CANDIDA ALBICANS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1 Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Candida Albicans: 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: 0-597-84364-3 1. Candida Albicans-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.
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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 albicans. 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 ALBICANS ................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Candida Albicans .......................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 58 The National Library of Medicine: PubMed ................................................................................ 96 CHAPTER 2. NUTRITION AND CANDIDA ALBICANS .................................................................... 143 Overview.................................................................................................................................... 143 Finding Nutrition Studies on Candida Albicans....................................................................... 143 Federal Resources on Nutrition ................................................................................................. 146 Additional Web Resources ......................................................................................................... 146 CHAPTER 3. ALTERNATIVE MEDICINE AND CANDIDA ALBICANS .............................................. 149 Overview.................................................................................................................................... 149 National Center for Complementary and Alternative Medicine................................................ 149 Additional Web Resources ......................................................................................................... 163 General References ..................................................................................................................... 167 CHAPTER 4. DISSERTATIONS ON CANDIDA ALBICANS ................................................................ 169 Overview.................................................................................................................................... 169 Dissertations on Candida Albicans............................................................................................ 169 Keeping Current ........................................................................................................................ 169 CHAPTER 5. PATENTS ON CANDIDA ALBICANS ........................................................................... 171 Overview.................................................................................................................................... 171 Patents on Candida Albicans ..................................................................................................... 171 Patent Applications on Candida Albicans ................................................................................. 196 Keeping Current ........................................................................................................................ 211 CHAPTER 6. BOOKS ON CANDIDA ALBICANS............................................................................... 213 Overview.................................................................................................................................... 213 Book Summaries: Federal Agencies............................................................................................ 213 Book Summaries: Online Booksellers......................................................................................... 214 Chapters on Candida Albicans................................................................................................... 215 CHAPTER 7. MULTIMEDIA ON CANDIDA ALBICANS .................................................................... 219 Overview.................................................................................................................................... 219 Audio Recordings....................................................................................................................... 219 CHAPTER 8. PERIODICALS AND NEWS ON CANDIDA ALBICANS ................................................. 221 Overview.................................................................................................................................... 221 News Services and Press Releases.............................................................................................. 221 Newsletter Articles .................................................................................................................... 223 Academic Periodicals covering Candida Albicans ..................................................................... 223 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 227 Overview.................................................................................................................................... 227 NIH Guidelines.......................................................................................................................... 227 NIH Databases........................................................................................................................... 229 Other Commercial Databases..................................................................................................... 231 APPENDIX B. PATIENT RESOURCES ............................................................................................... 233 Overview.................................................................................................................................... 233 Patient Guideline Sources.......................................................................................................... 233 Finding Associations.................................................................................................................. 235 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 237 Overview.................................................................................................................................... 237 Preparation................................................................................................................................. 237
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Finding a Local Medical Library................................................................................................ 237 Medical Libraries in the U.S. and Canada ................................................................................. 237 ONLINE GLOSSARIES................................................................................................................ 243 Online Dictionary Directories ................................................................................................... 243 CANDIDA ALBICANS DICTIONARY .................................................................................... 245 INDEX .............................................................................................................................................. 315
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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 albicans 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 albicans, 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 albicans, 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 albicans. 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 albicans, 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 albicans. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON CANDIDA ALBICANS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Candida albicans.
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 albicans, 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 albicans” (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: •
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
4
Candida Albicans
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.
Federally Funded Research on Candida Albicans The U.S. Government supports a variety of research studies relating to Candida albicans. 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 albicans. 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 albicans. The following is typical of the type of information found when searching the CRISP database for Candida albicans: •
Project Title: A MODEL OF MORPHOLOGIC SWITCHING IN CANDIDA ALBICANS Principal Investigator & Institution: Gale, Cheryl A.; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: Dr. Cheryl A. Gale is a neonatologist at the University of Minnesota. The candidate's long-term goal is to pursue an academic career devoted primarily to basic research. During Dr. Gale's pediatric residency and neonatal fellowship training, she was exposed to the high morbidity and mortality associated with systemic candidiasis in her premature patients on the neonatal intensive care unit. This experience solidified Dr. Gale's interest in understanding fungal pathogenesis as a means toward developing more effective therapies. The proposed application will provide the candidate the additional training necessary to be competitive for independent funding. The rich academic and research environment at the University of Minnesota is extremely well suited for the candidate's career development. Under the direct mentorship of Dr. Judith Berman, Dr. Gale will study the molecular mechanism of morphologic switching in C. albicans. She will focus on characterizing in vivo the localization of cytoskeletal-
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
associated proteins during morphologic switching and determining the role of cell cycle checkpoints during morphogenesis. Morphologic switching is postulated to contribute to the success of C. albicans as a pathogen because it gives the fungus versatility in the face of changing environments. Dr. Gale previously found that the C. albicans gene INT1 encodes a protein that is important for the morphologic switch from yeast-form to filamentous-form. Expression of INT1 in the usually non- pathogepic yeast, S. cerevisiae, results in the formation of extremely elongated buds that appear similar to C. albicans germ tubes. Her more recent characterization of these elongated buds in S. cerevisiae has shown that Int1p expression causes a novel localization of cytoskeletal-associated proteins (septins) that mimics that of Int1p itself. She also found that INT1 expression results in a delay in the nuclear cell cycle partially due to the activation of the morphogenesis checkpoint protein, Swe1p. The Specific Aims of this proposal will build on these preliminary results to directly determine, in C. albicans, the role of Int1p, septins, and cell cycle checkpoints in morphologic switching. Dr. Gale will develop a technique of genomic epitope tagging in C. albicans that will allow in vivo localization of Int1p and septins in C. albicans during the cell cycle and during morphologic switching in both wild-type and mutant C. albicans morphologic strains (Specific Aims 1 and 2). The candidate will disrupt the C. albicans SWE1 homolog and study the effect of such a mutation on the viability and ability of the strain to undergo morphologic switching (Specific Aim 3). These studies will allow Dr. Gale to determine the how Int1p, septins and cell cycle control proteins are related in the process of morphologic switching and may identify new therapeutic targets for anti- fungal agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 941222747 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 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
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Candida Albicans
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 hyperexpression 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 hyper-expression of Cdrlp to screen a unique combinatorial Doctapeptide library for peptides that inhibit the pump. This work will validate a novel approach to combating azole-resistance in C. albicana An understanding of drug pumping mechanisms may indicate 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
Studies
7
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 •
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 2002; 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 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
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Candida Albicans
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 Ralph.; 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
•
Project Title: BIOFILMS
ANTIMICROBIAL
RESISTANCE
IN
CANDIDA
ALBICANS
Principal Investigator & Institution: Tyler, Bonnie J.; Associate Chemical/Fuels Engineering; University of Utah Salt Lake City, Ut 84102
Professor;
Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 30-JUN-2004 Summary: Oral candidias is a biofilm based fungal infection that can have severe implications particularly in the growing population of immunocompromised patients. Despite their clincal importance, very little research has been done on fungal biofillms including candida. Few if any studies involving in situ analysis of C. albincans biofilms have been published. One ex situ study has shown that Candida biofilms, like those of bacteria, are resistant to antimicrobial agents. Although a variety of mechanisms have been proposed to explain the recalcitrance of bacterial biofilms to antibiotics, the mechanisms by which Candida biofilms resist the action of antifungal agents are unknown. The goal of this proposed research is to delineate the relationship between the structure of C. albicans biofilms and their resistance to antimicrobial agents. In this
Studies
9
study a combination of in situ methods will be used to quantitatively investigate the structure of C. albicans biofilms. These methods will include Attenuated Total Reflectance Infrared Spectroscopy (ATR/FTIR), Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), electrochemical microsensors, fluorescent microscopy and scanning laser confocal microscopy. The influence of a variety of environmental factors including fluid shear, growth media, serum and saliva proteins and substratum chemistry on the biofilm structure will be investigated. These factors will then be used to manipulate the biofilm structure in order to determine the influence of structural features on the antifungal resistance of the biofilms. The efficacy of three antimicrobial agents, hydrogen peroxide, chlorhexidine gluconate, and fluconazole, against both biofilms and planktonic C. albicans will be measured. In addition, penetration of these agents into the biofilm will be measured with a combination of ATR/FTIR, ToF-SIMS imaging of cryosections, and microelectrodes. Multivariate statistical modeling will be used to identify relationships between the biofilm structure and antimicrobial resistance. Mechanistic differential equation based models will be used to identify possible causal relationships between biofilm structure and antifungal efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 2002; 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
•
Project Title: BIOLOGY AND DRUG RESISTANCE OF CANDIDA BIOFILMS Principal Investigator & Institution: Ghannoum, Mahmoud A.; Professor and Center Director; 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
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Candida Albicans
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 •
Project Title: C. ALBICANS FROM HIV+ INDIVIDUALS&ITS ROLE IN DRUG RESIS Principal Investigator & Institution: Vargas, Kaaren G.; Dows Inst for Dental Research; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (provided by applicant) As a recent graduate from a PhD program and newly appointed assistant professor at The University of Iowa, I feel that I would benefit significantly from the Faculty Transition portion of the K22. In conjunction with the completion of the research proposed, the PI will receive training in the ethics of biomedical research. The research project itself will receive guidance from a number of very experienced researchers. Drs. Michael Pfaller, Christopher Squier, Georgia Johnson, Philip Wertz and David Soll. The research experience that is outlined in this proposal will enable me to develop into an independent investigator and contributor to the advancement of science. I will receive extensive support from my advisors and the College of Dentistry. Research facilities are available for my use and courses are offered that will enable me to conduct research in a responsible manner. The. experimental portion sets out to answer the following questions: 1. What is the antifungal susceptibility of C. albicans switch phenotypes isolated from HIV-positive individuals? 2. Are there differences in uptake of antifungals among different switch phenotypes or differences in ergosterol content in the presence of antifungals and are there differences in expression of known multi-drug resistance genes (MDR1, CDR1 and ERG11) among the different switch phenotypes? and 3. Are different switch phenotypes better able to survive under in vivo conditions of antifungal drug therapy for candidiasis? For this, a collection of samples from HIV+ and HIV- individuals previously collected by the PI and Dr. Michael Pfaller will be used. From these studies we hope to increase our understanding of the role that phenotypic switching plays in antifungal drug resistance, which is an increasing problem in severely immunosuppressed individuals. This increased knowledge could lead to improvements in treatment of oral candidiasis in all immunocompromised individuals. In the long-term, I would like to make significant contributions to science in the area of antifungal drug resistance. It is an exciting area of research and I feel strongly that I have the motivation to accomplish this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPITHELIA
C.ALBICANS
REGULATION
BETA-DEFENSINS
IN
11
ORAL
Principal Investigator & Institution: Weinberg, Aaron; Associate Professor; Periodontics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 28-SEP-2000; Project End 31-JUL-2004 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 betadefensin 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 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 2002; 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
12
Candida Albicans
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 •
Project Title: CANDIDA INVASION OF ENDOTHELIUM AND VIRULENCE Principal Investigator & Institution: Filler, Scott G.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2004; Project Start 20-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The incidence of bloodstream infections caused by Candida species has increased dramatically; these organisms now account for 10% of all bloodstream isolates. The mortality associated with candidemia approaches 40%, even with therapy. Because of this unacceptably high mortality, new strategies to treat and prevent this infection are necessary. Our goal is to identify new Candida albicans virulence genes and to determine the mechanisms by which they contribute to pathogenicity. This information holds promise to identify new targets for antifungal strategies. Our hypothesis is that the ability of C. albicans to invade and damage host cells is critical for the organism to establish and maintain a deep-seated infection. Support for this hypothesis comes from our finding that many C. albicans mutants with decreased virulence in the mouse model of hematogenously disseminated infection also have reduced ability to invade and damage endothelial cells in vitro. Furthermore, we have screened a collection of random C. albicans homozygous insertion mutants to identify strains with impaired capacity to damage endothelial cells in vitro. We discovered that zed1/zed1 and cka2/cka2 insertion mutants caused much less endothelial cell damage than did the isogenic control strain. Also, the zed1/zed1 insertion mutant had significantly attenuated virulence in mice (the virulence of the cka2/cka2 strain has not yet been tested). These results strongly suggest that C. albicans genes required for in vitro endothelial cell damage are also required for virulence. Our objective is to use in vitro studies of the interactions between C. albicans and endothelial cells to define mechanisms of host-pathogen interaction. In this project, we will 1) identify the endothelial cell receptors that C. albicans uses to invade this host cell; 2) determine the mechanisms by which C. albicans Zed1p, Cka2p, and other newly identified gene products contribute to virulence; 3) use defined C. albicans mutants to elucidate functional relationships among C. albicans virulence regulators, endothelial cell receptors, and endothelial cell damage; and 4) use a random insertional mutagenesis
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approach to identify new C. albicans genes that promote endothelial cell damage in vitro and virulence. 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 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
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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 2002; 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
14
Candida Albicans
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 •
Project Title: CONTROL OF BIOFILMS BY NATURAL PRODUCTS Principal Investigator & Institution: Costerton, John William.; Professor & Director; Sequoia Sciences 11199 Sorrento Valley Rd, Ste H San Diego, Ca 92121 Timing: Fiscal Year 2003; Project Start 01-APR-2001; Project End 31-JAN-2005 Summary: (provided by applicant): Chronic bacterial infections are serious medical problems in the United States. In chronic bacterial infections, biofilms protect bacteria from antibiotics and immune response mechanisms, thus increasing the rates of reoccurring symptoms and resistance to antibiotics. We discovered four novel compounds in Phase I under this STTR project that prevent the formation and disrupt biofilms, and we expect to identify additional novel compounds in Phase II. We propose to use the strategies developed in Phase I to prioritize the other active samples that have been identified. We will elucidate the structures of the active compounds and characterize their biological activity as biofilm inhibitors or antibacterials. We will also continue the discovery process for additional active samples. This work will enable us to commercialize these compounds that regulate biofilms and to further optimize or methods and strategies by which to discover more novel compounds that regulate formation of biofilms that are needed for a wide range of applications. In the United States, the market for microbial biofilm inhibitors is contained within the $8.5 billion market for antibiotics. Biofilms are involved in 65% of human bacterial infections; accordingly, biofilm inhibitors could capture a $4 to $6-billion segment of the antibiotic market. Biofilm inhibitors will have the greatest medical impact by treating many chronic infections, reducing catheter- and medical device-related infections, and in treating cystic fibrosis patients. Research has clearly established that biofilms play a significant role in these areas, representing a large market whose needs are unmet. The potential market penetration for potent biofilm inhibitors is exemplified by the sheer number of cases in which biofilms cause medical problems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DENDRITIC CELL DEFENSIN AND TYPE I IFN RESPONSES IN HIV Principal Investigator & Institution: Pope, Melissa J.; Scientist; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The dendritic cell (DC) system, comprising the myeloid (MDC) and plasmacytoid (PDC) subsets, orchestrates innate and adaptive immunity to pathogens. DCs are located within the epithelial tissues (Langerharis cells, LCs) and in the underlying lymphoid follicles (PDCs and MDCs) that line the oral cavity. Therefore, DCs are in prime positions to encounter oral pathogens and may play an important role in sustaining a healthy oral mucosa. Increasing evidence highlights how DCs both produce and respond to innate factors such as type I IFNs and defensins that possibly provide important barriers against HIV infection as well as in controlling commensal organisms in the oral cavity. We hypothesize that unlike HIV, organisms like herpes simplex virus (HSV) or Candida albicans will trigger strong innate type I IFN and defensin responses in DCs that contribute to the resistance of the oral mucosa to HIV infection as well as controlling HSV and Candida infections in healthy people. However, prior exposure to HIV will impede these innate DC responses rendering individuals more susceptible to HSV infection and reactivation as well as candidiasis. Three major questions will be addressed to investigate this. 1. Are defensin responses in LCs induced by HIV and organisms present in the oral cavity? 2. What are the innate type I IFN and defensin responses of PDCs and MDCs to HIV and oral pathogens? 3. Do epithelial cells and keratinocytes influence the innate responses of DCs to HIV and oral pathogens? By investigating these issues we will reveal the innate responses of distinct DC subsets that are found in the tissues of the oral cavity to HIV and related copathogens, how these responses are influenced by cell-cell (DCs, epithelial cells, and keratinocytes) contact, and whether prior exposure to one organism alters a DCs' response to another. The involvement of specific receptors (toll like receptors, TLRs and C-type lectin receptors, CLRs) will be examined to elucidate their role in capture of a pathogen vs signaling of cellular responses. These extensive in vitro studies will uncover pertinent information about the innate responses of DCs to various infections and how these contribute to a healthy oral environment that is perturbed in HIV infected individuals. This will afford critical insight as to how such responses could be boosted to prevent opportunistic infections and also identify potential targets for the development of strategies to prevent HIV transmission across the oral and other mucosal surfaces. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DETERMINANTS IN PLATELET MICROBICIDAL PROTEINS Principal Investigator & Institution: Yeaman, Michael R.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the Applicant's Abstract): Human and rabbit platelets contain platelet microbicidal proteins (PMPs). The investigators' data show that PMPs play key roles in platelet antimicrobial functions. PMPs exert potent microbicidal actions against antibiotic-resistant bloodstream pathogens, including Staphylococcus aureus and Candida albicans. Specific PMPs are released from platelets exposed to pathogens or agonists at sites of endovascular infection, and intensify locally at these sites. PMPsusceptible pathogens are less virulent in animal models than their isogenic PMPresistant counterparts. These compelling facts support their hypothesis that PMPs
16
Candida Albicans
significantly contribute to antimicrobial host defense. PMPs are minimally toxic to human vascular endothelial cells or erythrocytes, and differ markedly in structure and mechanism from antimicrobial peptides that are not released into the bloodstream. These facts suggest PMPs have key functional determinants that optimize microbicidal activity without concomitant host cytotoxicity. Beyond its microbicidal effects, they have discovered that PMP-2 also potentiates neutrophil chemotaxis, phagocytosis and intracellular killing of S. aureus. PMP-2 has a cystine-X-cystine (CXC) motif distinctive of alpha-chemokines such as human platelet factor-4 (hPF-4) that amplify antimicrobial mechanisms of neutrophils. These facts indicate that PMP-2 is a unique molecule that exerts both direct microbicidal and neutrophil-potentiating effects. The investigators' central hypothesis contends that PMP-2 has specific determinants responsible for these distinct host defense functions. They further hypothesize these determinants can be defined, modeled, and used to establish key structure-activity relationships (SARs) governing specific functions. The proposed studies are designed to explore these hypotheses. Defining SARs in PMP-2 functional determinants is crucial to their eventual goal of designing anti-infective agents with potent and/or selective activity against antibiotic-resistant pathogens. Therefore, their Specific Aims are: i) to define the structural determinants responsible for direct microbicidal functions of PMP-2; ii) define the PMP-2 structural determinants that potentiate the antimicrobial functions of neutrophils; and iii) establish the key SARs in antimicrobial determinants of PMP-2. Comparison of PMP-2 and hPF-4 determinants responsible for their potent and/or discriminative antimicrobial functions will enable future studies of human PMPs in the rabbit model that cannot be conducted in humans. Moreover, SAR themes discovered in PMP-2 will accelerate discovery of novel anti-infective strategies against pathogens resistant to conventional agents. Thus, these studies will significantly advance our understanding of antimicrobial host defense, and may yield new modes for its amplification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF ANTIFUNGALS OF CLINICAL IMPORTANCE Principal Investigator & Institution: Judd, Amrit K.; President; Synvax 969-C Industrial Rd San Carlos, Ca 94070 Timing: Fiscal Year 2004; Project Start 15-FEB-2004; Project End 31-JAN-2005 Summary: (provided by applicant): Fungal infections have increased dramatically in recent years to become important causes of mortality in hospitalized patients. The increase in life-threatening fungal infections has brought about an increased use of antifungal drugs and a pressing need for new, broad-spectrum, fungicidal agents that can be used empirically in immunocompromised patients e.g., AIDS and organ transplant patients. There is still a treatment failure of more than 50% among patients with acute invasive aspergillosis, and a 20 to 30% failures with candidemia. Current available therapies for treating fungal infections often suffer from drug-related toxicity, hazardous drug-drug interactions, non-optimal pharmacokinetics, and development of drug resistance. Preliminary studies have shown that several peptides from our chemical library have antifungal activity against Rhodotorula pilimanae, a nonpathogenic fungus. Three of the compounds tested so far showed activity against Candida albicans. These peptides are found to be nontoxic in several human and monkey cell lines and therefore show promise for further pursuing. It is proposed to conduct antifungal activity studies on all the peptides against Candida, Aspergillus, and Cryptococcus, the fungi of clinical importance. The specific aims of Phase I studies are (a) resynthesize all the compounds, (b) evaluate compounds for antifungal activity
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17
against Candida, Aspergillus, and Cryptococcus, (c) determine minimum inhibitory concentrations and minimum fungicidal concentrations, and (d) conduct in vivo experiment on the most promising compound against Candida, Aspergillus, and Cryptococcus. These experiments will include inhibition of colony forming incidences and survival of mice. Based on the data obtained in Phase I studies, Phase II studies will focus on designing metabolically stable analogs for oral activity using computer-based molecular modeling, developing pharmacologically-based and physiologic-based appropriate administration strategies, conduct extensive in vivo studies, determine the mechanism of action; conduct toxicology and pharmacokinetic studies, and file IND. The data generated by these studies will provide important information to raise this technology to a level of maturity where it can compete successfully for commercial funding to bring a new class of antifungal drugs to clinical use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 2002; Project Start 01-FEB-1991; Project End 31-JAN-2004 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 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
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Candida Albicans
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 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 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 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
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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
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Timing: Fiscal Year 2002; 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 2002; 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 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
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Candida Albicans
(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.; Associate Professor; Dows Inst for Dental Research; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-MAY-2004 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 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
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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 113 Bowne Hall Syracuse, Ny 13244 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, 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
22
Candida Albicans
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 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
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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 ANALYSIS OF PLEIOTROPIC DRUG RESISTANCE Principal Investigator & Institution: Moye-Rowley, W Scott.; Associate Professor; Physiology and Biophysics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 30-NOV-2002 Summary: Description (Adapted from the abstract). Multiple drug resistance refers to the acquisition of broad range of resistance phenotypes through genetic changes at a small number of loci. Multidrug resistance is a clinical problem in chemotherapeutic treatment of tumors and infectious disease. The applicant is studying pleiotropic drug resistance (Pdr) in Saccharomyces cerevisiae as a model of eukaryotic multiple drug resistance. Previous work has demonstrated tha the zinc finger transcription factor Pdr1p is a major contributor to the ability of cells to tolerate a range of otherwise toxic compounds. Pdr1p carries this function through transcriptional activation of several ATP binding cassette transporter encoding genes like PDR5 and YOR1. A gene that encodes a Hsp70 homolog was recently cloned that regulates the activity of Pdr1p. This Hsp70 homologue (Pdr13p) can up-regulate Pdr1p function and thereby increase expression of Pdr1p target genes and associated drug resistance. The goal of this proposal is to understand the molecular details behind Pdr13p modulation of Pdr1p activity. Antisera has been prepared against both Pdr13p and Pdr1p. The plan is use this sera to localize these factors within the cell to determine if these proteins are likely to directly interact. Along with its effect on Pdr1p, Pdr13p has other protein targets. These other target proteins will be identified using two hybrid sand co-immunoprecipitation approaches. An important functional domain in a Hsp70 protein is its ATPase domain. It is proposed to explore the role of Pdr13p-dependent ATPas activity in its biological function through construction and assay of mutations that are predicted ot lack this enzymatic function. The regions(s) of Pdr1p that are required to receive the positive regulatory signal from Pdr13p will be mapped by deletion mutagenesis of the Pdr1p coding sequence. The finding that the function of a Hsp70 protein is required for normal drug resistance has provided a unique opportunity to analyze the action of an eukaryotic Hsp70 in a genetically tractable organism. Additionally, continue progress in understanding the control of Pdr in S. cerevisiae will provide and important basic model for multidrug resistance in human tumor cells and a direct model for multidrug tolerance in pathogenic fungi like Candida albicans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC CONTROL OF NUTRITION STARVATION 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 2004; Project Start 01-JUL-1984; Project End 30-NOV-2007 Summary: (provided by applicant): This proposal will use the molecular genetics of Saccharomyces cerevisiae and Candida albicans to determine the role of polyploidy and gene duplications in gene expression. Genomes have evolved by duplication of existing genetic material, either whole genomes or individual genes; however, such duplications can lead to abnormal growth. Many tumors contain a large proportion of cells that are hyperploid, and, for some, increased ploidy carries a good prognosis, predicting an increased sensitivity to anti-mitotic drugs. Experiments are designed to identify all the
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Candida Albicans
Saccharomyces genes required for polyploid formation and for the survival of polyploid cells in stationary phase using whole genome knockout libraries. The role of gene silencing in the control of gone expression in polyploids will be determined by whole genome chromatin immunoprecipitation. The mechanism of gene silencing and variegation will be elucidated for the FLO genes, a highly duplicated gone family with one expressed locus (FL011), and many silent subtelomeric members. These experiments will determine the role of chromatin factors, nutrition, mutation, and recombination in silencing and desilencing the ensemble of FLO genes. Experiments are also designed to reveal the mechanism by which the non-telomeric gene FL011 switches epigenetically between the "on" and "off" states. A genome wide screen will identify the prevalence of variegation in gene expression. As FLO genes are the cell surface adhesins of fungi, their ability to switch could be critical virulence factors in pathogens. The importance of silencing and desilencing for human health will be determined in the human fungal pathogen, Candida albicans, an obligate diploid. Candida's resistance to the antifungal agent, fluconazole, is unstable in strains heterozygous for the recessive erg3 mutation. We will determine the role of diploidy and the histone deactylases in generating highlevel drug resistance and will screen the Candida genome for other genes that lead to fluconazole resistance by this silencing mechanism. These Candida studies could identify the factors that will improve the effectiveness of current antifungal therapies. Experiments using DNA microarrays are designed to identify compounds used by Saccharomyces to sense its density. The experiments proposed will lead to a deeper understanding of the ability to proliferate at low cell densities, a more realistic scenario for fungal pathogens. 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 2002; 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
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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 •
Project Title: GENOMIC DATABASE FOR CANDIDA ALBICANS Principal Investigator & Institution: Sherlock, Gavin J.; Director, Stanford Microarray Database; Genetics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The goal of the Candida Genome Database (CGD) is to implement and develop a database containing comprehensive annotated information about the genome of the human fungal pathogen, Candida albicans. CGD will reuse the database structures and software that have been successfully developed for the Saccharomyces Genome Database, and modify them where appropriate to accommodate the differences between C. albicans and S. cerevisiae. CGD will work with the C. albicans community to complete the primary annotation of the genome, and connect the known genomic features to their gene names and the published literature. CGD will annotate all C. albicans gene products to the Gene Ontology (GO), using both literature curation, and transfer of annotation from S. cerevisiae. We will also record phenotypes for mutants, and whether a gene is know to be essential. We will provide tools for the retrieval, manipulation and retrieval of C. albicans sequences, and tools for analyzing C. albicans genes in the context of their annotations to GO. We will forge relationships with the scientific community, especially the C. albicans community, in an effort to make sure that their needs are served. In doing so we expect that CGD will accelerate research on C. albicans, and thus positively impact human health, and make technical improvements that will allow us to better serve our users. The database and its associated resources will be made publicly available via the World Wide Web. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 2002; 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.
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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 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: TARGETS?
