan E. (Boston, MA) Assignee(s): GPC Biotech Inc. (Waltham, MA) Patent Number: 6,455,281 Date filed: December 20, 1996 Abstract: The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell

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wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products. Excerpt(s): Work described herein was supported in part by funding from the National Institute of Health. The United States Government has certain rights in inventions pertaining to that work. Fungal infections of humans range from superficial conditions, usually caused by dermatophytes or Candida species, that affect the skin (such as dermatophytoses) to deeply invasive and often lethal infections (such as candidiasis and cryptococcosis). Pathogenic fungi occur worldwide, although particular species may predominate in certain geographic areas. In the past 20 years, fungal infections have increased dramatically--along with the numbers of potentially invasive species. Indeed, fungal infections, once dismissed as a nuisance, have begun to spread so widely that they are becoming a major concern in hospitals and health departments. Fungal infections occur more frequently in people whose immune system is suppressed (because of organ transplantation, cancer chemotherapy, or the human immunodeficiency virus), who have been treated with broad-spectrum antibacterial agents, or who have been subject to invasive procedures (catheters and prosthetic devices, for example). Fungal infections are now important causes of morbidity and mortality of hospitalized patients: the frequency of invasive candidiasis has increased tenfold to become the fourth most common blood culture isolate (Pannuti et al. (1992) Cancer 69:2653). Invasive pulmonary aspergillosis is a leading cause of mortality in bone-marrow transplant recipients (Pannuti et al., supra), while Pneumocystis carinii pneumonia is the cause of death in many patients with acquired immunodeficiency syndrome in North America and Europe (Hughes (1991) Pediatr Infect. Dis J. 10:391). Many opportunistic fungal infections cannot be diagnosed by usual blood culture and must be treated empirically in severely immunocompromised patients (Walsh et al. (1991) Rev. Infect. Dis. 13:496). Web site: http://www.delphion.com/details?pn=US06455281__ •

Peptides which mimic candida carbohydrate epitopes and their use in a vaccine Inventor(s): Cutler; Jim E. (Bozeman, MT), Glee; Pati M. (Bozeman, MT) Assignee(s): The Research and Development Institute, Inc. (Bozeman, MT) Patent Number: 6,309,642 Date filed: May 13, 1998 Abstract: A composition, pharmaceutical composition, vaccine and method for the treatment of disseminated candidiasis due to infection by C. albicans. The composition includes phosphomannan of C. albicans, peptide mimotopes of phosphomannan epitopes, or polynucleotides encoding the peptide mimotopes. Monoclonal antibodies for use in passive immunization against candida infections are also provided. Excerpt(s): The present invention relates to peptides which mimic carbohydrate epitopes (mimotopes) of Candida and to a vaccine comprising the peptide or polynucleotides encoding the peptide mimotopes or antibodies to the peptides and a method for the treatment of disseminated candidiasis due to infection by Candida albicans. Candida albicans is a fungus responsible for various forms of candidiasis, a condition which may be found in normal and immunocompromised patients, such as those with acquired immune deficiency syndrome. Humans and mice who are neutropenic are especially at risk of developing disseminated candidiasis (Denning, D. W., et al. 1992. Antifungal

Patents 217

prophylaxis during neutropenia or allogeneic bone marrow transplantation: what is the state of the art? Chemotherapy 38(suppl 1):43-49; Matsumoto, M. S., et al. 1991. Effect of combination therapy with recombinant human granulocyte colony-stimulating factor (rG-CSF) and antibiotics in neutropenic mice unresponsive to antibiotics alone. J. Antimicrob. Chemother. 28:447-453; Meunier, F. 1987. Prevention of mycoses in immunocompromised patients. Rev. Infect. Dis. 9:408-416; Meunier, F., et al. 1992. Candidemia in immunocompromised patients. Clin. Infect. Dis. 14 (Suppl 1):S120-S125; and Van't Wout, J. W. et al. 1989. Comparison of the efficacies of amphotericin B, Fluconazole, and Itraconazole against a systemic Candida albicans infection in normal and neutropenic mice. Antimicrob. Agents Chemother. 33: 147-151). Several attempts have been made in the prior art to achieve immunostimulating compounds for the treatment of candidiasis as evidenced below. Web site: http://www.delphion.com/details?pn=US06309642__ •

Process for producing levodione Inventor(s): Fukuoka; Masatsuka (Shizuoka-ken, JP), Hiraga; Koki (Kakegawa, JP), Sekihara; Toru (Fukuroi, JP) Assignee(s): Roche Vitamins Inc. (Parsippany, NJ) Patent Number: 6,428,991 Date filed: July 28, 2000 Abstract: The present invention provides a process for producing (6R)-2,2,6trimethylcyclohexene-1,4-dione. This process includes contacting, in a reactor, 2,6,6trimethyl-2-cyclohexene-1,4-dione with a yeast selected from the group consisting of Saccharomyces rouxii (Zygosaccharomyces rouxii), Saccharomyces delbrueckii (Saccharomyces unisporus, Tonilaspora delbrueckii), Saccharomyces willianus, Zygosaccharomyces bailii, Candida tropicalis, functional equivalents, subcultures, mutants, and variants thereof, in water, a water-miscible organic solvent, or a mixture of water and the water-miscible. organic solvent containing at least one assimilable carbon source; and isolating (6R)-2,2,6-trimethylcyclohexane-1,4-dione produced by the yeast from the reaction medium. Excerpt(s): The present invention relates to the microbial production of (6R)-2,2,6trimethylcyclohexane-1,4-dione (hereinafter referred to as levodione), a useful intermediate in the production of carotenoids, such as (3R,3'R)-zeaxanthin. More particularly, the present invention relates to a process for producing levodione of high purity and in high yield by the catalytic reaction of 2,6,6-trimethyl-2-cyclohlexene-1,4dione (hereinafter referred to as ketoisophorone) with a specific yeast. Levodione has previously been prepared through the reduction of the carbon-carbon double bond in ketoisophorone by contacting the ketoisophorone with baker's yeast, such as Saccharomyces cervisiae, which functions as an enantioselective biocatalyst (Biotechnology of Vitamins, Pigments and Growth Factors, Ed. Erick J. Vandamme, page 71, Elsevier Applied Science, London and New York). However, baker's yeast is not suitable for use in the industrial production of levodione because the yields are too low. In addition, the use of baker's yeast in the production of levodione is inefficient because the yeast cells cannot be reused because of the short lifetime of the reaction activity of the yeast. In addition, a complicated purification process is necessary when baker's yeast is used in the production process because it is difficult to separate the yeast from the culture solution after the catalytic reaction. One embodiment of the invention is a process for producing (6R)-2,2,6-trimethylcyclohexane-1,4-dione. This process includes

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contacting, in a reactor, 2,6,6-trimethyl-2-cyclohexene-1,4-dione with a yeast selected from the group consisting: of Saccharomyces rouxii (Zygosaccharomyces rouxii), Saccharomyces delbrueckii (Saccharomyces unisporus, Torulaspora delbrueckii), Saccharomyces willianus, Zygosaccharomyces bailii, Candida tropicalis, functional equivalents, subcultures, mutants, and variants thereof, in water, a water-miscible organic solvent, or a mixture of water and the water-miscible organic solvent containing at least one assimilable carbon source; and isolating (6R)-2,2,6-trimethylcyclohexane-1,4dione produced by the yeast from the reaction medium. Web site: http://www.delphion.com/details?pn=US06428991__ •

Production of lactate using crabtree negative organisms in varying culture conditions Inventor(s): Carlson; Ting (Dayton, OH), Eyal; Aharon (Jerusalem, IL), Hatzimanikatis; Vassily (Minneapolis, MN), Kolstad; Jeffrey J. (Wayzata, MN), Olson; Stacey (Minneapolis, MN), Rajgarhia; Vineet (Minnetonka, MN), Starr; John N. (Chaska, MN) Assignee(s): Cargill Dow Polymers, LLC (Minnetonka, MN) Patent Number: 6,485,947 Date filed: May 19, 2000 Abstract: Crabtree negative organisms such as Kluyveromyces, Pichia, Hansenula and Candida, are used to make selected organic products such as lactic acid. The organisms are cultured in a first culture medium that includes glucose, under conditions that promote cellular respiration. The organisms are then cultured under a second set of conditions that promote production of the selected organic product. The organisms preferably contain an exogenous lactate dehydrogenase gene. Excerpt(s): The invention relates to methods and materials involved in the production of organic products. Organic products such as lactic acid have many important industrial uses. For example, organic acids can be used to synthesize plastic materials as well as other products. To meet the increasing need for organic products, more efficient and cost effective production methods are being developed. One such method involves the use of bacteria. Specifically, certain bacteria can produce large quantities of particular organic products under certain fermentation conditions. The use of living bacteria as factories, however, is limited by the inability of the bacteria to grow as the organic product accumulates in the growth media. To circumvent such limitations, various product purification techniques have been employed during product synthesis. In addition, the use of microorganisms other than bacteria has been attempted. In fact, Saccharomyces cerevisiae, which is known to be acid tolerant, has been genetically modified in an attempt to produce lactic acid. Specifically, S. cerevisiae cells were modified by providing the cells with a bovine lactate dehydrogenase cDNA and disrupting endogenous pyruvate decarboxylase genes (PDC1, PDC5, and PDC6). While these modified S. cerevisiae cells produced some lactic acid, cell growth was suppressed leading to the conclusion that both cell growth and lactic acid production need improvement. The present invention relates generally to methods and materials for producing organic products. Specifically, the invention provides yeast cells, methods for culturing yeast cells, methods for making yeast cells, nucleic acid constructs, and methods and materials for producing various organic products. The invention is based on the discovery that particular microorganisms (e.g., bacterial and fungal microorganisms) can be genetically manipulated such that they have the ability, under specific culture conditions, to grow, utilize various carbon sources for growth as well as product production, and produce a desired organic product for commercial purposes.

Patents 219

For example, the yeast cells provided herein can grow and produce an organic product when cultured at low pH and high temperature. Having the ability to grow rapidly and produce an organic product efficiently under, for example, low pH and high temperature conditions is particularly advantageous. Specifically, the ability of a microorganism to tolerate low pH obviates the need to maintain a neutral pH environment, which can be difficult and expensive during large-scale production processes. In addition, the methods and materials needed to recover the desired organic product from a low pH broth can be more practical and efficient than those required to recover the same organic product from a broth having a more neutral pH. For example, certain organic acid products can precipitate out of solution as the pH drops below the product's pKa value, making recovery quite simple. Further, the ability of a microorganism to tolerate high temperatures obviates the need to maintain cool temperatures during the growth and production phases. Clearly, reducing the need to lower the temperature in a large volume tank of broth during large-scale production processes makes the overall process more efficient and less expensive. Moreover, the ability of a microorganism to tolerate both low pH and high temperature provides a convenient method for preventing contamination by other less tolerant microorganisms during the large-scale production processes. Web site: http://www.delphion.com/details?pn=US06485947__ •

Solid-chemical composition for sustained release of organic substrates and complex inorganic phosphates for bioremediation Inventor(s): Hince; Eric Christian (Campbell Hall, NY) Assignee(s): Geovation Technologies, Inc. (Florida, NY) Patent Number: 6,620,611 Date filed: January 6, 2001 Abstract: A slow-release solid chemical composition for environmental bioremediation is provided. The composition comprises a source of soluble organic substrates which include sugars, soluble organic polymers and mixtures of them in an amount of 7% to 90%, insoluble organic substrates an amount of 10% to 70%, complex inorganic phosphates in an amount of 0.5% to 7% and soluble organic salts in an amount of 2% to 70%. The insoluble organic substrates include fibrous plant materials, starches, cellulosic materials and mixtures of these substrates. The complex inorganic phosphates include ringed metaphosphates, linear polyphosphates and mixtures. The organic salts include lactates, formates, acetates, citrates, etc. Also the composition further comprises microorganisms which include Bacillus spp., Rhizobium spp., Bradyrhibzobium spp., Fibrobacter spp., Clostridium spp., Pseudomonas. spp., Geobacter spp., Arthrobacter spp., Nocardia, spp., aspergillus spp., Trichoderma spp., Candida spp., Yarrowia spp. and combinations of these microorganisms. The composition can be prepared in various forms, including granules, briquettes, pellets, tablets or capsules. Excerpt(s): This invention discloses advanced solid-chemical compositions which provide balanced, sustained-release sources of soluble and insoluble organic substrates and complex inorganic phosphates, as well as other beneficial agents, which when used as intended, promote the bioremediation of contaminated environmental media. Specifically, the present invention was developed to provide a relatively simple and inexpensive means of enhancing the anaerobic bioremediation and dehalogenation of halogenated organic contaminants, such as trichloroethene (TCE), as well as the biologically mediated chemical reduction of oxidized forms of certain inorganic

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contaminants, such as chromium (VI), uranium (VI), and arsenate-based pesticides. Either alone or in combination with other liquid- and solid-chemical compositions, it is the inventor's belief that the present invention also has the potential for the remediation of the gasoline additive methyl tertiary butyl ether (MTBE). The disclosed solidchemical compositions of the present invention provide improved means for (1) creating, enhancing, and maintaining anaerobic if not anoxic conditions by facilitating the biologically mediated removal of the available oxygen from the media; and (2) creating and maintaining reducing conditions (i.e., negative Eh values) and near neutral to slightly acidic pH conditions (6.ltoreq.pH.ltoreq.8) which favor anaerobic, biologically mediated chemical-reduction reactions, e.g., the reductive dehalogenation of halogenated organic contaminants and the reduction of the oxidized forms of certain metals. The disclosed solid-chemical compositions also provide means for maintaining the aforementioned conditions for sufficiently long periods of time to enable the biologically mediated degradation, transformation, and/or detoxification reactions to proceed to the extent that the concentrations and/or toxicity of the contaminants are reduced to acceptable levels. Soil and ground-water pollution caused by chemical contaminants released into the environment is a well documented, world-wide problem. Such chemical contamination is associated with many different types of industrial activities over the last two centuries. Common environmental contaminants include several different types and forms of petroleum hydrocarbons, halogenated organic compounds including solvents (e.g., tetra- and trichloroethene, methylene chloride), organochlorine pesticides (e.g., DDT and toxaphene), polychlorinated biphenyls (i.e., PCBs), and heavy metals and other inorganic contaminants such as cyanides. The available toxicological data indicates that many of these contaminants, in particular many of the halogenated organic compounds, are toxic, carcinogenic or potentially carcinogenic to humans, animals and other environmental receptors. In addition, the available environmental and ecological data have shown that many of these contaminants tend to persist in the environment for long time periods. The long-term stability and extremely slow degradation of many such environmental contaminants presents a substantial, long-term hazard to human health and the environment throughout the industrialized world. Web site: http://www.delphion.com/details?pn=US06620611__ •

Telomerase reverse transcriptase (TERT) genes from Candida albicans Inventor(s): Long; David M. (Livingston, MT), Love; Ruschelle A. (Bozeman, MT), Metz; Anneke M. (Bozeman, MT) Assignee(s): Research & Development Institute, Inc. (Bozeman, MT) Patent Number: 6,541,202 Date filed: October 13, 1999 Abstract: The present invention pertains, in general, to the identification, isolation and use of Telomerase Reverse Transcriptase (TERT) genes and the proteins encoded by such genes. In particular, the present invention pertains to the identification, isolation and use of TERT genes and TERT proteins from several genetically diverse and economically important organisms, including two human pathogens, Candida albicans and Plasmodium falciparum and an agronomic crop species, Oryza sativa. Excerpt(s): The present invention pertains, in general, to the identification and use of Telomerase Reverse Transcriptase (TERT) genes and the proteins encoded by such genes. In particular, the present invention pertains to the identification and use of TERT

Patents 221

genes and TERT proteins from several genetically diverse and economically important organisms, including two human pathogens and an agronomic crop species. All publications and patent applications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The protein encoded by the TERT gene, together with an RNA subunit, comprise telomerase, an enzyme required for the maintenance of telomeres. Telomeres, which are long stretches of short DNA sequence repeats located on the ends of linear chromosomes, are an essential component of the eukaryotic genome. They serve as "caps" on chromosomal termini, preventing loss of terminal sequence information and degradation of chromosomal DNA, as well as regulating expression of nearby genes. Telomerase has been shown to be responsible for maintenance of telomere length, as cells lacking this enzyme experience a shortening and eventual loss of telomeric sequence. For a recent review, see Bryan and Cech, 1999. Web site: http://www.delphion.com/details?pn=US06541202__ •

TFIIB transcription factor from Candida albicans and methods of screening for inhibitors of Candida albicans growth Inventor(s): Bradley; John Douglas (St. Louis, MO), Buratowski; Stephen (Needham, MA), Wobbe; C. Richard (Lexington, MA) Assignee(s): Harvard College, President & Fellows (Cambridge, MA), Scriptgen Pharmaceuticals (Medford, MA) Patent Number: 6,300,067 Date filed: December 3, 1998 Abstract: The invention encompasses a novel transcription factor from Candida albicans, TFIIB, a nucleic acid sequence encoding TFIIB, and methods of screening for inhibitors of Candida albicans growth by targeting TFIIB. Excerpt(s): The invention relates in general to transcription factors and to methods for screening for antifungal agents. The yeast Candida albicans (C. albicans) is one of the most pervasive fungal pathogens in humans. It has the capacity to opportunistically infect a diverse spectrum of compromised hosts, and to invade many diverse tissues in the human body. It can in many instances evade antibiotic treatment and the immune system. Although Candida albicans is a member of the normal flora of the mucous membranes in the respiratory, gastrointestinal and female genital tracts, in such locations, it may gain dominance and be associated with pathologic conditions. Sometimes it produces progressive systemic disease in debilitated or immunosuppressed patients, particularly if cell-mediated immunity is impaired. Sepsis may occur in patients with compromised cellular immunity, e.g., those undergoing cancer chemotherapy or those with lymphoma, AIDS, or other conditions. Candida may produce bloodstream invasion, thrombophlebitis, endocarditis, or infection of the eyes and virtually any organ or tissue when introduced intravenously, e.g., via tubing, needles, narcotics abuse, etc. Candida albicans has been shown to be diploid with balanced lethals, and therefore probably does not go through a sexual phase or meiotic cycle. This yeast appears to be able to spontaneously and reversibly switch at high frequency between at least seven general phenotypes. Switching has been shown to occur not only in standard laboratory strains, but also in strains isolated from the mouths of healthy individuals. Web site: http://www.delphion.com/details?pn=US06300067__

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TUP1 sequences from Candida albicans and methods for screening agents for inhibiting virulence in Candida albicans using TUP1 Inventor(s): Braun; Burkhard (San Francisco, CA), Johnson; Alexander D. (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,433,137 Date filed: July 1, 1998 Abstract: The present invention provides TUP1 polynucleotides, including TUP1 polynucleotides encoding Tup1, and Tup1 polypeptides, from Candida albicans. Disruption of TUP1 function in C. albicans is associated with filamentous formation as well as low infectivity. These TUP1 polynucleotide and Tup1 polypeptide sequences (and anti-Tup1 antibodies derived from Tup1 polypeptides) may be used in methods of detecting C. albicans sequences in a biological sample. Further, the invention provides methods for screening agents which may control C. albicans virulence and compositions comprising these agents. The invention also provides methods of obtaining gene(s) and/or gene product(s) which are involved in a TUP1 pathway, as well as methods of controlling C. albicans virulence by comprising TUP1 function. Excerpt(s): This invention relates to the field of polynucleotides and polypeptides. More specifically, this invention relates to TUP1 polynucleotides from Candida albicans, Tup1 polypeptides, and methods using these polynucleotides and polypeptides, especially for screening candidate anti-fungal agents. The yeast Candida is a ubiquitous human commensal, known as the causative agent of candidiasis. The majority of the diseases are caused by the species Candida albicans. It is the most prevalent commensal and opportunistic fungal pathogen of humans, causing common superficial infections as well as more serious systemic and organ infections. Cannon et al. (1995) J. Dental Research. 74:1152-1161. Exposure to C. albicans at or shortly after birth results in lifelong colonization in the host tissues, such as the gastrointestinal tract, oral cavity and genital area. It has been noted that approximately 75% of women would suffer from vaginal candidiasis at some stage in their lifetime. Bossche et al. (1993) Fungal Dimorphism 3-10; Fidel et al. (1996) Clin. Micro. Rev. 9(3):335-348. Whereas C. albicans infection often remains localized to the initial sites of contact in healthy individuals, C. albicans cells can invade submucosal vessels, disseminate hematogenously and become lifethreatening, especially to immunocompromised patients. The invasive forms of C. albicans infection are not only dangerous in their own right, but they are believed to facilitate infections by other opportunistic pathogens. In the last decades, the incidence of severe and systemic candidiasis has increased dramatically because of the growing number of immunocompromised patients suffering from AIDS, diabetes, cancer and other conditions. In addition, the widespread use of immunosuppressants for organ transplant patients, the common practice of radiation and chemotherapy for treating malignancies, as well as the growing size of the aging population have increased the morbidity of this opportunistic pathogen. For reviews, see Rubin et al. (1993) Eur. J Clin. Microbiol. Infect. Dis. 12 Suppl. 1, 542; Dudley et al. (1990) Pharmacotherapy 10:133; Paya (1993) Clin. Infect. Dis. 16:677-688; Rubin (1993) Eur. J Clin. Micro. Infect. Dis. 12 Suppl. 1: S42-S48. Web site: http://www.delphion.com/details?pn=US06433137__

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Use of polyols in combating yeast infection and polyol preparations for said use Inventor(s): Pearson; Julita (Kent, GB), Pepper; Tammy (Weybridge, GB), Saunders; David (Farnham, GB), Vargas Munita; Sergio Luis (Santiago, CL), Virkki; Markku (Espoo, FI) Assignee(s): Xyrofin Oy (Kotka, FI) Patent Number: 6,414,035 Date filed: September 25, 2000 Abstract: The invention relates to the use of polyols such as xylitol for the preparation of a composition to be administered in the treatment or prophylaxis of mucosal yeast infection in mammals, as well as to preparations for use in the systemic or topical therapeutic or prophylactic treatment of mucosal yeast infections. The invention relates specifically but not solely to the combating of infections caused by Candida s.p. in mucosa in connection with exocrine glands of the mammalian body. Excerpt(s): The present invention relates to the use of polyols such as xylitol for the preparation of a composition to be administered in the treatment or prophylaxis of mucosal yeast infection in mammals, as well as to preparations for use in the systemic or topical therapeutic or prophylactic treatment of mucosal yeast infections. The invention relates specifically but not solely to the combating of infections caused by Candida s.p. in mucosa in connection with exocrine glands of the mammalian body. Despite the availability of effective antifungal drugs, optimal prophylactic and therapeutic approaches for mucositis are still controversial. Factors that might have a stimulatory effect on fungal growth or decrease the effectiveness of antifungal therapy of mucositis have received little attention. Oral candidiasis is the most common opportunistic infection in AIDS, affecting up to 90% of the patients. It importantly interferes with nutrition. Studies suggest that the presence of oral candidiasis increases progression to AIDS, and that oral candidiasis is an independent risk factor for the development of Pneumocystis carinii pneumonia. Oral candidiasis is also one of the most common reasons for premature cessation of chemotherapy in cancer patients. Web site: http://www.delphion.com/details?pn=US06414035__

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Yeast extract composition, yeast for obtaining the same, and process for producing yeast extract composition Inventor(s): Nakajo; Yukihiro (Shizuoka, JP), Sano; Hiroyuki (Miyazaki, JP) Assignee(s): Nihon Tobacco Inc. (Tokyo, JP) Patent Number: 6,344,231 Date filed: May 9, 2000 Abstract: A composition of yeast extract from genus Candida is provided. In the said composition, contents of mannitol, glutamic acid, alanine, 5'-IMP and 5'-GMP are above 0.5%, above 2.0%, above 0.5%, above 1.5% and above 1.5%, respectively, all of which should simultaneously be satisfied the condition. Increased contents of alanine and 5'-IG of the extract of Candida yeast resulted to obtain yeast extract having sea tangle (kombu) (Laminariales, kelps)-like taste and flavor. Excerpt(s): A composition of yeast extract and yeast for obtaining the same, and a process for production of the composition of yeast extract. This invention relates to a composition of yeast extract having taste, of kombu (Laminariales, kelps) and

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mushrooms and flavor thereof, new yeast strain for obtaining the same, and a process for production of the composition of yeast extract. Conventionally used extracts of mushrooms and kombu (Laminariales, kelps, hereinafter designated as kombu) have good flavors, but addition of these natural extracts to the foods can only show simple taste. In order to increase richness in flavor, heaviness of the taste and better taste, various seasonings have simultaneously to be added. Consequently, the said extracts are not satisfactory for the purpose of commonly used or all-purpose seasonings. Web site: http://www.delphion.com/details?pn=US06344231__

Patent Applications on Candida 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 Candida: •

(R)-2-octanol dehydrogenases, methods for producing the enzymes, DNA encoding the enzymes, and methods for producing alcohols using the enzymes Inventor(s): Kudoh, Masatake; (Ibaraki, JP), Yamamoto, Hiroaki; (Ibaraki, JP) Correspondence: JANIS K. FRASER, PH.D., J.D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2084; US Patent Application Number: 20020192783 Date filed: October 16, 2001 Abstract: This invention provides (R)-2-octanol dehydrogenase that catalyzes oxidationreduction reaction using NAD.sup.+ (NADH) as a coenzyme and the genes that encodes them. The enzymes of this invention can be obtained from microorganisms such as the genera Pichia, Candida, and Ogataea, and so on. It is possible to produce alcohols, in particular, alcohols such as (S)-4-halo-3-hydroxybutyric acid esters and (R)propoxybenzene derivatives by reducing ketones with this (R)-2-octanol dehydrogenase. Moreover, the (R)-2-octanol dehydrogenase of this invention is excellent in activity and stereoselectivity. Excerpt(s): This is a continuation-in-part of PCT Application No. PCT/JP01/01082, filed Feb. 15, 2001, which claims priority from Japanese Application No. 2000-43506, filed Feb. 16, 2000, and Japanese Application No. 2000-374593, filed Dec. 8, 2000. These applications are incorporated herein by reference in their entirety. The present invention relates to novel (R)-2-octanol dehydrogenases useful for producing alcohols, ketones, particularly for producing optically active alcohols such as (S)-4-halo-3-hydroxybutyric acid esters and (R)-propoxybenzene derivatives, DNAs encoding the enzyme, methods for producing the enzymes, and methods for producing alcohols, ketones, particularly for producing optically active alcohols such as (S)-4-halo-3-hydroxybutyric acid esters and (R)-propoxybenzene derivatives using the enzymes. (S)-4-halo-3-hydroxybutyric acid esters are compounds used as intermediates in synthesizing HMG-CoA reductase inhibitors, D-carnitine, etc. These compounds are useful for syntheses of medicines and pesticides. Especially, how to get (to synthesize or separate) optically pure enantiomers of (S)-4-halo-3-hydroxybutyric acid esters is industrially important problem. So far,

10

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

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asymmetric synthesis, crystallization, and asymmetric reduction method using microorganisms such as baker's yeast (Unexamined Published Japanese Patent Application (JP-A) Sho 61-146191, JP-A Hei 6-209782, and such) are known as methods for producing (S)-4-halo-3-hydroxybutyric acid esters. However, these known methods are inappropriate for industrial use because of the problems such as low optical purities of products, low yield, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antibodies to the propeptide of candida albicans and methods of use Inventor(s): Devore-Carter, Denise; (Guilford, CT), Hostetter, Margaret K.; (Milford, CT) Correspondence: LARSON & TAYLOR, PLC; 1199 NORTH FAIRFAX STREET; SUITE 900; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030096975 Date filed: September 28, 2001 Abstract: Antibodies and agents which can bind to the propeptide of the Int1p protein of yeast microorganisms such as Candida albicans are provided which can be useful in methods for treating or preventing infections arising from such microorganisms. Microorganisms expressing the Int1p protein, such as C. albicans and S. cerevisiae, have shown an ability to immunomodulate host cells which allows infections of these microorganisms enhances to thrive and become virulent. In accordance with the present invention, peptide regions involved in the activation of the Int1p protein are isolated and targeted so as to provide a method of disrupting said activation and allow for treatment or prevention of infection by microorganisms expressing the int1p protein. In one preferred embodiment of the invention, an antibody or agent which can bind to the propeptide of the Int1p protein from C. albicans is utilized in methods to prevent or treat infections caused by C. albicans or other microorganisms expressing the Int1p protein. Excerpt(s): The present invention relates in general to antibodies which can bind to the propeptide sequence of the Int1p protein of Candida albicans and methods of utilizing such antibodies to prevent and treat infections from microorganisms such as C. albicans, and in particular to agents and antibodies capable of disrupting the propeptide region or other subregions of the Int1p protein and the use of such agents and antibodies in the treatment and prevention of infection from yeasts such as Candida albicans and other microorganisms expressing the Int1p protein. The dimorphic yeast, Candida albicans, is the leading fungal pathogen in normal hosts and in patients with damaged immune systems. In normal hosts, disease caused by C. albicans ranges from mild, easily treated, superficial disease (e.g., thrush in newborn infants; paronychia in workers whose hands are immersed in water) to more severe, chronic or recurrent infections (e.g., candidal vaginitis). It is estimated that 5% of women of child-bearing age will suffer from recurrent candidal vaginitis (Hurley, Proc. R. Soc. Med. 70 (Suppl., 4), 1-8 (1970), and that virtually every woman will experience at least one episode during her reproductive years. Vaginitis is particularly frequent in otherwise normal females with diabetes or a history of prolonged antibiotic or oral contraceptive use. While short-term topical therapy is effective in treating individual episodes of vaginitis, such agents do not prevent recurrences. Thus, even in the normal host, infection with C. albicans can occur at epithelial surfaces, and recurrences are not prevented by presently available therapies. In immunocompromised hosts such as cancer patients, transplant patients, post-operative surgical patients, premature newborns, or HIV-infected people, C.

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albicans ranks as the leading fungal pathogen. Invasion leading to systematic infection may also develop in neutropenic patients whose t-cell function is comprised. (Hostetter M K, Clinical Microbiology Reviews, Jan 1994, pp. 29-42.) In this population, disease ranges from aggressive local infections such as periodontitis, oral ulceration, or esophagitis in HIV-infected patients, to complex and potentially lethal infections of the bloodstream with subsequent dissemination to brain, eye, heart, liver, spleen, kidneys, or bone. Such grave prognoses require more toxic therapy, with attendant consequences from both the underlying infection and the treatment. Here again, the infection typically begins at an epithelial site, evades local defenses, and invades the bloodstream in the face of immunosuppression. Strategies to interrupt candidal adhesion therefore have broad applicability to the prevention of mild but recurrent disease in the normal host and to the reduction of substantial morbidity and mortality in the immunocompromised. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antifungal compounds and methods of use Inventor(s): Bradley, John; (St. Louis, MO), Buurman, Ed T.; (Arlington, MA), Davidov, Eugene; (Natick, MA), Desilva, Thamara; (Brookline, MA), Haq, Tariq; (Norwood, MA), Harris, Sandra; (Dayton, NJ), Komarnitsky, Svetlana; (Brookline, MA), Long, Fan; (Waltham, MA), McCoy, Melissa; (Arlington, MA), Mendillo, Marc; (Brighton, MA), Moore, Daniel; (Medford, MA), Moore, Jeffrey; (Brookline, MA), Sanderson, Karen; (Charlestown, MA), Thompson, Craig; (Arlington, MA), Zhu, Shuhao; (Waltham, MA) Correspondence: DARBY & DARBY P.C.; POST OFFICE BOX 5257; NEW YORK; NY; 10150-5257; US Patent Application Number: 20030027243 Date filed: June 28, 2001 Abstract: The invention provides screening methods for detecting and identifying compounds that bind to fungal specific target proteins and nucleic acids, as well as compounds which, upon binding or otherwise interacting with the target protein, can inhibit fungal growth, a method of preventing or inhibiting fungal growth in culture, a method of preventing or inhibiting fungal growth in a mammal and a method of studying pathogenic mycetes using such nucleic acid and/or protein sequences. Particularly preferred is the inhibition of the fungus Candida albicans. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119 from Provisional Patent Application Serial No. 60/215,164, filed Jun. 29, 2000, and Provisional Patent Application Serial No. 60/224,457, filed Aug. 10, 2000, which are hereby incorporated by reference in their entireties. The invention encompasses the use of fungal cidal targets in the screening for, isolation and development of antifungal chemicals and drugs to be used in the treatment of fungal infections, such as infections with Candida albicans. The invention encompasses methods of determining fungal cidal targets. Such fungal cidal targets are encompassed by nucleic acid and protein sequences encoded by such nucleic acid sequences which are isolated from S. ceriviseae, shown to be present in other fungi such as Candida albicans, and are shown to be both essential and fungal specific in both Sacchromyces ceriviseae and Candida albicans. The essential fungal specific nucleic acid and protein sequences may also be used in studying pathogenic mycetes or fungi. Fungi are a distinct class of microorganisms, of which most are free-living. They are eukaryotic organisms containing a nuclear membrane, mitochondria and endoplasmic reticulum. In addition, they are non-motile, do not contain chlorophyl and develop from spores (i.e.

