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

PSEUDOMONAS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Pseudomonas: 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: 0-597-84565-4 1. Pseudomonas-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on pseudomonas. 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 PSEUDOMONAS ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Pseudomonas................................................................................. 6 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 97 CHAPTER 2. NUTRITION AND PSEUDOMONAS ............................................................................. 147 Overview.................................................................................................................................... 147 Finding Nutrition Studies on Pseudomonas ............................................................................. 147 Federal Resources on Nutrition ................................................................................................. 152 Additional Web Resources ......................................................................................................... 153 CHAPTER 3. DISSERTATIONS ON PSEUDOMONAS ......................................................................... 155 Overview.................................................................................................................................... 155 Dissertations on Pseudomonas .................................................................................................. 155 Keeping Current ........................................................................................................................ 161 CHAPTER 4. CLINICAL TRIALS AND PSEUDOMONAS ................................................................... 163 Overview.................................................................................................................................... 163 Recent Trials on Pseudomonas .................................................................................................. 163 Keeping Current on Clinical Trials ........................................................................................... 165 CHAPTER 5. PATENTS ON PSEUDOMONAS ................................................................................... 167 Overview.................................................................................................................................... 167 Patents on Pseudomonas............................................................................................................ 167 Patent Applications on Pseudomonas........................................................................................ 199 Keeping Current ........................................................................................................................ 233 CHAPTER 6. BOOKS ON PSEUDOMONAS ....................................................................................... 235 Overview.................................................................................................................................... 235 Book Summaries: Online Booksellers......................................................................................... 235 Chapters on Pseudomonas ......................................................................................................... 236 CHAPTER 7. PERIODICALS AND NEWS ON PSEUDOMONAS ......................................................... 239 Overview.................................................................................................................................... 239 News Services and Press Releases.............................................................................................. 239 Newsletter Articles .................................................................................................................... 241 Academic Periodicals covering Pseudomonas............................................................................ 242 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 243 Overview.................................................................................................................................... 243 U.S. Pharmacopeia..................................................................................................................... 243 Commercial Databases ............................................................................................................... 244 Researching Orphan Drugs ....................................................................................................... 244 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 249 Overview.................................................................................................................................... 249 NIH Guidelines.......................................................................................................................... 249 NIH Databases........................................................................................................................... 251 Other Commercial Databases..................................................................................................... 253 APPENDIX B. PATIENT RESOURCES ............................................................................................... 255 Overview.................................................................................................................................... 255 Patient Guideline Sources.......................................................................................................... 255 Finding Associations.................................................................................................................. 258 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 261 Overview.................................................................................................................................... 261 Preparation................................................................................................................................. 261

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Finding a Local Medical Library................................................................................................ 261 Medical Libraries in the U.S. and Canada ................................................................................. 261 ONLINE GLOSSARIES................................................................................................................ 267 Online Dictionary Directories ................................................................................................... 267 PSEUDOMONAS DICTIONARY .............................................................................................. 269 INDEX .............................................................................................................................................. 351

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with pseudomonas 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 pseudomonas, 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 pseudomonas, 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 pseudomonas. 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 pseudomonas, 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 pseudomonas. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON PSEUDOMONAS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on pseudomonas.

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

Norfloxacin Prophylaxis for Acute Recurrent Uncomplicated Urinary Tract Infection in Women Source: International Urogynecology Journal. 3(2): 150-154. June 1992. Summary: Long-term, low dose antimicrobial prophylaxis is effective for the prevention of recurrent uncomplicated urinary infections in women. This review article discusses norfloxacin prophylaxis for these infections. In two of the three studies reported, norfloxacin was effective for prophylaxis compared to placebo. In the third study, it was as effective as nitrofurantoin macrocrystals. Infections that occurred during prophylaxis were with organisms resistant to norfloxacin, particularly Enterococcus faecalis and Pseudomonas aeruginosa. The author concludes that further studies comparing norfloxacin to standard regimens are required to identify its specific niche in the management of this common problem. 1 table. 25 references. (AA-M).

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Surgical Emphysema and Pneumomediastinum Complicating Dental Extraction Source: British Dental Journal. 188(11): 589-590. June 10, 2000. Contact: Available from Stockton Press. Houndmills, Basingstoke, Hampshire, RG21 6XS, United Kingdom. E-mail: [email protected]. Summary: Subcutaneous and mediastinal emphysema is a rare complication of dental extraction and the use of air turbines has often been implicated. In this article, the authors describe a case which highlights a serious complication of the use of an air rotor for the removal of a right second mandibular molar. During this procedure, potential microbial contaminants such as pseudomonas and legionella in dental compressed air lines may be passed into tissue spaces. The authors conclude by recommending that the use of an air rotor during dental surgery be abandoned. 2 figures. 1 references.

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Chronic Health Effects of Microbial Foodborne Disease Source: World Health Statistics Quarterly. 50(1-2): 51-56. 1997. Contact: Available from World Health Organization. 1211 Geneva 27, Switzerland. Phone (41 22) 791 24 76. Fax (41 22) 791 48 57. Summary: This article discusses the chronic health effects of microbial foodborne disease. The authors note that as the incidence of foodborne microbial disease increases, chronic disease sequelae may also be expected to rise. The authors explore how foodborne pathogens may act as 'triggers' in chronic disease pathology, within the context of mechanistic theories. Topics include rheumatoid disease, inflammatory bowel disease (IBD), superantigens and autoimmunity. The authors review clinical research studies in each area. Although the etiology of IBD and the mechanism(s) for spontaneous exacerbations and remissions are unknown, much research has focused on transmissible agents, including foodborne pathogens. The authors briefly discuss the implications of a variety of agents in the etiology of IBD, including Pseudomonas, Mycobacterium paratuberculosis, Streptococcus fecalis, Listeria, and E. coli. 45 references. (AA-M).

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Complicated UTI: Targeting the Pathogens Source: Patient Care. 31(7): 212-216, 221-223. April 15, 1997. Summary: This article guides physicians through the diagnosis and treatment of complicated urinary tract infections (UTIs). Complicated UTI is defined as a symptomatic UTI in a setting that increases the risk of persistence, recurrence, or treatment failure. Such infections usually result from an anatomic abnormality, underlying disease, the presence of an indwelling bladder catheter, or older age. Complicating factors may not be obvious at first, and the clinical spectrum ranges from mild cystitis to life threatening urosepsis. The author notes that complicated UTIs are more likely than uncomplicated infections to involve multiple or unusual organisms, many of which may be resistant to first-line antimicrobials such as ampicillin or trimethoprim-sulfamethoxazole. Pathogens frequently seen include Proteus mirabilis (particularly common in patients with kidney stones), Staphylococcus epidermidis, Klebsiella species, and Enterococcus faecalis. Patients with diabetes are at greater risk for infection with Pseudomonas aeruginosa; this group and patients on dialysis are at increased risk for staphylococcal infections. Other topics include the use and abuse of quinolones, the bioavailability of IV versus oral drugs, and followup care for patients with complicated UTIs. Low-dose antibiotics are sometimes prescribed for several months in patients at risk for recurrence of UTI, but this suppressive therapy is usually

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reserved for children, symptomatic patients, and those at high risk for progressive renal damage. The author cautions, however, that chronic suppressive therapy is not without risks. 3 tables. 14 references. (AA-M). •

Relationships Between Activity of Daily Living, and Oral Cavity Care and the Number of Oral Cavity Microorganisms in Patients with Cerebrovascular Diseases Source: Journal of Medical Investigation. 46(1-2): 79-85. February 1999. Contact: Available from University of Tokushima School of Medicine. 3 Kuramoto-cho, Tokushima, 770-8503, Japan. +81-88-633-7104. Fax +81-88-633-7115. E-mail: [email protected]. Summary: This article reports on a study that examined the relationships among the activity of daily living (ADL), oral cavity care, and the number of oral cavity microorganisms in 40 patients with cerebrovascular diseases (CVD). The CVD patients were classified into four groups: I, II, III, and IV based on their ADL and the method used for oral cavity care. The ADL was highest in group I and lowest in group III. Only the patients of group III could not eat by themselves and were receiving naso esophageal feeding. Oral cavity care was performed by the patients themselves in groups I and IV, but was performed by caregivers in groups II and III. Group I patients could brush their teeth and eat by themselves; Group II patients could eat by themselves, but were receiving oral cavity care from caregivers. The group IV patients had no teeth, but could eat by themselves using full dentures. The numbers of microorganisms in the pharyngeal swabs from the 4 groups were measured and expressed as colony forming units (cfu). The numbers of both Staphylococci spp. and Candida spp. were significantly higher in group III than in the other groups. Moreover, Pseudomonas aeruginosa was isolated only from patients of group III (in about 66 percent). The oral cavity care by caregivers was almost the same in groups II and III, but the numbers of oral cavity microorganisms were significantly higher in group III than in group II. These results indicated that microorganisms grow more easily in the oral cavities of CVD patients with low ADL compared with CVD patients with higher ADL, and that eating is thought to be important for the prevention of an increase of microorganisms in the oral cavity. 3 figures. 2 tables. 17 references.

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Necrotizing External Otitis Source: Journal of Louisiana State Medical Society. 145(2): 43-45. 1993. Summary: This article, addressing health professionals, discusses necrotizing external otitis, a severe osteomyelitis of the temporal bone principally affecting elderly diabetics. It is caused by the gram negative bacillus, Pseudomonas aeruginosa. Clinical findings and diagnosis are reviewed. Long-term therapy with intravenous antibiotics is recommended for cure, although newer antimicrobial agents give promise of being successful when administered orally (AA-M).

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Malignant Otitis Externa: The Therapeutic Evolution of a Lethal Infection Source: Journal of Antimicrobial Chemotherapy. 30(6): 745-751. 1992. Summary: This article, directed toward health professionals, discusses malignant otitis externa (MOE), a potentially fatal infection of the external auditory canal usually caused by Pseudomonas aeruginosa. Treatment of MOE has changed over the years. Surgical debridement of all infected tissue is no longer considered the treatment of choice and has been replaced by localized surgical debridement supplemented with long-term

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antimicrobial chemotherapy. The recent availability of the fluroquinolones and, in particular, ciprofloxacin has opened up new therapeutic opportunities (AA-M). •

Diagnosis and Management of Osteomyelitis Source: American Family Physician. 63(12): 2413-2420. June 15, 2001. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the etiology, diagnosis, and management of osteomyelitis. Acute osteomyelitis is the clinical term for a new infection in bone. This infection occurs predominantly in children and is often seeded hematogenously. In adults, osteomyelitis is usually a subacute or chronic infection that develops secondary to an open injury to bone and surrounding soft tissue. The diagnosis of osteomyelitis is based mainly on the clinical findings, with data from the initial history, physical examination, and laboratory tests serving primarily as benchmarks against which treatment response is measured. In osteomyelitis of the extremities, plain film radiography and bone scintigraphy are the primary investigative tools. For nuclear imaging, technetium Tc-99m methylene diphosphonate is the radiopharmaceutical agent of choice. Magnetic resonance imaging can be helpful in unclear situations. Ultrasonography and computer tomographic scanning may be helpful in the evaluation of suspected osteomyelitis. Histopathologic and microbiologic examination of bone is the gold standard for diagnosing osteomyelitis. The specific organism isolated in bacterial osteomyelitis is often associated with the age of the patient or with trauma or recent surgery. Staphylococcus aureus is implicated in most patients with acute hematogenous osteomyelitis. Staphylococcus epidermidis, S. aureus, Pseudomonas aeruginosa, Serratia marcescens, and Escherichia coli are commonly isolated in patients with chronic osteomyelitis. For optimal results, antibiotic therapy must be started early, with antimicrobial agents administered parenterally for at least 4 to 6 weeks. Treatment generally involves evaluation, staging, determination of microbial etiology and susceptibilities, antimicrobial therapy, and, if necessary, debridement, dead space management, and stabilization of bone. 3 figures, 7 tables, and 34 references. (AAM).

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

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

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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 pseudomonas. The following is typical of the type of information found when searching the CRISP database for pseudomonas: •

Project Title: ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE Principal Investigator & Institution: Schuchman, Edward H.; Professor &Vice Chairman for Research; Human Genetics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JAN-2007 Summary: (provided by applicant): Types A & B Niemann-Pick Disease (NPD) are lipid storage disorders resulting from the deficient activity of the lysosomal hydrolase, acid sphingomyelinase (ASM). Type A NPD is a severe neuro-degenerative disorder, which leads to death in early childhood, while patients with Type B NPD have little or no neurological abnormalities and often survive into adulthood. The overall goals of this research are to investigate the underlying causes of the distinct neurological & nonneurological forms of NPD, including the role of ASM in ceramide-mediated cell signaling & disease pathogenesis, and to develop effective treatments for these disorders. Previously, our laboratory: 1) Isolated the full-length cDNAs & genes encoding human & murine ASM, 2) Identified the first ASM mutations causing NPD & developed the first NPD molecular diagnostic program, 3) Constructed a knock-out mouse model for this disorder, 4) Stably over-expressed, purified & characterized recombinant human ASM from CHO cells, 5) Evaluated enzyme replacement, bone marrow transplantation & hematopoietic stem cell gene therapy in the NPD mouse model, and 6) Characterized ceramide-mediated signal transduction in the NPD mouse. In the upcoming funding period we are proposing four specific aims: 1) Investigate the pulmonary disease in NPD mice & develop lung-specific therapies for Type B NPD, 2) Investigate the neurological disease in NPD mice & develop CNS-specific therapies for Type A NPD, 3) Investigate the reproductive biology of NPD mice, including the development of approaches for the selection of normal vs. NPD gametes and preimplantation embryos, and 4) Continue to conduct world-wide ASM mutation analysis & structure/function studies. We believe that this research will provide fundamental insights into the underlying biology of NPD & ASM, and lead to the development of effective treatments for these disorders and/or methods to prevent or minimize NPD births. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AEROSOL INFECTION MOUSE MODEL FOR CYSTIC FIBROSIS Principal Investigator & Institution: Yu, Hongwei; Micro/Immunol/Molec Genetics; Marshall University Huntington, Wv 25701 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Chronic respiratory infections with Pseudomonas aeruginosa are the primary causes of high morbidity and mortality in cystic fibrosis (CF). We have recently developed a unique pulmonary infection mouse model that depends on the artificially generated P. aeruginosa aerosol to cause a uniform whole-lung infection in mice. The focus of this revised proposal is to test a group of 90 clinical CF isolates of P. aeruginosa for innate lung clearance, cytokine profiles and histopathology in this aerosol infection model. The hypothesis to be tested here is that the hypervariable chromosomal restriction fragment length polymorphisms (RFLPs) of the clinical CF sputum isolates

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may contribute to i) variations in bacterial respiratory colonization capacity, ii) altered levels of cytokine production by the host, and iii) the different outcomes of lung pathology. This is based on our following recent observations. First, we have applied the technique of pulsed field gel electrophoresis (PFGE) to analyze a collection of 90 clinical CF isolates for their genomic profiles. We have established a database composed of 75 unique Spe-I restriction digest PFGE profiles. Out of 90 strains tested, we identified one isolate CF32 that had identical Spe-I, Xba-I and Dpn-I digest PFGE patterns as P. Aeruginosa PAO1, a standard reference strain of a wound origin. Secondly, we passed PAO1 and 3 other CF isolates including the PAO-1 like CF isolate through the aerosol infection system to test for the pulmonary clearance and production of tumor necrosis factor (TNF)-a. PA01 and CF32 showed a similar pattern of lung clearance and TNF-a induction in the C57BL/6J and BALB/cJ mice. However, the other 2 CF isolates were more resistant to the clearance by the BALB/cJ mice. One isolate (CF45) caused a significant induction of TNF-a by the murine lungs. These results indicate that the genomes of the CF isolates are highly diversified, and the genomic diversity may affect their intrinsic biological properties. More importantly, it's feasible to use the aerosol apparatus to assess the remaining CF isolates for their virulence properties. The future directions that this project may lead to include i) investigations of the novel Pseudomonas genes induced due to lung colonizations; ii) exploration of the novel DNA fragments missing in the PAO1 genome but present in a subset of the CF isolates; iii) DNA immunization and testing for protection, and iv) evaluation of some selected CF isolates in the aerosol mouse model. By achieving the research objective of this Academic Research Enhancement Award (AREA) that is to establish and infection database for the CF isolates in the aerosol model, we will have an essential base of knowledge from which to prepare a future R01 application to investigate the novel virulence mechanisms associated with the clinical CF isolates of P. aeruginosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERATION WITH AGE OF RESISTANCE TO EYE INFECTIONS Principal Investigator & Institution: Hazlett, Linda D.; Professor and Chair; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-1979; Project End 31-MAR-2004 Summary: The long term objectives of the proposed studies are to precisely define specific interactions between host cells and their secreted factors with the opportunistic bacterial pathogen, Pseudomonas aeruginosa (PA). Knowledge of these interactions and their sequelae will provide information critical to rational development of therapies to lessen or prevent the consequences of corneal inflammation which often lead to visual impairment. A single hypothesis will be tested: That appropriate regulation of immune cells, chemokines, and cytokines and an effective, controlled early host inflammatory (e.g., PMN) response determines whether or not PA keratitis is resolved and whether vision is restored or lost. Specific aims to test the above hypothesis are: Aim 1. To characterize the role of specific CXC and CC chemokines in the inflammatory response to PA ocular infection in genetically and aged susceptible vs. resistant inbred mice. Aim 2. To characterize the role of specific cytokines in the inflammatory response to PA ocular; infection in susceptible and resistant mouse models. Aim 3. To determine the role of specific cells [macrophages, PMNs, T cells, and Langerhans cells (LC)] in PA ocular infection in susceptible and resistant mouse models. To achieve these aims, molecular microbiological, immunological and biochemical methods will be used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIBIOTIC SUSCEPTIBILITY OF BACTERIA IN BIOFILMS Principal Investigator & Institution: Stewart, Philip S.; Deputy Director & Research Coordinator; Chemical Engineering; Montana State University (Bozeman) Bozeman, Mt 59717 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): When bacteria attach to a surface and grow as a biofilm they are protected from killing by antibiotics. Biofilm formation is increasingly recognized as a factor in the persistence of varied infections. The goal of this project is to complement ongoing experimental investigations of antibiotic resistance in biofilms by developing the first comprehensive, phenomenological model of biofilm reduced susceptibility to killing by antibiotics. An existing mathematical model of biofilm development will be expanded to include four hypothesized protective mechanisms. These mechanisms address retarded antibiotic penetration, reduced metabolic activity or growth in parts of the biofilm due to local nutrient depletion, stress response activation by some biofilm bacteria, and differentiation of some biofilm cells into a dormant persister state analogous to spore formation. The model will be improved by developing mathematical expressions for the release of cells from the biofilm based on a mechanical analysis of the biofilm as a viscoelastic fluid. Finally, model results will be compared to experimental data. Experiments will be performed to measure spatiotemporal responses, including both killing and detachment, to antibiotic treatment in a P. aeruginosa experimental system, and these results will be compared with output of the mathematical model. Progress in understanding the stubborn persistence of biofilm infections in the face of antibiotic chemotherapy has been surprisingly slow. This modeling effort will accelerate this effort by integrating the many constituent phenomena that must be considered and serving as a vehicle for dialogue between the diverse disciplines that must communicate to solve this problem. The model will ultimately be a tool for investigating the consequences of hypothesized resistance mechanisms, designing experiments to test these mechanisms, identifying novel treatment strategies, and determining optimal antibiotic dosing protocols. This project will afford a rich interdisciplinary training experience for the three participating graduate students. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ASSEMBLY AND STRUCTURE OF TYPE IV PILI Principal Investigator & Institution: Tainer, John A.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 31-JAN-2005 Summary: This renewal aims to characterize structure-function relationships for type IV pili fibers, which key virulence factors for pathogenic Gram-negative bacteria. Structural analyses for type IV pilin subunits will be integrated with electron microscopy (EM), fiber diffraction, and small angle x-ray scattering (SAXS) structures of native fibers via objective Fourier correlation methods. These proposed studies, which span atomic to subcellular resolutions, will focus upon type IV pili from Neisseria gonorrhoeae, the causative agent of gonorrhea. Successful methods and results on gonococcal pili will allow complementary structural and mutational studies on pili from Pseudomonas aeruginosa, the causative agent on deadly opportunistic nosocomial infections, and Vibrio cholerae, the causative agent of cholera, to define conserved and variable aspects of type IV pili. Key questions concerning pilus structure-function relationships will be addressed including whether the N. gonorrhoeae pilin fold is representative of all type

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IV pilins, how extreme antigenic variation avoids disrupting the pilin fold and fiber assembly, the nature and significance of post-translational modifications, structural changes associated with fiber formation, species-specific conservation of surface regions acting in target cell recognition and accessory protein binding, the structural chemistry controlling bundling, structural characteristics of immunodominant regions, and optimal approaches to the design of cross- species vaccines. Structural results and hypotheses will be experimentally tested by quantitative correlations among diffraction and electron microscopy results and by mutational analyses. The proposed integrated multi-disciplinary studies provide innovation in determining challenging fiber-forming protein structures and in bridging the huge resolution gap between protein crystal structures and EM image reconstructions of subcellular organelles. Overall, these structural and mutational results will promote integration of ongoing biochemical, immunobiological, genetic, and functional studies to decipher the structural chemistry governing pilus actions in pathogenicity: host cell surface attachment, twitching motility, bacteriophage absorption, modulation of transformation efficiency and toleration of extreme sequence variability while retaining structural integrity and flexibility. This understanding of pilus structure-function relationships has long-term potential applications for drug and vaccine design against major bacterial diseases now showing increasing antibiotic resistance and threats to public health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PNEUMONIA

BACTERIAL

PREDICTORS

OF

SEVERE

NOSOCOMIAL

Principal Investigator & Institution: Hauser, Alan R.; Microbiology and Immunology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The long-term objective of the proposed study is to better understand the pathogenesis of hospital-acquired pneumonia caused by Pseudomonas aeruginosa. The general strategy is to characterize the role of the P. aeruginosa type III secretion system in hospital-acquired pneumonia. This complex secretion pathway transports and injects four known effector proteins into host cells: ExoS, ExoT, ExoU (also known as PepA), and ExoY. Interestingly, clinical isolates differ in the combination of effector proteins they secrete. Recent studies are beginning to define the role of individual effector proteins in pathogenesis. Preliminary studies using bacterial mutants indicate that ExoS, ExoT, ExoU, and ExoY all have cytotoxic effects on mammalian cells in cell culture systems. ExoT, ExoU, and possibly ExoS contribute to virulence in animal models of pneumonia. In addition, ExoU secretion is associated with worse clinical outcomes in humans with hospital-acquired pneumonia. Together, these findings support an important role for type III effector proteins in the acute pneumonia, although the exact role of each effector protein and the mechanisms by which these proteins lead to the pathophysiological consequences of pneumonia remain to be defined and are the subject of this proposal. Our preliminary data suggest that type III secretion contributes to bacterial persistence, dissemination, and mortality as well as neutrophil killing and suppression of proinflammatory cytokine release in a mouse model of pneumonia. Further defining the role of individual effector proteins in these processes is crucial to our understanding of the pathogenesis of hospital-acquired pneumonia caused by P. aeruginosa. It is hypothesized that specific effector proteins play an important role in the pathogenesis of hospital-acquired pneumonia, including the prevention of bacterial clearance by neutrophils. Furthermore, it is hypothesized that because of these effects secretion of specific effector proteins can be used as markers for

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strains associated with especially severe hospital-acquired pneumonia in human patients. Studies using both mice and humans will be performed to define the roles of these effector proteins in the pathogenesis of acute pneumonia, including modulation of the inflammatory response and resistance to neutrophil-mediated clearance, and to determine whether secretion of particular effector proteins serves as a marker for strains capable of causing especially severe disease in human patients with hospital-acquired pneumonia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOCHEMICAL ROLE OF AIRWAY MUCINS IN CYSTIC FIBROSIS Principal Investigator & Institution: Sachdev, Goverdhan P.; Pharmaceutical Sciences; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Cystic Fibrosis (CF) is the most lethal genetic disease in Caucasians and is characterized by production of excessive amounts of viscous mucus secretions in the airways of the patient. This causes airway obstruction as well as chronic bacterial infections which eventually lead to respiratory failure. Mucins provide protection to epithelia through interaction of their saccharides with bacterial adhesins. Chronic colonization with Pseudomonas aeruginosa, is considered the principal cause of death in CF patients. Our laboratory and others have shown that P. aeruginosa had considerably stronger binding affinity for CF airway mucin than normal airway mucin. These observations implicate altered glycosylation of CF mucins. Indeed, aberrant glycosylation has been reported for CF mucin. However, to date, the molecular basis of increased interaction between P. aeruginosa and CF airway mucin has not been established. We hypothesize that altered glycosylation of CF mucin is responsible for its stronger binding with P. aeruginosa. We will determine structural features of the CF mucin carbohydrate ligand(s) that provide increased binding to P. aeruginosa by preparing glycopeptides and individual saccharides from CF and control mucins. The glycopeptide(s) which show high inhibition of asialo-GM; binding to P. aeruginosa will be used to isolate 0-linked glycans for further testing of inhibitory activity and structural determination using state-of-the-art highly sensitive mass spectrometry and enzymnatic methods. Affinity gels containing selected mucin glycopeptide or mucin saccharide will be used to purify the P. aeruginosa adhesins which interact with airway mucins and glycolipids, respectively. The primary structure of the major adhesins will be determined using molecular cloning techniques. Structural characterization of major adhesins will open additional approaches to prevent the binding of P. aeruginosa to airway epithelial cells and mucins of CF patients. Information on the adhesin binding sites will permit molecular modeling, design and synthesis of potent 0-glycan inhibitors of the P. aeruginosa infection. The overall long-term goal of this study is to prevent and/or treat lung infections in CF patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOFILM FORMATION AND P. AERUGINOSA INFECTION OF THE EYE Principal Investigator & Institution: Zegans, Michael E.; Surgery; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007

12

Pseudomonas

Summary: (Applicant's Abstract) Bacterial infections of the eye can have visionthreatening complications and often are associated with prosthetic devices such as contact lenses, scleral buckles, and intraocular lenses. Pseudomonas aeruginosa (PA) is one of the most common causes of bacterial keratitis. The central hypothesis of this proposal is that biofilm formation plays an important role in the pathogenesis of ocular infections of PA and that an understanding of the biology and genetics of Pseudomonas aeruginosa biofilm formation will have relevance to the development of novel antimicrobial therapies. Bacteria grow as planktonic (or free-living) cells or as surfaceattached communities known as biofilms. Biofilm formation contributes to the pathogenesis of many clinical infections associated with prosthetic devices by allowing bacteria to persist on abiotic surfaces which come in contact with the body, by facilitating colonization of biotic surfaces and by rendering bacteria more resistant to antimicrobial agents. However, the relevance of biofilm formation to ocular infections has not been extensively studied. Bacterial keratitis caused by PA will be the model system studied in this project. Existing biofilm mutants of PA, as well as additional mutants that will be developed in the course of the project, will be used to elucidate the biology and genetics related to PA biofilm formation on abiotic and biotic surfaces relevant to the eye. The functions mutated in these strains may define novel drug targets. In addition, inhibitor studies may identify new classes of compounds that prevent and/or eliminate eye infections. The ability of growth in a biofilm to render PA resistant to the innate immune system, specifically the human B-defensin (hBD) 1 and 2 will be investigated. hBD 1 and 2 are recently described antimicrobial peptides secreted by the corneal and conjunctival epithelium. hBD 1 and 2 are active against PA under planktonic conditions, but have not been tested against organisms growing in a biofilm. If biofilm-based resistance exists, it would presumably contribute to keratitis and identification of genes that play a role in this process may be novel targets for rendering biofilm bacteria sensitive to antibiotics and defensins. If biofilm and planktonic cells are as equally sensitive to hBD-l and hBD-2, this would suggest that B-defensins can bypass biofilm-specific biocide resistance, and furthermore, these compounds (or derivatives) might make excellent therapeutics to prevent and/or treat biofilm-based infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOTHREAT DETECTION WITH IMPROVED BACKGROUND REJECTION Principal Investigator & Institution: Kebabian, Paul L.; Aerodyne Research, Inc. the Research Ctr at Manning Park Billerica, Ma 01821 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): The Quartz Crystal Microbalance (QCM) is a wellestablished technology for quantifying small changes in mass. The long-term objective of this program is to improve the QCM so that it is suitable for use as a field test for the common, foodborne bacteria. To do this, we will modify the standard quartz crystal (QC) used in the QCM so as to increase its background rejection capabilities. This will involve innovations to the design of the QC used as the detector to the electronics. We will utilize standard technology to deposit a uniform coating of antibody directed against E. coli onto the surface of the QC. We will use utilize commercially available preparations of E. coli and Pseudomonas to demonstrate that the innovations introduced to the QC design and the electronics of the QCM allow a single QC to serve as both the experimental and the reference detectors. Thus, the modified QCM can discriminate between specific and non-specific binding of mass to the QC. We will use a second antibody, labeled with horseradish peroxidase to generate an insoluble reaction