HOUSEKEEPING
GENES:
POSSIBLE
ANTIFUNGAL
DRUG
Principal Investigator & Institution: Broedel, Sheldon E.; Athenaes 1450 S Rolling Rd, Ste 4.075 Baltimore, Md 21227 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2004 Summary: (provided by investigator): The occurrence of fungal infections has escalated significantly in recent years. Increases in the number of patients presenting with candidiasis and aspergillosis in particular, has been profound, especially in those immunocompromised by disease or therapies. Unfortunately, only a limited number of antifungal drugs are available for treatment of these and other fungal infections. The paucity of effective agents is due in part to the high degree of relatedness between the biochemical machinery of fungi and the mammalian host. Thus, only a few targets, primarily those associated with fungal cell wall and memebrane biosynthesis, have been successfully exploited. In contrast, "housekeeping enzymes", those enzymes involved in the general biosynthetic and metabolic functions of the cell, have not been seriously considered as potential antifungal drug targets since counterpart proteins usually exist in the host. However, a number of amino acid and vitamin biosynthetic enzymatic pathways that are not present in mammalian cells occur in, and are presumed essential for, survival of certain pathogenic fungi. In this context, the primary aim of the proposed Phase I investigation is to provide proof of principle to validate the use of two such housekeeping enzymes as potential antifungal drug targets. 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 2002; Project Start 29-SEP-2000; Project End 31-JUL-2004
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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 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 2002; 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
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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 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 2002; 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
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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 •
Project Title: INTERESTING BIOACTIVE SUBSTANCES Principal Investigator & Institution: Williams, David R.; Professor; Chemistry; Indiana University Bloomington P.O. Box 1847 Bloomington, in 47402 Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 30-JUN-2003 Summary: Plans describe the continuation of an ambitious and highly successful program investigating the fundamental chemical behavior of recently discovered, biologically-active marine metabolites. The research plan details innovative solutions to the most challenging aspects presented by these unique natural products. Studies will advance basic synthesis methodology for stereocontrolled strategies toward highly functionalized target molecules. The program is organized in two categories. I. Macrolide Anti-tumor Antibiotics Part A: Plans for synthesis of amphidinolide P are presented. The amphidinolides are among the most potent anti-tumor agents discovered, with remarkable activity in nearly all NCI tumor cell lines. Extremely limited quantities have hampered biological research. The proposed chemistry will develop functionalized amphidinolide P. Part B. Efforts for synthesis of leucascandrolide A are presented. The recently discovered macrolide displays powerful anti- tumor and anti-fungal properties, and inhibits Candida albicans, an opportunistic yeast infection of many immunocompromised patients. Allylstannane methodology will offer innovative solutions for rapid construction of the alternating 1, 3, 5.oxygenation pattern. Efficient stereoselective syntheses of substituted tetrahydropyran rings, as bridging elements of this antibiotic will be addressed. II. Marine Diterpenes. Part A. Studies of the novel, nine-membered xenicanes are focused on the synthesis of 4hydroxydictyolactone, a representative structure with anti-tumor and anti-bacterial activity. Investigations of intramolecules alpha-sulfonyl carbanion condensations with omega-aldehydes will provide for assembly of the rigid ring system. Studies of the three contiguous stereocenters (stereotriad) as presented in the xenicanes. Part B. Synthesis of the eleven-membered dolabellane diterpene 4,5-deoxyneodolabelline, will document two strategies for stereocontrolled formation of [9.3.0] cyclotetradecanes. Investigations will highlight previous discoveries for alpha-sulfonyl carbanion chemistry, used to trigger a transannular oxidative ring closure of the bridging pyran. Palladium-catalyzed macrocyclization offers an innovative strategy for stereocontrolled ring formation. A particularly rich spectrum of biological activity, including important anti-tumor activity, is exhibited throughout this class of novel medium-ring metabolites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 2002; 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
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Candida Albicans
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 2002; 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 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
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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: LEUKOCYTE TRANSMIGRATION IN NEONATAL CANDIDA MENINGITIS Principal Investigator & Institution: Lossinsky, Albert S.; Huntington Medical Research Institutes 734 Fairmount Ave Pasadena, Ca 91105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Neonatal meningitis produced by opportunistic pathogenic microorganisms such as the yeast Candida albicans is an inflammatory condition that can occur during the first month after birth and is a leading cause of neurodegenerative states and morbidity in premature and immunocompromised infants. Meningitis in neonates is attributable to the incomplete development of the CNS, the blood-brain barrier (BBB) and the immune system. The precise nature of adhesion and transmigration of pathogenic organisms and leukocytes across the BBB during inflammatory conditions remains unclear and is an issue of great interest in modern medicine. This research program will focus at the mechanisms of adhesion and transmigration of C. albicans and inflammatory leukocytes that appear in response to the microorganisms during the process of meningitis. Our study will be conducted in an in vivo model of experimentally induced meningitis in neonatal rats. Our hypothesis states that the pathogenic yeast C. albicans initially induce the inflammatory state in the meningeal blood vessels. Subsequently, leukocytes adhere to and traverse the endothelial cell (EC) barrier stimulated by the local release of chemoattractant substances in response to the yeast cells. The entire process of adhesion and transmigration across the BBB is facilitated by adhesion molecules including ICAM-1, PECAM-1 and VCAM-1 either across the ECs by a transcellular pathway, through EC junctional complexes by a paracellular pathway, or by both mechanisms. Our specific aim of the project will be to define and compare the light microscopic, immunohistochemical, ultrastructural and immunoultrastructural nature of adhesion and transmigration of a virulent strain of C. albicans, and the different major subsets of inflammatory leukocytes including neutrophils, mononuclear cells and lymphocytes that appear in response to the yeast-induced meningoencephalitis in neonatal rats. This will lay the groundwork for us to investigate how adhesion molecules regulate the attachment and transmigration of pathogenic yeast cells and leukocytes across the BBB via specialized anatomical "gateways to the brain" through either modified EC conduit-
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Candida Albicans
like structures, open EC junctional complexes or by both pathways. Such studies will hopefully establish a framework that may lead to the development of therapeutic intervention for the treatment of neonatal meningitis and several other inflammatory conditions of the CNS. 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 2002; Project Start 01-AUG-2000; Project End 31-MAY-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 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
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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 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 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
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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 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
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Candida Albicans
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: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Cheng, Georgina; Animal Sciences and Veterinary Pathobiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Vaginal candidiasis affects approximately 75% of all women. Hormone levels have been associated with an increased incidence of vaginal candidiasis, especially during pregnancy, and for individuals who use oral contraceptives or hormone replacement therapy. C. albicans is the etiological agent in over 80% of vaginal candidiasis cases, thus making the relationship between estrogen and C. albicans an important one to study. Research into the effect of estrogen on C. albicans has been limited and the signaling mechanisms involved are unknown. Because great variability exists in various estrogen response elements in mammalian genes and because of the differences between mammalian systems and yeast, it is unlikely that a genome database search will identify all of the estrogen response mechanisms at work in C. albicans. This proposal seeks to determine the cellular growth characteristics of C. albicans in the presence of estrogen, identify C. albicans genes responsive to estrogen and define estrogen-responsive promoter elements using molecular biology techniques. Upon completion of these studies, we will have significant new knowledge about the interaction between C. albicans and estrogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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
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Timing: Fiscal Year 2002; 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 BASIS OF VIRULENCE FACTORS OF ORAL FUNGAL SP. Principal Investigator & Institution: Jabra-Rizk, Mary A.; Pathology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): This is a Revision of a K22 Scholar Development and Faculty Transition Award application, submitted on behalf of Mary Ann Jabra-Rizk who is currently a Post-Doctoral Fellow in the Department of Diagnostic Sciences and Pathology at the U of MD Dental School. A 2 year Scholar Development phase and three years of Faculty Transition win be centered at U of MD involving co-mentors and consultants at Johns Hopkins, the U of VA and the U of Wurzburg and will establish Dr. Jabra-Rizk as an independent expert in oral fungal diseases. An Advisory Committee at the U of MD will evaluate her progress and aid in the Faculty Transition. The hypothesis to be tested during the Scholar Development is that C. dubliniensis is a species that exhibits constant cell surface hydrophobicity, possessing a homologue to the C. albicans CSHl gene which encodes a hydrophobic cell wall protein involved in cell adherence but differs in the expression of the MNN mannosylation family of genes and other putative virulence genes. Two aims are planned: 1. (a) Determine the presence of the C. albicans CSHl and CaMNN9 genes or homologues of the genes in C. dubliniensis using PCR primers designed based on the C albicans CSIII and CaMNN9 gene sequences. These will be subsequently amplified and cloned using C. dubliniensis CDS6 genomic DNA
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Candida Albicans
and probe hybridization. A C. dubliniensis knockout of the CSH 1 homologue gene will be generated using the latest technique (ura3 amxotrophic C. dubliniensis mutants in the URA-blaster) in gene disruption technique (b) Determine the effect of the disruption of the CdCShl gene on adherence by assessing the C. dubliniensis knockout clone for cell surface hydrophobicity7 adhesion to fibronectin, adherence to Fusobacterium nucleatum and pooled human buccal epithelial cells, in comparison to the wild type (c) Determine differences in the ability of macrophages to phagocytize 37C-grown C. albicans, 37C grown CdCSH1 mutant and wild type C. dubliniensis and the C. albicans mnn9 mutant in order to determine the effect of structural changes in the side chains of cell wall mannan on the ability of C. dubliniensis and C. albicans to evade host cell phagocytosis. 2. Based on cDNA microarray sequences of genes in the C. albicans genome, we will determine levels of differential expression of the CSHl and CaMNN9 genes between hydrophilic (37C-grown C. albicans) and hydrophobic (250C-grown C. albicans, 25 and 37C-grown C. dubliniensis and C. albicans mutants, A9V10 and Camnn9) yeast cells, as well as the C. dubliniensis CdCSHl mutant generated in Aim 1. Dr. Jabra-Rizic will subsequently utilize the information and mutants generated to investigate whole genome differences between C. dubliniensis and C. albicans in the Faculty Transition phase using DNA microarrays. She will also analyze differences in the levels of expression of hsp90 gene and other glycosylation and heat shock proteins genes in C. dubliniensis. In addition, a hsp90 knock out mutant of C. albicans will be generated and assessed for thermotolerance and phagcytosis by macrophages. Long range plans include using the mutants generated to study Candida mannoproteinspecific host immunomodulation, such as stimulation of cytokines and chemokines. 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 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
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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 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
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Candida Albicans
Project Title: MUCOSAL CANDIDIASIS
CELL
MEDIATED
IMMUNITY
IN
VAGINAL
Principal Investigator & Institution: Fidel, Paul L.; Professor; Microbiol/Immunolgy/Parasitlgy; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 31-MAY-2005 Summary: (Adapted from applicants abstract): Host defenses at the vaginal mucosa are poorly understood. This includes those against C. albicans, the causative agent of >90 percent of cases of vulvovaginal candidiasis (VVC). Cell-mediated immunity (CMI) is important in host defense against C. albicans infections at several mucosal sites. Our laboratory has employed clinical studies and an estrogen-dependent murine model of vaginal candidiasis to understand the role of CMI as a host defense mechanism against vaginitis. To date, our data suggests that anti-Candida host defense mechanisms at the vaginal mucosa may be distinct from those protecting other mucosal tissues. To this end, studies show that systemic-derived Candida-specific CD4+ Th1-type cells associated with resistance against candidal infections does not provide protection against clinical or experimental vaginitis. Partial protection from experimental infection in the absence of Candida-specific systemic CMI suggested that protective mechanisms were localized to the vaginal mucosa consistent with clinical data. Analysis of local immunity showed that while phenotypically distinct T cells were present in the vagina, they did not significantly change during experimental vaginal infection and there was no evidence for infiltration of systemic T cells into the vaginal mucosa. In addition, polymorphonuclear leukocytes (PMNL) present at times during infection do not influence vaginal C. albicans burden. Together, these data suggest that some level of immunoregulation acts at the vaginal mucosa that limits the function of the local and possibly systemic immune responses. This is supported by the vaginal presence of down-regulatory cytokines. In light of limited activity by conventional immune cells at the vaginal mucosa, we discovered that vaginal epithelial cells have anti-Candida activity in vitro. Based on these findings, we hypothesize that immunoregulatory events at the vaginal mucosa significantly affect local cellular immune mechanisms (innate and/or acquired) important for protection against C. albicans vaginal infection, and that vaginal epithelial cells provide some level of innate resistance against C. albicans. To test this hypothesis, we will (i) further characterize vaginal CMI responses during C. albicans vaginal infection, (ii) elucidate immunoregulatory mechanisms potentially responsible for inefficient anti-Candida responses, and (iii) elucidate properties critical to the mechanism for the epithelial cell-mediated anti-Candida activity. The long term goal is to understand vaginal host defense mechanisms against C. albicans so that immunotherapeutic strategies can be developed to prevent or treat disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUCOSAL CANDIDIASIS
IMMUNIZATION--PREVENTION
OF
SYSTEMIC
Principal Investigator & Institution: Freytag, Lucia C.; Research Assistant Professor; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; 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
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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 •
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 2002; Project Start 01-AUG-1999; Project End 31-JAN-2004 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 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
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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 2002; 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 cryptococcosis and candidiasis. Our long term goal is to identify unique targets and develop novel antifungal drug therapies.
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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 2002; 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 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
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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 AND VAGINAL GENE EXPRESSION BY CANDIDA DURING AIDS Principal Investigator & Institution: Clancy, Cornelius J.; Molecular Genetics & Microbiol; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Oropharyngeal and vulvovaginal candidiasis (OPC and VVC), mucosal infections caused by Candida albicans, are the leading opportunistic infections among HIV-infected persons. In most humans, C. albicans is a harmless commensal of the gastrointestinal tract. The mechanisms by which the organism switches to an invasive pathogen are poorly understood. We hypothesize that pathogenesis at the oral and vaginal mucosa is facilitated by the expression of a subset of candidal genes that are specific to the mucosal surfaces. The major overall objective of our laboratory is to understand C. albicans gene expression during the pathogenesis of human infections. The goal of this R21 project is to identify C. albicans genes that are specifically expressed at the oral and/or vaginal mucosa, in order to identify genes that contribute to the pathogenesis of HIV associated candidiasis. To accomplish this, we will use saliva and vaginal fluid that are rich in locally produced anti-candidal antibodies to identify immunogenic C. albicans antigens. In preliminary studies, we created separate pools of saliva and vaginal fluid from HIV-infected persons with active OPC and VVC, respectively. The pooled samples were adsorbed against yeast and hyphae of C. albicans strains grown in vitro, as well as cell lysates. In Specific Aim 1, we will use the adsorbed samples, now concentrated in antibodies directed against antigens expressed uniquely within the human host, to screen a C. albicans genomic expression library in parallel. The complete sequences of the genes encoding immunogenic antigens will be identified using the C. albicans sequence databases. In Specific Aim 2, we will confirm that these genes are induced at the oral or vaginal mucosa, but not during routine growth in vitro, using quantitative real-time reverse transcription-polymerase chain reaction. We will also directly detect the in vivo induced antigens by using routine antibodies raised against the purified antigens to probe OPC and VVC samples recovered from HIV-infected persons. The mucosal-specific genes identified in this
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project will be studied in future projects for their specific roles during candidal pathogenesis, with the ultimate goal of designing strategies to treat and prevent OPC and VVC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 2002; 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.; Interim Department Head; Periodontology; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-JUL-2004 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
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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 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 2002; 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
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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. 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 2002; 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: POTENTIATORS OF FLUCONAZOLE ACTIVITY IN CANDIDA Principal Investigator & Institution: Markham, Penelope N.; Director of Research; Influx, Inc. 2201 W Campbell Park Dr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-DEC-2003 Summary: (provided by applicant): The goal of this Phase II SBIR project is to develop a clinically useful potentiator of the most widely used antifungal drugs, azoles. The major shortcoming of azole drugs is that they do not kill fungi but merely inhibit their growth. In fact, for the most medically important fungal pathogen, Candida albicans, this growth inhibition is only partial. The survival of the pathogen in the presence of the drug is the likely cause of the recurrence of fungal infections and emergence of azole resistance. Our Phase I studies identified two compounds in whose presence azoles become strongly fungicidal. These compounds show no antifungal activity on their own and no toxicity to human cells in culture. Structural derivatives of these two leads, displaying improved activity and pharmacological properties, will be obtained through intensive synthetic efforts. The biological activity of these derivatives will be thoroughly characterized in vitro. Their ability to improve antifungal activity of fluconazole will be tested in a murine model of systemic candidiasis. Finally, the molecular mechanism of action of the potentiators will be investigated in biochemical and genetic experiments. It is expected that the compounds developed in this project will significantly improve the improve the effectiveness of antifungal therapy. PROPOSED COMMERCIAL APPLICATION: The commercial product envisioned is a fungicidal combination of fluconazole with an adjuvant that potentiates antifungal activity. Such a product would have a major impact on the therapeutic and prophylactic treatment options for systemic Candida infections Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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
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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 •
Project Title: RAPID EVALUATION OF DRUG RESISTANCE IN PATHOGENIC FUNGI Principal Investigator & Institution: Perlin, David S.; Scientific Director and Professor; 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. 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
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Project Title: REGULATION OF COMPLEMENT ACTIVATION BY CANDIDA ALBICANS Principal Investigator & Institution: Kozel, Thomas R.; Professor and Chair; Microbiology and Immunology; University of Nevada Reno 204 Ross Hall Mailstop 325 Reno, Nv 89557
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Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Candida albicans yeast cells and hyphae and the surfaces of all other fungi studied to date activate the complement system. The importance of the complement system in host resistance is demonstrated by the markedly increased susceptibility of experimental animals with complement deficiencies to experimental fungal infection. Less well appreciated is the role of naturally occurring antibodies and other putative initiators, e.g., mannan-binding lectin (MBL), in initiation and/or regulation of C3 deposition. Recent studies in the Kozel laboratory found that anti-mannan IgG in normal human serum plays a critical role in C3 deposition on C. albicans via both the classical and alternative pathways. In the absence of this anti- mannan antibody, C3 deposition is profoundly delayed, suggesting that anti-mannan antibody or near initiators of the complement system such as MBL may be critical components in host resistance. The overall hypothesis for this proposal is that naturally occurring antibodies or other initiators found in normal human serum are essential for efficient deposition of C3 on C. albicans. As a corollary to this deposition. The Specific Aims for the study are: 1) to evaluate the contribution of epitope specificity of anti-mannan antibodies to C3 deposition on C. albicans, 2) to determine the contribution of antibody isotype to C3 deposition via the classical and alternative pathways, 3) to assess the contribution of mannan-binding lectin to activation and binding of C3, and 4) to compare individual sera with high and low C3 deposition activity for the presence of factors that would support C3 deposition. Results of this study will contribute to our understanding of natural host resistance system. An understanding of this system is fundamental to identification of individuals at possible risk for opportunistic Candida infections and the development of immunological means to prevent infection. 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 2002; 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
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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 •
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 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 post-transcriptional 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: SALIVARY HISTATIN--THERAPEUTIC AGENT Principal Investigator & Institution: Bobek, Libuse A.; Professor of Oral Biology; Oral Biology; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2002; Project Start 15-MAR-1992; Project End 30-JUN-2004
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Candida Albicans
Summary: Fungal infections are a serious public-health hazard, particularly for the growing population of immunocompromised patients, including those with AIDS and organ transplant recipients. A rise in fungal infections is also seen in elderly people, denture wearers and individuals with salivary dysfunction. Many presently available antifungal agents are toxic and/or not effective against an increasing number of the drug-resistant fungal strains. Human salivary histatins (Hsns) are a group of cationic peptides that have been shown to possess fungicidal activity. This property coupled with the fact that Hsns are natural products of the human body and thus most likely nontoxic makes them promising antifungal therapeutic agents. In particular, the ability of histatins to kill azole-resistant strains of C. albicans and Cryptococcus neoformans indicates that they may have therapeutic potential in treating fungal infections associated with AIDS. During the previous grant period, we examined the structurefunction relationship of Hsn-5 (24 amino acid residue protein) with respect to its candidacidal activity using recombinant Hsn-5 variants as well as chemically synthesized Hsn-5 fragments. In this proposal, we will explore the hypotheses that Hsns can be effective natural antifungal therapeutic agents and that Hsn variants with enhanced protective functions can be designed if the Hsn structure-function relationship (Specific Aim 1) and its mode of action on C. albicans (Specific Aim 2) are better defined and understood. Based on the outcomes from the first two specific aims and our previous results, we will design Hsn-5 variants with enhanced activity and/or stability and examine them for their potential suitability as antifungal therapeutic agents both in vitro and in vivo (Specific Aim 3). We will also examine whether Hsn-5 and relevant variants possess fungicidal activity against other opportunistic fungal species, and act synergistically with other antifungal agents (Specific Aim 4). The long-term objective of this research is to design and produce novel Hsns with enhanced protective function that may serve as effective and non-toxic natural antifungal therapeutic agents that would help to outpace the growing list of the drug resistant and opportunistic fungi causing life-threatening, disseminated diseases. The same molecules could also be used as components of artificial saliva for patients with salivary dysfunction. Collectively, the information obtained can be used to effectively design Hsn-based therapeutic delivery systems for future clinical use. 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 2002; Project Start 15-JUN-1999; Project End 31-JUL-2002 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
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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 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 DEMETHYLASES
REQUIREMENTS
FOR
STEROL
14ALPHA-
Principal Investigator & Institution: Waterman, Michael R.; Professor and Chairman; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): CYP51 catalyzes the 3-step 14?-demethylation reaction that is essential in sterol biosynthesis, being required for conversion of lanosterol to cholesterol (animals), 24-methylenedihydrolanosterol to ergosterol (fungi/yeast) and obtusifoliol to phytosterols (plants). It is the most widely distributed member of the cytochrome P450 superfamily, also being found in lower eukaryotes and some bacteria. We have determined the first high resolution structure of a CYP51, the soluble form from Mycobacterium tuberculosis (MT). The goal of this grant application is to take advantage of this structural information and the relatively large number of known CYP51 sequences to provide a detailed understanding of CYP51 structure/function. This is a revision of a new application. Aim 1 - Alignment of the more than 50 CYP51 sequences from different phyla shows about 40 amino acids completely or very highly conserved. We propose the conserved residues to be the minimal structural requirement for 14?-demethylases. Site-directed mutagenesis of MT and human CYP51 will permit analysis of the role of each of these residues. Levels of bacterial expression, spectral analysis of substrate binding and catalytic activity will be studied in each mutant. X-ray structure, fluorescence and circular dichroism analysis of substrate-induced conformational changes, and stopped flow analysis of substrate binding will also provide biophysical detail of selected mutations. Aim 2 - CYP51 from plants metabolizes only a single substrate (obtusifoliol--the biological CYP51 substrate having just a single methyl group at C4) while forms from other phyla metabolize multiple sterols. Site-directed mutagenesis of a second set of residues conserved strictly in plants will be used to determine the structural basis of plant CYP51 substrate specificity, relying on methods cited above. Aim 3 - Treatment of pathogenic Candida albicans infections with azole CYP51 inhibitors leads to mutant forms of CYP51 in some drug-resistant Candida strains. These mutant forms bind azole inhibitors less well while binding substrate normally, both in the single CYP51 active site. Investigation of biophysical properties of these mutations in MTCYP51 will provide an explanation for CYP51 drug resistance in pathogens. Together these aims will provide new and extensive insight into structure/function of CYP51, the first opportunity for such detailed analysis of a widely distributed and essential CYP family. In addition we expect that these studies will lead to general information about P450 structure/function and provide useful insight into drug design for treatment of pathogenic infections.
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Candida Albicans
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 2002; 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
•
Project Title: STRUCTURE AND FUNCTION OF FUNGAL CELL ADHESION PROTEINS Principal Investigator & Institution: Lipke, Peter N.; Professor; Hunter College Room E1424 New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SWITCHING AND CANDIDA PATHOGENESIS-A MOLECULAR ANALYSIS Principal Investigator & Institution: Soll, David R.; Professor; Biological Sciences; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-MAY-2006 Summary: (Verbatim from Applicant's Abstract): Candida albicans switches spontaneously, reversibly and at high frequency between a limited number of general phenotypes distinguishable by colony morphology. Switching is highly pleiotropic, regulating a variety of phenotypic characteristics and involving the differential expression of phase-specific genes. Switching therefore, provides colonizing populations
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with spontaneous variants for rapid adaptation during commensalism and pathogenesis. Using the white-opaque phase transition in strain WO-1 as an experimental system, we have demonstrated that the histone deacetylase Hda1p functions as a suppressor of switching in the white-to-opaque direction, that the silent information regulatory Sir2p is not involved in the white-opaque transition, but functions as a suppressor of a second switching system analogous to that in strain 3153A, and that phase specific genes are regulated downstream of the switch event through phase-specific trans-acting factors. We now propose 1) to develop a more accurate model of the downstream regulatory circuitry involved in phase specific gene expression, 2) to elucidate the protein-DNA and protein-protein interactions involved in the regulation of select white and opaque phase genes, with emphasis on the role of the MADS box proteins in opaque phase expression of OP4, Rbf1p in white phase expression of WH11 and transcription of the phase regulated trans-acting factor EFG1, 3) to elucidate the roles of acetylation/deacetylation and gene silencing in switching, and 4) to assess the impact of the deletion of phase-specific regulatory molecules on pathogenesis in two animal models, one in which white phase cells are more pathogenic than opaque phase cells, and the other in which opaque phase cells are more pathogenic than white phase cells. The first three aims have been formulated so that they provide several independent starting points for a reverse genetic approach for elucidating switch loci and the switching mechanism. 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
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Candida Albicans
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 •
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 2002; 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
•
Project Title: THE GLYOXYLATE CYCLE AS A NEW TARGET FOR ANTIFUNGALS Principal Investigator & Institution: Selitrennikoff, Claude P.; Professor; Mycologics, Inc. 12635 E Montview Blvd, Ste 131 Aurora, Co 800107336 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JUL-2003 Summary: (provided by applicant): Fungi cause a wide spectrum of disease states. The most common examples are relatively minor, localized infections of the skin and mucous membranes such as athlete's foot, vaginal yeast infections, and infections of keratinized nails. However, an ominously increasing number of fungi cause systemic disease with the involvement of internal organs. These have become serious and lifethreatening problems that are very difficult to diagnose and even more challenging to treat in patients with impaired host-defense mechanisms. Part of the difficulty in treating fungal infections, especially in immunocompromised hosts, is the limited armamentarium of antifungal drugs. Currently-available drugs include polyenes (e.g., amphotericin B) that complex with fungal-membrane ergosterol, a number of azoles and allylamines that inhibit steps in the ergosterol biosynthetic pathway, flucytosine that inhibits nucleic acid synthesis, and Cancidas, a (1,3)beta-glucan synthase inhibitor. Unfortunately, amphotericin B has a number of acute and chronic adverse effects. Flucytosine has a narrow spectrum of activity and is plagued with treatment failures due to the development of resistant fungi. Azoles are only fungistatic and resistance to commonly-used azoles is becoming a significant clinical problem. There is general agreement that there is a critical and immediate need for novel drugs with mechanisms of action different from current drugs. The applicant's long-term goal is to discover novel antifungals that are active against enzymes of the glyoxylate cycle. The glyoxylate cycle, which is absent in humans, is essential for fungal pathogenicity and represents an unexploited pathway for the development of antifungal drugs. The investigators will accomplish this in Two Aims: (1) to isolate and identify 5 to10 inhibitors of the glyoxylate cycle enzymes and determine their potency against fungal cells and toxicity against human cells; (2) to determine the in vivo efficacy of two of the most active compounds using a Candida albicans murine model. Ultimately, this work will lead to the isolation of new classes of compounds for treatment of human fungal disease. The applicant predicts that, since humans do not have the glyoxylate cycle, the inhibitors will be safe and effective therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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55
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
•
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
56
Candida Albicans
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 •
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 2002; 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
•
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
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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 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 2002; 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
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Candida Albicans
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 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 albicans” (or synonyms) into the search box. This search gives you access
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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to full-text articles. The following is a sample of items found for Candida albicans in the PubMed Central database: •
[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&artid=128217
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A 19F nuclear magnetic resonance study of uptake and metabolism of 5fluorocytosine in susceptible and resistant strains of Candida albicans. by Di Vito M, Podo F, Torosantucci A, Carpinelli G, Whelan WL, Kerridge D, Cassone A.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176396
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A Candida albicans surface antigen mediating adhesion and autoaggregation in Saccharomyces cerevisiae. by Barki M, Koltin Y, van Wetter M, Rosenberg M.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303083
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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&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&artid=104361
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A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans. by Petter R, Chang YC, Kwon-Chung KJ.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175708
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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 Monoclonal Antibody Directed against a Candida albicans Cell Wall Mannoprotein Exerts Three Anti-C. albicans Activities. by Moragues MD, Omaetxebarria MJ, Elguezabal N, Sevilla MJ, Conti S, Polonelli L, Ponton J.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187351
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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=abstr act&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&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&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&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&artid=128749
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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&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&artid=108662
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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&artid=105395
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Analysis of mannans of two relatively avirulent mutant strains of Candida albicans. by Saxena A, Hammer CF, Cihlar RL.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313112
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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&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&artid=95254
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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&artid=89399
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Antifungal Effects of Lysozyme and Lactoferrin against Genetically Similar, Sequential Candida albicans Isolates from a Human Immunodeficiency Virus-
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Infected Southern Chinese Cohort. by Samaranayake YH, Samaranayake LP, Pow EH, Beena VT, Yeung KW.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88334 •
Application of a numerical index of discriminatory power to a comparison of four physiochemical typing methods for Candida albicans. by Hunter PR, Fraser CA.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266984
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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&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&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&artid=89108
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Asynchronous Cell Cycle and Asymmetric Vacuolar Inheritance in True Hyphae of Candida albicans. by Barelle CJ, Bohula EA, Kron SJ, Wessels D, Soll DR, Schafer A, Brown AJ, Gow NA.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161449
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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&artid=98888
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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&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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Azole susceptibility and hyphal formation in a cytochrome P-450-deficient mutant of Candida albicans. by Lees ND, Broughton MC, Sanglard D, Bard M.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171701
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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&artid=95423
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C3bi-binding protein on Candida albicans: temperature-dependent expression and relationship to human complement receptor type 3. by Eigentler A, Schulz TF, Larcher C, Breitwieser EM, Myones BL, Petzer AL, Dierich MP.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313141
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Ca3 Fingerprinting of Candida albicans Bloodstream Isolates from the United States, Canada, South America, and Europe Reveals a European Clade. by Pujol C, Pfaller M, Soll DR.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120649
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Ca3 Fingerprinting of Candida albicans Isolates from Human Immunodeficiency Virus-Positive and Healthy Individuals Reveals a New Clade in South Africa. by Blignaut E, Pujol C, Lockhart S, Joly S, Soll DR.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120250
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Calcineurin Is Essential for Candida albicans Survival in Serum and Virulence. by Blankenship JR, Wormley FL, Boyce MK, Schell WA, Filler SG, Perfect JR, Heitman J.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161442
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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&artid=125859
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Calcineurin Is Essential for Virulence in Candida albicans. by Bader T, Bodendorfer B, Schroppel K, Morschhauser J.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187310
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Candida albicans colony identification in 5 minutes in a general microbiology laboratory. by Dealler SF.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269943
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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&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&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&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&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&artid=89682
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Candida albicans Mutations in the Ergosterol Biosynthetic Pathway and Resistance to Several Antifungal Agents. by Sanglard D, Ischer F, Parkinson T, Falconer D, Bille J.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166068
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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&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 Septin Mutants Are Defective for Invasive Growth and Virulence. by Warenda AJ, Kauffman S, Sherrill TP, Becker JM, Konopka JB.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161988
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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&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 albicans VPS11 Is Required for Vacuole Biogenesis and Germ Tube Formation. by Palmer GE, Cashmore A, Sturtevant J.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161452
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Candida detection system (CAND-TEC) to differentiate between Candida albicans colonization and disease. by Fung JC, Donta ST, Tilton RC.; 1986 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268967
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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&artid=95223
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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&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&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&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&artid=98909
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Characterization of a tetraploid derivative of Candida albicans ATCC 10261. by Hubbard MJ, Poulter RT, Sullivan PA, Shepherd MG.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214954
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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&artid=103306
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Characterization of cerulenin-resistant mutants of Candida albicans. by Hoberg KA, Cihlar RL, Calderone RA.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261071
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Characterization of echinocandin-resistant mutants of Candida albicans: genetic, biochemical, and virulence studies. by Kurtz MB, Abruzzo G, Flattery A, Bartizal K, Marrinan JA, Li W, Milligan J, Nollstadt K, Douglas CM.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174214
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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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Chromosomal alterations of Candida albicans are associated with the gain and loss of assimilating functions. by Rustchenko EP, Howard DH, Sherman F.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205493
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Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans. by Rustchenko-Bulgac EP, Sherman F, Hicks JB.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208595
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Ciclopirox Olamine Treatment Affects the Expression Pattern of Candida albicans Genes Encoding Virulence Factors, Iron Metabolism Proteins, and Drug Resistance Factors. by Niewerth M, Kunze D, Seibold M, Schaller M, Korting HC, Hube B.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155814
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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&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&artid=95234
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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&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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Colonization of congenitally athymic, gnotobiotic mice by Candida albicans. by Balish E, Balish MJ, Salkowski CA, Lee KW, Bartizal KF.; 1984 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239742
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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 evaluation of macrodilution and chromogenic agar screening for determining fluconazole susceptibility of Candida albicans. by Patterson TF, Kirkpatrick WR, Revankar SG, McAtee RK, Fothergill AW, McCarthy DI, Rinaldi MG.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229494
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Comparative evaluation of three antifungal susceptibility test methods for Candida albicans isolates and correlation with response to fluconazole therapy. by Ruhnke M, Schmidt-Westhausen A, Engelmann E, Trautmann M.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229485
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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&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=abstr act&artid=163328
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Comparison between methods for serotyping of Candida albicans produces discrepancies in results. by Brawner DL.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269927
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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&artid=127692
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Comparison of D0870, a new triazole antifungal agent, to fluconazole for inhibition of Candida albicans cytochrome P-450 by using in vitro assays. by Venkateswarlu K, Denning DW, Manning NJ, Kelly SL.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163335
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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&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 restriction enzyme analysis and pulsed-field gradient gel electrophoresis as typing systems for Candida albicans. by Vazquez JA, Beckley A, Sobel JD, Zervos MJ.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269916
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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&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 Three Methods for Testing Azole Susceptibilities of Candida albicans Strains Isolated Sequentially from Oral Cavities of AIDS Patients. by Tortorano AM,
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Viviani MA, Barchiesi F, Arzeni D, Rigoni AL, Cogliati M, Compagnucci P, Scalise G.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104880 •
Comparison of two alternative microdilution procedures with the National Committee for Clinical Laboratory Standards reference macrodilution method M27-P for in vitro testing of fluconazole-resistant and -susceptible isolates of Candida albicans. by Espinel-Ingroff A, Rodriguez-Tudela JL, Martinez-Suarez JV.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228663
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Conserved Serine/Threonine Kinase Encoded by CBK1 Regulates Expression of Several Hypha-Associated Transcripts and Genes Encoding Cell Wall Proteins in Candida albicans. by McNemar MD, Fonzi WA.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134915
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Contribution of Candida albicans ALS1 to the Pathogenesis of Experimental Oropharyngeal Candidiasis. by Kamai Y, Kubota M, Kamai Y, Hosokawa T, Fukuoka T, Filler SG.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128218
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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&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&artid=96790
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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&artid=86484
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D-arabitol metabolism in Candida albicans: construction and analysis of mutants lacking D-arabitol dehydrogenase. by Wong B, Leeson S, Grindle S, Magee B, Brooks E, Magee PT.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176981
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D-arabitol metabolism in Candida albicans: studies of the biosynthetic pathway and the gene that encodes NAD-dependent D-arabitol dehydrogenase. by Wong B, Murray JS, Castellanos M, Croen KD.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206728
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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&artid=105649
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Decreased activity of UMP pyrophosphorylase associated with resistance to 5fluorocytosine in Candida albicans. by Whelan WL, Kerridge D.; 1984 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=179965
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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&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&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&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&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&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 Individual mRNA Capping Genes Is Unexpectedly Not Lethal to Candida albicans and Results in Modified mRNA Cap Structures. by Dunyak DS, Everdeen DS, Albanese JG, Quinn CL.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138750
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Deletion of the Two-Component Histidine Kinase Gene (CHK1) of Candida albicans Contributes to Enhanced Growth Inhibition and Killing by Human Neutrophils In Vitro. by Torosantucci A, Chiani P, De Bernardis F, Cassone A, Calera JA, Calderone R.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127696
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Depletion of a Polo-like Kinase in Candida albicans Activates Cyclase-dependent Hyphal-like Growth. by Bachewich C, Thomas DY, Whiteway M.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165105
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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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Detecting Candida albicans in Human Milk. by Morrill JF, Pappagianis D, Heinig MJ, Lonnerdal B, Dewey KG.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149590
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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&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 albicans mRNA from Formalin-Fixed, Paraffin-Embedded Mouse Tissues by Nested Reverse Transcription-PCR. by Schofield DA, Westwater C, Paulling EE, Nicholas PJ, Balish E.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149710
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Different levels of DNA methylation in yeast and mycelial forms of Candida albicans. by Russell PJ, Welsch JA, Rachlin EM, McCloskey JA.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213760
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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&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&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&artid=150300
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Candida Albicans
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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&artid=87722
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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&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&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&artid=127825
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Distinct characteristics of initiation of the classical and alternative complement pathways by Candida albicans. by Kozel TR, Weinhold LC, Lupan DM.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174230