Patents 227

yeasts, molds, mushrooms and rusts). The cell structure usually includes a rigid cell wall of mannan, glucan and chitin and a cytoplasmic membrane with a large percentage of ergosterol. The size and morphology of fungi vary from monomorphic yeasts like Cryptococcus and Saccharomyces species and dimorphic fungi like Candida albicans to filamentous fungi like Aspergillus species. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulati- ng hormone Inventor(s): Catania, Anna Pia; (Milano, IT), Lipton, James M.; (Woodland Hills, CA) Correspondence: Lyon & Lyon LLP; Suite 4700; 633 West Fifth Street; Los Angeles; CA; 90071; US Patent Application Number: 20020137685 Date filed: September 21, 2001 Abstract: The presence of the ancient anti-inflammatory peptide.alpha.-melanocyte stimulating hormone (.alpha.-MSH [1-13], SYSMEHFRWGKPV) in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense system.alpha.MSH and other amino acid sequences derived from.alpha.-MSH were determined to have antimicrobial influences, including against two major and representative cutaneous and mucosal pathogens: Staphylococcus aureus and Candida albicans.alpha.MSH peptides had antimicrobial effects against S. aureus and significantly reversed the enhancing effect of urokinase on S. aureus colony formation.alpha.-MSH and other amino acid sequences reduced C. albicans viability and germination.alpha.-MSH peptides also enhanced C. albicans killing by human neutrophils. The antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence KPV, one or more peptides including the amino acid sequence MEHFRWG, or a biologically functional equivalent of any of the foregoing. The most effective of the peptides were those bearing the C-terminal amino acid sequence of.alpha.-MSH, i.e.,.alpha.-MSH (1-13), (6-13), and (11-13). The.alpha.-MSH "core" sequence (4-10), important for melanotropic effects, was also effective but significantly less potent. Antimicrobial influences of.alpha.-MSH peptides could be mediated by their well-known capacity to increase cellular cAMP; this messenger was significantly augmented in peptide-treated yeast.alpha.-MSH has potent anti-inflammatory effects and is expected to be useful for treatment of inflammation in human and veterinary disorders. Reduced killing of pathogens is a detrimental consequence of therapy with corticosteroids and nonsteroidal anti-inflammatory drugs during infection. Therefore, anti-inflammatory agents based on.alpha.-MSH peptides that do not reduce microbial killing, but rather enhance it, would be very useful. The antimicrobial effects of these.alpha.-MSH peptides occurred over a broad range of concentrations including the physiological (picomolar) range. Excerpt(s): The present invention relates to new pharmaceutical compositions useful as antimicrobial agents, including, for example, for use in reducing the viability of microbes, reducing the germination of yeasts, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation in which there is microbial infection without reducing microbial killing, and for increasing the accumulation of cAMP in microbes. More particularly, this invention relates to antimicrobial agents including amino acid sequences derived from alpha-melanocytestimulating hormone (.alpha.-MSH) and biologically functional equivalents thereof.

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Mucosal secretions, phagocytes, and other components of the nonspecific (innate) host defense system initiate the response to microbial penetration before time-consuming adaptive immunity starts. Survival of plants and invertebrates, which lack adaptive immunity, illustrates effectiveness of host defense based on such innate mechanisms. Endogenous antimicrobial peptides are significant in epithelia, the barrier to environmental challenge that provides the first line of defense against pathogens. Production of natural antimicrobial peptides by phagocytes has been recognized for a long time. These natural antimicrobial peptides generally have a broad spectrum of activity against bacteria, fungi, and viruses. Martin, E., Ganz, T., Lehrer, R. I., Defensins and Other Endogenous Peptide Antibiotics of Vertebrates, J. Leukoc. Biol. 58, 128-136 (1995); Ganz, T., Weiss, J., Antimicrobial Peptides of Phagocytes and Epithelia, Sem. Hematol. 34, 343-354 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Assays and reagents for identifying anti-fungal agents, and uses related thereto Inventor(s): Berlin, Vivian; (Dunstable, MA), Damagnez, Veronique; (Cambridge, MA), Smith, Susan E.; (Boston, MA) Correspondence: ROPES & GRAY; ONE INTERNATIONAL PLACE; BOSTON; MA; 02110-2624; US Patent Application Number: 20020168748 Date filed: August 31, 2001 Abstract: The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products Excerpt(s): This application is a continuation-in-part of 08/838,973 filed Apr. 23, 1997, which is a continuation-in-part of Ser. No. 08/771,212 filed Dec. 20, 1996, which is a continuation-in-part of Ser. No. 08/631,319 filed Apr. 11, 1996, the specification of each of which is incorporated by reference herewith. Fungal infections of humans range from superficial conditions, usually caused by dermatophytes or Candida species, that affect the skin (such as dermatophytoses) to deeply invasive and often lethal infections (such as candidiasis and cryptococcosis). Pathogenic fungi occur worldwide, although particular species may predominate in certain geographic areas. In the past 20 years, fungal infections have increased dramatically--along with the numbers of potentially invasive species. Indeed, fungal infections, once dismissed as a nuisance, have begun to spread so widely that they are becoming a major concern in hospitals and health departments. Fungal infections occur more frequently in people whose immune system is suppressed (because of organ transplantation, cancer chemotherapy, or the human immunodeficiency virus), who have been treated with broad-spectrum antibacterial agents, or who have been subject to invasive procedures (catheters and prosthetic devices, for example). Fungal infections are now important causes of morbidity and mortality of hospitalized patients: the frequency of invasive candidiasis has increased tenfold to become the fourth most common blood culture isolate (Pannuti et al (1992) Cancer 69:2653). Invasive pulmonary aspergillosis is a leading cause of mortality in bone-marrow transplant recipients (Pannuti et al, supra), while Pneumocystis carinii pneumonia is the cause of death in many patients with acquired immunodeficiency

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syndrome in North America and Europe (Hughes (1991) Pediatr Infect. Dis J. 10:391). Many opportunistic fungal infections cannot be diagnosed by usual blood culture and must be treated empirically in severely immunocompromised patients (Walsh et al (1991) Rev. Infect. Dis. 13:496). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bacterial isolates from organisms that respire at least partially through their skin and biologically active extracts derived therefrom Inventor(s): Austin, Richard M. JR.; (Demorest, GA) Correspondence: Kent A. Herink, Esq.; The Financial Center; Suite 2500; 666 Walnut Street; Des Moines; IA; 50309; US Patent Application Number: 20030072829 Date filed: January 4, 2002 Abstract: Extracts including a biologically active compound or combination of compounds derived from microorganisms isolated from mucus-producing organisms that respire at least partially through their skin. Rod-shaped bacteria isolated from the skin of salamanders and frogs are found to produce compound(s) which have antiviral, antitumor, antibacterial and antifungal properties. These compound(s) have an inhibitory effect on opportunistic human pathogens, including Candida sp., Microsporum sp., Staphylococcus sp., Pseudomonas sp., Escherichia sp, and Enterococcus sp, as well as on HIV strains and tumor cell lines. Excerpt(s): This application claims priority to provisional application Serial No. 60/260,022, filed Jan. 5, 2001. All amphibians respire, to varying degrees, cutaneously. As such, their integument must serve as a gas permeable barrier to their external environment (Lilleywhite, H. B., and P. F. A. Maderson. 1988. The structure and permeability of the integument. American Zoologist 28:945-962). Moisture is requisite for skin to be utilized as a respiratory organ (Fox, H. 1994. Structure of the integument. Cpt. 1 in "Amphibian Biology, Vol 1, The Integument", ed by H. Heatwole and G. T. Barthalmus, Surrey Beatty and Sons, Chipping Norton). This necessary moisture is achieved through the production of mucus via mucus-producing glands associated with the integument (Duellman, W. E., and L. Trueb. 1986. Biology of Amphibians. McGraw Hill, New York, N.Y., U.S.A.; Fox 1994). The primary component of mucus in amphibians is a mucopolysaccharide (glycoprotein) (Duellman and Trueb 1986). Glycoproteins contain one or more carbohydrate chains covalently linked to a polypeptide backbone (Schaechter, M., and I. Brockhausen. 1989. The biosynthesis of branched O-glycans. In Mucus and related topics. E. Chantler and N. A. Ratcliffe (eds). Symposia of the Society for Experimental Biology, no. XLIII, University of Cambridge, Cambridge). The mucus is rich in carbon, a necessary element to support microbial growth and synthesis of most, if not all, cellular compounds (Guirard, B. M., and E. E. Snell. 1962. Nutritional requirements of microorganisms. Pp. 33-93. In I. C. Gunsalis and R. Y. Staneir (Eds.), The Bacteria. A Treatise on Structure and Function. Vol. IV: The Physiology of Growth. Academic Press, New York, N.Y., U.S.A.). Thus, the mucus layer necessarily produced by amphibians in order to accomplish cutaneous respiration represents a nutrient rich habitat for microorganisms (Austin, Jr., R.M. 2000. Cutaneous microbial flora and antibiosis in Plethodon ventralis: inferences for parental care in the Plethodontidae. Pp. 451-461. In R. C. Bruce, R. G. Jaeger and L. D. Houck (Eds.), The Biology of Plethodontid Salamanders, Kluwer Academic/Plenum Pub., New York, N.Y., U.S.A.). The majority of microorganisms in most ecosystems are attached to surfaces

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(Wimpenny, J. W. T., S. L. Kinniment, and M. A. Scourfield. 1993. The physiology and biochemistry of biofilms. Pp. 274-318. In S. Denyer, P. Gorman, and M. Sussman, (Eds.), Microbial Biofilms: Formation and Control. Blackwell Scientific Publications, London, U.K.), and the integuments of animals often serve as suitable habitats for the development of microbial communities (Alexander, M. 1971. Microbial Ecology. John Wiley and Sons, New York, N.Y., U.S.A.). These microcommunities often exhibit the same types of community-level interactions that communities of larger organisms (macrocommunities) exhibit. Members of microcommunities compete for limited resources and form intimate, and, at times, ammensalistic relationships (Atlas, R. M., and R. Bartha. 1993. Microbial Ecology. Fundamentals and Applications, 3rd ed. Benjamin Cummings, New York, N.Y., U.S.A.; Bull, A. T., and J. H. Slater. 1982. Microbial Interactions and Communities. Vol. 1. Academic Press, New York, N.Y., U.S.A.; Frederickson, A. G., and G. Stephanopoulos. 1981. Microbial competition. Science 213:972-979). Such amensalistic strategies include, but are not limited to, the production of antibiotics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Biooxidation capabilities of candida sp Inventor(s): Anderson, Kevin W.; (Indian Springs, OH), Biermann, Manfred; (Cincinnati, OH), Eirich, L. Dudley; (Milford, OH), Gates, Jeffrey A.; (West Chester, OH), Vice, Gilbert H.; (Cincinnati, OH), Wilson, C. Ron; (Loveland, OH) Correspondence: Jeffrey S. Steen; Dilworth & Barrese, LLP; 333 Earle Ovington Blvd.; Uniondale; NY; 11553; US Patent Application Number: 20020061566 Date filed: March 20, 2001 Abstract: A bioprocess for producing carboxylic acids, alcohols and aldehydes is provided by culturing Candida sp. in a fermentation medium containing various defined substrates. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn.119(e) of earlier filed and copending U.S. Provisional Application No. 60/190,626, filed Mar. 20, 2000, the contents of which are incorporated herein by reference. The present invention relates to the use of yeast strains to modify substrates via biooxidation. More particularly, the present invention relates to processes for converting certain substrates into alcohols or carboxylic acids utilizing yeast. Aliphatic dioic acids, alcohols and compounds having combinations of alcohols and acids are versatile chemical intermediates useful as raw materials for the preparation of adhesives, fragrances, polyamides, polyesters, and antimicrobials. While chemical routes for the synthesis of long-chain.alpha.,.omega.)dicarboxylic acids are available, the synthesis is complicated and results in mixtures containing dicarboxylic acids of shorter chain lengths. As a result, extensive purification steps are necessary. While it is known that long-chain dioic acids can also be produced by microbial transformation of alkanes, fatty acids or esters, chemical synthesis has remained the preferred route, presumably due to limitations with the previously available biological approaches. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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CaESS1: a Candida albicans gene, methods for making and using, and targeting it or its expression products for antifungal applications Inventor(s): Chaturvedi, Vishnu; (Slingerlands, NY), Devasahayam, Gina; (Madras, IN), Hanes, Steven D.; (Albany, NY) Correspondence: FROMMER LAWRENCE & HAUG; 745 FIFTH AVENUE- 10TH FL.; NEW YORK; NY; 10151; US Patent Application Number: 20030143615 Date filed: January 15, 2003 Abstract: Disclosed and claimed is the CaESS1 gene, portions thereof such as primers or probes, expression products therefrom, and methods for using the gene, and expression products; for instance, for diagnostic, therapeutic or preventive compositions. Excerpt(s): The present invention relates to compositions and methods for diagnosing and/or detecting and/or preventing and/or treating Candida albicans or conditions or symptoms associated therewith, as well as to process and products for preparing such compositions and methods. The present invention further relates to CaESS1, an important Candida albicans gene, e.g., nucleic acid molecules therefor, and/or fragments or portions thereof, expression products therefrom, e.g., the protein CaEss1 or fragments or portions thereof, methods for making and using the gene, portions thereof and expression products therefrom, and to targeting the gene or portions thereof and/or the expression products therefrom for antifungal applications. The identification of the CaESS1 gene allows for identifying compounds or agents that specifically bind to and/or inhibit the gene, or portions thereof and/or expression products therefrom, and methods for preventing and/or treating Candida albicans and/or symptoms or conditions associated therewith, as well as generally for making and using such compounds or agents. Thus, the invention relates to antifungal preparations and/or compositions and methods for making and using them. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Candida albicans kinase genes and polypeptides and uses thereof Inventor(s): Amidon, Benjamin Stone; (Arlington, MA), Bulawa, Christine Ellen; (Arlington, MA) Correspondence: J. Peter Fasse; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020128456 Date filed: June 22, 2001 Abstract: Disclosed are Candida albicans kinase genes and polypeptides and their use in identifying antifungal agents, for example. Excerpt(s): This application claims priority from U.S. Provisional Patent Application No. 60/213,621, filed on Jun. 23, 2000, which is incorporated herein by reference in its entirety. The invention relates to kinase genes of the fungus Candida albicans and their use in identifying antifungal agents. Kinases are responsible for phosphorylation of protein substrates, usually via tyrosine, serine, threonine, or other substrates residues of the substrate protein. Since phosphorylation and de-phosphorylation of proteins are common means of modulating protein activity or function, kinases are expected to be involved in the regulation of other proteins.

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

Candida albicans phosphomannan complex as a vaccine Inventor(s): Cutler, Jim E.; (Bozeman, MT), Han, Yongmoon; (Bozeman, MT) Correspondence: MORGAN, LEWIS & BOCKIUS; 1800 M STREET NW; WASHINGTON; DC; 20036-5869; US Patent Application Number: 20020054886 Date filed: December 11, 2000 Abstract: A composition, pharmaceutical composition, vaccine and method for the treatment of disseminated candidiasis due to infection by C. albicans. The composition includes phosphomannan of C. albicans. Monoclonal antibodies for use in passive immunization against candidal infections. Excerpt(s): This application contains subject matter related to Ser. Nos. and 08/247,972 and 08/483,558 incorporated herein by reference in their entireties. The present invention relates to a vaccine and method for the treatment of disseminated candidiasis due to infection by Candida albicans. Candida albicans is a fungus responsible for various forms of candidiasis, a condition which may be found in normal and immunocompromised patients, such as those with acquired immune deficiency syndrome. Humans and mice who are neutropenic are especially at risk of developing disseminated candidiasis (Denning, D. W., et al. 1992. Antifungal prophylaxis during neutropenia or allogeneic bone marrow transplantation: what is the state of the art? Chemotherapy 38(suppl 1):43-49; Matsumoto, M. S., et al. 1991. Effect of combination therapy with recombinant human granulocyte colony-stimulating factor (rG-CSF) and antibiotics in neutropenic mice unresponsive to antibiotics alone. J. Antimicrob. Chemother. 28:447-453; Meunier, F. 1987. Prevention of mycoses in immunocompromised patients. Rev. Infect. Dis. 9:408-416; Meunier, F., et al. 1992. Candidemia in immunocompromised patients. Clin. Infect. Dis. 14 (Suppl 1):S120-S125; and Van't Wout, J. W. et al. 1989. Comparison of the efficacies of amphotericin B, Fluconazole, and Itraconazole against a systemic Candida albicans infection in normal and neutropenic mice. Antimicrob. Agents Chemother. 33: 147-151). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Candida albicans proteins associated with virulence and hyphal formation and uses thereof Inventor(s): Leberer, Ekkehard; (Beaconsfield, CA), Thomas, David Y.; (Montreal West, CA) Correspondence: OGILVY RENAULT; 1981 MCGILL COLLEGE AVENUE; SUITE 1600; MONTREAL; QC; H3A2Y3; CA Patent Application Number: 20030166886 Date filed: March 11, 2002 Abstract: The present invention relates to Candida albicans proteins, such as CaCla4p, Cst20p, CaCdc42p and CaBem1p, associated with virulence and hyphal formation and uses thereof, such as to design screening tests for inhibitors for the treatment of pathogenic fungi infections and/or inflammation conditions. The invention also relates

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to an in vitro screening test for compounds to inhibit the biological activity of at least one protein selected from the group consisting of CaCla4p, Cst20p, CaCdc42p and CaBem1p, which comprises: a) at least one of said proteins; and b) means to monitor the biological activity of said at least one protein; thereby compounds are tested for their inhibiting potential. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/301,132 filed Apr. 28, 1999, which is a continuation of PCT/CA97/00809 filed Oct. 29, 1997 designating the United States and claiming priority from U.S. provisional patent application Ser. No. 60/029,458 filed Oct. 30, 1996. The invention relates to Candida albicans proteins, such as CaCla4p, Cst20p, CaCdc42p and CaBem1p, associated with virulence and hyphal formation and uses thereof, such as to design screening tests for inhibitors for the treatment of pathogenic fungi infections and/or inflammation conditions. Candida albicans is the major fungal pathogen in humans, causing various forms of candidiasis. The incidence of infections is increasing in immunocompromised patients. This fungus is diploid and is capable of a morphological transition from a unicellular budding yeast to a filamentous form. Extensive filamentous growth leads to the formation of a mycelium displaying hyphae with branches and lateral buds. In view of the observation that hyphae seem to adhere to and invade host tissues more readily than does the yeast form, the switch from the yeast to the filamentous form probably contributes to the virulence of this organism (for a review see Fidel, P. L. & Sobel, J. D. (1994) Trends Microbiol. 2, 202-205). The molecular mechanisms by which morphological switching is regulated are poorly understood (Whiteway review 2000, Curr. Op. Microbio., 3:582-588). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

CANDIDA ALBICANS TWO-COMPONENT HYBRID KINASE GENE, CANIK1, AND USE THEREOF Inventor(s): SOLL, DAVID R.; (IOWA CITY, IA), SRIKANTHA, THYAGARAJAN; (CORALVILLE, IA) Correspondence: STEPHEN A BENT; FOLEY & LARDNER; WASHINGTON HARBOUR; 3000 K STREET NW SUITE 500; WASHINGTON; DC; 20007-5109; US Patent Application Number: 20020137034 Date filed: January 20, 2000 Abstract: A Candida albicans gene, CaNik1, is involved in phenotypic switching which is significant because of a direct correlation between the switching and the level of virulence of the organism. A method of screening for anti-fungal pharmaceutical candidates entails bringing a test substance into contact with cells containing a CaNik1 gene or a variant thereof and then monitoring the effect, if any, on the level of expression of the gene. Excerpt(s): Candida is an opportunistic yeast that lives in the mouth, throat, intestines, and genitourinary tract of most humans. In a healthy human body, the population of Candida is kept in check by the immune system and by a competitive balance with other microorganisms. But when the body's immune system is compromised, as in AIDS patients and in patients undergoing immunosuppressive therapy, Candida will grow uncontrolled, leading to systemic infection called "Candida mycosis." If left untreated, such systemic infections frequently lead to the death of the patients. Candida albicans is a species of particular interest to scientists and doctors because 90% of all cases of

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Candida mycosis are caused by this species. At present, the therapy principally available for invasive infections is based on relatively few antimycotics, such as amphotericin B and flucytosine, or the azole derivatives fluconazole and itraconazole. These antimycotics cause serious side effects, such as renal insufficiency, hypocalcaemia and anaemia, as well as unpleasant constitutional symptoms such as fever, shivering and low blood pressure. Amphotericin B is toxic to the kidneys, for example, and yet the pharmaceutical is therapeutic only if administered at dose levels near to being toxic. A discussion of the pharmaceuticals used for treatment and their corresponding side effects can be found, for example, in Boyd, et al., BASIC MEDICAL MICROBIOLOGY (2d ed.), Little, Brown and Company, (1981). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cytochrome P450 monooxygenase and NADPH cytochrome P450 oxidoreductase genes and proteins related to the omega hydroxylase complex of candida tropicalis and methods relating thereto Inventor(s): Brenner, Alfred A.; (Santa Rosa, CA), Cornett, Cathy A.; (Crescent Springs, KY), Craft, David L.; (Fort Thomas, KY), Eirich, L. Dudley; (Cincinnati, OH), Eshoo, Mark; (Fairfax, CA), Gleeson, Martin; (San Diego, CA), Loper, John C.; (Cincinnati, OH), Madduri, Krishna M.; (Westfield, IN), Tang, Maria; (Fairfield, CA), Wilson, C. Ron; (Loveland, OH) Correspondence: COGNIS CORPORATION; 2500 RENAISSANCE BLVD., SUITE 200; GULPH MILLS; PA; 19406 Patent Application Number: 20030049821 Date filed: May 3, 2002 Abstract: Novel genes have been isolated which encode cytochrome P450 and NADPH reductase enzymes of the.omega.-hydroxylase complex of C. tropicalis 20336. Vectors including these genes, transfected host cells and transformed host cells are provided. Methods of producing of cytochrome P450 and NADPH reductase enzymes are also provided which involve transforming a host cell with a gene encoding these enzymes and culturing the cells. Methods of increasing the production of a dicarboxylic acid and methods of increasing production of the aforementioned enzymes are also provided which involve increasing in the host cell the number of genes encoding these enzymes. A method for discriminating members of a gene family by quantifying the expression of genes is also provided. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/123,555 filed Mar. 10, 1999, U.S. Provisional Application Serial No. 60/103,099 filed Oct. 5, 1998, and U.S. Provisional Application Serial No. 60/083,798 filed May 1, 1998. The present invention relates to novel genes which encode enzymes of the.omega.hydroxylase complex in yeast Candida tropicalis strains. In particular, the invention relates to novel genes encoding the cytochrome P450 and NADPH reductase enzymes of the.omega.-hydroxylase complex in yeast Candida tropicalis, and to a method of quantitating the expression of genes. Aliphatic dioic acids are versatile chemical intermediates useful as raw materials for the preparation of perfumes, polymers, adhesives and macrolid antibiotics. While several chemical routes to the synthesis of long-chain alpha,.omega.-dicarboxylic acids are available, the synthesis is not easy and most methods result in mixtures containing shorter chain lengths. As a result, extensive purification steps are necessary. While it is known that long-chain dioic acids can also be produced by microbial transfonration of alkanes, fatty acids or esters thereof, chemical

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synthesis has remained die most commercially viable route, due to limitations with the current biological approaches. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Enzymatic hydrolysis of a polymer comprising vinyl acetate monomer Inventor(s): Borch, Kim; (Birkerod, DK), Fitzhenry, James William; (Memphis, TN), Lund, Henrik; (Skodsborg, DK), Pedersen, Hanne Host; (Lyngby, DK), Sakaguchi, Hiromichi; (Chiba city, JP), Sharyo, Masaki; (Matsudo-shi, JP) Correspondence: NOVOZYMES NORTH AMERICA, INC.; 500 FIFTH AVENUE; SUITE 1600; NEW YORK; NY; 10110; US Patent Application Number: 20030051836 Date filed: May 21, 2002 Abstract: The invention relates to the use of certain lipolytic enzymes such as cutinases and lipases in the manufacture of paper and paper products from recycled paper. Examples of such enzymes are derived from strains of Humicola, Candida, Fusarium and Pseudomonas. By use of these enzymes, the problems relating to the so-called "stickies" derived from waste paper are reduced. Excerpt(s): This application claims under 35 U.S.C. 119 priority from or the benefit of Danish application No. PA 2001 00813 filed May 21, 2001, and U.S. Provisional No. 60/294,539 filed May 30, 2001, the contents of which are fully incorporated herein by reference. This invention relates to the use of certain lipolytic enzymes in the manufacture of paper and paper products from recycled paper. By use of these enzymes, the problems relating to the so-called stickies derived from waste paper are reduced. Polymers comprising vinyl acetate are very commonly used as an adhesive and coating material throughout industrial sectors (paper, textiles etc.). However, because of their adhesive properties these polymers often cause problems at later process stages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Heat shock genes and proteins from Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus Inventor(s): Wisniewski, Jan; (Sooke, CA) Correspondence: FISH & RICHARDSON PC; 225 FRANKLIN ST; BOSTON; MA; 02110; US Patent Application Number: 20030099664 Date filed: October 11, 2002 Abstract: Methods and compositions comprising isolated nucleic acid molecules specific to Neisseria meningitidis, Candida glabrata and Aspergillus fumigatus heat shock proteins (Hsps), as well as vector constructs and isolated polypeptides specific to the same are provided. Such compositions and methods are useful for the diagnosis of infections by these organisms and for generating an immune response to the organisms. Excerpt(s): This invention relates to heat shock proteins of the Hsp60 family from Candida glabrata and Aspergillus fumigatus and a heat shock protein of the Hsp70

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family from Neisseria meningitidis, including fragments thereof, and uses of such proteins and nucleic acid molecules encoding these proteins. Meningitis is an infection of the fluid of the spinal cord and the fluid that surrounds the brain. The disease is caused either by a viral or a bacterial infection. Viral meningitis is typically less severe than bacterial meningitis and resolves without specific treatment. In contrast, bacterial meningitis can be rather severe and can cause brain damage, hearing loss or learning disability. Symptoms of meningitis are high fever, headache and stiff neck. These symptoms may develop over a span of several hours, or may take 1-2 days. Other symptoms may be nausea, vomiting, discomfort looking into bright light, confusion or sleepiness. In young children, the classical symptoms may be absent or may not be easily detected, and the child may appear to be slow, inactive, irritable, vomiting or feeding poorly. As the disease progresses, seizures may occur. Bacterial meningitis may be caused by Haemophilus influenzae, Streptococcus pneumoniae or Neisseria meningitidis. Because all children (in the U.S.) are now given a vaccine against Haemophilus influenzae in the course of their routine immunizations, meningitis due to this organism is now relatively uncommon. Thus, the major bacterial disease-causing agents are now Streptococcus pneumoniae and Neisseria meningitidis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Histidine kinase two-component in candida albicans Inventor(s): Abad, Antonio Jose C.; (Washington, DC), Calderone, Richard A.; (Washington, DC), Choi, Gil H.; (Rockville, MD) Correspondence: HUMAN GENOME SCIENCES INC; 9410 KEY WEST AVENUE; ROCKVILLE; MD; 20850 Patent Application Number: 20020146738 Date filed: April 5, 2002 Abstract: The present invention relates to a histidine kinase, two-component gene (CaHK1) from Candida albicans. CaHK1 encodes a 2471 amino acid protein with an estimated molecular mass of 281.8 kDa. Also provided are vectors, host cells, antibodies and recombinant methods for producing the same. The invention further relates agonists and antagonists and to screening methods for identifying agonists and antagonists of CaHK1 polypeptide activity. The invention additionally relates to diagnostic methods for detecting CaHK1 nucleic acids, polypeptides, and antibodies in a biological sample. The present invention further relates to novel antagonists and vaccines for the prevention or attenuation of infection by Candida albicans. Excerpt(s): This application is a divisional of and claims priority under 35 U.S.C.sctn. 120 to U.S. application Ser. No. 09/419,291, filed Oct. 15, 1999, which is a divisional of and claims priority under 35 U.S.C.sctn. 120 to U.S. application Ser. No. 09/112,450, filed Jul. 9, 1998, which is a non-provisional of and claims benefit under 35 U.S.C.sctn. 119(e) of U.S. Provisional Application Nos. 60/052,273, filed Jul. 10, 1997, and 60/074,308, filed Feb. 11, 1998, which provisional applications are hereby incorporated herein in their entirety. All cells must sense changes in their environment and respond appropriately. In this regard, the two-component signal transduction regulatory system was initially described in prokaryotic organisms where it is thought to play a function in chemotaxis, osmoregulation, sporulation, host-pathogen interactions and response to carbon, nitrogen and phosphate availability. In these microorganisms, the prototypical twocomponent regulator system is comprised of two proteins, a histidine protein kinase (also called a sensor protein and usually cell membrane-bound) and a response

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regulator (or effector protein), which is associated with an internal response. The sensor kinase, when activated by a signal, autophosphorylates a histidine residue using ATP as a phosphodonor; the histidine is a part of a conserved block of residues, typically referred to as the H-box. Subsequently, the phosphorylated sensor kinase serves as a phosphodonor to a conserved aspartate residue in the response regulator. This phosphorylation modulates the activity of the effector protein to elicit an adaptive response to the stimulus (reviewed in Hoch and Silhavy, Two-component signal transduction, ASM Press. Washington, D.C. USA (1995)). Although the general sequence of events and the number of proteins involved is similar for all of these organisms, each pathway exhibits some variation on the basic scheme (Appleby et al., Signal transduction via the multi-step phosohorelay: not necessarily a road less traveled, Cell 86, 845-848 (1996)). For instance, in Bordetella pertussis, the BvgS-BvgA two-component modulates the transcriptional control of several virulence factors. Although there are two proteins, four phosphorylation events occur in sequence, creating a four-step HisAsp-His-Asp phosphorelay (Uhl and Miller; Integration of multiple domains in a twocomponent sensor protein: the Bordetella pertussis BvgAS phosphorelay, EMBO J. 15, 1028-1036 (1996)). A similar mechanism has been the plant pathogenic bacterium, Pseudomonas syringae. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Immunotherapy of epithelial tumors using intralesional injection of antigens that induce a delayed type hypersensitivity reaction Inventor(s): Horn, Thomas Dag; (Little Rock, AR), Johnson, Sandra Marchese; (Little Rock, AR) Correspondence: FOLEY AND LARDNER; SUITE 500; 3000 K STREET NW; WASHINGTON; DC; 20007; US Patent Application Number: 20020142005 Date filed: February 25, 2002 Abstract: The pharmaceutical composition is useful for treating epithelial tumors in a subject and contains at least two antigens and a pharmaceutically acceptable carrier, where each of the antigens induces or is capable of inducing a cutaneous delayed type hypersensitivity (DTH) response in the subject. This composition is particularly useful in treating epithelial tumors, such as warts or verrucae, that are induced by or related to papillomavirus. Antigens useful in the present pharmaceutical composition are anergy panel antigens, such as killed mumps virus, candida extract, trichophyton extract or comparable antigenic extracts. An additional pharmaceutical composition, also useful for treating epithelial tumors, contains at least one antigen that induces or is capable of inducing a cutaneous DTH response in a subject, at least one cytokine or colony stimulating factor and a pharmaceutically acceptable carrier. Kits containing these pharmaceutical compositions are useful for this immunotherapy. Excerpt(s): This application is a divisional of application Ser. No. 09/344,257, filed Jun. 25, 1999. This application claims only subject matter disclosed in the parent application and therefore presents no new matter. The present invention relates to immunotherapy of epithelial tumors, particularly tumors that are induced by infectious agents, particularly viruses, and particularly papilloma viruses. The immunotherapy of the present invention relates to the intralesional injection of at least one antigen into a epithelial tumor of a subject in need of treatment, wherein the subject to be injected had previously developed a naturally-occurring delayed type hypersensitivity (DTH) response to the antigen. The immunotherapy of the present invention is particularly