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product to further amplify the mass of bacteria attached to the QC. Furthermore, we will utilize glutaraldehyde to non-selectively bind bovine serum albumin to antibody on the surface of both the conventional and modified QCs. Only the modified QC will be able to discriminate between specific binding of E. coli to the antibody and the non-specific cross-linking of BSA to antibody. We believe that our innovations will be of particular value in field tests in which there will be relatively small amounts of pathogenic agent and relatively large amounts of nonhazardous materials. In Phase II of the project, we will apply the technology developed in Phase I to the detection of other common foodborne bacterial contaminants. We will also extend our working relationship with academic laboratories to further test the device. We will work with diagnostics companies to determine their willingness to commercialize this technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN TUMORS - IMMUNOLOGICAL AND BIOLOGICAL STUDIES Principal Investigator & Institution: Bigner, Darell D.; Jones Cancer Research Professor; Pathology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-DEC-1976; Project End 31-MAR-2008 Summary: (provided by applicant): There will be more than 17,000 new cases of primary malignant brain tumors diagnosed in 2002 and more than 13,100 deaths. There has been little progress in the treatment of malignant gliomas in the last 30 years. Unarmed and armed MAbs are now being approved by the FDA for treatment of systemic cancers such as breast carcinoma, non-Hodgkin's lymphoma and hairy cell leukemia. Our hypothesis is that poor drug delivery and widespread migration of GBM cells will be overcome by using intracranial microdiffusion [(convection-enhanced delivery (CED)] of MAbs or their fragments as unarmed MAbs, toxin conjugates, or radiolabeled conjugates. Genotypic and phenotypic heterogeneity and cellular resistance to chemotherapy will be overcome by targeting multiple cell-surface expressed molecular targets of GBMs, namely EGFRvIII, MRP3, GPNMBwt and GPNMBsv, and 3'-isoLM1 and 3'6'-isoLD1. Anti-EGFRvIII MAbs have been developed in the last period of this grant and an scFv-PE38 KDEL single fragment chain Pseudomonas exotoxin construct will enter clinical trial in late 2002. We propose raising three additional MAbs, one reactive with GPNMBwt and GPNMBsv, another specific for 3'-isoLM1 and 3'6'-isoLD1, and anti-MRP3 MAbs. All of these molecules are involved in the malignant phenotype of GBM. Elimination of cells expressing these four molecules should result in significant survival increases in GBM patients. Our specific aims are: 1) To prepare high affinity MAbs reactive with GPNMBwt and GPNMBsv, MRP3, and 3'-isoLM1 and 3'6'-isoLD1.2) To use the MAbs from Specific Aim 1 and anti-EGFRvIII MAbs from the previous grant period to determine the true incidence of expression, cell and tissue localization and heterogeneity of expression of GPNMB, MRP3, 3'-isoLM1 and 3'6'-isoLD1, and EGFRvIII in malignant gliomas. 3) To determine in vitro whether unarmed MAbs reactive with GPNMBwt and GPNMBsv, MRP3, and 3'-isoLM1 and 3'6'-isoLD1 have anti-proliferative and/or apoptosis-initiating activity. 4) To prepare scFv-Pseudomonas toxin constructs and 131I and 211Atlabeled divalent minibodies reactive with GPNMBwt and GPNMBsv, MRP3, and 3'-isoLM1, and 3'6'- isoLD1, and to compare their cystostatic and cytocidal activity in vitro and in vivo. 5) Under D. Bigner's Brain Tumor Center grant, perform FDA-required toxicity and efficacy of three best toxin and three best radiolabeled constructs and submit IND and carry out clinical studies in glioma patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

14

Pseudomonas

•

Project Title: CELL-CELL COMMUNICATON IN BACTERIAL QUORUM SENSING Principal Investigator & Institution: Levchenko, Andre; Assistant Professor; Biomedical Engineering; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Quorum sensing is a complex, collective behavior displayed by a variety of bacterial species when the cell population density exceeds the critical value. Examples of processes modulated by quorum sensing are the development of genetic competence, conjugative plasmid transfer, sporulation and cell differentiation, biofilm formation, virulence response, production of antibiotics, antimicrobial peptides and toxins, and bioluminescence. Collective behavior in quorum sensing can result in the formation of biofilms, highly organized and spatially structured bacterial colonies encased in polysaccharide gels. The U.S. Centers for Disease Control has estimated that biofilms cause 65 percent of infections in the developed world. Biofilm formation plagues the use of intravenous, endotracheal and urinary tubes, surgical sutures, catheters and contact lenses. Biofilms can display very sophisticated temporal and spatial self-organizing behavior characteristic of complex systems. Therefore quantitative understanding of the mechanisms underlying quorum sensing is essential for combating developing infectious diseases in clinic. Here we propose to investigate adaptive properties of quorum sensing both theoretically, by construction of computational model of randomly seeded interacting cells and experimentally, by investigating single cell and population responses in an experimental model of quorums sensing: Vibrio fischeri. In particular, we will investigate the hypothesis that biphasic regulation of diffusible autoinducer production by individual cells on the local autoinducer concentration makes quorum sensing robust to global and local variations in cell density. In addition, we will verify the prediction that biphasic nature of autoinducer autoregulation allows cells to reduce high metabolic load necessary to maintain high level quorum response. These hypotheses suggest high degree of adaptability and robustness in quorum sensing response. The model proposed is an example of an algorithmic, bottom-up approach that allows to take the natural noisiness and variability into account in the analysis of experimental data. As a part of the proposal we will develop a novel method for analysis of V. fischeri quorum sensing at very high cell densities, normally not allowed in the batch liquid cell culture. Following verification, the model development will be extended to include multi-species interaction in biofilm formation and analysis of biofilm structure in light of quorum sensing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHIMERIC VIRUS VACCINES FOR P. AERUGINOSA INFECTIONS Principal Investigator & Institution: Staczek, John; Professor; Microbiology and Immunology; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2003; Project Start 01-JUL-1998; Project End 31-MAR-2007 Summary: (provided by applicant): Pseudomonas infection is an underappreciated cause of morbidity and mortality. Nosocomial infections can be life-threatening in immunocompromized populations, cancer patients, the elderly, and patients with cystic fibrosis. Physicians try to protect patients with antibiotic therapy, but the bacteria quickly develop antibiotic resistance. A complementary approach to antibiotic therapy is therefore urgently needed, and one such approach is vaccination. Our long-range goal is to develop vaccines that protect against Pseudomonas lung infection. We have developed two effective outer membrane protein F (OprF)-based vaccines that protect

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15

against both nonmucoid and mucoid Pseudomonas phenotypes. These vaccines are called F/I and F/HG. The F/I vaccine consists of three biolistic inoculations of naked DNA sequences for the fusion protein OprF/l. The F/HG vaccine uses a prime-boost strategy with two biolistic inoculations of naked DNA-oprF sequences followed by an intramuscular booster containing the chimeric influenza virus HG10-11. Each vaccine appears to induce a polarized immune response. The F/I vaccine induced antibodymediated immunity (AMI) while F/HG induced cell-mediated immunity (CMI). Insufficient information is available regarding the immune mechanisms whereby Pseudomonas infection is controlled or how Pseudomonas vaccines work. AMI in pulmonary Pseudomonas infection is believed to be important, but the definitive mechanism for clearance is unknown. We propose to define the mechanisms of antibody protection by identifying antibody isotypes and serum cytokines in infected and F/Iimmunized mice that are immune-intact or immune-deficient. Likewise, the role of CMI in Pseudomonas pneumonia is poorly understood. Our F/HG vaccine will allow us to define the mechanism(s) of Pseudomonas-specific, cell-mediated protection in the lungs of infected and immunized mice that are immune-intact or immune-deficient. Defining these mechanisms will allow us to rationally modify immune responses to protect more effectively against pulmonary Pseudomonas infection. As researchers delineate the immune responses to pulmonary Pseudomonas infection in humans, we will be uniquely positioned to modify our vaccines to induce specific Th-1 or Th-2 responses. These rationally designed vaccines tested in a pulmonary chronic infection model will provide guiding principles to prevent and treat more effectively Pseudomonas pneumonia in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTACT LENS EFFECTS ON HUMAN OCULAR MUCIN Principal Investigator & Institution: Mcnamara, Nancy A.; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: The goal of this project is to continue my development as an independent scientist and teacher. To achieve this goal, a five-year postdoctoral training program is proposed that will supplement my experience in clinical corneal research, with advanced training in the basic science disciplines of ocular surface biochemistry, molecular biology, microbiology, and bacterial pathogenesis. The program will include courses, seminars and laboratory experience at the Universities of California, San Francisco (UCSF) and Berkeley (UCB). Both UCSF and UCB document incredibly strong research programs in molecular and cell biology, biochemistry, and chemistry, and several key faculty will serve as sponsors. The proposed research project has been carefully designed to complement and enhance those skills obtained during the development period and will provide me with the necessary expertise to analyze the pathogenesis of various ocular surface diseases. Ocular mucins have been shown to protect against corneal infection by inhibiting Pseudomonas aeruginosa adherence to the ocular surface. The purpose of this project is to test the hypothesis that contact lens wear alters the quantity or composition of ocular mucins and thereby interferes with bacterial binding to tear film glycoproteins. The initial phase of this project will investigate the effects of hydrogel contact lens wear on the quantity and composition of secreted ocular mucins. Mucin samples will be obtained by irrigating the human ocular surface, and the optimal technique for purifying mucous glycoproteins will be determined. The quantity of secreted mucin and mucin RNA levels will be compared in contact lens wearers versus controls, and the composition of ocular mucin will be

16

Pseudomonas

assessed using lectins and specific exoglycosidases. The second phase of experiments will examine the nature of the interaction between P. aeruginosa and ocular mucins, using competitive inhibition studies, and will determine whether or not contact lens wear affects this interaction. The risk of sight-threatening corneal ulceration resulting from overuse of hydrogel lenses is a significant public health concern, and this project will analyze whether or not changes to ocular mucin contribute to this risk. Understanding the effects of contact lens wear on ocular mucin may aid in the design of strategies to prevent or lessen the risk of ulcerative keratitis. This program and research experience will integrate my clinical and basic science training and enable me to formulate hypotheses about clinically observed phenomenon based upon a firm understanding of fundamental ocular biology. 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: CRYSTALLOGRAPHIC STUDIES OF POLYPHOSPHATE KINASE Principal Investigator & Institution: Xu, Wenqing; Biological Structure; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Polyphosphate (poly (P)) is a linear polymer of hundreds of orthophosphate (Pi) residues linked by high-energy phosphoanhydride bonds. Many lines of evidence indicate that poly (P) plays a critical role in regulatory responses to stresses and nutritional deficiencies. Polyphosphate kinase (PPK) is an

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enzyme responsible for the reversible synthesis of poly (P) from ATP. It has been shown recently that PPK is essential for biofilm development, quorum sensing, motility and release of virulence factors of many pathogenic microorganisms, including P. aeruginosa. Knockout of the PPK gene leads to the loss of viability of the pathogenic microorganism. Thus PPK specific inhibitors could become a novel family of antibiotics, which can be very useful to overcome antibiotic resistance in cystic fibrosis and other immunodeficient patients, and could play a role in combating bioterrorism. PPK is a membrane-associated enzyme that does not have apparent sequence homology with other proteins. No three-dimensional structural information is available for the PPK family. We have recently purified and crystallized the full-length E. coli PPK, and the initial phases for structure determination by x-ray crystallography have been obtained. The main goal of this proposal is the determination of crystal structures of PPK and its complexes with various substrates and reaction intermediate mimics. Our structural studies will aid in determining the PPK catalytic mechanism and provide insights into drug design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF SHUTTLE VECTOR FOR GENE TRANSFER IN MICROCYSTIS AERUGINOSA Principal Investigator & Institution: Raps, Shirley; 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

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Project Title: DISCOVERY OF B. PSEUDOMALLEI THERAPEUTICS FOR BIODEFENSE Principal Investigator & Institution: Moir, Donald T.; Genome Therapeutics Corporation 100 Beaver St Waltham, Ma 02453 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-OCT-2003 Summary: (provided by investigator): Burkholderia pseudomallei is a bioterrorist threat. With the best current therapies, lethality is typically as high as 40%. The overall goal of this application is the development of new drugs against this organism. In Phase I, we will exploit the high sequence similarity between B. pseudomallei and its less virulent relative Pseudomonas aeruginosa to build innovative screens for rapid, safe discovery of effective therapeutic agents. The two species are similar in genome size and composition, with nucleotide and amino acid sequence identities for many genes in the 50-70% range, and in their mechanisms of drug resistance. We will identify genes for new drug targets in B. pseudomallei with orthologs in P. aeruginosa, validate them as essential for survival or growth of both species, and move them into P. aeruginosa as replacements for the native orthologs. Then, we will measure the whole-genome expression profile of P. aeruginosa strains engineered to under express each B. pseudomallei target gene, and use the results to construct a validated set of sensitive whole-cell reporter screens. In Phase II, we will apply these screens to a library of over 100,000 compounds and advance the most promising candidates into lead optimization and efficacy testing in animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIVERSITY AND EVOLUTION OF P SYRINGAE TYPE III EFFECTORS Principal Investigator & Institution: Dangl, Jeffrey L.; John N. Couch Professor; Biology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Identification of virulence factors is a necessary first step to study the mechanisms and evolution of pathogenicity. We propose to compare the type III disease effector proteins from a phylogenetically diverse set of plant pathogenic Pseudomonads chosen to represent the most broad distribution of the species possible. P. syringae is an ideal model organism to study the distribution and evolution of type III effectors. Type III effectors interact with cellular host targets, and modulate host defense responses or metabolism in a manner conducive to pathogen proliferation. Most of the P. syringae effectors have not yet been characterized, and we remain naive as to the collective diversity of host cellular functions they manipulate. Although the functions of P. syringae effector proteins during disease remain poorly understood, they can often be monitored via their phenotypes following in planta expression of a given type III effector. Bacterial pathogens of both animals, such as Salmonella spp., Yersinia spp., Shigella spp. and pathogenic E. coli also rely on type III secretion systems for pathogenesis. Thus, our results will inform studies of these bacteria and their animal hosts, including humans. Because P. syringae is pathogenic on a variety of distantly related plant hosts, many of which can be genetically manipulated, our system has advantages over models of type III pathogenesis of animals, which generally focus only on strains pathogenic on phylogenetically related mammalian hosts. We have devised and implemented a high throughput Fluorescence Activated Cell Sorter (FACS) based experimental approach to capture all of the type III effectors from the genome of any given P. syringae isolate. We chose 13 P syringae isolates that are pathogens of an evolutionarily diverse set of host plants. We intend to sieve through these 13 genomes to describe their suites of type III effectors. We further intend to begin dissection of their effects on host cell biology, using the easily manipulated Arabidopsis plant as a model where appropriate. This proposal is highly interdisciplinary, drawing on methodologies and expertise in microbiology, bioinformatics and plant-pathogen interactions in conjunction with high throughput bacterial cell sorting using the FACS. Our work will broadly impact the understanding of a widely distributed pathogenicity mechanism that affects both human health and agriculture. Additionally, our work may have relevance in biodefense with respect to basic understanding of pathogenesis in bacteria that can potentially be weaponized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AERUGINOSA

DNA

REPLICATION

SYSTEM

FROM

PSEUDOMONAS

Principal Investigator & Institution: Janjic, Nebojsa; Vice President, R&d; Replidyne, Inc. 1450 Infinite Dr Louisville, Co 80027 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: (provided by applicant): The ongoing emergence of drug-resistant bacteria is rapidly reducing the efficacy of existing antibiotics leading to increased mortality, morbidity and public health burden due to bacterial infections. Since most drugs in latestage clinical development are analogs of existing drugs to which resistance is expected to develop rapidly, there is an acute need for novel, mechanistically distinct

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antibacterials. To date, none of the antibacterials target any of the central components of the DNA replication system of bacteria. The overall aim of this project is to assemble a minimal DNA replication system from Pseudomonas aeruginosa, a clinically important pathogen in which the emergence of multidrug resistance is beginning to limit treatment options. We anticipate that 5 subunits will be minimally required to reconstitute the replicative polymerase capable of rapid and processive DNA synthesis: DnaE (DNA polymerase III subunit), DnaN (sliding clamp processivity factor), DnaX (clamp loader ATPase), HoIA and HoIB (accessory subunits of the clamp loader complex). All of these genes are apparent in the recently completed Pseudomonas aeruginosa genome. We plan to clone, express and purity these five proteins and use them to reconstitute a functional DNA replicase. This multiprotein assembly will then be used in highthroughput screens to identify new drug candidates that inhibit this and other bacterial replication systems. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELECTROSTATIC SAMPLING OF AIRBORNE MICROORGANISMS Principal Investigator & Institution: Willeke, Klaus; Environmental Health; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: Each year millions of respiratory allergies and infections are caused by airborne microorganisms present in agricultural, industrial and indoor environments. The level of exposure indicated by bioaerosol samplers depends on the instrument used and the sensitivity of the microorganisms. In an effort to collect such microorganisms more gently, at low power and at minimal pressure drop, an electrostatic sampling technique has been developed and evaluated in the laboratory under the present NIOSH grant. As a major part of this development, an electrostatic particle-size classifier and a microorganism dispersion device with optional induction charging were developed to study the electric charges on airborne microorganisms. It has experimentally been proven that laboratory-dispersed indoor air bacteria, such as Pseudomonas fluorescens, had a net negative charge. Some of the bacteria were found to carry several thousand negative or positive charges. In contrast, particles of non-biological origin were found to carry very few positive or negative charges. This finding suggests that the electrostatic sampler will be capable of retaining airborne microorganisms by its electrostatic collecting field without first charging the microorganisms in the inlet section, thus reducing the complexity and power consumption for sampling in occupational environments. During the two years of the proposed grant continuation, this discovery will be evaluated in the laboratory with common bacteria and fungal spores and in the field through sampling of (1) microorganisms present in indoor air environments, (2) liquid-borne microorganisms in metalworking fluid environments, and (3) high concentrations of airborne microorganisms in agricultural environments. The physical and biological collection efficiencies will be determined from the relationship between the total and viable microorganisms collected by the new sampler and the number of uncollected microorganisms passed through the new sampler and collected by other means. The testing will indicate under what release conditions the microorganisms are sufficiently charged for collection by the simplified version of the new sampler. Microorganisms dispersed by mechanical action are expected to carry a particularly high charge and to be collected very efficiently by the electrostatic sampler without having to charge them in the inlet section. The new method will be used in occupational environments where airborne microorganisms are naturally present or are released by industrial processes.

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Pseudomonas

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

Project Title: ELR+ CXC CHEMOKINES IN PSEUDOMONAS AIRWAY INFECTION Principal Investigator & Institution: Tsai, Wan C.; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 10-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from applicant's abstract) Persistent Pseudomonas endobronchial infection is a common complication of airway diseases such as cystic fibrosis, resulting in progressive airway destruction despite currently available therapy. While mechanisms by which Pseudomonas persist within the airways have not been well defined, studies suggest that neutrophils may be critically important in host defense against this infection. Recently, members of the ELR+CXC chemokine family have been shown to mediate neutrophil recruitment in pulmonary infections. The hypothesis of this proposal is that the influx of neutrophils into the airways in chronic Pseudomonas endobronchial infection is mediated by ELR+CXC chemokines, and that manipulation of these ligands or their receptor will impact the outcome of infection in airways of mice infected with Pseudomonas. A murine model has been developed to assess the following Specific Aims: I) to examine the time-course and magnitude of expression of the ELR+ CXC chemokines, (KC, Lungkine, MIP-2), and their receptor, CXC chemokine receptor- 2 (CXCR2) in mice with mucoid P. Aeruginosa endobronchial infection; II) to determine the contribution of specific ELR+ CXC chemokines and their receptor CXCR2 in mucoid Pseudomonas endobronchial infection by evaluating the outcome of infection in animals passively immunized with neutralizing antibodies against CXCR2 or selected ligands; and III) to evaluate the effect of airway- specific transgenic expression of relevant ELR+ CXC chemokines in Pseudomonas endobronchial infection, by examining the outcome of infection: a) airway- specific chemokine transgenic animals, and b) animals transiently expressing the chemokine transgene in the airways using adeno-associated viral gene therapy. These studies will provide important insights into mechanisms of the innate antibacterial host response in the airways and potentially identify novel therapeutic strategies to be employed in treatment of this deviating disease. (End of Abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENHANCED ANTIMICROBIAL ACTIVITY BY SYNTHETIC PEPTIDE NTP Principal Investigator & Institution: Coleman, Chris L.; Chrysalis Biotechnology, Inc. 2200 Market, Ste 600 Galveston, Tx 77550 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): In the United States (U.S.), approximately 50 percent of all major hospitalization complications involve nosocomial infections. This represents over two million patients at a cost in excess of $4.5 billion per year. The widespread prophylactic and acute use (and misuse) of antibiotics to combat infection contributes to increased numbers of drug resistant bacteria. Thus, there is a continuing need to develop new antibiotics, but these new antibiotics also quickly loose their efficacy as new resistant strains of bacteria arise. The applicants believe the answer is to utilize therapeutics that can stimulate natural cell-mediated killing of bacteria or stimulate the recruitment of antimicrobial cells to the site of infection. The investigators have discovered a novel 15-amino acid peptide that is released at the site of tissue injury by

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thrombin cleavage of specific cell surface receptors and is selectively chemotactic for neutrophils. This human Neutrophil Targeting Peptide (hNTP15) may therefore target neutrophils to the site of injury where if needed they can be activated to eliminate microbial infestations. Preliminary data show that the synthetic hNTP15 peptide is nearly as chemotactic as interleukin 8 (IL-8) or thrombin and that there appears to be a neutrophil-specific cell surface receptor to which hNTP15 binds. In the proposed Phase I studies the applicants will: (1) determine the chemotactic efficacy of highly-purified Good Laboratory Practice (GLP) synthesized hNTP15 in vitro using Modified Boyden Chambers and fluorescent chemotactic assays and in animal wound models using implanted polyvinyl alcohol (PVA) sponges and full-thickness excisional wounds; (2) determine if treatment of wounds in animal models helps reduce infection when live Pseudomonas are added to the wounds; and (3) determine if hNTP15 has major safety or stability issues that would prevent it from moving forward as a drug candidate. For these studies intravenous (I.V.) and Intraperitoneal (I.P.) bolus injections into mice will be conducted under GLP conditions (Stillmeadow Laboratories) and stability testing will be assessed using established high-performance liquid chromatography (HPLC) and activity measurements. If hNTP15 shows potential efficacy in the animal models, the applicants will move forward with Phase II development of a commercial formulation for topical application to reduce infection in acute or chronic wounds to be used alone or as an adjunct therapy to existing antibiotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENTERAL VS IV FEEDING: EFFECT ON MUCOSAL IMMUNITY Principal Investigator & Institution: Kudsk, Kenneth A.; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-MAR-2006 Summary: Hospital acquired pneumonia costs up to 2 billion dollars per year in the United States, and any inexpensive therapy which reduces this septic complication could greatly impact health care costs. Enteral feeding significantly reduces the complications of pneumonia compared with intravenous (IV-TPN) feedings by 60-70 percent in trauma patients. Our experimental and clinical work implicates previously unrecognized defects in mucosal immunity which develop when the intestinal tract is not stimulated with enteral feeding or when surrogates of enteral feeding are not provided. The principal specific immunologic defense at mucosal surfaces is secretory IgA produced by the mucosal-associated lymphoid tissue (MALT). The principal anatomic site for immunologic sensitization of Peyer's patches within the small intestine. Adhesion molecules direct unsensitized immunocytes through the Peyer's patches where these lymphocytes are sensitized and change their own surface integrins. They are then directed to both intestinal and extraintestinal sites, such as the respiratory tract, where they produce IgA against those antigens. The antibody binds to bacteria, preventing their attachment and their ability to infect. This proposal focuses on how route and type of nutrition affects the expression of the specific adhesion molecules, modified MAdCAM-1, unmodified MAdCAM-1, and ICAM-1 which are important in directing unsensitized immunocytes into Peyer's patches. The proposal tests the hypothesis that interaction between these adhesion molecules and their ligands on naive T and B cells are critical in maintaining mucosal immunity in both intestinal and extraintestinal sites. The proposal is designed to test the hypothesis that inhibition of these interactions recreates the defects in in vivo mucosal defenses that are induced when enteral feeding is not provided. It also focuses on previous observations that a specific immunocyte fuel, glutamine, and the enteric nervous system neuropeptide,

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Pseudomonas

bombesin, can act as surrogates for enteral feeding and exert beneficial effects upon the MALT in IV-TPN-fed animals by upregulating MAdCAM-1 and ICAM- 1 expression. The experiments are designed to confirm that IgA is a critical element of specific immunity and respiratory defenses against pneumonia with in vivo experiments. These experiments use a monoclonal antibody produced by a hybridoma cell line which is specific for polysaccharide antigen(s) found on a high percentage of clinical isolates of Pseudomonas aeruginosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENZYMOLOGY OF ALGINATE BIOSYNTHESIS Principal Investigator & Institution: Tipton, Peter A.; Associate Professor; Biochemistry; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract): The proposed research program is a detailed investigation into the enzymology of alginate biosynthesis in the pathogenic bacterium Pseudomonas aeruginosa. P. aeruginosa infections are common and present significant health hazards to humans. Complications arising from colonization of lung tissues by P. aeruginosa are the leading cause of morbidity and mortality in cystic fibrosis patients. Alginate is a linear polysaccharide composed of mannuronate and guluronate residues, and is secreted by the bacteria to form an extracellular capsule, which contributes to their ability to effectively colonize lung tissue, resist antibiotic therapies and evade the host's immune system response. A potential strategy to combat P. aeruginosa infections is to develop agents which inhibit alginate biosynthesis and thereby render the bacteria susceptible to conventional antibiotics. Reports in the literature suggest that this strategy has merit, but to date, there are no effective specific inhibitors or inactivators of P. aeruginosa alginate biosynthetic enzymes. In order to approach the inhibition of alginate biosynthesis in a rational way, a deeper understanding of the functional properties and catalytic mechanisms of the constituent enzymes of the pathway is required. The research program described in the proposal focuses on C5 mannuronan epimerase and the enzymes which catalyze the first four steps of the alginate biosynthetic pathway. GDP-mannose dehydrogenase catalyzes the committed step in alginate biosynthesis, a mechanistically interesting four-electron oxidation, and will receive particularly close scrutiny. Detailed kinetic studies using transient kinetic approaches and kinetic isotope effect measurements will be performed in order to determine the energetics of the reactions; potential inhibitors and inactivators which have been designed based on hypotheses about the enzyme's chemical mechanisms will be characterized. The structure of phosphomannomutase, which catalyzes the second step in the pathway, will be determined by X-ray crystallography; GDP-mannose dehydrogenase has also been crystallized, and the determination of its structure will be pursued. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENZYMOLOGY OF ANTIBIOTIC RESISTANCE Principal Investigator & Institution: Armstrong, Richard N.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-DEC-2007 Summary: (provided by applicant): In the last two decades it has become increasingly clear that the efficacy of antibiotics for the treatment of infectious diseases is in jeopardy due to the common appearance of drug resistant strains of microorganisms.