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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&artid=105968
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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&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&artid=94848
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Dosage of the smallest chromosome affects both the yeast-hyphal transition and the white-opaque transition of Candida albicans WO-1. by McEachern MJ, Hicks JB.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212507
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Drug Resistance Is Not Directly Affected by Mating Type Locus Zygosity in Candida albicans. by Pujol C, Messer SA, Pfaller M, Soll DR.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152535
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Dynamic expression of cell surface hydrophobicity during initial yeast cell growth and before germ tube formation of Candida albicans. by Hazen BW, Hazen KC.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259601
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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&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&artid=105707
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Effect of nonylphenol on growth of Neurospora crassa and Candida albicans. by Karley AJ, Powell SI, Davies JM.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168425
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Effect of Prolonged Fluconazole Treatment on Candida albicans in Diffusion Chambers Implanted into Mice. by Sohnle PG, Hahn BL.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128792
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Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans. by Ryder NS, Seidl G, Troke PF.; 1984 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185557
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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&artid=89204
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Effects of cyclophosphamide and ceftriaxone on gastrointestinal colonization of mice by Candida albicans. by Samonis G, Karyotakis NC, Anaissie EJ, Barbounakis E, Maraki S, Tselentis Y, Bodey GP.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163505
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Effects of squalene epoxidase inhibitors on Candida albicans. by Georgopapadakou NH, Bertasso A.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192047
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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&artid=89410
72
Candida Albicans
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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&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&artid=95293
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Electrophoretic karyotyping of typical and atypical Candida albicans. by Mahrous M, Lott TJ, Meyer SA, Sawant AD, Ahearn DG.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267828
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Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus. by De Bernardis F, Chiani P, Ciccozzi M, Pellegrini G, Ceddia T, D'Offizzi G, Quinti I, Sullivan PA, Cassone A.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173787
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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&artid=87443
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Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection. by Ruhnke M, Eigler A, Tennagen I, Geiseler B, Engelmann E, Trautmann M.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263948
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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&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&artid=89845
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Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans. by Domer JE, Hector RF.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174816
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Environmental alteration and phenotypic regulation of Candida albicans adhesion to plastic. by Kennedy MJ, Rogers AL, Yancey RJ Jr.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259920
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Epidemiological analysis of Candida albicans strains by multilocus enzyme electrophoresis. by Caugant DA, Sandven P.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262738
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Evidence for adhesin activity in the acid-stable moiety of the phosphomannoprotein cell wall complex of Candida albicans. by Kanbe T, Cutler JE.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186380
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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 for the presence of a high-affinity laminin receptor-like molecule on the surface of Candida albicans yeast cells. by Lopez-Ribot JL, Casanova M, Monteagudo C, Sepulveda P, Martinez JP.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186171
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Evidence implicating phospholipase as a virulence factor of Candida albicans. by Ibrahim AS, Mirbod F, Filler SG, Banno Y, Cole GT, Kitajima Y, Edwards JE Jr, Nozawa Y, Ghannoum MA.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173255
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Evidence that Candida stellatoidea type II is a mutant of Candida albicans that does not express sucrose-inhibitable alpha-glucosidase. by Kwon-Chung KJ, Hicks JB, Lipke PN.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313570
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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&artid=94447
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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&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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Expression, cloning, and characterization of a Candida albicans gene, ALA1, that confers adherence properties upon Saccharomyces cerevisiae for extracellular matrix proteins. by Gaur NK, Klotz SA.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175761
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Candida Albicans
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Fab fragments from a monoclonal antibody against a germ tube mannoprotein block the yeast-to-mycelium transition in Candida albicans. by Casanova M, Martinez JP, Chaffin WL.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313733
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Farnesol Biosynthesis in Candida albicans: Cellular Response to Sterol Inhibition by Zaragozic Acid B. by Hornby JM, Kebaara BW, Nickerson KW.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161837
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Filamentous growth and elevated vaginopathic potential of a nongerminative variant of Candida albicans expressing low virulence in systemic infection. by De Bernardis F, Adriani D, Lorenzini R, Pontieri E, Carruba G, Cassone A.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281392
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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 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&artid=105969
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Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency viruspositive patients: persistence of Candida albicans strains with the same genotype. by Millon L, Manteaux A, Reboux G, Drobacheff C, Monod M, Barale T, Michel-Briand Y.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267201
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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&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&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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Functional Similarities and Differences between Candida albicans Cdr1p and Cdr2p Transporters. by Gauthier C, Weber S, Alarco AM, Alqawi O, Daoud R, Georges E, Raymond M.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153331
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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&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&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&artid=101590
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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 evidence for role of extracellular proteinase in virulence of Candida albicans. by Kwon-Chung KJ, Lehman D, Good C, Magee PT.; 1985 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261208
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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 similarity and maintenance of Candida albicans strains from a group of AIDS patients, demonstrated by DNA fingerprinting. by Schmid J, Odds FC, Wiselka MJ, Nicholson KG, Soll DR.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265189
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Genetic similarity and phenotypic diversity of commensal and pathogenic strains of Candida albicans isolated from the oral cavity. by Hellstein J, Vawter-Hugart H, Fotos P, Schmid J, Soll DR.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266374
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Genetic similarity of Candida albicans strains from vaginitis patients and their partners. by Schmid J, Rotman M, Reed B, Pierson CL, Soll DR.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262617
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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. by Rogers PD, Barker KS.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152536
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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&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&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&artid=97077
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Glycolytic enzymes of Candida albicans are nonubiquitous immunogens during candidiasis. by Swoboda RK, Bertram G, Hollander H, Greenspan D, Greenspan JS, Gow NA, Gooday GW, Brown AJ.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281153
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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&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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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&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&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&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&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&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&artid=94032
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Hydrophobic surface protein masking by the opportunistic fungal pathogen Candida albicans. by Hazen KC, Hazen BW.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257023
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Hypha formation in the white-opaque transition of Candida albicans. by Anderson J, Cundiff L, Schnars B, Gao MX, Mackenzie I, Soll DR.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313119
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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&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 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&artid=149553
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Identification of Elongation Factor 2 as the Essential Protein Targeted by Sordarins in Candida albicans. by Dominguez JM, Martin JJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105815
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Identification of Major Glucan-Associated Cell Wall Proteins of Candida albicans and Their Role in Fluconazole Resistance. by Angiolella L, Micocci MM, D'Alessio S, Girolamo A, Maras B, Cassone A.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127269
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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=abstr act&artid=162588
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Candida Albicans
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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&artid=96209
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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&artid=128731
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In vitro determination of optimal antifungal combinations against Cryptococcus neoformans and Candida albicans. by Ghannoum MA, Fu Y, Ibrahim AS, Mortara LA, Shafiq MC, Edwards JE Jr, Criddle RS.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162965
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In vitro interaction between amphotericin B and azoles in Candida albicans. by Vazquez JA, Arganoza MT, Vaishampayan JK, Akins RA.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163566
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In Vitro Killing of Candida albicans by Fatty Acids and Monoglycerides. by Bergsson G, Arnfinnsson J, Steingrimsson O, Thormar H.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90807
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In Vitro Low-Level Resistance to Azoles in Candida albicans Is Associated with Changes in Membrane Lipid Fluidity and Asymmetry. by Kohli A, Smriti, Mukhopadhyay K, Rattan A, Prasad R.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127087
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In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus. by Korting HC, Ollert M, Georgii A, Froschl M.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266959
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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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Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. by White TC.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163944
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Increased sensitivity of Candida albicans cells accumulating 14 alpha-methylated sterols to active oxygen: possible relevance to in vivo efficacies of azole antifungal agents. by Shimokawa O, Nakayama H.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192020
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Induced chromosome rearrangements and morphologic variation in Candida albicans. by Barton RC, Scherer S.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205113
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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&artid=90239
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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&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&artid=94952
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Inhibition of 2,3-oxidosqualene-lanosterol cyclase in Candida albicans by pyridinium ion-based inhibitors. by Goldman RC, Zakula D, Capobianco JO, Sharpe BA, Griffin JH.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163259
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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&artid=129887
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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=abstr act&artid=162777
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Inhibitory effect of cerulenin and sodium butyrate on germination of Candida albicans. by Hoberg KA, Cihlar RL, Calderone RA.; 1983 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185332
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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&artid=133048
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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&artid=128316
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Candida Albicans
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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&artid=116558
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Investigation of Candida albicans transmission in a surgical intensive care unit cluster by using genomic DNA typing methods. by Voss A, Pfaller MA, Hollis RJ, Rhine-Chalberg J, Doebbeling BN.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227993
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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&artid=105891
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Isoenzyme changes in Candida albicans during domestication. by Lehmann PF, Wu LC, Mackenzie DW.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270388
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Isolation and characterization of Candida albicans morphological mutants derepressed for the formation of filamentous hypha-type structures. by Gil C, Pomes R, Nombela C.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208873
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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=abstr act&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 and characterization of yeast monomorphic mutants of Candida albicans. by Elorza MV, Sentandreu R, Ruiz-Herrera J.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205355
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Isolation and morphological characterization of a mycelial mutant of Candida albicans. by Hubbard MJ, Markie D, Poulter RT.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214370
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Isolation of a germ-tube-forming revertant from Candida albicans B311V6. by Buckley HR, Daneo-Moore L, Ahrens JC, Sobel JD.; 1986 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260068
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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&artid=103554
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Isolation of avirulent clones of Candida albicans with reduced ability to recognize the CR2 ligand C3d. by Franzke S, Calderone RA, Schaller K.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280898
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Killing of Candida albicans by Human Salivary Histatin 5 Is Modulated, but Not Determined, by the Potassium Channel TOK1. by Baev D, Rivetta A, Li XS, Vylkova S, Bashi E, Slayman CL, Edgerton M.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155775
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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&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&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&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&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&artid=95751
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Lysine biosynthesis in selected pathogenic fungi: characterization of lysine auxotrophs and the cloned LYS1 gene of Candida albicans. by Garrad RC, Bhattacharjee JK.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207434
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Mannan composition of the hyphal form of two relatively avirulent mutants of Candida albicans. by Saxena A, McElhaney-Feser GE, Cihlar RL.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258776
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Mechanism of Fluconazole Resistance in Candida albicans Biofilms: Phase-Specific Role of Efflux Pumps and Membrane Sterols. by Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165995
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Candida Albicans
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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=abstr act&artid=162951
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Metabolic specialization associated with phenotypic switching in Candida albicans. by Lan CY, Newport G, Murillo LA, Jones T, Scherer S, Davis RW, Agabian N.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137518
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Microdilution antifungal susceptibility testing of Candida albicans and Cryptococcus neoformans with and without agitation: an eight-center collaborative study. by Anaissie EJ, Paetznick VL, Ensign LG, Espinel-Ingroff A, Galgiani JN, Hitchcock CA, LaRocco M, Patterson T, Pfaller MA, Rex JH, Rinaldi MG.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163539
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Microsatellite polymorphism in the promoter sequence of the elongation factor 3 gene of Candida albicans as the basis for a typing system. by Bretagne S, Costa JM, Besmond C, Carsique R, Calderone R.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229840
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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&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&artid=97079
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Misexpression of the white-phase-specific gene WH11 in the opaque phase of Candida albicans affects switching and virulence. by Kvaal CA, Srikantha T, Soll DR.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175642
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Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans. by Buurman ET, Westwater C, Hube B, Brown AJ, Odds FC, Gow NA.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22718
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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&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&artid=84325
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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&artid=88541
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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 characterization of the Candida albicans enolase gene. by Mason AB, Buckley HR, Gorman JA.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204565
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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&artid=93902
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Molecular cloning of the secretory acid proteinase gene from Candida albicans and its use as a species-specific probe. by Ganesan K, Banerjee A, Datta A.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258121
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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&artid=94490
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Multidrug resistance in Candida albicans: disruption of the BENr gene. by Goldway M, Teff D, Schmidt R, Oppenheim AB, Koltin Y.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162553
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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&artid=89590
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Candida Albicans
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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&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=abstr act&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&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&artid=118025
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New aniline blue dye medium for rapid identification and isolation of Candida albicans. by Goldschmidt MC, Fung DY, Grant R, White J, Brown T.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269951
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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&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&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&artid=104810
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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&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&artid=125592
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Opaque-white phenotype transition: a programmed morphological transition in Candida albicans. by Rikkerink EH, Magee BB, Magee PT.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210739
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Optimization and Validation of Multilocus Sequence Typing for Candida albicans. by Tavanti A, Gow NA, Senesi S, Maiden MC, Odds FC.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179823
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Oral Candida albicans isolates from nonhospitalized normal carriers, immunocompetent hospitalized patients, and immunocompromised patients with or without acquired immunodeficiency syndrome. by Brawner DL, Cutler JE.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267553
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Overexpression of a cloned IMP dehydrogenase gene of Candida albicans confers resistance to the specific inhibitor mycophenolic acid. by Kohler GA, White TC, Agabian N.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178971
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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&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&artid=96991
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Overlapping coding regions and trancriptional units of two essential chromosomal genes (CCT8, TRP1)in the fungal pathogen Candida albicans. by Gerads M, Ernst JF.; 1998 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147973
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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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Partial characterization of a Candida albicans fimbrial adhesin. by Yu L, Lee KK, Ens K, Doig PC, Carpenter MR, Staddon W, Hodges RS, Paranchych W, Irvin RT.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302889
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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&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&artid=88488
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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&artid=89798
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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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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&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&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&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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PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression. by Muhlschlegel FA, Fonzi WA.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232444
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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&artid=89826
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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&artid=90716
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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&artid=103737
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Propranolol Inhibits Hyphal Development in Candida albicans. by Baker CA, Desrosiers K, Dolan JW.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128717
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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&artid=94209
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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&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&artid=90017
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Quantitative microculture system with standardized inocula for strain typing, susceptibility testing, and other physiologic measurements with Candida albicans and other yeasts. by Odds FC.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270424
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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&artid=92970
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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&artid=90798
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Rapid detection and identification of Candida albicans and Torulopsis (Candida) glabrata in clinical specimens by species-specific nested PCR amplification of a
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cytochrome P-450 lanosterol-alpha-demethylase (L1A1) gene fragment. by BurgenerKairuz P, Zuber JP, Jaunin P, Buchman TG, Bille J, Rossier M.; 1994 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263900 •
Rapid Detection of Candida albicans in Clinical Blood Samples by Using a TaqManBased PCR Assay. by Maaroufi Y, Heymans C, De Bruyne JM, Duchateau V, RodriguezVillalobos H, Aoun M, Crokaert F.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165319
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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&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&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&artid=104892
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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&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&artid=103768
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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&artid=84240
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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 Candida albicans mutants affected in multidrug resistance. by Becker JM, Henry LK, Jiang W, Koltin Y.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173643
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Reduced virulence of Candida albicans PHR1 mutants. by Ghannoum MA, Spellberg B, Saporito-Irwin SM, Fonzi WA.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173646
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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&artid=97378
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Reevaluation of the Role of HWP1 in Systemic Candidiasis by Use of Candida albicans Strains with Selectable Marker URA3 Targeted to the ENO1 Locus. by Sundstrom P, Cutler JE, Staab JF.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128023
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Relationship between cell surface composition, adherence, and virulence of Candida albicans. by McCourtie J, Douglas LJ.; 1984 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263245
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Relationship between Switching and Mating in Candida albicans. by Soll DR, Lockhart SR, Zhao R.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161441
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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
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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&artid=97832
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Resistance Mechanisms in Clinical Isolates of Candida albicans. by White TC, Holleman S, Dy F, Mirels LF, Stevens DA.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127245
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Restriction fragment length polymorphism analysis of azole-resistant and azolesusceptible Candida albicans strains. by Pearce MA, Howell SA.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270118
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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&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&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&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 cell defense against oxidative damage in the resistance of Candida albicans to the killing effect of amphotericin B. by Sokol-Anderson M, Sligh JE Jr, Elberg S, Brajtburg J, Kobayashi GS, Medoff G.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172255
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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&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&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&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&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&artid=118011
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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&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&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&artid=105764
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Serologic Response to Cell Wall Mannoproteins and Proteins of Candida albicans. by Martinez JP, Gil ML, Lopez-Ribot JL, Chaffin WL.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121378
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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&artid=88280
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Serotype prevalence of Candida albicans from blood culture isolates. by Brawner DL, Anderson GL, Yuen KY.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265011
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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&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&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&artid=97861
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Skin Facilitates Candida albicans Mating. by Lachke SA, Lockhart SR, Daniels KJ, Soll DR.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187354
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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&artid=93895
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Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media. by Yan S, Negre E, Cashel JA, Guo N, Lyman CA, Walsh TJ, Roberts DD.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174169
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Strain relatedness of Candida albicans strains isolated from children with leukemia and their bedside parents. by Doi M, Homma M, Iwaguchi S, Horibe K, Tanaka K.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263977
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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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Structural modification of cell wall mannans of Candida albicans serotype A strains grown in yeast extract-Sabouraud liquid medium under acidic conditions. by Kobayashi H, Takahashi S, Shibata N, Miyauchi M, Ishida M, Sato J, Maeda K, Suzuki S.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186211
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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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Sublethal Injury and Resuscitation of Candida albicans after Amphotericin B Treatment. by Liao RS, Rennie RP, Talbot JA.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152497
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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=abstr act&artid=163524
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Switching of Candida albicans during successive episodes of recurrent vaginitis. by Soll DR, Galask R, Isley S, Rao TV, Stone D, Hicks J, Schmid J, Mac K, Hanna C.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267398
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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&artid=132753
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Temporal Expression of the Candida albicans Genes CHK1 and CSSK1, Adherence, and Morphogenesis in a Model of Reconstituted Human Esophageal Epithelial Candidiasis. by Li D, Bernhardt J, Calderone R.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127796
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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&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&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 HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins. by Bailey DA, Feldmann PJ, Bovey M, Gow NA, Brown AJ.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178351
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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 albicans plasma membrane and H(+)-ATPase during yeast growth and germ tube formation. by Monk BC, Niimi M, Shepherd MG.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206613
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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&artid=108162
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The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. by Santos MA, Tuite MF.; 1995 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306886
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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&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&artid=95357
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The Hog1 Mitogen-Activated Protein Kinase Is Essential in the Oxidative Stress Response and Chlamydospore Formation in Candida albicans. by Alonso-Monge R, Navarro-Garcia F, Roman E, Negredo AI, Eisman B, Nombela C, Pla J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154845
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The inducible N-acetylglucosamine catabolic pathway gene cluster in Candida albicans: Discrete N-acetylglucosamine-inducible factors interact at the promoter of NAG1. by Kumar MJ, Jamaluddin MS, Natarajan K, Kaur D, Datta A.; 2000 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18898
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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&artid=108348
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The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14alpha demethylase in Candida albicans. by White TC.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163945
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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&artid=89629
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The sea pansy Renilla reniformis luciferase serves as a sensitive bioluminescent reporter for differential gene expression in Candida albicans. by Srikantha T, Klapach A, Lorenz WW, Tsai LK, Laughlin LA, Gorman JA, Soll DR.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177628
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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&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&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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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&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&artid=90061
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Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection. by Staib P, Kretschmar M, Nichterlein T, Hof H, Morschhauser J.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127704
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Transformations of inorganic mercury by Candida albicans and Saccharomyces cerevisiae. by Yannai S, Berdicevsky I, Duek L.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182692
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Two mechanisms of butenafine action in Candida albicans. by Iwatani W, Arika T, Yamaguchi H.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187760
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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&artid=87978
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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&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&artid=90168
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Unique phenotype of opaque cells in the white-opaque transition of Candida albicans. by Anderson JM, Soll DR.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213989
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Uptake and antifungal activity of oligonucleotides in Candida albicans. by Disney MD, Haidaris CG, Turner DH.; 2003 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149866
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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&artid=140389
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Variability in expression of a cell surface determinant on Candida albicans as evidenced by an agglutinating monoclonal antibody. by Brawner DL, Cutler JE.; 1984 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264279
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Variability in expression of cell surface antigens of Candida albicans during morphogenesis. by Brawner DL, Cutler JE.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261107
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Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model. by Barchiesi F, Najvar LK, Luther MF, Scalise G, Rinaldi MG, Graybill JR.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163320
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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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Variations in the number of ribosomal DNA units in morphological mutants and normal strains of Candida albicans and in normal strains of Saccharomyces cerevisiae. by Rustchenko EP, Curran TM, Sherman F.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206860
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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&artid=98190
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals.
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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To generate your own bibliography of studies dealing with Candida albicans, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Candida albicans” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Candida albicans (hyperlinks lead to article summaries): •
A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance. Author(s): de Micheli M, Bille J, Schueller C, Sanglard D. Source: Molecular Microbiology. 2002 March; 43(5): 1197-214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918807&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 molecular epidemiological study of sequential oral isolates of Candida albicans from terminally ill patients. Author(s): Wilson MJ, Williams DW, Forbes MD, Finlay IG, Lewis MA. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 April; 30(4): 206-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302239&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 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. 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
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A novel type 2C protein phosphatase from the human fungal pathogen Candida albicans. Author(s): Jiang L, Whiteway M, Shen SH. Source: Febs Letters. 2001 November 30; 509(1): 142-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734222&dopt=Abstract
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A patient with subdural spinal granuloma due to Candida albicans who was treated successfully by surgical and antimicrobial therapy. Author(s): Kastenbauer S. Source: Spine. 2003 May 1; 28(9): 960-1; Author Reply 961-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942017&dopt=Abstract
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A quantitative radiometric assay to measure mammalian cell binding to hyphae of Candida albicans. Author(s): Forsyth CB, Mathews HL. Source: Journal of Immunological Methods. 1993 September 27; 165(1): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8409462&dopt=Abstract
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A simple PCR/RFLP analysis can differentiate between Candida albicans, Aspergillus niger, and Aspergillus fumigatus. Author(s): Isik N, White L, Barnes R, Poynton CJ, Mills KI. Source: Molecular Biotechnology. 2003 July; 24(3): 229-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777690&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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ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida albicans are general phospholipid translocators. Author(s): Smriti, Krishnamurthy S, Dixit BL, Gupta CM, Milewski S, Prasad R. Source: Yeast (Chichester, England). 2002 March 15; 19(4): 303-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870854&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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Adherence of yeast and filamentous forms of Candida albicans to cultured enterocytes. Author(s): Wiesner SM, Bendel CM, Hess DJ, Erlandsen SL, Wells CL. Source: Critical Care Medicine. 2002 March; 30(3): 677-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990933&dopt=Abstract
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Adhesion and cell-surface-hydrophobicity of sequentially isolated genetic isotypes of Candida albicans in an HIV-infected Southern Chinese cohort. Author(s): Samaranayake YH, Samaranayake LP, Yau JY, Ellepola AN, Anil S, Yeung KW. Source: Mycoses. 2003; 46(9-10): 375-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622385&dopt=Abstract
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Allergens of Pityrosporum ovale and Candida albicans. I. Cross-reactivity of IgEbinding components. Author(s): Doekes G, van Ieperen-van Dijk AG. Source: Allergy. 1993 August; 48(6): 394-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8238794&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 susceptibility testing of Candida albicans by flow cytometry. Author(s): Gokahmetoglu S, Nedret Koc A, Patiroglu T. Source: Mycoses. 2003 September; 46(8): 307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950899&dopt=Abstract
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Application of biotyping and DNA typing of Candida albicans to the epidemiology of recurrent vulvovaginal candidiasis. Author(s): Mercure S, Poirier S, Lemay G, Auger P, Montplaisir S, de Repentigny L. Source: The Journal of Infectious Diseases. 1993 August; 168(2): 502-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8101553&dopt=Abstract
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Atypical strains of Candida albicans recovered from AIDS patients. Author(s): Pujol C, Renaud F, Mallie M, de Meeus T, Bastide JM. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1997 March-April; 35(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9147271&dopt=Abstract
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Benzydamine inhibits the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1 by Candida albicans-stimulated human peripheral blood cells. Author(s): Sironi M, Milanese C, Vecchi A, Polenzani L, Guglielmotti A, Coletta I, Landolfi C, Soldo L, Mantovani A, Pinza M. Source: International Journal of Clinical & Laboratory Research. 1997; 27(2): 118-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266282&dopt=Abstract
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Beta-1,2- and alpha-1,2-linked oligomannosides mediate adherence of Candida albicans blastospores to human enterocytes in vitro. Author(s): Dalle F, Jouault T, Trinel PA, Esnault J, Mallet JM, d'Athis P, Poulain D, Bonnin A. Source: Infection and Immunity. 2003 December; 71(12): 7061-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638796&dopt=Abstract
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Bilateral Candida albicans endophthalmitis associated with an infected deep venous thrombus. Author(s): Arroyo JG, Bula DV, Grant CA, Murtha T. Source: Japanese Journal of Ophthalmology. 2004 January-February; 48(1): 30-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14767647&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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Binding of resting platelets to Candida albicans germ tubes. Author(s): Robert R, Mahaza C, Miegeville M, Ponton J, Marot-Leblond A, Senet JM. Source: Infection and Immunity. 1996 September; 64(9): 3752-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8751925&dopt=Abstract
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Biochemical and immunological characterization of MP65, a major mannoprotein antigen of the opportunistic human pathogen Candida albicans. Author(s): Gomez MJ, Maras B, Barca A, La Valle R, Barra D, Cassone A. Source: Infection and Immunity. 2000 February; 68(2): 694-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639435&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 in infectious crystalline keratopathy due to Candida albicans. Author(s): Elder MJ, Matheson M, Stapleton F, Dart JK. Source: Cornea. 1996 May; 15(3): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8713934&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-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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Biological activities of naturally occurring antibodies reactive with Candida albicans mannan. Author(s): Kozel TR, MacGill RS, Percival A, Zhou Q. Source: Infection and Immunity. 2004 January; 72(1): 209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14688098&dopt=Abstract
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Biomaterial-associated infection with Candida albicans in mice. Author(s): Rozalska B, Ljungh A, Burow A, Rudnicka W. Source: Microbiology and Immunology. 1995; 39(7): 443-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8569528&dopt=Abstract
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Biotypes of oral Candida albicans isolated from AIDS patients and HIV-free subjects in Thailand. Author(s): Teanpaisan R, Nittayananta W, Chongsuvivatwong V. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2000 May; 29(5): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801035&dopt=Abstract
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Biotypes of oral Candida albicans isolates in a Tanzanian child population. Author(s): Matee MI, Samaranayake LP, Scheutz F, Simon E, Lyamuya EF, Mwinula J. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1996 September; 104(9): 623-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8972686&dopt=Abstract
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Blood group glycolipids as epithelial cell receptors for Candida albicans. Author(s): Cameron BJ, Douglas LJ. Source: Infection and Immunity. 1996 March; 64(3): 891-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8641797&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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Breast cancer-specific expression of the Candida albicans cytosine deaminase gene using a transcriptional targeting approach. Author(s): Anderson LM, Krotz S, Weitzman SA, Thimmapaya B. Source: Cancer Gene Therapy. 2000 June; 7(6): 845-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880014&dopt=Abstract
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Bromelain is an accelerator of phagocytosis, respiratory burst and Killing of Candida albicans by human granulocytes and monocytes. Author(s): Brakebusch M, Wintergerst U, Petropoulou T, Notheis G, Husfeld L, Belohradsky BH, Adam D. Source: European Journal of Medical Research. 2001 May 29; 6(5): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410400&dopt=Abstract
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Burn-associated Candida albicans infection caused by CD30+ type 2 T cells. Author(s): Kobayashi M, Kobayashi H, Herndon DN, Pollard RB, Suzuki F. Source: Journal of Leukocyte Biology. 1998 June; 63(6): 723-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9620665&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 clades. Author(s): Soll DR, Pujol C. Source: Fems Immunology and Medical Microbiology. 2003 October 24; 39(1): 1-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556989&dopt=Abstract
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Candida albicans colonization of surface-sealed interim soft liners. Author(s): Olan-Rodriguez L, Minah GE, Driscoll CF. Source: Journal of Prosthodontics : Official Journal of the American College of Prosthodontists. 2000 December; 9(4): 184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320469&dopt=Abstract
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Candida albicans colonization on thermal cycled maxillofacial polymeric materials in vitro. Author(s): Nikawa H, Chen J, Hamada T, Nishimura M, Polyzois G. Source: Journal of Oral Rehabilitation. 2001 June; 28(6): 526-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422678&dopt=Abstract
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Candida albicans induces selectively transcriptional activation of cyclooxygenase-2 in HeLa cells: pivotal roles of Toll-like receptors, p38 mitogen-activated protein kinase, and NF-kappa B. Author(s): Deva R, Shankaranarayanan P, Ciccoli R, Nigam S. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 September 15; 171(6): 304755. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960330&dopt=Abstract
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Candida albicans molecular biology reaches its maturity. Author(s): Larriba G, Rubio Coque JJ, Ciudad A, Andaluz E. Source: International Microbiology : the Official Journal of the Spanish Society for Microbiology. 2000 December; 3(4): 247-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334309&dopt=Abstract
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Candida albicans myocardial abscess. Author(s): Bhatti MA, Karmarkar R, Wagner DK. Source: J Coll Physicians Surg Pak. 2003 August; 13(8): 456-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921685&dopt=Abstract
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Candida albicans proteinases: resolving the mystery of a gene family. Author(s): Hube B, Naglik J. Source: Microbiology (Reading, England). 2001 August; 147(Pt 8): 1997-2005. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495978&dopt=Abstract
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Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Author(s): Naglik JR, Challacombe SJ, Hube B. Source: Microbiology and Molecular Biology Reviews : Mmbr. 2003 September; 67(3): 400-28, Table of Contents. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966142&dopt=Abstract
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Candida albicans strain carriage in patients and nursing staff of an intensive care unit: a study of morphotypes and resistotypes. Author(s): Khan ZU, Chandy R, Metwali KE. Source: Mycoses. 2003 December; 46(11-12): 479-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14641621&dopt=Abstract
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Candida albicans yeast and germ tube forms interfere differently with human monocyte differentiation into dendritic cells: a novel dimorphism-dependent mechanism to escape the host's immune response. Author(s): Torosantucci A, Romagnoli G, Chiani P, Stringaro A, Crateri P, Mariotti S, Teloni R, Arancia G, Cassone A, Nisini R. Source: Infection and Immunity. 2004 February; 72(2): 833-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14742527&dopt=Abstract
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Candida dubliniensis infections in a pediatric population: retrospective identification from clinical laboratory isolates of Candida albicans. Author(s): Kim JO, Garofalo L, Blecker-Shelly D, McGowan KL. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3354-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843092&dopt=Abstract
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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. Author(s): Bahn YS, Sundstrom P. Source: Journal of Bacteriology. 2001 May; 183(10): 3211-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325951&dopt=Abstract
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Cervical lymphadenitis caused by Candida albicans. Author(s): Sang H, Wu B, Zhang X. Source: Mycoses. 2003; 46(9-10): 422-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622393&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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Clonal identity of Candida albicans in the oral cavity and the gastrointestinal tract of pre-school children. Author(s): Hossain H, Ansari F, Schulz-Weidner N, Wetzel WE, Chakraborty T, Domann E. Source: Oral Microbiology and Immunology. 2003 October; 18(5): 302-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930522&dopt=Abstract
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Combined action of fluconazole and PMNs from uremic patients in clearing intracellular Candida albicans. Author(s): Tullio V, Cuffini AM, Giacchino F, Mandras N, Roana J, Comune L, Merlino C, Carlone NA. Source: J Chemother. 2003 June; 15(3): 301-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868562&dopt=Abstract
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Comparison of media for optimal recovery of Candida albicans and Candida glabrata from blood culture. Author(s): Moore JE, McMullan R. Source: Ir J Med Sci. 2003 April-June; 172(2): 60-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930053&dopt=Abstract
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COS-l, a putative two-component histidine kinase of Candida albicans, is an in vivo virulence factor. Author(s): Selitrennikoff CP, Alex L, Miller TK, Clemons KV, Simon MI, Stevens DA. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2001 February; 39(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270409&dopt=Abstract