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useful for treating verrucae, condyloma, cervical carcinoma and bowenoid papulosis. Verrucae or human warts are benign epidermal tumors caused by human papilloma virus (HPV). HPV is a member of the papovavirus family. HPV is a non-enveloped double-stranded deoxyribonucleic acid (DNA) virus that replicates in epithelial cells. This means that HPV has a predilection for the mucosa and skin. Currently, there are more than 70 distinct HPV types recognized each with at least a 10% genome difference. Because papillomaviruses tend to be host-specific and HPV has not been successfully grown in culture; the majority of the research with papilloma virus has been conducted with animal papillomaviruses. (37) Papillomaviruses are considered responsible for several forms of viral infection ranging from relatively benign warts of the skin or mucous membranes to cancer, the most significant being cervical cancer. Papillomaviruses are known to infect mammals, including humans, rabbits, canines, felines, bovines and equines. Papillomaviruses are highly species and tissue-specific, and are characterized by a specific mode of interaction with the squamous epithelia they infect. These viridae colonize various stratified epithelia like skin and oral and genital mucosae, and induce the formation of self-limited benign tumors, known as warts or condylomas. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Magnetic resonance spectroscopy to identify and classify microorganisms Inventor(s): Bourne, Roger; (Marrickville, AU), Himmelreich, Uwe; (Mays Hill, AU), Mountford, Carolyn E.; (East Ryde, AU), Somorjai, Rajmund L.; (Headingly, CA), Sorrell, Tania C.; (Riverview, AU) Correspondence: Cooper & Dunham LLP; 1185 Avenue of the Americas; New York; NY; 10036; US Patent Application Number: 20030097059 Date filed: February 21, 2002 Abstract: A statistical classifier identifies microorganisms, such as bacteria and fungi, using magnetic resonance spectroscopy, with multivariate analysis.The bacteria may include species within Staphylococcus, Enterococcus and Streptococcus. The fungi may include pathogenic yeasts including species with Candida and Cryptococcus. Excerpt(s): This application claims priority on U.S. provisional application Serial No. 60/270,367, filed Feb. 21, 2001. The present invention relates to identifying and classifying microorganisms, such as bacteria and fungi, using magnetic resonance spectroscopy, with multivariate analysis. Throughout this application, various publications are referenced 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. Full bibliographic citations for these references may be found at the end of this application, preceding the claims. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and formulation for treating candidiasis using morinda citrifolia Inventor(s): Gerson, Scott; (Brewster, NY), Jensen, Claude Jarakae; (Cedar Hills, UT), Ogden, Robert V.; (Cedar Hills, UT), Palu, Afa Kehaati; (Orem, UT), West, Brett Justin; (Orem, UT) Correspondence: KIRTON AND MCCONKIE; 1800 EAGLE GATE TOWER; 60 EAST SOUTH TEMPLE; P O BOX 45120; SALT LAKE CITY; UT; 84145-0120; US Patent Application Number: 20030161901 Date filed: November 14, 2002 Abstract: The present invention features a novel use of processed ingredients from the Indian mulberry plant, and particularly a novel use of one or more processed Morinda citrifolia-based naturaceutical formulations comprising one or more of a processed Morinda citrifolia fruit juice, puree juice, oil or oil extract, dietary fiber, alcohol extract, etc., for inhibiting and preventing the overgrowth of Candida fungus and for treating Candidiasis and its associated symptoms. Excerpt(s): The present invention is directed toward methods and formulations for treating Candidiasis, and particularly towards various methods and naturaceutical formulations, compositions, and substances comprising Morinda citrifolia for inhibiting, blocking, and preventing the overgrowth of Candida albicans in mammals. There exists in the body literally billions of microorganisms that function to assist in everyday maintenance and development. This normal resident microbial population includes potential pathogens as well as organisms that help to keep the potential pathogens in check. Microorganisms Candida albicans, and other strains of Candida, are yeast or yeast-like fungi that are capable of growing on and within the human body and that normally or naturally inhabit our digestive system: the mouth, throat, intestines and genitourinary tract. Candida is a normal part of the bowel flora (the organisms that naturally live inside our intestines, and are not parasitic). It has many functions inside our digestive tract, one of them which is to recognize and destroy harmful bacteria. Without Candida albicans in our intestines we would be defenseless against many pathogenic bacteria. Under normal circumstances, a healthy individual can have millions of Candida albicans in their system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and materials for the production of organic products in cells of candida species Inventor(s): Ilmen, Marja; (Helsinki, FI), Koivuranta, Kari; (Helsinki, FI), Penttila, Merja; (Helsinki, FI), Rajgarhia, Vineet; (Hopkins, MN), Ruohonen, Laura; (Helsinki, FI), Suominen, Pirkko; (Maple Grove, MN) Correspondence: MCDONNELL BOEHNEN HULBERT & BERGHOFF; 300 SOUTH WACKER DRIVE; SUITE 3200; CHICAGO; IL; 60606; US Patent Application Number: 20030190630 Date filed: September 23, 2002 Abstract: The present invention relates to biocatalysts that are cells, optimally of the Crabtree-negative phenotype, comprising expression vectors encoding genes heterologous to the cell that enable increased production of organic products. More specifically, the invention relates to genetically modified Candida cells, methods for

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making the Candida cells, and their use in production of organic products, particularly lactic acid. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/992,430, filed Nov. 23, 2001, which claims priority to U.S. Provisional Application Serial No. 60/252,541, filed Nov. 22, 2000. The use of microorganisms for synthesizing industrially important organic products is well known. Biosynthetic approaches for producing organic products can be extremely efficient when compared to large-scale chemical synthesis. Advantages a biosynthetic approach may have over a chemical synthetic approach for manufacturing an organic product include more rapid and more efficient product yield, isomeric purity, and reduced cost (see Thomas et al., 2002, Trends Biotechnol. 20: 238-42). Lactic acid has wide industrial applicability, including uses in chemical processing and synthesis, cosmetics, pharmaceuticals, plastics, and food production. Lactic acid is a relatively simple organic molecule, and can be produced either by chemical synthesis or by fermentation in microorganisms (biosynthesis). As genetic manipulation of microorganisms has become more advanced, fermentation processes for lactic acid production have become commercially preferred over chemical synthesis. One reason for this preference is that using genetically modified microorganisms enables production of optically pure (i.e., either the L(+) or D(-) isomer) product. Such methods obviate the need for separating racemic product mixtures, thereby reducing cost. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microbial SUMO protease homologs Inventor(s): Godzik, Adam; (San Diego, CA), Reed, John C.; (Rancho Santa Fe, CA) Correspondence: CAMPBELL & FLORES LLP; 4370 LA JOLLA VILLAGE DRIVE; 7TH FLOOR; SAN DIEGO; CA; 92122; US Patent Application Number: 20030203473 Date filed: November 20, 2002 Abstract: The invention provides isolated SUMO-specific protease-like (or "SSP") domain-containing polypeptides from microorganisms, including bacteria, protozoans and yeast, including Eschericia, Salmonella, Pseudomonas, Chlamydia, Plasmodium, Trypanosma, Mesorhizobium, Rickettsia, Cryptosporidium and Candida species, as well as modifications of such polypeptides, functional fragments therefrom, encoding nucleic acid molecules and specific antibodies. Also provided are methods for identifying polypeptides and compounds that associate with or modulate the activity of the SSP domain-containing polypeptides. Further provided are methods of modulating a biological activity in a cell, and treating pathological conditions, using the described nucleic acid molecules, polypeptides and compounds. Excerpt(s): This application claims benefit of the filing date of U.S. Provisional Application No. 60/331,895, filed Nov. 20, 2001, and which is incorporated herein by reference. The invention relates generally to the fields of medicine and cell biology and, more specifically, to the fields of infectious disease and regulation of apoptosis and inflammation. Post-translational modification of proteins is an important means of regulating protein activity, stability or localization. For example, post-translational modification of target proteins by conjugation to the small protein ubiquitin earmarks the target protein for degradation by the 26S proteasome. Recently, several small proteins have been identified with sequence similarity to ubiquitin and which modify

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target proteins. These ubiquitin-like modifiers (UBLs) include SUMO (small ubiquitinrelated modifier), Rubi (also called Nedd8), Apg8 and Apg12. In mammals, three members of the SUMO family have been described: SUMO-1, also known as PIC-1, sentrin or GMP1, which in humans is a 101 amino acid polypeptide; and the highly homologous polypeptides SUMO-2 and SUMO-3. Although SUMO-1 shares only about 18% sequence identity to ubiquitin, both polypeptides share a common threedimensional structure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Multivalent silver pharmaceuticals Inventor(s): Antelman, Marvin S.; (Rehovot, IL) Correspondence: AKIN, GUMP, STRAUSS, HAUER & FELD, L.L.P.; ONE COMMERCE SQUARE; 2005 MARKET STREET, SUITE 2200; PHILADELPHIA; PA; 19103; US Patent Application Number: 20020127282 Date filed: February 5, 2002 Abstract: Novel pharmaceuticals are described based on multivalent silver compounds containing Ag(II) or Ag(III) capable of killing pathogenic gram positive and negative bacteria, fungi and algae such as E. coli, Staphylococcus aureus and epidermidis, and Candida albicans. The efficacy of these compounds is enhanced by oxidizing agents such as persulfates. They can also be utilized to preserve pharmaceutical, cosmetic and chemical specialty products against these pathogens. Excerpt(s): This patent application is a continuation of copending U.S. patent application Ser. No. 07/802,478, filed on Dec. 5, 1991, entitled "Multivalent Silver Pharmaceuticals." The entire disclosure of U.S. patent Ser. No. 07/805,478 as filed is incorporated herein by reference. The present invention relates to the employment of multivalent silver compounds and their utilization as pharmaceuticals. This invention, however, relates more particularly to the utilization of bactericidal, viricidal, algicidal and fungicidal activity exhibited by this class of compounds in pharmaceuticals. The compounds involved range from divalent to trivalent silver compositions including mixed crystals in which silver is present in a multivalent state along with monovalent silver, such as tetrasilver tetroxide which contains two monovalent silver ions and two trivalent ions per molecule. The utilization of water-soluble divalent silver (Ag II) complex bactericides is the subject of U.S. Pat. No. 5,017,295 of the present inventor. I have also been granted U.S. Pat. Nos. 5,073,382, 5,078,902, 5,089,275, and 5,098,582 which all deal with Ag(II) bactericides but more particularly with (respectively), alkaline pH, halides, stabilized complexes, and the divalent oxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nanosilver-containing antibacterial and antifungal granules and methods for preparing and using the same Inventor(s): Cheng, Jiachong; (Beijing, CN), Yan, Jixiong; (Wuhan, CN) Correspondence: VENABLE; Post Office Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20020051823 Date filed: April 25, 2001

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Abstract: The present invention relates to nanosilver-containing antibacterial and antifungal granules ("NAGs"). The NAGs have longlasting inhibitory effect on a broadspectrum of bacteria and fungi, which include, but are not limited to, Escherichia coli, Methicillin resistant Staphylococcus aureus, Chlamydia trachomatis, Providencia stuartii, Vibrio vulnificus, Pneumobacillus, Nitrate-negative bacillus, Staphylococcus aureus, Candida albicans, Bacillus cloacae, Bacillus allantoides, Morgan's bacillus (Salmonella morgani), Pseudomonas maltophila, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Bacillus subtilis, Bacillus foecalis alkaligenes, Streptococcus hemolyticus B, Citrobacter, and Salmonella paratyphi C. The NAGs contain ground stalk marrow of the plant Juncus effuses L. which has been dispersed with nanosilver particles. The nanosilver particles are about 1-100 mn in diameter. Each of the nanosilver particles contain a metallic silver core which is surrounded by silver oxide. The present invention also provides a process for making the NAGs. The NAGs can be used in a variety of healthcare and industrial products. Examples of the healthcare products include, but are not limited to, ointments or lotions to treat skin trauma, soaking solutions or cleansing solutions for dental or women hygiene, medications for treating gastrointestinal bacteria infections, sexual related diseases, and eye diseases. Examples of industrial products include, but are not limited to, food preservatives, water disinfectants, paper disinfectants, construction filling materials (to prevent mold formation). Excerpt(s): This application claims the priority of U.S. Provisional Application No. 60/230,925, filed on Sep. 13, 2000, which is herein incorporated by reference. The present invention relates to nanosilver particles-containing antibacterial and antifungal granules (NAGs). The nanosilver particles are attached to the surfaces and pores of stalk marrow of Juncus effuses L, which acts as an inert carrier for nanosilver. Each of the nanosilver particles contains a metallic silver core which is surrounded by silver oxide. The size of the nanosilver particle is between 1-100 nm in diameter. The present invention also relates to methods for preparing the NAGs and for using the NAGs. The NAGs can be used in a variety of healthcare, medicinal and industrial products. Metals including silver, copper, mercury, and zinc are known for anti-bacterial properties. Bacteria treated by these metals do not acquire resistance to the metals. Therefore, the bactericidal metals have advantages over the conventional antibiotics which often cause the selection of antibiotic-resistant microorganism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel mutants of the formate dehydrogenase from Candida boidinii Inventor(s): Felber, Stephan; (Juelich, DE), Kula, Maria-Regina; (Muenchen, DE), Pohl, Martina; (Aachen, DE), Slusarczyk, Heike; (Uebach-Palenberg, DE) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20030157664 Date filed: September 23, 2002 Abstract: Novel improved enzymes prepared by recombination, especially to rec-FDHs. Directed evolution has made it possible to generate catalytically more active and more stable muteins which can preferably be used in an industrial process for the preparation of e.g. amino acids. The invention further relates to the nucleic acids coding for these enzymes, to vehicles containing these nucleic acids and to advantageous primers for the preparation of the nucleic acids by means of PCR. The invention additionally relates to a

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process for the preparation of further improved rec-FDHs, and a method of screening more stable and/or more active dehydrogenases is claimed. Excerpt(s): The present invention relates to novel mutants of a rec-FDH from Candida boidinii (ATCC 32195). The invention also describes the nucleic acids coding for these mutants and vehicles containing these nucleic acids. The invention also relates to a process for the preparation of further improved FDHs and to a process for the advantageous screening of more stable and more active dehydrogenases. Biocatalysts, inter alia, are successfully used for the preparation of L-amino acids, a starting point being the conversion of prochiral.alpha.-keto acids by reductive amination. The amino acid dehydrogenases used in this reaction require stoichiometric amounts of NADH or NADPH as coenzyme to convert the.alpha.-keto acids. These coenzymes are very expensive and therefore render the above-mentioned process of little economic value for the industrial scale. Scheme 1 shows the in situ regeneration of NADH with NADdependent formate dehydrogenase in the reductive amination of trimethyl pyruvate to L-tert-leucine (Bommarius et al., Tetrahedron Asymmetry 1995, 6, 2851-2888). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel vector for C. glabrata and the use thereof Inventor(s): Cottarel, Guillaume; (Arlington, MA), Willins, Debra Aker; (Watertown, MA) Correspondence: BURNS DOANE SWECKER & MATHIS L L P; POST OFFICE BOX 1404; ALEXANDRIA; VA; 22313-1404; US Patent Application Number: 20020192827 Date filed: February 22, 2002 Abstract: The present invention is directed to a vector for expressing a gene of interest in a Candida species. The vector of the present invention comprises promoter and terminator sequences from a native Candida gene. This vector can be used to complement deleted genes in a Candida species. The present invention is also directed to a method for identifying genes essential for growth of a Candida species. Additionally, the present invention is directed to a method for screening for anti-fungal compounds effective against Candida species. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/711,940, filed Nov. 15, 2000, the entire content of which is hereby incorporated by reference. The present invention is directed to novel Candida vectors which can be used to express genes in Candida species. The present invention also is directed to a method of deleting a gene from a Candida species and complementing that gene using the novel Candida vector to express the deleted gene. The present invention further is directed to a method for determining what genes in a Candida species are necessary for growth. Finally, the present invention is directed to a method of screening for anti-fungal compounds. Fungal infections of humans range from superficial conditions, usually caused by dermatophytes or Candida species, that affect the skin (such as dermatophytoses) to deeply invasive and often lethal infections (such as candidiasis). Pathogenic fungi occur worldwide, although particular species may predominate in certain geographic areas. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Oral administration of lactobacillus for the treatment and prevention of urogenital infection Inventor(s): Bruce, Andrew W.; (Toronto, CA), Reid, Gregor; (London, CA) Correspondence: SCULLY, SCOTT, MURPHY & PRESSER; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020044926 Date filed: June 11, 2001 Abstract: The present invention provides methods and compositions for the oral administration of at least one Lactobacillus and/or other probiotic organisms, such as Bifidobacterium, for improving vaginal health. The invention also provides methods and compositions to treat vaginitis, bacterial vaginosis and reduce candida colonization. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/459,292, filed Dec. 10, 1999. The present invention provides methods and compositions for the oral administration of lactobacilli or other probiotic organisms such as Bifidobacterium, for reduction of the risk of urogenital infection and concomitant restoration and/or maintenance of the desired urogenital flora. Urogenital infections, including urinary tract infections (UTI), bacterial vaginosis (BV) and yeast vaginitis, afflict an estimated one billion women in the world annually. While antimicrobial agents are effective at providing clinical remediation, the incidence of infections by multi-drug resistant Gram positive cocci appears to be rising and there is great concern that methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE) may thwart even the most potent antimicrobial agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions and methods to vaccinate against candidiasis Inventor(s): Edwards, John E. JR.; (Palos Verdes Estates, CA), Filler, Scott G.; (Rancho Palos Verdes, CA), Fu, Yue; (La Habra, CA), Ibrahim, Ashraf; (Playa Del Rey, CA), Sheppard, Donald C.; (Marina Del Rey, CA) Correspondence: ORRICK, HERRINGTON & SUTCLIFFE, LLP; 4 PARK PLAZA; SUITE 1600; IRVINE; CA; 92614-2558; US Patent Application Number: 20030124134 Date filed: September 13, 2002 Abstract: A Candida albicans bloodstream infections cause significant morbidity and mortality in hospitalized patients. Filament formation and adherence to host cells are critical virulence factors of C. albicans. Multiple filamentation regulatory pathways have been discovered, however the downstream effectors of these regulatory pathways remain unknown. The cell surface proteins in the ALS group are downstream effectors of the filamentation regulatory pathway. Particularly, Als1p mediates adherence to endothelial cells in vitro and is required for virulence. The blocking of adherence by the organism is described resulting from the use of a composition and method disclosed herein. Specifically, a pharmaceutical composition comprised of a gene, gene product, or specific antibody to the ALS gene family is administered as a vaccine to generate an immune response capable of blocking adherence of the organism. Excerpt(s): This application is a continuation-in-part of Ser. No. 09/715,876 filed on Nov. 18, 2000, which is a priority from Provisional Application Serial No. 60/166,663 filed

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Nov. 19, 1999. This invention was made with Government support under Public Health Service grants PO-1AI-37194, RO1AI-19990, and MO1 RR0425. The Government has certain rights in this invention. The priority of the prior applications are expressly claimed, and the disclosure of each of these prior applications are hereby incorporated by reference in their entirety. This invention relates to Candida albicans surface adhesin proteins, to antibodies resulting from an immune response to vaccination, to compositions used as prophylactic or therapeutic vaccines, and to methods for the prevention and/or treatment of candidiasis. A dramatic increase in the incidence of nosocomial infections caused by Candida species has been observed in recent years. The incidence of hematogenously disseminated candidal infections increased 11-fold from 1980 to 1989. This increasing incidence has continued through the 1990s and into the 2000s. Infections by Candida species are now the fourth most common cause of nosocomial septicemia, are equal to that of Escherichia coli, and surpass the incidence caused by Klebsiella species. Furthermore, Candida species are the most common cause of deep-seated fungal infections in patients who have extensive bums. Up to 11% of individuals undergoing bone marrow transplantation and 13% of those having an orthotopic liver transplant will develop an invasive candidal infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical compositions primarily for the treatment of genitourinary infections Inventor(s): Milankovits, Marton; (Budapest, HU) Correspondence: HAUGEN LAW FIRM PLLP; 1130 TCF Tower; 121 South Eighth Street; Minneapolis; MN; 55402; US Patent Application Number: 20030073646 Date filed: July 10, 2002 Abstract: Compositions having synergistic effective amounts of one or more antibacterial agents, a nitroimidazole, and an antifungal agent effective against a Candida species. The compositions are particularly useful in the treatment of genitourinary infections. Excerpt(s): This application is a continuation-in-part (CIP) of co-pending U.S. patent application Ser. No. 08/776,273, filed Jan. 22, 1997, the contents of which are herein incorporated by reference. This invention relates to novel compositions and their uses in treatments as suppositories, especially vaginal suppositories, ointments, vaginal drops and talc powders, and painting solutions, or any form of the compositions useful for systemic treatment. A variety of vaginal suppositories are currently commercially available for the treatment of various maladies. The attending physician ordinarily decides which composition is best suited to the patient's needs following physical examination. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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PNA probes, probe sets, methods and kits pertaining to the detection of candida Inventor(s): Hyldig-Nielsen, Jens J.; (Holliston, MA), Oliveira, Kenneth M.; (Newton, MA), Rigby, Susan; (Acton, MA), Stender, Henrik; (Waltham, MA) Correspondence: BRIAN D. GILDEA; APPLIED BIOSYSTEMS; 15 DEANGELO DRIVE; BEDFORD; MA; 01730; US Patent Application Number: 20030175727 Date filed: May 17, 2002 Abstract: 3This invention is related to novel PNA probes, probe sets, methods and kits pertaining to the detection of one or more species of Candida yeast. Non-limiting examples of probing nucleobase sequences that can be used for the probes of this invention can be selected from the group consisting of: AGA-GAG-CAG-CAT-GCA (Seq. Id. No. 1), AGA-GAG-CAA-CAT-GCA (Seq. Id. No. 2), ACA-GCA-GAA-GCCGTG (Seq. Id. No. 3), CAT-AAA-TGG-CTA-CCA-GA (Seq. Id. No. 4), CAT-AAA-TGGCTA-CCC-AG (Seq. Id. No. 5), ACT-TGG-AGT-CGA-TAG (Seq. Id. No. 6), CCA-AGGCTT-ATA-CTC-GC (Seq. Id. No. 7), CCC-CTG-AAT-CGG-GAT (Seq. Id. No. 8), GACGCC-AAA-GAC-GCC (Seq. Id. No. 9), ATC-GTC-AGA-GGC-TAT-AA (Seq. Id. No. 10), TAG-CCA-GAA-GAA-AGG (Seq. Id. No. 11), CAT-AAA-TGG-CTA-GCC-AG (Seq. Id. No. 12), CTC-CGA-TGT-GAC-TGC-G (Seq. Id. No. 13), TCC-CAG-ACT-GCT-CGG (Seq. Id. No. 14), TCC-AAG-AGG-TCG-AGA (Seq. Id. No. 15), GCC-AAG-CCA-CAA-GGA (Seq. Id. No. 16), GCC-GCC-AAG-CCA-CA (Seq. Id. No. 17), GGA-CTT-GGG-GTT-AG (Seq. Id. No. 18), CCG-GGT-GCA-TTC-CA (Seq. Id. No. 19), ATG-TAG-AAC-GGAACT-A (Seq. Id. No. 20), GAT-TCT-CGG-CCC-CAT-G (Seq. Id. No. 21), CTG-GTT-CGCCAA-AAA-G (Seq. Id. No. 22) and AGT-ACG-CAT-CAG-AAA (Seq. Id. No. 23). Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/292,147 filed on May 18, 2001. This invention is related to the field of probe-based detection, analysis and/or quantitation of microorganisms. More specifically, this invention relates to novel PNA probes, probe sets, methods and kits pertaining for the detection, identification and/or enumeration of organisms of the various species of the Candida genus. Nucleic acid hybridization is a fundamental process in molecular biology. Probe-based assays are useful in the detection, quantitation and/or analysis of nucleic acids. Nucleic acid probes have long been used to analyze samples for the presence of nucleic acid from bacteria, fungi, virus or other organisms and are also useful in examining genetically-based disease states or clinical conditions of interest. Nonetheless, probe-based assays have been slow to achieve commercial success. This lack of commercial success is, at least partially, the result of difficulties associated with specificity, sensitivity and reliability. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Polynucleotide probes for detection and quantitation of candida albicans and candida dubliniensis Inventor(s): Bee, Gary G.; (Vista, CA), Hogan, James J.; (Coronado, CA), Milliman, Curt L.; (St. Louis, MO) Correspondence: GEN PROBE INCORPORATED; 10210 GENETIC CENTER DRIVE; SAN DIEGO; CA; 92121 Patent Application Number: 20020038015 Date filed: May 1, 2001

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Abstract: Hybridization assay probes and accessory oligonucleotides for detecting ribosomal nucleic acids from Candida albicans and/or Candida dubliniensis. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/201,247, filed May 1, 2000. The entire disclosure of this related application is hereby incorporated by reference. The present invention relates to compositions and methods for detecting the pathogenic yeast species, Candida albicans and Candida dubliniensis. More specifically, the invention relates to hybridization probes and accessory polynucleotides having specificity for the ribosomal nucleic acids of these species. The yeast Candida albicans (C. albicans) is one of the most common fungal pathogens that infect humans. Although it is part of the normal flora of the mucous membranes in the respiratory, gastrointestinal and female genital tracts, this opportunistic pathogen may gain dominance in these locations and result in disease conditions. Indeed, while C. albicans infections of otherwise healthy individuals are rarely fatal, infections can lead to life-threatening conditions in persons having comprised immune systems such as, for example, AIDS patients, cancer patients undergoing chemotherapy, and organ transplant patients receiving immunosuppressive drugs. Disseminated (systemic) candidiasis is most prevalent in immunosuppressed individuals and is usually established following passage of the organism across the mucosal epithelium into the bloodstream. Once in the bloodstream, this organism can cause thrombophlebitis, endocarditis, or infection of the eyes. Further, C. albicans can invade virtually any organ or tissue when introduced intravenously, e.g., via tubing, needles or narcotics abuse. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Polynucleotide probes for detection and quantitation of candida species Inventor(s): Gordon, Patricia C.; (Spring Valley, CA), Hogan, James J.; (Coronado, CA) Correspondence: GEN PROBE INCORPORATED; 10210 GENETIC CENTER DRIVE; SAN DIEGO; CA; 92121 Patent Application Number: 20030165833 Date filed: May 1, 2001 Abstract: Hybridization probes and accessory oligonucleotides useful for detecting ribosomal nucleic acids from Candida albicans, Candida tropicalis, Candida dubliniensis, Candida viswanathii and Candida parapsilosis with high specificity. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/201,249, filed May 1, 2000. The entire disclosure of this related application is hereby incorporated by reference. The present invention relates to compositions and methods for detecting one or more species of yeast in the genus Candida. More specifically, the invention relates to hybridization probes and accessory polynucleotides having specificity for ribosomal nucleic acids from a defined collection of Candida species. It is well established that two single strands of deoxyribonucleic acid ("DNA") or ribonucleic acid ("RNA") can associate or "hybridize" with one another to form a double-stranded structure having two strands held together by hydrogen bonds between complementary base pairs. The individual strands of nucleic acid are formed from nucleotides that comprise the bases: adenine (A), cytosine (C), thymine (T), guanine (G), uracil (U) and inosine (I). In the double helical structure of nucleic acids, the base adenine hydrogen bonds with the base thymine or uracil, the base guanine hydrogen bonds with the base cytosine and the base inosine hydrogen bonds with adenine, cytosine or uracil. At any point along the chain, therefore, one may find the classical "Watson-Crick" base pairs

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A:T or A:U, T:A or U:A, and G:C or C:G. However, one may also find A:G, G:U and other "wobble" or mismatched base pairs in addition to the traditional ("canonical") base pairs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for the production of piperidine derivatives with microorganisms Inventor(s): Michels, Peter C.; (Des Moines, IA), Zirbes, Eric L.; (Coralville, IA) Correspondence: Michael L. Goldman; NIXON PEABODY LLP; Clinton Square; P.O. Box 31051; Rochester; NY; 14603; US Patent Application Number: 20020087003 Date filed: January 4, 2001 Abstract: The present invention relates to the production of a product compound having a structure according to Formulae IA and/or IB: 1whereinn is 0 or 1;R.sup.1 is hydrogen or hydroxy;R.sup.2 is hydrogen;or, when n is 0, R.sup.1 and R.sup.2 taken together form a second bond between the carbon atoms bearing R.sup.1 and R.sup.2, provided that when n is 1, R.sup.1 and R.sup.2 are each hydrogen;R.sup.3 is --COOH or -COOR.sup.4;R.sup.4 is an alkyl or aryl moiety;A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, and alkoxy.This process involves incubating a starting compound having a structure according to Formulae IIA and/or IIB: 2wherein R.sup.3 is --CH.sub.3 and R.sup.1, R.sup.2, A, B, and D are defined above. in the presence of a microorganism under conditions effective to produce the product compound. The microorganism can be from the genus Streptomyces, Stemphylium, Gliocladium, Bacillus, Botrytis, Cyathus, Rhizopus, Pycniodosphora, Psuedomonas, Helicostylum, Aspergillus, Mucor, Gelasinospora, Rhodotorula, Candida, Mycobacterium, or Pennicillium. Alternatively, the microorganism can be Cunninghamella bainieri. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/708,959, filed Nov. 8, 2000. The present invention relates to a process for the production of piperidine derivatives with microorganisms. U.S. Pat. No. 3,806,526 to Carr, et. al. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Production of a highly active, soluble form of the cytochrome P450 reductase (CPR A) from Candida tropicalis Inventor(s): Donnelly, Mark; (Warrenville, IL) Correspondence: COGNIS CORPORATION; 2500 RENAISSANCE BLVD., SUITE 200; GULPH MILLS; PA; 19406 Patent Application Number: 20030119145 Date filed: October 15, 2002 Abstract: The present invention provides soluble cytochrome p450 reductase (CPR) proteins from Candida sp. having an altered N-terminal region which results in reduced hydrophobicity of the N-terminal region. Also provided are host cells comprising the subject soluble CPR proteins. In addition, the present invention provides nucleotide and corresponding amino acid sequences for soluble CPR proteins and vectors comprising