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Understanding the mechanisms of antimicrobial resistance is crucial for effective patient care in the clinic and essential for developing strategies to enhance biodefense against intentionally disseminated of pathogens. Fosfomycin is a potent, broad-spectrum antibiotic effective against both Gram-positive and Gram-negative microorganisms. A decade after its introduction plasmid-mediated resistance to fosfomycin was observed in the clinic. Investigations supported by this project have established that the resistance is due to a metalloenzyme (FosA) that catalyzes the addition of glutathione to the antibiotic, rendering it inactive. Similar resistance elements have now been shown to exist in the genomes of several pathogenic microorganisms including, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus anthrasis, Brucella melitensis, Listeria monocytogenes and Clostridium botulinum. Genomic and biochemical analysis from this project suggest that there are three distinct subgroups of metalloenzymes, termed FosA, FosB and FosX, that confer resistance through somewhat different chemical mechanisms. The objectives of this research project are to identify plasmid and genomically encoded proteins involved in microbial resistance to fosfomycin and to elucidate the underlying structural and mechanistic enzymology of resistance. These objectives will be accomplished by integrating enzymological, biophysical and genomic analyses of the resistance problem. The three-dimensional structures of the FosA from Pseudomonas aeruginosa and its relatives FosB and FosX will be determined by X-ray crystallography. The chemical mechanisms of catalysis will be elucidated by: (i) examination of the inner coordination sphere of Mn 2+ in FosA and FosX by EPR and ENDOR spectroscopy; (ii) a steady state kinetic analysis of the thiol selectivity of FosA and FosB, and (iii) a mechanistic study of the unique hydration reaction catalyzed by FosX. Potential transition state inhibitors will investigated by structural, spectroscopic and kinetic techniques. The thermodynamics of the interaction of substrates and inhibitors with the enzymes will be examined by isothermal titration calorimetry Particular emphasis will be placed on the enzymes from the pathogens Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Clostridium botulinum. The intent of this investigation is to establish the mechanistic and structural bases for the design of drugs to counter both plasmid borne and genomically encoded resistance to fosfomycin. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ERADICATING BIOFILMS WITH ATMOSPHERIC GLOW PLASMA Principal Investigator & Institution: Kelly-Wintenberg, Kimberly K.; President & Ceo; Atmospheric Glow Technologies, Llc 924 Corridor Park Blvd Knoxville, Tn 37932 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: (provided by applicant): Atmospheric Glow Technologies proposes a novel method of cold sterilization and biofilm destruction of medical and dental materials. The effort will use the One Atmosphere Uniform Glow Discharge Plasma (OAUGDP) technology to attack and destroy biofilms, which cause serious problems on medical and dental instruments and devices. The use of atmospheric plasma to sterilize/decontaminate instrumentation contaminated with biofilms is a new application of a proven baseline technology. The efficacy of the OAUGDP using direct exposure was clearly demonstrated in Phase I studies. In this proposed effort, a remote atmospheric plasma reactor will be optimized to create a flow of concentrated reactive oxidative species (ROS) over 3-D workpieces and a novel direct plamsa delivery system for treating lumened devices. The performance of this reactor will be assessed against mixed species biofilms and in the presence of organic debris. Analytical studies will be

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undertaken to examine the composition of plasma ROS and any physical or chemical alterations that occur in materials and biological substances. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVOLUTION OF ANTIBIOTIC RESISTANCE PLASMIDS Principal Investigator & Institution: Top, Eva M.; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2002; Project Start 23-FEB-2002; Project End 31-JAN-2007 Summary: Plasmids play a central role in the spread of resistance among bacterial species thereby decreasing the effectiveness of various chemotherapeutic agents for the treatment of infectious diseases. They carry genes that encode essential functions, such as replication, maintenance and transfer, as well as a variety of accessory functions, such as antibiotic resistance determinants. The objective of the proposed research is to obtain a more systematic and comprehensive understanding of plasmid evolution through experimental evolution studies. The specific aims are 1) To assess the tempo and mechanisms of plasmid evolution during vertical transmission in a single host as compared to vertical and horizontal transmission among phylogenetically distinct hosts, in the presence of selective pressure; 2) To characterize and compare the genetic and phenotypic changes that occur during such experimental plasmid evolution; 3) To test the ability of various algorithms to accurately reconstruct the true phylogenies of independently evolved plasmids and specific genes. The broad host range Inc-1beta plasmid pB10, which encodes resistance to four antibiotics and mercury, will be experimentally evolved in replicate cultures of three genetically distinct hosts (Escherichia coli, Pseudomonas aeruginosa, Burkholderia cepacia) as previously described in studies of microbial evolution. Plasmid evolution in one single host will be compared with evolution in alternating hosts, and in each case plasmids evolved for differing periods of time will be characterized. Phenotypic changes will be characterized by examining the effect of the evolved plasmid on host fitness and by assessing differences in the stability and broad host range characteristics of the evolved and ancestral plasmids. Genetic changes that may account for the observed phenotypic differences will be identified by characterizing macroscale and microscale variations in the evolved replicons. Possible correlations between phenotypic changes and genotypic variations will be examined. In addition an experimental plasmid phlogeny will be constructed that has the same topology as described in Project 1 (Experimental Evolution of Viruses), and which will permit us to test the ability of currently available algorithms and those developed in Project 4 to accurately reconstruct the phylogeny of a BHR plasmid that evolves in more than one genetic background. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE EXPRESSION PATTERNS BY URINARY TRACT PATHOGENS Principal Investigator & Institution: Lory, Stephen; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: The ability of pathogenic bacteria to sense the changes in their environment and respond by expressing essential virulence is one of the key components of the infectious process. The long term objectives of the proposal are to examine the patterns of gene expression of two important human uropathogens-Escherichia coli and Pseudomonas aeruginosa-during various growth conditions, including growth in the urinary tract of infected patients. Specifically, a library will be prepared of cloned DNA

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from a uropathogenic E. coli strain containing sequences which are absent in the genomes of laboratory E. coli strains. Similarly, a genomic library of uropathogenic P. aeruginosa strain will be constructed. These libraries will be used to prepare filters containing high-density DNA arrays of clones, and they will be probed with cDNA probes derived from mRNAs isolated under various conditions that mimic the human urinary tract. Two such conditions will include growth in human urine, and bacterial attachment to human bladder epithelial cells in culture. In order to identify genes that are differentially expressed, the hybridization patterns of two different probes with the cloned DNA in arrays will be compared. RNA will be isolated from the pathogens propagated in urine or in the presence of primary bladder epithelial cells, and the same organisms grown in standard laboratory media. Probes from E. coli and P. aeruginosa, directly isolated in urine samples from patients with urinary tract infections will also be prepared, and these will be used for the analysis of gene expression during natural infections of humans. Genes of E. coli and P. aeruginosa, which are expressed in isolates from patients with urinary tract infections-or under conditions mimicking such infections-will be cloned and sequenced. The transcriptional start sites of these genes will be determined, in order to identify any urine-tract specific regulatory genes, which may be targets of transcriptional regulators. It is believed that the proposed research will lead to the identification of genes and regulatory circuits which are responsible for the expression of virulence factors in the human urinary tract infected by uropathogenic E. coli and P. aeruginosa. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC ANALYSIS OF MG-TETRAPYRROLE BIOSYNTHESIS Principal Investigator & Institution: Bauer, Carl E.; Biology; Indiana University Bloomington P.O. Box 1847 Bloomington, in 47402 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-MAR-2006 Summary: (provided by applicant): The tetrapyrrole biosynthetic pathway is responsible for synthesizing important metabolities such as vitamin B12, hemes, bilins and chlorophylls. The "common trunk" of the pathway, from 5-aminolevulinate to protoporphyrin IX, has received much attention owing to the fact that a number of heredity diseases (porphyrias) are caused by the overproduction of heme precursors. Clinical manifestations of overproducing these intermediates range from simple skin lesions, to psychotic disorders, to death. The vitamin B12 branch of the pathway has also received recent attention genes involved in vitamin B12 synthesis characterized from Pseudomonas denitrificans and in Salmonella typhimurium. In contrast to the wealth of information on heme and vitamin B12 synthesis, information is just emerging on the synthesis of the Mg-tetrapyrrole family of chlorophylls. In this proposal, we outline plans to perform detailed biochemical and genetic analysis of the Mg-tetrapyrrole biosynthetic pathway. This analysis includes (i) biochemical characterization of enzymes from the Mg-tetrapyrrole branch of the biosynthetic pathway, (ii) biochemical and genetic characterization of a redox responding transcription factor that regulates expression of heme, Mg-tetrapyrroles and carotenoid biosynthesis genes, as well as polypeptides that comprise the light harvesting-II portion of the photosystem. A thorough understanding of the tetrapyrrole biosynthetic pathway has some far ranging practical implications, such as the design of herbicides that target enzymes in the Mg tetrapyrrole pathway, and the health implications of overproducing tetrapyrrole endproducts such as vitamin B12 and heme. It should also not be overlooked that tetrapyrrole driven photosynthesis is the primary route of capturing and supplying

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energy to living cells and, consequently, it is the most important source of energy in our technological world. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOME-WIDE DISSECTION OF C. ELEGANS INNATE IMMUNITY Principal Investigator & Institution: Tan, Man-Wah; Assistant Professor; Genetics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Our goal is to understand the mechanisms of innate immunity at the molecular level. The innate immune system provides the body with its first line of defense against infections and is crucial for survival. Many human diseases result from a failure of the innate immune system. In order to identify and characterize novel mechanisms and effectors of the innate immune system, we will use the infections of C. elegans by several human bacterial pathogens - Pseudomonas aeruginosa, Salmonella enterica and Enterococcus faecalis - as a model. C. elegans is an excellent model for the study of innate immunity; it allows us to combine the power of genetic and functional genomic approaches to systematically and comprehensively dissect the innate immune system. For this proposal, we seek to address the following questions. Within a single organism, what are the molecules that make up the innate immune system? What intracellular pathways are triggered in response to infections by different classes of bacterial pathogens? What molecules are produced that directly destroy or inhibit the growth of the invading pathogens? We will use a variety of approaches, including the combination of genetic screens, full genome gene expression profiling, bioinformatic searches for homologous sequences known to be involved in the innate immune response, and epigenetic inhibition of gene function by double-stranded RNA interference (RNAi) to address the above questions. C. elegans has an inducible defense system and uses the evolutionarily conserved MAP kinase and TGF-beta pathways for defense against bacterial infection. The MAP kinase and TGF-beta pathways have also been implicated in innate immune response in Drosophila and in mice, respectively. Thus, we also propose to identify downstream targets to the TGF-beta pathway, and to determine how the TGF-beta pathway interacts with the MAP kinase pathway in mediating antibacterial defense. Because the signaling pathways in anti-bacterial defense are conserved across phylogeny, these studies should provide significant insights into anti-bacterial response in other organisms, including humans. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEME PATHOGENESIS

OXYGENASE:

STRUCTURE,

FUNCTION

AND

Principal Investigator & Institution: Wilks, Angela; Associate Professor; Pharmaceutical Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Pathogenic bacteria require iron for their survival and ability to cause infection. Heme comprises 90% of the iron available within the host. Therefore, understanding the mechanism of heme acquisition and iron release will provide the knowledge required for the development of new therapeutic targets. Both gram-negative and gram-positive pathogenic bacteria have evolved receptor mediated heme uptake systems by which they acquire iron. A key step in the process is the release of iron from the heme macrocycle by the action of heme oxygenase (HO). The specific aims of the proposal are to a) structurally characterize the soluble bacterial HO enzymes

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from C. diphtheriae (cd-HO), N. meningitides (nm-HO) and P. aeruginosa (pa-HO). The cd-HO is structurally homologous to the mammalian HO proteins and will serve as a model system for the larger membrane bound proteins. The nm-HO and pa-HO represent a new unique class of HO enzymes that in the case of pa-HO show an altered regioselectivity. Using both X-ray crystallographic and NMR methodologies we will be able to obtain significant insight into the role of protein conformation and dynamics in heme reactivity in this unique family of enzymes; b) elucidate the mechanism of heme hydroxylation and regioselectivity by a combination of site-directed mutagenesis and spectroscopic studies designed to identify key structural and electronic factors in determining both regioselectivity and the formation of a key intermediate in the HO reaction; c) To elucidate the mechanistic formation and biophysical properties of verdoheme and biliverdin. The elucidation of the mechanism of action of the bacterial HO proteins will be crucial in understanding the role of heme utilization in pathogenesis, as well as in future development of inhibitors as potential therapeutic agents. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEME PROTEIN REDUCTASES Principal Investigator & Institution: Sligar, Stephen G.; Professor; None; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 01-AUG-1982; Project End 31-JUL-2004 Summary: Through the research outlined in this competitive renewal, we seek a precise understanding of the mechanisms of biological oxidations through knowledge of the detailed chemistry and physical operation of oxygenase and oxidase catalysis. Proposed for investigation are the heme protein reductases, termed cytochromes P450, which play central and crucial roles in mammalian metabolism and human health. Understanding the functioning of the cytochrome P450 systems is critical to defining the control points of drug metabolism, pro- carcinogen processing, and the regulation and method for hormonal control of development and gene regulation. Our approach is problem rather than technique or system focused. We choose amongst the 800+ known P450 sequences those cytochrome systems where there is substantial structural and functional background information. One such system is P450cam, from Pseudomonas putida, which catalyzes the regiospecific hydroxylation of camphor and with which we have been working since the inception of this grant. Other structurally defined P450 systems to be employed include P450(BM3) and P450eryF for which we have the genetic basis in hand to utilize the powerful tools of recombinant DNA technology to express a variety of variant proteins. We have focused our next funding period on four highly specific aims. First, to obtain further high resolution structural information from xray crystallography and physical - chemical definition of the intermediate states of iron and oxygen involved in the P450 catalytic cycle. Second, to further define and elucidate the mechanisms of acid base catalysis and proton delivery that are responsible for the unique chemistry displayed by the P450 cytochromes. Third, to understand the controlling features of the branch points in the catalytic cycle where the path is open to productive commitments for catalysis as well as various abortive autoxidative processes that leak reducing equivalents into the cell and form potentially toxic reduced dioxygen species. Finally, we seek to understand the role of amino acid residues proximal to the heme plane in control of redox movement in protein-protein complexes and the chemical structure/activities of intermediate states. Through these interdisciplinary efforts we hope to shed light on some of the most important problems of modern molecular biochemistry, providing insight into the inner workings of these processes

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and aiding therapeutic prescription and understanding of disease states through detailed mechanistic knowledge. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEXA-D-ARG: A FURIN INHIBITOR FOR ANTHRAX BIODEFENSE Principal Investigator & Institution: Sunkara, Prasad S.; Molecular Therapeutics, Inc. 924 N Main, Ste 100 Ann Arbor, Mi 48104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by investigator): There are two key steps involved in the ability of anthrax toxin to target and kill mammalian cells. The first step involves binding to the mammalian cell surface through the recently cloned Anthrax Toxin Receptor (ATR). The second step involves proteolytic cleavage of the anthrax toxin-PA (protective antigen) residue by a ubiquitously expressed mammalian cell protease furin, such that it now is able to form a multimeric complex (pore) that enables entry of the LF (lethal factor) and EF (edema factor) subunits of anthrax toxin into the cell. The advantage of targeting these two steps for the development of anti-toxin strategies is that a single hit would neutralize both the LF and EF mediated toxicities. The validity of these two steps as targets comes from recent work that used a soluble ATR receptor (to prevent binding to cells) to protect cells from anthrax toxin as well as studies that demonstrate that inhibition of furin using hexa-D-arginine (D6R) protects mice from the toxicity associated with Pseudomonas exotoxin A as well as anthrax toxin. The ability of D6R to protect from the lethal effects of toxin was greatest when mice were pretreated with the drug. Since it is impossible to predict when an individual is going to be exposed to toxin, successful use of D6R in the field will require the development of a slow release formulation such that an individual is protected for 1-4 weeks. In specific aim 1, we will determine the pharmacokinetics of D6R in a rat model to determine the optimal dose of the peptide by subcutaneous (sc) route of administration. Experiments in specific aim 2 will focus on the determination of the maximum tolerated dose (MTD) as a single injection as well as toxicological assessment of therapeutic dose for a period of 4 weeks. Results of studies in aims 1 and 2 will be used in specific aims 3 and 4, to develop a slow release subcutaneous formulation such that protective concentrations of the drug within the plasma are maintained for a prolonged period (4 weeks). These studies will result in a formulation of D6R that will provide prolonged protection of an individual (e.g. a soldier in the field) from the lethal effects of anthrax toxin. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIGH THROUGHPUT BIOENGINEERING OF DETOXIFICATION ENZYMES Principal Investigator & Institution: Bradley, Margaret K.; Modular Genetics, Inc. 65 Cummings Pk Woburn, Ma 01801 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): Our revised project High Throughput Bioengineering of Detoxification Enzymes focuses on organophosphate hydrolases, which have immediate value for mediation or detection of chemical warfare agents (CW; i.e., nerve gases), and long term value for dealing with contaminating pesticides in humans and the environment. Two candidate organophosphate hydrolases have been structurally determined; a TIM barrel-like, dimeric organophosphate hydrolase (OPH) from Pseudomonas diminuta, and a 13-propeller peptide diisopropylfluorophosphatase (DFPase) from Lo/igo vu/garis (squid). Each has some proven, but

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inefficient, effect against organophosphate CW agents and pesticides, and modification of certain residues has been shown to increase their ability to hydrolyze some of these agents [1, 3, 3b, 11-15]. We propose to use our patented technologies for seamless gene assembly (TOPPs) to generate a large library of designed, substrate-specific substitutions (DPSSs). By making multiple modifications in 24-25 residues shown lining the active sites of both OPH and DFPase [1,2,3], we will generate at least 1,000 modified genes for each in 6 months. By screening the expressed genes for their enzyme kinetics with 3-4 substrates (including pesticides and surrogate CW agents), data will be available for designing new modifications in these sets. Preliminary data have already been integrated into our iterative, primer design, and we are preparing to automate the whole process. Our Phase I work will be to expand enormously the number of mutants available for both enzymes, and we believe this approach is a novel way to produce the desired improvements. Phase II aims will likely include i) verification of enzyme activities in the resource library, ii) further analyses of their stability, optimal conditions of assay and other substrates (by us or by collaborators), and iii) finally adding adaptors and modifications to these enzymes for use as biosensors or as a detoxification and/or decontamination tools. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST CELL DETERMINANTS IN PSEUDOMONAS PNEUMONIA Principal Investigator & Institution: Mostov, Keith E.; Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): In immunocompromised and other severely ill patients, Pseudomonas aeruginosa (PA) causes an acute pneumonitis, which has an extremely high fatality rate. Improved methods for prevention and therapy are urgently needed. An in vitro model of PA infection using polarized Madin-Darby canine kidney (MDCK) cells or cultured lung epithelial cells mimics many important features of in vivo pneumonia. Live Pseudomonas organisms added to the apical surface of these cultures attach to and kill the cells. These foci of infection spread centripetally. The current proposal will study the host cell factors that determine susceptibility to Pseudomonas pneumonia using these in vitro model systems. There are four aims in this study: to investigate how modification of cell polarity affects virulence; to identify the receptors for PA and how their regulation affects bacterial interaction; to determine the pathway for internalization of PA organisms; and to examine the role of the actin cytoskeleton in interaction of PA with cells. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOST-PATHOGEN INTERACTIONS IN CYSTIC FIBROSIS Principal Investigator & Institution: Moskowitz, Samuel M.; Pediatrics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 05-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The goal of this application is to establish the independent research career of the candidate in the study of chronic lung disease, including that affecting individuals with cystic fibrosis (CF). The candidate is a pediatric pulmonary fellow with the career goal of developing an active program of diseaserelated basic research as a faculty member at a medical school. The training environments are the laboratory of the sponsor, Dr. Samuel Miller, at the University of Washington School of Medicine, and the CF Center at Children's Hospital and Regional

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Medical Center in Seattle, directed by the co-sponsor, Dr. Ronald Gibson. The proposed project seeks to clarify molecular mechanisms underlying chronic lung infection and inflammation in individuals with CF. The opportunistic pathogen Pseudomonas aeruginosa (PA) infects the lungs of most individuals with CF, frequently (but not invariably) causing severe progressive lung injury and premature death. Study of the interaction between PA and the CF lung is necessary to understand both the cellular processes that promote or permit CF lung infection, and the precise means by which PA interacts with lung cells to cause airway damage. The structure of lipopolysaccharide (LPS), the principal constituent of Gram-negative bacterial surfaces, appears to play a pivotal role in both microbial and human aspects of this interaction. The candidate's preliminary results indicate that resistance of laboratory and clinical isolates of PA to antimicrobial peptides (key components of host innate immunity) correlates with alterations in the structure of the lipid A moiety of LPS. Moreover, mutation of a PA locus that regulates LPS-modifying enzymes influences the antimicrobial peptide resistance phenotype. The microbiological phase of the project thus seeks to define PA genes necessary for this putative resistance mechanism, and to identify potential inhibitors using antimicrobial peptide-resistant strains. The human phase of the project builds on the clinical observation that some individuals with a severe CF genotype and chronic PA airway infection nevertheless have minimal lung disease. A case-control design will be utilized to test the hypothesis that polymorphisms in innate immune genes may limit CF lung disease. Those innate immune genes encoding the LPS receptor are leading candidates as CF modifier loci, based on the recent finding that CF-specific PA LPS structures have increased inflammatory activity. When prevalence of an LPS receptor variant differs in mild and severe CF lung disease, receptor function will be assayed in cell culture models of LPS signaling. Identifying innate immune genes as modifiers of the CF lung phenotype may suggest new avenues for treating the inflammatory consequences of CF airway infection. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERACIDIFICATION AND PSEUDOMONAS INFECTIONS IN CF Principal Investigator & Institution: Deretic, Vojo P.; Professor; Molecular Genetics & Microbiol; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 20-JUN-2002; Project End 31-MAY-2007 Summary: Cystic fibrosis (CF) is the most common inheritable lethal disorder in Caucasians. The main cause of high morbidity and mortality in CF are the recurring Pseudomonas aeruginosa infections and associated inflammation. A clear connection between the genetic lesion in CF and Pseudomonas infection has not been unequivocally established. CF is caused by mutations in the CFTR gene, which encodes a chloride channel that has pleiotropic affects on transport of other ions in epithelial cells. Using a novel pH-sensitive GFP technology, we have recently reported that transGolgi network (TGN) is hyperacidified in CF respiratory epithelial cells. We hypothesize that dysfunction of this main cellular biosynthetic and sorting organelle in leads to defects in CF respiratory cells contributing to the initiation of bacterial infection. We hypothesize that at least one manifestation of the previously unanticipated lower than normal pH in the TGN of CF cells is the well known glycosylation defect including undersialylation of cell surface glycoconjugates which act as receptors for increased Pseudomonas aeruginosa binding. In addition, we have observed that another intracellular organelle, the cellubrevin-labeled recycling endosome, is also hyperacidified in CF respiratory epithelial cells. We hypothesize that the dysfunctional

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recycling endosome in CF may affect various events following bacterial adhesion, such as intoxication of host cells and bacterial uptake and elimination by host cells. In addition, a defective endosomal pathway may result in an overabundance, overstimulation, or defective downregulation of proinflammatory receptors on CF epithelial cells. The aims of this proposal are: 1) To delineate the molecular mechanisms leading to the hyperacidification of TGN and cellubrevin endosomal compartments in CF. 2) To investigate how hyperacidification of TGN in CF affects interactions of respiratory epithelial cells with P. aeruginosa. 3) To investigate how hyperacidification of endosomal compartments in CF influences interactions of respiratory epithelial cells with P. aeruginosa and whether it plays a role in increased inflammation. In addition, as a part of all three aims, we will determine whether normalizing the pH of intracellular compartments in CF corrects interactions with P. aeruginosa and suppress inflammation. These studies are expected to establish a connection between the CFTR defect and infection and inflammation in CF, and provide a basis for development of new chemotherapies using appropriately formulated antacids or inhibitors of pumps and ion channels. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOXIA, HYPEROXIA, AND AIRWAY INFLAMMATION Principal Investigator & Institution: Gerard, Norma P.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (Applicant's Abstract) Prior studies demonstrate the value of targeted deletion of genes encoding molecules believed to be involved in inflammatory reactions. In the absence of potent and selective antagonists, this approach has been useful for dissecting the role of chemokines, anaphylatoxins and neuropeptides in defined models of injury and disease. In this section of the SCOR application the investigators propose four specific aims to extend these studies. In Aim 1, they will test the hypothesis that the inflammation and smooth muscle hyperplasia associated with hypoxia and/or hyperoxia results in increased basal and/or allergic airway responsiveness. They will compare reactions of wild type mice and animals with targeted deletion of genes for inflammatory mediators as a mechanistic approach to determine their role in contributing to hypoxic and hyperoxic airway injury. In Aim 2 they will test the hypothesis that the inflammation and smooth muscle hyperplasia associated with hypoxia and/or hyperoxia alters the animals? ability to clear infections in the lung. Findings will be corroborated by comparison with responses of established gene deleted mouse strains currently under study. In Aim 3 they will test several additional mouse strains in our established models of airway infection and allergic airway hyperresponsiveness. These strains have been identified in preliminary studies as potentially important for lung development and inflammation by other members of the SCOR. Finally, in Aim 4 the investigators will pursue the observation that deletion of the C3a receptor in the mouse affords protection from the development of allergic airway hyperresponsiveness and that at least some asthmatic humans have elevated levels of C3a in bronchoalveolar lavage fluid following antigen challenge compared with nonasthmatic subjects. The investigators hypothesize that airway hyperresponsiveness is a consequence of activating the C3a/C3a receptor signaling pathway. They propose to analyze this signaling pathway using molecular biological and biochemical techniques. They will additionally extend the human studies by examining C3a levels in tracheal aspirates of preterm infants and correlate findings with clinical outcomes. In achieving these aims, they will gain a better appreciation for the inflammatory components

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Pseudomonas

involved in the airway injury associated with newborns and may be able to identify targets for therapy. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IGG SUBCLASS AND FUNCTION OF ANTI-POLYSACCHARIDE ABS Principal Investigator & Institution: Schreiber, John R.; Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-MAY-2006 Summary: (provided by applicant): Anti-polysaccharide (PS) antibodies (Ab) are critical to host defense against encapsulated bacteria. The function of anti-PS Ab includes complement fixation and opsonization of bacteria for killing by phagocytes, and modulation of cytokine producing cells via binding to Fcgamma receptors (FcgammaR). IgG anti-PS Ab response has delayed ontogeny and isotype restriction (IgG3 in mice IgG2 in man), and conjugation of PS to proteins induces class switching to IgG1. Determining the effect of isotype restriction and IgG subclass on function of anti-PS Ab is crucial to better understand immunity to PS-encapsulated bacteria, the pathogenesis of human IgG subclass deficiency and for improved serological correlates of immunity with PS and PS conjugate vaccines. In this proposal, we will continue our studies of the role of IgG subclass in anti-PS Ab effector function, determine the role of constant region genes and the dominant IgG subclass in immunity to encapsulated bacteria and in class switching that occurs when PS are conjugated to proteins, and investigate the effect of lgG subclass on FcyR mediated regulation of cytokine production. We will utilize V region-identical human monoclonal Abs of all four IgG subclasses against P. aeruginosa LPS O-side chain and S. pneumoniae (Pn) capsular PS made in a new transgenic mouse reconstituted with human Ig genes, to determine the mechanism of functional differences in Ab protective efficacy. Next, to determine the in vivo relevance of the dominant IgG subclass made to PS, we will use the new BALB/c IgG3 knockout mouse to determine the importance of anti-PS Ab subclass in the host response to PS, PSprotein conjugates and to infection with encapsulated bacteria. We have found that the absence of IgG3 renders these animals more susceptible to fatal infection with Pn but that induction of anti-PS IgG1 can correct this defect. Finally, we will investigate the FcR mediated regulatory role of IgG subclass in cytokine production by macrophages, and we hypothesize that there are differences in the ability of IgG subclass to modulate cytokine production based on differential binding to FcgammaR. These studies will allow more rational strategies of active and passive immunization against bacteria, improved understanding of IgG subclass deficiency, and new information about which IgG subclass has the best FcgammaR-mediated anti-inflammatory properties. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERCELLULAR SIGNALING IN MYXOCOCCUS XANTHUS Principal Investigator & Institution: Shi, Wenyuan; Professor; Oral Biology/Medicine/Orofacial Pain; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: Myxococcus xanthus cells exhibit coordinated cell movements on a solid surface during vegetative growth and multicellular fruiting body formation. These complex social behaviors make this bacterium an excellent model system for studying intercellular signaling and microbial development. The focus of our research is to

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understand the mechanical and physiological basis of social gliding motility (S-motility) and the chemotactic control of motility during fruiting body formation. During the last grant period, we discovered some important molecular functions of two cell surface appendages that are required for social motility: the type IV pili and fibrils. Based on these findings, we hypothesize that directed motility in M.xanthus involves the control of pilus switching frequency by the frz chemosensory system. We also hypothesize that fibril, a self-generated extracellular matrix material, is a major chemoattractant for M. xanthus and provides an important signal for fruiting body formation in M. xanthus. We propose the following specific aims to test these hypotheses: 1. to obtain direct physical evidence of pilus dependent motility and study its interaction with the frz chemosensory system; 2. to obtain direct visual evidence of fibril-guided chemotactic movement during fruiting body formation; 3. to identify molecular components involved in self-generation of fibril gradient. The studies will help us to understand the molecular mechanisms of social swarming, social hunting, intercellular signaling, and fruiting body formation. It will also provide a molecular understanding of gliding motility and the evolution of bacterial motility/chemotaxis systems. Since the S-motility and aggregation of M. xanthus are very similar to twitching motility and biofilm formation in pathogenic bacteria like Pseudomonas and Neisseria, the studies may also provide clues for further molecular characterization of these events, leading to new treatments against these pathogenic bacteria. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISOLATION AND CHARACTERIZATION MONOOXYGENASE FROM P. PUTIDA

OF

STYRENE

Principal Investigator & Institution: Gassner, George T.; San Francisco State University 1600 Holloway Ave San Francisco, Ca 94132 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: Styrene, isoprene, and 1,3-butadiene are important synthonsin the rubber and plastics industry. They have further utility in the production of epoxides which may be useful in a range of organic syntheses including the production pharmaceuticals. As waste products, these alkenes are released into the environment though natural processes, including the mineralization of plastics and rubbers, and as exhaust gas emissions resulting from the incomplete combustion of fossil fuels. Because of the widespread distributionof these compounds, and their reactivity as alkylating agents, there is growing concernand uncertainty regarding the risks of human exposure. For these reasons, significant research directed toward elucidation of the enzyme mechanisms involved in the processing of alkenes by humans and by microorganisms in the natural environment is warented. We will isolate, clone, express, and mechanistically characterize the two component syrene monoxgenase system from Pseudomonas putida (S12). Studies of the purified enzyme will be designed to elucidate the kinetics and thermodynamics of protein-protein, protein-substrate, and proteincoenzyme interactions as they pertain to the styrene epoxidation reaction. The steady state and pre-steady state kinetics of the oxidative and reductive half reactions will be analyzed by multiple wave length single and double mixing stopped-flow studies. Steps in the reductive half reaction corresponding to NADH-binding, FAD-binding, hydridetransfer, and the dissociation of NAD reduced FAD will be identified. The stereochemistry and deuterium isotope effects associted with hydride transfer will be established. Titrametric methods will be used to determine the redox potential of the bound-FAD and to establishany linkage between binding affinity and reduction state. Substrate analogs including isoprene, butadiene, and deuterated and halogenated