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Decrease in Candida albicans strains with reduced susceptibility to fluconazole following changes in prescribing policies. Author(s): Lopez J, Pernot C, Aho S, Caillot D, Vagner O, Dalle F, Durnet-Archeray MJ, Chavanet P, Bonnin A. Source: The Journal of Hospital Infection. 2001 June; 48(2): 122-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11428879&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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Deletion of the two-component histidine kinase gene (CHK1) of Candida albicans contributes to enhanced growth inhibition and killing by human neutrophils in vitro. Author(s): Torosantucci A, Chiani P, De Bernardis F, Cassone A, Calera JA, Calderone R. Source: Infection and Immunity. 2002 February; 70(2): 985-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796636&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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Detachment activity of human saliva in vitro for Candida albicans cells attached to a plastic plate. Author(s): Kamagata-Kiyoura Y, Abe S, Yamaguchi H, Nitta T. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 September; 9(3): 215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513388&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 antibodies to Candida albicans germ tubes in heroin addicts with systemic candidiasis. Author(s): Linares MJ, Javier MR, Villanueva JL, Solis F, Torre-Cisneros J, Rodriguez F, Kindelan JM, Casal M. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2001 April; 7(4): 218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422247&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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Differences in Candida albicans adhesion to intact and denatured type I collagen in vitro. Author(s): Makihira S, Nikawa H, Tamagami M, Hamada T, Samaranayake LP. Source: Oral Microbiology and Immunology. 2002 April; 17(2): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929562&dopt=Abstract
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Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo. Author(s): Schaller M, Januschke E, Schackert C, Woerle B, Korting HC. Source: Journal of Medical Microbiology. 2001 August; 50(8): 743-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478679&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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Differentiation of Candida dubliniensis from Candida albicans on Pal's agar. Author(s): Al Mosaid A, Sullivan DJ, Coleman DC. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4787-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532221&dopt=Abstract
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Disk diffusion method for fluconazole susceptibility testing of Candida albicans strains. Author(s): Yucesoy M, Guldas NS, Yulug N. Source: J Chemother. 2001 April; 13(2): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11330363&dopt=Abstract
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Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans. Author(s): Cowen LE, Kohn LM, Anderson JB. Source: Journal of Bacteriology. 2001 May; 183(10): 2971-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325923&dopt=Abstract
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DNA fingerprinting of serial Candida albicans isolates obtained during itraconazole prophylaxis in patients with AIDS. Author(s): Le Monte AM, Goldman M, Smedema ML, Connolly PA, McKinsey DS, Cloud GA, Kauffman CA, Wheat LJ; National Institute of Allergy and Infectious Disease Mycoses Study Group. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2001 April; 39(2): 207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346270&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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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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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 metals on Candida albicans growth in the presence of chemical chelators and human abscess fluid. Author(s): Sohnle PG, Hahn BL, Karmarkar R. Source: The Journal of Laboratory and Clinical Medicine. 2001 April; 137(4): 284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11283523&dopt=Abstract
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Effect of prolonged fluconazole treatment on Candida albicans in diffusion chambers implanted into mice. Author(s): Sohnle PG, Hahn BL. Source: Antimicrobial Agents and Chemotherapy. 2002 October; 46(10): 3175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234841&dopt=Abstract
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Effect of sodium hypochlorite and five intracanal medications on Candida albicans in root canals. Author(s): Valera MC, de Moraes Rego J, Jorge AO. Source: Journal of Endodontics. 2001 June; 27(6): 401-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11487135&dopt=Abstract
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Electrophoretic karyotyping of Candida albicans strains isolated from premature infants and hospital personnel in a neonatal intensive care unit. Author(s): Dorko E, Viragova S, Jautova J, Pilipcinec E, Danko J, Svicky E, Tkacikova L. Source: Folia Microbiol (Praha). 2001; 46(5): 453-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899481&dopt=Abstract
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Electrophoretic protein patterns and numerical analysis of Candida albicans from the oral cavities of healthy children. Author(s): Boriollo MF, Rosa EA, Bernardo WL, Goncalves RB, Hofling JF. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2003 SeptemberOctober; 45(5): 249-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14743664&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. 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
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Endogenous Rhodotorula minuta and Candida albicans endophthalmitis in an injecting drug user. Author(s): Pinna A, Carta F, Zanetti S, Sanna S, Sechi LA. Source: The British Journal of Ophthalmology. 2001 June; 85(6): 759. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426427&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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Essential role of the Candida albicans transglutaminase substrate, hyphal wall protein 1, in lethal oroesophageal candidiasis in immunodeficient mice. Author(s): Sundstrom P, Balish E, Allen CM. Source: The Journal of Infectious Diseases. 2002 February 15; 185(4): 521-30. Epub 2002 January 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11865405&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 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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Evidence for a more recently evolved clade within a Candida albicans North American population. Author(s): Lott TJ, Effat MM. Source: Microbiology (Reading, England). 2001 June; 147(Pt 6): 1687-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390700&dopt=Abstract
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Evolution of drug resistance in Candida albicans. Author(s): Cowen LE, Anderson JB, Kohn LM. Source: Annual Review of Microbiology. 2002; 56: 139-65. Epub 2002 January 30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142485&dopt=Abstract
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Experimental Candida albicans lesions in healthy humans: dependence on skin pH. Author(s): Runeman B, Faergemann J, Larko O. Source: Acta Dermato-Venereologica. 2000 November-December; 80(6): 421-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243634&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 affecting the adherence of Candida albicans to human buccal epithelial cells in human immunodeficiency virus infection. Author(s): Tsang CS, Samaranayake LP. Source: The British Journal of Dermatology. 1999 November; 141(5): 852-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10583166&dopt=Abstract
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Factors affecting the adhesion of Candida albicans to epithelial cells of insulin-using diabetes mellitus patients. Author(s): Willis AM, Coulter WA, Hayes JR, Bell P, Lamey PJ. Source: Journal of Medical Microbiology. 2000 March; 49(3): 291-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10707950&dopt=Abstract
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Factors influencing the expression in vitro of Candida albicans stress mannoproteins reactive with salivary secretory IgA. Author(s): Vidotto V, Polonelli L, Conti S, Ponton J, Vieta I. Source: Mycopathologia. 1998; 141(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725025&dopt=Abstract
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Failure of all antifungal therapy for infection due to Candida albicans: a new AIDSrelated problem? Author(s): Landman D, Saurina G, Quale JM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 January; 26(1): 183-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9455530&dopt=Abstract
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Failure of indinavir to inhibit Candida albicans in vitro. Author(s): Diz Dios P, Otero Varela I, Iglesias Martin I, Ocampo Hermida A, Martinez Vazquez C. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 October; 18(10): 7556. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584909&dopt=Abstract
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Fas-FasL interactions modulate host defense against systemic Candida albicans infection. Author(s): Netea MG, van Der Meer JW, Meis JF, Kullberg BJ. Source: The Journal of Infectious Diseases. 1999 November; 180(5): 1648-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515828&dopt=Abstract
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Female genital tract bacterial coisolates with Candida albicans in patients without clinical vaginitis. Author(s): Monif GR, Carson HJ. Source: Infectious Diseases in Obstetrics and Gynecology. 1998; 6(2): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9702585&dopt=Abstract
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Fetal death associated with asymptomatic intrauterine Candida albicans infection and a retained intrauterine contraceptive device. Author(s): Segal D, Gohar J, Huleihel M, Mazor M. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(1): 77-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11234987&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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Fluconazole susceptibility and strain variation of Candida albicans isolates from HIV-infected patients with oropharyngeal candidosis. Author(s): Barchiesi F, Arzeni D, Del Prete MS, Sinicco A, Falconi Di Francesco L, Pasticci MB, Lamura L, Nuzzo MM, Burzacchini F, Coppola S, Chiodo F, Scalise G. Source: The Journal of Antimicrobial Chemotherapy. 1998 May; 41(5): 541-8. Erratum In: J Antimicrob Chemother 1998 September; 42(3): 413. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9630407&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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Fluconazole therapy in Candida albicans spondylodiscitis. Author(s): Rossel P, Schonheyder HC, Nielsen H. Source: Scandinavian Journal of Infectious Diseases. 1998; 30(5): 527-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10066061&dopt=Abstract
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Fluconazole versus Candida albicans: a complex relationship. Author(s): Graybill JR, Montalbo E, Kirkpatrick WR, Luther MF, Revankar SG, Patterson TF. Source: Antimicrobial Agents and Chemotherapy. 1998 November; 42(11): 2938-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9797229&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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Fucose-specific adhesins on germ tubes of Candida albicans. Author(s): Vardar-Unlu G, McSharry C, Douglas LJ. Source: Fems Immunology and Medical Microbiology. 1998 January; 20(1): 55-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514576&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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Functional characterization of the Candida albicans MNT1 mannosyltransferase expressed heterologously in Pichia pastoris. Author(s): Thomson LM, Bates S, Yamazaki S, Arisawa M, Aoki Y, Gow NA. Source: The Journal of Biological Chemistry. 2000 June 23; 275(25): 18933-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766761&dopt=Abstract
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Fungal endophthalmitis diagnosis by detection of Candida albicans DNA in intraocular fluid by use of a species-specific polymerase chain reaction assay. Author(s): Hidalgo JA, Alangaden GJ, Eliott D, Akins RA, Puklin J, Abrams G, Vazquez JA. Source: The Journal of Infectious Diseases. 2000 March; 181(3): 1198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10720555&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 activity of fluconazole against Candida albicans in a synthetic vaginasimulative medium. Author(s): Moosa MY, Sobel JD, Elhalis H, Du W, Akins RA. Source: Antimicrobial Agents and Chemotherapy. 2004 January; 48(1): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14693534&dopt=Abstract
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Gastrointestinal colonization by Candida albicans mutant strains in antibiotic-treated mice. Author(s): Wiesner SM, Jechorek RP, Garni RM, Bendel CM, Wells CL. Source: Clinical and Diagnostic Laboratory Immunology. 2001 January; 8(1): 192-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11139219&dopt=Abstract
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Gene expression in HL60 granulocytoids and human polymorphonuclear leukocytes exposed to Candida albicans. Author(s): Mullick A, Elias M, Harakidas P, Marcil A, Whiteway M, Ge B, Hudson TJ, Caron AW, Bourget L, Picard S, Jovcevski O, Massie B, Thomas DY. Source: Infection and Immunity. 2004 January; 72(1): 414-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14688123&dopt=Abstract
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Gene regulation and host adaptation mechanisms in Candida albicans. Author(s): Staib P, Wirsching S, Strauss A, Morschhauser J. Source: International Journal of Medical Microbiology : Ijmm. 2001 May; 291(2): 183-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437340&dopt=Abstract
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Generation of a recombinant 65-kilodalton mannoprotein, a major antigen target of cell-mediated immune response to Candida albicans. Author(s): La Valle R, Sandini S, Gomez MJ, Mondello F, Romagnoli G, Nisini R, Cassone A. Source: Infection and Immunity. 2000 December; 68(12): 6777-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11083795&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 control of chlamydospore formation in Candida albicans. Author(s): Nobile CJ, Bruno VM, Richard ML, Davis DA, Mitchell AP. Source: Microbiology (Reading, England). 2003 December; 149(Pt 12): 3629-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663094&dopt=Abstract
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Genetic structure of typical and atypical populations of Candida albicans from Africa. Author(s): Forche A, Schonian G, Graser Y, Vilgalys R, Mitchell TG. Source: Fungal Genetics and Biology : Fg & B. 1999 November; 28(2): 107-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587473&dopt=Abstract
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Genetically distinct strains of Candida albicans with elevated secretory proteinase production are associated with diarrhoea in hospitalized children. Author(s): Mathaba LT, Paxman AE, Ward PB, forbes DA, Warmington JR. Source: Journal of Gastroenterology and Hepatology. 2000 January; 15(1): 53-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10719748&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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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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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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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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Glycine metabolism in Candida albicans: characterization of the serine hydroxymethyltransferase (SHM1, SHM2) and threonine aldolase (GLY1) genes. Author(s): McNeil JB, Flynn J, Tsao N, Monschau N, Stahmann K, Haynes RH, McIntosh EM, Pearlman RE. Source: Yeast (Chichester, England). 2000 January 30; 16(2): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641038&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 competition between Candida dubliniensis and Candida albicans under broth and biofilm growing conditions. Author(s): Kirkpatrick WR, Lopez-Ribot JL, McAtee RK, Patterson TF. Source: Journal of Clinical Microbiology. 2000 February; 38(2): 902-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655413&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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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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Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV-infected southern Chinese cohort. Author(s): Samaranayake YH, Samaranayake LP, Tsang PC, Wong KH, Yeung KW. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2001 July; 30(6): 336-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11459319&dopt=Abstract
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Heterogeneity of metallo and serine extracellular proteinases in oral clinical isolates of Candida albicans in HIV-positive and healthy children from Rio de Janeiro, Brazil. Author(s): de Brito Costa EM, dos Santos AL, Cardoso AS, Portela MB, Abreu CM, Alviano CS, Hagler AN, de Araujo Soares RM. Source: Fems Immunology and Medical Microbiology. 2003 September 22; 38(2): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129652&dopt=Abstract
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Heterogeneity of oral isolates of Candida albicans in HIV-positive patients: correlation between candidal carriage, karyotype and disease stage. Author(s): Capoluongo E, Moretto D, Giglio A, Belardi M, Prignano G, Crescimbeni E, Cordiali-Fei P, Maini A, Di Carlo A, Mercantini R, Giannetti A, Ameglio F. Source: Journal of Medical Microbiology. 2000 November; 49(11): 985-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11073152&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 levels of hydrolytic enzymes secreted by Candida albicans isolates involved in respiratory infections. Author(s): Borst A, Fluit AC. Source: Journal of Medical Microbiology. 2003 November; 52(Pt 11): 971-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532341&dopt=Abstract
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High-affinity myo-inositol transport in Candida albicans: substrate specificity and pharmacology. Author(s): Jin JH, Seyfang A. Source: Microbiology (Reading, England). 2003 December; 149(Pt 12): 3371-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663071&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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Histidine kinase, two-component signal transduction proteins of Candida albicans and the pathogenesis of candidosis. Author(s): Calera JA, Calderone R. Source: Mycoses. 1999; 42 Suppl 2: 49-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865904&dopt=Abstract
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HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro. Author(s): Bektic J, Lell CP, Fuchs A, Stoiber H, Speth C, Lass-Florl C, Borg-von Zepelin M, Dierich MP, Wurzner R. Source: Fems Immunology and Medical Microbiology. 2001 July; 31(1): 65-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476984&dopt=Abstract
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HIV-1 Nef protein inhibits the in vitro induction of a specific antibody response to Candida albicans by an early up-regulation of IL-15 production. Author(s): Giordani L, Giacomini E, Quaranta MG, Viora M. Source: Clinical and Experimental Immunology. 2000 December; 122(3): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122241&dopt=Abstract
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HIV-Protease inhibitors reduce cell adherence of Candida albicans strains by inhibition of yeast secreted aspartic proteases. Author(s): Borg-von Zepelin M, Meyer I, Thomssen R, Wurzner R, Sanglard D, Telenti A, Monod M. Source: The Journal of Investigative Dermatology. 1999 November; 113(5): 747-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10571729&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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Human salivary histatin 5 fungicidal action does not induce programmed cell death pathways in Candida albicans. Author(s): Wunder D, Dong J, Baev D, Edgerton M. Source: Antimicrobial Agents and Chemotherapy. 2004 January; 48(1): 110-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14693527&dopt=Abstract
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HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans. Author(s): Park KS, Kang KC, Kim KY, Jeong PY, Kim JH, Adams DJ, Kim JH, Paik YK. Source: The Journal of Antimicrobial Chemotherapy. 2001 May; 47(5): 513-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328760&dopt=Abstract
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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. Author(s): Liu L, Kang K, Takahara M, Cooper KD, Ghannoum MA. Source: Infection and Immunity. 2001 July; 69(7): 4695-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11402019&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 characterization of a Candida albicans mating pheromone. Author(s): Bennett RJ, Uhl MA, Miller MG, Johnson AD. Source: Molecular and Cellular Biology. 2003 November; 23(22): 8189-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585977&dopt=Abstract
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Identification of Candida albicans genes induced during thrush offers insight into pathogenesis. Author(s): Cheng S, Clancy CJ, Checkley MA, Handfield M, Hillman JD, Progulske-Fox A, Lewin AS, Fidel PL, Nguyen MH. Source: Molecular Microbiology. 2003 June; 48(5): 1275-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787355&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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IL-5 production by peripheral blood Th cells of adult asthma patients in response to Candida albicans allergen. Author(s): Mori A, Ikeda Y, Taniguchi M, Aoyama C, Maeda Y, Hasegawa M, Kobayashi N, Akiyama K. Source: International Archives of Allergy and Immunology. 2001; 125 Suppl 1: 48-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408773&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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In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains. Author(s): D'Auria FD, Tecca M, Strippoli R, Simonetti N. Source: Letters in Applied Microbiology. 2001 April; 32(4): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298929&dopt=Abstract
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In vitro secreted aspartyl proteinase activity of Candida albicans isolated from oral diseases and healthy oral cavities. Author(s): Kuriyama T, Williams DW, Lewis MA. Source: Oral Microbiology and Immunology. 2003 December; 18(6): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14622349&dopt=Abstract
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Influence of human serum on antifungal pharmacodynamics with Candida albicans. Author(s): Zhanel GG, Saunders DG, Hoban DJ, Karlowsky JA. Source: Antimicrobial Agents and Chemotherapy. 2001 July; 45(7): 2018-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408217&dopt=Abstract
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Inhibition of Clotrimazole-resistant Candida albicans by plants used in Iranian folkloric medicine. Author(s): Bonjar GH. Source: Fitoterapia. 2004 January; 75(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14693224&dopt=Abstract
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Inhibition of hydrophobic protein-mediated Candida albicans attachment to endothelial cells during physiologic shear flow. Author(s): Glee PM, Cutler JE, Benson EE, Bargatze RF, Hazen KC. Source: Infection and Immunity. 2001 May; 69(5): 2815-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292693&dopt=Abstract
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Inhibition of hyphal growth of Candida albicans by activated lansoprazole, a novel benzimidazole proton pump inhibitor. Author(s): Biswas SK, Yokoyama K, Kamei K, Nishimura K, Miyaji M. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2001 June; 39(3): 283-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446532&dopt=Abstract
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Integration of Raman microscopy, differential interference contrast microscopy, and attenuated total reflection Fourier transform infrared spectroscopy to investigate chlorhexidine spatial and temporal distribution in Candida albicans biofilms. Author(s): Suci PA, Geesey GG, Tyler BJ. Source: Journal of Microbiological Methods. 2001 September; 46(3): 193-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438184&dopt=Abstract
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Interstitial lung disease induced by endogenous Candida albicans. Author(s): Schreiber J, Goring HD, Rosahl W, Struben C, Lakotta W, Amthor M. Source: European Journal of Medical Research. 2001 February 28; 6(2): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313193&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 characterization of the Candida albicans MOT2 gene. Author(s): Zhao XJ, Calderone RA, Krueger KE, Choi G, Cihlar RL. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2001 February; 39(1): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270411&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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Karyotyping of Candida albicans and Candida glabrata from patients with Candida sepsis. Author(s): Klempp-Selb B, Rimek D, Kappe R. Source: Mycoses. 2000; 43(5): 159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10948811&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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Karyotyping of Candida albicans isolates obtained longitudinally in women with recurrent vulvovaginal candidiasis. Author(s): Vazquez JA, Sobel JD, Demitriou R, Vaishampayan J, Lynch M, Zervos MJ. Source: The Journal of Infectious Diseases. 1994 December; 170(6): 1566-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7995997&dopt=Abstract
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Ketoconazole and itraconazole susceptibility of Candida albicans isolated from patients infected with HIV. Author(s): St-Germain G, Dion C, Espinel-Ingroff A, Ratelle J, de Repentigny L. Source: The Journal of Antimicrobial Chemotherapy. 1995 July; 36(1): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8537258&dopt=Abstract
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Ketoconazole in the treatment of osteomyelitis due to Candida albicans. Author(s): Bannatyne RM, Clarke HM. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 1989 May; 32(3): 201-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2713774&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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Lack of sialidase activity in Candida albicans and Candida glabrata. Author(s): Roggentin P, Krug G, Schauer R, Brasch J. Source: Mycoses. 1999 April; 42(1-2): 33-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394845&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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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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Linkage of adhesion, morphogenesis, and virulence in Candida albicans. Author(s): Hostetter MK. Source: The Journal of Laboratory and Clinical Medicine. 1998 October; 132(4): 258-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9794696&dopt=Abstract
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Long-distance bactericidal and fungicidal effectiveness of parachlorophenol and Formalin on Streptococcus faecalis and Candida albicans. Author(s): The SD. Source: Journal of Endodontics. 1975 September; 1(9): 300-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10697481&dopt=Abstract
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Longitudinal study of anti-Candida albicans mucosal immunity against aspartic proteinases in HIV-infected patients. Author(s): Millon L, Drobacheff C, Piarroux R, Monod M, Reboux G, Laurent R, Meillet D. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2001 February 1; 26(2): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11242180&dopt=Abstract
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Loss of heterozygosity, by mitotic gene conversion and crossing over, causes strainspecific adenine mutants in constitutive diploid Candida albicans. Author(s): Tsang PW, Cao B, Siu PY, Wang J. Source: Microbiology (Reading, England). 1999 July; 145 ( Pt 7): 1623-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439401&dopt=Abstract
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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. Author(s): Lopez-Ribot JL, McAtee RK, Kirkpatrick WR, La Valle R, Patterson TF. Source: Clinical and Diagnostic Laboratory Immunology. 1999 September; 6(5): 665-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473514&dopt=Abstract
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Low virulence of a morphological Candida albicans mutant. Author(s): Diez-Orejas R, Molero G, Rios-Serrano I, Vazquez A, Gil C, Nombela C, Sanchez-Perez M. Source: Fems Microbiology Letters. 1999 July 15; 176(2): 311-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10427713&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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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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Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients. Author(s): Maebashi K, Niimi M, Kudoh M, Fischer FJ, Makimura K, Niimi K, Piper RJ, Uchida K, Arisawa M, Cannon RD, Yamaguchi H. Source: The Journal of Antimicrobial Chemotherapy. 2001 May; 47(5): 527-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328762&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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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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Molecular bases of adhesion of Candida albicans. Author(s): Fukazawa Y, Kagaya K. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1997 March-April; 35(2): 87-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9147268&dopt=Abstract
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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. Author(s): Tamura M, Watanabe K, Mikami Y, Yazawa K, Nishimura K. Source: Journal of Clinical Microbiology. 2001 December; 39(12): 4309-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724837&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 heterogeneity of fluconazole-resistant and -susceptible oral Candida albicans isolates within a single geographic locale. Author(s): Dassanayake RS, Ellepola AN, Samaranayake YH, Samaranayak LP. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2002 April; 110(4): 315-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076267&dopt=Abstract
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Multifocal osteoarthritis due to Candida albicans in a neonate: serum level monitoring of liposomal amphotericin B and literature review. Author(s): Evdoridou J, Roilides E, Bibashi E, Kremenopoulos G. Source: Infection. 1997 March-April; 25(2): 112-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9108188&dopt=Abstract
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Multilocus genotyping indicates that the ability to invade the bloodstream is widespread among Candida albicans isolates. Author(s): Luu LN, Cowen LE, Sirjusingh C, Kohn LM, Anderson JB. Source: Journal of Clinical Microbiology. 2001 April; 39(4): 1657-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11283111&dopt=Abstract
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Neutrophils and the adaptive immune response to Candida albicans. Author(s): Romani L, Mencacci A, Cenci E, Puccetti P, Bistoni F. Source: Research in Immunology. 1996 October-December; 147(8-9): 512-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9127882&dopt=Abstract
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New evidence that Candida albicans possesses additional ATP-binding cassette MDR-like genes: implications for antifungal azole resistance. Author(s): Walsh TJ, Kasai M, Francesconi A, Landsman D, Chanock SJ. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1997 March-April; 35(2): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9147273&dopt=Abstract
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New milk medium for germ tube and chlamydoconidia production by Candida albicans. Author(s): Jitsurong S, Kiamsiri S, Pattararangrong N. Source: Mycopathologia. 1993 August; 123(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8264773&dopt=Abstract
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New PCR primer pairs specific for Candida dubliniensis and detection of the fungi from the Candida albicans clinical isolates in Japan. Author(s): Tamura M, Watanabe K, Imai T, Mikami Y, Nishimura K. Source: Clin Lab. 2000; 46(1-2): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10745979&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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Nosocomial acquisition of Candida albicans: an epidemiologic study. Author(s): Vazquez JA, Sanchez V, Dmuchowski C, Dembry LM, Sobel JD, Zervos MJ. Source: The Journal of Infectious Diseases. 1993 July; 168(1): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8515108&dopt=Abstract
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Nosocomial Candida albicans acquisition in a geriatric unit: epidemiology and evidence for person-to-person transmission. Author(s): Fanello S, Bouchara JP, Jousset N, Delbos V, LeFlohic AM. Source: The Journal of Hospital Infection. 2001 January; 47(1): 46-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161898&dopt=Abstract
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Nosocomial candidaemias due to species other than Candida albicans in cancer patients. Aetiology, risk factors, and outcome of 45 episodes within 10 years in a single cancer institution. Author(s): Krcmery V Jr, Mrazova M, Kunova A, Grey E, Mardiak J, Jurga L, Sabo A, Sufliarsky J, Sevcikova L, Sorkovska D, West D, Trupl J, Novotny J, Mateicka F. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 1999 November; 7(6): 428-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10541986&dopt=Abstract
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Novel fluorescent broth microdilution method for fluconazole susceptibility testing of Candida albicans. Author(s): Liao RS, Rennie RP, Talbot JA. Source: Journal of Clinical Microbiology. 2001 July; 39(7): 2708-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427602&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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Occurrence of Candida albicans in infections of endodontic origin. Author(s): Baumgartner JC, Watts CM, Xia T. Source: Journal of Endodontics. 2000 December; 26(12): 695-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471635&dopt=Abstract
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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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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 albicans. Author(s): Sheff B. Source: Nursing. 1999 July; 29(7): 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10446570&dopt=Abstract
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Oral colonization by Candida albicans. Author(s): Cannon RD, Chaffin WL. Source: Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 1999; 10(3): 359-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10759414&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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Oropharyngeal candidiasis in AIDS patients from Abidjan (Ivory Coast): antifungal susceptibilities and multilocus enzyme electrophoresis analysis of Candida albicans isolates. Author(s): Nebavi F, Arnavielhe S, Le Guennec R, Menan E, Kacou A, Combe P, Aoussi E, Mallie M, Kone M, Bastide JM. Source: Pathologie-Biologie. 1998 May; 46(5): 307-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9769890&dopt=Abstract
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Oropharyngeal candidosis in AIDS patients: an epidemiological study using restriction analysis of Candida albicans total genomic DNA. Author(s): Elias Costa MR, Carnovale S, Relloso MS. Source: Mycoses. 1999 April; 42(1-2): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394847&dopt=Abstract
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Outcome in critically ill patients with candidal fungaemia: Candida albicans vs. Candida glabrata. Author(s): Blot S, Vandewoude K, Hoste E, Poelaert J, Colardyn F. Source: The Journal of Hospital Infection. 2001 April; 47(4): 308-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11289775&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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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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Phagocytosis of candida albicans by lymphatic tumour cells in vitro. Author(s): Ghoneum M, Grewal I, Brown J, Osborne R, Elembabi H, Gill G. Source: Acta Histochemica. 2003; 105(2): 127-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831164&dopt=Abstract
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Phenotypes and randomly amplified polymorphic DNA profiles of Candida albicans isolates from root canal infections in a Finnish population. Author(s): Waltimo TM, Dassanayake RS, Orstavik D, Haapasalo MP, Samaranayake LP. Source: Oral Microbiology and Immunology. 2001 April; 16(2): 106-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240864&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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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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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. 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
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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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Prosthetic joint infections with osteomyelitis due to Candida albicans. Author(s): Lerch K, Kalteis T, Schubert T, Lehn N, Grifka J. Source: Mycoses. 2003 December; 46(11-12): 462-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14641618&dopt=Abstract
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Qualitative and quantitative differences in recognition patterns of Candida albicans protein and polysaccharide antigens by human sera. Author(s): Hernando FL, Cailliez JC, Trinel PA, Faille C, Mackenzie DW, Poulain D. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1993; 31(3): 219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8360813&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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Quantification of Candida albicans morphology in vaginal smears. Author(s): Merson-Davies LA, Odds FC, Malet R, Young S, Riley V, Schober P, Fisk PG. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1991 November 3; 42(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1778291&dopt=Abstract
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Quantitation and morphotyping of Candida albicans from healthy mouths and from mouths affected by erythematous candidosis. Author(s): Borromeo GL, McCullough MJ, Reade PC. Source: Journal of Medical and Veterinary Mycology : Bi-Monthly Publication of the International Society for Human and Animal Mycology. 1992; 30(6): 477-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1287167&dopt=Abstract
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Quantitative analysis of opsonophagocytosis and of killing of Candida albicans by human peripheral blood leukocytes by using flow cytometry. Author(s): Martin E, Bhakdi S. Source: Journal of Clinical Microbiology. 1991 September; 29(9): 2013-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1774329&dopt=Abstract
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Quantitative measurement of lymphocyte mediated growth inhibition of Candida albicans. Author(s): Beno DW, Mathews HL. Source: Journal of Immunological Methods. 1993 September 15; 164(2): 155-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8370923&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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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 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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Real-time automated polymerase chain reaction (PCR) to detect Candida albicans and Aspergillus fumigatus DNA in whole blood from high-risk patients. Author(s): Pryce TM, Kay ID, Palladino S, Heath CH. Source: Diagnostic Microbiology and Infectious Disease. 2003 November; 47(3): 487-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14596967&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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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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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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Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by white-opaque switching in Candida albicans. Author(s): Geiger J, Wessels D, Lockhart SR, Soll DR. Source: Infection and Immunity. 2004 February; 72(2): 667-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14742507&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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Reversal of antifungal resistance mediated by ABC efflux pumps from Candida albicans functionally expressed in yeast. Author(s): Schuetzer-Muehlbauer M, Willinger B, Egner R, Ecker G, Kuchler K. Source: International Journal of Antimicrobial Agents. 2003 September; 22(3): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678837&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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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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Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors. Author(s): Pichova I, Pavlickova L, Dostal J, Dolejsi E, Hruskova-Heidingsfeldova O, Weber J, Ruml T, Soucek M. Source: European Journal of Biochemistry / Febs. 2001 May; 268(9): 2669-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11322888&dopt=Abstract
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Serological differentiation of experimentally induced Candida dubliniensis and Candida albicans infections. Author(s): Moragues MD, Omaetxebarria MJ, Elguezabal N, Bikandi J, Quindos G, Coleman DC, Ponton J. Source: Journal of Clinical Microbiology. 2001 August; 39(8): 2999-3001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474033&dopt=Abstract
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Stability of allelic frequencies and distributions of Candida albicans microsatellite loci from U.S. population-based surveillance isolates. Author(s): Lott TJ, Fundyga RE, Brandt ME, Harrison LH, Sofair AN, Hajjeh RA, Warnock DW. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1316-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624076&dopt=Abstract
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Stage-specific gene expression of Candida albicans in human blood. Author(s): Fradin C, Kretschmar M, Nichterlein T, Gaillardin C, d'Enfert C, Hube B. Source: Molecular Microbiology. 2003 March; 47(6): 1523-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622810&dopt=Abstract
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Subgingival strains of Candida albicans in relation to geographical origin and occurrence of periodontal pathogenic bacteria. Author(s): Hannula J, Dogan B, Slots J, Okte E, Asikainen S. Source: Oral Microbiology and Immunology. 2001 April; 16(2): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240865&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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Superpeptide to treat Candida albicans. Author(s): Foubister V. Source: Drug Discovery Today. 2003 May 1; 8(9): 380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706649&dopt=Abstract
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Suppression by Candida albicans beta-glucan of cytokine release from activated human monocytes and from T cells in the presence of monocytes. Author(s): Nakagawa Y, Ohno N, Murai T. Source: The Journal of Infectious Diseases. 2003 February 15; 187(4): 710-3. Epub 2003 January 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12599093&dopt=Abstract
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Surveillance of nosocomial transmission of Candida albicans in an intensive care unit by DNA fingerprinting. Author(s): Taylor BN, Harrer T, Pscheidl E, Schweizer A, Rollinghoff M, Schroppel K. Source: The Journal of Hospital Infection. 2003 December; 55(4): 283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14629972&dopt=Abstract
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The ALS gene family of Candida albicans. Author(s): Hoyer LL. Source: Trends in Microbiology. 2001 April; 9(4): 176-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11286882&dopt=Abstract
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The effect of oral bacteria on Candida albicans germ-tube formation. Author(s): Nair RG, Anil S, Samaranayake LP. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2001 February; 109(2): 147-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398996&dopt=Abstract
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The impact of chlorhexidine gluconate on the relative cell surface hydrophobicity of oral Candida albicans. Author(s): Anil S, Ellepola AN, Samaranayake LP. Source: Oral Diseases. 2001 March; 7(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355437&dopt=Abstract
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The impact of norfloxacin, ciprofloxacin and ofloxacin on human gut colonization by Candida albicans. Author(s): Mavromanolakis E, Maraki S, Cranidis A, Tselentis Y, Kontoyiannis DP, Samonis G. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(6): 477-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450873&dopt=Abstract
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The influence of antifungal drugs on virulence properties of Candida albicans in patients with diabetes mellitus. Author(s): Willis AM, Coulter WA, Fulton CR, Hayes JR, Bell PM, Lamey PJ. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 March; 91(3): 317-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11250629&dopt=Abstract
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The interaction of human dendritic cells with yeast and germ-tube forms of Candida albicans leads to efficient fungal processing, dendritic cell maturation, and acquisition of a Th1 response-promoting function. Author(s): Romagnoli G, Nisini R, Chiani P, Mariotti S, Teloni R, Cassone A, Torosantucci A. Source: Journal of Leukocyte Biology. 2004 January; 75(1): 117-26. Epub 2003 October 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525965&dopt=Abstract
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Tissue infection and site-specific gene expression in Candida albicans. Author(s): Fradin C, Hube B. Source: Adv Appl Microbiol. 2003; 53: 271-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696322&dopt=Abstract
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Traversal of Candida albicans across human blood-brain barrier in vitro. Author(s): Jong AY, Stins MF, Huang SH, Chen SH, Kim KS. Source: Infection and Immunity. 2001 July; 69(7): 4536-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401997&dopt=Abstract
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Two telomerase reverse transcriptases (TERTs) expressed in Candida albicans. Author(s): Metz AM, Love RA, Strobel GA, Long DM. Source: Biotechnology and Applied Biochemistry. 2001 August; 34(Pt 1): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483154&dopt=Abstract
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Typing of Candida albicans isolates by sequence analysis of the cytochrome b gene and differentiation from Candida stellatoidea. Author(s): Biswas SK, Yokoyama K, Wang L, Nishimura K, Miyaji M. Source: Journal of Clinical Microbiology. 2001 April; 39(4): 1600-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11283095&dopt=Abstract
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Ultrastructural changes of Candida albicans under influence of cyclosporin A. Author(s): Krajewska-Kulak E, Niczyporuk W, Szynaka B. Source: Rocz Akad Med Bialymst. 1997; 42 Suppl 2: 208-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9646704&dopt=Abstract
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Ultrastructural effects of date extract on Candida albicans. Author(s): Shraideh ZA, Abu-Elteen KH, Sallal AK. Source: Mycopathologia. 1998; 142(3): 119-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052161&dopt=Abstract
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Undecylenic acid inhibits morphogenesis of Candida albicans. Author(s): McLain N, Ascanio R, Baker C, Strohaver RA, Dolan JW. Source: Antimicrobial Agents and Chemotherapy. 2000 October; 44(10): 2873-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991877&dopt=Abstract
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Unfortunate in vitro selection of resistant Candida albicans with severe clinical consequences. Author(s): Joly V, Carbon C. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 October; 27(4): 692-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9798017&dopt=Abstract
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Unique inflammatory features noted in intraorally transferred skin flaps: correlation with Candida albicans infection. Author(s): Katou F, Motegi K, Tagami H, Shirai N, Echigo S, Nagura H. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1999 June; 87(6): 676-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10397657&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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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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Use of microwave energy to disinfect a long-term soft lining material contaminated with Candida albicans or Staphylococcus aureus. Author(s): Baysan A, Whiley R, Wright PS. Source: The Journal of Prosthetic Dentistry. 1998 April; 79(4): 454-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9576322&dopt=Abstract
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Use of monoclonal antibody in diagnosis of candidiasis caused by Candida albicans: detection of circulating aspartyl proteinase antigen. Author(s): Na BK, Song CY. Source: Clinical and Diagnostic Laboratory Immunology. 1999 November; 6(6): 924-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548587&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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Vaginal colonization or infection with Candida albicans in human immunodeficiency virus-infected women during pregnancy and during the postpartum period. Women and Infants Transmission Study Group. Author(s): Burns DN, Tuomala R, Chang BH, Hershow R, Minkoff H, Rodriguez E, Zorrilla C, Hammill H, Regan J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 February; 24(2): 201-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9114148&dopt=Abstract
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Variable antifungal susceptibility of wild-type Candida albicans phenotypes from neutropenic hosts. Author(s): Velegraki A, Papalambrou D, Soremi S, Legakis NJ. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1996 November; 15(11): 854-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8997556&dopt=Abstract
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Variation in morphotype, karyotype and DNA type of fluconazole resistant Candida albicans from an AIDS patient. Author(s): Takasuka T, Baily GG, Birch M, Anderson MJ, Law D, Denning DW. Source: The Journal of Infection. 1998 January; 36(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9515670&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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Vasculitic basilar artery thrombosis in chronic Candida albicans meningitis. Author(s): Grimes DA, Lach B, Bourque PR. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1998 February; 25(1): 76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9532286&dopt=Abstract
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Virulence and hyphal formation of Candida albicans require the Ste20p-like protein kinase CaCla4p. Author(s): Leberer E, Ziegelbauer K, Schmidt A, Harcus D, Dignard D, Ash J, Johnson L, Thomas DY. Source: Current Biology : Cb. 1997 August 1; 7(8): 539-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9259554&dopt=Abstract
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Virulence factors of Candida albicans. Author(s): Calderone RA, Fonzi WA. Source: Trends in Microbiology. 2001 July; 9(7): 327-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435107&dopt=Abstract
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Virulence genes in the pathogenic yeast Candida albicans. Author(s): Navarro-Garcia F, Sanchez M, Nombela C, Pla J. Source: Fems Microbiology Reviews. 2001 April; 25(2): 245-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11250036&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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Western blot analysis of the immune response to Candida albicans antigens in 391 long-term intensive care patients. Author(s): Weis C, Kappe R, Sonntag HG. Source: Mycoses. 1997 October; 40(5-6): 153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9476481&dopt=Abstract
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What's new in the mechanisms of host resistance to Candida albicans infection? Author(s): Ashman RB, Papadimitriou JM. Source: Pathology, Research and Practice. 1990 August; 186(4): 527-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2247381&dopt=Abstract
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When to suspect fungal infection in neonates: A clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia. Author(s): Benjamin DK Jr, Ross K, McKinney RE Jr, Benjamin DK, Auten R, Fisher RG. Source: Pediatrics. 2000 October; 106(4): 712-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11015513&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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Whole and parotid saliva IgA and IgA-subclass responses to Candida albicans in HIV infection. Author(s): Sweet SP, Challacombe SJ, Naglik JR. Source: Advances in Experimental Medicine and Biology. 1995; 371B: 1031-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7502746&dopt=Abstract
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Worsening of endogenous Candida albicans endophthalmitis during therapy with intravenous lipid complex amphotericin B. Author(s): Virata SR, Kylstra JA, Brown JC, Wohl DA, Cohen MS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 May; 28(5): 1177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10452666&dopt=Abstract
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Xanthogranulomatous cholecystitis due to invasive Candida albicans in a patient with AIDS. Author(s): Brown H, Talamini M, Westra WH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 January; 22(1): 186-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8825002&dopt=Abstract
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X-ray crystallographic studies of Candida albicans dihydrofolate reductase. High resolution structures of the holoenzyme and an inhibited ternary complex. Author(s): Whitlow M, Howard AJ, Stewart D, Hardman KD, Kuyper LF, Baccanari DP, Fling ME, Tansik RL. Source: The Journal of Biological Chemistry. 1997 November 28; 272(48): 30289-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9374515&dopt=Abstract
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Y132H substitution in Candida albicans sterol 14alpha-demethylase confers fluconazole resistance by preventing binding to haem. Author(s): Kelly SL, Lamb DC, Kelly DE. Source: Fems Microbiology Letters. 1999 November 15; 180(2): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10556708&dopt=Abstract
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CHAPTER 2. NUTRITION AND CANDIDA ALBICANS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Candida albicans.