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the nucleotide sequences. Methods for producing a soluble CPR, for increasing production of a dicarboxylic acid, and for detecting a cytochrome P450 are also provided. Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/328,752 filed Oct. 12, 2001, which application is incorporated by reference herein. Cytochrome P450 reductase is part of the.omega.-hydroxylase enzyme complex that catalyzes the first step in the.omega.-oxidation pathway. Cytochrome P450 reductase (CPR) catalyzes the reduction of the heme iron of various cytochromes, including cytochrome c and cytochrome P450. CPR has been renamed in recent literature as NADPH:cytochrome P450 oxidoreductase (NCP). The present application however, refers to the enzyme by its older designation, CPR. In the case of cytochrome P450s, this reduction initiates the catalytic steps that activate oxygen and result ultimately in the oxidation of substrates. In C. tropicalis, one class of cytochrome P450s catalyzes the.omega.-hydroxylation of fatty acids and the.alpha.,.omega.-hydroxylation of alkanes. Subsequent reactions by other enzymes generate.alpha.,.omega.-dicarboxylic acids, which are useful as raw materials for the preparation of numerous products such as perfumes, polymers, adhesives, coatings, lubricants, and macrolid antibiotics. Cytochrome P450s are heme thiolate proteins consisting of a heme moiety bound to a single polypeptide chain of 45,000 to 55,000 daltons (Da). The iron of the heme prosthetic group is located at the center of a protoporphyrin ring. Four ligands of the heme iron can be attributed to the porphyrin ring. The fifth ligand is a thiolate anion from a cysteinyl residue of the polypeptide. The sixth ligand is probably a hydroxyl group from an amino acid residue, or a moiety with a similar field strength such as a water molecule as described, e.g., in Goeptar et al., Critical Reviews in Toxicology 25(1):25-65 (1995), incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant Candida rugosa lipases Inventor(s): Lee, Guan-Chiun; (Taipei, TW), Shaw, Jei-Fu; (Taipei, TW), Tang, Shye-Jye; (Taipei, TW) Correspondence: FISH & RICHARDSON PC; 225 FRANKLIN ST; BOSTON; MA; 02110; US Patent Application Number: 20030124701 Date filed: August 31, 2001 Abstract: The present invention features an isolated nucleic acid that includes a mutant DNA encoding a Candida rugosa lipase, wherein the mutant DNA is 80% identical to a wild-type DNA encoding the Candida rugosa lipase, and includes at least 12 (e.g., 13, 15, 17, or all) universal serine codons corresponding to CTG codons in the wild-type DNA. Each of the universal serine codons, independently, is TCT, TCC, TCA, TCG, AGT, or AGC. The Candida rugosa lipase can be Candida rugosa lipase 1, 2, 3, 4, 5, or 8. Excerpt(s): Lipase (EC 3.1.1.3) is able to catalyze a wide range of chemical reactions, which include nonspecific and stereo-specific hydrolysis, esterfication, transesterification, and interesterification. In addition, it catalyzes the hydrolysis of an ester bond at water-lipid interface. See, e.g., Ader et al. (1997) Methods Enzymot. 286: 351-385; Gandhi (1997) J Am Oil Chem. Soc. 74: 621-634; Klibanov (1990) Acc. Chem. Res. 23: 114120; Shaw et al. (1990) Biotechnol. Bioeng. 35: 132-137; and Wang et al. (1988) Biotechnol. Bioeng. 31: 628-633. Due to its catalytic abilities, a Candida rugosa lipase, among

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commercial lipases, is widely used in bioindustries. Generally, crude C. rugosa lipases are applied in almost all biocatalytic applications, however, enzymes from various suppliers have been reported to show variations in their catalytic efficiency and stereospecificity. See Barton et al. (1990) Enzyme Microb. Technol. 12: 577-583. Several lipase isomers (i.e., isozymes) have been isolated from the crude C. rugosa lipase, and the lipase isozymes were shown to be different in catalytic efficiency and specificity. See Shaw et al. (1989) Biotechnol. Lett. 11: 779-784; Ra et al. (1993) Biochem. Biophysl Acta 1156: 181-189; Diczfalusy et al. (1997) Arch. Biochem. Biophys. 348: 1-8. To date, five lipase-encoding genomic sequences from C. rugosa have been characterized. See, for example, Longhi et al. (1992) Biochim. Biophy. Acta 1131: 227-232; and Lotti et al. (1993) Gene 124: 45-55. The five lipase-encoding genes (LIP1, 2, 3, 4, and 5) have been isolated from a SacI genomic library of the yeast C. rugosa by colony hybridization. The five genes encode for mature proteins of 534 residues with putative signal peptides of 15 (in LIP1, 3, 4, and 5) and 14 (in LIP 2) amino acids in length, respectively. The five deduced amino acid sequences share an overall identity of 66% and similarity of 84%. Due to a high sequence homology among the five deduced amino acid sequences and the differential expression level of the five lipase genes (Lee et al. (1999) Appl. Environ. Microbiol. 65: 3888-3895), it is difficult to purify each isozyme directly from the cultures of C. rugosa on a preparative scale for industrial applications. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic agents that inhibit the TUP1 pathway Inventor(s): Lockhart, Shawn R.; (Iowa City, IA), Soll, David R.; (Iowa City, IA), Zhao, Rui; (Iowa City, IA) Correspondence: FOLEY AND LARDNER; SUITE 500; 3000 K STREET NW; WASHINGTON; DC; 20007; US Patent Application Number: 20030073154 Date filed: September 10, 2002 Abstract: A gene previously identified in the context of controlling filamentous growth in C. albicans, TUP1, plays a central role in the regulation of phenotype switching in Candida cells. Accordingly, compounds and therapeutic protocols can be screened for an ability to disrupt the pathway, controlled by TUP1, that is comprised of genes the expression of which affect switching specifically. Agents thus identified are candidates for use in treating or preventing candidiasis. Excerpt(s): The present invention relates generally to an approach for developing pharmaceuticals and treatment protocols that are effective against Candida-associated pathologies. Fungal diseases have become a major medical problem and are growing in severity, given the rising incidence of immunosuppression associated with AIDS, diabetes, cancer therapies, and organ transplantation, among other conditions. Debilitated patients thus affected are especially susceptible to fungal pathogens, most of which are opportunists. The yeast Candida can exist both as a non-virulent colonizer (commensal) and as a pathogen. Candidiasis is increasingly widespread, with hospitalized and immunocompromised patients at greatest risk, and has become the sixth most common form of pathogenic infection. Systemic Candida infections may be lethal, with a mortality rate of 50% in adults and up to 65% in infants. Reviewed in Pfaller (1996); see also Colombo et al. (1999). The risk of death from systemic infection most strongly correlates with the time between the first detected infection and the onset of anti-fungal treatment. Pacheco-Rios et al. (1997).

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Transformation systems for flavinogenic yeast Inventor(s): Abbas, Charles; (Champaign, IL), Dmytruk, Kostiantyn V.; (Lviv, UA), Fayura, Liubov R.; (Lviv, UA), Kshanovska, Barbara V.; (Lviv, UA), Sibirna, Kateryna A.; (Lviv, UA), Sibirny, Andrii A.; (Lviv, UA), Voronovsky, Andrii Y.; (Lviv, UA) Correspondence: STERNE, KESSLER, GOLDSTEIN & FOX PLLC; 1100 NEW YORK AVENUE, N.W., SUITE 600; WASHINGTON; DC; 20005-3934; US Patent Application Number: 20030082815 Date filed: July 13, 2001 Abstract: This invention is directed to the transformation of the flavinogenic yeasts, Pichia guilliermondii and Candida famata, and mutants thereof, by electroporation (electrotransformation) and by spheroplast transformation. The invention is also directed to nucleic acid constructs such as vectors, plasmids, and ARS sequences which transform flavinogenic yeasts, and mutants thereof, at a high level and in a stable manner so as to result in stably transformed yeast host cells which express/produce recombinant products. This invention also is directed to flavinogenic yeasts, Pichia guilliermondii and Candida famata, and mutants and temperature sensitive mutants thereof, which produce or overproduce riboflavin. Excerpt(s): This application claims benefit to the filing dates of U.S. Provisional Application No. 60/218,244, filed Jul. 14, 2000; U.S. Provisional Application No. 60/288,491, filed May 4, 2001; and U.S. Provisional Application No. 60/290,667, filed May 15, 2001, each of which is herein incorporated by reference. The present invention relates, in general, to the fields of yeast transformation, yeast cells thereby transformed and production of recombinant products therefrom. More specifically, the present invention relates to the transformation of yeast by electroporation and spheroplast formation. Riboflavin (vitamin B.sub.2) is synthesized by all plants and many microorganisms, but is not produced by higher animals. Because it is a precursor to coenzymes such as flavin adenine dinucleotide and flavin mononucleotide, that are required in the enzymatic oxidation of carbohydrates, riboflavin is essential to basic metabolism. In higher animals, insufficient riboflavin can cause loss of hair, inflammation of the skin, vision deterioration, and growth failure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Tricarboxylic acids, method, and branched polycarbonates prepared therefrom Inventor(s): Amaratunga, Mohan Mark; (Clifton Park, NY), Lobos, John Henry; (Ballston Spa, NY), Mobley, David Paul; (Niskayuna, NY) Correspondence: GENERAL ELECTRIC COMPANY; GLOBAL RESEARCH CENTER; PATENT DOCKET RM. 4A59; PO BOX 8, BLDG. K-1 ROSS; NISKAYUNA; NY; 12309; US Patent Application Number: 20020169339 Date filed: January 10, 2002 Abstract: Aliphatic tricarboxylic acids, as exemplified by 9-carboxy-1,18-octadecanedioic acid, may be prepared by the biotransformation of an olefinic monocarboxylic acid

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such as oleic acid to the corresponding olefinic dicarboxylic acid, preferably 1,18octadec-9-enedioic acid, in the presence of a strain of yeast, such as a strain of Candida tropicalis, followed by the carboxylation of the olefinic dicarboxylic acid by reaction with carbon monoxide and water in the presence of a catalyst. The product tricarboxylic acids are useful as branching agents for polycarbonates. Excerpt(s): This invention relates to the preparation of branched polycarbonates. More particularly, it relates to new tricarboxylic acid branching agents and the polycarbonates derived therefrom. Polycarbonate resins are a well known class of synthetic polymeric resins which may be prepared by various methods including the reaction of a dihydroxy compound, preferably a dihydroxyaromatic compound, with a carbonate precursor; see for example U.S. Pat. No. 3,028,365. For certain purposes such as blow molding, branched polycarbonates are superior to the linear polymers by reason of their melt rheology behavior. In particular, they exhibit high melt elasticity and high melt strength. Melt elasticity is the recovery of the elastic energy stored within the melt from distortion or orientation of the molecules by shearing stresses. Melt strength may be simply described as the tenacity of a molten strand and indicates the ability of the melt to support a stress. These advantageous properties of the branched resins are in large part a result of their non-Newtonian flow characteristics. In the typical preparation of branched polycarbonates, a linear polycarbonate or its precursor undergoes reaction with a branching agent. Commonly employed branching agents include 1,1,1-tris(4hydroxyphenyl)eth- ane (THPE) and trimellityl trichloride (TMTC). However, THPE is very expensive, partly by reason of its method of preparation in which an essential reactant is the expensive 4-hydroxyacetophenone. Branched polycarbonates prepared with TMTC are photochemically unstable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Yeast vector and method of producing proteins using the same Inventor(s): Kondo, Keiji; (Yokohama-shi, JP), Miura, Yutaka; (Yokohama-shi, JP) Correspondence: Stephen A. Bent; FOLEY & LARDNER; Washington Harbour; 3000 K Street, NW., Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20020115220 Date filed: July 20, 2001 Abstract: An object of the present invention is to provide a vector which can be integrated into a yeast chromosome in a high number of copies. Another object of the present invention is to provide a modified vector which can be integrated into the yeast chromosome in a high number of copies and of which expression units stably maintain on the chromosome. The vector according to the present invention comprises a marker gene for selecting transformants, a shortened promoter sequence which is operably linked to the marker gene and a sequence homologous to the chromosomal DNA of Candida utilis, and optionally a heterologous gene or a gene derived from C. utilis, wherein the vector is linearized by cleaving within said homologous DNA sequence or at both ends of the homologous DNA sequence with restriction enzymes, and wherein the heterologous gene or the gene derived from C. utilis can be integrated into the chromosomal DNA of C. utilis by homologous recombination. Excerpt(s): The present invention relates to a vector which is integrated into the chromosome of yeast, specifically Candida utilis, with a high number of copies and which can be stably maintained even under nonselective culture conditions. The present

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invention also relates to heterologous gene expression, specifically the high-level expression of a single chain monellin and amylase, using said vector, and further relates to a method for isolating and purifying a single-chain monellin from single-chain monellin-producing recombinant yeast cells. In order to prepare gene products in large quantities using recombinant DNA procedures, it is necessary not only to select an appropriate host but also to increase the number of gene transcripts, to improve the translation efficiency, and to improve the stability of proteins produced in the various steps of gene expression. In order to increase the number of gene transcript for highlevel production of gene products, it is necessary to use a highly effective transcription promoter and it is also important to increase the number of copies of the geneexpression unit which consists of the transcription promoter/terminator sequence and the gene to be expressed, thereby increasing the number of transcripts as a whole. Furthermore, for industrial scale production, it is extremely important that the geneexpression unit be stably maintained in the microbial cells. Plasmid vectors are at a disadvantage in this regard and generally stabilized by integration into a chromosome. Regarding several yeast species other than C. utilis, it has been recently reported that dozens of copies of a vector could be integrated into the ribosomal RNA gene (rDNA) regions by using the vector carrying a transformation marker gene in which the promoter region was trancated to reduce the expression level (Lopes T. S. et al., Gene, 79, 199-206, 1989; Bergkamp R. J. M. et al., Curr. Genet., 21, 365-370, 1992; Le Dall M. T. et al., Curr. Genet., 26, 38-44, 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with Candida, 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 “Candida” (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 Candida. You can also use this procedure to view pending patent applications concerning Candida. 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 CANDIDA Overview This chapter provides bibliographic book references relating to Candida. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Candida 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 “Candida” (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 Candida: •

Sjogren's Syndrome Source: Torrance, CA: Homestead Schools, Inc. 2001. 101 p. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail: [email protected]. Website: www.homesteadschools.com. PRICE: $48.00 plus shipping and handling. Course No. 6590. Summary: Sjogren's syndrome is a chronic disorder of unknown cause characterized by a particular form of dry mouth (xerostomia) and dry eyes. This continuing education program for dentists focuses on Sjogren's syndrome (SS). Topics include the symptoms of SS and how to distinguish between primary and secondary SS; autoimmune response systems and the role of hereditary and environmental factors in causing SS; other causes of dry eyes and xerostomia; the salivary and nonsalivary causes of xerostomia; treatment approaches for patients with SS; the advantages and side effects of certain

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medications used by SS patients; treatment alternatives to oral Candida mucositis, oral dryness, and tooth decay for patients with SS; other symptoms of SS and their treatments, including vaginal dryness, fatigue, depression, and heartburn; and the use of pilocarpine tables for the treatment of xerostomia and dry eye symptoms in patients with SS. The document concludes with a posttest with which readers can qualify for continuing education credit, a glossary of terms, and an appendix of product and manufacturer information. The document is illustrated with numerous black and white photographs. 4 figures. 14 tables. 62 figures. •

Microbiology of HIV-Associated Gingivitis and Periodontitis Source: Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections. San Diego, CA, January 18-20, 1988. Contact: PSG Publishing Company, 545 Great Rd, Littleton, MA, 01460, (508) 486-8971. Summary: These proceedings of the Conference Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections held in San Diego, CA, on January 18-20, 1988. They describes the investigation of microbiota associated with intraoral lesions associated with infection by the Human immunodeficiency virus (HIV) that causes Acquired immunodeficiency syndrome (AIDS). Subgingival plaque samples from HIV-seropositive males and from HIV-seronegative controls were examined by indirect immunofluorescence and microbiological culturing. Samples were classified as HIV-associated gingivitis, HIV-associated periodontitis, or disease-free in an HIVpositive person. Microbiological analysis revealed that HIV-gingivitis and HIVperiodontitis sites contained more Candida albicans compared with control sites. Also, Bacteroides gingivalis, B intermedius, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Eikenella Corrodens, and Wolinella were more prevalent in HIV-periodontitis sites and HIV-gingivitis sites than in HIV-positive healthy sites and control sites. Distribution of microbiota in HIV-periodontitis and HIV-gingivitis sites appeared similar to those found in classic periodontitis sites. The microbiota from HIVpositive healthy and HIV-negative control sites was characteristic of healthy periodontium. It is suggested that HIV-gingivitis may be a precursor to HIVperiodontitis.

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Common Oral Lesions Associated With HIV Infection Contact: Ohio State University, Department of Family Medicine, AIDS Education and Training Center, 1314 Kinnear Rd Area 300, Columbus, OH, 43212, (614) 292-4056. Summary: This pocket-sized monograph describes 11 oral opportunistic infections associated with HIV infection. They are broken into the following categories: Fungal infections caused by Candida Albicans, Kaposi's sarcoma, viral infections, and bacterial infections. Each entry includes a clinical photograph, a description, means of diagnosis, and method of treatment.

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

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books. When searching for “Candida” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Candida” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Candida” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Allergies and candida : with the 21st century solution by Steven Rochlitz; ISBN: 0945262256; http://www.amazon.com/exec/obidos/ASIN/0945262256/icongroupinterna

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Allergies and Candida: With the Physicist's Rapid Solution by Steven Rochlitz, et al; ISBN: 0945262213; http://www.amazon.com/exec/obidos/ASIN/0945262213/icongroupinterna

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Allergy & Candida cooking : rotational style by Sondra K. Lewis; ISBN: 0964346206; http://www.amazon.com/exec/obidos/ASIN/0964346206/icongroupinterna

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Allergy & Candida Cooking Made Easy by Sondra K. Lewis, et al (1996); ISBN: 0964346214; http://www.amazon.com/exec/obidos/ASIN/0964346214/icongroupinterna

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Back to the bio-basics : a collection of recipes, menus, and diet information to aid alternative treatment of cancer/candida as recommended by cancer/candida treatment centers in Mexico by Joy D. King; ISBN: 0939825007; http://www.amazon.com/exec/obidos/ASIN/0939825007/icongroupinterna

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Beat Candida by Jacobs; ISBN: 0091813867; http://www.amazon.com/exec/obidos/ASIN/0091813867/icongroupinterna

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Beat Candida Through Diet: A Complete Dietary Programme for Sufferers of Candidiasis by Gill Jacobs, Michelle Berridale-Johnson; ISBN: 0091815452; http://www.amazon.com/exec/obidos/ASIN/0091815452/icongroupinterna

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Bible Cure for Candida Recepies by Don Colbert (2004); ISBN: 0884199401; http://www.amazon.com/exec/obidos/ASIN/0884199401/icongroupinterna

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Candida by Luc, M.D., Ph.D., Lic.Ac., C.Hom., D.I.Hom. De Schepper (1990); ISBN: 094250108X; http://www.amazon.com/exec/obidos/ASIN/094250108X/icongroupinterna

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Candida by Pirkko Lindberg; ISBN: 951500814X; http://www.amazon.com/exec/obidos/ASIN/951500814X/icongroupinterna

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Candida by Antonio Spagnuolo; ISBN: 8870428680; http://www.amazon.com/exec/obidos/ASIN/8870428680/icongroupinterna

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Candida ("The Natural Way" Series) by Simon Martin; ISBN: 1862041938; http://www.amazon.com/exec/obidos/ASIN/1862041938/icongroupinterna

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Candida Adherence to Epithelial Cells by Mahmoud A. Ghannoum, et al; ISBN: 0849359791; http://www.amazon.com/exec/obidos/ASIN/0849359791/icongroupinterna

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Candida Albican Yeast-Free Cookbook, The : How Good Nutrition Can Help Fight the Epidemic of Yeast-Related Diseases by Pat Connolly, et al; ISBN: 0658002929; http://www.amazon.com/exec/obidos/ASIN/0658002929/icongroupinterna

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Candida Albicans by Sarah Brewer; ISBN: 0722533918; http://www.amazon.com/exec/obidos/ASIN/0722533918/icongroupinterna

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Candida Albicans by Ray C. Wunderlich, et al; ISBN: 0879833645; http://www.amazon.com/exec/obidos/ASIN/0879833645/icongroupinterna

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Candida Albicans: A Nutritional Approach by Louise Tenney, Rita Elkins (1997); ISBN: 0913923281; http://www.amazon.com/exec/obidos/ASIN/0913923281/icongroupinterna

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Candida Albicans: A User's Guide to Treatment and Recoverly by Gill Jacobs; ISBN: 035621088X; http://www.amazon.com/exec/obidos/ASIN/035621088X/icongroupinterna

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Candida Albicans: Cellular and Molecular Biology by R. Prasad (Editor); ISBN: 0387519262; http://www.amazon.com/exec/obidos/ASIN/0387519262/icongroupinterna

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Candida Albicans: Could Yeast Be Your Problem? by Leon Chaitow (1998); ISBN: 089281795X; http://www.amazon.com/exec/obidos/ASIN/089281795X/icongroupinterna

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Candida Albicans: How Your Diet Can Help by Stephen Terrass; ISBN: 0722531508; http://www.amazon.com/exec/obidos/ASIN/0722531508/icongroupinterna

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Candida Albicans: The Pathogenic Fungus by Cora G. Saltarelli; ISBN: 0891168974; http://www.amazon.com/exec/obidos/ASIN/0891168974/icongroupinterna

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Candida Albicans: The Quiet Epidemic by Stanley Weinberger (1995); ISBN: 0961618469; http://www.amazon.com/exec/obidos/ASIN/0961618469/icongroupinterna

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Candida Albicans: Yeast-Free Recipes for Renewed Health and Vitality (Special Diet Cookbooks) by Richard Turner, et al; ISBN: 0722519109; http://www.amazon.com/exec/obidos/ASIN/0722519109/icongroupinterna

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Candida and Candidamycosis (Fems Symposium, No 50) by Emel Tumbay (1991); ISBN: 0306438291; http://www.amazon.com/exec/obidos/ASIN/0306438291/icongroupinterna

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Candida and Candidiasis by Richard A. Calderone (Editor) (2002); ISBN: 1555812120; http://www.amazon.com/exec/obidos/ASIN/1555812120/icongroupinterna

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Candida and Candidosis by F. C. Odds; ISBN: 0702012653; http://www.amazon.com/exec/obidos/ASIN/0702012653/icongroupinterna

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Candida and How He Lied to Her Husband by George Bernard Shaw, J. Percy Smith (Editor) (1981); ISBN: 0824045793; http://www.amazon.com/exec/obidos/ASIN/0824045793/icongroupinterna

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Candida Directory/the Comprehensive Guidebook to Yeast-Free Living by Helen Gustafson, Maureen O'Shea (1994); ISBN: 0890877149; http://www.amazon.com/exec/obidos/ASIN/0890877149/icongroupinterna

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Candida in Paris by Virginia Lasalle; ISBN: 0352332158; http://www.amazon.com/exec/obidos/ASIN/0352332158/icongroupinterna

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Candida Yeast the Battle in Your Body by Jonathon D. Miller; ISBN: 0935815031; http://www.amazon.com/exec/obidos/ASIN/0935815031/icongroupinterna

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Candida, Me and Allergies: The Way Back to Good Health an A-Z by Jo Hampton, Ben Hampton (Editor); ISBN: 0952154439; http://www.amazon.com/exec/obidos/ASIN/0952154439/icongroupinterna

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Candida, Silver (1986); ISBN: 0930165020; http://www.amazon.com/exec/obidos/ASIN/0930165020/icongroupinterna

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Candida, Silver (Mercury Fillings and the Immune System) by Betsy Russell-Manning (Editor), et al; ISBN: 0930165101; http://www.amazon.com/exec/obidos/ASIN/0930165101/icongroupinterna

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Candida, the Silent Epidemic: Vital Information to Detect, Combat and Prevent Yeast Infections by Gail Burton; ISBN: 0970325606; http://www.amazon.com/exec/obidos/ASIN/0970325606/icongroupinterna

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Candida: A Mystery. by George Bernard, Shaw, et al; ISBN: 0672610884; http://www.amazon.com/exec/obidos/ASIN/0672610884/icongroupinterna

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Candida: A Natural Approach by Karen Brody, Shirley Trickett (1999); ISBN: 1569751536; http://www.amazon.com/exec/obidos/ASIN/1569751536/icongroupinterna

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Candida: A Practical Handbook for Sufferers by Angela Kilmartin; ISBN: 0954267729; http://www.amazon.com/exec/obidos/ASIN/0954267729/icongroupinterna

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Candida: A Twentieth Century Disease by Shirley Lorenzani; ISBN: 0879833750; http://www.amazon.com/exec/obidos/ASIN/0879833750/icongroupinterna

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Candida: Diet Against It: What You Eat Can Help Direct Your Immune System to Help You by Luc, M.D., Ph.D., Lic.Ac., C.Hom., D.I.Hom De Schepper, Luc De Schepper; ISBN: 0572015011; http://www.amazon.com/exec/obidos/ASIN/0572015011/icongroupinterna

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Candida: Looking After Inner Health by Hasnain, Ph.D. Walji (1997); ISBN: 1891294032; http://www.amazon.com/exec/obidos/ASIN/1891294032/icongroupinterna

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Candida: The Silent Epidemic: Vital Information to Detect, Combat, and Prevent Yeast Infections by Gail Burton, et al (2003); ISBN: 0944031935; http://www.amazon.com/exec/obidos/ASIN/0944031935/icongroupinterna

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Candida: The Symptoms the Causes the Cure by Luc, M.D., Ph.D., Lic.Ac., C.Hom., D.I.Hom De Schepper; ISBN: 096147341X; http://www.amazon.com/exec/obidos/ASIN/096147341X/icongroupinterna

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Candida-Related Complex: What Your Doctor Might Be Missing by Christine Winderlin, Keith Sehnert (Contributor) (1996); ISBN: 0878339353; http://www.amazon.com/exec/obidos/ASIN/0878339353/icongroupinterna

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Candida's Secret Mission by Virginia Lasalle; ISBN: 0352331410; http://www.amazon.com/exec/obidos/ASIN/0352331410/icongroupinterna

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Candidose (Candida Albicans) by S. Martin; ISBN: 2921556707; http://www.amazon.com/exec/obidos/ASIN/2921556707/icongroupinterna

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Complete Candida Yeast Guidebook: Everything You Need to Know About Prevention, Treatment & Diet by Zoltan P. Rona (Contributor), Jeanne Marie Martin (2000); ISBN: 0761527400; http://www.amazon.com/exec/obidos/ASIN/0761527400/icongroupinterna

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Conquer Candida: And Restore Your Immune System by Dr. Jack Tips (1988); ISBN: 0929167007; http://www.amazon.com/exec/obidos/ASIN/0929167007/icongroupinterna

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Cooking for Candida: Recipes and Diet Plans Using Food You Can Eat (Includes Vegetarian Options) by Jo Hampton (1996); ISBN: 0952154412; http://www.amazon.com/exec/obidos/ASIN/0952154412/icongroupinterna

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Coping With Candida by Shirley Trickett (2003); ISBN: 085969688X; http://www.amazon.com/exec/obidos/ASIN/085969688X/icongroupinterna

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Coping with Candida (A McCulloch Positive Health Book) by Peter De Ruyter; ISBN: 1863732616; http://www.amazon.com/exec/obidos/ASIN/1863732616/icongroupinterna

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Coping With Candida Cookbook by Sally Rockwell; ISBN: 0916575004; http://www.amazon.com/exec/obidos/ASIN/0916575004/icongroupinterna

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Dealing With Your Candida and Allergies; ISBN: 0961417315; http://www.amazon.com/exec/obidos/ASIN/0961417315/icongroupinterna

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Dealing With Your Candida and Allergies (And Feeling Better) by Howard Hagglund; ISBN: 0961417323; http://www.amazon.com/exec/obidos/ASIN/0961417323/icongroupinterna

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Development and Validation of a Localized Murine Candidiasis Model: The Pathogenesis, Chemotherapy and Defense Mechanisms to Candida Mastitis in the Lactating Mouse (Comprehensive Summaries of Uppsala Dissertations, 829) by Faisal Abdi Guhad (1999); ISBN: 9155444288; http://www.amazon.com/exec/obidos/ASIN/9155444288/icongroupinterna

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Diets to Help: Candida (Diets to Help) by Leon Chaitow; ISBN: 072253423X; http://www.amazon.com/exec/obidos/ASIN/072253423X/icongroupinterna

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Erica White's Beat Candida Cookbook: Over 300 Recipes With a 4-Point Plan for Attacking Candidiasis by Erica White (1999); ISBN: 0722538561; http://www.amazon.com/exec/obidos/ASIN/0722538561/icongroupinterna

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Food Combining Beating Candida; ISBN: 0722532482; http://www.amazon.com/exec/obidos/ASIN/0722532482/icongroupinterna

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Home Remedies for Candida by Betsy Russell-Manning (1995); ISBN: 0930165187; http://www.amazon.com/exec/obidos/ASIN/0930165187/icongroupinterna

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How to Stop Candida & Other Yeast Conditions in Their Tracks by Valerie Saxion (2003); ISBN: 0972456376; http://www.amazon.com/exec/obidos/ASIN/0972456376/icongroupinterna

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Natures Own Candida Cure (Natural Health Guide) by William G. Crook (2002); ISBN: 1553120027; http://www.amazon.com/exec/obidos/ASIN/1553120027/icongroupinterna

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Nutrition & Candida Albicans; ISBN: 0879834463; http://www.amazon.com/exec/obidos/ASIN/0879834463/icongroupinterna

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Overcoming Candida: The Ultimate Cookery Guide by Xandria Williams; ISBN: 1843330423; http://www.amazon.com/exec/obidos/ASIN/1843330423/icongroupinterna

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Overcoming Chronic Fatigue: Effective Self-Help Options to Relieve the Fatigue Associated With CFS, Candida, Allergies, PMS, Menopause, Anemia, Low Thyroid and Depression ((Good Health Guide Ser.: Women's Self Care Library)) by Susan M. Lark; ISBN: 0879837160; http://www.amazon.com/exec/obidos/ASIN/0879837160/icongroupinterna

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Oxygen Healing Therapies: For Optimum Health & Vitality Bio-Oxidative Therapies for Treating Immune Disorders: Candida, Cancer, Heart, Skin … by Nathaniel

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Altman, Charles H. Farr; ISBN: 0892815272; http://www.amazon.com/exec/obidos/ASIN/0892815272/icongroupinterna •

Peak Immunity: How to Fight CEBV, Candida, Herpes Simplex Viruses and Other Immuno-Suppressed Conditions and Win by Luc, M.D., Ph.D., Lic.Ac., C.Hom., D.I.Hom De Schepper; ISBN: 0961473428; http://www.amazon.com/exec/obidos/ASIN/0961473428/icongroupinterna

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Recipes for Health: Candida Albicans: Over 100 Yeast-Free and Sugar-Free Recipes by Shirley Trickett; ISBN: 0722529678; http://www.amazon.com/exec/obidos/ASIN/0722529678/icongroupinterna

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Relief from Candida: Allergies & Ill Health by Greta Sichel (1994); ISBN: 186351001X; http://www.amazon.com/exec/obidos/ASIN/186351001X/icongroupinterna

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The Arthritis Cookbook and Drug Free Treatment Plan: Includes Vegetarian and Candida Options by Jo Hampton, Ben Hampton (Editor); ISBN: 0952154420; http://www.amazon.com/exec/obidos/ASIN/0952154420/icongroupinterna

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The Bible Cure for Candida and Yeast Infections by Don, Md. Colbert, Don Colbert (2001); ISBN: 0884197433; http://www.amazon.com/exec/obidos/ASIN/0884197433/icongroupinterna

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The Candida Albicans Yeast-Free Cookbook by Pat Connolly; ISBN: 0879834099; http://www.amazon.com/exec/obidos/ASIN/0879834099/icongroupinterna

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The Candida Control Cookbook: What You Should Know and What You Should Eat to Manage Yeast Infections by Gail Burton, Michael E., MD Rosenbaum (Introduction) (2002); ISBN: 0944031803; http://www.amazon.com/exec/obidos/ASIN/0944031803/icongroupinterna

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The Candida Yeast Answer by Gary Carlsen, RH Gary Carlsen; ISBN: 1576360792; http://www.amazon.com/exec/obidos/ASIN/1576360792/icongroupinterna

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The Candida-Yeast Syndrome by Ray C.,Jr.M.D Wunderlich, Dwight K. Kalita (Contributor); ISBN: 0879836970; http://www.amazon.com/exec/obidos/ASIN/0879836970/icongroupinterna

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The Genetics of Candida by Donald R. Kirsch, et al; ISBN: 0849355702; http://www.amazon.com/exec/obidos/ASIN/0849355702/icongroupinterna

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The Way Back: the A-Z of Coping with Candida, M.E. and Allergies by Jo Hampton, David Gaiman (Editor) (1993); ISBN: 0952154404; http://www.amazon.com/exec/obidos/ASIN/0952154404/icongroupinterna

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Understanding Candida: Treatment and Recipes by Peter De Ruyter; ISBN: 1853270350; http://www.amazon.com/exec/obidos/ASIN/1853270350/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Candida” (or synonyms) into the search box, and select “books only.”