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Pseudomonas

styrenes will be used to probe the structure of the active site the nature of the oxygen reaction. Macroscopic pKa values of active site residuesinvolved in proton-transfer reactions will be established and steps involved in proton uptake or release will be identified. Activation energies associated with transition states in the oxygen and reduction reactions will be estimated by Eyring analysis. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: KERATITIS--ROLE OF THE TIMP-1 Principal Investigator & Institution: Soloway, Paul D.; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 05-FEB-1996; Project End 31-JAN-2003 Summary: Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) is an inhibitor of the 16 matrix metalloproteinases (MMPs) that collectively degrade all extracellular matrix. Mice deficient for TIMP-1 were shown to be hyper-resistant to P. aeruginosa corneal infections by a complement-dependent mechanisms. Long infections were also cleared more effectively and inflammatory responses to three additional stimuli were altered in mutant mice. Furthermore, differences in vascular structure and/or function were observed in mutant animals using four different assays. Vascular changes may underlie the altered responses to infection and inflammation in TIMP- 1-deficient mice. The goal of this proposal is to elucidate the mechanisms underlying the altered response to infection and inflammation in timp-1 mutants. The first two Aims seek to determine which of the two mechanisms used by complement to kill bacteria is required for the phenotype and if complement activity itself is affected by the timp-1 mutation. The third Aim is designed to determine whether TIMP-1 phenotype, and identify the structural changes in the vasculature that have occurred. The fourth Aim seeks to determine if TIMP-1 loss alters sensitivity to ocular inflammation and breakdown of the blood aqueous or blood retinal barriers. Evidence id described demonstrating that the effect of TIMP-1 loss on hyper-resistance to corneal infection is indirect, mediated by one or more MMPs. Aim 5 is designed to identify the key MMP(s) responsible for the mutant phenotype. The fact that hyper-resistance to pulmonary infections is seen in timp-1 mutants may be enormous clinical significance to immunocompromised individuals, or people with cystic fibrosis or pneumonia. Each of these groups is at risk of lifethreatening pulmonary infections. If loss of TIMP-1 facilitates more effective clearance of such infections, perhaps interfering with TIMP-1 function would be of great benefit to these people. A simple genetic experiment proposed in Aim 6 will confirm if this is the case. Im 7 propose to use phage display to identify TIMP-1 antagonists that may have a wide variety of therapeutic uses. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: KINETIC HYPORETINEMIA

STUDY

OF

INFLAMMATION-INDUCED

Principal Investigator & Institution: Rosales, Francisco J.; Nutritional Sciences; Pennsylvania State University-Univ Park 110 Technology Center University Park, Pa 16802 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The long-term objective of this proposal is to examine the consequences of inflammation-induced hyporetinemia on hepatic vitamin A (VA) stores and retinal function. Previously, it has been demonstrated that the synthesis of hepatic retinol-binding protein (RBP) and transthyretin (TTR) are reduced

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during acute inflammation causing a reduction of plasma retinol concentrations (hyporetinemia). The premise of the current study is that hyporetinemia, if prolonged, will impair the distribution of VA between hepatic and non-hepatic tissues. Two studies are proposed. In the first, the distribution and kinetic behavior of plasma retinol will be evaluated using kinetic data and model-based compartmental analysis during acute inflammation. Plasma containing labeled retinol {[3H]retinoI-RBP-TTR} will be injected iv to marginally-VA deficient rats and circulating tracer concentrations will be allowed to reach a terminal slope; then, the system will be perturbed by inducing acute inflammation with lipopolysaccharide from P. aeruginosa, and circulating tracer concentrations will be allowed to reach a new terminal slope. Tracer and tracee data will be collected from plasma, liver, kidneys, eyeballs and remaining carcass. Model-based compartmental analysis using the Simulation, Analysis and Modeling (SAAM) computer program will be used to adjust model parameters to best fit the data. Based on this analysis, hypotheses will be generated to explain the dynamics of pools of retinol among plasma, liver and kidneys, and how alterations in these pools may contribute to decrease retinal VA. in the second study, an animal model of chronic inflammation will be developed with continuous administration of recombinant human intedeukin-6 (rhlL6) to assess the effect of hyporetinemia on retinal function. Marginally-VA deficient rats will receive rhlL6 or saline by means of osmotic pumps for 7 to 14 d. VA concentrations in hepatic and non-hepatic tissues will be determined by HPLC at various times. Retinal function will be examined by means of electroretinography during the first and second weeks of experimentation. This information will help in redefining VA status in the presence of low circulating retinol concentrations during inflammation. In addition, the application of these methods and the development of a model of chronic inflammation will foster research on other micronutrients like iron and zinc that are similarly affected by inflammation. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: KRUPPEL LIKE FACTOR IN P. AERUGINOSA AIRWAY VIRULENCE Principal Investigator & Institution: Saavedra, Milene T.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Of the 2,500 children born every year with cystic fibrosis (CF) in the United States, 80% harbor P. aeruginosa by the time they reach 18 years of age. Recurrent Pseudomonas pulmonary infections are the major cause of morbidity and mortality in these patients. Airway structural damage is induced by excessive neutrophil populations in the airway, releasing large amounts of proteases which impair phagocytic killing of organisms. To date, the repertory of antiinflammatory therapies to limit excessive epithelial cell signaling to inflammatory mediators remains limited and imperfect, which may be partially due to a limited understanding of critical pathways to curb inflammation and their role in the pathogenesis of CF. Evidence suggests that the zinc finger protein, lung kruppel like factor (LKLF), described here for the first time as highly regulated by infection, plays a significant role in the regulation of the airway epithelial cell response to Pseudomonas infection. Based on preliminary data, Dr. Saavedra hypothesizes that a) the transcriptional activator LKLF is cytoprotective in normal airway cells, b) that it suppresses nuclear factor kappa B activation and c) that in cystic fibrosis, overexpression of LKLF is not protective due to alternate apoptotic/death pathway activation. These aims will be studied with an in vitro epithelial cell air liquid interface culture model system and the well characterized Pseudomonas strain PAO1. The

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Pseudomonas

approach will initially utilize functional genomics to define pathways activated by overexpression of this gene utilizing an LKLF plasmid construct. The true focus will be on elucidating gene function with apoptosis assays, luciferase reporter constructs, EMSA experiments and use of various constructs overexpressing genes involved in NFkappaB activation to ascertain target site of LKLF activity along that pathway. These experiments are designed to further understanding of how epithelial cells drive neutrophil recruitment, knowledge of which may contribute to development of new therapeutic interventions in inflammatory airways diseases such as CF. This project will allow Dr. Saavedra to become an independent investigator and expert in the realm of Pseudomonas and airway epithelial cell biology, via a multi-faceted approach of 75% dedicated laboratory time and didactic training with a special focus on mechanisms of microbial pathogenesis. Outside of the laboratory, 25% clinical time will be spent as an instructor in adult Pulmonary and Critical Care Medicine, taking care of both inpatients and outpatients with CF, with the ultimate goal of a closely knit research and clinical niche as a principal investigator and expert adult CF doctor. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF PSEUDOMONAS-MEDIATED EPITHELIAL CELL DAMAGE Principal Investigator & Institution: Engel, Joanne N.; Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-JUN-1998; Project End 31-MAY-2008 Summary: (provided by applicant): Pseudomonas aeruginosa (PA) is one of the most virulent opportunistic pathogens of man. The morbidity of PA infections results from the ability of the bacterium to colonize previously injured or disrupted epithelial cell layers leading to further epithelial cell damage, inhibition of wound healing, and access to other tissues or the blood stream. Our initial work utilized a novel genetic screen to identify new virulence factors of PA required for epithelial cell injury. These studies identified new virulence factors (the type III secretion system and the secreted effector protein ExoU) and also suggested new functions in virulence for previously identified virulence factors (type IV pili). The role of these genes in pathogenesis was validated using assays testing for virulence in the tissue culture system and in a mouse model of acute pneumonia. We discovered that PA can damage epithelial cells and macrophages by at least two type Ill-secretion dependent pathways. The first involves ExoU-mediated necrosis and the second pathway has features of apoptosis. In this competitive renewal we will continue these studies with the long term goals of (i) understanding the complex interplay between the bacterial type III secretion system, its secreted effectors, and the host eukaryotic cell and (ii) elucidating the role of type IV fimbriae as virulence factors in acute infections caused by PA. Our short term goals will focus on (i) the pathways by which ExoT alters the host cell cytoskeleton, (ii) the mechanism of type III secretiondependent apoptosis, (iii) and the role of type IV pill in type III secretion. Specific aim 1. We will test the hypothesis that multiple domains of ExoT contribute to its role in inhibiting bacterial internalization, inducing cytoskeletal changes and cell rounding, and inhibiting wound healing of eukaryotic cells. Specific Aim 2. We will dissect the mechanism by which type III secretion induces apoptotic like death in host cells. Specific Aim 3. We will explore the biological roles of the polarly located type IV pili in virulence. We will test the hypothesis that specific components of type IV pill are required for discrete steps in type Ill-mediated secretion and translocation. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF ENZYME CATALYSIS Principal Investigator & Institution: Dunaway-Mariano, Debra; Associate Professor; Chemistry; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-MAY-2006 Summary: (provided by applicant): The goal of this project is to determine structure, function, and mechanism of action of selected members of the PEP mutase/isocitrate lyase and 4-hydroxybenzoyl-CoA thioesterase enzyme families. This information will be used to relate active site structure to catalysis, and thereby identify markers, which can be applied in the assignment of function to all unknown proteins within each enzyme family. The novel protein functions and metabolic pathways that are anticipated to emerge from these efforts will, along with the active site structure determinations, serve as the foundation for drug discovery. Finally, from the proposed studies the principal investigator and her group will gain insight into the catalytic mechanisms of the enzymes mediating the diverse chemistries represented by the two enzyme families, and into how these catalytic mechanisms evolved from ancestral active site templates. Specific Aims 1-4 will address structure, function and catalytic mechanism in four members of the PEP mutase/ isocitrate lyase enzyme family: phosphonopyruvate hydrolase of Burkholderia cepacia, 5, 1 0-methylenetetrahydrofolate: 3-methyl-2oxobutanoate hydroxymethyl transferase of Pseudomonas aeruginosa, a protein associated with petal death in carnation, and a protein of unknown function present in Mycobacterium tuberculosis (Rv1998c). Specific Aims 5-9 will address structure, function and catalytic mechanism in five members of the 4-hydroxybenzoyl-CoA thioesterase enzyme family: 4-hydroxybenzoyl-CoA thioesterase, the YgbC enzyme of the Haemophilus influenza Tol-pal Pathway, the P76084 unknown protein of the E.coli Phenylacetate Catabolic Pathway, the BH1 997 unknown protein of the Bacillus halodurans Upper Gentisate Pathway and the Pseudomonas aeruginosa PA551 9 homologue to the Human Long Chain Acyl-CoA Thioesterase Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENTORED DEVELOPMENT AWARD

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Sagel, Scott D.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): In children with cystic fibrosis (CF) proteolytic activity causes bronchiectasis, resulting in progressive lung disease and marked shortening of life expectancy. One of the long-term objectives for this proposal is to define proteolytic biomarkers that are predictive of future clinical course and disease progression in children with CF. By identifying those children with excessive and more aggressive proteolytic activity, it may be possible to intervene with anti-proteolytic treatments before irreversible airway damage occurs. The main hypothesis is that CF children with more pronounced proteolytic activity, as measured in induced sputum, would have a greater degree of structural and functional lung damage. This hypothesis will be tested through the following specific aims: 1) to determine changes in proteolytic activity by quantitating levels of neutrophil derived proteases (elastase, matrix metalloproteinase Types 2 and 9), lung antiproteases (alpha1antiprotease, secretory leukoprotease inhibitor, tissue inhibitors of metalloproteinase), and elastin breakdown products (desmosine, isodesmosine) in clinical specimens (induced sputum, urine) from

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Pseudomonas

CF children, during times of clinical stability, annually over three years; and 2) to correlate these changes in proteolytic activity with structural airway damage (assessed by severity and extent of bronchiectasis on annual high resolution computed tomography scans), functional airway impairment (as determined by annual pulmonary function testing), lower airway bacterial colonization status and bacterial burden, and related morbidities (rates of hospitalization, pulmonary exacerbations). These results will be crucial to evaluating emerging antiproteolytic treatments in children with CF. Another objective of this application is to enhance and strengthen Dr. Sagel's approach to clinical investigation and patient-oriented research. Dr. Sagel will receive more formal training and education by completing his Ph.D. degree in the UC's Clinical Science Program. He will take courses in clinical epidemiology, bioethics, clinical trial design, pharmacokinetics, and human genetics, and complete a thesis about proteolytic activity in CF. In addition, he will actively participate and train in the Pediatric GCRC, and frequently interact with his sponsor, mentors, and collaborators. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROBIAL METABOLISMS OF REDUCED PHOSPHOROUS COMPOUNDS Principal Investigator & Institution: Metcalf, William W.; Microbiology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The long-term objective of the proposed research is the identification and molecular, genetic and biochemical characterization of microbial metabolic processes involved in oxidation-reduction reactions of phosphorus compounds. These reactions have been little studied and represent novel aspects of the biochemistry of this important element, which plays a central role in the metabolism of all living organisms. The production and consumption of reduced P compounds are known to occur in many organisms, including humans. The metabolism of these compounds has importance with respect to the natural roles of these compounds in the organisms where they are found, and with respect to the toxicity and environmental persistence of man-made reduced P compounds, which are widely used for industrial, agricultural and military purposes. Further, phosphorus is the limiting nutrient in many ecosystems. Redox reactions of phosphorus may play an important role in the bioavailability and global cycling of this required nutrient. To further our understanding of these processes we have isolated a number of microorganisms that possess novel biochemical pathways involving redox chemistry of P compounds. The experiments proposed here involve identification and characterization of these reactions at the genetic and biochemical levels. The specific goals of these experiments are: 1) purification and characterization by standard biochemical approaches of two novel enzymes involved in a P oxidation pathway in Pseudomonas stutzeri, 2) characterization of the functions and genetic regulation of the 14 genes (at least) involved in this P. stutzeri pathway using mutant analysis and transcriptional reporter gene studies, 3) molecular, genetic, and biochemical characterization of a novel pathway for oxidation of phosphite by Escherichia coli, 4) molecular genetic characterization of a novel pathway for anaerobic hypophosphite oxidation by a new bacterial isolate, and 5) isolation and characterization of organisms that possess other novel metabolic pathways involving P redox reactions. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULAR ENZYMATIC ASSEMBLY LINES FOR ANTIBIOTICS Principal Investigator & Institution: Walsh, Christopher T.; Assistant Professor; Biological Chem & Molecular Pharm; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 30-SEP-1987; Project End 31-DEC-2007 Summary: (provided by applicant): The main objectives of the proposal, detailed in specific aims la-d and 2a-c are to understand the molecular logic of the multimedia assembly lines for the biosynthesis of no ribosomal peptide antibiotics. Nonribosomal peptide synthetase (NRPS) assembly lines to be analyzed include the antibiotics novobiocin and clorobiocin, tyrocidine and gramicidin, the immunosuppressant rapamycin the phytotoxins coronatine and syringomycin from Pseudomonas syringae, and the antitumor drug candidate epothilones. All these medicinally active natural products are built up as acyl chains via initiation, elongation, and termination NRPS modules. This proposal focuses on initiation (specific aim 1a-d) and termination (specific aim 2a-c) module strategies. Specific aim 1 addresses the logic, organization, and catalytic specificity of free standing A-T didomain subunits acting as initiation modules in nontraditional NRP assembly. This includes the early steps that form the bicyclic aminocoumarin scaffold of novobiocin as well as the late stage reactions that generate the 5-methylpyrrolycarboxyl moiety that interacts with the ATP site of the GyrB subunit of DNA gyrase. It also focuses on companion 2 His/Asp- Fe (11)enzymes proposed to be cyclopropanation catalyst (coronamic acid formation) or chlorination catalyst (4chlorothreonine in syringomycin). Specific aim 2 explores the molecular logic for catalytic macrocyclization by the C-terminal domains of NRPS and hybrid polyketide/NRP assembly lines. Aim 2a deals with the range of macrolactamization by the Thioesterase (TE) domain excised from the tyrocidine syntherase assembly line, while aim 2b analyzes the cognate TE at the end of the EpoF subunit of the polyketide synthase for the 16 membered epothilone macrolide. Specific aim 2c examines the hybrid PK/NRP assembly line for rapamycin where the most C terminal domain in the RapP subunit is a Condensation (C) domain, not a TE domain, yet is thought to form the 34-membered macrolactone ring in both rapamycin and the cognate FK506 immunosuppressants. Deciphering the molecular logic of both chain initiation and chain termination strategies may facilitate subsequent efforts directed at reprogramming the initiation and termination machinery to make novel variants with altered and improved therapeutic activities. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION OF CELL SIGNALING BY PSEUDOMONAS EXOENZYME S Principal Investigator & Institution: Olson, Joan C.; Associate Professor; Pathology and Lab Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-JAN-2003 Summary: (Adapted from the Applicant's Abstract): Exoenzyme S (ExoS) is an ADPribosylating toxin produced by the opportunistic pathogen Pseudomonas aeruginosa which requires direct contact between the bacterium for translocation into the host cell. Once within the target cell, ExoS causes complex effects on cellular processes resulting in inhibition of DNA synthesis and alterations in the cytoskeleton affecting cell structure, movement, microvilli and focal adhesion turnover. Studies from the PI's laboratory have led to the development of a bacterial-eukaryotic cell co-culture system

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Pseudomonas

which allowed the toxic effects of ExoS to be identified. This system was also used to provide insight into the cellular mechanism of action of ExoS by identifying Ras as an in vivo target of ExoS ADP-ribosyltransferase (ADPRT) activity. The complex effects of ExoS on cellular function can to some extent be explained by its multi-domain structure. Current data support the possibility that ExoS can cause transient alterations in cytoskeletal structure via non-ADPRT mechanism which is then coordinated with the ADP-ribosylation of specific cellular proteins leading to long-term alterations in cytoskeletal structure and inhibition of DNA synthesis. The cellular mechanism for the diverse affects of ExoS on cell function, however, remains unknown, and may relate to the ADP-ribosylation of cellular Ras, which plays an integral role in multiple signal transduction pathways, the ADP-ribosylation of other cellular proteins, or to indirect effects of ExoS on proteins linked to the cytoskeleton. The goal of this proposal is to identify cellular processes and signaling pathways affected by ExoS following bacterial translocation. The purpose of the first specific aim is to gain further understanding of cellular proteins directly affected by ExoS by examining the in vivo substrate specificity of ExoS ADPRT activity. The second aim focuses on Ras, examining how ADPribosylation of Ras by ExoS affects Ras mediated cell signaling events. The third aim examines the cellular mechanism of ExoS associated alteration in cytoskeletal structure, focusing on both enzymatic and non-enzymatic effects of ExoS on Rho, Rac, and Cdc42, which function in the regulation of cytoskeletal structure, the combined picture will provide insight into how ExoS influences cellular signaling, and in turn, the role of ExoS in Pseudomonas pathogenesis. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISM OF HMG COA REDUCTASE Principal Investigator & Institution: Stauffacher, Cynthia V.; Professor of Biological Sciences; Biological Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-MAR-2004 Summary: Our laboratory is pursuing a multi-faceted research projects to understand the molecular mechanism of the enzyme 3-hydroxyl-3- methylglutaryl co-enzyme A (HMG-CoA) reductase by a combination of biophysical and X-ray crystallographic methods. From the 2.8A structure of the Pseudomonas mevalonii enzyme and a number of binary and ternary complexes with substrates, we have outlined a catalytic mechanism which we believe applies to all members of this class of enzymes. We now propose to investigate the mechanistic proposal with a combination of crystallographic and kinetic measures, with the goal of trapping structurally significant intermediates in the catalytic reaction, and will extend these studies to the HMG-CoA reductases of a number of different species. We will also begin to investigate the structural basis of the modulation of activity in HMG-CoA reductase by reversible phosphorylation in the mammalian enzymes, while attempting to crystallize one of the mammalian reductases. Finally, we intend to begin investigations of species specific differences in the active sites of HMG-CoA reductases from bacteria, archeabacter and eukaryotes which may lead to the development of species-selective inhibitors for this enzyme. The specific aims of this proposal are to: 1) Complete the crystallographic studies of the enzyme-substrate complexes involved in the molecular mechanism of Pseudomonas mevalonii HMG-CoA reductase. 2) Use steady-state and fast reaction kinetics with possible suicide inhibitors to identify and characterize intermediates produced during the Pseudomonas HMGCoA reductase reaction which can be examined by X- ray crystallographic techniques, and to extend these studies to the Sulfolobus and Syrian hamster enzymes. 3)

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Investigate the basis of phosphorylation control of HMG-CoA reductase with X-ray crystallographic studies of an engineered Pseudomonas enzyme. 4) Express, purify, characterize and crystallize representative HMG-CoA reductases from the Class I and Class II enzymes in order to examine how the observed differences in their biological and biochemical properties are expressed in their structures. 5) Use the crystallographic structures for these enzymes to identify differences that could be exploited to design species/specific inhibitors for HMG-CoA reductase. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATORS

P.

AERUGINOSA

BIOFILM-SPECIFIC

PROTEINS

AND

Principal Investigator & Institution: Sauer, Karin; Assistant Professor; Biological Sciences; State University New York Binghamton Vestal Pky E Binghamton, Ny 13901 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Cystic fibrosis (CF) is one of the most common lethal genetic diseases among people of European descent, affecting 30,000 individuals in the United States. It is believed that chronic CF lung infections are caused by surfaceassociated, antimicrobial-resistant communities of microorganisms called biofilms with Pseudomonas aeruginosa being one of the principal pathogens. Current treatment strategies for CF infections, including frequent antibiotic treatment and chest physiotherapy, fail to clear these infections and biofilm bacteria persist in the lung despite intact host immune defenses. Recently, it has been suggested that therapeutic strategies directed towards biofilms may be successful in treating CF lung infections. Our research goal proposed herein is designed to elucidate the nature and identity of proteins that are unique to the biofilm mode of growth for the development of therapeutic strategies directed towards biofilms. Previous work in our laboratories has demonstrated that P. aeruginosa PAO1 undergoes a major shift in its cellular protein profile during biofilm development. This shift is most profound in biofilms grown for 3 and 6 days (maturation-I and maturation-II stage, respectively). We hypothesize that we will identify biofilm-specific proteins - important regulatory, virulence and resistance proteins - that are unique to the maturation-I and maturation-II biofilm stages. We expect that many of the biofilm-specific proteins are post-translational modified and have regulatory functions involved in signal transduction. Our goal will be accomplished by utilizing two-dimensional gel electrophoresis (2D/PAGE) combined with 2D-image analysis and protein identification. Biofilm-specific proteins will be identified by peptide mass fingerprinting using Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF MS). Upon protein identification, functional proteomics will be used to provide an insight in signal transduction cascades: phosphorylated proteins will be immunoprecipitated and separated by 2D/PAGE. Comparative 2D-image analysis will reveal proteins that are uniquely phosphorylated in the protein patterns of biofilms grown to the maturation-I and -II biofilm stages. Uniquely phosphorylated, biofilm-specific proteins will then be analyzed by peptide mass fingerprinting and MALDI-ToF MS. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOTODYNAMIC THERAPY OF LOCALIZED INFECTIONS Principal Investigator & Institution: Hamblin, Michael R.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2006

42

Pseudomonas

Summary: (provided by applicant): The overall goal of this proposal is to explore a novel photochemical method for killing antibiotic resistant pathogenic bacteria in localized models of infection. Photodynamic therapy (PDT) employs a non-toxic dye termed a photosensitizer (PS) and low intensity visible light, which in the presence of oxygen produce cytotoxic species. PDT has the advantage of dual selectivity in that the PS can be targeted to its destination cell or tissue, and in addition the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but until now this has not been accomplished in animal models of infection. We have developed a novel method of targeting PS conjugates to both Gram (+) and Gram (-) pathogenic bacteria that can produce up to 6 logs of killing in vitro, while in vivo it increases the selectivity of the treatment for bacteria while sparing host tissue. This is based on the covalent attachment of the PS chlorin e6 to polycationic delivery vehicles such as poly-L-lysine, that increases the selective binding to bacteria and enables the PS to penetrate the cell walls of Gram (-) bacteria to gain access to sensitive intracellular sites. Multi-antibiotic resistant strains are as easily killed as wildtype strains. We have generated preliminary data using luminescent bacteria and a lowlight imaging camera, that PDT will kill both Gram (-) species (Escherichia coli and Pseudomonas aeruginosa) and Gram (+) species Staphylococcus aureus) in vivo in animal models of both early and established infections. In the case of the invasive P. aeruginosa mice are cured of an otherwise fatal infection. Localized PDT may have an additional advantage in that it is also possible to inactivate secreted extracellular virulence factors that pathogenic bacteria use to establish infections and invade tissue. This project will seek to explore the determinants of PDT for localized infections. Four specific aims will focus on optimizing the treatment in different mouse models of early, acute and chronic infections, comprising excisional wounds, established soft tissue infection, chronic abscesses, burns and urinary tract infections. Since one of the advantages of PDT is its rapidity compared to traditional antibiotic therapy, we will also study the use of PDT to quickly reduce the bacterial burden in the infection, followed by antibiotics to eliminate the residual bacteria. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT -- MOLECULAR MECHANISMS OF MERCURY INDUCED IMMUNOTOXICITY Principal Investigator & Institution: Reddy, Gopal; Tuskegee University Tuskegee Institute, Al 36088 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-MAY-2008 Summary: Deleterious effects of environmental toxicants such as mercury affect the poor and minorities first and most dramatically. Mercury levels in the environment have been rising 2-5 fold over the last century and 1.5% per year since 1970. Environmental Protection Agency (EPA) lists mercury as a hazardous air pollutant under Title Ill of the federal Clean Air Act. The main goal of the proposed five year project is to further delineate the molecular mechanisms involved in mercury-induced immunotoxicity. Exposure to mercury even at low levels may cause subtle immune system alterations which may indirectly affect ability to resist microbial infections or development of cancers. Mercury may have a devastating effect on the immune system of the neonatal child, but this aspect has not been well studied. Previous studies have shown that mercury may induce autoimmunity, especially in Brown-Norway (BN) rats or in some cases immunosuppression. In the proposed project, we will study the effects of methylmercury chloride (CH3HgCI) using both BN and Sprague-Dawley (SD) rats. We will also study the effects of CH3HgCI on the neonatal immune system in weanling

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43

pups by exposing pregnant and lactating rats of both BN and SD strains. Using DNA microarray technology, we will study the changes in cytokine gene expression in lymphoid cells exposed to CH3HgCI in vitro or in vivo as compared to control cells. Based on the results, we will study in-depth, the status of some important Th1 and Th2 cytokines. We will employ both realtime quantitative RT-PCR, ribonuclease protection assay (RPA) and ELISA. These different assays targeting the Th1/Th2 cell responses are expected to give us detailed information on the expression of the cytokines at the level of both transcription and protein production. We will study the control and mercuryexposed immune cells of adult and neonatal rats for activation markers, CD25 (IL-2R alpha) and MHC class II antigens and serum samples for antinuclear antibody, Creactive protein and circulating immune complexes. To study whether mercury-induced alterations of the immune responses adversely affect host disease resistance mechanisms in vivo, we will experimentally infect the weanling rats with Pseudomonas aeruginosa and study the morbidity and mortality. Comparison of the data obtained using adult and neonatal BN rats which are susceptible to mercury-induced autoimmune-like disease with that of SD rats and correlation of cytokine profiles with the expression of markers for activation and autoimmune disease as well as resistance to infection, will help us further delineate the molecular mechanisms involved in mercury-induced immunotoxicity. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PLANT VIRULENCE TARGETS OF BACTERIAL EFFECTORS Principal Investigator & Institution: Chisholm, Stephen T.; Plant and Microbial Biology; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Phytopathogenic bacteria such as Pseudomonas syringae pv. tomato deliver effector proteins to plant cells in order to modify the activities of the host to favor bacterial colonization. Plants produce specific immune receptors (R proteins) that recognize the presence of bacterial effectors and subsequently initiate plant disease resistance responses. An emerging paradigm in plant resistance to bacteria is that R proteins recognize modulation of host proteins by effectors and initiate resistance responses following perturbation of these host targets. A putative virulence target of the P. syringae effector AvrRpt2 has been identified. Expression of AvrRpt2, a cysteine protease, in Arabidopsis plants results in the degradation of host RIN4 protein. Degradation of RIN4 correlates with initiation of resistance responses elicited by AvrRpt2. The purpose of the proposed research is to determine whether AvrRpt2 directly degrades RIN4, to identify proteins associated with RIN4 and to establish how AvrRpt2-mediated degradation of RIN4 triggers resistance. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PORPHYRIN AND CORRINOID BIOSYNTHESIS Principal Investigator & Institution: Scott, Alastair I.; Distinguished Professor Of; Chemistry; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-JUN-1982; Project End 31-JAN-2004 Summary: Using a combination of organic chemistry, molecular biology, enzymology, and NMR spectroscopy the details of the biosynthesis of uroporphyrinogen III (the precursor of heme and chlorophyll) and its subsequent transformation to vitamin B12, the anti-perinicious anemia factor, will be elucidated. Knowledge of the pathway including control mechanisms and genetic mapping will define intermediates important