Finding Nutrition Studies on Candida Albicans 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 albicans” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “Candida albicans” (or a synonym): •
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: •
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
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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
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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
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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): 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 fluconazole on the growth and adhesion of Candida albicans in the presence of antineoplastic agents. Author(s): Department of Microbiology and Biotechnology, Kossuth Lajos University, Debrecen, Hungary. Source: Fekete Forgacs, K Kis, B Nagy, G Lenkey, B J-Basic-Microbiol. 1999; 39(5-6): 30510 0233-111X
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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
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Effects of Candida albicans infection on selenium-deficient mice. Source: Boyne, R. Arthur, J.R. Trace elements in man and animals : TEMA 5 : proceedings of the fifth International Symposium on Trace Elements in Man and Animals / editors C.F. Mills, I. Bremner, & J.K. Chesters. Farnham Royal, Slough : Commonwealth Agricultural Bureaux, c1985. page 240-243. ISBN: 085198553X
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Electrophoretic detection of cytoplasmic serine proteinases (Gelatinases) in Candida albicans. Source: Rodier, M.H. Moudini, B. el. Ghazali, M. Lacroix, C. Jacquemin, J.L. Exp-mycol. Orlando, Fla. : Academic Press. Sept 1994. volume 18 (3) page 267-270. 0147-5975
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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
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Evidence for the involvement of thiocyanate in the inhibition of Candida albicans by Lactobacillus acidophilus. Source: Jack, M. Wood, B.J.B. Berry, D.R. Microbios. Cambridge : Faculty Press. 1990. volume 62 (250) page 37-46. ill. 0026-2633
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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
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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
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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
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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
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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
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to Candida albicans; 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: •
Food and Diet Crème Fraîche Source: Healthnotes, Inc.; www.healthnotes.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 ALBICANS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Candida albicans. 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 albicans 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 albicans” (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 albicans: •
A comparison of the sterol content of multiple isolates of the Candida albicans Darlington strain with other clinically azole-sensitive and -resistant strains. Author(s): Howell SA, Mallet AI, Noble WC. Source: The Journal of Applied Bacteriology. 1990 November; 69(5): 692-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2276986&dopt=Abstract
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A monoclonal antibody that defines a surface antigen on Candida albicans hyphae cross-reacts with yeast cell protoplasts. Author(s): Ollert MW, Calderone RA. Source: Infection and Immunity. 1990 March; 58(3): 625-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1689699&dopt=Abstract
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A non-azole inhibitor of lanosterol 14 alpha-methyl demethylase in Candida albicans. Author(s): Capobianco JO, Doran CC, Goldman RC, De B. Source: The Journal of Antimicrobial Chemotherapy. 1992 December; 30(6): 781-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1289352&dopt=Abstract
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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. 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
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A role for complement receptor-like molecules in iron acquisition by Candida albicans. Author(s): Moors MA, Stull TL, Blank KJ, Buckley HR, Mosser DM. Source: The Journal of Experimental Medicine. 1992 June 1; 175(6): 1643-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1588285&dopt=Abstract
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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
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Adherence of Candida albicans to immobilized extracellular matrix proteins is mediated by calcium-dependent surface glycoproteins. Author(s): Klotz SA, Rutten MJ, Smith RL, Babcock SR, Cunningham MD. Source: Microbial Pathogenesis. 1993 February; 14(2): 133-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8502162&dopt=Abstract
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Antifungal activity of fluconazole in combination with lovastatin and their effects on gene expression in the ergosterol and prenylation pathways in Candida albicans. Author(s): Song JL, Lyons CN, Holleman S, Oliver BG, White TC. Source: Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. 2003 October; 41(5): 417-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14653518&dopt=Abstract
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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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Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans. Author(s): Roesler J, Steinmuller C, Kiderlen A, Emmendorffer A, Wagner H, LohmannMatthes ML. Source: International Journal of Immunopharmacology. 1991; 13(1): 27-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2026472&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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Bioassay for siderophore utilization by Candida albicans. Author(s): Minnick AA, Eizember LE, McKee JA, Dolence EK, Miller MJ. Source: Analytical Biochemistry. 1991 April; 194(1): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1907814&dopt=Abstract
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Biochemical changes associated with the antifungal action of the triazole ICI 153,066 on Candida albicans and Trichophyton quinckeanum. Author(s): Barrett-Bee K, Newboult L, Pinder P. Source: Fems Microbiology Letters. 1991 April 15; 63(2-3): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2060756&dopt=Abstract
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Ca ions stabilize the binding of complement factor iC3b to the pseudohyphal form of Candida albicans. Author(s): Spotl L, Most J, Dierich MP. Source: Infection and Immunity. 1994 March; 62(3): 1125-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8112846&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.
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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 •
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 death mechanisms in the human opportunistic pathogen Candida albicans. Author(s): Lemar KM, Muller CT, Plummer S, Lloyd D. Source: The Journal of Eukaryotic Microbiology. 2003; 50 Suppl: 685-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14736219&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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Changes in the cell wall glycoprotein composition of Candida albicans associated to the inhibition of germ tube formation by EDTA. Author(s): Gil ML, Casanova M, Martinez JP. Source: Archives of Microbiology. 1994; 161(6): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8048840&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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Characterization of DNA topoisomerase I from Candida albicans as a target for drug discovery. Author(s): Fostel JM, Montgomery DA, Shen LL. Source: Antimicrobial Agents and Chemotherapy. 1992 October; 36(10): 2131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1332588&dopt=Abstract
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Coaggregation of Candida albicans with oral Actinomyces species. Author(s): Grimaudo NJ, Nesbitt WE, Clark WB.
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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 •
Coaggregation of Streptococcus sanguis and other streptococci with Candida albicans. Author(s): Jenkinson HF, Lala HC, Shepherd MG. Source: Infection and Immunity. 1990 May; 58(5): 1429-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2182544&dopt=Abstract
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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 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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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 adherence of hydrophobic and hydrophilic Candida albicans yeast cells to mouse tissues. Author(s): Hazen KC, Brawner DL, Riesselman MH, Jutila MA, Cutler JE.
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Source: Infection and Immunity. 1991 March; 59(3): 907-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1900065&dopt=Abstract •
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 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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Effect of aqueous extract of miswak on the in vitro growth of Candida albicans. Author(s): al-Bagieh NH, Idowu A, Salako NO. Source: Microbios. 1994; 80(323): 107-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7898373&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 miconazole on the structure and function of plasma membrane of Candida albicans. Author(s): Ansari S, Prasad R.
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Source: Fems Microbiology Letters. 1993 November 15; 114(1): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8293965&dopt=Abstract •
Effect of supplementation of ergosterol on miconazole action in vivo and in vitro in Candida albicans. Author(s): Mago N, Khuller GK. Source: Indian J Exp Biol. 1991 September; 29(9): 841-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1794867&dopt=Abstract
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Effects of cilofungin (LY121019) on carbohydrate and sterol composition of Candida albicans. Author(s): Pfaller M, Riley J, Koerner T. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1989 December; 8(12): 1067-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2695329&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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Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans. Author(s): Pfaller MA, Riley J, Koerner T. Source: Diagnostic Microbiology and Infectious Disease. 1990 January-February; 13(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2184984&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. 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
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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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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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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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Identification and immunochemical characterization of a germ tube specific antigen of Candida albicans. Author(s): Marot-Leblond A, Robert R, Aubry J, Ezcurra P, Senet JM. Source: Fems Immunology and Medical Microbiology. 1993 August; 7(2): 175-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8401430&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 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: J Chemother. 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. 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
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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 Clotrimazole-resistant Candida albicans by plants used in Iranian folkloric medicine. Author(s): Bonjar GH. Source: Fitoterapia. 2004 January; 75(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14693224&dopt=Abstract
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Inhibition of ergosterol synthesis by sertaconazole in Candida albicans. Author(s): Agut J, Palacin C, Sacristan A, Ortiz JA. Source: Arzneimittel-Forschung. 1992 May; 42(5A): 718-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1627190&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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Mechanisms of aggregation accompanying morphogenesis in Candida albicans. Author(s): Holmes AR, Cannon RD, Shepherd MG. Source: Oral Microbiology and Immunology. 1992 February; 7(1): 32-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1528622&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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Multiple effects of green tea catechin on the antifungal activity of antimycotics against Candida albicans. Author(s): Hirasawa M, Takada K. Source: The Journal of Antimicrobial Chemotherapy. 2004 February; 53(2): 225-9. Epub 2003 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14688042&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. 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
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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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Phagocytosis of viable Candida albicans by alveolar macrophages: flow cytometric quantification. Author(s): Rosseau S, Seeger W, Pralle H, Lohmeyer J. Source: The American Journal of Physiology. 1994 August; 267(2 Pt 1): L211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8074245&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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Polyene resistance in ergosterol producing strains of Candida albicans. Author(s): Broughton MC, Bard M, Lees ND. Source: Mycoses. 1991 January-February; 34(1-2): 75-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1922193&dopt=Abstract
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Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes. Author(s): Steinmuller C, Roesler J, Grottrup E, Franke G, Wagner H, Lohmann-Matthes ML. Source: International Journal of Immunopharmacology. 1993 July; 15(5): 605-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8375943&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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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. 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
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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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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.
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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 •
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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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. Rustad T[corrected to Rustad Tr]. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9756759&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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Saperconazole: a selective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes. Author(s): Vanden Bossche H, Marichal P, Willemsens G, Bellens D, Gorrens J, Roels I, Coene MC, Le Jeune L, Janssen PA. Source: Mycoses. 1990 July-August; 33(7-8): 335-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2090934&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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Secretion of glycoproteins through the cell wall of Candida albicans. Author(s): Poulain D, Cailliez JC, Dubremetz JF. Source: European Journal of Cell Biology. 1989 October; 50(1): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2482183&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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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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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 effect of antifungal agents on the in vitro susceptibility of Candida albicans to apo-lactoferrin. Author(s): Nikawa H, Samaranayake LP, Tenovuo J, Hamada T. Source: Archives of Oral Biology. 1994 October; 39(10): 921-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7741664&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
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/
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The following is a specific Web list relating to Candida albicans; 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 Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Chronic Candidiasis Source: Healthnotes, Inc.; www.healthnotes.com Hives Source: Healthnotes, Inc.; www.healthnotes.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Healthnotes, Inc.; www.healthnotes.com Yeast Infection Source: Healthnotes, Inc.; www.healthnotes.com
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Homeopathy Candida albicans Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Acidophilus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,748,00.html 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
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Azithromycin Source: Healthnotes, Inc.; www.healthnotes.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 Cephalosporins Source: Healthnotes, Inc.; www.healthnotes.com Chlorhexidine Source: Healthnotes, Inc.; www.healthnotes.com 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 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 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
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Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gentamicin Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lapacho Source: Integrative Medicine Communications; www.drkoop.com Levofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Loracarbef Source: Healthnotes, Inc.; www.healthnotes.com Macrolides Source: Healthnotes, Inc.; www.healthnotes.com Minocycline Source: Healthnotes, Inc.; www.healthnotes.com Neomycin Source: Healthnotes, Inc.; www.healthnotes.com Nitrofurantoin Source: Healthnotes, Inc.; www.healthnotes.com Ofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Oregano/Wild Marjoram Alternative names: Origanum vulgare Source: Healthnotes, Inc.; www.healthnotes.com Pau d'Arco Alternative names: Tabebuia avellanedae, Lapacho Source: Integrative Medicine Communications; www.drkoop.com Penicillin V Source: Healthnotes, Inc.; www.healthnotes.com
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Penicillins Source: Healthnotes, Inc.; www.healthnotes.com Quinolones Source: Healthnotes, Inc.; www.healthnotes.com 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 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 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.
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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 ALBICANS Overview In this chapter, we will give you a bibliography on recent dissertations relating to Candida albicans. 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 albicans” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Candida albicans, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Candida Albicans 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 albicans. 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: •
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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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
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. PATENTS ON CANDIDA ALBICANS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Candida albicans” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Candida albicans, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Candida Albicans By performing a patent search focusing on Candida albicans, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on Candida albicans: •
11-hydroxysordarin and a process for producing it using actinomyces SSP Inventor(s): Chartrain; Michel M. (Westfield, NJ), Harris; Guy H. (Asbury, NJ), Heimbuch; Brian (North Brunswick, NJ), Nielsen-Kahn; Jennifer (East Brunswick, NJ), Sturr; Michael G. (Mountainside, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 6,228,622 Date filed: October 26, 1999 Abstract: 11-hydroxysordarin, biotransformation product of a fermentation with sordarin and Actinomyces spp., (Merck Culture Collection MA7235) ATCC No. 202103 is an antifungal agent. This compound may be useful in the treatment of diseases caused by fungal pathogens such as Candida albicans. Excerpt(s): The present invention is directed toward the synthesis of a novel antifungal agent prepared by biotransformation of known compound, sordarin. Sordarin is an antifungal antibiotic isolated from the ascomycete Sordaria araneosa (see GB 1,162,027 and Helvetica Chimica Acta, 1971, 51:119-20). Other compounds having the sordarin skeleton have also been reported as antifungal agents. Japanese Kokai J62040292 discloses the compound zofimarin isolated from Zopfiela marina sp.; Japanese Kokai J06157582 discloses the compound BE-31405 isolated from Penicillium sp.; and SCH57404 is reported in J. Antibiotics, 1995, 48:1171-1172. Semi-synthetic sordarin derivatives are reported in PCT Applications WO96/14326 and WO96/14327. The compounds exhibit antifungal activity against fungi including Saccharomyces cerevisiae, Candida albicans, C. glabrata and C. tropicalis. This compound is prepared by biotransformation of sordarin. The compound has antifungal activity against a number of pathogenic fungi including Candida spp., but is significant because it allows access to a series of sordarin derivatives that are chemically inaccessible. Web site: http://www.delphion.com/details?pn=US06228622__
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Absorbent article having a reduced viability of candida albicans Inventor(s): Akin; Frank Jerrel (Marietta, GA), Faulks; Michael John (Neenah, WI), Mayberry; Pamela Jean (Roswell, GA), Paul; Susan Carol (Alpharetta, GA), Wright; Audra Stefanik (Woodstock, GA) Assignee(s): Kimberly-clark Worldwide, Inc. (neenah, Wi) Patent Number: 6,287,286 Date filed: June 9, 1999 Abstract: An absorbent article includes a vapor permeable backsheet, a liquid permeable topsheet positioned in facing relation with the backsheet; and an absorbent body located between the backsheet and the topsheet which defines multiple zones of high air permeability. The absorbent article may also include a ventilation layer between the absorbent body and the backsheet and a surge management layer between the absorbent body and the topsheet. The article exhibits improved air exchange within the article during use. As a result, the article exhibits substantially reduced levels of hydration of
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the wearer's skin when in use which renders the skin less susceptible to the viability of microorganisms. Excerpt(s): Many known diaper configurations employ absorbent materials located between a liquid pervious topsheet and a vapor and liquid impermeable backsheet. Such backsheets are well suited to prevent the migration of liquid waste from the absorbent materials to the outer garments of a wearer. Unfortunately, the use of liquid and vapor impermeable backsheets can result in a high degree of humidity within the diaper when in use which may result in relatively high skin hydration levels. The occlusive, moist environment inside diapers incorporating such backsheets can promote the viability of microorganisms, including Candida albicans, which can undesirably lead to the onset of diaper dermatitis (diaper rash). Diaper dermatitis can afflict almost every infant at some time during the diaper wearing years. The most severe form of this condition is usually caused by secondary infection with the fungi Candida albicans. Although other factors influence the pathogenesis of this fungi, one critical factor is the relative humidity within the diaper which is directly related to the occlusion or semiocclusion of the diaper area. In order to reduce the humidity level within diapers, breathable polymer films have been employed as outer covers for absorbent garments, such as disposable diapers. The breathable films are typically constructed with micropores to provide desired levels of liquid impermeability and air permeability. Other disposable diaper designs have been arranged to provide breathable regions in the form of breathable panels or perforated regions in otherwise vapor-impermeable backsheets to help ventilate the garment. Web site: http://www.delphion.com/details?pn=US06287286__ •
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
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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__ •
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., 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__
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Antifungal compounds from pseudomonas viridiflava Inventor(s): Martinez-Miller; Concepcion (Bozeman, MT), Miller; Roger V. (Bozeman, MT), Strobel; Gary A. (Bozeman, MT) Assignee(s): Pharmagenesis, Inc. (palo Alto, Ca) Patent Number: 6,103,875 Date filed: November 26, 1997
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Abstract: The present invention is directed to a family of unique antimycotic lipopeptide compounds produced by Pseudomonas viridiflava. The lipopeptides are effective against both human and plant fungal pathogens, and are typically characterized by their ability to inhibit growth of Candida albicans. Representative lipopeptides of the invention have molecular weights of 1137, 1153, 1164 and 1181 daltons. Excerpt(s): The present invention relates to a family of unique antimycotic lipopeptide compounds produced by P. viridiflava, and to methods for treating fungal infections which employ these compounds. Ausubel, F. M., et al., in CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley and Sons, Inc., Media Pa. (1992). Galgiani, J. N., et al., NCCLS DOCUMENT M27-P, NCCLS, Villanova, Pa. (1992). Web site: http://www.delphion.com/details?pn=US06103875__ •
Antimicrobial denture adhesive and cleanser compositions Inventor(s): Gasman; Robert C. (Montville, NJ), Kolias; Fred G. (Bedminster, NJ), Wong; Eddie (New Providence, NJ) Assignee(s): Block Drug Company, Inc. (jersey City, Nj) Patent Number: 6,124,374 Date filed: May 29, 1998 Abstract: An antimicrobial denture adhesive, denture cleansing creme or denture soaking or brushing composition comprises a combination of 8-hydroxyquinoline (or its salt) and at least one copper(II) salt. The composition fights denture stomatitis by inhibiting Candida albicans. Excerpt(s): The invention relates to antimicrobial compositions for use in controlling the growth of microorganisms in the oral cavity and on dental prostheses. The antimicrobial compositions of the invention are useful as denture adhesives and as denture cleansing creams or soaking compositions. The invention also relates to methods for making and using such antimicrobial compositions. Dentures and dental plates function as a substitute for missing teeth in the mouth. While dentures are usually carefully fitted for the user, the fit can change over time, causing discomfort and slippage. To alleviate the discomfort and to control the slippage, a denture adhesive may be applied to the denture. Denture adhesives usually comprise water swellable gums and/or polymers suspended in oils and petrolatum. The gums and/or polymers hydrate and become tacky when introduced to the saliva in the oral cavity, thus holding the dentures in place. Oils and petrolatum are traditionally used in the composition to avoid the premature washing away of the adhesive actives due to the constant flow of saliva through the oral cavity. Candida albicans is one species of bacteria known to cause denture stomatitis, which is a serious infection of the oral mucosa. Denture stomatitis generally develops due to poor-fitting dentures or poor denture cleanliness. Normally, mucosal infections are not a problem since natural substances found in the saliva act to inhibit bacterial and fungal growth. Dentures however, are known to prevent saliva from getting to and contacting the mucosal surfaces beneath the denture. Without the presence of saliva to wash the mucosal surface under the denture, bacterial species such as C. albicans can flourish and cause disease. Web site: http://www.delphion.com/details?pn=US06124374__
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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 dehydroquinate synthase of candida albicans Inventor(s): Greenwood; Rebecca (Berwyn, PA), Nicholas; Richard (Collegeville, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,174,705 Date filed: October 22, 1999 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
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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". It is particularly preferred to employ candidal genes and gene products as targets for the development of antifungals. Candida spp. make up a medically important genus of microbes. They are known to produce two main types of infection, superficial infections of the mucosa and skin, and systemic infections, particularly in immuno-compromised patients, characterized by dissemination to the body tissues with poor prognosis without intervention. C. albicans is the principal species causing candida infections. 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 antifungal agents is small and resistance to existing agents is an emerging problem. This has created a demand for both new antifungal agents and diagnostic tests for this organism. Web site: http://www.delphion.com/details?pn=US06174705__ •
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 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
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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 integrin-like protein Inventor(s): Bendel; Catherine M. (Hopkins, MN), Gale; Cheryl A. (Minneapolis, MN), Hostetter; Margaret K. (Minneapolis, MN), Kendrick; Kathleen (Columbus, OH), Tao; Nian-jun (Malden, MA) Assignee(s): Regents of the University of Minnesota (minneapolis, Mn) Patent Number: 5,886,151 Date filed: May 3, 1996 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 other candidal species, and the responsible genes encoding these "integrin-like proteins" have not been identified.
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Web site: http://www.delphion.com/details?pn=US05886151__ •
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
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disclosed herein are vectors comprising the nucleic acid sequences, cells comprising the vectors, methods for producing the polypeptides and methods of use thereof. 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__ •
Carnitine analogues as topical, microbicidal spermicides Inventor(s): Doncel; Gustavo F. (Norfolk, VA), Gandour; Richard D. (Blacksburg, VA), Savle; Prashant S. (West Chester, PA) Assignee(s): Virginia Tech Intellectual Properties, Inc. (blacksburg, Va) Patent Number: 6,656,936 Date filed: July 5, 2002 Abstract: Acylcarnitine analogues having alkyl side chains of 10 to 30 carbon atoms display excellent spermicidal and anti-HIV activity, a well as being potent inhibitors of the growth of Candida albicans. Excerpt(s): The invention generally relates to novel acylcarnitine analogues and their use as topical, microbicidal spermicides. The acylcarnitine analogues are excellent spermicides, growth inhibitors of Candida albicans, and anti-HIV agents. Many women want to control their fertility and reduce their risk of becoming infected with a sexually transmitted disease (STD). The AIDS epidemic has intensified the need for femalecontrolled methods that provide effective protection against both pregnancy and STDs (Irwin et al. 1998). No currently available agent simultaneously protects against both pregnancy and infection. There is a need to develop safe prophylactic agents that are spermicidal and display activity against HIV and STD pathogens. Nonoxynol-9 (N-9), a nonionic surfactant, is the most widely used spermicides in the United States. Unfortunately, it does not appear to reduce the incidence of HIV infection (Rowe, 1997; Hira et al. 1997; Martin et al., 1997; Roddy et al. 1998). In fact, it has been demonstrated that N-9 actually increases the risk of genital inflammation (Stafford et al., 1998), urinary tract infections (Fihn et al., 1996), vulvovaginal candidiasis (Geiger and Foxman, 1996), and genital ulcers (Feldblum. 1996). One Canadian province no longer recommends the use of N-9 in any form (Rekart, 1992). Furthermore, N-9 is a mixture of oligomers (Yu and Chien, 1995) which may not meet future regulations as the health-care industry moves toward using pure compounds or mixtures whose individual components have met safety standards. For reasons of environmental toxicity (Thiele et al. 1997), several European nations have banned or restricted the use of N-9 and related compounds, sparking a debate (Renner, 1997) about the health risks of N-9. Clearly, other alternatives to N-9 as a microbicidal spermicide are needed.