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From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Acidophilus & colon health: Candida breakthrough post-antibiotic therapy. Author: Webster, David,; Year: 1968; Denver, CO, U.S.A.: Nutri-Books, c1991; ISBN: 0961670312 http://www.amazon.com/exec/obidos/ASIN/0961670312/icongroupinterna

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Allergies and candida: with the physicist's rapid solution Author: Rochlitz, Steven.; Year: 1994; New York: Human Ecology Balancing Sciences, c1991-; ISBN: 0945262205 http://www.amazon.com/exec/obidos/ASIN/0945262205/icongroupinterna

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Candida albicans: cellular and molecular biology Author: Prasad, R. (Rajendra),; Year: 1966; Berlin; New York: Springer-Verlag, c1991; ISBN: 3540519262 http://www.amazon.com/exec/obidos/ASIN/3540519262/icongroupinterna

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Candida albicans, by H. I. Winner and Rosalinde Hurley. Author: Winner, H. I. (Harold Ivor); Year: 1955; London, Churchill, 1964

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Laboratory studies on endomycin, with special reference to its antifungal effect against Candida albicans. Author: Perry, Harold O. (Harold Otto),; Year: 1979; [Minneapolis] 1953

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Serological studies in genus Candida. Author: Jonsen, Jon.; Year: 1953; [Oslo, 1955]

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Sub Cruce Candida: a celebration of one hundred years of army nursing, 1902-2002 Author: Great Britain. Army. Queen Alexandra's Royal Army Nursing Corps.; Year: 1990; Great Britain: QARANC Association, 2002; ISBN: 0954115902

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The effect of iron deficiency on the growth and glucose metabolism of Candida guilliermondii. Author: Kauppinen, Veli.; Year: 1974; Helsinki, 1963

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

Preventive Measures and Maintenance Care After Treatment Source: in Budtz-Jorgensen, E. Prosthodontics for the Elderly: Diagnosis and Treatment. Chicago, IL: Quintessence Publishing Co, Inc. 1999. p. 229-257. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail:

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

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[email protected]. Website: www.quintpub.com. PRICE: $89.00 plus shipping and handling. ISBN: 0867153687. Summary: The goal of dental and prosthetic care for older individuals is to maintain the health and function of the masticatory system by establishing adequate preventive measures without excessive therapeutic intervention. Therefore, before institution of any prosthetic treatment, it is important to establish, if possible, an optimal oral hygiene regimen and to introduce a rational treatment plan that takes into account the patient's degree of cooperation. This chapter on preventive measures and maintenance care after treatment is from a book that offers a comprehensive look at prosthodontics for older patients. Topics include preventive measures for caries (cavities) such as oral hygiene, diet, fluoride and chlorhexidine; preventive measures for periodontal disease; management of oral mucositis; management of Candida associated denture stomatitis; oral hygiene and maintenance care for fixed or removable partial dentures; the use of overdentures, implant support prostheses, and complete dentures; commercial denture cleansers and denture wearing habits; and the provision of oral hygiene by caregivers. The author concludes by stressing the importance of the older individual taking an active part in the procedures used for his or her hygiene care of the teeth. The chapter is illustrated with numerous full color photographs. 21 figures. 5 tables. 112 references. •

Fungal Arthritis Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 599-607. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals presents an overview of fungal arthritis. The epidemiology and clinical features of fungal arthritis are discussed. Some of the drugs used to treat fungal infections are identified. The clinical features, diagnosis, and treatment of various fungal infections are highlighted. These include Candida spp. infections, blastomycosis, sporotrichosis, coccidioidomycosis, histoplasmosis, cryptococcosis, and paracoccidioidomycosis. Miscellaneous fungi that have been implicated in joint infections are also identified. 91 references, 5 figures, and 2 tables.

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Cheilitis/Cheilosis Source: in Bottomley, W.K. and Rosenberg, S.W., eds. Clinician's Guide to Treatment of Common Oral Conditions. 4th ed. Baltimore, MD: American Academy of Oral Medicine (AAOM). 1997. p. 4. Contact: Available from American Academy of Oral Medicine (AAOM). 2910 Lightfoot Drive, Baltimore, MD 21209-1452. (410) 602-8585. Website: www.aaom.com. PRICE: $21.00 plus shipping and handling. Summary: This chapter is from a quick reference guide to the etiologic factors, clinical description, and currently accepted therapeutic management of some common oral conditions. This brief chapter discusses cheilitis/cheilosis, defined as fissured lesions in the corners of the mouth, caused by a mixed infection of the microorganisms candida albicans, staphylococci, and streptococci. The authors provide a summary of the etiology, clinical description, and rationale for treatment, then outline recommended prescription drugs used to treat the condition. The chapter discusses both angular cheilitis/cheilosis and actinic cheilitis/solar cheilosis.

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Esophagitis Source: in Feigin, R.D. and Cherry, J.D., eds. Textbook of Pediatric Infectious Diseases. 4th ed. Volume 1. Philadelphia, PA: W.B. Saunders Company. 1998. p. 562-566. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $315.00. ISBN: 0721664482. Summary: This chapter on esophagitis is from a textbook on pediatric infectious diseases. The authors stress that infectious esophagitis is distinct from other gastrointestinal (GI) infections because it is rare in previously healthy persons, is predominantly caused by fungal and viral agents, and is usually a sign of immunodeficiency (which can be due to acquired, drug-induced, or congenital causes). Infection by multiple organisms is common in these patients. Even in normal children, infectious esophagitis is commonly associated with conditions that compromise esophageal defense mechanisms. The authors consider the pathophysiology and causative organisms, the typical clinical presentation, the differential diagnosis (including the use of esophagoscopy, biopsies, and brushings), treatment options, and prognosis. Treatment options are summarized for esophagitis caused by Candida fungus, viruses, and bacteria. Patients with AIDS respond more poorly to the drug therapy than immunocompetent patients. Surgery is required for fistulas, obstruction, and perforations that may occur (most common with Candida esophagitis). 5 figures. 2 tables. 39 references. (AA-M).

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Infection and Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 485-499. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on infection and diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. The authors characterize infections related to diabetes as 'probable' (the data support the presence of the association), 'possible' (presence or absence of an association cannot be established from current data) and 'doubtful' (data argue for no association). People with diabetes probably have a higher risk of the following infections: asymptomatic bacteriuria, lower extremity infections, reactivation tuberculosis in American Indians, infections in surgical wounds after sternotomy and total hip replacement, and group B streptococcal. Support for these associations comes from controlled observational studies in all cases, except for lower extremity infections, where the magnitude of the association between foot and ankle infection and diabetes from hospital-based data appears too great to be explained by detection, selection, or other potential biases. Local and systemic immunologic defects probably account for higher infection rates in patients with diabetes. Autonomic and sensory neuropathy probably account for higher bacteriuria and lower extremity infection rates, while systemic immunologic effects of diabetes may be responsible for the increased risk of surgical wound infection and tuberculosis reinfection. Populationbased data also support a probable higher influenza and pneumonia mortality rate in patients with diabetes. There is a possible association between diabetes and prevalence

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of the following infections: cystitis, pyelonephritis, candida vulvovaginitis and cystitis, pneumonia, influenza, chronic bronchitis, bacteremia, primary tuberculosis, reactivation tuberculosis in non-American Indians, mucormycosis, malignant otitis externa, and Fournier's gangrene. Doubtful associations exist between diabetes and prevalence of chronic sinusitis or S. aureus colonization (staph infection). 6 tables. 103 references. (AAM). •

Oral Candidiasis and HIV Infection Source: in Greenspan, J.S.; Greenspan, D., eds. Oral Manifestations of HIV Infection: Proceedings of the Second International Workshop on the Oral Manifestations of HIV Infection. Carol Stream, IL: Quintessence Publishing Company, Inc. 1995. p. 80-84. Contact: Available from Quintessence Publishing Company, Inc. 551 North Kimberly Drive, Carol Stream, IL 60188-1881. (800) 621-0387 or (630) 682-3223; Fax (630) 682-3288; E-mail: [email protected]; http://www.quintpub.com. PRICE: $64.00 plus shipping and handling. ISBN: 0867152869. Summary: This chapter on oral candidiasis and HIV infection is from the proceedings of the Second International Workshop on the Oral Manifestations of HIV Infection, held in February 1993, in San Francisco, California. The chapter's topics include how the four types of oral mucosal lesions are caused by oral candida infection, i.e., pseudomembranous (thrush), erythematous, hyperplastic, and angular cheilitis; the diagnosis of oral candidiasis; treatment options, including drug therapy, topical approaches, and systemic treatment; and the importance of oral candidiasis in HIV infection. 4 figures. 12 references.

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Other Colitides Source: in Kirsner, J.B., ed. Inflammatory Bowel Disease. 5th ed. Saint Louis, MO: W.B. Saunders Company. 1999. p. 410-423. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522. Fax (800) 568-5136. E-mail: [email protected]. Website: www.wbsaunders.com. PRICE: $145.00 plus shipping and handling. ISBN: 0721676162. Summary: This chapter on other colitides in inflammatory bowel disease (IBD) is from a comprehensive textbook that describes all the latest scientific and clinical advances in the field of IBD, including etiology and pathogenesis, evaluation and classification, medical and surgical therapies, and patient care management. The other colitides include collagenous and lymphocytic colitis, and infectious colitis, including colitis due to bacteria (such as Clostridium difficile or Escherichia coli), mycobacteria (tuberculosis, Salmonella, Shigella, or Yersinia), viral infection (including cytomegalovirus or HIV), protozoa (including crytosporidium), other parasites, and fungal infection (including with candida and aspergillus). In each section the author discusses symptoms, diagnosis, associations with other gastrointestinal diseases, and treatment options. The author notes that the mimicry of ulcerative colitis and Crohn's disease by other forms of colitis and by many bacterial, viral, and protozoan infections reflects the well known limitation of the intestine's clinical and morphologic responsiveness to disease. This restriction emphasizes the importance of the careful evaluation of all patients with intestinal symptoms (diarrhea, rectal bleeding, and associated symptoms), not only to recognize treatable (curable) diseases but also to identify clues as to the nature and treatment of IBD. 4 figures. 8 tables. 101 references.

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Oral Thrush Source: in World Health Organization (WHO) Global Programme on AIDS. Guidelines for the Clinical Management of HIV Infection in Adults. Geneva, Switzerland: World Health Organization. 1991. p. 4:1-4:10. Contact: Available from WHO Publications Center USA. 49 Sheridan Avenue, Albany, NY 12210. Fax (518) 436-7433. E-mail: [email protected]. PRICE: $11.70 plus shipping and handling. Summary: This chapter provides a patient care algorithm for managing patients with HIV-infection who have oral thrush. The chapter is from a set of guidelines, published by the World Health Organization, on the clinical management of HIV infection in adults. The guidelines address the wide variations in the presentation of HIV-related diseases, availability of resources, and health infrastructures in various countries around the world. The algorithm for oral thrush begins with instructions for diagnosis, the describes recommended treatment options, including treatment for chronic or recurrent thrush problems. The author notes that candidiasis may extend into the esophagus and cause difficulty (dysphagia) and pain (odynophagia) on swallowing. Hairy leukoplakia may mimic thrush. Therapies discussed include ketoconazole, clotrimazole, miconazole, and amphotericin B. In the presence of oral candidiasis, gastroscopy is usually only performed after failure of adequate antifungal chemotherapy and in the presence of esophageal symptoms. A biopsy is important to confirm tissue invasion by Candida albicans or to identify other causes. 1 figure. (AA-M).

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Chapter 75: Perioral Dermatitis Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 794-799. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail: [email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on the epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of perioral dermatitis. This facial dermatosis predominantly affecting women of childbearing age is characterized by an erythematous, micropapular, fine scaling eruption classically affecting the nasolabial folds, chin, and upper lip. Factors implicated in causing perioral dermatitis include ultraviolet light, infective agents, demodectic infections, skin irritants, hormones, and glucocorticoids. Laboratory investigations that have been reported include patch testing, bacteriology, mycology for Candida, and a search for Demodex. Although diagnosis should be no problem in classic perioral dermatitis, when the clinical picture is not so distinctive, differential diagnosis should include rosacea, seborrheic dermatitis, contact dermatitis, acne, and papular sarcoid. Treatment involves the use of oral tetracycline. Prevention involves determining the cause, but many factors have been implicated in the etiology of perioral dermatitis, and none have been proven or confirmed. However, there is no doubt that the condition is precipitated or aggravated in many patients by using topical glucocorticoids. Untreated, the disease usually persists over several years, and the condition can resolve spontaneously. Prognosis is excellent with appropriate therapy. 3 figures and 72 references.

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Chapter 202: Fungal Skin Infections Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 5 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have fungal skin infections with information on the causes, symptoms, diagnosis, and treatment of ringworm, candidiasis, and tinea versicolor. Fungi that infect the skin live only in the topmost, dead layer. Ringworm is a fungal skin infection caused by several different fungi and is generally classified by where it appears on the body. Athlete's foot occurs on the feet and is caused by either Trichophyton or Epidermophyton. Jock itch occurs in the groin and can be caused by various fungi and yeasts. Scalp ringworm is caused by Trichophyton or Microsporum. Nail and body ringworm is caused by Tricophyton. Beard ringworm is rare. Most fungal skin infections can be cured with antifungal creams. Corticosteroids can be used to relieve itching and pain. Griseofulvin may be prescribed to treat more serious infections. Good hygiene is important to thwart fungal growth and promote healing. Candidiasis is caused by the yeast Candida, which usually infects the skin and mucous membranes. Symptoms vary with the location of the infection. Infections in the skinfolds usually cause a red rash. Vaginal Candida infections produce a white or yellow discharge from the vagina and burning, itching, and redness along the walls and external area of the vagina. Penile Candida infections produce a red, scaling, sometimes painful rash on the underside of the penis. Thrush, an infection inside the mouth, produces creamy white patches on the tongue and sides of the mouth. Perleche creates cracks and tiny cuts at the corners of the mouth. Candidal paronychia, which affects the nail beds, produces painful swelling and pus. Diagnosis is based on examination or culture of a skin sample. Most Candida skin infections are cured by medicated creams and lotions. Tinea versicolor causes white to light brown patches on the skin. The infection is diagnosed by its appearance. Dandruff shampoos usually cure this infection.

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Esophageal Infections Source: in Snape, W.J., ed. Consultations in Gastroenterology. Philadelphia, PA: W.B. Saunders Company. 1996. p. 237-243. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $125.00. ISBN: 0721646700. Summary: This chapter, from a gastroenterology text, covers esophageal infections. The authors note that infectious esophagitis was previously regarded to be rather uncommon; however, the AIDS epidemic has dramatically changed this perception and is probably the single most important factor accounting for the increasing incidence of infectious esophagitis. Growing numbers of immunosuppressed organ transplant patients also provide an at-risk population. These infections are responsible for serious morbidity and mortality in compromised patients. Most patients with esophageal infections present with odynophagia or dysphagia. Although reflux esophagitis is generally not a predisposing factor, other causes of esophagitis such as radiation therapy or cytotoxic chemotherapy may be responsible for symptoms in this group of patients or may provide a portal of entry for infection to occur. Still, gastroesophageal reflux disease, pill-induced esophageal injury, pericardial disease, and myocardial

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ischemia must be considered in the differential diagnosis of acute odynophagia and dysphagia. The authors discuss the infections by cause (fungi, viruses, and bacteria) and review the clinical presentation, diagnosis, and therapeutic options for each. They note that Candida albicans and herpes simplex virus are the most commonly encountered pathogens, although a number of other agents including cytomegalovirus (CMV), Aspergillus, and tuberculosis may infect the esophagus. 2 tables. 26 references. (AA-M).

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CHAPTER 8. MULTIMEDIA ON CANDIDA Overview In this chapter, we show you how to keep current on multimedia sources of information on Candida. 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 Candida is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “Candida” 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 “Candida” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on Candida: •

Nutrition Strategies in HIV Management Teleconference Contact: TKN - TV, 2000 5th Ave R-101, River Grove, IL, 60171. Summary: This videorecording documents a teleconference on the subject of nutrition and Human immunodeficiency virus (HIV) infection. Hosted by Novella Dudley, it features a panel of four experts from various areas of the field who discuss aspects of HIV and nutrition; they then field questions from both the studio audience and over the telephone. Short video segments introduce each new topic. The panel includes Dr. Donald Kotler, of St. Luke's - Roosevelt Hospital; Joyce Fitzpatrick, a nursing consultant; Frank San Miguel, coordinator of HIV services for travelers and immigrants in Chicago; and Annette Smerko of Caremark. The teleconference opens by considering nutrition as part of the psychosocial needs of a Person with AIDS (PWA). The symptoms of malnutrition are discussed, such as weight loss, anorexia, diarrhea, fever, and painful chewing or swallowing. It addresses financial issues of the cost of medication being so great that some patients cannot afford food. It looks at the different nutritional needs of PWA's, who must avoid weight loss by eating extra calories. The panel addresses the

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philosophy behind providing nutritional care for someone who is dying, and looks at the effect of alcohol use on nutrition. Case studies are examined; they say that the lack of ability to eat may be due to neurologic disease, drugs, or local pathology. PWA's are encouraged to consult with a dietitian, a physican, and a social worker. The connection between depression and malnutrition is established. The panel looks at specific opportunistic infections that may affect the appetite, such as hepatitis, thrush, and candida. A demonstration is given on safe handling of food to prevent salmonella and other foodborne diseases. The videorecording examines the devastating effects of weight loss on a patient, and looks at the barriers to motivating a patient to eat. It studies ethical concerns in treatment and legal issues involved in refusal to treat. The concluding segment studies the diagnosis and management of gastrointestinal disorders. It touches on steroid use and the use of nutritional supplements. At the end of the videorecording, viewers are urged to complete an evaluation. •

Now That You Know: Living Healthy With HIV; Part 4 - Understanding Treatment Contact: Kaiser Permanente, National Video Communications, 825 Colorado Blvd Ste 301, Los Angeles, CA, 90041, (323) 259-4776, http://www.kaiserpermanente.org/locations/index.html. Summary: This videorecording tells persons with Human immunodeficiency virus (HIV) infection about symptoms, opportunistic infections, and available treatment. Narrators Bob Goen and Susan Campos introduce the material by saying that infected persons need to take control of their own health, become educated, and become informed. The main portion of the videorecording opens with a segment on azidothymidine (AZT). It discusses early intervention and when it is appropriate to begin treatment. A model demonstrates how antiviral treatment, such as AZT intervention, slows the rate of growth. Viewers are warned that being on antiviral therapy does not prevent them from being infectious. Possible side effects of the medication are discussed. After turning to general background information on opportunistic infections, that videorecording takes a detailed look at some of the most common. It classifies symptoms into infections that do not lead to an AIDS diagnosis, such as candida, shingles, and weight loss; nonspecific symptoms, such as fatigue, fever, and night sweats; and opportunistic infections that lead to an AIDS diagnosis. Of those, it takes the most detailed looks at Pneumocystis carinii pneumonia (PCP), cytomegalovirus retinitis (CMV) infection, toxoplasmosis, and mycobacterium avium intracellulare (MAI). Holistic therapies are considered briefly at the conclusion of the videorecording.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio 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 “Sound Recordings.” Type “Candida” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on Candida: •

AIDS Update: ED Management, Part II Contact: California Medical Association, Audio Digest Foundation, 1577 E Chevy Chase Dr, Glendale, CA, 91206, (213) 245-8505.

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Summary: This sound recording, along with accompanying pre-test and post-test questions, comprises part of an ongoing series of educational activities. The first speaker, George F. Risi Jr., Assistant Professor of Medicine at Louisiana State University School of Medicine in New Orleans, looks at the evolution of the Acquired immunodeficiency syndrome (AIDS) epidemic between 1981 and 1986. He discusses the test for Human immunodeficiency virus (HIV) antibodies, HIV transmission, early theories about the origin of the illness, and the Centers for Disease Control and Prevention (CDC) classification system for AIDS patients. David F. Dreis, of the Section of Chest and Infectious Diseases at Virginia Mason Medical Center in Seattle, looks at symptoms and opportunistic infections associated with AIDS in the second presentation. He examines Pneumocystis carinii pneumonia (PCP), Candida Albicans, Kaposi's sarcoma, decreased vision, headache, unexplained fever, leukoplakia, pulmonary diseases, cryptosporidium, toxoplasmosis, and tuberculosis (TB). Asymptomatic carriers are discussed.

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CHAPTER 9. PERIODICALS AND NEWS ON CANDIDA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Candida.

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

Oral candidiasis in HAART era generally caused by azole-susceptible Candida Source: Reuters Medical News Date: October 02, 2002

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Candida-specific antibodies fail to explain HIV-related oropharyngeal candidiasis Source: Reuters Medical News Date: May 29, 2002

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Early, rapid increase in risk factors predicts Candida infection in SICU patients Source: Reuters Medical News Date: December 31, 2001

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Two new cases of invasive Candida dubliniensis infection reported Source: Reuters Medical News Date: April 17, 2001

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Versicor starts pivotal trial of fungicide in immune-deficient Candida patients Source: Reuters Industry Breifing Date: March 22, 2001

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Fluconazole, cyclosporine synergistic against Candida albicans Source: Reuters Industry Breifing Date: September 12, 2000

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Mycota identifies 900 Candida genes that may be targets for antifungals Source: Reuters Industry Breifing Date: September 07, 2000

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Candida albicans virulence in HIV-infected individuals specific to mucosal tissue Source: Reuters Medical News Date: August 30, 2000

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New antifungal agents show activity against fluconazole-resistant Candida Source: Reuters Medical News Date: November 23, 1999

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HIV load is primary correlate for oropharyngeal Candida colonization Source: Reuters Medical News Date: August 16, 1999

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HIV protease inhibitors may directly inhibit candida Source: Reuters Medical News Date: August 10, 1999

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Candida colonization in HIV+ women taking fluconazole shifts to less susceptible species Source: Reuters Medical News Date: May 10, 1999

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Emerging candida species causes invasive infection in immunosuppressed cancer patients Source: Reuters Medical News Date: December 28, 1998

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Prevalence of mucosal candida infection among HIV-positive US women reported Source: Reuters Medical News Date: November 13, 1998

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Less virulent Candida strain emerges as dominant species in candidemia episodes Source: Reuters Medical News Date: May 29, 1998

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Candida dubliniensis isolated in HIV-infected patients in USA Source: Reuters Medical News Date: May 28, 1998

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Candida Not Tied To Preterm Delivery Source: Reuters Health eLine Date: March 24, 1998

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Maternal Candida Infection Not Associated With Preterm Labor Or Low Birth Weight Source: Reuters Medical News Date: March 18, 1998

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Disruption Of Single Candida Gene Suppresses Virulence In Mice Source: Reuters Medical News Date: February 27, 1998

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Blocking Single Gene Disables Candida Source: Reuters Health eLine Date: February 26, 1998

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Voriconazole: Effective Antifungal Against Candida Species Source: Reuters Medical News Date: January 21, 1998

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Antibiotics Do Not Increase Risk Of Candida Vaginitis During Pregnancy Source: Reuters Medical News Date: January 08, 1998

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Voriconazole Inhibits Sterol Biosynthesis In Candida Strains Source: Reuters Medical News Date: November 28, 1997

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Mediastinitis Caused By Candida "An Emerging Clinical Entity" Source: Reuters Medical News Date: September 23, 1997

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New Antifungal Effective Against Fluconazole-Resistant Candida Source: Reuters Medical News Date: September 15, 1997

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New Candida Pathogen Reported in HIV Patients Source: Reuters Medical News Date: July 16, 1997

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Non-Candida Albicans Species On The Increase; Antifungal Resistance A Concern Source: Reuters Medical News Date: July 29, 1996

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Continuous Fluconazole Protects Against Oral Candida Source: Reuters Medical News Date: April 05, 1996 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.

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Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Candida” (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 “Candida” (or synonyms). If you know the name of a company that is relevant to Candida, 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 “Candida” (or synonyms).

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 “Candida” (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 Candida:

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Problems Associated with the Dry and Sore Mouth of Sjogren's Syndrome: Recognition and Management of Yeast Infections Source: Moisture Seekers Newsletter. 12(7-8): 1,3-5. July-August 1994. Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. Summary: This article discusses the problems associated with the dry and sore mouth of Sjogren's syndrome, particularly the recognition and management of yeast infections. Topics include the definition of xerostomia (dry mouth); the oscillating character of Sjogren's; presenting symptoms; the etiology of oral mucositis and soreness in Sjogren's patients; treatment recommendations; Candida infections (yeast); fissuring of the tongue; antibiotic treatments; burning mouth syndrome; risk factors for yeast infections; specific drugs used to treat yeast infections, including nystatin and clotrimazole; the use of mouthrinses; yeast infections and dentures; problems with angular cheilitis; the use of Benadryl; medication side effects; and self-care considerations. The author provides a brief list of suggested readings. 7 references.

•

Fingernail Infections Source: EDucator, The. p. 4. January-February 2000. Contact: Available from National Foundation for Ectodermal Dysplasias. 410 East Main Street, P.O. Box 114, Mascoutah, IL 62258-0114. (618) 566-2020. Fax (618) 566-4718. Website: www.nfed.org. Summary: This newsletter article provides people who have ectodermal dysplasia (ED) with information on the causes and treatment of fingernail infections. Infection of the nail and surrounding skin, known as paronychia, is caused by bacteria and yeasts as well as by fungi associated with ringworm infections on other parts of the body. Acute paronychia is usually caused by bacteria and preceded by trauma to the nail, cuticle, or skin. Unless very mild, these infections need to be treated promptly by a physician. People who have experienced acute paronychial infections are more susceptible to chronic nail infections. Chronic paronychia may be caused by bacteria but is more often caused by the yeast known as Candida albicans. Chronic nail infections require fastidious care to achieve healing, including protecting the hands with gloves, using only mild soaps, avoiding nail cosmetics, and applying topical antibiotics or antifungal agents. Fungal infections of the nails require treatment for many months with an oral medication. Nail changes associated with ED may mimic an infection, so appropriate medical advice needs to be sought.

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

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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 Candida. 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 Candida. 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 Candida: Ciclopirox •

Topical - U.S. Brands: Loprox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202140.html

Econazole •

Topical - U.S. Brands: Spectazole http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202211.html

Nystatin and Triamcinolone •

Topical - U.S. Brands: Dermacomb; Mykacet; Mytrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202420.html

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information 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.

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

Porfimer (Trade Name: Photofrin) http://www.rarediseases.org/nord/search/nodd_full?code=1194

•

Profimer (Trade Name: Photofrin) http://www.rarediseases.org/nord/search/nodd_full?code=1229

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 Institute12: •

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

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

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

•

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

•

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

•

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

12

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

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

•

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

•

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

•

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

•

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

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Candida” (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 31309 172 75 1230 1 32787

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “Candida” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

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

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

20 Adapted 21

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. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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 Candida 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 Candida. 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 Candida. 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 “Candida”:

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•

Other guides Candidiasis http://www.nlm.nih.gov/medlineplus/candidiasis.html Fungal Infections http://www.nlm.nih.gov/medlineplus/fungalinfections.html Mouth Disorders http://www.nlm.nih.gov/medlineplus/mouthdisorders.html Throat Disorders http://www.nlm.nih.gov/medlineplus/throatdisorders.html Vaginal Diseases http://www.nlm.nih.gov/medlineplus/vaginaldiseases.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 Candida. 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: •

Are You Sexually Active? Don't Get Sick Over It Contact: Quebec Ministere de la Sante et des Services Sociaux, Direction des Communications, 1075 Chemm Ste-Foy, Quebec, (418) 643-3380. Summary: This brochure cautions readers of the dangers they face from Sexually transmitted diseases (STD's). It lists symptoms, diagnosis, treatment, and complications associated with eight common STD's, including genital herpes, syphilis, gonorrhea, Hepatitis B, candida, and Acquired immunodeficiency syndrome (AIDS). Risk factors for contraction of STD's are given, and readers are told that many STD's can be treated and cured if they are detected early enough. Condom use is advocated. The brochure encourages readers to communicate with their partners in order to help prevent STD's.

•

Sexually Transmitted Diseases: Information & Assistance Contact: Massachusetts Department of Public Health, 150 Tremont St, Boston, MA, 02111, (617) 727-0368. Massachusetts Department of Public Health, Center for Laboratories and Communicable Disease Control, Sexually Transmitted Disease Program, 305 S St, Jamaica Plain, MA, 02130, (617) 522-3700.

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Summary: This brochure discusses the transmission, symptoms in both men and women and how soon after infection they appear, methods of testing for both men and women, and complications in both men and women, of 11 Sexually transmitted diseases. Among the STD's included are Human immunodeficiency virus (HIV) and Acquired immunodeficiency syndrome (AIDS); chlamydia; genital herpes; genital warts; gonorrhea; hepatitis B; syphilis; vaginitis, including trichomonas vaginalis, candida, and gardnerella; and scabies and crabs. Methods of preventing transmission of STD's included are limiting of sexual partners, using condoms, and avoiding alcohol and other drugs that might impair judgment. The reader is urged to learn the signs and symptoms of STD's and to seek medical help if infection is suspected. •

Vulvar Pain Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2000. [4 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 51 Monroe Street, Suite 1402, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 plus shipping and handling. Order number RBV00. Summary: This brochure familiarizes readers with the diagnosis and treatment of vulvar pain (vulvodynia). The brochure first reviews the anatomy of the vulva, defined as the visible parts of the female genitals. The brochure then discusses each of the four types of vulvodynia: vulvar vestibulitis, inflammation around the opening to the vagina; dysesthetic vulvodynia, vulvar pain caused by irritated or inflamed nerves; cyclic vulvovaginitis, chronic Candida (yeast) infection; and vulvar or mucous dermatoses, skin disorders which occur on the vulvar membranes. For reasons that are unclear, approximately 70 percent of women with vulvodynia are white with fair complexions; most are women of childbearing age. The precise cause of vulvodynia is unknown. The brochure reviews the symptoms and diagnostic hallmarks of each type of vulvodynia, then discusses the use of treatments including oral medications, biofeedback programs, Kegel exercises, interferon, anticandida creams, a low oxalate diet, and surgery. The brochure then lists self help strategies that patients can try to provide some relief or prevent flareups or worsening of symptoms. The brochure reiterates that vulvodynia is often misdiagnosed or undiagnosed and consequently mistreated or untreated. There is an urgent need for education and awareness about this condition among both patients and doctors. 1 figure.

•

Symptoms, Treatment, and Oral Thrush Prevention: Your Guide to Control Source: Mountain View, CA: Alza Pharmaceuticals. 1998. 10 p. Contact: Available from Alza Pharmaceuticals. 1550 Plymouth Avenue, Mountain View, CA 94043. (800) 634-8977. PRICE: Single copy free; bulk orders available. Order Numbers: 0008291 or 0008485. Summary: This brochure helps readers to prevent oral thrush (candidiasis). Oral thrush is an infection of the mouth by a yeast called Candida. Normally, the body's immune system keeps Candida in check. However, when the immune system is weakened (from chemotherapy, steroid therapy, HIV infection, or diabetes, for example), the person may be at risk for oral thrush. Written in a question and answer format, the brochure describes the symptoms of oral thrush, topical and systemic medications used to treat oral thrush, ways to lessen the discomfort of oral thrush, medications that can be used to prevent future infections, and daily self care steps to help control oral thrush. The brochure recommends that readers should check for symptoms daily, take all

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medications as prescribed, practice good oral hygiene (including regular dental checkups), avoid alcohol and foods that can aggravate oral thrush, and follow their physician's instructions. Two full color photographs show examples of Candida infections. 2 figures. •

Sexually Transmitted Diseases Contact: Planned Parenthood of the Greater Miami Valley, Downtown Dayton Medical Office and Administration Headquarters, 224 N Wilkinson St, Dayton, OH, 45402, (937) 226-0780, http://www.plannedparenthood.org. Summary: This brochure provides information on sexually transmitted diseases (STD's), outlining the types and methods of prevention. Most of the brochure consists of a foldout chart listing the following diseases: AIDS, gonorrhea, syphilis, herpes simplex, vaginitis, candida, vaginosis, non-gonococcal urethritis, venereal warts, molluscum contagiosum, and ecto-parasites. For each condition, the chart summarizes when symptoms first appear, usual symptoms, transmission, diagnosis, and complications.