44

Pseudomonas

in diseases such as B12 deficiency and acute intermittent porphyria. All of the biosynthetic enzymes necessary for the formation of cobyrinic acid, the simplest B12 analog, will be over-expressed using the sequenced cbi genes of Salmonella typhimurium and the cob genes of Pseudomonas denitrificans and their mechanisms studies by NMR spectroscopy ia 13C- labeling. Finally, the multi-enzyme synthesis of advanced intermediates and of B12 itself will be addressed. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF BIOFILMS IN MEDICAL DEVICES Principal Investigator & Institution: Shenoy, Bhami C.; Altus Biologics, Inc. 625 Putnam Ave Cambridge, Ma 021394807 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. We found that cross-linked enzyme crystals (CLECs) show remarkable stability at various pHs, on storage, against proteolysis and organic solvents. These properties make them ideal for treatment against biofilm formation on medical devices /implants such as urethral catheters, ureteric and prostatic stents, penile and testicular implants, artificial urinary sphincters, prostheses for hip and knee replacements, shunts for hydrocephalus, vascular grafts, heart valves, vascular access devices, voice prostheses, etc. In addition, the CLECS can be used for the prevention of blood clot formation, for example, in venous catheters. The CLEC agent will be used to coat the medical devices for the prevention of formation of bacterial biofilms on these devices as well as the prevention of blood clots. The biofilms form on the above medical devices by colonization of bacteria embedded in a matrix, which become resistant to commonly used antibiotics. In this Phase I study, we propose to develop two prototypes of CLECs of enzyme - Serratiopeptidase and Streptokinase for prevention of biofilms by Pseudomonas aeruginosa and Staphylococcus aureus microorganisms. The coating will prevent the adherence of these bacteria to medical devices. Currently, there are more than 850,000 case infections associated with aid devices annually in the United States. These may be associated with as many as 100,000 deaths per year. The CLECs of Serratiopeptidase and Streptokinase have enormous commercial potential over the currently available treatment for the prevention of contamination of medical devices by minimizing the need for replacement once they are implanted. The CLECs of Serratiopeptidase and Streptokinase will also be important in preventing biofilm-related infections which are resistant to commercially available antibiotics. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PROTECTIVE EFFECTS OF ANTI-C5A IN SEPSIS Principal Investigator & Institution: Ward, Peter A.; Godfrey D. Stobbe Professor and Chairman; Pathology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-MAY-2006 Summary: (provided by applicant): On the basis of our studies to date using the experimental model of sepsis induced by cecal ligation/puncture (CLP) in rats, serious impairment of innate immunity develops. This results in what appears to be a C5adependent defect in assembly of NADPH oxidase and defective phagocytic function of neutrophils. These defects can be reproduced by in vitro exposure of neutrophils to concentrations of C5a found in sepsis. In the first aim, we will evaluate how in vitro

Studies

45

exposure of neutrophils to C5a results in detective signaling pathways: phorbol 12myristate 13-acetate (PMA)-induced activation of phosphokinase C (PKC) which results in assembly of NADPH oxidase; and cell activation by engagement of FcyRs resulting in phagocytic responses. In the second aim, we will evaluate the same signaling pathways in blood neutrophils from CLP animals and determine if treatment with anti-C5a prevents defective signaling. In the third aim, we will determine if treatment of normal rats and mice and CLP rats and mice with anti-C5a compromises innate immunity, as assessed by bacterial clearance (Pseudomonas sp. and Klebsiella sp.) from lungs and evaluate the effects on survival. In the fourth aim, we will employ microarray analysis in CLP rats to define, as a function of time, alterations in global gene expression in organs that are predisposed to injury during sepsis (liver, lungs, kidneys, thymus) and determine if treatment with anti-C5a prevents this pattern of gene expression. It is possible that microarrary analysis will be predictive of organ susceptibility to damage during sepsis. Collectively, these studies should provide important evidence related to the mechanisms by which complement activation during sepsis impairs innate immunity. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOLYTIC ENZYMES AND INHIBITORS IN LUNG DISEASE Principal Investigator & Institution: Travis, James; Professor; Biochem and Molecular Biology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-JAN-1982; Project End 31-MAR-2006 Summary: (provided by applicant): Host proteolytic enzymes are believed to play a central role in the pathogenesis of pulmonary emphysema, through degradation of alveolar connective tissue proteins. However, little is known about whether this lung disease can be either caused or exacerbated by proteinases secreted by bacterial or fungal respiratory pathogens. Significantly, none of these enzymes are known to be regulated by host proteinase inhibitors. While it is believed that their primary function is to degrade host proteins to provide nutrients for the growth and proliferation of the invading organism, we propose that they also provide a means for evasion of host defense. For these reasons, the specific aims of this project are as follows: 1) to isolate and characterize selected proteinases secreted by lung pathogens, including Aspergillus fuimigatus, Stachybotrys chartarum, Pseudomonas aeruginosa, and Staphylococcus aureus, 2) to investigate the effect of pathogen-derived proteinases on the degradation/inactivation of host bactericidal peptides and proteins utilized to maintain homeostasis within the lung, and 3) to study the effect of exposure to these proteinases on a) the responsiveness of human monocytes and neutrophils to major pro-and antiinflammatory stimulation and b) the ability of proteinase-exposed monocytes to clear apoptotic neutrophils. Our long-term goals are to determine whether the proteinases to be investigated play major roles in host defense evasion and tissue destruction within the lung. If this is the case, then they might be considered as targets for the development of inhibitors in order to control or eradicate lung microbial infections. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PSEUDOMONAS' EFFECTS ON THE GUT BARRIER FROM SURGERY Principal Investigator & Institution: Alverdy, John C.; Professor of Surgery; Surgery; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005

46

Pseudomonas

Summary: The mere presence of Pseudomonas aeruginosa in the intestine of critically ill surgical patients is associated with a 70% mortality rate--a 3 fold increase above matched patients who culture negative for this pathogen. We propose that within the intestinal tract of a surgically stressed host, physical and chemical environmental signals cause critical shifts in the virulence phenotype of P. aeruginosa. These effects result in a change in the behavior of intestinal P. aeruginosa, causing this bacteria, upon proper cue, to shift from an indolent colonizer to a life-threatening pathogen. In this proposal we provide strong evidence that a virulence determinant in P. aeruginosa, the PA-I lectin/adhesin, plays a key role in lethal gut- derived sepsis in a surgically stressed host. The hypotheses to be tested in this project are: 1) the PA-I lectin of P. aeruginosa is expressed in vivo in response to environmental cues in the intestinal tract including pH, redox state, and norepinephrine following surgical stress (hepatectomy) 2) the PA-I lectin of P.aeruginosa induces an epithelial permeability defect at the level of the intercellular tight junction resulting in paracellular transport of its lethal cytotoxins, and 3) the PA-I lectin of P. aeruginosa alters epithelial tight junctional permeability by activation of regulatory molecules involved in the expression of occludin, the rate limiting seal of the paracellular pathway. We will test these hypotheses using a novel mouse model of endogenous P. aeruginosa sepsis and cultured intestinal epithelial cells that we have extensively studied. Our specific aims to test these hypotheses are: 1) Determine the expression, location, and function of PA-I in P. aeruginosa harvested from different tissue sites in mice following surgical stress (hepatectomy) and cecal injection of live P. aeruginosa and following in vitro manipulation of the its physical microenvironment (pH, redox, osmolality, norepinephrine). 2) Determine the route of transport of the P. aeruginosa cytotoxins, exotoxin A and elastase, across cultured intestinal epithelial cells (Caco-2) in response to purified PA-I and selected mutants of live P. aeurginosa. 3) Explore potential cellular mechanisms of PA-I-induced decreases in intestinal epithelial barrier function. We propose that we should rethink our understanding of the gut theory of sepsis to include mechanisms by which pathogenic bacteria alter their virulence strategies in response to stressful changes in their local environment. Understanding the virulence determinants and cellular mechanisms that pathogens use to adhere to and modify the intestinal epithelial barrier may lead to therapies which can avoid nosocomial infection at a more proximate point in the care of the critically ill. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PULMONARY BENEFITS OF CYSTIC FIBROSIS NEONATAL SCREENING Principal Investigator & Institution: Farrell, Philip M.; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-1985; Project End 31-MAR-2006 Summary: Although cystic fibrosis (CF) is the most common, life-threatening autosomal recessive genetic disorder of the white population, there are often delays in diagnosis and hence initiation of treatment. Advances of the past two decades have made CF screening feasible using routinely collected neonatal blood specimens and determining trypsinogen levels and CF mutations by DNA analyses. Our overall goal is to address the following hypothesis: Early diagnosis of CF through neonatal screening will be medically beneficial without major risks. "Medically beneficial" refers to better nutritional and/or pulmonary status, whereas "risks" include laboratory errors, potential iatrogenic medical sequelae, miscommunication or misunderstanding and adverse psychosocial consequences. Specific aims include assessment of the benefits,

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47

risks, costs, quality of life, and cognitive function associated with CF neonatal screening and delineation of the characteristic epidemiologic features of CF. A comprehensive, randomized clinical trial emphasizing early diagnosis as the key variable has been underway since 1985. Nutritional status has been assessed by anthropometric and biochemical methods, and the results have demonstrated significant benefits in the screened group. Answering the important questions about pulmonary outcome will require five more years of follow-up evaluation focused on lung function measures and quantitative chest radiology, including high resolution computerized tomography. If the questions underlying this study are answered favorably, it is likely that neonatal screening using a combination of trypsinogen and DNA tests will become the routine method for identifying new cases of CF and that diagnosis in early infancy will allow prevention of many clinically-significant problems such as malnutrition. If CF neonatal screening is implemented nationally, however, several epidemiologic gaps must be closed, and this will require more precise data on the course of this disease and determination of risk factors for pulmonary infections with Pseudomonas aeruginosa. This project will generate that important information, as well as essential data on the quality of life and cognitive function of children with CF who experience early or delayed diagnosis. We will also clarify the risks of screening and delineate for the first time the costs of diagnosis and treatment of CF throughout childhood as well as the cost-effectiveness of screening. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECOMBINOGENIC ENGINEERING OF PATHOGENIC BACTERIA Principal Investigator & Institution: Murphy, Kenan C.; Molecular Genetics & Microbiol; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (Provided by applicant): Gene deletion and/or replacement is the single most important tool for definitively identifying critical functions of infectivity and virulence in pathogenic bacteria. Yet the tools available to make such gene replacements in pathogenic bacteria have, for the most part, remained unchanged for the last 10 years. While genome sequencing projects continue to increase the number of open reading frames available for genetic analysis, gene knock-out technology in many bacterial systems remains technically cumbersome, and in some cases, unfeasible. This project is designed to explore a novel methodology for the enhancement of gene replacement in pathogenic bacteria. The Red recombination system from bacteriophage lambda, when expressed in Escherichia coli, generates a hyper-recombinogenic phenotype whereby gene replacement occurs at an extremely high efficiency following transformation with small (2-3 kb) linear DNA substrates. This gene replacement scheme is unique in that plasmid-chromosome co-integrants do not have to be formed (or resolved), and prior cloning of the gene of interest is not required. PCR-generated substrates with as little as 40 bp of flanking homology are substrates for efficient Red-mediated gene replacement. The recombination intermediates generated by lambda Red are channeled into the host recombination pathway. It is this "jump start" in the initiation of recombination that likely plays a key role in the generation of the hyper-rec phenotype of lambda Redcontaining E. coli. Since most bacteria contain homologs of many of the recombination functions described in E. coli (e.g., recA, recBCD, ruvAB), Red will likely serve to generate the same hyper-rec phenotype when expressed in other (pathogenic) strains of bacteria. This proposal is a test of this hypothesis. This project is designed to generate hyper-recombinogenic strains of Pseudomonas aeruginosa and Mycobacterium

48

Pseudomonas

tuberculosis by expression of red and phage anti-RecBCD functions in vivo from plasmids, or by replacing the chromosomal recBCD genes with a red-expressing operon. The system can be set up so that the hyper-rec phenotype is transient, resulting in pathogens that are altered only within the gene of interest. This project has the potential to revolutionize the methods of genetic manipulation in microorganisms, leading to faster identification of virulence genes, greater flexibility in the genetic analysis of these genes, and the speedy generation of bacterial mutants for vaccine development. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF PROINFLAMMATORY SIGNALING PATHWAYS BY CFTR Principal Investigator & Institution: Pollard, Harvey B.; Chair; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 15-JUN-1998; Project End 31-JAN-2005 Summary: (provided by applicant): The principal goal of this proposal is to identify the intracellular signaling pathways in the lung that mediate the chronic processes of inflammation and infection associated with cystic fibrosis (CF). Preliminary data indicate that airway epithelial cell lines derived from CF trachea secrete massive levels of pro-inflammatory IL8. Consistently, gene therapy with CFTR, or drug therapy with CPX, suppresses baseline levels of IL8 secretion, while still allowing physiological IL8 secretion in response to the presence of bacteria. In normal epithelial cells, IL8 secretion is mediated by activation of the NFkB pathway, and pharmacogenomic studies indicate that a subset of NFkB pathway genes parallel the secretion of IL8 as a function of CFTR, CPX and exposure to P. aeruginosa. We have therefore hypothesized that the mechanism by which CFTR suppresses IL8 secretion from CF epithelial cells is by direct action on a pro-inflammatory intracellular signaling pathway. We wish to identify and study this pathway, and propose the following Specific Aims. Aim #1: To determine the signaling pathways by which CFTR and CPX suppress IL8 secretion from CF epithelial cells. We will use cDNA microarrays to identify genes whose expression is altered by CFTR, or by the presence of CPX. Aim #2: To identify the molecular mechanisms by which CFTR or CPX permit CF epithelial cells to respond physiologically to the presence of Pseudomonas aeruginosa. We will identify cis-acting elements within the IL8 promoter which mediate activation or suppression by CFTR, CPX and P. aeruginosa. Aim #3: To identify subdomains in CFTR that suppress IL8 secretion from CF epithelial cells. We will prepare viral vector constructs expressing CFTR from which different subdomains have been deleted, and identify the CFTR domain(s) required for suppression of IL8 secretion. Expectations, Innovation and Impact: Our expectations are that this research will generate valuable new knowledge that will be useful for the development of novel therapies for CF. The proposed hypothesis-driven research is innovative because biochemistry and hypothesis-driven pharmacogenomics have not previously been used in this way to investigate a single gene disease such as cystic fibrosis. The impact of this research will be to identify novel pathways by which CFTR affects the ability of lung epithelial cells to respond to bacterial assault. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF PS. AERUGINOSA VIRULENCE FACTORS BY ALGR Principal Investigator & Institution: Schurr, Michael J.; Assistant Professor; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112

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Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Pseudomonas aeruginosa is ubiquitous, opportunistic pathogen that primarily infects immune-compromised individuals, including AIDS and transplant patients, severe burn patients, and those with cystic fibrosis (CF). In the context of CF, P. aeruginosa establishes a chronic condition whose morbidity and mortality results from lung damage. Due to the uncanny antibiotic resistance, CF patients infected with Pseudomonas often have chronic infections with limited therapeutic options. Therefore, for improved efficacy in treatment, a basic understanding of the pathogenic mechanisms utilized by this organism needs to be examined as possible therapeutic targets. While a majority of previous studies have focused on the initial stages of colonization and infection, we propose a new approach in searching for treatments. Mounting evidence indicates that microaerophilic metabolism and a biofilm mode of growth may be involved in P. aeruginosa pathogenesis; however, explanations for a mechanism have yet to be discussed. One virulence factor produced by P. aeruginosa under these growth conditions is HCN. Micromolar amounts of HCN inhibit the respiratory electron transport chain and several metalloenzymes (e.g., catalase, peroxidase, superoxide dismutase) of eukaryotic cells. We have discovered that AlgR, a regulator of the virulence factor, alginate, also activates HCN production in mucoid P. aeruginosa. Using the Pseudomonas Affymetrix GeneChip and S1 nuclease protection assays, we demonstrate that AlgR is controlling hcnA, encoding hydrogen cyanide synthase. Moreover, direct measurement of HCN production revealed that mucoid P. aeruginosa produce up to 2.5 mM of HCN in 4 h. Our preliminary data indicate two new roles for AlgR: i) AlgR controls HCN production and ii) AlgR is able to switch from a repressor in nonmcoid P. aeruginosa to an activator in mucoid bacteria on the hcnA promoter. Additionally, we demonstrate that AlgZ/FimS is playing a role in this process. The hypothesis to be tested is: AlgR activates HCN production in mucoid P. aeruginosa. We will test this hypothesis with four specific aims: i) we will determine the requirements for AlgR protein-DNA interaction within the hcnA promoter; ii) we will determine if phosphorylation is required for AlgR activation of hcnA expression in mucoid P. aeruginosa; iii) we will determine the amount of HCN production and hcnA expression within biofilms, and; iv) we will determine the effect of HCN production on lung epithelial and human neutrophil cells in vitro. Thus, at the end of our proposed studies, we hope to elucidate new possible therapeutic target as well as gaining a better understanding of Pseudomonas biology and pathogenesis. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION INFLAMMATION

OF

PSEUDOMONAS

INDUCED

LUNG

Principal Investigator & Institution: Wilson, Christopher B.; Professor and Chair; Immunology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: The mechanisms by which lung inflammation is initiated and perpetuated in response to infection are incompletely understood. Pro-inflammatory cytokines, chemokines and adhesion molecules contribute, as do alveolar macrophages and respiratory epithelial cells which produce them, but their relative importance may differ depending on the host and the nature of the infection. In patients with cystic fibrosis (CF), lung inflammation commonly develops in early infancy and then progresses, particularly following acquisition of infection with Pseudomonas aeruginosa. How the defect in CHR expression results in the intense and progressive lung inflammatory

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Pseudomonas

response and predisposition to refractory infection with P. aeruginosa is unclear. This lack of understanding parallels a paucity of information regarding the role which the respiratory epithelium plays in the regulation of lung inflammation in general. This reflects the absence heretofore of a selective and robust approach by which to test the contribution of the respiratory epithelium. Similarly, an important role for TNF in lung inflammation in response to infection with P. aeruginosa and in CF has been proposed based on correlative human data and results in some rodent models, but the latter studies have yielded contradictory results. This proposal addresses the general hypothesis that TNF acts in concert with the respiratory epithelium to regulate lung inflammation and innate immunity to Pseudomonas aeruginosa, and that aberrant regulation leads to excess lung inflammation in CF. Aim 1) Explore the basis for the increased early lung inflammatory response to P. aeruginosa in TNF receptor-deficient mice. Hypothesis: The selective early increase in neutrophil recruitment and bacterial clearance following acute aerosol infection with P. aeruginosa will be due to an altered inflammatory response by lung parenchymal cells; this will reflect, at least in part, altered expression by these cells of microbial pattern recognition receptors that transduce inflammatory signals in response to P. aeruginosa. Aim 2) Explore the role of the airway epithelium in the pulmonary inflammatory response to P. aeruginosa using mice in which NF-kappaB activation is blocked selectively and in a cell-autonomous fashion in the airway epithelium. Hypothesis: The airway epithelium will play an important role in initiating acute lung inflammation in response to P. aeruginosa. Aim 3) Determine the degree to which lung inflammation is increased in the lungs of CFTR knockout mice, and if so, if this is intrinsic to the lung and due in part to aberrant activation of NF-kappaB in the airway epithelium. Hypothesis: CFTR KO mice will have excessive lung inflammation. This will reflect a process intrinsic to the lung and will parallel and be dependent, at least in part, on NF-kappaB activation in the airway epithelium. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF A NEW SIGNAL MOLECULE IN P. AERUGINOSA VIRULENCE Principal Investigator & Institution: Pesci, Everett C.; Assistant Professor; Microbiology and Immunology; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-MAY-2005 Summary: Pseudomonas aeruginosa is the most prevalent Gram negative bacteria found in patient with hospital-acquired infections and produces a high mortality rate in both immunocompromised and cystic fibrosis patients. This opportunistic pathogen produces an arsenal of virulence factors, some of which are controlled by the cell density monitoring mechanism as quorum sensing. Quorum sensing involves a signal molecule, the autoinducer, that builds in concentration with bacterial density until a threshold concentration is reached where it binds and activates a transcriptional activator protein. P. aeruginosa uses two quorum sensing systems, las and rhl, to control numerous virulence factors (including LasB elastase) through two primary autoinducers, 3-oxoC12-HSL and C4-HSL. Recently a third inducer molecule designated as the Pseudomonas Quinolone Signal (PQS) was discovered. Preliminary results show that PQS is regulated by the las quorum sensing system and that it requires at least Rh1R to inducer lasB. To elucidate the PQS synthetic pathway, g3enes characterize factors controlling PQS expression. To elucidate pathway, genes responsible for anthranilate (a PQS precursor) synthesis will be studied, and a phenotypic, and a phenotypic screen based on LasB production will be used to clone other genes responsible for PQS

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production. To define the role of PQS in P. aeruginosa virulence, reporter gene fusions will be used to determine how PQS affects the expression of different virulence genes. Finally, to study PQS expression, or PQS bioassay will be used to monitor its production under various conditions. The long term goal of this proposal is to determine the role of PQS in the pathogenesis of P. aeruginosa infections with the hope it will lead to new and effective therapies against aeruginosa. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF LYSOZYME IN AIRWAYS HOST DEFENSE Principal Investigator & Institution: Akinbi, Henry T.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Lysozyme is a cationic protein of 146 amino acid residues (Mr approximately 14k) that is bactericidal against multiple gram-positive bacteria in vitro. Although lysozyme is the most abundant antimicrobial protein in airway surface fluid (ASL), its role in protecting the airways against infection, chronic colonization, and inflammation in vivo remains unproven. The results of preliminary studies reported in this application demonstrate a dose-dependent relationship between the level of lysozyme activity in bronchoalveolar lavage fluid and the rate of bacterial killing, of both gram positive and negative organisms, in acutely infected transgenic mice that overexpress lysozyme. Studies proposed in this application will test the central hypothesis that lysozyme is a critical component of airway host defense in vivo. Pathogen killing will be assessed in lysozyme (-/-) mice and lysozyme overexpressing mice following acute and chronic lung infection. The antimicrobial spectrum and potency of exogenouslyadministered recombinant lysozyme protein will also be assessed. These studies will provide insight into the role of lysozyme in airway host defense and provide a preliminary assessment of the therapeutic potential of exogenously administered lysozyme. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SERINE PROTEINASES & LUNG HOST DEFENSE AGAINST BACTERIA Principal Investigator & Institution: Belaaouaj, Abderazzaq; Assistant Professor in Medicine; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's abstract): Human and mouse neutrophils contain neutrophil elastase (NE), cathepsin G (CG) and proteinase 3 (PR 3). The capacity of these serine proteinases, especially NE, to kill bacteria in vitro and to cleave extracellular matrix (ECM) proteins leading to tissue damage is well established, but whether these enzymes kill bacteria in vivo and have specific bacterial target molecules remains unknown. Also, the potential role of the ECM degradation products generated by these proteinases in host defense against bacteria has not been explored. Using mice deficient in NE and CG, we have demonstrated that NE, but not CG, reduces mortality from Gram negative bacterial infections. To date, the antibacterial role of PR 3 has not been clarified in vivo. We propose to generate mice deficient in PR 3 by gene targeting and subject them to bacterial lung infections to determine the relative importance of PR 3 in host defense against bacteria in the lung. Our preliminary data show that the outer membrane protein (Omp) A represents a critical target for NE-mediated killing of E. coli. We hypothesize that Omps represent essential targets of NE to kill other Gram negative

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Pseudomonas

bacteria. Recently, we have found that NE kills Pseudomonas aeruginosa in vitro, and degrades its major Omp F, which is unrelated to Omp A. We propose to determine the importance of Omp F in NE-mediated killing of Pseudomonas aeruginosa in isolated neutrophils and in vivo models of acute and chronic pulmonary infections. Wild type Pseudomonas aeruginosa and isogenic strains deficient in Omp F will be used in these studies. We have observed that elastin peptides from NE-digested human lung elastin are bactericidal for Klebsiella pneumoniae in vitro. These data constitute the first evidence of antibacterial role of ECM derived peptides and reveal a novel role for ECM. We will isolate these elastin fragment(s) and investigate their bactericidal activity in vitro and in vivo. These studies will advance our knowledge of the functional properties of lung serine proteinases and ECM peptides. Also, characterization of NE-degraded elastin may provide novel antimicrobial peptides in humans. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING MECHANISM OF MUC1 MUCIN Principal Investigator & Institution: Kim, K Chul.; Professor; Pharmaceutical Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 07-JAN-1991; Project End 31-MAY-2005 Summary: This abstract is not available. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STCE, AN E.COLI O157:H7 PROTEASE SPECIFIC FOR C1-INH Principal Investigator & Institution: Welch, Rodney A.; Professor & Chair; Medical Microbiol & Immunology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 16-JAN-2003; Project End 31-DEC-2007 Summary: (Provided by applicant): Enterohemorrhagic Escherichia coli (EHEC), principally serotype O157:H7, cause an estimated 20,000 cases of diarrheal disease in the United States per year. 2-6 percent of the infected individuals, mostly young children progress to a severe renal disease, hemolytic uremic syndrome (HUS). The EHEC pathogenic factors that lead to bloody colitis and HUS are poorly understood, but knowledge of some mechanisms has recently emerged. Intimin-mediated adherence and type III effectors are encoded by a chromosomal locus termed LEE. The phage-encoded Shiga toxins (Stxs) are responsible for significant aspects of EHEC disease. EHEC strains commonly possess large plasmids, the prototype being pO157. We have identified a new pO157 gene, stcE, which encodes an extracellular zinc-metalloendoprotease (ZMP) that specifically cleaves the critical anti-inflammatory regulator C l-esterase inhibitor (C 1-Inh). C 1-Inh is a serine protease inhibitor (serpin) that provides the principal inhibition of the proteolytic cascades involved in classic and mannan-binding ligand complement activation, contact activation and intrinsic coagulation. C l-Inh inhibits diverse proteases: Clr and Cls, MASP-1, MASP-2, kallikrein, FXIIa, FXIa, and plasmin. Deficiencies in Cl-Inh cause profound clinical syndromes. The best known is hereditary angioedema (HAE), a genetic deficiency in Cl-Inh, which is characterized by transient, recurrent attacks of intestinal cramps, vomiting, diarrhea and life-threatening episodes of tracheal swelling. Fluorescenated StcE binds to cultured macrophages, B- and T-cells. Thus, StcE is an example of a growing class of ZMPs such as tetanus, botulinum and anthrax lethal factor toxins. These ZMPs, in contrast to the homologous Pseudomonas and Vibrio ZMPs, have specific, non-extracellular matrix protein targets. We will test the hypothesis that StcE degrades soluble or cell-associated Cl-Inh, and this results in poorly

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regulated serine protease cascades involving complement activation, contact activation and coagulation. This dysregulation would then contribute to local inflammation, tissue damage and edema. The elucidation of StcE structure and function(s) may result in new targets for chemotherapeutic or immune prevention or treatment of EHEC infections, which now are best managed only by supportive therapy. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL BIOLOGY OF DIOXYGENASES Principal Investigator & Institution: Ohlendorf, Douglas H.; Professor; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUL-1991; Project End 31-MAR-2004 Summary: Dioxygenases catalyze the incorporation of both atoms of molecular oxygen into a substrate. In bacteria, this ring- opening reaction is a key step in the degradation pathway for many aromatic compounds found in the environment. In plants and animals, dioxygenases are involved in the metabolism of indoles, aromatic amino acids, arachidonic acids and prostaglandins. Dioxygenases are typically metalloproteins many of which require a non-heme mononuclear iron center as a cofactor. This project has been understaken to discover the structural foundations for catalysis in these metalloenzymes. The principal target of this project has been protocatechuate 3,4dioxygenase (3,4-PCD; Fe+3 cofactor, cleaves aromatic rings between hydroxyls) which has been used as a model system. To date for 3,4-PCD from Pseudomonas putida we have determined the refined structures of the wild-type enzyme, of 6 mutants and of 16 substrate/inhibitor complexes; for 3,4-PCD from Acinetobacter calcoaceticus we have determined the refined structures of the wild-type enzyme, of a mutant, and of 4 complexes; for 3,4-PCD from Brevibacterium fuscum we have solved the structure of the wild-type enzyme. Other structures solved include catechol 1,2- dioxygenase (1,2-CTD; Fe+3 cofactor, cleaves aromatic rings between hydroxyls) from Pseudomonas arvilla and A. calcoaceticus and homoprotocatechuate 2,3-dioxygenase (2,3-HPCD; cleaves aromatic rings adjacent to hydroxyls) from B. fuscum (Fe+2 cofactor) and from Arthrobacter globiformis CM-2 (Mn+2 cofactor). This project builds upon a wealth of spectroscopic, kinetic and genetic data gathered over the past 35 years in a number of laboratories key among which are those of our collaborators. Thus our expertise in structural analysis and mutagenesis synergizes with those of our collaborators in spectroscopy, kinetics and genetics to produce a coordinated analysis of this family of metalloenzymes. Questions to be addressed by this combined approach include: What is the difference between Fe+3, Fe+2 and Mn+2 dioxygenases? How does metal ligation change during catalysis or as a function of oxidation state? What is the role of the active site residues in binding, positioning, and preparing metal, substrate and oxygen for catalysis? What is the basis of substrate specificity? And, what is the basis for selecting between intradiol and extradiol cleavage? Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL STUDIES OF BACTERIAL QUORUM SENSING REGULATOR Principal Investigator & Institution: Churchill, Mair E.; Associate Professor; Pharmacology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006