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Web site: http://www.delphion.com/details?pn=US06656936__ •
Control of infectious microorganisms by modulation of chorionic gonadotropinrelated protein activity Inventor(s): Carrell; Douglas T. (West Valley City, UT), Caticha; Omar (Salt Lake City, UT), Griffin; Jeanine T. (Holladay, UT), Grover; Sanjeev (Salt Lake City, UT), Odell; William D. (Salt Lake City, UT), Woods, II; Marion L. (Salt Lake City, UT) Assignee(s): University of Utah Research Foundation (salt Lake City, Ut) Patent Number: 6,139,839 Date filed: September 22, 1998 Abstract: A method of controlling, in a warm-blooded animal, an infectious microorganism expressing a chorionic gonadotropin-like growth-regulating protein comprises modulating the activity of the protein by administering to the warm-blooded animal an effective amount of an antibody capable of inhibiting the activity of the protein, the chorionic gonadotropin-like growth-regulating protein itself such that the animal develops a neutralizing immune response, or peptides that block the receptors of the chorionic gonadotropin-like growth-regulating protein in the infectious microorganism. Candida albicans is one such microorganism that can be controlled by delivering an antibody against the growth-regulating protein, CaCGLP. Mycobacteria can also be controlled by this method. A method of inhibiting transition of Candida albicans blastospores in vitro by contacting the blastospores with an antibody against CaCGLP is also disclosed. A method of inhibiting growth of mycobacteria in vitro comprises contacting the mycobacteria with an antibody against an endogenous chorionic gonadotropin-like growth-regulating protein. In vitro growth of microorganisms can also be stimulated by contacting the microorganism with a chorionic gonadotropin-like growth-regulating protein. Excerpt(s): This invention was made with government support under Grant No. 1R55DK44900-01 awarded by the National Institute of CHD. The government has certain rights in the invention. This invention relates to a method of controlling growth of microorganisms. More particularly, this invention relates to a method of controlling growth of fungi, such as Candida albicans, and bacteria, such as mycobacteria and xanthomonads, by modulating the activity of an endogenous chorionic gonadotropinrelated protein produced by such microorganisms. Candida is a genus of imperfect fungi characterized by two principal growth habits, yeast cells (or blastospores) and hyphae (or mycelia). It is the only fungus that is commonly part of the normal flora of the skin, mouth, intestinal tract, and vagina, but can cause a variety of infections, including candidiasis, onychomycosis, tinea corporis, tinea pedis, vaginitis, and thrush. C. albicans is the usual pathogen, but other species may also cause infection. Candidiasis is usually a superficial infection of the moist cutaneous areas of the body and most commonly involves the skin, oral mucous membranes, respiratory tract, and vagina. Rarely, there is a systemic infection or endocarditis. Pregnancy predisposes women to infection by C. albicans. E.g., O. S. Kinsman et al., Effect of Mammalian Steroid Hormones and Luteinizing Hormone on the Germination of Candida albicans and Implications for Vaginal Candidosis, 31 Mycoses 617 (1988). Opportunistic infections have become increasingly frequent with the expanding population of immunocompromised individuals. Web site: http://www.delphion.com/details?pn=US06139839__
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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 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__
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DNA encoding sterol methyltransferase Inventor(s): Bard; Martin (Carmel, IN) Assignee(s): Advanced Research and Technology Institute, Inc. (indianapolis, In) Patent Number: 6,225,075 Date filed: March 13, 1998 Abstract: The invention provides an isolated and purified nucleic acid molecule encoding a Candida albicans sterol methyltransferase (ERG6). Also provided is a C. albicans strain or isolate that has reduced levels of sterol methyltransferase as a result of the disruption of at least one sterol methyltransferase gene. Preferred isolates are more
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susceptible to a number of sterol synthesis and metabolic inhibitors relative to wild type isolates. Further provided are methods to identify sterol methyltransferase inhibitors and methods to screen for antifungals or metabolic inhibitors which are not normally permeable to the fungal cell. Excerpt(s): The frequency of occurrence of human fungal infections has been increasing over the past decade in response to a combination of factors (Georgopapadakou et al., 1994). These factors include advances in invasive surgical techniques which allow for opportunistic pathogen access, the administration of immunosuppressive agents employed in transplantation, and an increase in the number of immunosuppressed patients resulting from chemotherapy and disease states such as AIDS. The threat to human health is further compounded by the increased frequency with which resistance to the commonly employed antifungal agents is occurring. Currently, the most common antifungals include the polyenes and the azoles. The polyenes bind to ergosterol, the fungal membrane sterol, and induce lethal cell leakage (Brajtburg et al., 1990). However, polyenes often have negative side effects and resistance to polyenes has been reported (Hebeka et al., 1965; Powderley et al., 1988). The azoles are fungistatic agents that inhibit the cytochrome P450-mediated removal of the C-14 methyl group from the ergosterol precursor, lanosterol (Vanden Bossche et al., 1987). Resistance to azoles has been reported in Candida albicans (Clark et al., 1996; Sanglard et al., 1996; Sanglard et al., 1995; White, 1997a; White, 1997b) as well as in other species of Candida (Moran et al., 1997; Parkinson et al., 1995), and in other fungal pathogens, including species of Histoplasma (Wheat et al., 1997), Cryptococcus (Lamb et al., 1997; Venkateswarlu al., 1997), and Aspergillus (Denning et al., 1997). The pathway for fungal sterol biosynthesis is one target for antifungal development. In particular, fungal genes that catalyze a step in sterol biosynthesis that is not found in cholesterol biosynthesis (Pinto et al., 1983) are of interest in this regard. One such fungal gene is the sterol methyltransferase gene (ERG6). Non-recombinant Saccharomyces cerevisiae erg6 mutants have been available for some time (Molzhan et al., 1972). The S. cerevisiae ERG6 gene has been isolated, and recombinant strains prepared (i.e., via genetic engineering) in which the gene has been disrupted (Gaber et al., 1989). Although the absence of the ERG6 gene product in S. cerevisiae was not lethal, it did result in several severely compromised phenotypes (Bard et al., 1978; Kleinhans et al., 1979; Lees et al., 1979; Lees et al., 1980). Web site: http://www.delphion.com/details?pn=US06225075__ •
Dye treatment solution and photodynamic therapy and method of using same Inventor(s): Biel; Merrill A. (Mendota Heights, MN) Assignee(s): Advanced Photodynamic Technologies, Inc. (mendota Heights, Mn) Patent Number: 6,251,127 Date filed: August 25, 1998 Abstract: The invention relates to a method of treating an infection or sterilization including applying a dye such as methylene blue, toluidene blue, polymyxin B, or combinations thereof to the area of infection or area to be sterilized and exposing the area of infection or area of sterilization with a light having a light wavelength and light dosage and a light dosage rate. The dye may have a concentration ranging from about 10.mu.g/ml to about 500.mu.g/ml. The wavelength may range from about 610 nm to about 670 nm. The light dosage may range from about 0 J/cm.sup.2 to about 200 J/cm.sup.2. The light dosage rate may range from about 0 mw/cm.sup.2 to about 150 mw/cm.sup.2. The treatable infections include staphylococcus, Candida albicans,
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Escherichia coli, enterococcus, streptococcus, Pseudomanus aeruginosa, Hemophilus influenzae, or E-coli. The invention also relates to an infection treatment kit. Excerpt(s): The invention relates to use of a dye treatment solution with a photodynamic therapy (PDT) treatment device. More specifically, the invention relates to photodynamic inactivation of bacteria and fungal wound infections and sterilization of tissue using methylene blue or toluidene blue and a flexible conforming patch or pad and a shaped article which provides light sources for topical PDT. The present invention advantageously uses light energy in combination with photosensitizing agents to treat or detect pathologies of living tissue, including cancer and microbiological pathogens. U.S. Pat. No. 4,822,335, entitled, Apparatus For Treatment Of Cancer With Photodiode, purportedly discloses an apparatus for the treatment of a cancerous lesion part by irradiating a light energy from a light source to the cancerous lesion part having absorbed and accumulated in advance therein a photosensitive substance with an affinity for tumors. The light source comprises a first diode adapted to excite the photosensitive substance from the ground state to a singlet state of higher energy level and a second photodiode adapted to excite an energy level of the photosensitive substance which has transited from the singlet state to a triplet state to a still higher energy level. U.S. Pat. No. 5,358,503, entitled, Photo-Thermal Therapeutic Device and Method, purportedly discloses an apparatus for simultaneous or selective treatment of an area of the skin and adjacent subcutaneous structure of a patient utilizing photo energy and therapeutic heat, which includes a plurality of juxtaposed diodes. Each diode has a longitudinal axis and is capable of projecting a non-coherent cone of light which overlaps the cone of light from each juxtaposed diode so that the light completely covers the treatment area. A flexible pad or appliance holds the diodes in juxtaposed position with each other. Web site: http://www.delphion.com/details?pn=US06251127__ •
Extraction of DNA by boiling cells in an alkaline phenol/guanidine thiocyanate solution Inventor(s): Kline; Bruce C. (Rochester, MN), Sandhu; Gurpreet S. (Rochester, MN) Assignee(s): Bayer Corporation (e. Walpole, Ma) Patent Number: 5,958,693 Date filed: September 22, 1997 Abstract: Nucleic acid probes and primers are described for detecting fungi that cause disease in humans and animals, as well as spoilage of food and beverages. These probes can detect rRNA, rDNA or polymerase chain reaction products from a majority of fungi in clinical, environmental or food samples. Nucleic acid hybridization assay probes specific for Acremonium sp., Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus glaucus, Aspergillus nidulans, Aspergillus niger, Aspergillus ochraceus, Aspergillus terreus, Aspergillus unguis, Aspergillus ustus, Beauveria sp., Bipolaris sp., Blastoschizomyces sp., Blastomyces dermatitidis, Candida albicans, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Chrysosporium sp., Cladosporium sp., Coccidioides immitis, Cryptococcus neoformans var gattii serotype B, Cryptococcus neoformans serotype A, Cryptococcus laurentii, Cryptococcus terreus, Curvularia sp., Fusarium sp., Filobasidium capsuligenum, Filobasidiella (Cryptococcus) neoformans var bacillispora serotype C, Filobasidiella (Cryptococcus) neoformans var neoformans serotype D, Filobasidium uniguttulatum, Geotrichum sp., Histoplasma capsulatum,
Patents 185
Malbranchea sp., Mucor sp., Paecilomyces sp., Penicillium species, Pseudallescheria boydii, Rhizopus sp., Sporothrix schenkii, Scopulariopsis brevicaulis, Scopulariopsis brumpti, Saccharomyces cerevisiae, and Trichosporon beigelii are also described. Excerpt(s): The inventions described and claimed herein relate to the design and composition of two nucleic acid probes capable of detecting many different fungal organisms in clinical, food, environmental and other samples. The inventions described and claimed herein also relate to the design and composition of probes capable of specifically detecting and identifying Acremonium sp., Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus glaucus, Aspergillus nidulans, Aspergillus niger, Aspergillus ochraceus, Aspergillus terreus, Aspergillus unguis, Aspergillus ustus, Beauveria sp., Bipolaris sp., Blastoschizomyces sp., Blastomyces dermatitidis, Candida albicans, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Chrysosporium sp., Cladosporium sp., Coccidioides immitis, Cryptococcus neoformans var gattii serotype B, Cryptococcus neoformans serotpe A, Cryptococcus laurentii, Cryptococcus terreus, Curvularia sp., Fusarium sp., Filobasidium capsuligenum, Filobasidiella (Cryptococcus) neoformans var bacillispora serotype C, Filobasidiella (Cryptococcus) neoformans var neoformans serotype D, Filobasidium uniguttulatum, Geotrichum sp., Histoplasma capsulatum, Malbranchea sp., Mucor sp., Paecilomyces sp, Penicillium species, Pseudallescheria boydii, Rhizopus sp., Sporothrix schenkii, Scopulariopsis brevicaulis sp., Scopulariopsis brumpti, Saccharomyces cerevisiae, and Trichosporon beigelii. in clinical, food, environmental and other samples. Fungi are eukaryotic microorganisms that are universally distributed. While in nature fungi play a major role in the decomposition of plant materials, they are also responsible for spoilage of food, beverage and pharmaceutical preparations. Out of an estimated 100,000 species of fungi described by mycologists, approximately 150 species are pathogenic to man and animals. The increasing incidence of AIDS and the development of newer treatments for hematologic malignancies and organ transplants has lead to an increase in the number of immunocompromised patients. These patients have a high risk of developing fungal infections, which if not rapidly diagnosed and treated are capable of causing death in a matter of days. The number of antifingal drugs is limited and their toxic side effects on the patient are much higher than that of comparable antibacterial therapy. A rapid diagnosis of fingal infection and start of treatment is critical in these patients. Books by Kwon-Chung and Bennett, along with Sarosi and Davies, provide an overview into the medical importance of fungi. Fungal organisms are identified by morphology and nutritional characteristics. Fungi may take anywhere from two days to several weeks to grow in culture and often the same organism can take radically different forms depending on the growth conditions. This makes timely identification difficult even for the classically trained expert and impedes the treatment of patients where rapid identification of genus and species is of medical advantage. Web site: http://www.delphion.com/details?pn=US05958693__ •
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
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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 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__
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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). Web site: http://www.delphion.com/details?pn=US06337314__
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Method and preparations for the treatment of fungus Inventor(s): Chen; Yu (1520 Taylor Ave., Baltimore, MD 21234) Assignee(s): None Reported Patent Number: 6,090,389 Date filed: October 26, 1998 Abstract: A method and preparations for the treatment of vaginal yeast and other yeast infections is provided for the treatment of infections caused by Candida albicans and Cryptococcus neoformans. The method and preparations of the invention can also be used for other yeast and fungal infections including systemic, mucosal and cutaneous caused by Candida and Cryptococcus. The vaginal antiyeast and antifungal preparations include, in addition to suppositories and mouth washes, troches, lotions, creams, tablets and capsules containing gentian preparations as an active ingredient obtained from the plant Radix gentianae Longdancao. For systemic fungal infections gentian preparations from the plant Radix gentianae Longdancao are taken orally in the form of lozenges, tablets, capsules or in solution form for gargling or swallowing. Excerpt(s): The present invention pertains to a method and novel compositions containing gentian from the gentianaceae family of plants for the treatment of vaginal yeast infections and other fungal infections caused by various fungal and yeast forms such as Candida and Cryptoccus. More particularly, the invention pertains to novel compositions and preparations obtained from the root or seeds of the plant having the pharmaceutical name of Radix gentianae Longdancao for the treatment of vaginal yeast infections and other fungus and yeast infections caused by Candida albicans and Cryptoccus. The plant Radix gentianae Longdancao is also known by the botanical names Gentiana scabra Bge, Gentiana triflora Pall, Gentiana manshurica Kitag, Gentiana algida Pall, Gentiana regescens Fransh and Gentiana lutea which will be referred to collectively as Radix gentianae Longdancao. Radix gentianae Longdancao may be used to prepare novel antifungal preparations and novel medicaments in the form of topical creams, liquids, lotions, capsules, lozenges and suppositories. The novel preparations from Radix gentianae Longdancao may be applied topically or transmucosally to treat cutaneous and mucosal syndromes caused by candida infection or taken internally in the form of lotions, liquids, tablets and capsules for the treatment of systemic Candida and Cryptoccus infections. The novel method of treatment of Candida and Cryptoccus infection with novel preparations from Radix gentianae Longdancao is effective in treating not only cutaneous and mucosal candidiasis but also systemic candidiasis involving the bloodstream and metastatic invasion of the meninges, bones, joints, peritonium and myocardium. The novel Radix gentianae Longdancao preparations, when taken internally, pass through the digestive system and enter the blood stream for the treatment of systemic Candida infections and pass the blood brain barrier to treat meningeal candidiasis and Cryptoccus meningitis in AIDS patients. The novel preparations of the invention do not require injection or IV application for the treatment of fungal infections of Candida albicans, Candida tropicalis and other Candida species referred to collectively as Candida and Cryptoccus neoformans and other Cryptoccus species collectively referred to as Cryptoccus. The novel Radix gentianae Longdancao preparations are advantageous over the prior art since they are nontoxic to the patient and may be utilized in patients having weak or compromised immune systems such as in the case of AIDS patients, leukemia, Hodgkin's disease, neutropenia, hematologic diseases and endocrinopathies. Web site: http://www.delphion.com/details?pn=US06090389__
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Method of treating HIV by a topical composition Inventor(s): Ratcliff; Perry A. (7439 E. Lincoln Dr., Scottsdale, AZ 85253) Assignee(s): None Reported Patent Number: 6,200,557 Date filed: October 14, 1999 Abstract: A solution or gel composition containing activated stabilized chlorine dioxide and phosphates, such as disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, and sodium monofluorophosphate, is disclosed for destroying HIV. The preferred concentration ranges are between about 0.005%-2.0% chlorine dioxide, and between about 0.02%-3.0% phosphate. The phosphate compound retards escape of chlorine dioxide in the pH range of 6.0 to 7.4, at which pH stabilized chlorine dioxide becomes activated and releases sufficient chlorine dioxide to reduce motility and become lethal to the involved micro-organisms. Using a lubricant as a vehicle for the chlorine dioxide/phosphate composition; development of vaginal itching due to Candida Albicans will be stopped. Excerpt(s): The present invention is directed to a method and composition for destroying Human Immuno Virus (HIV) and other bacterial and fungus viral forms and the present invention is directed to a related method and composition which provide lubricity, stops vaginal itching and destroys HIV. More particularly, the present invention relates to the use of activated stabilized chlorine dioxide in conjunction with a phosphate compound to destroy HIV and other viral forms and wherein the phosphate compound provides stability and serves as a surfactant or nonsudsing detergent to reduce surface tension on mucosal tissues assisting in the exposure of the epithelial covering to the activated chlorine dioxide. Thiols, particularly the volatile sulfur compounds such as hydrogen sulfide, methylmercaptan and dimethylsulfide, are recognized in the current literature as being major contributors to the penetration of bacterial toxins through the epithelial barrier into the underlying basal lamina and connective tissue. A. Rizzo, Periodontics, 5:233-236 (1967), W. Ng and J. Tonzetich, J. Dental Research, 63(7):994-997 (1984); M. C. Solis-Gaffar, T. J. Fischer and A. Gaffar, J. Soc. Cosmetic Chem., 30:241-247 (1979); I. Kleinberg and G. Westbay, J. Periodontal, 63(9): 768-774 (1992). The penetration of this barrier makes possible the invasion of antigenic substances such as viral and bacterial toxins and bacteria into the underlying substrate. Thus, by removing the volatile sulfur compounds and maintaining the epithelial barrier there is a reduction in the penetration capacity of antigens and microbiota (A. Rizzo, Periodontics, 5:233-236 (1967); W. Ng and J. Tonzetich, J. Dental Research, 63(7): 994-997 (1984); M. C. Solis-Gaffar, T. J. Fischer and A. Gaffar, J. Soc. Cosmetic Chem., 30:241-247 (1979)) as well as the destruction of the motility and the death of bacterial and viral forms. Studies done in the mouth have demonstrated that the penetration of bacteria takes place in the presence of the volatile sulfur compounds, resulting in initiation of the inflammatory reaction including initiation of the complement cascade. I. Kleinberg and G. Westbay, J. Periodontal, 63(9): 768-774 (1992). Initiation of the inflammatory reaction and development of the complement cascade leads to an eightfold increase in the cell division or mitosis of epithelial cells in the attachment apparatus of the gingiva. W. O. Engler, S. P. Ramfjiord and J. J. Hiniker, J. Periodont., 36:44-56 (1965). Because the epithelia of other orifices, and particularly vaginal epithelium, are very similar to the gingival epithelium, reactions similar to those described above for the gingival epithelium occur in all other parts of the body, as demonstrated by the occurrence of vaginitis and endometriosis of the vagina. Examples of such bacteria which may appear in any bodily orifice include Porphyromonas
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(formerly known as Bacteroides) gingivitis, Actinobacillus actinomycetemcomitans, and Pseudomonades. Web site: http://www.delphion.com/details?pn=US06200557__ •
Methods and reagents for detecting fungal pathogens in a biological sample Inventor(s): Bhattacharjee; Jnanendra K. (Oxford, OH), Bhattacherjee; Vasker (Oxford, OH) Assignee(s): Miami University (oxford, Oh) Patent Number: 5,910,409 Date filed: May 20, 1996 Abstract: The present invention provides materials and methods for sensitively and selectively screening biological samples for the presence of Candida albicans, a fungal pathogen of increasing clinical concern. Specifically, nucleic acids, reagents, and primers for DNA amplification are provided that will allow amplification of a 526 base pair oligonucleotide from DNA containing Candida albicans. Methods for using such primers in DNA amplification are also provided. Excerpt(s): The present invention relates to novel methods for identifying fungal pathogens in a biological sample. In particular, this invention relates to methods for screening biological samples for the presence of Candida albicans that employ novel DNA amplification primers. Candida albicans, once considered a relatively minor fungal pathogen, has recently become a particularly serious health concern as the causative agent of candidosis (also called candidiasis). The incidence of C. albicans infections is rising rapidly with the increase in immune deficiency diseases and immunosuppressive therapy (Bodey and Fainstein, In Systemic Candidiasis, pp. 135 (Eds., Raven Press, New York 1985). Candidosis is a common nosocomial infection afflicting both immunosuppressed and postoperative patients. (Holmes, A. R., et al. Yeast-specific DNA probes and their application for the detection of Candida albicans, J. Med. Microbiol., 37:346-351 (1992)). Although candidosis is a particular concern among immunocompromised individuals, Candida infections are not limited to this group. C. albicans is the major opportunistic fungal pathogen in humans (Odds, F. C., In Candida and candidosis, (Ed.) Leicester University Press, Leicester, United Kingdom (1989)) and is capable of establishing infection whenever the host immune system or normal flora are perturbed. Although the C. albicans species is a particular health concern, other species of the Candida genus are also pathogenic. The genus Candida is comprised of approximately 200 diverse yeast species classified together due to their lack of a sexual cycle (Meyer et al., In Genus 4, Candida, pp. 1-12, (Ed.) N. J. W. Kregervan Riij, Elsevier, Amsterdam (1984)). A minority of Candida species are pathogenic and 80% of the clinical isolates are either C. albicans or C. tropicalis (Hopfer, R. L. In Mycology of Candida Infections, G. P. Bodey, an V. Fainstein (eds.), Raven Press, New York (1985)). Web site: http://www.delphion.com/details?pn=US05910409__
Patents 191
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Methods of combatting infectious diseases using dicationic bis-benzimidazoles Inventor(s): Boykin; David W. (Atlanta, GA), Dykstra; Christine C. (Chapel Hill, NC), Perfect; John (Durham, NC), Tidwell; Richard R. (Pittsboro, NC), Wilson; W. David (Atlanta, GA) Assignee(s): Duke University (durham, Nc), Georgia State University Research Foundation, Inc. (atlanta, Ga), The University of North Carolina at Chapel Hill (chapel Hill, Nc) Patent Number: 5,939,440 Date filed: August 7, 1998 Abstract: The present invention provides methods for treating Cryptococcus neoformans and Candida albicans in a subject in need of such treatment. The methods comprises administering to the subject a dicationic bis-benzimidazole in an amount effective to treat the conditions. Excerpt(s): The present invention relates to methods useful in combatting infectious diseases. Specifically, this invention relates to methods of combatting infectious diseases using dicationic bis-benzimidazole compounds. The need for new antifungal agents has become more pronounced because of the increase in the number of fungal infections which occur in patients who are immunocompromised. There is an increased incidence of fungal infections attributed, for example, to the aggressive use of cancer chemotherapy, organ transplantation, and opportunistic infections associated with acquired immunodeficiency syndrome (AIDS) patients. Fungal infections are among the most common complications of AIDS, as well as of cancer chemotherapy. The major opportunistic fungal pathogens causing disseminated mycoses in immunocompromised hosts include Candida and Cryptococcus. Currently used antifungal agents for the treatment of systemic mycoses can be classified as polyene antibiotics, including Amphotericin B, flucytosine and synthetic azoles. There can, however, be significant drawbacks to the use of these agents, including limited efficacy and/or toxicity. Accordingly, it is an object of the present invention to provide new compounds useful in the treatment of fungal infections. Web site: http://www.delphion.com/details?pn=US05939440__
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Synergistic antifungal protein and compositions containing same Inventor(s): Laue; Bridget E. (Davis, CA), Potter; Sharon L. (Raleigh, NC), Roberts; Walden K. (Denver, CO), Selitrennikoff; Claude P. (Evergreen, CO) Assignee(s): Novartis Finance Corporation (new York, Ny), University Research Corporation (boulder, Co) Patent Number: 5,981,844 Date filed: December 19, 1997 Abstract: Novel plant proteins (SAFPs) which synergize the activity of antifungal antibiotics are identified. SAFPs are demonstrated to synergize antifungal antibiotics, such as nikkomycins, polyoxins and amphotericins. SAFPs alone also display antifungal activity against several species of fungi, including strains of Candida, Trichoderma, Neurospora and strains of the plant pathogens Fusarium, Rhizoctonia and Chaetomium. Synergistic antifungal compositions containing SAFP and antifungal antibiotics are provided. In particular, synergistic compositions of corn-SAFP (zeamatin), sorghum-
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SAFP (sormatin) or oat-SAFP (avematin) and nikkomycin are found to be effective as antifungal compositions, especially against the opportunistic human pathogen Candida albicans. Method for employing SAFPs and synergistic compositions containing them for the inhibition of fungi are provided. In addition, a method for purifying SAFP from grain meal is provided. Excerpt(s): This invention relates to novel antifungal plant proteins which synergize and enhance the activity of antifungal antibiotics which are designated synergistic antifungal proteins (SAFPs), particularly those isolated from grains, and especially that isolated from corn (zeamatin). SAFPs alone are useful for the inhibition of growth of certain fungi. The synergistic antifungal compositions of the present invention are generally useful in vitro and in vivo for inhibition of fungal growth and for combatting fungal infections. Zeamatin/nikkomycin compositions are particularly useful in inhibiting the growth of the opportunities human pathogen Candida albicans and for combatting candidal infections. Furthermore, the invention relates to genes for novel an antifungal proteins and their use in transgenic technologies. There is significant need for effective antimycotic drugs especially for the treatment of systemic fungal infections which are life-threatening, common complications in immune-compromised patients, see for example Hart et al. (1969) J. Infect. Dis. 120:169-191. Among the most virulent organisms are strains of the yeast Candida, most particularly strains of C. albicans. While there are several effective topical agents for treatment of candidiases, treatment of systemic infection is much more difficult. The drug of choice for systemic infection is amphotericin B, however this drug is highly toxic to the host (see, for example, Medoff and Kobayashi (1980) New Eng. J. Med. 302:145-55). Antimycotic agents that are more effective and/or less toxic than existing drugs are highly desirable. Several classes of nucleoside antibiotics, including polyoxins (Hori et al. (1971) Agr. Biol. Chem. 35:1280; Hori et al. (1974) Agr. Biol. Chem. 38:699; Sasaki et al. (1968) Ann. Phytopathol. Soc. Japan 34:272) and nikkomycins (Dahn et al. U.S. Pat. Nos. 4,046,881 and 4,158,608; Zahner et al. U.S. Pat. No. 4,287,186; Hagenmaier et al. U.S. Pat. No. 4,315,922) have been reported. Polyoxins and nikkomycins are reported to be useful in agriculture against phytopathogenic fungi and insect pests. Early reports indicated that polyoxins were not effective against zoopathogenic fungi, such as C. albicans (see, for example, Gooday (1977) J. Gen. Microbiol. 99:1; Shenbagamurthi et al. (1983) J. Med. Chem. 26:1518-1522). It was believed that the polyoxins were not taken up by target cells. More recently, polyoxins have been reported to inhibit the growth in vitro of certain zoopathogenic fungi including C. albicans and Cryptococcus neoformans when provided at millimolar concentrations (Becker et al. Antimicro. Agents Chemother. (1983) 23:92-929 and Mehta et al. (1984) Antimicro. Agents Chemother. 25:373-374). Nikkomycins X and Z have now also been reported to inhibit growth of C. albicans in vitro (Yadan et al. (1984) J. Bacteriol. 160:884-888; McCarthy et al. (1985) J. Gen. Microbiol. 131:775-780). Polyoxins and nikkomycins are similar in structure and apparently both act as competitive inhibitors of chitin synthetase (Endo et al. (1970) J. Bacteriol. 104:189-196; Muller et al. (1981) Arch. Microbiol. 130:195-197). Chitin is an essential component of the cell wall of most fungi. Nikkomycins appear, however, to be more effective (about 100 fold) against certain fungi, for example C. albicans, than polyoxins which is in part due to a higher affinity of nikkomycin for chitin synthetase and more rapid uptake of nikkomycin by C. albicans cells (McCarthy et al. (1985) supra). The activity of polyoxins and nikkomycins is reported to be inhibited by peptides, such as those present in rich media (Becker et al., 1983, supra; McCarthy et al., 1985, supra Mehta et al., 1984, supra). Peptides are believed to inhibit uptake of the antibiotic by target cells. The usefulness of nikkomycins and polyoxins for clinical applications such as in the treatment of systemic fungal infection,
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where peptide inhibition is likely, is expected to be limited as the concentrations of antibiotic required for effective fungal inhibition are not likely to be achieved in vivo. Web site: http://www.delphion.com/details?pn=US05981844__ •
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 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__
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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
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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__ •
Transformation of Candida albicans by electroporation Inventor(s): Kelly; Rosemarie (Westfield, NJ), Kurtz; Myra B. (Martinsville, NJ), Register; Elizabeth A. (Watchung, NJ), Thompson; John R. (Scotch Plains, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 5,908,753 Date filed: September 17, 1997 Abstract: There is disclosed a procedure for DNA-mediated transformation of Candida albicans by electroporation utilizing lithium acetate and dithiothreitol to weaken the cell wall structure and optimize the yield of transformants. Excerpt(s): The present invention relates to a procedure for DNA-mediated transformation of Candida albicans by electroporation. More particularly, the invention relates to the treatment of the host strain with lithium acetate and dithiothreitol in order to weaken the cell wall structure and optimize the yield of transformants. Electroporation has become the preferred method for gene transfer due to its ease and efficiency of operation in comparison to alternate techniques. To date, electroporation has been utilized to transform a wide variety of cell types including mammalian cells, plant protoplasts, bacteria and fungi, including yeast. The technique involves subjecting cells to a high voltage electric field, which results in the temporary formation of pores in the membrane, thereby allowing exogenous DNA to enter the cells. For example, laboratory strains of the yeast Saccharomyces cerevisiae have been transformed by electroporation with either self-replicating plasmids or by integration of linearized plasmid DNA into the host genome. Candida albicans is a pathogenic, diploid yeast
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capable of causing a broad spectrum of infections, especially in immunocompromised individuals. As the number of persons with increased susceptibility to Candida has risen over the past decade, so has the importance of this organism as an agent of disease. Much work has been done on this organism to identify potential virulence factors and to study its biology. To further the understanding of C albicans biology at the molecular level, a number of transformation systems have been developed. Integrative transformation was the first method developed for the transformation of C. albicans (Kurtz et al., Mol. Cell. Biol. (1986) 6:142-149). It is now widely used for genetic manipulation. Other references regarding transformation of Candida albicans include Kelly et al. Mol. Cell. Biol. (1987) 7:199-207; Kurtz et al. Mol. Cell. Biol. (1987) 7:209-217; Kelly et al. Mol. Gen. Genet. (1988) 214:24-31; Cannon et al., Mol. Gen. Genet. (1990) 235:4453-457; A recent journal article, Brown et al., Mol. Gen. Genet. (1996) 251:75-80, discloses a transformation method for C. albicans using restriction enzyme-mediated integration. Web site: http://www.delphion.com/details?pn=US05908753__ •
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
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life-threatening, 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__
Patent Applications on Candida Albicans As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Candida albicans: •
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
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This has been a common practice outside the United States prior to December 2000.
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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. 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
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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. 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
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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. 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 •
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
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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 •
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. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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CANDIDA ALBICANS POLYNUCLEOTIDES
mRNA
5'5-TRIPHOSPHATASE
(CET-1)
Inventor(s): DALLMANN, GARY; (MENLO PARK, CA), GREEN, SIMON; (PLEASANTON, CA), HUNG, MAGDELEINE; (HAYWARD, CA), LANE, JULIE; (OAKLAND, CA), MOEHLE, CHARLES M.; (CASTRO VALLEY, CA) Correspondence: Heller Ehrman White & Mcauliffe Llp; 1666 K Street,nw; Suite 300; Washington; DC; 20006; US Patent Application Number: 20020018774 Date filed: December 17, 1998 Excerpt(s): The present invention relates to enzymes involved in capping of fungal mRNAs, and molecules that inhibit such enzymes. In particular, the invention relates to the novel C. albicans capping enzyme genes ABD1 and CET1 and their encoded protein products, as well as derivatives and analogs thereof. The invention also relates to
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methods of using of these enzymes to screen for fungal inhibitors. Fungal pathogens are responsible for a variety of diseases in humans and animals ranging from mycoses involving skin, hair, or mucous membranes to severe systemic infections, many of which are fatal. In recent years there has been a marked increase in the number of serious fungal infections as a result of the growing number of immunosuppressed and immunocompromised individuals. For example, fungal infections represent a major problem in patients with AIDS. Indeed, the appearance in the early 1980's of rare opportunistic fungal infections and malignancies was a harbinger of the AIDS pandemic. Many of the infections seen in AIDS patients are also observed in other patients who are immunocompromised, including transplant patients on immunosuppressive drugs and cancer patients (Rosenberg and Brown, 1993, Disease-amonth 39, 507-569). 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; 200365869; 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 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
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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
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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 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 •
Dominant selectable marker for gene transformation and disruption in yeasts Inventor(s): Bussey, Howard; (Westmount, CA), Davison, John; (Montreal, CA), Roemer, Terry; (Montreal, CA) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20010031724 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 application claims priority to the U.S. provisional application No. 60/183,462, filed Feb. 18, 2000, which is incorporated herein by reference in its entirety. 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
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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. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Gene disruption methodologies for drug target discovery Inventor(s): Boone, Charles; (Toronto, CA), Bussey, Howard; (Westmount, CA), Jiang, Bo; (Montreal, CA), Ohlsen, Kari L.; (San Diego, CA), Roemer, Terry; (Montreal, CA) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030180953 Date filed: December 20, 2001 Abstract: The present invention provides methods and compositions that enable the experimental determination as to whether any gene in the genome of a diploid pathogenic organism is essential, and whether it is required for virulence or pathogenicity. The methods involve the construction of genetic mutants in which one allele of a specific gene is inactivated while the other allele of the gene is placed under conditional expression. The identification of essential genes and those genes critical to the development of virulent infections, provides a basis for the development of screens for new drugs against such pathogenic organisms.The present invention further provides Candida albicans genes that are demonstrated to be essential and are potential targets for drug screening. The nucleotide sequence of the target genes can be used for various drug discovery purposes, such as expression of the recombinant protein, hybridization assay and construction of nucleic acid arrays. The uses of proteins encoded by the essential genes, and genetically engineered cells comprising modified alleles of essential genes in various screening methods are also encompassed by the invention. Excerpt(s): This application claims priority to the U.S. provisional application serial No. 60/259,128, filed Dec. 29, 2000, U.S. non-provisional application Ser. No. 09/792,024, filed Feb. 20, 2001; and U.S. provisional application serial No. 60/314,050, filed Aug. 22, 2001, which are all incorporated herein by reference in their entirety. The present invention is directed toward (1) methods for constructing strains useful for identification and validation of gene products as effective targets for therapeutic intervention, (2) methods for identifying and validating gene products as effective targets for therapeutic intervention, (3) a collection of identified essential genes, and (4) screening methods and assay procedures for the discovery of new drugs. Validation of a cellular target for drug screening purposes generally involves an experimental demonstration that inactivation of that gene product leaves the cell inviable.
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Accordingly, a drug active against the same essential gene product expressed, for example, by a pathogenic fungus, would be predicted to be an effective therapeutic agent. Similarly, a gene product required for fungal pathogenicity and virulence is also expected to provide a suitable target for drug screening programs. Target validation in this instance is based upon a demonstration that inactivation of the gene encoding the virulence factor creates a fungal strain that is shown to be either less pathogenic or, ideally, avirulent, in animal model studies. Identification and validation of drug targets are critical issues for detection and discovery of new drugs because these targets form the basis for high throughput screens within the pharmaceutical industry. 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 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
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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 •
Hypha-specific factors from candida albicans Inventor(s): Johannes, Franz-Josef; (Leonberg, DE), Rupp, Steffen; (Stuttgart, DE), Sohn, Kai; (Schwabisch-Gmund, DE) Correspondence: Morriss O'bryant Compagni, P.C.; 136 South Main Street; Suite 700; Salt Lake City; UT; 84101; US Patent Application Number: 20040014061 Date filed: July 2, 2003 Abstract: The present invention relates to biochips, in particular nucleotide chips, which contain hyphen-specific proteins coding nucleotides, protein chips which contain hyphen-specific proteins, and antibody chips which contain antibodies directed against these hyphen-specific proteins, diagnostic compositions which contain these nucleotide, protein, or antibody chips, processes for the location and identification of substances which are therapeutically effective against diseases caused by types of Candida and processes for the diagnosis of a disease caused by Candida. Excerpt(s): The present application is a nationalization of PCT Application No. PCT/EP01/05363, filed May 10, 2001, claiming priority to German Patent Application 10023130.6, filed May 11, 2000. The present invention relates to biochips, in particular nucleotide chips, which contain nucleotide sequences coding hyphen-specific proteins, protein chips, which contain hyphen-specific proteins, and antibody chips, which contain antibodies directed against these hyphen-specific proteins, diagnostic compositions which contain these nucleotide, protein, or antibody chips, processes for the location and identification of substances, which are therapeutically effective against diseases caused by types of Candida and processes for the diagnosis of a disease caused by Candida. Along with the yeasts of the Saccharomycetaceae family, which have been used commercially, e. g. in the food industry, for a long time, asporogenous yeasts such as, for example, yeasts of the genus Candida, also number among the budding funguses or yeasts. Several members of the genus Candida are able to form mycel aggregates. Others reproduce only by sprouting. Candida albicans is the most frequently isolated human pathogenic fungus. Candida albicans frequently causes opportunistic infections, i. e. infections in immunosuppressed patients by normally relatively unproblematic microbes. Infections of this type take a serious course in these patients and decisively shorten the survival time, for example, of HIV-infected patients or of cancer patients treated with chemotherapy or radiation therapy. Presently, the treatment of systemic infections with Candida albicans is carried out principally by means of azoles or polyenes. However, the treatment by means of these two classes of substances has disadvantages. Polyenes lead to strong side effects while resistance to the azoles is
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increasingly developing (DiDomenico, 1999, Curr Opin Microbiol 2, 509 to 515, Georgopapadakou, 1998, Curr Opin Microbiol 1, 547 to 557). 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 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
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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 •
Personal care article and method for inhibiting attachment of yeast to skin Inventor(s): Koenig, David W.; (Menasha, WI) Correspondence: Pauley Petersen Kinne & Erickson; 2800 West Higgins Road; Suite 365; Hoffman Estates; IL; 60195; US Patent Application Number: 20030224034 Date filed: May 31, 2002 Abstract: A personal care article including an isoprenoid compound, and a method of inhibiting attachment of pathogenic fungi to skin using an isoprenoid compound in combination with a personal care article. The isopreniod compound may be farnesol, which is particularly effective against the pathogenic yeast Candida albicans. Excerpt(s): This invention is directed to a personal care article including an isoprenoid compound, such as farnesol, and a method of inhibiting attachment of yeast to skin using an isoprenoid compound, such as farnesol. The growth and attachment of the pathogenic yeast Candida albicans on human skin has been associated with numerous ailments such as thrush in infants, diaper rash in infants, and urinary/vaginal infections in adult females. Other fungi that adhere to human skin and subsequently grow, causing ailments, include Mallessia, Tricophyton, Epidermophyton, Scytalidium, Fusarium, Acremonium, Aspergillus, Scopulariopsis, and Pityrosporum. Adherence to
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epithelial cells is the first step in colonization by Candida and other fungi, followed by establishment of mucocutaneous infection. Similarly, adherence to intravascular structures is considered to be a critical step in the infection of blood-borne fungi to target organs. Optimal therapy in treating Candida and other fungi requires strategies to increase host resistance to yeast or other fungal infection, combined with the use of antifungal agents. Antifungal agents destroy or inhibit the growth of fungi, thereby fighting fungal infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
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 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.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
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 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
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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 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
Keeping Current In order to stay informed about patents and patent applications dealing with Candida albicans, 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 albicans” (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 albicans. You can also use this procedure to view pending patent applications concerning Candida albicans. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON CANDIDA ALBICANS Overview This chapter provides bibliographic book references relating to Candida albicans. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Candida albicans 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 albicans” (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 albicans: •
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 HIV-
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positive 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. •
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 books. When searching for “Candida albicans” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Candida albicans” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Candida albicans” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
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 by Sarah Brewer; ISBN: 0722533918; http://www.amazon.com/exec/obidos/ASIN/0722533918/icongroupinterna
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CANDIDA ALBICANS by Gill Jacobs (Author); ISBN: 035621088X; http://www.amazon.com/exec/obidos/ASIN/035621088X/icongroupinterna
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Candida Albicans: A Nutritional Approach by Louise Tenney, Rita Elkins; ISBN: 0913923281; http://www.amazon.com/exec/obidos/ASIN/0913923281/icongroupinterna
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Candida Albicans: A User's Guide to Treatment and Recovery by Gill Jacobs; ISBN: 0356186857; http://www.amazon.com/exec/obidos/ASIN/0356186857/icongroupinterna
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Candida Albicans: Cellular and Molecular Biology by R. Prasad; ISBN: 3540519262; http://www.amazon.com/exec/obidos/ASIN/3540519262/icongroupinterna
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Candida Albicans: Could Yeast Be Your Problem? by Leon Chaitow; 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; 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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Candidose (Candida Albicans) by S. Martin; ISBN: 2921556707; http://www.amazon.com/exec/obidos/ASIN/2921556707/icongroupinterna
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Nutrition & Candida Albicans; ISBN: 0879834463; http://www.amazon.com/exec/obidos/ASIN/0879834463/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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The Candida Albicans Yeast-Free Cookbook by Pat Connolly; ISBN: 0879834099; http://www.amazon.com/exec/obidos/ASIN/0879834099/icongroupinterna
Chapters on Candida Albicans In order to find chapters that specifically relate to Candida albicans, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Candida albicans 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 albicans” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Candida albicans: •
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
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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. •
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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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 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
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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 7. MULTIMEDIA ON CANDIDA ALBICANS Overview In this chapter, we show you how to keep current on multimedia sources of information on Candida albicans. 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.