•

When AIDS Comes to Work Contact: American Federation of State County and Municipal Employees, 1625 L St NW, Washington, DC, 20036-5687, (202) 429-1000, http://www.afscme.org. Summary: This brochure, written for shop stewards, discusses issues relevant to employees with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in the workplace. The brochure describes the effects that HIV/AIDS can have on the unprepared workplace and the steward's role in a labor organization. It makes recommendations about how to set up an HIV/AIDS workplace policy to deal with issues that arise with infected employees. The brochure discusses workplace transmission of HIV, the workplace environment, infected individuals' medical situations, and opportunistic infections/diseases that HIV-positive individuals may develop (i.e., pneumocystis carinii pneumonia, Kaposi's sarcoma, wasting syndrome, cyto-megalo-virus, candidiasis candida, herpes, and tuberculosis). The brochure also discusses emotional factors, the union's role in helping out the families of HIV-positive employees, preserving those employees' benefits, sick leave policies relevant to infected workers, and the expenses associated with the acquisition of drugs to treat HIV/AIDS.

•

Fungal Infections Source: KidsHealth. 2000. 3 p. Contact: Nemours Foundation. Website: www.Kidsheath.org. Summary: This fact sheet presents an overview of common fungal infections that children may have. A common, contagious type of fungal infection is tinea which includes athlete's foot, jock itch, and ringworm. Another type is candida, a yeast-like fungus. Athlete's foot causes cracking and itching between the toes, red scaly blisters on the feet, and watery discharge from the blisters. It can be prevented by washing and completely drying the feet everyday; wearing footwear in public pools, showers, and locker rooms; and wearing clean, dry socks. Jock itch is characterized by a rash with raised edges accompanied by itching and burning sensations. To prevent jock itch boys and men should wear clean, cotton underwear; loose-fitting pants; and keep the groin clean and dry. Ringworm can appear on the head, arms, legs, and chest and looks like red spots that grow into rings. Candida causes the infected area to itch and may cause the skin to be red and swollen. These yeast infections can be prevented by changing

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from wet swimsuits into dry clothing as soon as possible and wearing clean, cotton underpants. •

Candidiasis: Diaper Rash, Oral Thrush, Vaginal Yeast Infection Source: KidsHealth. June 2001. 3 p. Contact: Nemours Foundation. Website: www.kidshealth.org. Summary: This fact sheet provides an overview of different types of candidiasis that can affect children. Diaper rash is the most common form of candidiasis, appearing in healthy newborns and older babies, and is characterized by red, tender skin, especially in skin folds and creases. Diaper rash can be prevented by changing cloth diapers as soon as they get wet or soiled and thoroughly rinsing soaps and other irritants from the diapers. Zinc oxide and other nonprescription ointments can be applied. Oral thrush is candidiasis of the mouth and appears in healthy newborns or older children. The fungus causes cracks in the corners of the mouth and yellow or white patches on the lips, tongue, palate and inside the cheeks. In healthy children, thrush requires no treatment. In children with cancer or HIV, treatment is necessary to prevent infection spreading to other organs. Another common ailment is Candida paronychia, which infects the skin around the nails. The cuticles around the nails become red, swollen, and painful. Antifungal medications are prescribed to treat this disorder. Candida vulvovaginitis, or yeast infections, affect older girls and women and are characterized by vaginal itching, redness, and thick white discharge. To prevent vaginal candidiasis, keep the vagina area clean, avoid vaginal sprays and douches, wear cotton underpants, and change into dry clothing after swimming.

•

What Is AIDS? Contact: University of New Mexico School of Medicine, New Mexico AIDS Education and Training Center, New Mexico AIDS InfoNet, PO Box 810, Arroyo Seco, NM, 87514, (505) 776-8032, http://www.aidsinfonet.org. Summary: This fact sheet provides general information about the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). It distinguishes between HIV and AIDS and lists methods of transmission including having unprotected sex with an infected person, sharing needles for injection drug use with infected persons, and being infected during pregnancy. It describes what happens to the body once infected with HIV, how to diagnose AIDS, and how HIV is treated. It discusses how persons with AIDS often develop opportunisitc infections including pneumocystis carinii pneumonia (PCP), Kaposi's sarcoma, cytomegalovirus (CMV), and candida.

•

Esophageal Candidiasis Contact: Community AIDS Treatment Information Exchange, PO Box 1104, Toronto, (416) 203-7122, http://www.catie.ca. Summary: This fact sheet, for persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), discusses the infection esophageal candidiasis, an AIDS-defining illness, which is caused by an overgrowth of candida. It discusses symptoms, which can include difficulty swallowing, a sore throat, and chest pain behind the breastbone; its diagnosis; and its prevention through using antiretroviral therapy for HIV/AIDS, reducing intakes of sugars and starchy foods, and

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eating unsweetened yogurt with live bacteria culture. It discusses the medical treatments of fluconazole, itraconazole, intravenous fluconazole, and amphotericin B. •

Candidiasis Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org. Summary: This fact sheet, written for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), presents information about candidiasis, a term for infections (such as esophagitis, thrush, and vaginitis) caused by the yeast Candida, which can involve the mouth, throat, esophagus, vagina, or skin. Candidiasis can often signal the onset of HIV/AIDS, as it is a common sign of the weakening of the immune system. Some of the symptoms of candidiasis include soreness or a bad taste in the mouth, creamy white patches, red spots on the tongue or roof of the mouth, cracks and redness in the skin at the corners of the mouth, difficulty swallowing, and pain in the chest. Candidiasis is often diagnosed using a combination of visual and laboratory examinations. Medical therapy can be topical. Systemic treatment is needed for Candida esophagitis. In HIV-positive individuals, candidiasis can be prevented with topical medicines or through alternative/complementary treatments. A table is provided that identifies some topical and systemic medications available to treat candidiasis.

•

The Eleventh National Lesbian and Gay Health Conference and Seventh National AIDS Forum, Cathedral Hill Hotel, San Francisco, CA, April 5 - 9, 1989 Contact: National Lesbian and Gay Health Association, 1407 F St NW, Washington, DC, 20009, (202) 939-7880, http://www.nlgha.com. George Washington University Medical Center, Clinical Research, 2300 I St NW, Washington, DC, 20037, (202) 994-2417, http://www.gwu.edu/~ctu. Summary: This information package provides resource materials for participants in the National Lesbian and Gay Health Conference held in San Francisco, CA, April 5-9, 1989. It contains a conference assessment, information about the Shanti Project session, NAMES Project session, a presentation about the immunomodulation of Candida infection in Acquired immunodeficiency syndrome (AIDS), brochures about the National Association of Lesbian and Gay Alcoholism Professionals (NALGAP), health agenda suggestions, a list of pertinent publications, and questionnaires on bisexuality and caregivers. 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 Candida. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

299

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.23

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

23

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)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

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

•

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

•

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

•

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

307

CANDIDA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [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] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [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] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH]

308 Candida

Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agglutinins: Substances, usually of biological origin, that cause cells or other organic

Dictionary 309

particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] 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] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [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] Amination: The creation of an amine. It can be produced by the addition of an amino group to an organic compound or reduction of a nitro group. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines

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include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino 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] 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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve

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function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiitis: Inflammation of a vessel, chiefly of a blood or a lymph vessel; called also vasculitis. [EU] 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] Ankle: That part of the lower limb directly above the foot. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiosis: A property of microorganisms which enables one microorganism to kill, injure, or inhibit the growth of a different microorganism. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU]

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Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [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] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a

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neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [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] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriocins: Substances elaborated by specific strains of bacteria that are lethal against other strains of the same or related species. They are protein or lipopolysaccharide-protein complexes used in taxonomy studies of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in

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the urine. [NIH] Balanitis: Inflammation of the glans penis. [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] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Glucosidase: An enzyme that catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of beta-glucose. EC 3.2.1.21. [NIH] Bewilderment: Impairment or loss of will power. [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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH]

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Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [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] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [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] Bisexuality: Sexual attraction or relationship between members of the same and opposite sex. [NIH] Bladder: The organ that stores urine. [NIH] Blastomyces: A genus of onygenacetous mitosporic fungi whose perfect state is Ajellomyces. The species Blastomyces dermatitidis (perfect state Ajellomyces dermatitidis) causes blastomycosis. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood Preservation: The process by which blood or its components are kept viable outside of the organism from which they are derived (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). [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

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network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burning Mouth Syndrome: A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. [NIH] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH]

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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] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [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 Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candida albicans: A unicellular budding fungus which is the principal pathogenic species causing candidiasis (moniliasis). [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [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] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsicum: A genus of Solanaceous shrubs that yield capsaicin. Several varieties have sweet or pungent edible fruits that are used as vegetables when fresh and spices when the pods

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are dried. [NIH] 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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] 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] Caspofungin acetate: A drug used to prevent or treat infections caused by a fungus (a type of microorganism). It belongs to the family of drugs called antifungal agents. [NIH] 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] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject

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or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [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] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell 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 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] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [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 Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [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]

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Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cetylpyridinium: Cationic bactericidal surfactant used as a topical antiseptic for skin, wounds, mucous membranes, instruments, etc.; and also as a component in mouthwash and lozenges. [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] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chitin Synthase: An enzyme that converts UDP glucosamine into chitin and UDP. EC 2.4.1.16. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [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] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A

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peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [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] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus. [NIH]

Chorion: The outermost extraembryonic membrane. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroidal Neovascularization: A pathological process consisting of the formation of new blood vessels in the choroid. [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] Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid. [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] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [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] 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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [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] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [NIH] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [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] 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] Colloidal: Of the nature of a colloid. [EU] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease

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inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Commensalism: A relationship between two kinds of living organism whereby one (the commensal) benefits and the other (the host) remains relatively or absolutely unaffected, and which is often obligatory for the commensal. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU]

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Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [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] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] 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] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH]

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Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Transplantation: Partial or total replacement of the cornea from one human or animal to another. [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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH]

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Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptosporidium: A genus of coccidian parasites of the family Cryptosporidiidae, found in the intestinal epithelium of many vertebrates including humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [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 A: A 33-kD protein identical to adenovirus E1A-associated protein p60. Cyclin A regulates p33cdk2 and p34cdc2, and is necessary for progression through the S phase of 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]

Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. [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]

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Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytochrome b5: A cytochrome occurring in the endoplasmic reticulum that acts as an intermediate electron carrier in some reactions catalyzed by mixed function oxidases, e.g., fatty acid desaturation. It further activates molecular oxygen for an attack on the substrate. MW 16kDa. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Retinitis: Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. [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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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]

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De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [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] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentin Permeability: The property of dentin that permits passage of light, heat, cold, and chemical substances. It does not include penetration by microorganisms. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Denture Cleansers: Substances used to clean dentures; they are usually alkaline peroxides or hypochlorites, may contain enzymes and release oxygen. Use also for sonic action cleaners. [NIH] Denture Liners: Material applied to the tissue side of a denture to provide a soft lining to the parts of a denture coming in contact with soft tissue. It cushions contact of the denture

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with the tissues. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] 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] 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] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis, Contact: A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. [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] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can

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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] Dihydroxyacetone: A ketotriose compound. Its addition to blood preservation solutions results in better maintenance of 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by triokinase in erythrocytes. In combination with naphthoquinones it acts as a sunscreening agent. [NIH] Dihydroxyacetone Phosphate: An important intermediate in lipid biosynthesis and in glycolysis. [NIH] Dilatation: The act of dilating. [NIH] Dilatation and Curettage: Dilatation of the cervix uteri followed by a scraping of the endometrium with a curette. [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] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of

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dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Dross: Residue remaining in an opium pipe which has been smoked; contains 50 % of the morphine present in the original drug. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dysphagia: Difficulty in swallowing. [EU] Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] 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]

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Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [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] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of

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a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] 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] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [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] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

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Enterovirus: A genus of the family Picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [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]

Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] 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] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warm-blooded animals. The species are

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either nonpathogenic or opportunistic pathogens. [NIH] Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce diarrhea and pyogenic infections. [NIH]

Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagoscopy: Endoscopic examination, therapy, or surgery of the esophagus. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [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] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryote: An organism (or a cell) that carries its genetic material physically constrained within a nuclear membrane, separate from the cytoplasm. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] 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] Expeditions: Usually refers to planned scientific data-gathering excursions. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

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 Space: Interstitial space between cells, occupied by fluid as well as amorphous

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and fibrous substances. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Faecal: Pertaining to or of the nature of feces. [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] 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] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [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 vessels at the time of delivery. [NIH] Fetal Death: Death of the young developing in utero. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [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] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] 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] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU]

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Fistulas: An abnormal passage from one hollow structure of the body to another, or from a hollow structure to the surface, formed by an abscess, disease process, incomplete closure of a wound, or by a congenital anomaly. [NIH] Flagellum: A whiplike appendage of a cell. It can function either as an organ of locomotion or as a device for moving the fluid surrounding the cell. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent. [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] 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] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fornix: A bundle of nerves connected to the hippocampus. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [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] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH]

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Fungicide: An agent that destroys fungi. [EU] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gardnerella: A genus of bacteria found in the human genital and urinary tract. It is considered to be a major cause of bacterial vaginosis. [NIH] Gardnerella vaginalis: The only species in the genus Gardnerella, and previously classed as Haemophilus vaginalis. This bacterium, also isolated from the female genital tract of healthy women, is implicated in the cause of bacterial vaginosis. It occasionally causes postpartum bacteremia and bacteremia following a transurethral resection of the prostate. [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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the

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esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroscopy: Endoscopic examination, therapy, or surgery of the interior of the stomach. [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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] 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] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU]

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Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in

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a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Glycosyltransferases: Enzymes that catalyze the transfer of glycosyl groups to an acceptor. Most often another carbohydrate molecule acts as an acceptor, but inorganic phosphate can also act as an acceptor, such as in the case of phosphorylases. Some of the enzymes in this group also catalyze hydrolysis, which can be regarded as transfer of a glycosyl group from the donor to water. Subclasses include the hexosyltransferases, pentosyltransferases, sialyltransferases, and those transferring other glycosyl groups. EC 2.4. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [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]

GP41: 41-kD HIV transmembrane envelope glycoprotein which mediates the fusion of the viral membrane with the membrane of the target cell. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH]

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Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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] 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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Halogens: A family of nonmetallic, generally electronegative, elements of group VIIa of the periodic table. They are all multivalent and have oxidation numbers of -1 (the most common), 1, 3, 5, and 7. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematologic Diseases: Disorders of the blood and blood forming tissues. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH]

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Hemocytes: Any blood or formed element especially in invertebrates. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] 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] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hexosyltransferases: Enzymes that catalyze the transfer of hexose groups. EC 2.4.1.-. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH]

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Homeobox: Distinctive sequence of DNA bases. [NIH] Homeodomain Proteins: Proteins encoded by homeobox genes that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (gene expression regulation, developmental). [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Homozygotes: An individual having a homozygous gene pair. [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] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [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] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [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 Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]

Hydrogen Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [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]

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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] 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] 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] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH]

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Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] 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] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impregnation: 1. The act of fecundation or of rendering pregnant. 2. The process or act of saturation; a saturated condition. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU]

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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] Incineration: High temperature destruction of waste by burning with subsequent reduction to ashes or conversion to an inert mass. [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incontinence Pads: Absorbent pads made of various materials used for personal hygiene usually in urinary incontinence and usually in the elderly. They may be worn as underpants or as pants liners. They are made of absorbent materials such as fluff wood pulp and hydrogel absorbent with viscose rayon, polyester, polypropylene, or polyethylene coverstock. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Industrial Microbiology: The study, utilization, and manipulation of those microorganisms capable of economically producing desirable substances or changes in substances, and the control of undesirable microorganisms. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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]

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Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [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] Instillation: . [EU] 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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH]

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Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-13: T-lymphocyte-derived cytokine that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature Blymphocytes. It appears to play a role in regulating inflammatory and immune responses. [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-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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [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] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intravascular: Within a vessel or vessels. [EU]

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Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invertebrates: Animals that have no spinal column. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as

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defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketosteroids: Steroid derivatives formed by oxidation of a methyl group on the side chain or a methylene group in the ring skeleton to form a ketone. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney 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] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetic: Pertaining to or producing motion. [EU] Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lactates: Salts or esters of lactic acid containing the general formula CH3CHOHCOOR. [NIH] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [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

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colon. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] 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]

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] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU]

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Lipopolysaccharide: 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]

Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lubricants: Oily or slippery substances. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [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]

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Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysophospholipase: An enzyme that catalyzes the hydrolysis of a single fatty acid ester bond in lysoglycerophosphatidates with the formation of glyceryl phosphatidates and a fatty acid. EC 3.1.1.5. [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] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] 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] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mannosyltransferases: Enzymes that catalyze the transfer of mannose from a nucleoside diphosphate mannose to an acceptor molecule which is frequently another carbohydrate. The group includes EC 2.4.1.32, EC 2.4.1.48, EC 2.4.1.54, and EC 2.4.1.57. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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

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with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] 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] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body

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functions. It is a chelating agent for heavy metals. [NIH] Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [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] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

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] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Miscible: Susceptible of being mixed. [EU] 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] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is

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the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]

Mitotic: Cell resulting from mitosis. [NIH] Mixed Function Oxidases: Catalyse the insertion of one oxygen atom of molecular oxygen into the organ substrate. Require a second substrate to donate electrons for the reduction of the second atom in the oxygen molecule to water. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU]

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Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Mumps Virus: The type species of rubulavirus that causes an acute infectious disease in humans, affecting mainly children. Transmission occurs by droplet infection. [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] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Mycobacterium avium: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [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] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to

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the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] 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] Naphthoquinones: Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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

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swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] 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] 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] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [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] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Niflumic Acid: An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis. [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

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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]

Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from cyanides, which denotes inorganic salts of hydrogen cyanide. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Noel: The highest dose level of a chemical that, in a given toxicity test, causes no observable adverse effect in the test animals. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] 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] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nystatin: Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex are nystatin A1, A2, and A3. [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] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Odynophagia: A painful condition of the esophagus. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a

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vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Onychomycosis: Mycosis of the nails, possibly due to some extent to humidity. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orderly: A male hospital attendant. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Oropharynx: Oral part of the pharynx. [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] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of

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hearing, hearing loss, tinnitus, and vertigo. [EU] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [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] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [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] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous

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membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paracoccidioidomycosis: A mycosis affecting the skin, mucous membranes, lymph nodes, and internal organs. It is caused by Paracoccidioides brasiliensis. It is also called paracoccidioidal granuloma. Superficial resemblance of P. brasiliensis to Blastomyces brasiliensis (blastomyces) may cause misdiagnosis. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Paratyphoid Fever: A prolonged febrile illness commonly caused by serotypes of Salmonella paratyphi. It is similar to typhoid fever but less severe. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paronychia: Inflammation involving the folds of tissue surrounding the nail. Called also perionychia. [EU] 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] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH]

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Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentosyltransferases: Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another. (Dorland, 28th ed) EC 2.4.2. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perianal: Located around the anus. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering

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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] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by 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] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [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] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipases A: Phosphatide acylhydrolases. Catalyze the hydrolysis of one of the acyl

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groups of phosphoglycerides or glycerophosphatidates. Phospholipase A1 hydrolyzes the acyl group attached to the 1-position (EC 3.1.1.32) and phospholipase A2 hydrolyzes the acyl group attached to the 2-position (EC 3.1.1.4). [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] 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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plant Diseases: Diseases of plants. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many 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]

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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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. [NIH] Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Polyphosphates: Linear polymers in which orthophosphate residues are linked with energy-rich phosphoanhydride bonds. They are found in plants, animals, and microorganisms. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH]

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Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [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] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [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] Profusion: Profusion is the number of small rounded opacities per unit area, that is, per zone. [NIH] Progeny: The offspring produced in any generation. [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]

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Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prokaryote: Unicellular organism having a less complex structure than a eukaryote; it's characterized by the absence of a nucleus and by having the genetic material in the form of simple filaments of DNA. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propolis: Resinous substance obtained from beehives; contains many different substances which may have antimicrobial or antimycotic activity topically; its extracts are called propolis resin or balsam. Synonyms: bee bread; hive dross; bee glue. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prosthodontics: A dental specialty concerned with the restoration and maintenance of oral function by the replacement of missing teeth and structures by artificial devices or prostheses. [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 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] Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that

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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] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [NIH]

Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan Infections: Infections with unicellular organisms of the subkingdom Protozoa. [NIH]

Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] 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] 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]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH]

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Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyruvate Decarboxylase: Catalyzes the decarboxylation of an alpha keto acid to an aldehyde and carbon dioxide. Thiamine pyrophosphate is an essential cofactor. In lower organisms, which ferment glucose to ethanol and carbon dioxide, the enzyme irreversibly decarboxylates pyruvate to acetaldehyde. EC 4.1.1.1. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation 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] 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] 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.

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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] Reactivation: The restoration of activity to something that has been inactivated. [EU] 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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [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 blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Standards: A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Refusal to Treat: Refusal of the health professional to initiate or continue treatment of a patient or group of patients. The refusal can be based on any reason. The concept is differentiated from patient refusal of treatment see treatment refusal which originates with the patient and not the health professional. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU]

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Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative,

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noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrotransposons: DNA sequence which is a copy of a RNA virus into a host's DNA and which can reinsert itself elsewhere in the genome. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [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] 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] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [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] 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] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rubulavirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the species have hemagglutinin and neuraminidase activities but lack a C protein. Mumps virus is the type species. [NIH] Saccharomyces: A genus of ascomycetous fungi of the family Saccharomycetaceae, order

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saccharomycetales. [NIH] Saccharomycetales: An order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivary Proteins: Proteins found in saliva and the salivary glands. These proteins show some enzymatic activity, but their composition varies in different individuals. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Salmonella typhi: A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. [NIH] Salmonella typhimurium: A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes paratyphoid fever. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [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] Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [NIH]

Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate

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affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerotic: Pertaining to the outer coat of the eye; the sclera; hard, indurated or sclerosed. [NIH]

Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [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] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] 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] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines,

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pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serratia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the natural environment (soil, water, and plant surfaces) or as an opportunistic human pathogen. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [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]

Sialyltransferases: A group of enzymes with the general formula CMP-Nacetylneuraminate:acceptor N-acetylneuraminyl transferase. They catalyze the transfer of Nacetylneuraminic acid from CMP-N-acetylneuraminic acid to an acceptor, which is usually the terminal sugar residue of an oligosaccharide, a glycoprotein, or a glycolipid. EC 2.4.99.-. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH]

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Silver Compounds: Inorganic compounds that contain silver as an integral part of the molecule. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [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] Sludge: A clump of agglutinated red blood cells. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smear Layer: Adherent debris produced when cutting the enamel or dentin in cavity preparation. It is about 1 micron thick and its composition reflects the underlying dentin, although different quantities and qualities of smear layer can be produced by the various instrumentation techniques. Its function is presumed to be protective, as it lowers dentin permeability. However, it masks the underlying dentin and interferes with attempts to bond dental material to the dentin. [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] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs

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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] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spices: The dried seeds, bark, root, stems, buds, leaves, or fruit of aromatic plants used to season food. [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] Spirochete: Lyme disease. [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] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sporotrichosis: The commonest and least serious of the deep mycoses, characterized by nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound. [NIH] Squamous: Scaly, or platelike. [EU] Stabilization: The creation of a stable state. [EU] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Statistically significant: Describes a mathematical measure of difference between groups.

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The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

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] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [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] 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] 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,

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resonance, and inductive effects. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submandibular: 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] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfates: Inorganic salts of sulfuric acid. [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] Sulfur Compounds: Inorganic or organic compounds that contain sulfur as an integral part of the molecule. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

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Surgical Wound Infection: Infection occurring at the site of a surgical incision. [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] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Talc: A native magnesium silicate. [NIH] Tea Tree Oil: Essential oil extracted from Melaleuca alternifolia (tea tree). It is used as a topical antimicrobial due to the presence of terpineol. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH]

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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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH]

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Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] 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] Translocation: The movement of material in solution inside the body of the plant. [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] Transurethral resection of the prostate: Surgical procedure to remove tissue from the prostate using an instrument inserted through the urethra. Also called TURP. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichomonas: A genus of parasitic flagellate protozoans distinguished by the presence of

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four anterior flagella, an undulating membrane, and a trailing flagellum. [NIH] Trichomonas vaginalis: A species of trichomonas that produces a refractory vaginal discharge in females, as well as bladder and urethral infections in males. [NIH] Trichomonas Vaginitis: Inflammation of the vagina, marked by a purulent discharge. This disease is caused by the protozoan Trichomonas vaginalis. [NIH] Trichophyton: A mitosporic fungal genus and an anamorphic form of Arthroderma. Various species attack the skin, nails, and hair. [NIH] Triclosan: A diphenyl ether derivative used in cosmetics and toilet soaps as an antiseptic. It has some bacteriostatic and fungistatic action. [NIH] Tricuspid Valve: The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. [NIH] Trivalent: Having a valence of three. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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] TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [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] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [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] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH]

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Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] 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]

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

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginal Discharge: A common gynecologic disorder characterized by an abnormal, nonbloody discharge from the genital tract. [NIH] Vaginal Smears: Collection of pooled secretions of the posterior vaginal fornix for cytologic examination. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vaginosis: A condition caused by the overgrowth of anaerobic bacteria (e. g., Gardnerella vaginalis), resulting in vaginal irritation and discharge. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH]

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Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] 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 to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] 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] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation

Dictionary 389

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] Voriconazole: A drug that treats infections caused by fungi. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Vulvovaginitis: Inflammation of the vulva and vagina, or of the vulvovaginal glands. [EU] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [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] Xylulose: A 5-carbon keto sugar. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

391

INDEX 3 3-dimensional, 46, 307, 370 A Abdomen, 307, 316, 342, 349, 353, 365, 380, 381, 384 Abdominal, 307, 338, 363, 365, 366, 386 Abdominal Pain, 307, 338, 366, 386 Abscess, 115, 307, 337 Acatalasia, 307, 318 Acceptor, 307, 341, 352, 354, 363, 378, 385 ACE, 307 Acetaldehyde, 190, 307, 372 Acetylcholine, 307, 321, 361 Acetylgalactosamine, 307, 341 Acetylglucosamine, 65, 307, 341 Acne, 266, 307 Acquired Immunodeficiency Syndrome, 204, 216, 229, 307 Acrylonitrile, 307, 375 Actin, 24, 48, 96, 119, 143, 307, 359 Acute leukemia, 113, 308 Acyl, 308, 335, 366 Adaptability, 308, 319 Adenine, 247, 251, 308, 372 Adenovirus, 308, 326 Adenylate Cyclase, 18, 69, 308, 321 Adhesives, 127, 208, 230, 234, 249, 307, 308 Adjuvant, 36, 41, 308, 339 Adsorption, 44, 140, 198, 199, 215, 308 Adsorptive, 308 Adverse Effect, 37, 45, 308, 361, 378 Aerobic, 308, 356, 358, 386 Afferent, 308, 336 Affinity, 13, 18, 24, 44, 105, 175, 179, 308, 309, 352, 354, 379 Affinity Chromatography, 18, 308 Agar, 12, 75, 78, 95, 117, 141, 144, 149, 171, 308, 322, 326, 346, 367 Age Groups, 3, 308 Aged, 80 and Over, 308 Agglutinins, 56, 308 Agonist, 309, 331, 367 Airway, 21, 309 Alanine, 155, 158, 223, 309 Aldehydes, 230, 309 Algorithms, 309, 315 Alimentary, 309, 329, 364 Alkaline, 200, 241, 309, 310, 317, 328

Alkaloid, 309, 314, 317 Alkylating Agents, 309, 387 Alleles, 210, 309, 343 Allogeneic, 69, 217, 232, 309, 341 Allogeneic bone marrow transplantation, 217, 232, 309 Alpha Particles, 309, 372 Alpha-Defensins, 309, 328 Alternative medicine, 276, 309 Amination, 243, 309 Amine, 309, 343 Amino Acid Sequence, 179, 198, 227, 248, 250, 310, 311, 339 Amino Acid Substitution, 63, 105, 179, 310 Ammonia, 309, 310, 340, 387 Amnion, 310, 321 Amplification, 20, 50, 52, 96, 97, 144, 310 Amylase, 253, 310 Anaemia, 234, 310 Anaerobic, 219, 310, 334, 335, 376, 378, 380, 387 Anaesthesia, 310, 347 Anal, 310, 358 Analgesic, 310, 360 Analog, 20, 94, 209, 310, 337 Analogous, 40, 310, 331, 385 Anaphylatoxins, 310, 323 Anatomical, 11, 151, 310, 313, 320, 332, 346, 364 Anergy, 237, 310 Anesthesia, 309, 310 Angiitis, 115, 311 Animal model, 23, 27, 32, 36, 43, 45, 49, 54, 311 Anions, 311, 350, 382 Ankle, 264, 311 Anorexia, 269, 311, 338 Antibacterial, 15, 167, 208, 216, 228, 229, 241, 242, 245, 311, 380, 387 Antibiosis, 229, 311 Anticoagulant, 311, 370 Antigen-Antibody Complex, 311, 323 Anti-infective, 311, 320, 344, 379 Anti-inflammatory, 23, 157, 160, 227, 312, 325, 340, 360 Anti-Inflammatory Agents, 227, 312, 325 Antimycotic, 157, 173, 207, 312, 322, 370 Antineoplastic, 169, 309, 312, 325

392 Candida

Antineoplastic Agents, 169, 309, 312 Antioxidant, 312, 363 Antiproliferative, 132, 312 Antiseptic, 312, 320, 386 Antiviral, 229, 270, 312, 349, 365 Anus, 310, 312, 316, 365, 373 Aplasia, 312, 331 Apoptosis, 30, 34, 240, 312 Applicability, 24, 209, 210, 226, 240, 312 Aqueous, 200, 206, 312, 314, 327, 332, 344 Arachidonic Acid, 52, 312, 352, 370 Arginine, 310, 312, 360, 362, 386 Aromatic, 201, 312, 318, 366, 380, 382 Arterial, 312, 325, 340, 345, 370 Arteries, 312, 315, 316, 325, 356, 358, 359, 384, 386 Arterioles, 312, 316, 317, 359 Aspartate, 237, 312 Aspartic, 44, 95, 100, 101, 146, 157, 160, 174, 175, 312, 333 Aspartic Acid, 312 Aspergillosis, 45, 216, 228, 313, 350 Assay, 29, 38, 42, 54, 85, 92, 98, 100, 108, 116, 117, 144, 151, 166, 214, 247, 313, 375, 386 Astringents, 313, 355 Asymptomatic, 128, 264, 271, 307, 313 Atopic, 21, 137, 313 Atrium, 313, 325, 386, 388 Attenuated, 62, 65, 145, 313 Attenuation, 65, 236, 313 Atypical, 70, 313 B Bacillus, 40, 198, 219, 242, 248, 313, 316 Bacteremia, 265, 313, 338, 376 Bacterial Infections, 256, 313, 319, 342, 374 Bacterial Physiology, 39, 313 Bacterial toxin, 38, 313 Bactericidal, 8, 241, 242, 313, 320, 335 Bacteriocins, 213, 313 Bacteriophage, 313, 367, 376, 385, 388 Bacteriostatic, 313, 386 Bacterium, 40, 237, 313, 323, 324, 338, 358, 386 Bacteriuria, 264, 313 Balanitis, 152, 314 Base, 7, 13, 247, 308, 314, 317, 327, 329, 337, 339, 351, 383, 386 Base Sequence, 314, 337, 339 Basement Membrane, 314, 335 Basophils, 314, 341, 352 Benign, 238, 314, 342, 360, 363, 372, 389