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Pseudomonas

Summary: (provided by applicant): Persistent bacterial infections are a major cause of death in cystic fibrosis patients and immune-compromised individuals. A number of gram-negative bacteria including Pseudomonas aeruginosa, a major pathogen in cystic fibrosis, cause infections that are difficult to treat because the bacteria form a "biofilm community" that renders them less sensitive to traditional antibiotics. Quorum sensing, mediated by acylhomoserine lactone (AHL) signaling molecules, regulates pathogenesis and biofilm formation in P. aeruginosa. Therefore, understanding the molecular basis of quorum sensing is a high priority in the development of novel anti-bacterial agents. The long term goal of this project is to extend the understanding of the quorum-sensing system to the atomic level to develop a detailed description of the mechanisms that control bacterial pathogenesis. The main focus of this proposal is the class of enzymes that produce the AHL signal, AHL-synthases, because bacteria lacking the AHL signal fail to become pathogenic or form stable biofilms. Although there are models of the mechanism of action of the AHL-synthases, there are currently no structures of any AHL synthase. High resolution structural information is absolutely essential for fully understanding the mechanism of AHL synthesis and will provide the basis for future structure-based inhibitor design for development of novel therapeutics. The specific aims for this project are: (I) determine the high resolution crystal structure of the Pantoea stewartii subsp. Stewartii AHL-synthase (EsaI) to understand its function, mechanism, and relationship to other enzymes that utilize similar substrates. Perform mutagenesis, binding and kinetics experiments with EsaI to better understand the catalytic mechanism and substrate specificity. (II) Study the P. aeruginosa AHLsynthase, LasI, using structural and biochemical techniques to understand how specificity of AHL production is determined. (III) Establish whether the AHL-synthase homologues in divergent organisms produce a homoserine lactone signal using mass spectrometry and activity assays. Study the structures and mechanisms to determine similarities to other AHL synthases. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF METABOLIC MEMBRANE PROTEINS Principal Investigator & Institution: Yeh, Joanne I.; Molecular Biology, Cell Biology and Biochemistry; Brown University Box 1929 Providence, Ri 02912 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): We have obtained diffracting crystals of two membrane proteins involved in the glycerol metabolic pathway in bacteria, glycerol facilitator and glycerol-3-phosphate dehydrogenase. This is a significant step towards crystal structure determination and these structures will yield valuable new insight, linking protein folds to function and protein-protein interactions as well as mechanisms of catalysis, regulation, and transmembrane uptake of solute molecules. Underlying effective mechanisms of bacterial proliferation are means of mediating oxidative and carbohydrate metabolism. This structural study focuses on elucidating structurefunction relationships of key bacterial membrane proteins that mediate fundamental oxidative and carbohydrate metabolism. We have been engaged in structural studies of these metabolic proteins for several years and are at pivotal point in integrating all of our results into a comprehensive and coherent picture of metabolism in these pathogenic bacteria. We have determined the structures of three other members of the oxidative and glycerol metabolism pathways, including NADH peroxidase, NADH oxidase, and glycerol kinase. This proposal addresses key questions correlating structure to function and regulation. Gly-3-phosphate dehydrogenase is of particular medical importance as it is a key player in providing triose phosphate intermediates for

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biosynthesis of polysaccharides that form biofilm and protects the bacterium from dehydration as well as antibiotic therapy. This membrane-protein structural study has the potential to yield new and novel results, which are not provided by high-throughput structural genomics. We have overcome some of the most difficult and rate-limiting hurdles in membrane protein structural studies by obtained diffracting crystals of the glycerol facilitator (2.4 A) from Gram-positive Streptococcus pneumonia, a membrane protein involved in glycerol uptake and likely to be regulated via protein-protein interactions with glycerol kinase, whose structure we've recently determined. Subtle but significant differences exist between this and the Gram-negative E. coli facilitator. We have diffracting crystals of the glycerol-3-phosphate dehydrogenase (3.3 A) from Pseudomonas aeruginosa and have promising indications for better diffracting crystals. Our specific aims are to obtain atomic resolution structures of both membrane proteins, both of which are likely to be novel targets for antibiotic design and therapy. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE/FUNCTION STUDIES ON FLAVOPROTEINS Principal Investigator & Institution: Sevrioukova, Irina F.; Molecular Biology and Biochem; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The aim of the proposed work is to use a combination of structural, biochemical and genetic approaches to study structure/function relationships in flavoproteins. The work will focus on two structurally homologous FAD-containing enzymes, putidaredoxin reductase from Pseudomonas putida and apoptosis inducing factor from mice. Putidaredoxin reductase catalyzes electron transfer from NADH to an iron-sulfur protein, putidaredoxin, in cytochrome P450cam monooxygenase. The mechanism of complex formation and electron transfer between putidaredoxin reductase and putidaredoxin is not well understood. We have recently demonstrated that putidaredoxin reductase has redox active cysteines and can function as dithiol/disulfide oxidoreductase. Since there are no putative disulfide redox centers encoded by CysXXCys or CysXXXXCys motifs characteristic for traditional disulfide reductases, the mechanism of dithiol/disulfide oxidoreduction catalyzed by putidaredoxin reductase seems to be unique and needs to be elucidated. Apoptosis inducing factor is a phylogenetically old mammalian, caspaseindependent death effector which, upon apoptosis induction, translocates from its normal localization, the mitochondrial intermembrane space, to the nucleus where it causes chromatin condensation and DNA fragmentation. Neither physiological function nor mechanism of apoptosis induced by this protein is known. Our research will address the question of how the structures of putidaredoxin reductase and apoptosis inducing factor are related to their catalytic function. Crystal structures of putidaredoxin reductase and apoptosis inducing factor will be solved, compared, and related to the catalytic properties of the enzymes. From structural interpretations, these relationships will be further probed and modified by genetic engineering and the effect of specific structural changes on catalytic function of the proteins will be assessed. The study will explain the mechanisms of electron transfer and dithiol/disulfide oxidoreduction catalyzed by putidaredoxin reductase and will provide an insight into the mechanism and function of apoptosis inducing factor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYNDECANS: MODULATORS OF LUNG INFLAMMATION Principal Investigator & Institution: Bernfield, Merton R.; Clements Smith Professor of Pediatrics; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (Applicant's Abstract) The "new BPD" seen in infants of < 1000g is characterized by pathologic changes hypothesized to arise from injury to the lung that lead to inflammation and increased susceptibility to infection. These in turn are proposed to interrupt pulmonary development, especially retarding alveolarization and angiogenesis. The consequence is pulmonary insufficiency, resulting in difficult oxygenation and susceptibility to nosocomial infection. This BPD is difficult to prevent or treat and, paradoxically, its incidence is increasing because of improved survival of these infants. Recent evidence indicates that the syndecans, highly abundant cell surface heparan sulfate proteoglycans (HSPGs), modulate inflammation and host defense. These transmembrane proteins have extracellular domains (ectodomains) that bear HS chains near their N-termini, distant from the plasma membrane. Syndecans are on the surface of every adherent cell where, by virtue of the high affinity of their HS chains for proteins, they act as co-receptors for molecules involved in the repair of injury and host defense. Syndecan-1 and -4 are induced in the lung in response to hyperoxia, and agents produced during tissue injury cause their ectodomains to be shed into inflammatory fluids (skin wound fluids, tracheal aspirates from ventilated infants and baboons) where they can modify growth factor and proteolytic balance. Both syndecan-1 null mice and mice that transgenically overexpress syndecan-1 under a broadly acting promotor show defective wound repair; the null mice are impaired in epithelial repolarization and the overexpressing mice excessively shed syndecan-1 ectodomains, which alter cell proliferation and proteolytic activity in the wound. A known Pseudomonas aeruginosa virulence factor accelerates syndecan-1 shedding in the lung where the ectodomain enhances the microbe?s virulence, presumably by interfering with host defenses. This grant is designed to test the hypothesis that excessive shedding of syndecan ectodomains contributes to the pathogenesis of BPD, a previously unappreciated role that provides new approaches to preventive and/or therapeutic interventions. To explore this hypothesis, the investigators aim to i) use transgenic and null mice to establish the regulatory role of syndecans in the response to lung injury in the mouse; ii) determine the mechanisms of syndecan-1 and -4 induction and shedding in response to lung injury; iii) Evaluate consequences of syndecan ectodomain shedding for pulmonary inflammation and host defense; iv) correlate clinical outcomes of pre-term ventilated infants with their tracheal aspirate levels and activities of syndecan-1 and -4 ectodomains. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYNTHETIC DEVELOPMENT

PEPTIDE

CONSENSUS

SEQUENCE

VACCINE

Principal Investigator & Institution: Hodges, Robert S.; Biochem & Molecular Genetics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2006 Summary: (provided by applicant): Hospital acquired infections such as Pseudomonas aeruginosa (PA) affect up to 10% of patients admitted to acute care hospitals, representing upwards of 10 million hospital days annually in North America. PA infection results in significant patient morbidity and mortality (ca. 80,000 deaths in

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North America per year due to PA ventilator-associated pneumonia in intensive care unit (ICU) patients). Patients considered being at risk of PA infections are those whose immune systems have been weakened because of accident, disease or other causes. PA infections are commonly found in patients with cancer, cystic fibrosis, AIDS, burn wounds or who have a long history of hospitalization. Although antibiotic therapy is employed in treatment it is often incapable of resolving the infection. This lack of effectiveness is due in part to antibiotic resistance of the bacteria, difficulty in establishing an exact diagnosis, and, paradoxically, antibiotic use which selects resistant bacteria. New approaches are needed to control infection which are based on prevention. The research described here is such an approach. Our laboratory has investigated PA infection for the last 10 years and has demonstrated the feasibility of preventing PA infection by using novel approaches to both active vaccination or by passive use of antibody therapeutics. Both these methods attack the infection process at its initial stage: attachment of the bacterium to the host's cell surfaces. However, the problem exists that there are multiple strains of PA bacteria and an efficacious vaccine or antibody therapeutic must account for all existing strains of this pathogen. In this proposal we are developing 1) a novel consensus sequence vaccine approach forcoverage against all strains of PA, 2) a constrained peptidomimetic of the immunogen to enhance immunogenicity when used as an active peptide vaccine to block bacteria attachment and 3) monoclonal antibodies (prepared to selected peptide immunogens) that are broadly cross-reactive with maximal affinity for use as an antibody therapeutic. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE MULTIPLE ANTIBIOTIC RESISTANCE (MAR)REGULON Principal Investigator & Institution: Levy, Stuart B.; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 30-SEP-1980; Project End 31-DEC-2007 Summary: (provided by applicant): Multidrug resistance in bacteria has become more the norm than the unusual. While characteristically mediated by plasmids and transposons, increasing evidence shows that chromosomal (intrinsic) regulatory genes and multidrug efflux pumps mediate resistance to multiple antibiotics and hazardous substances. One such regulatory system is the marRAB operon discovered in Escherichia coil whose MarA protein product controls expression of over 80 genes in the mar regulon. Initially described as an activator, MarA appears to have direct repressor activity as well. Homologs of the E.coli MarA and MarR (the repressor of the mar operon) have been found in many different genera including both gram positive and gram-negative organisms. Studies of Salmonella and E.coli reveal not only marmediation of drug resistance, but also of colonization and virulence. The DNA binding sites for MarR and MarA have been identified as well as their crystal structures. Still the molecular and biochemical elements which define MarA activation or repression of different genes is not understood, nor is the regulation of the operon by genes other than MarR. To improve knowledge about the molecular control and activity of the mar regulon in E.coli and other clinically important bacteria, this proposal seeks to: 1) determine the molecular basis for the difference between negative and positive transcriptional control by the MarA protein of genes in the mar regulon; studies in vitro and in vivo will define the sequence, orientation and location of the regulatory DNA sequences near the promoters of particular genes in the regulon. 2) enhance understanding of MarR function through two-hybrid studies of its interaction with other proteins, use of macro/micro arrays to determine possible regulation of other loci by MarR, and determination of the crystal structure of MarR with DNA or a ligand. 3)

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identify other chromosomal genes besides marR that regulate expression of the mar operon. 4) investigate mar loci in other bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, and Yersinia pestis. Studies of the E.coli marRAB serve as a paradigm for insights into related genetic loci in other bacteria also of consequence to human health. Improved understanding will help to suggest novel approaches towards preventing and curing infections. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TLR4 AND PULMONARY INNATE IMMUNITY TO P.AERUGINOSA Principal Investigator & Institution: Hajjar, Adeline M.; Immunology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Patients with cystic fibrosis (CF) develop persistent inflammation and chronic infections with Pseudomonas aeruginosa that ultimately result in their death. Toll-like receptors (TLRs) are type-I transmembrane proteins that transduce signals triggering the inflammatory and innate immune response to a variety of pathogens. TLR4, in concert with a co-receptor, MD-2, has been shown to mediate responses to lipopolysaccharide (LPS), a pro-inflammatory component of Gramnegative bacteria. This proposal will address the role that TLR4 plays in the pulmonary immune and inflammatory response to P. aeruginosa. The rationale for these studies derives from several novel observations made by our group. We have found that the structure of P. aeruginosa LPS isolated from CF patients is distinct from that of P. aeruginosa isolated from non-CF patients. Our preliminary in vitro data suggest that there are differences in the recognition of P. aeruginosa LPS by murine (mu) as compared to human (hu) TLR4. Specifically, muTLR4 mediates equivalent responses to both LPS from CF strains (CF-specific LPS) and non-CF strains (unmodified LPS) of P. aeruginosa, whereas huTLR4 responds much more poorly to non-CF than CF LPS. We hypothesize that CF LPS directly contributes to the chronic inflammation seen in CF and does so in part due to the unique recognition specificity of huTLR4, which recognizes and responds to CF LPS much more intensely than to unmodified LPS. The rapid and intense inflammatory response to P. aeruginosa in mouse lungs has limited the usefulness of mouse models for CF, possibly due to the more efficient recognition of unmodified LPS by muTLR4. We therefore propose to engineer a mouse that will mimic the decreased responsiveness of huTLR4 to unmodified LPS in order to evaluate the role that TLR4 plays in the immune response to P. aeruginosa. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM

TYPE

III

POLYKETIDE

SYNTHASES:

STRUCTURE

AND

Principal Investigator & Institution: Moore, Bradley S.; Assistant Professor; Pharmacology and Toxicology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2007 Summary: A new mechanism of polyketide assembly has emerged in bacteria for the biosynthesis of small aromatic residues that serve as important structural elements in a growing number of biologically active natural products. These small aromatic polyketides are synthesized by homodimeric (type III) polyketide synthases (PKSs) that are phylogenetically and biochemically related to ubiquitous plant PKSs such as chalcone synthase. Thus far, type III PKSs have been shown to be responsible for the

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biosynthesis of natural products such as 1,3,6,8- tetrahydroxynaphthalene (THN) and the formation of key components of more complex antimicrobial and antitumor natural products such as vancomycin, naphterpin, marinone, and kendomycin. While type III PKSs are architecturally simple, they arguably represent the most sophisticated PKSs mechanistically since embodied within their homodimeric architecture is the catalytic machinery necessary for starter molecule recognition and loading, malonyl- CoA decarboxylation and polyketide chain extension, and ultimately, multiple pathways for termination. Their simple gene and protein architecture makes them amendable for study using a variety of sophisticated approaches including heterologous biosynthesis, in vitro and in vivo biochemical analysis, directed and random approaches towards enzyme engineering, and atomic resolution protein x-ray crystallography. Although the analysis of related plant enzymes is fairly mature, research on the bacterial counterparts is only beginning and can be expected to yield novel, interesting, and potentially important information on these simple condensing enzymes. Moreover, the mechanistic and structural understanding of bacterial type III PKSs is likely to be relevant for the productive reengineering of modular type I and iterative type II bacterial PKSs. With the high resolution three-dimensional crystal structure of the first bacterial PKS, THN synthase from Streptomyces coelicolor A3(2), nearly in hand, the stage is set for a comprehensive structural and mechanistic analysis of this new subclass of bacterial PKS. Studies will extend to other bacterial type III PKSs, including those involved in the biosynthesis of the clinically important glycopeptide vancomycin, the broad spectrum antibiotic 2,4- diacetylphloroglucinol, and the antitumor antibiotic marinone. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TYPE IV PILI: STRUCTURAL ASPECTS OF THE ASSEMBLY MECHANI Principal Investigator & Institution: Forest, Katrina T.; Bacteriology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Abstract): Many pathogenic microorganisms have Type IV pili to attach to and colonize eukaryotic host cells for virulent infection. The type IV pili are long filamentous organelles comprised of thousands of copies of the pilin subunit. The long term objective of this work is to understand the molecular assembly mechanism of this virulence factor by solving the x-ray crystal structures of type IV pilins and the pilus biogenesis proteins. This information will ultimately be used to design inhibitors that block assembly, eukaryotic cell binding, and/or signaling by pili, thereby serving as antibiotics. In particular, during this funding cycle crystallization and x-ray structure determination will be done for the pilin subunit from Pseudomonas aeruginosa and the pilus assembly/motility factor PilT from the hyperthermophile Aquifex aeolicus. The subunit structure of pilin is needed to test the hypothesis that the 3-D subunit structure and oligomeric packing of type IV pili is conserved across species. It will also reveal posttranslational modifications. The structure of the pilin subunit will be used to model the subunit contacts in an assembled pilus fiber. Combined, the subunit structure and oligomer model will be the basis for design of hybrid pilin molecules to test hypotheses about which parts of the pilin molecule must interact specifically with each other and with other proteins in the biogenesis machinery. Two main roles of pili, twitching motility and signaling among bacteria and with eukaryotic cells, require the PilT protein. The PilT structure will reveal PilT surfaces likely to interact with other proteins in the biogenesis pathway. Logical site-directed mutants will be made to test the in vivo roles of these surfaces. Critical functional residues,

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effector binding sites in addition to the expected nucleotide binding pocket, and possible phosphorylation sites will furthermore be identified. Together with available biochemical and genetic data, these structural results will eventually lead to a high resolution model of the molecular mechanisms of pilus biogenesis and function. This understanding will be the foundation for blocking pilus functions to control infection by microbes. Website: Http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: XENOGRAFT MODEL OF CYSTIC FIBROSIS THERAPY Principal Investigator & Institution: Wilson, James M.; John Herr Musser Professor and Chair; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-MAR-2006 Summary: (provided by applicant): Studies of the pathogenesis of cystic fibrosis (CF) have highlighted the importance of host defenses at the airway surface in combating microbial infections. The airway epithelial cell plays a key role in pulmonary host defense through a number of different pathways. During the last cycle of this grant, we identified and characterized from humans and mice novel molecules, called betadefensins, which are secreted by epithelial cells on to the surface of the airway where they contribute to bacterial killing. Mice individually deficient in two mouse betadefensin genes were created and subjected to preliminary analysis. Recent work by others has determined a family of transmembrane proteins called Toll Like Receptors (TLRs) important signaling innate immunity and initiating acquired immune responses. The goal of this proposal is to evaluate the role of the pulmonary epithelia in initiating the innate immune response in murine models to two pathogens important to the pathogenesis of CF, H. influenzae and P. aeruginosa. In preclinical studies, we document expression of human TLR in airway epithelia cells and its role in signaling innate immunity. Studies in mice challenged with H. influenzae documented the importance of murine beta-defensin 1 in clearing the infection and TLR4 in sensing the infection and signaling an innate immune response. Studies with P. aeruginosa suggest a critical role of TLR4 in the effector response of innate immunity. Specific Aim 1 will evaluate the relative role of the epithelia versus macrophages in sensing and signaling innate immunity and will attempt to confirm/identify specific TLRs involved in detecting the pathogens under study. Specific Aim 2 will characterize the role of mBD- 1 and mBD-3 in responding to intrapulmonary challenge of prototypic pathogens. Specific Aim 3 will delineate the proposed defect(s) in effector cell function to P. aeruginosa observed in TLR deficient mice. 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

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.

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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “pseudomonas” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for pseudomonas in the PubMed Central database: •

A 90-Kilobase Conjugative Chromosomal Element Coding for Biphenyl and Salicylate Catabolism in Pseudomonas putida KF715. by Nishi A, Tominaga K, Furukawa K.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101889

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A Dose-Response Study of Antibiotic Resistance in Pseudomonas aeruginosa Biofilms. by Brooun A, Liu S, Lewis K.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89739

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A Highly Selective PCR Protocol for Detecting 16S rRNA Genes of the Genus Pseudomonas (Sensu Stricto) in Environmental Samples. by Widmer F, Seidler RJ, Gillevet PM, Watrud LS, Di Giovanni GD.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106424

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A New Biocatalyst for Production of Optically Pure Aryl Epoxides by Styrene Monooxygenase from Pseudomonas fluorescens ST. by Di Gennaro P, Colmegna A, Galli E, Sello G, Pelizzoni F, Bestetti G.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91418

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A novel cell surface polysaccharide in Pseudomonas putida WCS358, which shares characteristics with Escherichia coli K antigens, is not involved in root colonization. by de Weger LA, Bloemberg GV, van Wezel T, van Raamsdonk M, Glandorf DC, van Vuurde J, Jann K, Lugtenberg BJ.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177891

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A Novel Serine/Threonine Protein Kinase Homologue of Pseudomonas aeruginosa Is Specifically Inducible within the Host Infection Site and Is Required for Full Virulence in Neutropenic Mice. by Wang J, Li C, Yang H, Mushegian A, Jin S.; 1998 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107787

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A Protease-Resistant Catalase, KatA, Released upon Cell Lysis during Stationary Phase Is Essential for Aerobic Survival of a Pseudomonas aeruginosa oxyR Mutant at Low Cell Densities. by Hassett DJ, Alsabbagh E, Parvatiyar K, Howell ML, Wilmott RW, Ochsner UA.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94627

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A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism. by Cao H, Krishnan G, Goumnerov B, Tsongalis J, Tompkins R, Rahme LG.; 2001 Dec 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64730

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A Second Quorum-Sensing System Regulates Cell Surface Properties but Not Phenazine Antibiotic Production in Pseudomonas aureofaciens. by Zhang Z, Pierson LS III.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93161

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The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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A Set of Genes Encoding a Second Toluene Efflux System in Pseudomonas putida DOT-T1E Is Linked to the tod Genes for Toluene Metabolism. by Mosqueda G, Ramos JL.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94367

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A Seven-Gene Locus for Synthesis of Phenazine-1-Carboxylic Acid by Pseudomonas fluorescens 2-79. by Mavrodi DV, Ksenzenko VN, Bonsall RF, Cook RJ, Boronin AM, Thomashow LS.; 1998 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107199

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A simple alfalfa seedling infection model for Pseudomonas aeruginosa strains associated with cystic fibrosis shows AlgT (sigma-22) and RhlR contribute to pathogenesis. by Silo-Suh L, Suh SJ, Sokol PA, Ohman DE.; 2002 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137779

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Ability of the VITEK 2 Advanced Expert System To Identify [beta]-Lactam Phenotypes in Isolates of Enterobacteriaceae and Pseudomonas aeruginosa. by Sanders CC, Peyret M, Moland ES, Shubert C, Thomson KS, Boeufgras JM, Sanders WE Jr.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86150

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Accumulation of 2-Aminophenoxazin-3-one-7-Carboxylate during Growth of Pseudomonas putida TW3 on 4-Nitro-Substituted Substrates Requires 4Hydroxylaminobenzoate Lyase (PnbB). by Hughes MA, Baggs MJ, al-Dulayymi J, Baird MS, Williams PA.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126382

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Accumulation of Polyhydroxyalkanoic Acid Containing Large Amounts of Unsaturated Monomers in Pseudomonas fluorescens BM07 Utilizing Saccharides and Its Inhibition by 2-Bromooctanoic Acid. by Lee HJ, Choi MH, Kim TU, Yoon SC.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93259

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Acquisition of a deliberately introduced phenol degradation operon, pheBA, by different indigenous Pseudomonas species. by Peters M, Heinaru E, Talpsep E, Wand H, Stottmeister U, Heinaru A, Nurk A.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168818

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Acquisition of Expression of the Pseudomonas aeruginosa ExoU Cytotoxin Leads to Increased Bacterial Virulence in a Murine Model of Acute Pneumonia and Systemic Spread. by Allewelt M, Coleman FT, Grout M, Priebe GP, Pier GB.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101680

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Activation of the Pseudomonas aeruginosa Type III Secretion System Requires an Intact Pyruvate Dehydrogenase aceAB Operon. by Dacheux D, Epaulard O, de Groot A, Guery B, Leberre R, Attree I, Polack B, Toussaint B.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128050

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Active Efflux of Organic Solvents by Pseudomonas putida S12 Is Induced by Solvents. by Kieboom J, Dennis JJ, Zylstra GJ, de Bont JA.; 1998 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107788

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Activities of Tobramycin and Six Other Antibiotics against Pseudomonas aeruginosa Isolates from Patients with Cystic Fibrosis. by Shawar RM, MacLeod DL, Garber RL, Burns JL, Stapp JR, Clausen CR, Tanaka SK.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89580

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Adenylate Kinase as a Virulence Factor of Pseudomonas aeruginosa. by Markaryan A, Zaborina O, Punj V, Chakrabarty AM.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99632

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Advancing the Quorum in Pseudomonas aeruginosa: MvaT and the Regulation of NAcylhomoserine Lactone Production and Virulence Gene Expression. by Diggle SP, Winzer K, Lazdunski A, Williams P, Camara M.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135012

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Alginate Lyase Promotes Diffusion of Aminoglycosides through the Extracellular Polysaccharide of Mucoid Pseudomonas aeruginosa. by Hatch RA, Schiller NL.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105585

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Alginate Overproduction Affects Pseudomonas aeruginosa Biofilm Structure and Function. by Hentzer M, Teitzel GM, Balzer GJ, Heydorn A, Molin S, Givskov M, Parsek MR.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95424

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Alteration of the Lipopolysaccharide Structure Affects the Functioning of the Xcp Secretory System in Pseudomonas aeruginosa. by Michel G, Ball G, Goldberg JB, Lazdunski A.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94332

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Ambler Class A Extended-Spectrum [beta]-Lactamases in Pseudomonas aeruginosa: Novel Developments and Clinical Impact. by Weldhagen GF, Poirel L, Nordmann P.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166056

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Amplified Fragment Length Polymorphism Fingerprinting of Pseudomonas Strains from a Poultry Processing Plant. by Geornaras I, Kunene NF, von Holy A, Hastings JW.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99707

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An Altered Pseudomonas Diversity Is Recovered from Soil by Using Nutrient-Poor Pseudomonas-Selective Soil Extract Media. by Aagot N, Nybroe O, Nielsen P, Johnsen K.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93295

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An aromatic effector specificity mutant of the transcriptional regulator DmpR overcomes the growth constraints of Pseudomonas sp. strain CF600 on parasubstituted methylphenols. by Pavel H, Forsman M, Shingler V.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=197212

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Analysis of fluorescent pseudomonads based on 23S ribosomal DNA sequences. by Christensen H, Boye M, Poulsen LK, Rasmussen OF.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201626

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Analysis of Promoters Recognized by PvdS, an Extracytoplasmic-Function Sigma Factor Protein from Pseudomonas aeruginosa. by Wilson MJ, McMorran BJ, Lamont IL.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95118

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Analysis of the pmsCEAB Gene Cluster Involved in Biosynthesis of Salicylic Acid and the Siderophore Pseudomonine in the Biocontrol Strain Pseudomonas

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fluorescens WCS374. by Mercado-Blanco J, van der Drift KM, Olsson PE, Thomas-Oates JE, van Loon LC, Bakker PA.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95085 •

Analysis of the Role of recA in Phenotypic Switching of Pseudomonas tolaasii. by Sinha H, Pain A, Johnstone K.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94806

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AnkB, a Periplasmic Ankyrin-Like Protein in Pseudomonas aeruginosa, Is Required for Optimal Catalase B (KatB) Activity and Resistance to Hydrogen Peroxide. by Howell ML, Alsabbagh E, Ma JF, Ochsner UA, Klotz MG, Beveridge TJ, Blumenthal KM, Niederhoffer EC, Morris RE, Needham D, Dean GE, Wani MA, Hassett DJ.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94626

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Antibiograms, serotypes, and plasmid profiles of Pseudomonas aeruginosa associated with corneal ulcers and contact lens wear. by Mayo MS, Cook WL, Schlitzer RL, Ward MA, Wilson LA, Ahearn DG.; 1986 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268916

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Application of Different Genotyping Methods for Pseudomonas aeruginosa in a Setting of Endemicity in an Intensive Care Unit. by Speijer H, Savelkoul PH, Bonten MJ, Stobberingh EE, Tjhie JH.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85717

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Application of Siderotyping for Characterization of Pseudomonas tolaasii and "Pseudomonas reactans" Isolates Associated with Brown Blotch Disease of Cultivated Mushrooms. by Munsch P, Geoffroy VA, Alatossava T, Meyer JM.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92388

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Assignment of the Substrate-Selective Subunits of the MexEF-OprN Multidrug Efflux Pump of Pseudomonas aeruginosa. by Maseda H, Yoneyama H, Nakae T.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89743

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Autoinduction of 2,4-Diacetylphloroglucinol Biosynthesis in the Biocontrol Agent Pseudomonas fluorescens CHA0 and Repression by the Bacterial Metabolites Salicylate and Pyoluteorin. by Schnider-Keel U, Seematter A, Maurhofer M, Blumer C, Duffy B, Gigot-Bonnefoy C, Reimmann C, Notz R, Defago G, Haas D, Keel C.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94405