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 albicans” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on Candida albicans: •
AIDS Update: ED Management, Part II Contact: California Medical Association, Audio Digest Foundation, 1577 E Chevy Chase Dr, Glendale, CA, 91206, (213) 245-8505. 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,
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pulmonary diseases, cryptosporidium, Asymptomatic carriers are discussed.
toxoplasmosis,
and
tuberculosis
(TB).
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CHAPTER 8. PERIODICALS AND NEWS ON CANDIDA ALBICANS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Candida albicans.
News Services and Press Releases One of the simplest ways of tracking press releases on Candida albicans 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 albicans” (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 albicans. 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 albicans” (or synonyms). The following was recently listed in this archive for Candida albicans: •
Fluconazole, cyclosporine synergistic against Candida albicans Source: Reuters Industry Breifing Date: September 12, 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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Non-Candida Albicans Species On The Increase; Antifungal Resistance A Concern Source: Reuters Medical News Date: July 29, 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. 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 albicans” (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 albicans” (or synonyms). If you know the name of a company that is relevant to Candida albicans, 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/.
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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 albicans” (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 albicans” (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 albicans: •
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 Albicans Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Candida albicans. In addition to these sources, you can search for articles covering Candida albicans 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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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Candida albicans” (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 16802 56 956 540 37 18391
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “Candida albicans” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Candida albicans 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 albicans. 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 albicans. 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 albicans”:
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Other guides Candidiasis http://www.nlm.nih.gov/medlineplus/candidiasis.html Chronic Fatigue Syndrome http://www.nlm.nih.gov/medlineplus/chronicfatiguesyndrome.html Fungal Infections http://www.nlm.nih.gov/medlineplus/fungalinfections.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 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 albicans. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Candida albicans. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Candida albicans. 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 albicans. 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 albicans” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Candida albicans”. 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 albicans” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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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 albicans” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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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
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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/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
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
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
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
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CANDIDA ALBICANS 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: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [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] Actin: Essential component of the cell skeleton. [NIH] Actinomyces: A genus of gram-positive, rod-shaped bacteria whose organisms are nonmotile. Filaments that may be present in certain species are either straight or wavy and may have swollen or clubbed heads. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In
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microbiology, the adjustment of bacterial physiology to a new environment. [EU] 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] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] 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]
Agonists: Drugs that trigger an action from a cell or another drug. [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
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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] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha 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-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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
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organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [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] 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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood
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thinner. [NIH] 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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] 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
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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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] 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 neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [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] 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]
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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] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basilar Artery: The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. [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]
Beta-Defensins: Defensins found mainly in epithelial cells. [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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] 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 Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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]
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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] 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] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH] Bladder: The organ that stores urine. [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 Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body 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]
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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] 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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] 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] 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
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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] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [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] 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] Cardiac: Having to do with the heart. [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] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject 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] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] 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]
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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] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerulenin: Antifungal antibiotic isolated from several species, including Acremonium (Cephalosporium), Acrocylindrum, and Helicoceras. It inhibits the biosynthesis of several lipids by interfering with enzyme function and is used as a biochemical tool. [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] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The
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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] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chitin Synthase: An enzyme that converts UDP glucosamine into chitin and UDP. EC 2.4.1.16. [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] Cholecystitis: Inflammation of the gallbladder. [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] 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] 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] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] 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,
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prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] 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] 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] 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] Complement 3: The fourth component to attach in the complement reaction sequence. It is a beta-globulin with a sedimentation coefficient of 5.5, a molecular weight of 185,000 and a serum concentration of 1.3 micrograms/ml. Its fragments have anaphylatoxic, chemotactic, and histaminic action and affect smooth muscle. [NIH] Complement 3b: The larger fragment formed when C3 convertase splits C3 into C3a and C3b. In both the classical and alternate pathway, C3b participates in immune adherence and enhances phagocytosis. It also forms a cellular intermediate which continues the complement process. In the alternate pathways, C3b initiates a positive feedback activation of C3Pase. [NIH] Complement Factor I: Serine proteinase that acts on iC3b (inactivated complement 3b) to cleave it into C3c and C3dg with the help of a trypsin-like proteolytic enzyme. Complement factor I was formerly called KAF, C3bINF, or enzyme 3b inactivator. EC 3.4.21.45. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]
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Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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
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groups of muscles, in a complex action or series of actions. [NIH] 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [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] 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]
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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] 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]
Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
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]
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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] 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] 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] De novo: In cancer, the first occurrence of cancer in the body. [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] 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]
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Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [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] 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] 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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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
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that depends on possessing both hydrophilic and hydrophobic properties. [NIH] 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] Diaper Rash: A type of irritant dermatitis localized to the area in contact with a diaper and occurring most often as a reaction to prolonged contact with urine, feces, or retained soap or detergent. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Diploidy: The chromosomal constitution of somatic cells, in which each type of chromosome is represented twice. Symbol: 2N or 2X. [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] 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] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a
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cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]
Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] 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] 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
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to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [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] 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] Emollient: Softening or soothing; called also malactic. [EU] 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 a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] 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] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH]
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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-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] Enhancer: Transcriptional element in the virus genome. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enterococcus: A genus of gram-positive, coccoid bacteria consisting of organisms causing variable hemolysis that are normal flora of the intestinal tract. Previously thought to be a member of the genus Streptococcus, it is now recognized as a separate genus. [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] 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]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] 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]
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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]
Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [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] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU]
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Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] 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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] 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] 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] 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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure
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of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [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] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Food and Beverages: Edible or potable substances. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Forearm: The part between the elbow and the wrist. [NIH] 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] 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] 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
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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] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] 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 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 Conversion: The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa. [NIH]
Gene 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]
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Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [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] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] 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] Geriatric: Pertaining to the treatment of the aged. [EU] 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] 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.
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[NIH]
Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (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] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] 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] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to
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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] 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] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [NIH] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [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] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]
Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] 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]
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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] 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] 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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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] 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]
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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] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] 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] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [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
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T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] 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]
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Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] 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] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic
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acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] 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] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inpatients: Persons admitted to health facilities which provide board and room, for the
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purpose of observation, care, diagnosis or treatment. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, 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] 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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-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] 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
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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] 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] 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] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] 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,
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interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Isoprenoid: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [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 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] 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] 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] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH]
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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] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] 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] 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] 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] 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]
Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [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]
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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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [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]
Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] 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]
Lymphadenitis: Inflammation of the lymph nodes. [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] 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] 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
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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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Manic: Affected with mania. [EU] 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] 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] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] 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] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [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] Meningoencephalitis: An inflammatory process involving the brain (encephalitis) and meninges (meningitis), most often produced by pathogenic organisms which invade the
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central nervous system, and occasionally by toxins, autoimmune disorders, and other conditions. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body 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] 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
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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] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] 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]
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Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [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] 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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] 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 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]
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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] 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] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatologist: Doctor who specializes in treating the diseases and disorders of newborn babies. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] 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]
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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] 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 endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [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 Staff: Personnel who provide nursing service to patients in an organized facility, institution, or agency. [NIH]
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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] Odynophagia: A painful condition of the esophagus. [NIH] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] 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] Opacity: Degree of density (area most dense taken for reading). [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] 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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] 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]
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Ovum: A female germ cell extruded from the ovary at ovulation. [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] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] 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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal,
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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] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [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] 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]
Peripheral blood: Blood circulating throughout the body. [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
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cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] 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] 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] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] 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] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] 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] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH]
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Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [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] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which vegetable proteins is available. [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
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of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] 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] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyploid: An organism with more than two chromosome sets in its vegetative cells. [NIH]
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Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of chromosomes; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc. [NIH]
Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] 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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] 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] 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]
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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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] 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] Propyl Gallate: Antioxidant for foods, fats, oils, ethers, emulsions, waxes, and transformer oils. [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
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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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [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]
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Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] 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] 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. 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]
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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] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] 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] 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] 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] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] 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
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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] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [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] Retrospective: Looking back at events that have already taken place. [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] 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] 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] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU]
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Rod: A reception for vision, located in the retina. [NIH] Saccharomyces: A genus of ascomycetous fungi of the family Saccharomycetaceae, order 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] 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] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [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] 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] 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] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] 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]
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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, pyrimidines, and other amino acids. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] Silver Compounds: Inorganic compounds that contain silver as an integral part of the molecule. [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]
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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] 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] Somatic cells: All the body cells except the reproductive (germ) cells. [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]
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Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermicide: An agent that is destructive to spermatozoa. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] 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] 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] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [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] 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]
Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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]
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Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] 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] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [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] Superoxide: Derivative of molecular oxygen that can damage cells. [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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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole 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] 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] 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] 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] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment
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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] Tinea Pedis: Dermatological pruritic lesion in the feet, caused by Trichophyton rubrum, T. mentagrophytes, or Epidermophyton floccosum. [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] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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
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"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] 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] Triclosan: A diphenyl ether derivative used in cosmetics and toilet soaps as an antiseptic. It has some bacteriostatic and fungistatic action. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Trivalent: Having a valence of three. [EU] 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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [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]
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Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unguis: The inelastic, translucent, horny plate formed of flat cornified epidermal cells. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [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]
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 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] Variegation: The appearance of different kinds of tissue in patterns, patches, or bands, frequently caused by the presence of special pigments or the absence of normal pigments. [NIH]
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]
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Vegetable Proteins: Proteins which are present in or isolated from vegetables or vegetable products used as food. The concept is distinguished from plant proteins which refers to nondietary proteins from plants. [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] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] 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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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] 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
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by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] 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] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]
315
INDEX 3 3-dimensional, 43, 245, 298 A Abdomen, 245, 252, 281, 283, 293, 306 Abdominal, 245, 292, 293, 294 Abdominal Pain, 245, 294 Abscess, 104, 109, 245 Acceptor, 245, 273, 283, 285, 292, 304, 309 Acetylcholine, 245, 290 Acetylgalactosamine, 245, 273 Acetylglucosamine, 61, 94, 245, 273 Acquired Immunodeficiency Syndrome, 85, 180, 191, 245 Actin, 21, 45, 87, 109, 132, 245, 289 Actinomyces, 152, 172, 176, 245 Acute leukemia, 102, 245 Adaptability, 245, 255 Adaptation, 53, 99, 115, 245, 288 Adenine, 125, 211, 246, 300 Adenovirus, 246, 261 Adenylate Cyclase, 14, 64, 104, 246 Adhesives, 175, 246 Adjustment, 245, 246 Adjuvant, 39, 46, 246, 271 Adsorption, 41, 246 Adsorptive, 246 Adverse Effect, 33, 54, 246, 304 Aerobic, 246, 287, 299, 310 Affinity, 13, 21, 41, 73, 94, 119, 132, 160, 163, 184, 192, 246, 285, 305 Affinity Chromatography, 13, 246 Agar, 65, 70, 108, 246, 257, 261, 278, 295 Agonists, 15, 177, 205, 246 Alanine, 144, 246 Aldehydes, 29, 246 Algorithms, 246, 252 Alimentary, 247, 292 Alkaline, 176, 184, 207, 247, 253, 263 Alkylating Agents, 247, 311 Alleles, 204, 247, 276 Allergen, 122, 247 Allogeneic, 201, 247, 274 Allogeneic bone marrow transplantation, 201, 247 Alopecia, 247, 261 Alpha Particles, 247, 300 Alpha-1, 100, 247 Alpha-Defensins, 247, 262
Alternative medicine, 222, 247 Alveoli, 247, 312 Amino Acid Sequence, 173, 198, 199, 247, 248, 272 Amino Acid Substitution, 60, 94, 163, 247 Ammonia, 247, 273, 311 Amplification, 16, 18, 47, 87, 88, 133, 190, 248 Anaemia, 203, 248 Anaerobic, 248, 306 Anaesthesia, 248, 279 Analgesic, 248, 290 Analog, 18, 86, 178, 248, 270 Analogous, 37, 53, 248, 265, 309 Anaphylatoxins, 248, 258 Anatomical, 8, 31, 248, 266 Angiitis, 105, 248 Animal model, 15, 20, 27, 40, 49, 53, 205, 248 Anions, 248, 281 Annealing, 248, 296 Antibacterial, 11, 182, 185, 207, 208, 248, 290, 291, 305 Anticoagulant, 248, 298 Antigen-Antibody Complex, 249, 258 Antigen-presenting cell, 249, 263 Anti-infective, 16, 249, 256, 277, 305 Anti-Infective Agents, 16, 249 Anti-inflammatory, 20, 145, 198, 249, 272, 290 Anti-Inflammatory Agents, 199, 249 Antimycotic, 71, 144, 158, 175, 182, 192, 249, 257, 298 Antineoplastic, 144, 154, 247, 249, 261 Antineoplastic Agents, 144, 154, 247, 249 Antioxidant, 249, 292, 298 Antiproliferative, 123, 249 Antiseptic, 249, 255, 310 Antiviral, 249, 293 Anus, 249, 252 Aplasia, 249, 265 Apoptosis, 30, 249 Applicability, 21, 178, 197, 203, 250 Aqueous, 154, 176, 250, 251, 262, 266, 277, 283 Arginine, 248, 250, 290, 291, 310 Arterial, 250, 260, 272, 277, 299
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Candida Albicans