Benign tumor, 238, 314 Berberine, 173, 314 Beta-Defensins, 15, 23, 314, 328 Beta-Glucosidase, 175, 314 Bewilderment, 314, 324 Bile, 314, 338, 343, 344, 353, 381 Bile Acids, 314, 338, 381 Biliary, 314, 343 Bioassay, 19, 101, 314 Biofilms, 14, 16, 39, 64, 70, 76, 85, 87, 135, 143, 230, 314 Biological response modifier, 314, 349 Biological Transport, 314, 329 Biomass, 206, 315 Biopsy, 194, 266, 315 Biotechnology, 61, 107, 155, 159, 171, 172, 173, 177, 206, 209, 217, 262, 276, 287, 315 Bioterrorism, 29, 315 Biotin, 315, 362 Biotransformation, 251, 315 Bisexuality, 296, 315 Bladder, 7, 315, 327, 347, 386, 387 Blastomyces, 315, 364 Blastomycosis, 263, 315, 350 Blood Glucose, 315, 343, 348 Blood Platelets, 315, 378 Blood Preservation, 315, 330 Blood pressure, 234, 315, 340, 345, 357, 379 Blood vessel, 307, 315, 318, 320, 321, 325, 333, 350, 353, 355, 365, 372, 379, 381, 384, 388 Blot, 93, 100, 316, 362 Body Fluids, 316, 331, 379 Bone Marrow, 69, 142, 245, 308, 316, 322, 326, 342, 345, 353, 358, 379 Bone Marrow Transplantation, 69, 142, 245, 316 Bowel, 47, 239, 265, 310, 316, 330, 347, 349, 352, 366, 381, 386 Bowel Movement, 316, 330, 381 Brachiocephalic Veins, 316, 382 Brachytherapy, 316, 349, 350, 372, 389 Bradykinin, 316, 361 Branch, 303, 316, 342, 353, 364, 371, 380, 383 Breakdown, 3, 316, 319, 329, 338 Broad-spectrum, 7, 216, 228, 242, 316 Bronchi, 316, 334 Bronchial, 21, 316, 343 Bronchiseptica, 316, 366 Bronchitis, 265, 316 Buccal, 4, 316, 381

Index 393

Burning Mouth Syndrome, 277, 316 Bursitis, 139, 316 Bypass, 13, 316, 359 C Cadmium, 154, 158, 170, 317 Cadmium Poisoning, 317 Calcineurin, 43, 66, 77, 113, 170, 317 Calcium, 113, 317, 323, 359, 363, 378 Calcium Oxalate, 317, 363 Callus, 156, 159, 317 Calmodulin, 317 Candidosis, 4, 5, 6, 93, 115, 127, 258, 317 Canonical, 248, 317 Capillary, 97, 144, 316, 317, 340, 388 Capsaicin, 182, 183, 317 Capsicum, 8, 170, 182, 183, 211, 317 Capsules, 219, 318, 336, 339, 340 Carbohydrate, 27, 46, 75, 99, 119, 143, 178, 216, 229, 318, 325, 340, 341, 354, 368, 377 Carbon Dioxide, 204, 318, 328, 372, 374 Carboxy, 251, 318 Carboxylic Acids, 230, 318 Carcinogenesis, 7, 318 Carcinogenic, 220, 309, 318, 348, 362, 370, 381 Carcinogens, 318, 321, 358, 363 Carcinoma, 92, 238, 318 Cardiac, 318, 325, 333, 334, 358, 359, 381 Cardiovascular, 155, 159, 181, 318, 352, 378 Carnitine, 224, 318 Carotene, 95, 175, 318, 374 Carotenoids, 95, 175, 217, 318 Case report, 115, 118, 126, 140, 165, 318 Caspofungin acetate, 148, 318 Catalase, 70, 94, 204, 307, 318 Catalytic Domain, 18, 318 Catheterization, 7, 318, 350, 359 Catheters, 7, 203, 216, 228, 318, 337, 346, 349 Cations, 319, 350 Causal, 26, 319 Cause of Death, 40, 216, 228, 319 Caustic, 319, 379 Cell Adhesion, 24, 35, 36, 55, 66, 165, 319, 348 Cell Cycle, 40, 54, 83, 129, 171, 319, 326, 351, 388 Cell Death, 61, 312, 319, 360 Cell Differentiation, 319, 378 Cell Division, 17, 313, 319, 349, 355, 356, 367, 370, 377

Cell membrane, 20, 38, 43, 213, 236, 314, 319, 322, 329, 332, 350 Cell proliferation, 319, 349, 378 Cell Respiration, 319, 356, 374 Cellular metabolism, 16, 319 Cellulose, 319, 338, 367 Central Nervous System, 45, 114, 307, 309, 317, 319, 338, 340, 342, 352, 378 Central Nervous System Infections, 319, 342 Centromere, 17, 91, 319 Cervical, 124, 150, 238, 319 Cervix, 319, 320, 330 Cetylpyridinium, 4, 320 Character, 277, 320, 328 Cheilitis, 263, 265, 277, 320 Chemical Warfare, 320, 328 Chemical Warfare Agents, 320, 328 Chemotactic Factors, 320, 323, 360 Chemotaxis, 212, 236, 320 Chest Pain, 295, 320 Chimeras, 33, 320 Chin, 266, 320 Chitin Synthase, 61, 62, 101, 320 Chlamydia, 240, 242, 293, 320 Chlorhexidine, 4, 63, 183, 263, 320 Chlorine, 320, 345 Chlorophyll, 320, 338 Cholera, 36, 320, 388 Cholera Toxin, 36, 320 Cholesterol, 314, 321, 376, 381 Choline, 99, 321 Chorioamnionitis, 134, 321 Chorion, 321 Choroid, 321, 374, 387 Choroidal Neovascularization, 151, 321 Chromatin, 18, 312, 321 Chromatography, Liquid, 11, 321 Chromium, 220, 321 Chromosomal, 26, 135, 221, 252, 310, 321, 367, 375, 383 Chromosome, 18, 26, 91, 102, 252, 319, 321, 324, 342, 343, 350, 352, 377, 383 Chromosome Segregation, 18, 91, 321 CIS, 28, 61, 321, 374 Clear cell carcinoma, 321, 329 Clinical Medicine, 321, 369 Clinical trial, 4, 7, 8, 193, 194, 213, 287, 321, 326, 371, 372 Clone, 18, 32, 35, 50, 134, 321 Cloning, 49, 70, 90, 115, 315, 322 Clot Retraction, 322, 367

394 Candida

Clotrimazole, 199, 266, 277, 322 Coagulation, 315, 317, 322, 343, 375, 384 Coccidioidomycosis, 263, 322 Coculture, 47, 322 Codon, 178, 322, 339 Coenzyme, 224, 243, 322, 351 Cofactor, 322, 360, 370, 372, 384 Colitis, 265, 322 Collagen, 168, 308, 314, 322, 336, 339, 368, 370 Colloidal, 322, 332 Colony-Stimulating Factors, 322, 341 Combination Therapy, 33, 217, 232, 322 Combinatorial, 9, 23, 323 Commensal, 6, 16, 32, 37, 38, 55, 94, 110, 222, 250, 323 Commensalism, 9, 323 Competency, 212, 323 Complement, 11, 13, 31, 56, 105, 130, 243, 310, 323, 339, 348, 350 Complementary and alternative medicine, 163, 187, 323 Complementary medicine, 163, 323 Computational Biology, 287, 323 Conception, 323, 324, 336, 369 Concomitant, 32, 244, 324 Condoms, 293, 324 Condyloma, 238, 324 Cone, 324, 382 Confusion, 236, 324, 330 Congenita, 324, 331 Congestion, 324, 334 Conjugated, 20, 39, 324, 327 Conjugation, 240, 315, 324 Conjunctiva, 324, 348 Connective Tissue, 47, 316, 322, 324, 338, 339, 340, 353, 355, 365, 376 Connective Tissue Cells, 324 Consciousness, 310, 324, 328, 330 Constipation, 324, 366 Constitutional, 234, 324, 374 Constriction, 324, 350 Contamination, 213, 219, 220, 324 Contraceptive, 134, 209, 225, 324 Contraindications, ii, 324 Coordination, 41, 324 Cor, 325, 340 Cornea, 325, 377, 381 Corneal Transplantation, 118, 325 Coronary, 325, 356, 358, 359 Coronary Arteriosclerosis, 325, 359 Coronary Thrombosis, 325, 356, 358, 359

Corpus, 325, 365, 369 Cortex, 325, 335, 362, 369 Cortical, 325, 335, 377 Corticosteroid, 325, 381 Cost Savings, 58, 325 Cranial, 325, 336, 342, 364, 365 Craniocerebral Trauma, 325, 342, 384 Creatinine, 214, 326 Critical Care, 51, 148, 326 Crossing-over, 326, 373 Crowns, 326, 329 Cryptococcosis, 44, 45, 216, 228, 263, 326 Cryptosporidium, 240, 271, 326 Crystallization, 225, 326 Cues, 40, 326 Culture Media, 109, 308, 326 Curative, 207, 326, 360, 383 Curette, 326, 330 Cutaneous, 85, 89, 96, 118, 143, 227, 229, 237, 315, 317, 326, 350, 376, 380 Cyanide, 326, 356 Cyanogen Bromide, 213, 326 Cyclic, 69, 72, 207, 293, 308, 317, 326, 342, 361 Cyclin, 40, 62, 326 Cyclin A, 40, 326 Cyclin-Dependent Kinases, 40, 326 Cycloheximide, 143, 326 Cyclosporine, 47, 274, 326 Cyst, 114, 326 Cysteine, 326, 328, 333, 382 Cystitis, 265, 293, 327 Cytochrome, 63, 83, 106, 167, 175, 208, 234, 248, 249, 327, 374 Cytochrome b, 83, 106, 208, 327, 374 Cytochrome b5, 208, 327 Cytokine, 33, 41, 47, 59, 67, 237, 327, 349 Cytomegalovirus, 265, 268, 270, 295, 327 Cytomegalovirus Retinitis, 270, 327 Cytoplasm, 312, 314, 319, 321, 327, 334, 335, 341, 375 Cytosine, 123, 247, 327, 337 Cytoskeletal Proteins, 53, 327 Cytoskeleton, 24, 48, 327, 348, 356 Cytotoxic, 44, 267, 317, 327, 346, 372, 378 Cytotoxic chemotherapy, 267, 327 Cytotoxicity, 58, 167, 327, 351 D Databases, Bibliographic, 287, 327 De novo, 11, 112, 328 Decarboxylation, 328, 343, 372 Decontamination, 142, 328

Index 395

Defense Mechanisms, 46, 176, 260, 264, 328, 348 Defensins, 15, 23, 44, 213, 228, 309, 314, 328 Degenerative, 328, 343, 374 Dehydration, 320, 328 Deletion, 25, 42, 62, 72, 73, 77, 312, 328, 339 Dementia, 307, 328 Demethylation, 63, 78, 86, 173, 328 Dendrites, 328 Dendritic, 30, 328 Dental Abutments, 328, 329 Dental Caries, 328 Dental Plaque, 14, 328 Dentin Permeability, 328, 379 Dentists, 255, 328 Denture Cleansers, 112, 263, 328 Denture Liners, 6, 328 Dentures, 4, 5, 6, 16, 200, 263, 277, 328, 329 Deoxyribonucleic, 56, 238, 247, 329, 375 Deoxyribonucleic acid, 56, 238, 247, 329, 375 Deoxyribonucleotides, 329 Depolarization, 329, 378 Dermal, 329, 331 Dermatitis, 114, 137, 266, 329 Dermatitis, Contact, 266, 329 Dermatosis, 266, 329 DES, 44, 154, 157, 292, 310, 329 Detergents, 200, 329 Detoxification, 220, 329 Deuterium, 329, 344 Diabetes Mellitus, 5, 16, 20, 329, 340, 343 Diagnostic procedure, 197, 276, 329 Diarrhea, 119, 132, 265, 269, 329, 335 Diarrhoea, 166, 329, 338 Dietary Fats, 329, 352 Dietary Fiber, 239, 329 Dietitian, 270, 329 Diffusion, 63, 73, 79, 109, 121, 123, 155, 158, 167, 314, 329, 346, 350 Digestion, 102, 309, 314, 316, 329, 349, 352, 353, 381 Digestive system, 195, 239, 329, 338, 358 Digestive tract, 239, 330, 379 Dihydrotestosterone, 330, 373 Dihydroxy, 207, 252, 330 Dihydroxyacetone, 99, 204, 330 Dihydroxyacetone Phosphate, 330 Dilatation, 120, 330, 369, 388 Dilatation and Curettage, 120, 330

Diploid, 13, 17, 43, 53, 62, 210, 221, 233, 330, 367 Direct, iii, 26, 35, 38, 42, 75, 84, 118, 210, 233, 259, 279, 321, 330, 331, 373 Discrimination, 24, 53, 75, 330 Disinfectant, 320, 330, 335 Disorientation, 324, 330 Dissection, 42, 330 Dissociation, 44, 308, 330 Dissociative Disorders, 330 Distal, 24, 330, 338, 371 Diuretic, 330, 354, 380 Dominance, 221, 247, 330 Dopamine, 330, 366 Drive, ii, vi, 6, 59, 153, 262, 263, 264, 265, 267, 331, 350 Dross, 331, 370 Drug Delivery Systems, 212, 331 Drug Design, 19, 55, 61, 281, 331 Drug Interactions, 43, 280, 331 Drug Tolerance, 331, 384 Duct, 147, 318, 331, 335, 376 Dura mater, 331, 355, 363 Dysphagia, 266, 267, 331 E Ecosystem, 203, 331 Ectoderm, 331 Ectodermal Dysplasia, 277, 331 Edema, 320, 327, 331, 351, 358, 359 Effector, 46, 59, 60, 237, 307, 323, 331, 351 Effector cell, 46, 59, 331, 351 Efficacy, 8, 13, 15, 46, 60, 64, 169, 171, 241, 331, 332, 385 Elasticity, 252, 325, 332 Elastin, 322, 332 Elective, 178, 332 Electrocardiogram, 193, 332 Electrolyte, 325, 332, 369, 379 Electrons, 312, 314, 332, 350, 354, 357, 363, 372 Electrophoresis, 78, 79, 93, 99, 106, 132, 139, 175, 332, 346 Electroporation, 251, 332 Elementary Particles, 332, 354, 360, 371 Emaciation, 307, 332 Embryo, 310, 319, 331, 332, 347, 369, 380, 386 Embryo Transfer, 332, 369 Emollient, 332, 361 Empiric, 45, 332 Empirical, 112, 332 Emulsions, 140, 308, 332

396 Candida

Enamel, 328, 332, 351, 379 Encapsulated, 49, 333, 353 Endemic, 320, 333 Endocarditis, 110, 147, 221, 247, 317, 333 Endocardium, 333 Endometrium, 330, 333, 355 Endopeptidases, 333, 370 Endophthalmitis, 111, 120, 151, 333 Endothelial cell, 15, 50, 67, 93, 111, 119, 155, 156, 159, 160, 165, 169, 212, 244, 333, 384 Endothelium, 50, 333, 360, 367 Endothelium, Lymphatic, 333 Endothelium, Vascular, 333 Endothelium-derived, 333, 360 Endotoxic, 333, 352 Endotoxin, 17, 333, 386 Enteric Nervous System, 47, 333 Enterocytes, 17, 333 Enteropeptidase, 333, 386 Enterovirus, 48, 334 Environmental Health, 286, 288, 334 Environmental Pollutants, 334, 368 Enzymatic, 35, 120, 170, 214, 235, 251, 317, 318, 323, 326, 328, 334, 335, 343, 374, 376 Eosinophil, 21, 334 Eosinophilia, 21, 334 Eosinophilic, 21, 334 Epidemic, 208, 257, 258, 259, 267, 271, 334 Epidemiological, 74, 334 Epidermal, 238, 334, 351, 389 Epidermis, 331, 334, 351, 369 Epinephrine, 330, 334, 386 Epithelial Cells, 4, 15, 23, 30, 47, 86, 127, 131, 238, 257, 314, 320, 334, 343 Epithelium, 15, 47, 145, 204, 247, 314, 324, 326, 333, 334, 364 Epitope, 13, 18, 32, 46, 95, 334 Erectile, 334, 365 Erythema, 30, 334 Erythrocytes, 310, 316, 330, 334, 373 Escherichia, 36, 179, 198, 213, 229, 242, 245, 265, 334, 335, 338 Escherichia coli, 36, 179, 198, 213, 242, 245, 265, 335, 338 Esophageal, 37, 40, 42, 45, 54, 194, 199, 264, 266, 267, 295, 335, 339 Esophagitis, 146, 194, 209, 226, 264, 267, 296, 335, 339 Esophagoscopy, 264, 335 Esophagus, 194, 266, 268, 296, 330, 335, 338, 339, 342, 353, 361, 366, 373, 381

Esterification, 170, 249, 335 Ethanol, 155, 158, 169, 215, 335, 336, 372 Ether, 220, 335, 386 Eukaryote, 335, 370 Eukaryotic Cells, 33, 327, 335, 347, 362, 386 Evoke, 335, 381 Excitatory, 335, 340 Excrete, 208, 335, 351 Exocrine, 223, 335, 363 Exogenous, 9, 218, 308, 315, 335 Expeditions, 29, 335 Expiration, 335, 374 Extensor, 335, 371 External-beam radiation, 335, 350, 372, 389 Extracellular, 16, 32, 38, 44, 49, 54, 72, 77, 82, 93, 122, 130, 314, 324, 335, 336, 348, 370, 379 Extracellular Matrix, 16, 44, 54, 72, 93, 130, 324, 335, 336, 348 Extracellular Space, 335 Extremity, 264, 336 F Facial, 115, 266, 336, 364 Facial Nerve, 115, 336, 364 Faecal, 329, 336 Family Planning, 287, 336 Fat, 312, 316, 318, 325, 336, 340, 352, 353, 368, 376, 379, 382 Fatigue, 256, 260, 270, 336 Fatty acids, 208, 230, 234, 249, 318, 336, 370, 379, 384 Febrile, 45, 93, 336, 364 Fermentation, 155, 159, 205, 215, 218, 230, 240, 336, 337, 376 Fertilization in Vitro, 336, 369 Fetal Blood, 321, 336 Fetal Death, 134, 336 Fetus, 321, 336, 380, 381, 386, 387 Fibrin, 322, 336, 366, 367, 384 Fibrinogen, 34, 336, 367, 384 Fibroblasts, 324, 336, 349 Fibronectin, 15, 104, 336 Filler, 50, 62, 67, 77, 81, 89, 93, 99, 100, 101, 106, 108, 155, 159, 169, 174, 205, 244, 336 Filtration, 89, 120, 336 Fistulas, 264, 337 Flagellum, 337, 386 Flatus, 337, 338 Flucytosine, 25, 43, 122, 123, 149, 234, 337 Fluorescence, 39, 45, 80, 124, 337

Index 397

Folate, 201, 337 Fold, 32, 245, 294, 337 Folic Acid, 337 Food Preservatives, 242, 337 Food Technology, 337, 356 Foramen, 320, 337, 365 Forearm, 315, 337 Fornix, 337, 387 Frameshift, 337, 386 Frameshift Mutation, 337, 386 Freeze-dried, 171, 337 Fructose, 88, 205, 337, 341 Fungemia, 31, 58, 62, 77, 106, 113, 118, 122, 133, 134, 140, 143, 165, 337 Fungicide, 207, 274, 338 Fungicides, Industrial, 311, 338 Fungistatic, 103, 338, 386 G Gallbladder, 307, 314, 330, 338 Gamma Rays, 338, 372 Ganglia, 307, 333, 338, 360 Gangrene, 265, 307, 338 Gardnerella, 28, 124, 293, 338, 387 Gardnerella vaginalis, 28, 124, 338, 387 Gas, 74, 214, 215, 229, 310, 318, 320, 329, 337, 338, 344, 358, 360, 361, 382 Gasoline, 220, 338 Gastric, 318, 338, 342, 343 Gastrin, 338, 344 Gastroenteritis, 338, 376 Gastroenterology, 6, 267, 338 Gastroesophageal Reflux, 267, 338 Gastroesophageal Reflux Disease, 267, 338 Gastrointestinal, 6, 43, 81, 109, 155, 158, 199, 221, 222, 242, 247, 264, 265, 270, 316, 317, 334, 335, 339, 352, 378, 382, 388 Gastrointestinal tract, 109, 222, 335, 339, 352, 378 Gastroscopy, 266, 339 Gelatin, 15, 326, 339, 340, 382, 384 Gene Deletion, 18, 339 Gene Fusion, 40, 55, 339 Gene Library, 339 Gene Silencing, 54, 339 Genetic Code, 178, 339, 361 Genetic Engineering, 315, 322, 339 Genetics, 13, 38, 39, 42, 43, 49, 53, 60, 109, 135, 141, 210, 261, 324, 330, 339, 357 Genital, 51, 150, 181, 221, 222, 238, 247, 292, 293, 321, 338, 339, 387, 389 Genitourinary, 233, 239, 245, 339, 387 Genomic Library, 26, 212, 250, 339

Genomics, 26, 39, 79, 94, 190, 339 Genotype, 67, 71, 90, 210, 339, 366 Gestation, 339, 365, 380 Ginseng, 176, 184, 185, 340 Gland, 115, 147, 325, 340, 353, 363, 364, 377, 381, 382, 384 Glomerular, 340, 354 Glomerular Filtration Rate, 340, 354 Glomeruli, 340, 372 Glottis, 340, 366 Glucans, 94, 178, 340 Glucocorticoids, 23, 266, 325, 340 Gluconeogenesis, 340 Glucose Intolerance, 329, 340 Glutamate, 340 Glutamic Acid, 223, 337, 340, 370 Glutamine, 88, 207, 340 Glycine, 212, 340, 377 Glycogen, 320, 340 Glycolysis, 38, 330, 340 Glycoprotein, 50, 59, 117, 229, 336, 340, 341, 354, 378, 384, 386 Glycosaminoglycans, 156, 160, 340 Glycoside, 211, 341 Glycosylation, 27, 89, 105, 148, 341 Glycosyltransferases, 27, 341 Goblet Cells, 333, 341 Gonadal, 341, 381 Gonorrhea, 292, 293, 294, 341 Governing Board, 341, 369 Gp120, 341, 365 GP41, 128, 341 Graft, 341, 344, 346, 359 Graft Rejection, 341, 346 Grafting, 341, 346 Gram-negative, 59, 213, 316, 320, 333, 334, 335, 341, 376, 378, 388 Gram-positive, 213, 341, 351, 358, 380, 381 Granulocyte Colony-Stimulating Factor, 63, 217, 232, 322, 341 Granulocytes, 322, 341, 352, 378, 389 Granuloma, 342, 364 Granulomatous Disease, Chronic, 342, 374 Groin, 267, 294, 342 Guanylate Cyclase, 342, 361 H Habitat, 17, 229, 342, 358 Habitual, 320, 342 Haematological, 150, 342 Haematology, 342 Hair follicles, 342, 380, 389 Halogens, 248, 342

398 Candida

Haploid, 13, 49, 342, 367 Haptens, 308, 342 Headache, 236, 271, 342, 348 Headache Disorders, 342 Heartburn, 256, 342 Hematogenous, 50, 127, 342 Hematologic Diseases, 108, 342 Hematologic malignancies, 73, 138, 342 Heme, 24, 213, 249, 327, 342, 363 Hemocytes, 213, 343 Hemoglobin, 213, 334, 342, 343, 352 Hemorrhage, 325, 327, 342, 343, 359, 381 Hemostasis, 343, 348, 378 Hepatitis, 48, 270, 292, 293, 343 Hepatobiliary, 48, 343 Hepatocytes, 343 Hereditary, 8, 255, 331, 343 Heredity, 339, 343 Hernia, 118, 343 Herpes, 33, 47, 181, 261, 268, 292, 293, 294, 343 Herpes Zoster, 343 Heterochromatin, 54, 343 Heterodimers, 343, 348 Heterogeneity, 106, 136, 308, 343 Heterotrophic, 337, 343 Heterozygotes, 330, 343 Hexosyltransferases, 341, 343 Histamine, 138, 310, 343 Histidine, 24, 37, 60, 101, 236, 343 Homeobox, 344 Homeodomain Proteins, 152, 344 Homeostasis, 9, 344 Homologous, 18, 54, 88, 103, 104, 198, 241, 252, 309, 326, 343, 344, 358, 377, 383 Homotypic, 34, 344 Homozygotes, 330, 344 Hormone, 227, 314, 325, 329, 334, 338, 344, 348, 355, 369, 375, 378, 383, 384 Human papillomavirus, 150, 344 Humoral, 32, 41, 73, 74, 341, 344 Humour, 344 Hybrid, 18, 38, 43, 44, 55, 60, 198, 321, 344, 362 Hybridization, 26, 93, 97, 100, 102, 144, 246, 247, 250, 344, 357, 361, 362 Hybridomas, 332, 344, 349 Hydrogel, 190, 344, 347 Hydrogen, 204, 247, 248, 307, 309, 314, 318, 329, 344, 345, 352, 357, 360, 361, 363, 371, 382 Hydrogen Bonding, 344, 361

Hydrogen Cyanide, 344, 361 Hydrogen Peroxide, 204, 318, 344, 352, 382 Hydrolysis, 170, 171, 235, 249, 312, 314, 315, 341, 345, 350, 354, 366, 368, 371, 386 Hydrophilic, 329, 344, 345 Hydrophobic, 24, 35, 38, 71, 79, 212, 329, 345 Hydroxylation, 249, 345 Hydroxylysine, 322, 345 Hydroxyproline, 322, 345 Hypersensitivity, 25, 180, 237, 334, 345, 352, 375 Hypertension, 325, 342, 345, 384 Hypochlorous Acid, 138, 345 Hypoplasia, 331, 345 Hypotension, 205, 345 Hypoxia, 17, 129, 345 I Id, 161, 180, 246, 297, 302, 304, 345 Ileostomy, 345, 360 Imidazole, 173, 315, 322, 343, 345, 356 Immortal, 59, 345 Immune function, 34, 43, 345, 346 Immune Sera, 345 Immunization, 13, 15, 36, 41, 216, 232, 345, 346 Immunocompromised, 4, 7, 8, 9, 14, 25, 27, 29, 44, 46, 53, 55, 57, 60, 194, 199, 202, 204, 208, 209, 210, 211, 216, 222, 225, 229, 232, 233, 250, 345, 346 Immunocompromised Host, 7, 47, 209, 225, 346 Immunodeficiency syndrome, 256, 271, 292, 293, 296, 346 Immunodiffusion, 308, 346 Immunoelectrophoresis, 308, 346 Immunofluorescence, 97, 116, 256, 346 Immunogenic, 46, 103, 346, 352 Immunoglobulin, 311, 346, 349, 357 Immunohistochemistry, 23, 32, 50, 346 Immunologic, 21, 35, 36, 264, 320, 345, 346, 372 Immunophilin, 317, 346 Immunosuppressive, 41, 43, 46, 96, 203, 204, 233, 247, 317, 346 Immunosuppressive Agents, 203, 346 Immunosuppressive therapy, 204, 233, 346 Immunotherapy, 15, 34, 130, 154, 158, 237, 346 Impairment, 314, 346, 355

Index 399

Implant radiation, 346, 349, 350, 372, 389 Implantation, 7, 11, 323, 346 Impregnation, 199, 346 In situ, 23, 73, 124, 243, 346 In Situ Hybridization, 23, 73, 74, 80, 124, 347 Incineration, 215, 347 Incision, 347, 350, 383 Incompetence, 338, 347 Incontinence, 8, 347 Incontinence Pads, 8, 347 Incubation, 347, 366 Incubation period, 347, 366 Indicative, 257, 347, 364, 388 Induction, 41, 54, 59, 64, 72, 79, 116, 347 Industrial Microbiology, 8, 347 Infant, Newborn, 308, 347 Infarction, 347, 374 Inflammatory bowel disease, 265, 347 Influenza, 264, 348 Infusion, 348, 356, 359 Ingestion, 317, 348, 355, 368 Inhalation, 322, 348, 356, 368, 380 Initiation, 33, 35, 47, 52, 54, 348, 381, 385 Inlay, 348, 374 Inner ear, 348, 387 Innervation, 336, 348 Inoculum, 86, 207, 348 Inorganic, 198, 199, 219, 341, 348, 358, 361, 366, 379, 382 Inpatients, 133, 348 Insecticides, 348, 366 Insight, 30, 32, 46, 348 Instillation, 21, 348 Insulin, 5, 348 Insulin-dependent diabetes mellitus, 348 Integrins, 34, 209, 348 Intensive Care, 58, 68, 90, 92, 116, 126, 128, 129, 134, 136, 142, 150, 348 Intensive Care Units, 58, 150, 348 Interferon, 66, 67, 86, 131, 154, 157, 293, 349 Interferon-alpha, 349 Interleukin-1, 46, 66, 72, 83, 86, 131, 154, 157, 349 Interleukin-13, 154, 157, 349 Interleukin-2, 92, 349 Interleukin-6, 148, 349 Interleukins, 346, 349 Intermittent, 349, 353, 365 Internal Medicine, 22, 33, 122, 338, 349 Internal radiation, 349, 350, 372, 389

Interphase, 343, 349 Interstitial, 293, 316, 335, 349, 350, 389 Intestinal, 17, 47, 104, 132, 147, 166, 168, 265, 309, 318, 320, 326, 333, 334, 349, 351, 363 Intestine, 265, 316, 334, 335, 349, 351, 381 Intoxication, 349, 389 Intracellular Membranes, 349, 355 Intramuscular, 11, 349, 364 Intraocular, 333, 349 Intravascular, 50, 349 Intravenous, 11, 15, 203, 296, 337, 348, 350, 356, 364 Intrinsic, 21, 26, 308, 314, 350 Introns, 339, 350 Intubation, 318, 350 Invertebrates, 10, 228, 343, 350 Ion Transport, 47, 350 Ions, 241, 314, 317, 330, 332, 344, 350 Irradiation, 203, 350, 389 Irritants, 266, 295, 350 Ischemia, 34, 350, 359, 374 Isoenzyme, 67, 350 Isozymes, 81, 250, 350 J Joint, 114, 263, 350, 383 K Karyotype, 77, 78, 91, 350 Kb, 212, 286, 351 Keratin, 351 Keratinocytes, 23, 30, 351 Keto, 243, 351, 372, 389 Ketoconazole, 6, 170, 184, 266, 351 Ketosteroids, 62, 164, 351 Kidney Failure, 351, 354 Kidney stone, 351, 363 Killer Cells, 351 Kinetic, 24, 39, 351 Kinetochores, 17, 351 L Labile, 36, 323, 351 Lacrimal, 336, 351 Lactate Dehydrogenase, 218, 351 Lactates, 219, 351 Lactobacillus, 172, 175, 184, 244, 351 Large Intestine, 330, 349, 351, 373, 379 Laxative, 308, 352, 380 Lectin, 133, 168, 352, 355 Leprosy, 82, 127, 352 Lesion, 20, 315, 342, 352, 353, 376, 378, 386 Lethal, 15, 20, 34, 41, 176, 209, 216, 226, 228, 243, 250, 313, 326, 352, 358

400 Candida

Leucine, 212, 243, 352 Leucocyte, 334, 352 Leukemia, 88, 148, 342, 352 Leukocytes, 34, 48, 59, 145, 314, 316, 320, 341, 349, 352, 386 Leukoplakia, 115, 266, 271, 352 Leukotrienes, 312, 352 Library Services, 302, 352 Life cycle, 11, 24, 47, 337, 352 Ligands, 16, 34, 56, 157, 249, 348, 352 Linkage, 44, 352 Lip, 118, 171, 266, 352 Lipase, 52, 154, 158, 170, 171, 173, 190, 249, 352 Lipid, 46, 64, 118, 140, 249, 321, 330, 332, 348, 351, 352, 353, 363, 386 Lipid A, 46, 352 Lipid Peroxidation, 352, 363 Lipophilic, 352, 368 Lipopolysaccharide, 59, 86, 131, 313, 341, 353 Liposomal, 39, 49, 353 Liposomes, 49, 353 Localization, 9, 23, 25, 28, 97, 240, 346, 353 Localized, 32, 65, 222, 260, 328, 333, 347, 353, 358, 362, 367, 386 Locomotion, 337, 353, 367 Long-Term Care, 37, 53, 94, 140, 353 Loop, 104, 343, 345, 353 Lower Esophageal Sphincter, 338, 339, 353 Lubricants, 249, 353, 366 Lycopene, 95, 175, 353 Lymph, 311, 319, 333, 344, 353, 364, 376, 382 Lymph node, 319, 353, 364, 376 Lymphatic, 333, 347, 353, 355, 379, 380, 384 Lymphatic system, 353, 379, 380, 384 Lymphocyte, 134, 307, 311, 349, 351, 353, 355 Lymphocyte Count, 307, 353 Lymphocytic, 265, 353 Lymphoid, 311, 352, 353 Lymphoma, 221, 342, 353 Lysine, 92, 345, 354, 386 Lysophospholipase, 176, 354 Lytic, 354, 388 M Macrophage, 39, 47, 59, 63, 67, 74, 88, 125, 127, 322, 349, 354 Macrophage Colony-Stimulating Factor, 63, 88, 127, 322, 354