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Autolysis and Autoaggregation in Pseudomonas aeruginosa Colony Morphology Mutants. by D'Argenio DA, Calfee MW, Rainey PB, Pesci EC.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135425

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Bacteria Associated with Hazelnut (Corylus avellana L.) Decline Are of Two Groups: Pseudomonas avellanae and Strains Resembling P. syringae pv. syringae. by Scortichini M, Marchesi U, Rossi MP, Di Prospero P.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126672

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Bacteria in the Leaf Ecosystem with Emphasis on Pseudomonas syringae ---a Pathogen, Ice Nucleus, and Epiphyte. by Hirano SS, Upper CD.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99007

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Bacterioferritin A Modulates Catalase A (KatA) Activity and Resistance to Hydrogen Peroxide in Pseudomonas aeruginosa. by Ma JF, Ochsner UA, Klotz MG, Nanayakkara VK, Howell ML, Johnson Z, Posey JE, Vasil ML, Monaco JJ, Hassett DJ.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93851

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Biochemical-Genetic Characterization and Distribution of OXA-22, a Chromosomal and Inducible Class D [beta]-Lactamase from Ralstonia (Pseudomonas) pickettii. by Nordmann P, Poirel L, Kubina M, Casetta A, Naas T.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90041

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Biodegradation of petroleum hydrocarbons by psychrotrophic Pseudomonas strains possessing both alkane (alk) and naphthalene (nah) catabolic pathways. by Whyte LG, Bourbonniere L, Greer CW.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168679

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Biogeography and Degree of Endemicity of Fluorescent Pseudomonas Strains in Soil. by Cho JC, Tiedje JM.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92480

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Biotransformation of 2,4,6,8,10,12-Hexanitro-2,4,6,8,10,12-Hexaazaisowurtzitane (CL20) by Denitrifying Pseudomonas sp. Strain FA1. by Bhushan B, Paquet L, Spain JC, Hawari J.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194975

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blaVIM-2 Cassette-Containing Novel Integrons in Metallo-[beta]-LactamaseProducing Pseudomonas aeruginosa and Pseudomonas putida Isolates Disseminated in a Korean Hospital. by Lee K, Lim JB, Yum JH, Yong D, Chong Y, Kim JM, Livermore DM.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127086

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Bromoalkane-degrading Pseudomonas strains. by Shochat E, Hermoni I, Cohen Z, Abeliovich A, Belkin S.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182096

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Carbon Limitation Induces [final sigma]S-Dependent Gene Expression in Pseudomonas fluorescens in Soil. by Koch B, Worm J, Jensen LE, Hojberg O, Nybroe O.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93029

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Catabolite Repression Control by Crc in 2xYT Medium Is Mediated by Posttranscriptional Regulation of bkdR Expression in Pseudomonas putida. by Hester KL, Madhusudhan KT, Sokatch JR.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94393

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Catabolite-mediated mutations in alternate toluene degradative pathways in Pseudomonas putida. by Leddy MB, Phipps DW, Ridgway HF.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177237

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Cefepime-Aztreonam: a Unique Double [beta]-Lactam Combination for Pseudomonas aeruginosa. by Lister PD, Sanders WE Jr, Sanders CC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105655

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Characterization by 16S rRNA Sequence Analysis of Pseudomonads Causing Blotch Disease of Cultivated Agaricus bisporus. by Godfrey SA, Harrow SA, Marshall JW, Klena JD.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93162

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Characterization of a Pseudomonas aeruginosa Efflux Pump Contributing to Aminoglycoside Impermeability. by Westbrock-Wadman S, Sherman DR, Hickey MJ, Coulter SN, Zhu YQ, Warrener P, Nguyen LY, Shawar RM, Folger KR, Stover CK.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89597

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Characterization of a Pseudomonas putida Allylic Alcohol Dehydrogenase Induced by Growth on 2-Methyl-3-Buten-2-ol. by Malone VF, Chastain AJ, Ohlsson JT, Poneleit LS, Nemecek-Marshall M, Fall R.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91387

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Characterization of an Endoprotease (PrpL) Encoded by a PvdS-Regulated Gene in Pseudomonas aeruginosa. by Wilderman PJ, Vasil AI, Johnson Z, Wilson MJ, Cunliffe HE, Lamont IL, Vasil ML.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98648

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Characterization of an OprL null mutant of Pseudomonas putida. by Rodriguez-Herva JJ, Ramos JL.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178433

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Characterization of Cell Lysis in Pseudomonas putida Induced upon Expression of Heterologous Killing Genes. by Ronchel MC, Molina L, Witte A, Lutbiz W, Molin S, Ramos JL, Ramos C.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90941

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Characterization of Class 1 Integrons from Pseudomonas aeruginosa That Contain the blaVIM-2 Carbapenem-Hydrolyzing [beta]-Lactamase Gene and of Two Novel Aminoglycoside Resistance Gene Cassettes. by Poirel L, Lambert T, Turkoglu S, Ronco E, Gaillard JL, Nordmann P.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90325

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Characterization of elastase-deficient clinical isolates of Pseudomonas aeruginosa. by Hamood AN, Griswold J, Colmer J.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174201

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Characterization of Fluorescent and Nonfluorescent Peptide Siderophores Produced by Pseudomonas syringae Strains and Their Potential Use in Strain Identification. by Bultreys A, Gheysen I, Maraite H, de Hoffmann E.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92790

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Characterization of hemolysin in extracellular products of Pseudomonas cepacia. by Nakazawa T, Yamada Y, Ishibashi M.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265865

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Characterization of impermeability variants of Pseudomonas aeruginosa isolated during unsuccessful therapy of experimental endocarditis. by Bayer AS, Norman DC, Kim KS.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=174654

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Characterization of pseudomonads isolated from diseased fleece. by London CJ, Griffith IP.; 1984 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=240037

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Characterization of Pseudomonas spp. Associated with Spoilage of Gilt-Head Sea Bream Stored under Various Conditions. by Tryfinopoulou P, Tsakalidou E, Nychas GJ.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126548

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Characterization of the hcnABC Gene Cluster Encoding Hydrogen Cyanide Synthase and Anaerobic Regulation by ANR in the Strictly Aerobic Biocontrol Agent Pseudomonas fluorescens CHA0. by Laville J, Blumer C, Von Schroetter C, Gaia V, Defago G, Keel C, Haas D.; 1998 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107821

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Characterization of the MexC-MexD-OprJ Multidrug Efflux System in [Delta]mexAmexB-oprM Mutants of Pseudomonas aeruginosa. by Gotoh N, Tsujimoto H, Tsuda M, Okamoto K, Nomura A, Wada T, Nakahashi M, Nishino T.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105713

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Characterization of the Serogroup O11 O-Antigen Locus of Pseudomonas aeruginosa PA103. by Dean CR, Franklund CV, Retief JD, Coyne MJ Jr, Hatano K, Evans DJ, Pier GB, Goldberg JB.; 1999 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93929

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Charged Amino Acids Conserved in the Aromatic Acid/H + Symporter Family of Permeases Are Required for 4-Hydroxybenzoate Transport by PcaK from Pseudomonas putida. by Ditty JL, Harwood CS.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134867

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Chemotaxis of Pseudomonas spp. to the polyaromatic hydrocarbon naphthalene. by Grimm AC, Harwood CS.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168726

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Chromosomal Integration, Tandem Amplification, and Deamplification in Pseudomonas putida F1 of a 105-Kilobase Genetic Element Containing the Chlorocatechol Degradative Genes from Pseudomonas sp. Strain B13. by Ravatn R, Studer S, Springael D, Zehnder AJ, van der Meer JR.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107442

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Chromosomal Locus for Cadmium Resistance in Pseudomonas putida Consisting of a Cadmium-Transporting ATPase and a MerR Family Response Regulator. by Lee SW, Glickmann E, Cooksey DA.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92752

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Clavulanate Induces Expression of the Pseudomonas aeruginosa AmpC Cephalosporinase at Physiologically Relevant Concentrations and Antagonizes the Antibacterial Activity of Ticarcillin. by Lister PD, Gardner VM, Sanders CC.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89221

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Clonal Population Structure of Pseudomonas stutzeri, a Species with Exceptional Genetic Diversity. by Rius N, Fuste MC, Guasp C, Lalucat J, Loren JG.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94931

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Cloning and characterization of a 3-N-aminoglycoside acetyltransferase gene, aac(3)Ib, from Pseudomonas aeruginosa. by Schwocho LR, Schaffner CP, Miller GH, Hare RS, Shaw KJ.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162827

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Cloning and Comparison of fliC Genes and Identification of Glycosylation in the Flagellin of Pseudomonas aeruginosa a-Type Strains. by Brimer CD, Montie TC.; 1998 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107824

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Cloning and Molecular Analysis of the Poly(3-hydroxybutyrate) and Poly(3hydroxybutyrate-co-3-hydroxyalkanoate) Biosynthesis Genes in Pseudomonas sp. Strain 61-3. by Matsusaki H, Manji S, Taguchi K, Kato M, Fukui T, Doi Y.; 1998 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107745

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Cloning of pectate lyase gene pel from Pseudomonas fluorescens and detection of sequences homologous to pel in Pseudomonas viridiflava and Pseudomonas putida. by Liao CH.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208100

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Cloning, Expression, and Nucleotide Sequence of the Pseudomonas aeruginosa 142 ohb Genes Coding for Oxygenolytic ortho Dehalogenation of Halobenzoates. by Tsoi TV, Plotnikova EG, Cole JR, Guerin WF, Bagdasarian M, Tiedje JM.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91311

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Cloning, sequencing, and expression of isopropylbenzene degradation genes from Pseudomonas sp. strain JR1: identification of isopropylbenzene dioxygenase that mediates trichloroethene oxidation. by Pflugmacher U, Averhoff B, Gottschalk G.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168215

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Coexistence of Two Distinct Copies of Naphthalene Degradation Genes in Pseudomonas Strains Isolated from the Western Mediterranean Region. by Ferrero M, Llobet-Brossa E, Lalucat J, Garcia-Valdes E, Rossello-Mora R, Bosch R.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126682

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Combined Physical and Genetic Map of the Pseudomonas putida KT2440 Chromosome. by Ramos-Diaz MA, Ramos JL.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107723

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Comparative Genetic Diversity of the narG, nosZ, and 16S rRNA Genes in Fluorescent Pseudomonads. by Delorme S, Philippot L, Edel-Hermann V, Deulvot C, Mougel C, Lemanceau P.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143668

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Comparison of Agar Diffusion Methodologies for Antimicrobial Susceptibility Testing of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients. by Burns JL, Saiman L, Whittier S, Larone D, Krzewinski J, Liu Z, Marshall SA, Jones RN.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86597

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Comparison of Flagellin Genes from Clinical and Environmental Pseudomonas aeruginosa Isolates. by Morgan JA, Bellingham NF, Winstanley C, Ousley MA, Hart CA, Saunders JR.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91160

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Complementation Analysis of the Dichelobacter nodosus fimN, fimO, and fimP Genes in Pseudomonas aeruginosa and Transcriptional Analysis of the fimNOP Gene Region. by Johnston JL, Billington SJ, Haring V, Rood JI.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107890

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Conservation of the 2,4-diacetylphloroglucinol biosynthesis locus among fluorescent Pseudomonas strains from diverse geographic locations. by Keel C, Weller DM, Natsch A, Defago G, Cook RJ, Thomashow LS.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167820

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Construction and Analysis of Photolyase Mutants of Pseudomonas aeruginosa and Pseudomonas syringae: Contribution of Photoreactivation, Nucleotide Excision Repair, and Mutagenic DNA Repair to Cell Survival and Mutability following Exposure to UV-B Radiation. by Kim JJ, Sundin GW.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92747

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Construction and Characterization of a Live, Attenuated aroA Deletion Mutant of Pseudomonas aeruginosa as a Candidate Intranasal Vaccine. by Priebe GP, Brinig MM, Hatano K, Grout M, Coleman FT, Pier GB, Goldberg JB.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127764

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Construction of a Pseudomonas hybrid strain that mineralizes 2,4,6-trinitrotoluene. by Duque E, Haidour A, Godoy F, Ramos JL.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204515

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Construction of a rhizosphere pseudomonad with potential to degrade polychlorinated biphenyls and detection of bph gene expression in the rhizosphere. by Brazil GM, Kenefick L, Callanan M, Haro A, de Lorenzo V, Dowling DN, O'Gara F.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167456

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Contribution of phenazine antibiotic biosynthesis to the ecological competence of fluorescent pseudomonads in soil habitats. by Mazzola M, Cook RJ, Thomashow LS, Weller DM, Pierson LS 3rd.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195829

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Controlling Instability in gacS-gacA Regulatory Genes during Inoculant Production of Pseudomonas fluorescens Biocontrol Strains. by Duffy BK, Defago G.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92126

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Crc Is Involved in Catabolite Repression Control of the bkd Operons of Pseudomonas putida and Pseudomonas aeruginosa. by Hester KL, Lehman J, Najar F, Song L, Roe BA, MacGregor CH, Hager PW, Phibbs PV Jr, Sokatch JR.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94392

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Cross-Regulation between a Novel Two-Component Signal Transduction System for Catabolism of Toluene in Pseudomonas mendocina and the TodST System from Pseudomonas putida. by Ramos-Gonzalez MI, Olson M, Gatenby AA, Mosqueda G, Manzanera M, Campos MJ, Vichez S, Ramos JL.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135474

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cumA Multicopper Oxidase Genes from Diverse Mn(II)-Oxidizing and Non-Mn(II)Oxidizing Pseudomonas Strains. by Francis CA, Tebo BM.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93157

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cumA, a Gene Encoding a Multicopper Oxidase, Is Involved in Mn2 + Oxidation in Pseudomonas putida GB-1. by Brouwers GJ, de Vrind JP, Corstjens PL, Cornelis P, Baysse C, de Vrind-de Jong EW.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91248

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Degradation of 1,3-Dichloropropene by Pseudomonas cichorii 170. by Poelarends GJ, Wilkens M, Larkin MJ, van Elsas JD, Janssen DB.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106795

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Degradation of 2-chloroallylalcohol by a Pseudomonas sp. by van der Waarde JJ, Kok R, Janssen DB.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202138

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Degradation of 3-Phenoxybenzoic Acid in Soil by Pseudomonas pseudoalcaligenes POB310(pPOB) and Two Modified Pseudomonas Strains. by Halden RU, Tepp SM, Halden BG, Dwyer DF.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91504

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Degradation of Chloronitrobenzenes by a Coculture of Pseudomonas putida and a Rhodococcus sp. by Park HS, Lim SJ, Chang YK, Livingston AG, Kim HS.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91148

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Degradation of poly(3-hydroxyoctanoic acid) [P(3HO)] by bacteria: purification and properties of a P(3HO) depolymerase from Pseudomonas fluorescens GK13. by Schirmer A, Jendrossek D, Schlegel HG.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202264

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Degradation of triglycerides by a pseudomonad isolated from milk: molecular analysis of a lipase-encoding gene and its expression in Escherichia coli. by Johnson LA, Beacham IR, MacRae IC, Free ML.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195672

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Degradation of Triphenyltin by a Fluorescent Pseudomonad. by Inoue H, Takimura O, Fuse H, Murakami K, Kamimura K, Yamaoka Y.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92176

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Designing recombinant Pseudomonas strains to enhance biodesulfurization. by Gallardo ME, Ferrandez A, De Lorenzo V, Garcia JL, Diaz E.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179658

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Detection and Characterization of a Macrolide 2[prime prime or minute]Phosphotransferase from a Pseudomonas aeruginosa Clinical Isolate. by Nakamura A, Miyakozawa I, Nakazawa K, O'Hara K, Sawai T.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101646

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Detection of gyrA Mutations among 335 Pseudomonas aeruginosa Strains Isolated in Japan and Their Susceptibilities to Fluoroquinolones. by Takenouchi T, Sakagawa E, Sugawara M.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89091

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Detection of Pseudomonas pseudomallei by PCR and hybridization. by Lew AE, Desmarchelier PM.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263685

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Detection of Pseudomonas savastanoi pv. savastanoi in Olive Plants by Enrichment and PCR. by Penyalver R, Garcia A, Ferrer A, Bertolini E, Lopez MM.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110599

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Development and Dynamics of Pseudomonas sp. Biofilms. by Tolker-Nielsen T, Brinch UC, Ragas PC, Andersen JB, Jacobsen CS, Molin S.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94796

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Development of a defined medium and two-step culturing method for improved exotoxin A yields from Pseudomonas aeruginosa. by Blumentals II, Kelly RM, Gorziglia M, Kaufman JB, Shiloach J.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204050

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Different Responses of Pyoverdine Genes to Autoinduction in Pseudomonas aeruginosa and the Group Pseudomonas fluorescens-Pseudomonas putida. by Ambrosi C, Leoni L, Visca P.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124028

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Differential Ability of Genotypes of 2,4-Diacetylphloroglucinol-Producing Pseudomonas fluorescens Strains To Colonize the Roots of Pea Plants. by Landa BB, Mavrodi OV, Raaijmakers JM, McSpadden Gardener BB, Thomashow LS, Weller DM.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126803

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Differential Effects of Permeating and Nonpermeating Solutes on the Fatty Acid Composition of Pseudomonas putida. by Halverson LJ, Firestone MK.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110547

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Differential Expression of the Components of the Two Alkane Hydroxylases from Pseudomonas aeruginosa. by Marin MM, Yuste L, Rojo F.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154056

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Differential Roles of the Pseudomonas aeruginosa PA14 rpoN Gene in Pathogenicity in Plants, Nematodes, Insects, and Mice. by Hendrickson EL, Plotnikova J, MahajanMiklos S, Rahme LG, Ausubel FM.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95561

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Disruption of narG, the Gene Encoding the Catalytic Subunit of Respiratory Nitrate Reductase, Also Affects Nitrite Respiration in Pseudomonas fluorescens YT101. by Ghiglione JF, Philippot L, Normand P, Lensi R, Potier P.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94003

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Divergent Structure and Regulatory Mechanism of Proline Catabolic Systems: Characterization of the putAP Proline Catabolic Operon of Pseudomonas aeruginosa PAO1 and Its Regulation by PruR, an AraC/XylS Family Protein. by Nakada Y, Nishijyo T, Itoh Y.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139622

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DNA hybridization probe for the Pseudomonas fluorescens group. by Festl H, Ludwig W, Schleifer KH.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239196

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DNA sequence and transcriptional analysis of the tblA gene required for tabtoxin biosynthesis by Pseudomonas syringae. by Barta TM, Kinscherf TG, Uchytil TF, Willis DK.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202127

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Dual-Function Vaccine for Pseudomonas aeruginosa: Characterization of Chimeric Exotoxin A-Pilin Protein. by Hertle R, Mrsny R, Fitzgerald DJ.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100076

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Dynamics of a Nosocomial Outbreak of Multidrug-Resistant Pseudomonas aeruginosa Producing the PER-1 Extended-Spectrum [beta]-Lactamase. by Luzzaro F, Mantengoli E, Perilli M, Lombardi G, Orlandi V, Orsatti A, Amicosante G, Rossolini GM, Toniolo A.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88040

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Ecological and genetic analysis of copper and streptomycin resistance in Pseudomonas syringae pv. syringae. by Sundin GW, Bender CL.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202231

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Effect of Catalase on Hydrogen Peroxide Penetration into Pseudomonas aeruginosa Biofilms. by Stewart PS, Roe F, Rayner J, Elkins JG, Lewandowski Z, Ochsner UA, Hassett DJ.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91906

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Effect of Genetically Modified Pseudomonas putida WCS358r on the Fungal Rhizosphere Microflora of Field-Grown Wheat. by Glandorf DC, Verheggen P, Jansen T, Jorritsma JW, Smit E, Leeflang P, Wernars K, Thomashow LS, Laureijs E, ThomasOates JE, Bakker PA, van Loon LC.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93030

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Effect of Starvation and the Viable-but-Nonculturable State on Green Fluorescent Protein (GFP) Fluorescence in GFP-Tagged Pseudomonas fluorescens A506. by Lowder M, Unge A, Maraha N, Jansson JK, Swiggett J, Oliver JD.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92128

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Effect of Stress on the Ability of a phlA-Based Quantitative Competitive PCR Assay To Monitor Biocontrol Strain Pseudomonas fluorescens CHA0. by Rezzonico F, Moenne-Loccoz Y, Defago G.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152391

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Effect of temperature shifts on extracellular proteinase-specific mRNA pools in Pseudomonas fluorescens B52. by McKellar RC, Cholette H.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204038

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Effects of Combination of Different [minus sign]10 Hexamers and Downstream Sequences on Stationary-Phase-Specific Sigma Factor [final sigma]S-Dependent Transcription in Pseudomonas putida. by Ojangu EL, Tover A, Teras R, Kivisaar M.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111414

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Effects of FP2 and a mercury resistance plasmid from Pseudomonas aeruginosa PA103 on exoenzyme production. by Johnson J, Warren RL, Branstrom AA.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269912

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Effects of Mutations in the Pseudomonas putida miaA Gene: Regulation of the trpE and trpGDC Operons in P. putida by Attenuation. by Olekhnovich I, Gussin GN.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95228

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Efficient production and processing of elastase and LasA by Pseudomonas aeruginosa require zinc and calcium ions. by Olson JC, Ohman DE.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206126

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Efflux Pumps Involved in Toluene Tolerance in Pseudomonas putida DOT-T1E. by Ramos JL, Duque E, Godoy P, Segura A.; 1998 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107285

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Efflux-Mediated Resistance to Tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. by Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149306

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Elastase Deficiency Phenotype of Pseudomonas aeruginosa Canine Otitis Externa Isolates. by Petermann SR, Doetkott C, Rust L.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96114

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Elucidation of the Flavonoid Catabolism Pathway in Pseudomonas putida PML2 by Comparative Metabolic Profiling. by Pillai BV, Swarup S.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126565

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Enhanced binding of polycationic antibiotics to lipopolysaccharide from an aminoglycoside-supersusceptible, tolA mutant strain of Pseudomonas aeruginosa. by Rivera M, Hancock RE, Sawyer JG, Haug A, McGroarty EJ.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172247

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Enhancer-Binding Proteins HrpR and HrpS Interact To Regulate hrp-Encoded Type III Protein Secretion in Pseudomonas syringae Strains. by Hutcheson SW, Bretz J, Sussan T, Jin S, Pak K.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95450

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Epidemic Population Structure of Pseudomonas aeruginosa: Evidence for a Clone That Is Pathogenic to the Eye and That Has a Distinct Combination of Virulence Factors. by Lomholt JA, Poulsen K, Kilian M.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98763

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Epidemiological Analysis of Sequential Pseudomonas aeruginosa Isolates from Chronic Bronchiectasis Patients without Cystic Fibrosis. by Pujana I, Gallego L, Martin G, Lopez F, Canduela J, Cisterna R.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85036

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Evaluation of Genetic Diversity among Pseudomonas citronellolis Strains Isolated from Oily Sludge-Contaminated Sites. by Bhattacharya D, Sarma PM, Krishnan S, Mishra S, Lal B.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150093

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Evaluation of the Osiris Expert System for Identification of [beta]-Lactam Phenotypes in Isolates of Pseudomonas aeruginosa. by Bert F, Ould-Hocine Z, Juvin M, Dubois V, Loncle-Provot V, Lefranc V, Quentin C, Lambert N, Arlet G.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179830

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Evidence for a novel pathway in the degradation of fluorene by Pseudomonas sp. strain F274. by Grifoll M, Selifonov SA, Chapman PJ.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201668

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Evidence for different pyoverdine-mediated iron uptake systems among Pseudomonas aeruginosa strains. by Cornelis P, Hohnadel D, Meyer JM.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259858

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Evidence for Spread of a Clonal Strain of Pseudomonas aeruginosa among Cystic Fibrosis Clinics. by Armstrong D.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154738

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Exploiting Genotypic Diversity of 2,4-Diacetylphloroglucinol-Producing Pseudomonas spp.: Characterization of Superior Root-Colonizing P. fluorescens Strain Q8r1-96. by Raaijmakers JM, Weller DM.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92906

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Expression of the Pseudomonas putida OCT Plasmid Alkane Degradation Pathway Is Modulated by Two Different Global Control Signals: Evidence from Continuous Cultures. by Dinamarca MA, Aranda-Olmedo I, Puyet A, Rojo F.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166476

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Factors Influencing Expression of luxCDABE and nah Genes in Pseudomonas putida RB1353(NAH7, pUTK9) in Dynamic Systems. by Neilson JW, Pierce SA, Maier RM.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91522

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Fate of the Biological Control Agent Pseudomonas aureofaciens TX-1 after Application to Turfgrass. by Sigler WV, Nakatsu CH, Reicher ZJ, Turco RF.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93054

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First Isolation of a Carbapenem-Hydrolyzing [beta]-Lactamase in Pseudomonas aeruginosa in Spain. by Prats G, Miro E, Mirelis B.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127514

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fleQ, the Gene Encoding the Major Flagellar Regulator of Pseudomonas aeruginosa, Is [sigma]70 Dependent and Is Downregulated by Vfr, a Homolog of Escherichia coli Cyclic AMP Receptor Protein. by Dasgupta N, Ferrell EP, Kanack KJ, West SE, Ramphal R.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135356

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FlhA, a Component of the Flagellum Assembly Apparatus of Pseudomonas aeruginosa, Plays a Role in Internalization by Corneal Epithelial Cells. by Fleiszig SM, Arora SK, Van R, Ramphal R.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98584

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Fluorescent Pseudomonad Pyoverdines Bind and Oxidize Ferrous Ion. by Xiao R, Kisaalita WS.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106172

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FpvA Receptor Involvement in Pyoverdine Biosynthesis in Pseudomonas aeruginosa. by Shen J, Meldrum A, Poole K.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135083

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Functional Analysis and Regulation of the Divergent spuABCDEFGH-spuI Operons for Polyamine Uptake and Utilization in Pseudomonas aeruginosa PAO1. by Lu CD, Itoh Y, Nakada Y, Jiang Y.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135167

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Functional Analysis of Genes for Biosynthesis of Pyocyanin and Phenazine-1Carboxamide from Pseudomonas aeruginosa PAO1. by Mavrodi DV, Bonsall RF, Delaney SM, Soule MJ, Phillips G, Thomashow LS.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100142

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Functional Analysis of PvdS, an Iron Starvation Sigma Factor of Pseudomonas aeruginosa. by Leoni L, Orsi N, de Lorenzo V, Visca P.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94443

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Functions Required for Extracellular Quinolone Signaling by Pseudomonas aeruginosa. by Gallagher LA, McKnight SL, Kuznetsova MS, Pesci EC, Manoil C.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135424

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Gene Expression in Pseudomonas aeruginosa: Evidence of Iron Override Effects on Quorum Sensing and Biofilm-Specific Gene Regulation. by Bollinger N, Hassett DJ, Iglewski BH, Costerton JW, McDermott TR.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95094

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Genes Expressed in Pseudomonas putida during Colonization of a Plant-Pathogenic Fungus. by Lee SW, Cooksey DA.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92071

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Genes from Pseudomonas sp. Strain BS Involved in the Conversion of l-2-Amino[Delta]2-Thiazolin-4-Carbonic Acid to l-Cysteine. by Shiba T, Takeda K, Yajima M, Tadano M.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127550

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Genetic Analysis of the AdnA Regulon in Pseudomonas fluorescens: Nonessential Role of Flagella in Adhesion to Sand and Biofilm Formation. by Robleto EA, LopezHernandez I, Silby MW, Levy SB.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145307

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Genetic analysis of the antifungal activity of a soilborne Pseudomonas aureofaciens strain. by Vincent MN, Harrison LA, Brackin JM, Kovacevich PA, Mukerji P, Weller DM, Pierson EA.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183899

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Genetic and Molecular Organization of the Alkylbenzene Catabolism Operon in the Psychrotrophic Strain Pseudomonas putida 01G3. by Chablain PA, Zgoda AL, Sarde CO, Truffaut N.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92599

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Genetic and Phenotypic Variations of a Resistant Pseudomonas aeruginosa Epidemic Clone. by Hocquet D, Bertrand X, Kohler T, Talon D, Plesiat P.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155826

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Genetic Characterization and Evolutionary Implications of a car Gene Cluster in the Carbazole Degrader Pseudomonas sp. Strain CA10. by Nojiri H, Sekiguchi H, Maeda K, Urata M, Nakai SI, Yoshida T, Habe H, Omori T.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95244

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Genetic Diversity and Biological Control Activity of Novel Species of Closely Related Pseudomonads Isolated from Wheat Field Soils in South Australia. by Ross IL, Alami Y, Harvey PR, Achouak W, Ryder MH.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92030

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Genetic Diversity and Spoilage Potentials among Pseudomonas spp. Isolated from Fluid Milk Products and Dairy Processing Plants. by Dogan B, Boor KJ.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152439

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Genetic Evidence of Distinct Physiological Regulation Mechanisms in the [final sigma]54 Pu Promoter of Pseudomonas putida. by Cases I, de Lorenzo V.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94370

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Genetic Evidence that Loss of Virulence Associated with gacS or gacA Mutations in Pseudomonas syringae B728a Does Not Result from Effects on Alginate Production. by Willis DK, Holmstadt JJ, Kinscherf TG.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92744

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Genetic Investigation of the Catabolic Pathway for Degradation of Abietane Diterpenoids by Pseudomonas abietaniphila BKME-9. by Martin VJ, Mohn WW.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94551