Arteries, 250, 251, 252, 255, 260, 284, 286, 288 Arterioles, 250, 252, 254, 288 Articular, 250, 291 Aspartate, 205, 250 Aspartic, 41, 72, 87, 90, 120, 125, 135, 145, 159, 250, 267 Aspartic Acid, 250 Aspergillosis, 16, 26, 250, 282 Assay, 23, 34, 50, 78, 84, 88, 98, 115, 133, 152, 184, 204, 210, 250, 310 Astringents, 250, 286 Asymptomatic, 113, 220, 250 Attenuated, 9, 12, 60, 61, 123, 134, 250 Attenuation, 61, 205, 250 Atypical, 65, 72, 100, 116, 250 B Bacillus, 37, 207, 250, 253, 296 Bacteremia, 141, 250 Bacterial Infections, 14, 214, 250, 255, 274, 302 Bacterial Physiology, 36, 246, 250 Bacterial toxin, 34, 189, 250 Bactericidal, 125, 207, 208, 250, 255, 268, 290 Bacteriocins, 187, 250 Bacteriophage, 251, 295, 309, 312 Bacteriostatic, 251, 310 Bacterium, 36, 206, 251, 258, 259 Base, 190, 211, 246, 251, 253, 262, 263, 270, 272, 274, 282, 294, 308, 310 Basement Membrane, 251, 269, 282 Basilar Artery, 140, 251 Basophils, 251, 274, 283 Benign, 251, 275, 289, 300 Beta-Defensins, 11, 20, 251, 262 Bile, 251, 271, 275, 276, 283, 306 Bile Acids, 251, 271, 306 Biliary, 251, 275 Bioavailability, 251, 279 Biochemical, 14, 22, 25, 26, 32, 34, 35, 36, 40, 46, 47, 48, 64, 100, 145, 151, 163, 247, 251, 255, 265, 270, 273, 283, 291, 294 Biofilms, 8, 9, 11, 14, 36, 66, 71, 78, 80, 81, 123, 126, 133, 251 Biological Transport, 251, 264 Biopsy, 216, 251 Biotechnology, 58, 96, 98, 138, 144, 222, 229, 252 Biotransformation, 172, 252 Biotypes, 78, 101, 102, 252 Bladder, 252, 311
Blastomycosis, 252, 282 Blood Coagulation, 252, 253, 308 Blood Glucose, 252, 275, 280 Blood pressure, 203, 252, 272, 277, 287, 305 Blood vessel, 31, 252, 260, 267, 282, 284, 286, 305, 308, 311 Blood-Brain Barrier, 31, 137, 252 Blot, 85, 130, 141, 252 Body Fluids, 252, 265, 305 Bone Marrow, 209, 245, 252, 257, 261, 275, 277, 284, 288, 305, 307 Bone Marrow Transplantation, 209, 252 Bowel, 44, 252, 264, 281, 283, 294 Bowel Movement, 252, 264 Brachytherapy, 253, 281, 282, 300, 313 Bradykinin, 253, 290 Branch, 241, 253, 284, 293, 305, 308 Breakdown, 253, 255, 264, 271 Broad-spectrum, 16, 207, 253, 254, 291 Bronchiseptica, 253, 294 Buccal, 3, 4, 36, 112, 253, 306 C Calcineurin, 40, 62, 103, 156, 253 Calcium, 103, 150, 253, 258, 288, 304 Calmodulin, 253 Candidosis, 3, 72, 86, 107, 113, 119, 130, 132, 181, 190, 253 Canonical, 211, 253 Capillary, 88, 133, 253, 254, 312 Capillary Fragility, 254 Capsules, 188, 254, 271 Carbohydrate, 25, 43, 155, 162, 254, 272, 273, 285, 297, 304 Carbon Dioxide, 254, 262, 271, 302 Carcinogenic, 247, 254, 279, 291, 298, 306 Carcinogens, 254, 292 Cardiac, 254, 260, 266, 268, 288, 289, 306 Case report, 117, 254 Catalytic Domain, 14, 254 Catechin, 159, 254 Catheters, 179, 254, 270, 278, 281 Cations, 254, 281 Causal, 9, 24, 254, 275 Cause of Death, 37, 254 Caustic, 254, 305 Ceftriaxone, 71, 254 Cell Adhesion, 21, 31, 32, 62, 151, 254, 280 Cell Cycle, 5, 37, 50, 61, 77, 116, 121, 156, 254, 261, 282, 312 Cell Death, 58, 121, 249, 255, 289 Cell Differentiation, 255, 304
Index 317
Cell Division, 13, 189, 250, 254, 255, 281, 285, 286, 287, 295, 298, 303 Cell membrane, 17, 33, 40, 187, 205, 251, 255, 257, 263, 266, 281, 282, 295, 296 Cell proliferation, 255, 280, 304 Cell Respiration, 255, 287, 302 Cell Size, 255, 270 Cellular metabolism, 12, 255 Cellulose, 255, 270, 295 Central Nervous System, 245, 246, 253, 255, 271, 272, 273, 275, 286, 297 Central Nervous System Infections, 255, 275 Centromere, 13, 255 Cerebral, 251, 252, 255, 268 Cerebral Arteries, 251, 255 Cerulenin, 64, 79, 255 Cetylpyridinium, 3, 255 Cheilitis, 215, 255 Chemokines, 16, 36, 255 Chemotactic Factors, 255, 258, 290 Chemotaxis, 16, 186, 205, 256 Chimeras, 28, 256 Chitin Synthase, 58, 59, 90, 256 Chlorhexidine, 3, 9, 60, 123, 137, 165, 256 Chlorine, 189, 256 Chlorophyll, 256, 270 Cholecystitis, 142, 256 Cholesterol, 51, 183, 251, 256, 284, 303, 306 Chromatin, 13, 24, 249, 256, 267, 306 Chromatography, Liquid, 7, 256 Chromosomal, 24, 64, 65, 85, 126, 193, 248, 256, 264, 295, 297, 302, 308 Chromosome, 13, 24, 70, 79, 91, 255, 256, 259, 264, 274, 275, 282, 283, 296, 303, 308 Chromosome Segregation, 13, 256 Ciprofloxacin, 137, 165, 256 CIS, 26, 58, 256, 302 Clear cell carcinoma, 256, 263 Cleave, 256, 258 Clinical Medicine, 109, 125, 256, 297 Clinical trial, 4, 187, 229, 256, 261, 300 Clone, 13, 27, 32, 36, 126, 257 Cloning, 65, 73, 83, 252, 257, 280 Clot Retraction, 257, 296 Clotrimazole, 122, 158, 174, 216, 257 Coagulation, 252, 257, 275, 309 Coculture, 44, 257 Codon, 93, 257, 272 Coenzyme, 257, 284 Cofactor, 257, 290, 299, 308
Collagen, 107, 153, 246, 251, 254, 257, 269, 271, 296, 298 Colloidal, 257, 266, 294 Colony-Stimulating Factors, 257, 274 Combination Therapy, 28, 201, 257 Combinatorial, 6, 19, 258 Commensal, 11, 15, 27, 33, 34, 42, 75, 86, 195, 258 Commensalism, 5, 53, 258 Competency, 186, 258 Complement, 7, 48, 54, 62, 70, 94, 150, 151, 189, 248, 258, 259, 272, 280, 282 Complement 3, 258 Complement 3b, 258 Complement Factor I, 151, 258 Complementary and alternative medicine, 149, 167, 258 Complementary medicine, 149, 259 Computational Biology, 229, 259 Conception, 259, 306 Concomitant, 16, 27, 259 Cone, 184, 259, 307 Congenita, 259, 265 Conjugated, 17, 35, 259, 261 Conjugation, 252, 259 Connective Tissue, 44, 189, 252, 257, 259, 269, 271, 272, 284, 286, 303 Connective Tissue Cells, 259 Consciousness, 248, 259, 262, 264 Constipation, 259, 294 Constitutional, 203, 259, 288 Constriction, 259, 282 Contamination, 187, 259 Contraceptive, 113, 178, 197, 259 Contraindications, ii, 259 Coordination, 37, 259 Cor, 260, 272 Cornea, 101, 260, 303 Corneal Transplantation, 108, 260 Coronary, 260, 286, 288 Coronary Arteriosclerosis, 260, 288 Coronary Thrombosis, 260, 286, 288 Cortex, 255, 260, 268, 291, 298 Corticosteroids, 179, 180, 199, 260, 272 Cranial, 260, 269, 275 Craniocerebral Trauma, 260, 275 Critical Care, 46, 99, 260 Crossing-over, 260, 301 Crowns, 260, 263 Cryptococcosis, 40, 260 Cryptosporidium, 220, 260 Cues, 36, 261
318
Candida Albicans
Culture Media, 246, 261 Curative, 261, 308 Cutaneous, 82, 87, 107, 132, 181, 188, 198, 252, 253, 261 Cyanide, 261, 286 Cyanogen Bromide, 187, 261 Cyclic, 64, 67, 104, 182, 246, 253, 261, 274, 290 Cyclin, 37, 59, 261 Cyclin A, 37, 261 Cyclin-Dependent Kinases, 37, 261 Cyclophosphamide, 71, 261 Cyclosporine, 44, 221, 261 Cysteine, 255, 261, 262, 264, 267, 307 Cystine, 16, 261, 265 Cytochrome, 51, 60, 62, 66, 88, 95, 132, 138, 153, 160, 162, 183, 261, 262, 302 Cytochrome b, 95, 138, 262, 302 Cytokine, 28, 39, 44, 56, 63, 136, 262, 280 Cytomegalovirus, 217, 262 Cytoplasm, 249, 251, 255, 262, 267, 268, 274, 302 Cytosine, 102, 211, 262, 270 Cytoskeletal Proteins, 48, 262 Cytoskeleton, 21, 45, 262, 280, 287 Cytotoxic, 41, 216, 262, 278, 300, 304 Cytotoxic chemotherapy, 216, 262 Cytotoxicity, 16, 55, 262, 282 D Databases, Bibliographic, 229, 262 De novo, 7, 262 Defense Mechanisms, 38, 44, 54, 160, 262, 280 Defensins, 11, 15, 20, 41, 187, 199, 247, 251, 262 Degenerative, 262, 275, 291 Deletion, 22, 23, 53, 60, 68, 106, 249, 262, 271 Dementia, 245, 262 Demethylation, 51, 60, 79, 158, 262 Denaturation, 263, 296 Dendrites, 263 Dendritic, 15, 104, 137, 263 Dendritic cell, 15, 104, 137, 263 Density, 24, 263, 270, 291 Dental Abutments, 263 Dental Caries, 263 Dental Plaque, 9, 263 Dentin Permeability, 263, 305 Denture Cleansers, 101, 263 Dentures, 12, 175, 176, 263 Deoxyribonucleic, 53, 211, 263, 302
Deoxyribonucleic acid, 53, 211, 263, 302 Deoxyribonucleotides, 263 Depolarization, 263, 304 Depressive Disorder, 263, 283 Dermal, 263, 265 Dermatitis, 173, 263, 264 DES, 41, 248, 263 Detergents, 176, 263 Deuterium, 264, 277 Diabetes Mellitus, 11, 18, 112, 137, 264, 273, 275 Diagnostic procedure, 171, 222, 264 Diaper Rash, 173, 208, 264 Diarrhoea, 116, 264 Diffusion, 71, 108, 109, 251, 264, 278, 279, 281 Digestion, 247, 251, 252, 264, 281, 283, 306 Digestive system, 188, 264, 271 Dihydrotestosterone, 264, 301 Dihydroxy, 182, 264 Dilatation, 264, 298, 311 Diploid, 24, 40, 47, 59, 125, 194, 202, 204, 264, 295, 296 Diploidy, 24, 264 Direct, iii, 4, 16, 23, 25, 32, 34, 77, 203, 256, 264, 284, 301 Discrimination, 21, 47, 70, 264 Disinfectant, 256, 264, 268 Dissection, 39, 264 Dissociation, 41, 246, 264 Dissociative Disorders, 264 Distal, 21, 264, 271, 299 Disulphides, 264, 265 Dithiothreitol, 194, 265 Dominance, 194, 210, 265 Drive, ii, vi, 56, 143, 215, 216, 265, 281 Dross, 265, 298 Drug Delivery Systems, 186, 265 Drug Design, 51, 52, 58, 265 Drug Interactions, 16, 40, 265 Drug Tolerance, 265, 309 Duct, 265, 303 Dura mater, 265, 285, 292 Dysphagia, 216, 265 E Ecosystem, 179, 265 Ectoderm, 265 Ectodermal Dysplasia, 223, 265 Effector, 44, 56, 57, 205, 245, 258, 265, 282 Effector cell, 44, 56, 265, 282 Efficacy, 9, 43, 54, 57, 96, 155, 191, 207, 265, 266, 310
Index 319
Elastin, 257, 266, 269 Electrolyte, 266, 297, 305 Electrons, 249, 251, 266, 281, 292, 300 Electrophoresis, 66, 72, 74, 85, 95, 124, 129, 130, 159, 266, 278 Electroporation, 194, 266 Emaciation, 245, 266 Embryo, 255, 265, 266, 279 Emollient, 266, 291 Emulsions, 130, 246, 266, 298 Enamel, 263, 266, 282, 305 Encapsulated, 266, 283 Encephalitis, 266, 285 Endocarditis, 136, 181, 194, 210, 253, 266 Endocardium, 266 Endometrial, 266 Endometriosis, 189, 266 Endometrium, 266, 267 Endopeptidases, 267, 298 Endophthalmitis, 100, 110, 115, 142, 267 Endothelium, 267, 290, 296 Endothelium-derived, 267, 290 Endotoxic, 267, 283 Endotoxin, 267, 310 Enhancer, 267, 302 Enteric Nervous System, 45, 267 Enterococcus, 184, 267 Enterocytes, 99, 100, 267 Enterovirus, 45, 267 Environmental Health, 228, 230, 267 Enzymatic, 23, 26, 32, 253, 254, 258, 261, 263, 267, 276, 296, 302, 303 Eosinophils, 267, 274, 283 Epidemic, 180, 182, 215, 216, 219, 267 Epidemiological, 72, 97, 130, 267 Epidermal, 267, 282, 311 Epidermis, 265, 267, 268, 282, 298 Epinephrine, 268, 310 Epithelial Cells, 3, 11, 15, 20, 36, 38, 44, 79, 112, 118, 120, 189, 209, 251, 268, 275, 282 Epithelium, 11, 45, 134, 180, 189, 210, 251, 260, 267, 268 Epitope, 5, 13, 27, 43, 48, 87, 268 Erythrocytes, 16, 248, 252, 268, 275, 301 Esophageal, 33, 37, 39, 50, 92, 174, 216, 268, 271 Esophagitis, 178, 197, 216, 268, 271 Esophagus, 216, 217, 264, 268, 271, 284, 291, 294, 301, 306 Estrogen, 34, 38, 268 Ethanol, 109, 144, 154, 268, 269 Ether, 268, 310
Eukaryote, 268, 298 Eukaryotic Cells, 28, 262, 268, 278, 291 Evoke, 268, 306 Excitation, 268, 269 Exogenous, 6, 194, 246, 252, 268, 274 Expiration, 268, 301 External-beam radiation, 268, 281, 300, 313 Extracellular Matrix, 12, 41, 50, 68, 73, 85, 122, 150, 259, 269, 280 Extracellular Matrix Proteins, 73, 85, 150, 269 Extracellular Space, 269 F Facial, 269, 293 Facial Nerve, 269, 293 Faecal, 264, 269 Family Planning, 229, 269 Fat, 252, 260, 269, 272, 283, 303, 305, 307 Fatty acids, 269, 305 Feces, 259, 264, 269 Fermentation, 172, 269, 270 Fibrin, 252, 257, 269, 294, 296, 308 Fibrinogen, 30, 269, 296, 308 Fibronectin, 36, 92, 93, 269 Fibrosis, 14, 88, 269 Flow Cytometry, 99, 133, 269 Flucytosine, 22, 40, 54, 191, 203, 270 Fluorescence, 35, 42, 51, 74, 114, 269, 270 Fluorescent Dyes, 269, 270 Fold, 27, 192, 209, 270 Follicles, 15, 270 Food and Beverages, 184, 270 Food Preservatives, 208, 270 Forearm, 252, 270 Fornix, 270, 311 Frameshift, 270, 310 Frameshift Mutation, 270, 310 Fructose, 80, 270 Fungemia, 59, 102, 141, 270 Fungicides, Industrial, 249, 270 Fungistatic, 54, 183, 270, 310 Fungus, 5, 16, 19, 31, 38, 39, 45, 49, 50, 87, 90, 91, 169, 181, 182, 187, 188, 189, 198, 200, 201, 202, 205, 206, 215, 253, 260, 270, 288 G Gallbladder, 245, 251, 256, 264, 271 Gamma Rays, 271, 300 Ganglia, 245, 267, 271, 289 Gas, 69, 247, 254, 256, 264, 271, 277, 290, 312
320
Candida Albicans
Gas exchange, 271, 312 Gastric, 271, 276 Gastrin, 271, 276 Gastroenterology, 116, 216, 271 Gastroesophageal Reflux, 216, 271 Gastroesophageal Reflux Disease, 216, 271 Gastrointestinal tract, 42, 105, 195, 268, 271 Gastroscopy, 216, 271 Gelatin, 261, 271, 273, 307, 308 Gene Conversion, 125, 271 Gene Deletion, 13, 271 Gene Duplication, 23, 272 Gene Fusion, 37, 51, 272 Gene Library, 272 Gene Silencing, 24, 49, 53, 272 Genetic Code, 272, 290 Genetic Engineering, 183, 252, 257, 272 Genetic testing, 272, 296 Genetics, 23, 25, 36, 40, 42, 48, 58, 98, 116, 126, 131, 204, 259, 265, 272, 287 Genital, 113, 180, 194, 195, 210, 256, 272, 311 Genitourinary, 203, 272, 311 Genomic Library, 25, 186, 272 Genomics, 86, 272 Genotype, 63, 74, 83, 127, 203, 272, 294 Geriatric, 128, 272 Gland, 272, 284, 285, 292, 293, 303, 306, 307, 309 Glottis, 272, 294 Glucans, 86, 162, 272 Glucocorticoids, 20, 272 Gluconeogenesis, 272 Glucose, 14, 93, 252, 255, 264, 272, 273, 275, 279, 280 Glucose Intolerance, 264, 273 Glutamic Acid, 273, 298 Glutamine, 80, 182, 273 Glutathione Peroxidase, 273, 303 Glycine, 117, 186, 273, 304 Glycogen, 272, 273 Glycoprotein, 57, 107, 152, 269, 273, 274, 282, 285, 304, 308, 310 Glycosaminoglycans, 145, 269, 273 Glycosylation, 25, 36, 82, 93, 273 Glycosyltransferases, 25, 273 Goblet Cells, 267, 273 Gonadal, 273, 306 Gonadotropin, 181, 273 Governing Board, 273, 297 Gp120, 273, 293
Graft, 273, 274, 276, 278, 288 Graft Rejection, 274, 278 Grafting, 274, 278 Gram-negative, 56, 187, 253, 267, 274, 291, 299 Gram-positive, 187, 245, 267, 274, 291, 306 Granulocyte Colony-Stimulating Factor, 60, 201, 257, 274 Granulocytes, 102, 257, 274, 283, 304, 312 Granuloma, 98, 274 Granulomatous Disease, Chronic, 274, 302 Growth, 5, 8, 9, 10, 13, 17, 19, 21, 23, 27, 32, 34, 40, 41, 42, 44, 46, 50, 52, 59, 60, 61, 63, 64, 68, 70, 71, 72, 74, 76, 80, 81, 85, 86, 89, 90, 91, 93, 95, 104, 106, 109, 116, 118, 123, 133, 144, 145, 152, 154, 156, 157, 169, 173, 175, 180, 181, 185, 186, 192, 193, 194, 197, 202, 203, 208, 248, 249, 250, 251, 255, 261, 270, 274, 280, 285, 289, 295, 309, 310, 312 Growth Inhibitors, 180, 274 Guanidine, 184, 274 Guanylate Cyclase, 274, 290 Gyrase, 274, 290 H Hair follicles, 274, 312 Half-Life, 254, 274 Haploid, 274, 295, 296 Haptens, 246, 274 Headache, 219, 275 Headache Disorders, 275 Hematologic Diseases, 188, 275 Hematologic malignancies, 69, 185, 275 Heme, 21, 187, 261, 262, 275, 292 Hemocytes, 187, 275 Hemoglobin, 92, 187, 268, 275, 283 Hemolysis, 267, 275 Hemorrhage, 260, 275, 288 Hemostasis, 275, 280 Hepatitis, 45, 275 Hepatobiliary, 45, 275 Hepatocytes, 275 Hereditary, 5, 265, 275 Heredity, 271, 272, 275 Herpes, 15, 28, 45, 216, 275 Herpes Zoster, 275 Heterochromatin, 49, 275 Heterodimers, 276, 280 Heterogeneity, 95, 118, 119, 127, 246, 276 Heterotrophic, 270, 276 Heterozygotes, 265, 276 Hexosyltransferases, 273, 276
Index 321
Histamine, 248, 276 Histidine, 21, 33, 57, 68, 90, 105, 106, 119, 205, 276 Histone Deacetylase, 53, 77, 94, 276 Homeobox, 276 Homeodomain Proteins, 141, 276 Homeostasis, 5, 276 Homologous, 13, 49, 50, 59, 81, 92, 173, 247, 260, 276, 288, 303, 308 Homotypic, 30, 276 Homozygotes, 265, 276 Hormone, 34, 181, 198, 199, 260, 263, 268, 271, 276, 280, 285, 298, 302, 304, 308, 309 Hormone Replacement Therapy, 34, 276 Housekeeping, 26, 276 Humoral, 27, 39, 68, 69, 274, 276 Humour, 276 Hybrid, 13, 23, 34, 40, 41, 51, 57, 173, 257, 276 Hybridization, 22, 36, 85, 88, 133, 184, 204, 210, 211, 276, 287, 290 Hybridomas, 266, 276 Hydration, 172, 173, 277 Hydrogen, 9, 189, 211, 245, 251, 254, 263, 264, 269, 273, 277, 283, 287, 289, 290, 292, 299 Hydrogen Peroxide, 9, 273, 277, 283 Hydrolysis, 250, 252, 273, 277, 281, 284, 295, 296, 299, 310 Hydrophilic, 36, 153, 264, 277 Hydrophobic, 21, 32, 33, 35, 66, 73, 77, 123, 153, 186, 264, 277, 282 Hydroxylysine, 257, 277 Hydroxyproline, 257, 277 Hypersensitivity, 22, 164, 247, 277, 302 Hypertension, 260, 275, 277 Hypoplasia, 265, 277 I Id, 146, 163, 234, 240, 242, 277 Imidazole, 158, 257, 276, 277, 286 Immortal, 56, 277 Immune function, 30, 40, 277, 278 Immune Sera, 277 Immunization, 39, 201, 277, 278 Immunocompromised Host, 44, 54, 178, 191, 197, 278 Immunodeficiency, 37, 60, 62, 64, 65, 70, 71, 72, 74, 78, 81, 83, 86, 87, 89, 94, 95, 101, 112, 120, 126, 131, 134, 139, 179, 213, 219, 245, 278 Immunodeficiency syndrome, 213, 219, 278
Immunodiffusion, 246, 278 Immunoelectrophoresis, 246, 278 Immunofluorescence, 213, 278 Immunogenic, 42, 43, 92, 278, 283 Immunoglobulin, 248, 278, 287 Immunohistochemistry, 20, 27, 278 Immunologic, 32, 256, 277, 278, 300 Immunophilin, 253, 278 Immunosuppressive, 39, 40, 43, 87, 179, 180, 183, 190, 201, 203, 210, 253, 261, 278 Immunosuppressive Agents, 179, 183, 278 Immunosuppressive therapy, 180, 190, 203, 278 Immunotherapy, 30, 278 Implant radiation, 278, 281, 300, 313 Implantation, 8, 259, 278 In situ, 8, 20, 114, 278 In Situ Hybridization, 20, 69, 74, 114, 278 Incision, 279, 281 Incompetence, 271, 279 Incubation, 279, 294 Incubation period, 279, 294 Indicative, 214, 279, 293, 311 Indinavir, 71, 113, 279 Induction, 39, 51, 56, 60, 68, 92, 106, 120, 279 Infarction, 279, 301 Infiltration, 38, 279 Infusion, 279, 286, 288 Initiation, 28, 32, 44, 48, 50, 70, 189, 279, 298, 309 Initiator, 279, 280 Inner ear, 254, 279 Inorganic, 95, 273, 279, 294, 304, 307 Inositol, 119, 279 Inpatients, 125, 279 Insertional, 12, 280 Insight, 15, 27, 43, 51, 121, 280 Insulin, 112, 280 Insulin-dependent diabetes mellitus, 280 Integrins, 30, 178, 280 Intensive Care, 4, 80, 83, 84, 104, 110, 117, 127, 136, 139, 141, 280 Intensive Care Units, 139, 280 Interferon, 63, 79, 280 Interleukin-1, 44, 68, 77, 79, 121, 280 Interleukin-12, 68, 77, 121, 280 Interleukin-2, 84, 280 Interleukins, 278, 280 Intermittent, 281, 284, 294 Internal Medicine, 18, 28, 271, 281 Internal radiation, 281, 300, 313
322
Candida Albicans
Interphase, 275, 281 Interstitial, 123, 253, 269, 281, 282, 313 Intestinal, 45, 92, 153, 181, 247, 260, 267, 281, 292 Intestine, 252, 281, 282, 306 Intracellular, 16, 19, 31, 35, 45, 105, 132, 144, 160, 161, 279, 280, 281, 285, 290, 297, 303, 304 Intracellular Membranes, 281, 285 Intramuscular, 8, 281, 292 Intraocular, 115, 267, 281 Intravascular, 209, 281 Intravenous, 8, 142, 179, 270, 279, 281, 286, 293 Intrinsic, 23, 246, 251, 281 Introns, 272, 281 Invertebrates, 7, 199, 275, 281 Involuntary, 281, 289, 304, 305 Ion Transport, 45, 281 Ions, 151, 207, 251, 253, 264, 266, 274, 277, 281 Irradiation, 179, 281, 313 Ischemia, 30, 282, 288, 301 Isoenzyme, 63, 80, 282 Isoprenoid, 208, 282 Itraconazole, 60, 66, 74, 76, 108, 122, 124, 150, 155, 174, 201, 203, 282 J Joint, 132, 250, 256, 282, 291 K Karyotype, 83, 119, 140, 282 Kb, 186, 228, 282 Keratin, 282 Keratinocytes, 15, 20, 282 Ketoconazole, 124, 156, 216, 282 Ketosteroids, 60, 150, 282 Killer Cells, 282 Kinetic, 21, 35, 282 Kinetochores, 13, 282 L Labile, 258, 282 Laminin, 73, 93, 251, 269, 282 Large Intestine, 264, 281, 282, 301, 305 Laxative, 246, 283 Lectin, 15, 48, 153, 283, 285 Lens, 259, 283, 301 Lesion, 18, 184, 252, 274, 283, 309, 311 Lethal, 17, 30, 39, 68, 111, 160, 178, 183, 189, 197, 250, 261, 283 Leucine, 93, 186, 283 Leucocyte, 247, 283 Leukemia, 80, 92, 188, 275, 283
Leukocytes, 30, 31, 38, 45, 56, 115, 133, 134, 251, 252, 255, 256, 267, 274, 280, 283, 310 Leukoplakia, 216, 219, 283 Library Services, 240, 283 Life cycle, 7, 21, 44, 270, 283 Ligands, 30, 280, 283 Linkage, 41, 125, 283 Lip, 108, 283 Lipid, 43, 78, 130, 142, 266, 280, 283, 292, 310 Lipid A, 43, 283 Lipid Peroxidation, 283, 292 Lipopolysaccharide, 56, 79, 250, 274, 283 Liposomal, 35, 127, 283 Lithium, 194, 283 Liver, 178, 197, 209, 245, 251, 261, 262, 264, 269, 271, 272, 273, 275, 283, 284, 311 Localization, 4, 6, 20, 21, 26, 278, 283 Localized, 28, 38, 54, 61, 195, 245, 263, 264, 266, 279, 282, 283, 291, 295, 311 Locomotion, 284, 295 Long-Term Care, 32, 48, 86, 131, 284 Lovastatin, 150, 284 Low-density lipoprotein, 284 Lower Esophageal Sphincter, 271, 284 Lucida, 282, 284 Luciferase, 94, 284 Lymph, 248, 267, 276, 284, 307 Lymph node, 284 Lymphadenitis, 105, 284 Lymphatic, 131, 267, 279, 284, 286, 305, 306, 309 Lymphatic system, 284, 305, 306, 309 Lymphocyte, 126, 133, 245, 249, 282, 284, 285 Lymphocyte Count, 245, 284 Lymphoid, 15, 248, 260, 283, 284 Lymphoma, 194, 275, 284 Lysine, 81, 84, 277, 284, 310 Lysophospholipase, 161, 284 Lytic, 285, 312 M Macrophage, 35, 44, 56, 57, 60, 63, 69, 81, 116, 118, 257, 280, 285 Macrophage Colony-Stimulating Factor, 60, 81, 118, 257, 285 Malignant, 245, 249, 285, 289, 300, 303, 308 Manic, 283, 285 Manifest, 30, 285 Mannans, 60, 92, 270, 285 Mannosyltransferases, 26, 285
Index 323
Mastitis, 252, 285 Mediate, 22, 25, 30, 91, 95, 100, 282, 285 Mediator, 280, 285 Medicament, 285, 307 MEDLINE, 229, 285 Meiosis, 256, 285, 288, 308 Melanin, 285, 294, 310 Membrane Proteins, 5, 114, 285, 299 Meningeal, 31, 188, 285 Meninges, 188, 254, 255, 260, 265, 285 Meningitis, 31, 40, 59, 75, 140, 164, 188, 270, 282, 285 Meningoencephalitis, 31, 285 Mental Processes, 264, 286, 299 Mentors, 35, 286 Mercury, 95, 208, 269, 286 Mesenchymal, 285, 286 Metabolite, 109, 252, 284, 286, 295 Metaphase, 282, 286 Metastasis, 286 Metastatic, 188, 286 Methionine, 286, 307 Methylene Blue, 183, 184, 286 Methyltransferase, 52, 91, 182, 183, 286 MI, 102, 105, 109, 154, 163, 243, 286 Miconazole, 154, 155, 216, 286 Microbe, 17, 286, 309 Microbiological, 123, 184, 213, 286 Microorganism, 44, 181, 208, 257, 286, 293, 312 Micro-organism, 189, 263, 265, 274, 286, 295 Microscopy, 9, 37, 123, 251, 286 Microspheres, 35, 287 Microtubules, 282, 287 Migration, 30, 173, 287 Mitochondria, 33, 198, 287, 288, 291 Mitochondrial Swelling, 287, 289 Mitosis, 189, 250, 256, 287 Mitotic, 23, 125, 282, 287 Modeling, 9, 17, 20, 43, 265, 287 Modification, 7, 22, 25, 32, 92, 272, 287, 300 Molecular mass, 182, 205, 287 Molecular Probes, 266, 287 Monitor, 35, 202, 287, 290 Monoclonal, 56, 59, 74, 84, 87, 96, 97, 139, 149, 178, 201, 276, 282, 287, 300, 313 Monocyte, 100, 104, 285, 287 Mononuclear, 31, 274, 285, 287, 310 Morphological, 48, 49, 65, 71, 77, 80, 85, 96, 126, 202, 266, 270, 287
Morphology, 10, 19, 39, 49, 50, 52, 61, 132, 163, 169, 185, 198, 287 Motility, 189, 288 Mucins, 263, 267, 273, 288, 303 Mucocutaneous, 106, 174, 209, 288 Mucosa, 11, 15, 27, 38, 42, 44, 175, 177, 267, 288, 306 Multidrug resistance, 7, 23, 83, 89, 156, 288 Multivalent, 207, 288 Muscle Fibers, 288, 289 Mutagenesis, 12, 13, 21, 23, 30, 48, 51, 288 Mutagens, 270, 288 Myasthenia, 274, 288 Mycosis, 179, 203, 204, 288, 291 Mycotic, 6, 8, 50, 61, 288 Myelofibrosis, 98, 150, 288 Myocardial infarction, 260, 286, 288 Myocardial Ischemia, 216, 288 Myocardial Reperfusion, 288, 301 Myocardial Reperfusion Injury, 288, 301 Myocardium, 188, 286, 288, 289 Myosin, 58, 84, 253, 289 N Naive, 39, 289 Natural killer cells, 84, 280, 289 NCI, 1, 29, 227, 256, 289 Necrosis, 18, 109, 249, 267, 279, 286, 288, 289, 301 Need, 3, 16, 45, 54, 180, 191, 192, 213, 215, 223, 235, 246, 273, 289, 309 Neonatal, 4, 31, 83, 84, 110, 117, 289 Neonatologist, 4, 289 Neoplasm, 289, 303, 310 Neoplastic, 276, 284, 289 Nerve, 263, 267, 269, 285, 289, 292, 297, 303, 306, 311 Nervous System, 45, 255, 285, 289, 307, 312 Networks, 5, 7, 289 Neural, 276, 289 Neuromuscular, 245, 289, 296 Neutralization, 34, 289 Neutrons, 247, 281, 289, 300 Neutropenia, 43, 179, 188, 201, 270, 289 Neutrophil, 16, 35, 44, 81, 289, 290 Neutrophil Activation, 44, 290 Nickel, 151, 290 Niflumic Acid, 145, 290 Nitric Oxide, 21, 290 Nitrogen, 35, 69, 186, 205, 261, 269, 273, 287, 290, 310
324
Candida Albicans
Norfloxacin, 137, 290 Nosocomial, 8, 39, 57, 73, 84, 128, 129, 136, 190, 209, 290 Nuclear, 5, 7, 43, 59, 198, 259, 266, 268, 271, 289, 290 Nuclei, 247, 259, 266, 272, 281, 287, 289, 290, 299 Nucleic Acid Hybridization, 276, 290 Nucleic Acid Probes, 69, 74, 114, 185, 290 Nucleus, 249, 251, 256, 261, 262, 264, 267, 268, 271, 285, 287, 289, 290, 298, 299, 306 Nursing Staff, 104, 290 Nystatin, 174, 291 O Odynophagia, 216, 291 Ofloxacin, 137, 166, 291 Ointments, 208, 291, 305 Oncogenic, 280, 291 Onychomycosis, 181, 291 Opacity, 263, 291 Open Reading Frames, 27, 291 Opportunistic Infections, 15, 17, 42, 191, 206, 214, 219, 245, 291 Oral Health, 291 Oral Hygiene, 33, 291 Orderly, 256, 291 Organ Transplantation, 180, 191, 291 Organelles, 262, 291 Ornithine, 182, 291 Osmolarity, 57, 291 Osmoles, 291 Osmosis, 291 Osmotic, 21, 287, 291 Osteoarthritis, 127, 291 Osteomyelitis, 124, 132, 291 Ovum, 283, 292, 298 Oxidants, 35, 292 Oxidation, 35, 116, 245, 249, 252, 261, 264, 265, 273, 282, 283, 292 Oxidation-Reduction, 252, 292 Oxidative Stress, 35, 93, 94, 292 Oxygen Consumption, 292, 302 Oxygenase, 118, 292 Oxygenation, 29, 292 P Pachymeningitis, 285, 292 Palate, 292, 306 Palliative, 292, 308 Palmitic Acid, 182, 292 Pancreas, 245, 264, 271, 280, 292, 310 Pancreatic, 271, 292 Pancreatic Juice, 271, 292
Paneth Cells, 247, 267, 292 Parenteral, 130, 155, 292 Paronychia, 178, 197, 223, 293 Parotid, 33, 141, 293 Paroxysmal, 275, 293, 294, 312, 313 Particle, 208, 293, 309 Patch, 184, 283, 293 Pathologic, 194, 250, 251, 253, 260, 277, 293, 299 Pathologic Processes, 250, 293 Pathologies, 184, 293 Pelvic, 266, 293 Penicillin, 72, 166, 293 Pentosyltransferases, 273, 293 Peptide T, 186, 293 Perception, 216, 259, 293 Perforation, 174, 293 Periodontal disease, 20, 27, 293 Periodontitis, 18, 178, 197, 213, 293 Peripheral blood, 28, 100, 122, 133, 293 Peritoneal, 128, 144, 293 Peritoneal Cavity, 293, 294 Peritoneal Dialysis, 128, 293 Peritoneum, 293, 294 Peritonitis, 5, 76, 128, 294 Pertussis, 206, 294, 312 Petrolatum, 175, 294 Petroleum, 294 Phagocyte, 285, 292, 294 Phagocytosis, 16, 30, 36, 44, 45, 102, 120, 126, 131, 144, 159, 258, 294 Pharmaceutical Preparations, 185, 255, 268, 271, 294 Pharmacodynamics, 79, 122, 294 Pharmacokinetic, 17, 294 Pharmacologic, 274, 294, 309 Pharynx, 271, 294 Phenotype, 26, 72, 79, 85, 95, 186, 271, 294 Phenylalanine, 294, 310 Pheromone, 121, 294 Phosphates, 189, 294 Phospholipases, 295, 304 Phospholipids, 269, 279, 295 Phosphorus, 253, 295 Phosphorylated, 205, 257, 295 Phosphorylation, 57, 62, 110, 145, 151, 155, 200, 205, 261, 295 Photodynamic therapy, 183, 184, 295 Photosensitizing Agents, 184, 295 Physiologic, 17, 87, 123, 251, 274, 295, 301, 304 Physiology, 23, 159, 271, 295
Index 325
Pigments, 295, 302, 311 Plant Growth Regulators, 274, 295 Plant Proteins, 191, 192, 295, 312 Plaque, 9, 27, 41, 213, 256, 295 Plasma, 19, 22, 90, 93, 120, 154, 159, 186, 246, 248, 255, 257, 269, 271, 273, 275, 290, 295, 296 Plasma cells, 248, 295 Plasmid, 13, 27, 186, 194, 295, 311 Plasmin, 100, 295, 296 Plasminogen, 295, 296 Plasminogen Activators, 295, 296 Platelet Activation, 296, 304 Platelet Aggregation, 248, 290, 296 Platelets, 15, 100, 290, 296, 308 Ploidy, 23, 296 Poisoning, 286, 296, 304 Polymerase, 42, 115, 134, 184, 296, 298 Polymerase Chain Reaction, 42, 115, 134, 184, 296 Polymers, 175, 251, 296, 299 Polymorphic, 58, 66, 76, 77, 85, 113, 117, 119, 131, 140, 296 Polymorphism, 24, 82, 89, 135, 296 Polymyxin, 183, 296 Polypeptide, 173, 177, 179, 187, 195, 205, 247, 257, 269, 276, 295, 296, 298, 313 Polyploid, 24, 296 Polyploidy, 23, 297 Polysaccharide, 22, 132, 249, 255, 297, 299 Pons, 251, 297 Posterior, 251, 292, 297, 303, 311 Postoperative, 190, 270, 297 Postsynaptic, 297, 304 Post-translational, 57, 297 Potassium, 81, 124, 297, 305 Potentiate, 16, 297 Potentiating, 16, 297 Potentiation, 297, 304 Practicability, 297, 310 Practice Guidelines, 230, 297 Precipitating Factors, 38, 275, 297 Precursor, 183, 214, 261, 265, 267, 274, 294, 296, 297, 310 Presumptive, 66, 297 Prevalence, 11, 18, 24, 87, 91, 131, 297 Prickle, 282, 298 Probe, 36, 42, 58, 83, 85, 88, 133, 274, 298 Profusion, 182, 298 Progesterone, 298, 306 Progression, 35, 37, 248, 261, 298
Progressive, 194, 255, 262, 265, 274, 289, 291, 296, 298, 310 Projection, 262, 298 Prokaryote, 186, 298 Proline, 182, 257, 277, 298 Promoter, 34, 74, 82, 94, 298 Promotor, 298, 302 Prophase, 288, 298, 308 Prophylaxis, 46, 108, 201, 298, 311 Propolis, 109, 144, 154, 298 Propyl Gallate, 122, 298 Protease, 19, 42, 120, 257, 279, 298 Protease Inhibitors, 120, 298 Protein C, 181, 206, 247, 250, 251, 257, 272, 282, 298, 311 Protein Conformation, 247, 282, 298 Protein Kinases, 22, 91, 298 Protein S, 19, 21, 25, 85, 174, 198, 200, 202, 252, 272, 298, 299, 302, 308 Protein Transport, 19, 299 Proteoglycans, 251, 269, 299 Proteolytic, 69, 247, 258, 269, 296, 299 Proton Pump, 40, 123, 299 Proton Pump Inhibitors, 40, 299 Protons, 247, 277, 299, 300 Protozoa, 259, 286, 299, 306 Proximal, 264, 299 Pruritic, 299, 309 Pseudomonas, 36, 174, 175, 187, 206, 208, 299 Psoriasis, 295, 299 Psychiatry, 299, 312 Psychology, 264, 299 Public Policy, 229, 299 Publishing, 58, 213, 299 Pulmonary, 220, 252, 256, 260, 299, 300, 307, 312 Pulmonary Artery, 252, 300 Pulmonary Edema, 256, 300 Pulse, 287, 300 Purifying, 192, 263, 300 Purines, 300, 304 Purulent, 267, 300, 311 Pyogenic, 291, 300 Q Quality of Life, 7, 33, 300 R Race, 282, 287, 300 Radiation, 49, 196, 204, 206, 216, 245, 268, 270, 271, 278, 281, 295, 300, 313 Radiation therapy, 49, 204, 206, 216, 245, 268, 281, 282, 300, 313
326
Candida Albicans
Radioactive, 274, 277, 278, 281, 282, 287, 290, 291, 300, 313 Radiolabeled, 186, 282, 300, 313 Radiotherapy, 253, 282, 300, 313 Randomized, 33, 47, 266, 300 Randomized clinical trial, 33, 300 Reactivation, 15, 301 Reactive Oxygen Species, 33, 301 Reagent, 256, 261, 265, 284, 301 Receptor, 30, 56, 62, 73, 126, 135, 145, 150, 245, 249, 259, 273, 285, 293, 301, 304 Recombinant, 20, 34, 50, 69, 108, 115, 176, 183, 201, 204, 205, 271, 301, 311 Recombination, 24, 79, 259, 301 Rectum, 249, 252, 264, 271, 282, 301, 307 Recurrence, 33, 46, 301 Red blood cells, 268, 292, 301 Reductase, 63, 84, 142, 284, 301 Refer, 1, 253, 258, 270, 275, 283, 284, 289, 290, 301 Reflux, 216, 271, 301 Refraction, 301, 305 Regimen, 266, 301 Regurgitation, 271, 301 Remission, 301 Reperfusion, 30, 288, 301 Reperfusion Injury, 30, 301 Resolving, 104, 301 Respiration, 33, 63, 254, 287, 301 Respiratory Burst, 30, 102, 302 Respiratory Physiology, 302, 312 Response Elements, 34, 302 Restoration, 30, 260, 288, 301, 302, 313 Retinal, 259, 302 Retrospective, 104, 302 Retrovirus, 45, 302 Reversion, 302, 310 Rheumatoid, 290, 292, 302 Rheumatoid arthritis, 290, 302 Ribonuclease, 20, 302 Ribonucleic acid, 211, 302 Ribosome, 302, 310 Rigidity, 295, 302 Risk factor, 43, 129, 179, 302 Risk patient, 134, 302 Rod, 245, 250, 251, 299, 303 S Saccharomycetales, 303 Saliva, 9, 12, 34, 41, 42, 50, 88, 106, 141, 175, 303
Salivary, 33, 41, 49, 50, 63, 77, 81, 103, 112, 116, 121, 124, 133, 262, 263, 264, 269, 303, 307 Salivary glands, 262, 263, 264, 269, 303 Salivary Proteins, 33, 303 Saponin, 160, 303 Sarcoma, 214, 219, 303 Saturated fat, 292, 303 Sclera, 303 Sclerotic, 58, 303 Sebaceous, 303, 312 Secretion, 19, 20, 44, 72, 162, 272, 276, 280, 288, 303 Secretory, 19, 22, 70, 71, 78, 83, 112, 116, 247, 303 Secretory Vesicles, 19, 303 Segregation, 256, 271, 301, 303 Selenium, 144, 303 Sensor, 57, 205, 303 Sepsis, 124, 194, 270, 303 Septicemia, 209, 304 Sequence Analysis, 95, 111, 138, 304 Sequence Homology, 293, 304 Sequencing, 6, 18, 22, 49, 65, 91, 296, 304 Serine, 67, 93, 117, 118, 144, 145, 200, 258, 267, 304, 310 Serum, 9, 27, 48, 62, 79, 88, 91, 122, 127, 152, 162, 248, 258, 273, 277, 284, 294, 304, 310 Shivering, 203, 304 Shock, 36, 121, 156, 304, 310 Sialyltransferases, 273, 304 Side effect, 183, 185, 203, 206, 246, 261, 304, 309 Signal Transduction, 14, 28, 40, 119, 205, 253, 279, 304 Silver Compounds, 207, 304 Skeleton, 172, 245, 282, 304 Skull, 260, 304, 308 Small intestine, 276, 281, 305, 310 Smear Layer, 97, 305 Sneezing, 294, 305 Soaps, 223, 305, 310 Social Environment, 300, 305 Sodium, 79, 110, 129, 144, 189, 305 Soft tissue, 252, 304, 305 Solid tumor, 179, 305 Solvent, 7, 21, 268, 291, 305 Somatic, 264, 276, 285, 287, 305, 308 Somatic cells, 264, 285, 287, 305 Spasmodic, 294, 305 Specialist, 235, 305
Index 327
Specificity, 42, 48, 57, 77, 210, 211, 246, 267, 305 Spectrum, 20, 22, 29, 30, 54, 177, 187, 194, 195, 199, 257, 282, 290, 305 Sperm, 180, 256, 305 Spermatozoa, 306 Spermicide, 180, 306 Spinal cord, 255, 256, 265, 267, 285, 289, 292, 306 Spinous, 268, 282, 306 Spleen, 178, 197, 262, 284, 306 Spores, 198, 306 Stabilization, 25, 306 Staphylococcus, 15, 126, 139, 183, 187, 198, 207, 306 Stem Cells, 247, 306 Sterility, 261, 306 Sterilization, 183, 184, 306 Steroid, 40, 156, 181, 282, 306 Stimulus, 205, 265, 268, 306 Stomach, 245, 264, 268, 271, 276, 284, 293, 294, 299, 301, 305, 306 Stomatitis, 9, 11, 29, 108, 134, 175, 306 Strand, 296, 306 Streptococci, 153, 215, 306 Streptococcus, 41, 125, 133, 153, 176, 184, 186, 187, 208, 267, 306 Stress, 13, 21, 27, 40, 57, 58, 62, 92, 112, 254, 292, 302, 307 Stromal, 266, 307 Structure-Activity Relationship, 16, 18, 307 Subacute, 279, 307 Subarachnoid, 275, 307 Subclinical, 279, 307 Subcutaneous, 184, 292, 307 Submandibular, 33, 307 Subspecies, 305, 307 Substance P, 286, 303, 307 Substrate, 8, 51, 111, 119, 186, 189, 200, 254, 307 Substrate Specificity, 51, 119, 307 Sulfates, 176, 307 Sulfur, 189, 269, 286, 307 Sulfur Compounds, 189, 307 Sulfuric acid, 307 Superoxide, 302, 307 Supplementation, 153, 155, 307 Suppositories, 188, 271, 307 Suppression, 136, 272, 307 Surfactant, 180, 189, 255, 307 Symptomatic, 18, 308
Synaptic, 304, 308 Synergistic, 40, 191, 192, 221, 308 Systemic disease, 40, 54, 194, 304, 308 T Tachycardia, 250, 308 Tachypnea, 250, 308 Tea Tree Oil, 145, 157, 308 Telomerase, 138, 193, 308 Telomere, 193, 308 Temporal, 37, 92, 123, 275, 308 Terminator, 257, 308 Testosterone, 301, 308 Tetracycline, 72, 157, 167, 308 Therapeutics, 54, 308 Thermal, 103, 184, 264, 289, 296, 308 Threonine, 67, 117, 144, 182, 200, 293, 304, 308 Thrombin, 269, 296, 298, 308 Thrombocytes, 296, 308 Thrombomodulin, 298, 308 Thrombophlebitis, 194, 210, 308 Thrombosis, 140, 280, 299, 308 Thrombus, 100, 260, 279, 288, 296, 308 Thymus, 30, 167, 277, 284, 309 Thyroid, 309, 310 Tinea Pedis, 181, 309 Tissue, 7, 34, 37, 50, 57, 69, 137, 184, 194, 210, 216, 222, 245, 246, 249, 251, 252, 254, 256, 257, 259, 265, 266, 267, 269, 271, 272, 273, 274, 277, 279, 281, 283, 284, 285, 286, 288, 289, 290, 291, 293, 295, 296, 301, 302, 304, 305, 307, 309, 310, 311, 313 Tolerance, 23, 93, 245, 273, 309 Tooth Preparation, 245, 309 Toxicity, 16, 17, 22, 35, 41, 46, 54, 90, 180, 191, 265, 286, 309 Toxicology, 17, 19, 230, 309 Toxins, 35, 70, 189, 249, 266, 279, 286, 304, 309 Toxoplasmosis, 220, 309 Trace element, 144, 290, 309 Transcriptase, 193, 302, 308, 309 Transcription Factors, 22, 194, 302, 309 Transduction, 28, 91, 205, 304, 309 Transfection, 28, 252, 266, 309 Transfer Factor, 277, 309 Transferases, 273, 309 Translation, 52, 310 Translational, 46, 272, 310 Translocation, 5, 153, 186, 299, 310 Transplantation, 40, 41, 183, 277, 310
328
Candida Albicans
Trauma, 208, 223, 268, 289, 310, 313 Treatment Failure, 9, 16, 54, 310 Treatment Outcome, 18, 310 Trees, 295, 310 Triclosan, 3, 310 Trimethoprim-sulfamethoxazole, 72, 310 Trivalent, 207, 310 Trypsin, 258, 310, 313 Tryptophan, 257, 310 Tuberculosis, 51, 217, 220, 310 Tumor Necrosis Factor, 100, 310 Tumour, 131, 310 Typhimurium, 186, 310 Tyrosine, 62, 110, 145, 151, 155, 200, 310 U Ubiquinone, 144, 310 Ulcer, 311 Ulceration, 178, 197, 311 Unconscious, 262, 277, 311 Unguis, 184, 185, 311 Uracil, 211, 311 Urea, 291, 311 Ureters, 311 Urethra, 311 Urinary, 114, 180, 208, 254, 256, 272, 290, 311 Urinary tract, 114, 180, 254, 311 Urinary tract infection, 114, 180, 311 Urine, 252, 257, 264, 274, 290, 311 Urogenital, 272, 311 Urokinase, 198, 311 Uterus, 266, 267, 298, 311 Uvea, 267, 311 V Vaccination, 39, 209, 311 Vaccine, 27, 32, 39, 43, 79, 201, 209, 246, 311 Vagina, 38, 115, 181, 189, 253, 263, 311 Vaginal, 34, 38, 42, 54, 57, 107, 113, 118, 124, 132, 139, 181, 188, 189, 195, 208, 234, 311 Vaginal Smears, 132, 311 Vaginitis, 38, 75, 92, 113, 164, 178, 181, 189, 197, 253, 311 Variegation, 24, 311 Vascular, 16, 110, 145, 155, 267, 275, 279, 290, 296, 309, 311 Vasculitis, 248, 311 Vasodilators, 290, 311 Vector, 13, 53, 204, 280, 309, 311 Vegetable Proteins, 295, 312
Vegetative, 21, 296, 312 Vein, 281, 290, 293, 308, 312 Venous, 100, 179, 299, 312 Ventilation, 172, 312 Venules, 252, 254, 312 Vertebral, 251, 312 Vesicular, 275, 299, 312 Veterinary Medicine, 229, 312 Viral, 44, 52, 189, 214, 266, 291, 302, 309, 312 Virulence, 11, 12, 18, 19, 22, 24, 27, 28, 31, 34, 35, 37, 39, 40, 41, 48, 49, 55, 57, 58, 59, 60, 61, 62, 63, 64, 65, 67, 68, 69, 70, 72, 73, 74, 75, 76, 78, 82, 86, 88, 89, 90, 91, 94, 95, 96, 99, 103, 104, 105, 106, 111, 112, 120, 125, 126, 134, 137, 140, 186, 195, 202, 203, 204, 205, 206, 209, 222, 250, 309, 312 Virulent, 15, 18, 31, 57, 161, 192, 196, 204, 312 Vitamin A, 279, 312 Vitro, 3, 4, 5, 6, 7, 8, 10, 12, 15, 19, 22, 27, 31, 37, 38, 40, 42, 44, 46, 50, 55, 57, 61, 66, 67, 68, 71, 77, 78, 87, 100, 101, 102, 103, 106, 107, 109, 112, 113, 120, 122, 131, 134, 137, 138, 144, 145, 152, 153, 154, 155, 157, 161, 162, 179, 181, 192, 202, 209, 279, 296, 312 Vivo, 4, 5, 7, 8, 10, 12, 17, 22, 26, 27, 31, 34, 40, 42, 50, 54, 56, 57, 66, 73, 79, 87, 93, 105, 107, 155, 161, 179, 192, 279, 292, 312 Voriconazole, 59, 60, 312 Vulgaris, 167, 312 W White blood cell, 248, 283, 284, 285, 287, 289, 295, 312 Whooping Cough, 294, 312 Wound Healing, 280, 313 Wound Infection, 184, 313 X Xenograft, 248, 313 X-ray, 7, 21, 43, 51, 142, 270, 271, 281, 290, 300, 313 X-ray therapy, 282, 313 Z Zymogen, 298, 313