Magnetic Resonance Imaging, 354 Magnetic Resonance Spectroscopy, 144, 238, 354 Malignancy, 150, 354, 364 Malignant, 265, 307, 312, 354, 360, 372, 376, 383 Malnutrition, 269, 354 Mandible, 320, 354 Manifest, 34, 354 Mannans, 49, 338, 354 Mannitol, 205, 214, 223, 354 Mannosyltransferases, 28, 354 Maxillary, 6, 354, 364 Mediate, 15, 25, 27, 34, 50, 56, 102, 331, 351, 354 Mediator, 349, 354, 378 Medicament, 355, 382 MEDLINE, 287, 355 Meiosis, 321, 355, 358, 383 Melanin, 355, 366, 386 Membrane Proteins, 8, 124, 353, 355, 371 Memory, 311, 328, 355 Meninges, 319, 325, 331, 355 Meningitis, 43, 62, 81, 137, 181, 236, 337, 350, 355 Menstrual Cycle, 133, 355, 369 Menstruation, 355 Mental Disorders, 195, 355 Mental Health, iv, 7, 195, 286, 288, 355, 371 Mental Processes, 330, 355, 371 Mercury, 242, 259, 355 Mesenchymal, 354, 355 Metabolite, 119, 315, 355 Metaphase, 351, 355 Methanol, 99, 204, 355 Methionine, 355, 382 Methylene Blue, 95, 141, 356 Methylene Chloride, 220, 356 Methyltransferase, 55, 101, 356 MI, 150, 169, 179, 305, 356 Miconazole, 266, 356 Microbe, 19, 356, 384 Microbiological, 6, 7, 120, 256, 356 Microorganism, 47, 215, 219, 242, 248, 311, 318, 322, 356, 364, 389 Micro-organism, 328, 331, 356 Microscopy, 41, 189, 314, 356 Microspheres, 29, 39, 356 Microtubules, 351, 356 Migration, 17, 34, 356 Miotic, 356, 367

Index 401

Miscible, 217, 218, 356 Mitochondria, 38, 157, 160, 226, 356, 359, 362 Mitochondrial Swelling, 356, 360 Mitosis, 312, 321, 356, 357 Mitosporic Fungi, 313, 315, 356 Mitotic, 351, 357 Mixed Function Oxidases, 327, 357 Modeling, 23, 31, 38, 46, 331, 357 Modification, 11, 25, 27, 35, 240, 339, 357, 372 Molecular mass, 8, 207, 211, 236, 357 Molecular Probes, 332, 357 Monitor, 39, 108, 233, 326, 357, 361 Monoclonal, 49, 59, 92, 95, 108, 209, 216, 232, 344, 350, 357, 372, 389 Monocyte, 354, 357 Mononuclear, 66, 342, 354, 357, 386 Morphological, 53, 54, 76, 83, 179, 202, 233, 332, 338, 357 Morphology, 14, 22, 38, 42, 54, 65, 69, 115, 179, 190, 227, 342, 357 Motility, 357, 378 Motion Sickness, 357, 359 Mucins, 328, 333, 341, 357, 376 Mucociliary, 357, 379 Mucocutaneous, 116, 199, 357 Mucosa, 16, 27, 32, 47, 109, 119, 223, 238, 333, 357, 381 Mucositis, 223, 256, 263, 277, 358 Mucus, 229, 357, 358, 386 Multidrug resistance, 10, 115, 170, 358 Multiple Organ Failure, 138, 358 Multivalent, 241, 342, 358 Multivariate Analysis, 238, 358 Mumps Virus, 237, 358 Muscle Fibers, 358, 359 Mustard Gas, 350, 358 Mutagenesis, 18, 24, 35, 53, 358 Mutagenicity, 358 Mutagens, 337, 358 Myalgia, 348, 358 Mycobacterium, 248, 270, 352, 358, 386 Mycobacterium avium, 270, 358 Mycosis, 203, 210, 233, 358, 362, 364 Mycotic, 10, 11, 54, 65, 358 Myelofibrosis, 163, 358 Myocardial infarction, 325, 356, 358, 359 Myocardial Ischemia, 268, 358 Myocardial Reperfusion, 359, 374 Myocardial Reperfusion Injury, 359, 374 Myocardium, 356, 358, 359

Myosin, 61, 92, 317, 359 N Naive, 41, 359 Naphthoquinones, 330, 359 Narcotic, 307, 356, 359 Nasal Mucosa, 348, 359 Natural killer cells, 92, 359 Nausea, 236, 338, 359 NCI, 1, 193, 195, 285, 321, 359 Necrosis, 20, 119, 312, 327, 333, 347, 356, 358, 359, 374, 376 Necrotizing Enterocolitis, 147, 360 Neonatal, 68, 90, 92, 116, 118, 126, 128, 135, 137, 149, 360 Neoplasm, 360, 363, 376 Neoplastic, 344, 353, 360 Nerve, 310, 320, 328, 333, 336, 348, 354, 360, 363, 368, 374, 377, 381, 384, 388 Nervous System, 48, 308, 319, 354, 360, 382, 388 Networks, 9, 10, 360 Neural, 308, 344, 360 Neurologic, 270, 360 Neuropathy, 264, 360 Neutralization, 38, 360 Neutrons, 309, 350, 360, 372 Neutropenia, 46, 203, 217, 232, 337, 360 Neutrophil, 30, 39, 46, 50, 88, 138, 360 Neutrophil Activation, 46, 360 Niacin, 360, 386 Nickel, 165, 360 Niflumic Acid, 157, 160, 360 Nitric Oxide, 24, 360 Nitriles, 361 Nitrogen, 13, 39, 74, 206, 212, 236, 309, 340, 344, 357, 361, 386 Noel, 52, 63, 93, 95, 115, 123, 125, 361 Nosocomial, 11, 12, 16, 42, 60, 78, 92, 120, 140, 142, 146, 211, 245, 361 Nuclear, 11, 46, 144, 226, 324, 332, 335, 338, 360, 361, 387 Nuclei, 309, 324, 332, 339, 350, 354, 356, 360, 361, 371 Nucleic Acid Hybridization, 29, 344, 361 Nucleic Acid Probes, 74, 80, 124, 361 Nucleus, 312, 314, 321, 326, 327, 329, 332, 335, 338, 355, 357, 360, 361, 370, 371, 381 Nursing Care, 8, 361, 364 Nystatin, 199, 277, 280, 361 O Observational study, 58, 361 Odour, 312, 361

402 Candida

Odynophagia, 266, 267, 361 Ointments, 242, 245, 295, 361, 379 Oligonucleotide Probes, 29, 362 Oliguria, 351, 354, 362 Oncogenic, 348, 362 Onychomycosis, 108, 149, 152, 362 Open Reading Frames, 32, 362 Opportunistic Infections, 4, 19, 256, 270, 271, 294, 307, 362 Oral Health, 362 Oral Hygiene, 37, 263, 294, 362 Orderly, 321, 362 Organ Transplantation, 204, 216, 228, 250, 362 Organelles, 327, 362 Ornithine, 207, 362 Orofacial, 116, 362 Oropharynx, 6, 362 Osmolarity, 60, 354, 362 Osmoles, 362 Osmosis, 362 Osmotic, 24, 356, 362 Osteomyelitis, 110, 362 Otitis, 265, 362 Ovum, 339, 352, 363, 369, 389 Oxalate, 293, 363 Oxidants, 39, 363 Oxidation, 39, 125, 214, 224, 249, 251, 307, 312, 315, 327, 342, 351, 352, 363 Oxidation-Reduction, 224, 315, 363 Oxidative Stress, 39, 104, 116, 363 Oxygen Consumption, 363, 374 Oxygenase, 127, 363 P Pachymeningitis, 355, 363 Palate, 295, 363, 381 Palliative, 363, 383 Palmitic Acid, 207, 363 Pancreas, 307, 315, 330, 338, 348, 352, 363, 386 Pancreatic, 318, 338, 363 Pancreatic Juice, 338, 363 Paneth Cells, 309, 333, 363 Papilloma, 237, 324, 363 Papillomavirus, 237, 364 Paracoccidioidomycosis, 263, 364 Paralysis, 115, 307, 364 Paranasal Sinuses, 364, 379 Parasite, 364 Parasitic, 239, 314, 364, 385 Paratyphoid Fever, 364, 376 Parenchyma, 50, 364

Parenteral, 17, 45, 140, 169, 364 Paronychia, 209, 225, 267, 277, 295, 364 Parotid, 37, 115, 147, 364, 376 Paroxysmal, 342, 364, 366, 389 Particle, 242, 364, 385 Patch, 266, 352, 364 Pathologic, 21, 221, 312, 315, 317, 325, 345, 364, 371 Pathologic Processes, 312, 364 Pathologies, 250, 364 Pathophysiology, 264, 364 Patient Care Management, 265, 364 Patient Education, 292, 300, 302, 305, 365 Penis, 267, 314, 324, 365 Pentosyltransferases, 341, 365 Peptide T, 212, 365 Perception, 267, 324, 365, 376 Perforation, 147, 199, 337, 365 Perfusion, 345, 365 Perianal, 324, 365 Perinatal, 51, 365 Perineum, 365, 380 Periodontal disease, 23, 30, 32, 263, 365 Periodontitis, 20, 209, 226, 256, 365 Perioral, 266, 365 Peripheral blood, 33, 114, 349, 365 Peripheral Nerves, 352, 365 Peritoneal, 138, 140, 141, 154, 157, 158, 365 Peritoneal Cavity, 365 Peritoneal Dialysis, 138, 365 Peritoneum, 365, 366 Peritonitis, 9, 82, 138, 141, 147, 366 Peroxide, 204, 366 Pertussis, 237, 366, 389 Pesticides, 207, 220, 224, 348, 366 Petroleum, 205, 206, 220, 338, 366 Phagocyte, 354, 363, 366 Phagocytosis, 34, 47, 48, 129, 134, 154, 158, 366 Pharmaceutical Preparations, 319, 335, 339, 366 Pharmacodynamic, 31, 194, 366 Pharmacokinetic, 31, 194, 366 Pharmacologic, 311, 366, 384 Pharynx, 338, 348, 362, 366 Phenotype, 12, 27, 77, 86, 210, 212, 239, 250, 339, 366 Phenylalanine, 201, 366, 386 Phosphates, 219, 366 Phospholipases, 52, 366, 378 Phospholipases A, 52, 366 Phosphorus, 317, 367

Index 403

Phosphorylated, 237, 322, 330, 367 Phosphorylation, 60, 66, 155, 159, 165, 169, 231, 237, 326, 367 Physical Examination, 245, 367 Physiologic, 309, 315, 355, 367, 373, 378 Physiology, 229, 338, 367 Pigment, 94, 353, 367 Pilocarpine, 256, 367 Pilot study, 172, 367 Plant Diseases, 206, 207, 367 Plaque, 14, 32, 44, 256, 320, 367 Plasma cells, 311, 367 Plasmid, 18, 32, 42, 165, 212, 253, 367, 388 Plasmin, 111, 367 Plasminogen, 367 Plasminogen Activators, 367 Platelet Activation, 368, 378 Platelet Aggregation, 310, 361, 368, 384 Platelets, 164, 173, 361, 368, 384 Poisoning, 164, 317, 338, 349, 355, 356, 359, 368, 376, 377 Polychlorinated Biphenyls, 220, 368 Polyesters, 230, 368 Polyethylene, 347, 368 Polymerase, 168, 368 Polymers, 119, 208, 218, 219, 234, 235, 249, 252, 314, 368, 370, 382 Polymorphic, 61, 70, 82, 84, 93, 96, 122, 126, 128, 151, 368 Polymorphism, 26, 84, 107, 146, 150, 368 Polypeptide, 198, 200, 201, 203, 213, 222, 229, 236, 241, 249, 310, 322, 336, 344, 367, 368, 370, 389 Polyphosphates, 219, 368 Polysaccharide, 13, 25, 311, 319, 368 Posterior, 310, 321, 363, 368, 377, 387 Postoperative, 337, 358, 368 Postsynaptic, 368, 378 Post-translational, 60, 240, 368 Potassium, 133, 369, 379 Potentiates, 349, 369 Potentiation, 369, 378 Practicability, 369, 385 Practice Guidelines, 288, 369 Precipitating Factors, 41, 342, 369 Preclinical, 45, 369 Precursor, 201, 251, 252, 256, 312, 321, 330, 331, 334, 341, 366, 367, 369, 386 Pregnancy Outcome, 52, 369 Presumptive, 71, 89, 93, 95, 141, 369 Prevalence, 5, 15, 20, 82, 95, 127, 142, 150, 264, 274, 369

Prickle, 351, 369 Probe, 28, 61, 70, 90, 93, 97, 102, 144, 246, 362, 369 Profusion, 208, 369 Progeny, 324, 369 Progesterone, 369, 381 Progression, 39, 40, 223, 311, 326, 370 Progressive, 221, 319, 328, 331, 342, 358, 359, 368, 370 Projection, 328, 370 Prokaryote, 212, 370 Proline, 207, 322, 345, 370 Promoter, 64, 80, 204, 243, 252, 253, 370 Prophase, 358, 370, 383 Prophylaxis, 6, 7, 12, 51, 121, 202, 217, 223, 232, 370, 387 Propolis, 154, 155, 157, 158, 165, 169, 370 Prostaglandins, 52, 93, 312, 370 Prosthodontics, 6, 262, 263, 370 Protease, 22, 36, 45, 240, 274, 322, 370 Protease Inhibitors, 274, 370 Protein C, 30, 49, 179, 310, 313, 322, 339, 351, 370, 387 Protein Conformation, 310, 351, 370 Protein Kinases, 25, 102, 370 Protein S, 22, 24, 27, 56, 93, 198, 226, 231, 233, 262, 315, 326, 339, 370, 375, 381, 383 Protein Transport, 22, 370 Proteolytic, 74, 323, 333, 336, 367, 370 Protocol, 28, 371 Proton Pump, 43, 371 Proton Pump Inhibitors, 43, 371 Protons, 309, 344, 354, 371, 372 Protozoa, 265, 324, 356, 371, 380 Protozoan Infections, 265, 319, 371 Proximal, 330, 371 Pruritic, 371, 376 Psoriasis, 135, 358, 371 Psychic, 371, 377 Psychology, 330, 371 Public Health, 29, 51, 52, 245, 288, 292, 371 Public Policy, 287, 371 Publishing, 61, 256, 262, 265, 371 Pulmonary, 216, 228, 271, 315, 320, 325, 334, 351, 352, 371, 382, 388 Pulmonary Artery, 315, 371, 388 Pulse, 108, 357, 371 Purifying, 253, 329, 371 Purines, 314, 372, 377 Purulent, 307, 333, 372, 386, 387 Putrefaction, 338, 372 Pyelonephritis, 265, 372

404 Candida

Pyogenic, 335, 362, 372 Pyruvate Decarboxylase, 218, 372 Q Quality of Life, 10, 28, 37, 372 R Race, 143, 240, 350, 356, 372 Radiation, 53, 68, 77, 137, 210, 222, 267, 307, 332, 335, 337, 338, 346, 349, 350, 372, 389 Radiation therapy, 53, 210, 267, 307, 335, 349, 350, 372, 389 Radioactive, 328, 344, 346, 349, 350, 357, 361, 362, 372, 387, 389 Radioisotope, 362, 372 Radiolabeled, 212, 350, 372, 389 Radiotherapy, 316, 350, 372, 389 Randomized, 37, 51, 108, 126, 142, 332, 372 Randomized clinical trial, 37, 372 Reactivation, 264, 373 Reactive Oxygen Species, 38, 373 Reagent, 320, 326, 373 Receptor, 16, 34, 52, 59, 134, 146, 156, 160, 311, 324, 331, 341, 354, 365, 373, 378 Receptors, Serotonin, 373, 378 Recombinant, 15, 23, 36, 38, 74, 117, 201, 217, 232, 236, 249, 251, 253, 373, 388 Recombination, 42, 86, 242, 252, 324, 373 Rectal, 265, 373 Rectum, 312, 316, 330, 337, 338, 347, 351, 373, 382 Recurrence, 37, 373 Red blood cells, 334, 363, 373, 379 Reductase, 67, 92, 176, 224, 234, 248, 249, 373 Refer, 1, 316, 323, 337, 343, 353, 359, 360, 361, 373 Reference Standards, 28, 373 Reflux, 267, 338, 339, 373 Refraction, 373, 380 Refractory, 140, 373, 386 Refusal to Treat, 270, 373 Regeneration, 243, 373 Regimen, 263, 332, 373 Regurgitation, 338, 342, 373 Relapse, 146, 374 Reliability, 29, 246, 374 Remission, 373, 374 Reperfusion, 34, 359, 374 Reperfusion Injury, 34, 374 Reproduction Techniques, 369, 374 Respiration, 38, 67, 99, 218, 229, 318, 357, 374

Respiratory Burst, 34, 374 Restoration, 34, 49, 244, 326, 359, 370, 373, 374, 389 Retina, 151, 321, 327, 374, 375 Retinal, 146, 324, 327, 374 Retinitis, 327, 374 Retinopathy, 111, 143, 374 Retrospective, 31, 100, 375 Retrotransposons, 150, 375 Retrovirus, 47, 375 Reversion, 375, 386 Rheology, 252, 375 Rheumatoid, 360, 363, 375 Rheumatoid arthritis, 360, 375 Riboflavin, 251, 375 Ribonuclease, 23, 375 Ribonucleic acid, 247, 375 Ribosome, 375, 385 Rigidity, 367, 375 Risk factor, 5, 30, 46, 52, 142, 146, 203, 223, 274, 277, 292, 375 Ristocetin, 375, 387 Rod, 229, 313, 334, 335, 351, 375, 376, 378 Rodenticides, 366, 375 Rubber, 103, 178, 307, 375 Rubulavirus, 358, 375 S Saccharomycetales, 376 Saline, 206, 376 Saliva, 16, 30, 38, 44, 99, 110, 113, 119, 149, 376 Salivary, 37, 44, 53, 67, 81, 83, 103, 113, 116, 125, 129, 133, 143, 255, 327, 328, 330, 336, 376, 382, 389 Salivary glands, 327, 328, 330, 336, 376 Salivary Proteins, 37, 376 Salmonella, 212, 240, 242, 265, 270, 338, 364, 376 Salmonella typhi, 212, 376 Salmonella typhimurium, 212, 376 Saponin, 8, 176, 211, 376 Sarcoid, 266, 376 Sarcoidosis, 376 Sarcoma, 256, 271, 294, 295, 376 Saturated fat, 363, 376 Scabies, 293, 376 Schizoid, 376, 389 Schizophrenia, 376, 377, 389 Schizotypal Personality Disorder, 376, 389 Sclera, 321, 324, 377 Sclerotic, 61, 377 Sebaceous, 350, 377, 389

Index 405

Sebaceous gland, 350, 377, 389 Secretion, 22, 23, 47, 325, 340, 343, 344, 348, 349, 357, 358, 377 Secretory, 22, 25, 76, 86, 309, 377 Secretory Vesicles, 22, 377 Segmental, 21, 377 Segmentation, 377 Segregation, 313, 321, 373, 377 Seizures, 236, 364, 377 Self Care, 260, 293, 377 Semisynthetic, 85, 94, 377 Sensor, 60, 236, 377 Sepsis, 134, 137, 143, 221, 337, 377 Septic, 114, 134, 377 Septicemia, 118, 149, 245, 377 Sequence Analysis, 106, 121, 377 Sequence Homology, 250, 365, 377 Sequencing, 10, 21, 26, 27, 53, 70, 101, 377 Serine, 155, 158, 231, 249, 333, 377, 386 Serotonin, 110, 373, 378, 386 Serous, 333, 378 Serratia, 378 Sertraline, 131, 378 Serum, 32, 49, 86, 98, 102, 110, 166, 178, 214, 310, 323, 345, 366, 378, 386 Sexual Partners, 293, 378 Sexually Transmitted Diseases, 181, 292, 294, 378 Shedding, 30, 378 Shivering, 234, 378 Shock, 129, 170, 235, 378, 385 Sialyltransferases, 341, 378 Side effect, 234, 255, 270, 277, 279, 281, 308, 378, 384 Signal Transduction, 18, 33, 43, 236, 317, 378 Signs and Symptoms, 293, 374, 378 Silver Compounds, 241, 379 Sinusitis, 265, 379 Skeleton, 307, 350, 351, 379 Skull, 325, 379, 383 Sludge, 205, 379 Small intestine, 344, 349, 379, 386 Smear Layer, 108, 379 Sneezing, 366, 378, 379 Soaps, 277, 295, 379, 386 Social Environment, 372, 379 Social Work, 270, 379 Sodium, 139, 155, 159, 379 Soft tissue, 316, 328, 379 Solid tumor, 203, 379

Solvent, 11, 24, 215, 217, 218, 335, 355, 356, 362, 379 Somatic, 344, 355, 356, 379, 383 Sorbitol, 354, 379 Spasmodic, 366, 380 Specialist, 297, 380 Specificity, 13, 28, 29, 45, 60, 83, 108, 154, 158, 214, 246, 247, 250, 308, 333, 380 Spectrum, 23, 25, 34, 201, 213, 221, 228, 322, 351, 380 Sperm, 147, 321, 380 Spices, 317, 380 Spinal cord, 236, 319, 321, 331, 333, 355, 360, 363, 365, 380 Spinous, 334, 351, 380 Spirochete, 380, 383 Spleen, 209, 226, 327, 353, 376, 380 Spontaneous Abortion, 369, 380 Spores, 226, 322, 348, 380 Sporotrichosis, 263, 380 Squamous, 30, 238, 380 Stabilization, 27, 380 Staphylococcus, 135, 198, 213, 227, 229, 238, 241, 242, 244, 338, 380 Staphylococcus aureus, 213, 227, 241, 242, 244, 338, 380 Statistically significant, 6, 380 Stem Cells, 309, 381 Steroid, 43, 170, 270, 293, 351, 381 Steroid therapy, 293, 381 Stillbirth, 369, 381 Stimulants, 340, 381 Stimulus, 237, 331, 348, 381 Stomach, 307, 330, 335, 338, 339, 344, 353, 359, 365, 366, 371, 373, 379, 380, 381 Stomatitis, 14, 16, 34, 110, 116, 118, 145, 263, 381 Stool, 347, 351, 381 Strand, 252, 368, 381 Streptococcal, 264, 381 Streptococci, 263, 381 Streptococcus, 44, 103, 143, 178, 200, 212, 213, 236, 238, 242, 381 Streptomycin, 326, 381 Stress, 18, 24, 32, 43, 60, 61, 66, 103, 170, 252, 264, 338, 359, 363, 375, 381 Stroke, 195, 286, 381 Stroma, 364, 381 Structure-Activity Relationship, 20, 381 Styrene, 375, 382 Subacute, 347, 379, 382 Subarachnoid, 342, 382

406 Candida

Subclinical, 347, 377, 382 Subcutaneous, 331, 364, 380, 382 Submandibular, 37, 382 Subspecies, 380, 382 Substance P, 355, 375, 377, 381, 382 Substrate, 11, 15, 55, 154, 158, 212, 231, 318, 327, 357, 382 Suction, 120, 336, 382 Sulfates, 200, 382 Sulfur, 119, 355, 382 Sulfur Compounds, 119, 382 Sulfuric acid, 382 Superior vena cava, 134, 316, 382 Superoxide, 116, 374, 382 Superoxide Dismutase, 116, 382 Supplementation, 86, 168, 382 Suppositories, 245, 339, 382 Suppression, 4, 325, 339, 382 Surfactant, 205, 320, 382 Surgical Wound Infection, 264, 383 Symphysis, 320, 383 Symptomatic, 20, 383 Synaptic, 378, 383 Synergistic, 43, 103, 207, 245, 274, 383 Syphilis, 292, 293, 294, 383 Systemic disease, 43, 221, 377, 383 Systemic therapy, 383 T Tachycardia, 313, 383 Tachypnea, 313, 383 Talc, 245, 383 Tea Tree Oil, 156, 159, 172, 174, 185, 383 Tear Gases, 350, 383 Telomerase, 220, 383 Telomere, 221, 383 Temporal, 40, 342, 383 Terminator, 204, 243, 253, 322, 383 Testosterone, 373, 383 Tetracycline, 172, 187, 266, 383 Therapeutics, 280, 383 Thermal, 330, 360, 383 Thigh, 342, 383 Thorax, 307, 382, 384 Threonine, 155, 158, 207, 231, 365, 377, 384 Thrombin, 336, 368, 370, 384 Thrombocytes, 368, 384 Thrombomodulin, 370, 384 Thrombophlebitis, 221, 247, 384 Thrombosis, 348, 370, 381, 384 Thromboxanes, 312, 384 Thrombus, 134, 325, 347, 359, 368, 384 Thymus, 34, 187, 345, 353, 384

Thyroid, 260, 384, 386 Thyroxine, 366, 384 Tinnitus, 363, 384 Tissue, 10, 14, 16, 38, 41, 50, 54, 60, 73, 74, 156, 159, 221, 238, 247, 266, 274, 307, 308, 309, 311, 312, 314, 315, 316, 317, 320, 322, 324, 328, 331, 332, 333, 334, 336, 338, 339, 341, 343, 344, 345, 349, 352, 353, 354, 355, 358, 359, 360, 362, 364, 365, 367, 368, 373, 374, 378, 379, 381, 382, 384, 385, 389 Tolerance, 105, 308, 340, 384 Toxicity, 8, 20, 25, 39, 44, 45, 100, 220, 331, 355, 361, 375, 384 Toxicology, 23, 207, 249, 288, 384 Toxins, 36, 39, 75, 311, 315, 347, 377, 385 Toxoplasmosis, 270, 271, 385 Trace element, 321, 360, 385 Transcriptase, 220, 375, 383, 385 Transcription Factors, 25, 221, 385 Transduction, 33, 102, 237, 378, 385 Transfection, 32, 315, 332, 385 Transfer Factor, 345, 385 Transferases, 341, 385 Translation, 55, 253, 385 Translational, 51, 240, 339, 385 Translocation, 8, 30, 168, 212, 370, 385 Transplantation, 43, 44, 142, 332, 345, 385 Transurethral, 338, 385 Transurethral resection of the prostate, 338, 385 Trauma, 17, 242, 277, 335, 359, 385, 389 Treatment Failure, 14, 385 Treatment Outcome, 21, 385 Trees, 375, 385 Trichomonas, 28, 124, 150, 293, 385, 386 Trichomonas vaginalis, 28, 124, 293, 386 Trichomonas Vaginitis, 28, 386 Trichophyton, 199, 207, 237, 267, 386 Triclosan, 4, 386 Tricuspid Valve, 110, 386 Trivalent, 241, 386 Tropism, 14, 16, 386 Trypsin, 179, 333, 386 Tryptophan, 201, 322, 378, 386 Tuberculosis, 264, 265, 268, 271, 294, 358, 386 Tumor Necrosis Factor, 148, 386 TYPHI, 386 Typhimurium, 386 Typhoid fever, 364, 376, 386

Index 407

Tyrosine, 66, 155, 159, 165, 169, 201, 231, 330, 386 U Ubiquinone, 155, 158, 201, 386 Ubiquitin, 240, 386 Ulcer, 386 Ulceration, 209, 226, 386 Ulcerative colitis, 265, 347, 386 Umbilical Cord, 321, 386 Unconscious, 328, 345, 387 Uracil, 247, 387 Uranium, 220, 387 Urea, 362, 387 Ureters, 351, 387 Urethra, 365, 385, 387 Urethritis, 294, 387 Urinary, 7, 28, 57, 69, 106, 123, 244, 313, 327, 338, 339, 347, 362, 387 Urinary tract, 28, 57, 123, 244, 313, 338, 387 Urinary tract infection, 28, 57, 123, 244, 313, 387 Urine, 7, 28, 58, 150, 313, 315, 317, 322, 326, 330, 347, 351, 362, 363, 375, 387 Urogenital, 8, 202, 244, 339, 341, 387 Urokinase, 227, 387 Uterus, 319, 320, 325, 333, 355, 369, 387 Uvea, 333, 387 V Vaccination, 41, 137, 245, 387 Vaccine, 13, 15, 32, 36, 41, 46, 49, 87, 137, 216, 232, 236, 244, 308, 371, 387 Vagina, 52, 267, 293, 295, 296, 317, 320, 329, 351, 355, 386, 387, 389 Vaginal Discharge, 386, 387 Vaginal Smears, 124, 387 Vaginitis, 28, 80, 91, 123, 151, 181, 209, 225, 244, 275, 293, 294, 296, 317, 387 Vaginosis, 28, 52, 244, 294, 338, 387 Vancomycin, 244, 387 Vascular, 15, 155, 159, 169, 321, 333, 342, 347, 360, 367, 384, 388 Vasculitis, 311, 388 Vasodilators, 361, 388 Vector, 18, 50, 56, 204, 210, 235, 243, 252, 385, 388 Vegetative, 24, 315, 388 Vein, 350, 361, 364, 382, 384, 386, 388 Vena, 388

Venereal, 294, 383, 388 Venous, 203, 370, 388 Ventricle, 325, 371, 386, 388 Venules, 316, 317, 333, 388 Vertebrae, 380, 388 Vertebral, 110, 388 Vertigo, 363, 388 Vesicular, 343, 370, 388 Veterinary Medicine, 287, 388 Vibrio, 36, 242, 320, 388 Vibrio cholerae, 36, 320, 388 Viral, 30, 36, 47, 55, 236, 238, 256, 264, 265, 341, 348, 362, 375, 385, 388, 389 Virulent, 17, 20, 60, 176, 225, 250, 274, 388 Viscosity, 375, 388 Vitro, 4, 7, 8, 9, 11, 14, 16, 17, 19, 22, 25, 31, 35, 41, 43, 47, 50, 58, 59, 60, 64, 65, 68, 70, 76, 82, 84, 85, 86, 87, 96, 110, 112, 113, 119, 121, 127, 128, 129, 130, 131, 145, 149, 155, 156, 158, 159, 166, 167, 169, 172, 174, 177, 178, 203, 214, 233, 244, 332, 347, 375, 388 Vivo, 4, 6, 8, 9, 11, 14, 16, 17, 19, 26, 27, 31, 35, 38, 42, 43, 50, 59, 60, 70, 79, 84, 85, 96, 145, 164, 177, 203, 347, 363, 384, 389 Voriconazole, 62, 63, 78, 79, 81, 85, 87, 109, 120, 121, 131, 149, 152, 275, 389 Vulgaris, 187, 389 Vulva, 293, 389 Vulvovaginitis, 152, 265, 293, 295, 389 W Warts, 130, 148, 237, 238, 293, 294, 344, 389 White blood cell, 311, 352, 353, 354, 357, 358, 359, 360, 367, 389 Whooping Cough, 366, 389 Withdrawal, 207, 389 Wound Healing, 348, 389 Wound Infection, 113, 389 X Xenograft, 311, 389 Xerostomia, 255, 277, 389 X-ray, 11, 24, 46, 337, 338, 350, 361, 372, 389 X-ray therapy, 350, 389 Xylulose, 204, 389 Z Zygote, 323, 324, 389 Zymogen, 370, 389

408 Candida