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Genetics of O-Antigen Biosynthesis in Pseudomonas aeruginosa. by Rocchetta HL, Burrows LL, Lam JS.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103745

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Genotypic and Phenotypic Diversity of phlD-Containing Pseudomonas Strains Isolated from the Rhizosphere of Wheat. by McSpadden Gardener BB, Schroeder KL, Kalloger SE, Raaijmakers JM, Thomashow LS, Weller DM.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101437

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Global GacA-steered control of cyanide and exoprotease production in Pseudomonas fluorescens involves specific ribosome binding sites. by Blumer C, Heeb S, Pessi G, Haas D.; 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24192

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Growth of genetically engineered Pseudomonas aeruginosa and Pseudomonas putida in soil and rhizosphere. by Yeung KH, Schell MA, Hartel PG.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203257

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Growth on octane alters the membrane lipid fatty acids of Pseudomonas oleovorans due to the induction of alkB and synthesis of octanol. by Chen Q, Janssen DB, Witholt B.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177558

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Growth Phase and Temperature Influence Promoter Activity, Transcript Abundance, and Protein Stability during Biosynthesis of the Pseudomonas syringae Phytotoxin Coronatine. by Budde IP, Rohde BH, Bender CL, Ullrich MS.; 1998 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107031

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Growth Phase-Dependent Invasion of Pseudomonas aeruginosa and Its Survival within HeLa Cells. by Ha U, Jin S.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98512

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Heterogeneity of Pseudomonas aeruginosa in Brazilian Cystic Fibrosis Patients. by Silbert S, Barth AL, Sader HS.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88474

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Highly Different Levels of Natural Transformation Are Associated with Genomic Subgroups within a Local Population of Pseudomonas stutzeri from Soil. by Sikorski J, Teschner N, Wackernagel W.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126724

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High-Performance Liquid Chromatography Analyses of Pyoverdin Siderophores Differentiate among Phytopathogenic Fluorescent Pseudomonas Species. by Bultreys A, Gheysen I, Wathelet B, Maraite H, de Hoffmann E.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143633

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Homologous Expression of the Lipase and ABC Transporter Gene Cluster, tliDEFA, Enhances Lipase Secretion in Pseudomonas spp. by Ahn JH, Pan JG, Rhee JS.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93336

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Hydroxyectoine Is Superior to Trehalose for Anhydrobiotic Engineering of Pseudomonas putida KT2440. by Manzanera M, Garcia de Castro A, Tondervik A, Rayner-Brandes M, Strom AR, Tunnacliffe A.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124095

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Identification and Characterization of a Gene Cluster for Synthesis of the Polyketide Antibiotic 2,4-Diacetylphloroglucinol from Pseudomonas fluorescens Q2-87. by Bangera MG, Thomashow LS.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93771

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Identification and Characterization of Inhibitors of Multidrug Resistance Efflux Pumps in Pseudomonas aeruginosa: Novel Agents for Combination Therapy. by Lomovskaya O, Warren MS, Lee A, Galazzo J, Fronko R, Lee M, Blais J, Cho D, Chamberland S, Renau T, Leger R, Hecker S, Watkins W, Hoshino K, Ishida H, Lee VJ.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90247

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Identification and Manipulation of Soil Properties To Improve the Biological Control Performance of Phenazine-Producing Pseudomonas fluorescens. by Ownley BH, Duffy BK, Weller DM.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161483

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Identification and Sequencing of [beta]-Myrcene Catabolism Genes from Pseudomonas sp. Strain M1. by Iurescia S, Marconi AM, Tofani D, Gambacorta A, Paterno A, Devirgiliis C, van der Werf MJ, Zennaro E.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91431

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Identification of a Genomic Island Present in the Majority of Pathogenic Isolates of Pseudomonas aeruginosa. by Liang X, Pham XQ, Olson MV, Lory S.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94950

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Pseudomonas

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Identification of a penicillin-binding protein 3 homolog, PBP3x, in Pseudomonas aeruginosa: gene cloning and growth phase-dependent expression. by Liao X, Hancock RE.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178857

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Identification of an Emergent and Atypical Pseudomonas viridiflava Lineage Causing Bacteriosis in Plants of Agronomic Importance in a Spanish Region. by Gonzalez AJ, Rodicio MR, Mendoza MC.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154557

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Identification of an Escherichia coli pepA Homolog and Its Involvement in Suppression of the algB Phenotype in Mucoid Pseudomonas aeruginosa. by Woolwine SC, Wozniak DJ.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103538

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Identification of Essential Charged Residues in Transmembrane Segments of the Multidrug Transporter MexB of Pseudomonas aeruginosa. by Guan L, Nakae T.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95059

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Identification of exopolysaccharides produced by fluorescent pseudomonads associated with commercial mushroom (Agaricus bisporus) production. by Fett WF, Wells JM, Cescutti P, Wijey C.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167311

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Identification of the Pseudomonas stutzeri OX1 Toluene --o-Xylene Monooxygenase Regulatory Gene (touR) and of Its Cognate Promoter. by Arenghi FL, Pinti M, Galli E, Barbieri P.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99741

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Immunochemical Characterization and Taxonomic Evaluation of the O Polysaccharides of the Lipopolysaccharides of Pseudomonas syringae Serogroup O1 Strains. by Ovod VV, Knirel YA, Samson R, Krohn KJ.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94168

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Immunological characterization of ice nucleation proteins from Pseudomonas syringae, Pseudomonas fluorescens, and Erwinia herbicola. by Deininger CA, Mueller GM, Wolber PK.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210707

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Impact of 2,4-Diacetylphloroglucinol-Producing Biocontrol Strain Pseudomonas fluorescens F113 on Intraspecific Diversity of Resident Culturable Fluorescent Pseudomonads Associated with the Roots of Field-Grown Sugar Beet Seedlings. by Moenne-Loccoz Y, Tichy HV, O'Donnell A, Simon R, O'Gara F.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93037

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Impact of Biocontrol Pseudomonas fluorescens CHA0 and a Genetically Modified Derivative on the Diversity of Culturable Fungi in the Cucumber Rhizosphere. by Girlanda M, Perotto S, Moenne-Loccoz Y, Bergero R, Lazzari A, Defago G, Bonfante P, Luppi AM.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92807

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Impact of Siderophore Production on Pseudomonas aeruginosa Infections in Immunosuppressed Mice. by Takase H, Nitanai H, Hoshino K, Otani T.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97355

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In Vivo and In Vitro Evidence that TtgV Is the Specific Regulator of the TtgGHI Multidrug and Solvent Efflux Pump of Pseudomonas putida. by Rojas A, Segura A, Guazzaroni ME, Teran W, Hurtado A, Gallegos MT, Ramos JL.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166463

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In Vivo Emergence of Multidrug-Resistant Mutants of Pseudomonas aeruginosa Overexpressing the Active Efflux System MexA-MexB-OprM. by Ziha-Zarifi I, Llanes C, Kohler T, Pechere JC, Plesiat P.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89065

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Inactivation of gltB Abolishes Expression of the Assimilatory Nitrate Reductase Gene (nasB) in Pseudomonas putida KT2442. by Eberl L, Ammendola A, Rothballer MH, Givskov M, Sternberg C, Kilstrup M, Schleifer KH, Molin S.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101894

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Inactivation of the ampD Gene in Pseudomonas aeruginosa Leads to Moderate-BasalLevel and Hyperinducible AmpC [beta]-Lactamase Expression. by Langaee TY, Gagnon L, Huletsky A.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89730

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Incidence and persistence of Pseudomonas aeruginosa in whirlpools. by Price D, Ahearn DG.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266689

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Influence of a Putative ECF Sigma Factor on Expression of the Major Outer Membrane Protein, OprF, in Pseudomonas aeruginosa and Pseudomonas fluorescens. by Brinkman FS, Schoofs G, Hancock RE, De Mot R.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93957

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Influence of Deletions within Domain II of Exotoxin A on Its Extracellular Secretion from Pseudomonas aeruginosa. by Voulhoux R, Taupiac MP, Czjzek M, Beaumelle B, Filloux A.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94592

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Influence of the TonB Energy-Coupling Protein on Efflux-Mediated Multidrug Resistance in Pseudomonas aeruginosa. by Zhao Q, Li XZ, Mistry A, Srikumar R, Zhang L, Lomovskaya O, Poole K.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105788

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Inhibition of Quorum Sensing by a Pseudomonas aeruginosa dksA Homologue. by Branny P, Pearson JP, Pesci EC, Kohler T, Iglewski BH, Van Delden C.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95037

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Inhibitory effect against pathogenic and spoilage bacteria of Pseudomonas strains isolated from spoiled and fresh fish. by Gram L.; 1993 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182257

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Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. by Rashid MH, Kornberg A.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18327

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Input of Protein to Lake Water Microcosms Affects Expression of Proteolytic Enzymes and the Dynamics of Pseudomonas spp. by Worm J, Nybroe O.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93258

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Integration of Matrix-Assisted Laser Desorption Ionization --Time of Flight Mass Spectrometry and Molecular Cloning for the Identification and Functional Characterization of Mobile ortho-Halobenzoate Oxygenase Genes in Pseudomonas aeruginosa Strain JB2. by Hickey WJ, Sabat G.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93356

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Integron-Located oxa-32 Gene Cassette Encoding an Extended-Spectrum Variant of OXA-2 [beta]-Lactamase from Pseudomonas aeruginosa. by Poirel L, Gerome P, De Champs C, Stephanazzi J, Naas T, Nordmann P.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127075

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Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. by Calfee MW, Coleman JP, Pesci EC.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58781

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Interplay between Chromosomal [beta]-Lactamase and the MexAB-OprM Efflux System in Intrinsic Resistance to [beta]-Lactams in Pseudomonas aeruginosa. by Masuda N, Gotoh N, Ishii C, Sakagawa E, Ohya S, Nishino T.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89089

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Involvement of an Active Efflux System in the Natural Resistance of Pseudomonas aeruginosa to Aminoglycosides. by Aires JR, Kohler T, Nikaido H, Plesiat P.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89534

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Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance. by Moore RA, Hancock RE.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=180620

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Involvement of the cis/trans Isomerase Cti in Solvent Resistance of Pseudomonas putida DOT-T1E. by Junker F, Ramos JL.; 1999 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94089

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Involvement of the TonB System in Tolerance to Solvents and Drugs in Pseudomonas putida DOT-T1E. by Godoy P, Ramos-Gonzalez MI, Ramos JL.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95410

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Isolation and Antifungal and Antioomycete Activities of Aerugine Produced by Pseudomonas fluorescens Strain MM-B16. by Lee JY, Moon SS, Hwang BK.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154783

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Isolation and Characterization of the cis-trans-Unsaturated Fatty Acid Isomerase of Pseudomonas oleovorans GPo12. by Pedrotta V, Witholt B.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93784

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Isolation and expansion of the catabolic potential of a Pseudomonas putida strain able to grow in the presence of high concentrations of aromatic hydrocarbons. by Ramos JL, Duque E, Huertas MJ, Haidour A.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177117

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Isolation of a methyl parathion-degrading Pseudomonas sp. that possesses DNA homologous to the opd gene from a Flavobacterium sp. by Chaudhry GR, Ali AN, Wheeler WB.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202445

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Isolation of Bacteriophages Specific to a Fish Pathogen, Pseudomonas plecoglossicida, as a Candidate for Disease Control. by Park SC, Shimamura I, Fukunaga M, Mori KI, Nakai T.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92002

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Kelthane degradation by genetically engineered Pseudomonas aeruginosa BS827 in a soil ecosystem. by Golovleva LA, Pertsova RN, Boronin AM, Travkin VM, Kozlovsky SA.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202700

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Kinetics of nirS Expression (Cytochrome cd1 Nitrite Reductase) in Pseudomonas stutzeri during the Transition from Aerobic Respiration to Denitrification: Evidence for a Denitrification-Specific Nitrate- and Nitrite-Responsive Regulatory System. by Hartig E, Zumft WG.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103545

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Lipase and Its Modulator from Pseudomonas sp. Strain KFCC 10818: Proline-toGlutamine Substitution at Position 112 Induces Formation of Enzymatically Active Lipase in the Absence of the Modulator. by Kim EK, Jang WH, Ko JH, Kang JS, Noh MJ, Yoo OJ.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99672

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Lipase modulator protein (LimL) of Pseudomonas sp. strain 109. by Ihara F, Okamoto I, Akao K, Nihira T, Yamada Y.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176731

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Lipopeptide Production in Pseudomonas sp. Strain DSS73 Is Regulated by Components of Sugar Beet Seed Exudate via the Gac Two-Component Regulatory System. by Koch B, Nielsen TH, Sorensen D, Andersen JB, Christophersen C, Molin S, Givskov M, Sorensen J, Nybroe O.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124083

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Lon Protease Influences Antibiotic Production and UV Tolerance of Pseudomonas fluorescens Pf-5. by Whistler CA, Stockwell VO, Loper JE.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92065

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Low-Frequency Horizontal Transfer of an Element Containing the Chlorocatechol Degradation Genes from Pseudomonas sp. Strain B13 to Pseudomonas putida F1 and to Indigenous Bacteria in Laboratory-Scale Activated-Sludge Microcosms. by Ravatn R, Zehnder AJ, van der Meer JR.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106288

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Low-Temperature-Induced Changes in Composition and Fluidity of Lipopolysaccharides in the Antarctic Psychrotrophic Bacterium Pseudomonas syringae. by Seshu Kumar G, Jagannadham MV, Ray MK.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135421

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Pseudomonas

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Mannitol, a novel bacterial compatible solute in Pseudomonas putida S12. by Kets EP, Galinski EA, de Wit M, de Bont JA, Heipieper HJ.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178559

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Mechanism for Biotransformation of Nonylphenol Polyethoxylates to Xenoestrogens in Pseudomonas putida. by John DM, White GF.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107438

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Mercury and Organomercurial Resistances Determined by Plasmids in Pseudomonas. by Clark DL, Weiss AA, Silver S.; 1977 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221844

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Metabolism of dibenzothiophene and naphthalene in Pseudomonas strains: complete DNA sequence of an upper naphthalene catabolic pathway. by Denome SA, Stanley DC, Olson ES, Young KD.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206814

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Metabolism of hexadecyltrimethylammonium chloride in Pseudomonas strain B1. by van Ginkel CG, van Dijk JB, Kroon AG.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183052

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Modification of Dienes Mutual Inhibition Test for Epidemiological Characterization of Pseudomonas aeruginosa Isolates. by Munson EL, Pfaller MA, Doern GV.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139714

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Molecular Analysis of Pseudomonas aeruginosa: Epidemiological Investigation of Mastitis Outbreaks in Irish Dairy Herds. by Daly M, Power E, Bjorkroth J, Sheehan P, O'Connell A, Colgan M, Korkeala H, Fanning S.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91402

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Molecular and Biochemical Characterization of OXA-45, an Extended-Spectrum Class 2d[prime prime or minute] [beta]-Lactamase in Pseudomonas aeruginosa. by Toleman MA, Rolston K, Jones RN, Walsh TR.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182593

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Molecular and Phenotypic Characterization of Pseudomonas spp. Isolated from Milk. by Wiedmann M, Weilmeier D, Dineen SS, Ralyea R, Boor KJ.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101459

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Molecular Characterization of OXA-20, a Novel Class D [beta]-Lactamase, and Its Integron from Pseudomonas aeruginosa. by Naas T, Sougakoff W, Casetta A, Nordmann P.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105865

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Molecular Characterization of the Genes pcaG and pcaH, Encoding Protocatechuate 3,4-Dioxygenase, Which Are Essential for Vanillin Catabolism in Pseudomonas sp. Strain HR199. by Overhage J, Kresse AU, Priefert H, Sommer H, Krammer G, Rabenhorst J, Steinbuchel A.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91128

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Molecular cloning of a Pseudomonas syringae pv. syringae gene cluster that enables Pseudomonas fluorescens to elicit the hypersensitive response in tobacco plants. by Huang HC, Schuurink R, Denny TP, Atkinson MM, Baker CJ, Yucel I, Hutcheson SW, Collmer A.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211517

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Molecular Diversity of Plasmids Bearing Genes That Encode Toluene and Xylene Metabolism in Pseudomonas Strains Isolated from Different Contaminated Sites in Belarus. by Sentchilo VS, Perebituk AN, Zehnder AJ, van der Meer JR.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92082

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Molecular Mechanisms of Fluoroquinolone Resistance in Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients. by Jalal S, Ciofu O, Hoiby N, Gotoh N, Wretlind B.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89751

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Molecular Surveillance of European Quinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa and Acinetobacter spp. Using Automated Ribotyping. by Brisse S, Milatovic D, Fluit AC, Kusters K, Toelstra A, Verhoef J, Schmitz FJ.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87449

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Monitoring Intracellular Levels of XylR in Pseudomonas putida with a Single-Chain Antibody Specific for Aromatic-Responsive Enhancer-Binding Proteins. by Fraile S, Roncal F, Fernandez LA, de Lorenzo V.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95448

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Monooxygenase-Mediated 1,2-Dichloroethane Degradation by Pseudomonas sp. Strain DCA1. by Hage JC, Hartmans S.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91363

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Morphological Change in Pseudomonas aeruginosa following Antibiotic Treatment of Experimental Infection in Mice and Its Relation to Susceptibility to Phagocytosis and to Release of Endotoxin. by Yokochi T, Narita K, Morikawa A, Takahashi K, Kato Y, Sugiyama T, Koide N, Kawai M, Fukada M, Yoshida T.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89656

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Multidrug Efflux Pumps: Expression Patterns and Contribution to Antibiotic Resistance in Pseudomonas aeruginosa Biofilms. by De Kievit TR, Parkins MD, Gillis RJ, Srikumar R, Ceri H, Poole K, Iglewski BH, Storey DG.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90543

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Mutational Analysis of the OprM Outer Membrane Component of the MexA-MexBOprM Multidrug Efflux System of Pseudomonas aeruginosa. by Li XZ, Poole K.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94845

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Mutations in Each of the tol Genes of Pseudomonas putida Reveal that They Are Critical for Maintenance of Outer Membrane Stability. by Llamas MA, Ramos JL, Rodriguez-Herva JJ.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111352

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Mutations in Genes Involved in the Flagellar Export Apparatus of the SolventTolerant Pseudomonas putida DOT-T1E Strain Impair Motility and Lead to Hypersensitivity to Toluene Shocks. by Segura A, Duque E, Hurtado A, Ramos JL.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95300

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Pseudomonas

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N-Acylhomoserine Lactones Undergo Lactonolysis in a pH-, Temperature-, and Acyl Chain Length-Dependent Manner during Growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. by Yates EA, Philipp B, Buckley C, Atkinson S, Chhabra SR, Sockett RE, Goldner M, Dessaux Y, Camara M, Smith H, Williams P.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128322

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NahY, a Catabolic Plasmid-Encoded Receptor Required for Chemotaxis of Pseudomonas putida to the Aromatic Hydrocarbon Naphthalene. by Grimm AC, Harwood CS.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93795

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Negative Control of Flagellum Synthesis in Pseudomonas aeruginosa Is Modulated by the Alternative Sigma Factor AlgT (AlgU). by Garrett ES, Perlegas D, Wozniak DJ.; 1999 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103708

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Nitric Oxide Signaling and Transcriptional Control of Denitrification Genes in Pseudomonas stutzeri. by Vollack KU, Zumft WG.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95168

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Nosocomial Outbreak Due to a Multiresistant Strain of Pseudomonas aeruginosa P12: Efficacy of Cefepime-Amikacin Therapy and Analysis of [beta]-Lactam Resistance. by Dubois V, Arpin C, Melon M, Melon B, Andre C, Frigo C, Quentin C.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88091

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Nosocomial Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa with a New blaIMP Allele, blaIMP-7. by Gibb AP, Tribuddharat C, Moore RA, Louie TJ, Krulicki W, Livermore DM, Palepou MF, Woodford N.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126979

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Nucleotide sequencing and transcriptional mapping of the genes encoding biphenyl dioxygenase, a multicomponent polychlorinated-biphenyl-degrading enzyme in Pseudomonas strain LB400. by Erickson BD, Mondello FJ.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205943

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O-Antigen Serotypes and Type III Secretory Toxins in Clinical Isolates of Pseudomonas aeruginosa. by Faure K, Shimabukuro D, Ajayi T, Allmond LR, Sawa T, Wiener-Kronish JP.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154700

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Occurrence of a Multidrug-Resistant Pseudomonas aeruginosa Clone in Different Hospitals in Rio de Janeiro, Brazil. by Pellegrino FL, Teixeira LM, Carvalho MD, Aranha Nouer S, Pinto de Oliveira M, Mello Sampaio JL, D'Avila Freitas A, Ferreira AL, Amorim ED, Riley LW, Moreira BM.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120547

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Operon Structure and Regulation of the nos Gene Region of Pseudomonas stutzeri, Encoding an ABC-Type ATPase for Maturation of Nitrous Oxide Reductase. by Honisch U, Zumft WG.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150149

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Outbreak of Infections Caused by Pseudomonas aeruginosa Producing VIM-1 Carbapenemase in Greece. by Tsakris A, Pournaras S, Woodford N, Palepou MF, Babini GS, Douboyas J, Livermore DM.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88610

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Outer Membrane Changes in a Toluene-Sensitive Mutant of Toluene-Tolerant Pseudomonas putida IH-2000. by Kobayashi H, Takami H, Hirayama H, Kobata K, Usami R, Horikoshi K.; 1999 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103577

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Overexpression of the MexEF-OprN Multidrug Efflux System Affects Cell-to-Cell Signaling in Pseudomonas aeruginosa. by Kohler T, van Delden C, Curty LK, Hamzehpour MM, Pechere JC.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95401

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OXA-16, a Further Extended-Spectrum Variant of OXA-10 [beta]-Lactamase, from Two Pseudomonas aeruginosa Isolates. by Danel F, Hall LM, Gur D, Livermore DM.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106009

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Oxacillinase-Mediated Resistance to Cefepime and Susceptibility to Ceftazidime in Pseudomonas aeruginosa. by Aubert D, Poirel L, Chevalier J, Leotard S, Pages JM, Nordmann P.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90522

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Oxygen-Sensing Reporter Strain of Pseudomonas fluorescens for Monitoring the Distribution of Low-Oxygen Habitats in Soil. by Hojberg O, Schnider U, Winteler HV, Sorensen J, Haas D.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99745

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Pathogenesis of the Human Opportunistic Pathogen Pseudomonas aeruginosa PA14 in Arabidopsis. by Plotnikova JM, Rahme LG, Ausubel FM.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59873

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Pathovars of Pseudomonas syringae Causing Bacterial Brown Spot and Halo Blight in Phaseolus vulgaris L. Are Distinguishable by Ribotyping. by Gonzalez AJ, Landeras E, Mendoza MC.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91909

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Pathways of Assimilative Sulfur Metabolism in Pseudomonas putida. by Vermeij P, Kertesz MA.; 1999 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94106

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PhaG-Mediated Synthesis of Poly(3-Hydroxyalkanoates) Consisting of MediumChain-Length Constituents from Nonrelated Carbon Sources in Recombinant Pseudomonas fragi. by Fiedler S, Steinbuchel A, Rehm BH.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101463

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Phase-Variable Expression of an Operon Encoding Extracellular Alkaline Protease, a Serine Protease Homolog, and Lipase in Pseudomonas brassicacearum. by Chabeaud P, de Groot A, Bitter W, Tommassen J, Heulin T, Achouak W.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95110

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Phenotypic and genotypic characterization of phenanthrene-degrading fluorescent Pseudomonas biovars. by Johnsen K, Andersen S, Jacobsen CS.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168190

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Physical and Metabolic Interactions of Pseudomonas sp. Strain JA5-B45 and Rhodococcus sp. Strain F9-D79 during Growth on Crude Oil and Effect of a Chemical Surfactant on Them. by Van Hamme JD, Ward OP.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93243

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Pseudomonas

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Physiological Analysis of the Expression of the Styrene Degradation Gene Cluster in Pseudomonas fluorescens ST. by Santos PM, Blatny JM, Di Bartolo I, Valla S, Zennaro E.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91985

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Physiological Characterization of Pseudomonas aeruginosa during Exotoxin A Synthesis: Glutamate, Iron Limitation, and Aconitase Activity. by Somerville G, Mikoryak CA, Reitzer L.; 1999 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93482

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Physiological properties of a Pseudomonas strain which grows with p-xylene in a two-phase (organic-aqueous) medium. by Cruden DL, Wolfram JH, Rogers RD, Gibson DT.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182999

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phzO, a Gene for Biosynthesis of 2-Hydroxylated Phenazine Compounds in Pseudomonas aureofaciens 30-84. by Delaney SM, Mavrodi DV, Bonsall RF, Thomashow LS.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94881

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Plasmid control of the Pseudomonas aeruginosa and Pseudomonas putida phenotypes and of linalool and p-cymene oxidation. by de Smet MJ, Friedman MB, Gunsalus IC.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210330

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Polymerase C1 levels and poly(R-3-hydroxyalkanoate) synthesis in wild-type and recombinant Pseudomonas strains. by Kraak MN, Smits TH, Kessler B, Witholt B.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179353

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Polynucleotide Phosphorylase-Deficient Mutants of Pseudomonas putida. by Favaro R, Deho G.; 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=180990

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Polyphosphate kinase is essential for biofilm development, quorum sensing, and virulence of Pseudomonas aeruginosa. by Rashid MH, Rumbaugh K, Passador L, Davies DG, Hamood AN, Iglewski BH, Kornberg A.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16917

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Positive Correlation between Virulence of Pseudomonas aeruginosa Mutants in Mice and Insects. by Jander G, Rahme LG, Ausubel FM.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94559

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Posttranscriptional Control of Quorum-Sensing-Dependent Virulence Genes by DksA in Pseudomonas aeruginosa. by Jude F, Kohler T, Branny P, Perron K, Mayer MP, Comte R, van Delden C.; 2003 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156223

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Presence of Pseudomonas putida Strains Harboring Plasmids Bearing the Metallo[beta]-Lactamase Gene blaIMP in a Hospital in Japan. by Yomoda S, Okubo T, Takahashi A, Murakami M, Iyobe S.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193810

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87

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Prevalence of gca, a gene involved in synthesis of A-band common antigen polysaccharide in Pseudomonas aeruginosa. by Currie HL, Lightfoot J, Lam JS.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170199

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Product of fosC, a gene from Pseudomonas syringae, mediates fosfomycin resistance by using ATP as cosubstrate. by Garcia P, Arca P, Evaristo Suarez J.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162783

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Production and Comparison of Peptide Siderophores from Strains of Distantly Related Pathovars of Pseudomonas syringae and Pseudomonas viridiflava LMG 2352. by Bultreys A, Gheysen I.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91825

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Production of Cyclic Lipopeptides by Pseudomonas fluorescens Strains in Bulk Soil and in the Sugar Beet Rhizosphere. by Nielsen TH, Sorensen J.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143599

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Proline Catabolism by Pseudomonas putida: Cloning, Characterization, and Expression of the put Genes in the Presence of Root Exudates. by Vilchez S, Molina L, Ramos C, Ramos JL.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94244

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Promoter Specificity Elements in Pseudomonas aeruginosa Quorum-SensingControlled Genes. by Whiteley M, Greenberg EP.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95443

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Proteome Analysis of the Effect of Mucoid Conversion on Global Protein Expression in Pseudomonas aeruginosa Strain PAO1 Shows Induction of the Disulfide Bond Isomerase, DsbA. by Malhotra S, Silo-Suh LA, Mathee K, Ohman DE.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94826

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Pseudobactin Biogenesis in the Plant Growth-Promoting Rhizobacterium Pseudomonas Strain B10: Identification and Functional Analysis of the l-Ornithine N5-Oxygenase (psbA) Gene. by Ambrosi C, Leoni L, Putignani L, Orsi N, Visca P.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94761

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Pseudomonas aeruginosa Cell-to-Cell Signaling Is Required for Virulence in a Model of Acute Pulmonary Infection. by Pearson JP, Feldman M, Iglewski BH, Prince A.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101761

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Pseudomonas aeruginosa Hemolytic Phospholipase C Suppresses Neutrophil Respiratory Burst Activity. by Terada LS, Johansen KA, Nowbar S, Vasil AI, Vasil ML.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115980

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Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. by Smith RS, Iglewski BH.; 2003 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=259138

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Pseudomonas aeruginosa Reveals High Intrinsic Resistance to Penem Antibiotics: Penem Resistance Mechanisms and Their Interplay. by Okamoto K, Gotoh N, Nishino T.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90586

88

Pseudomonas

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Pseudomonas aeruginosa selective adherence to and entry into human endothelial cells. by Plotkowski MC, Saliba AM, Pereira SH, Cervante MP, Bajolet-Laudinat O.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303288

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Pseudomonas aeruginosa sodA and sodB mutants defective in manganese- and ironcofactored superoxide dismutase activity demonstrate the importance of the ironcofactored form in aerobic metabolism. by Hassett DJ, Schweizer HP, Ohman DE.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177481

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Pseudomonas cepacia adherence to respiratory epithelial cells is enhanced by Pseudomonas aeruginosa. by Saiman L, Cacalano G, Prince A.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258858

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Pseudomonas fluorescens Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen. by Wei B, Huang T, Dalwadi H, Sutton CL, Bruckner D, Braun J.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133002

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Pseudomonas sp. Strain 273, an Aerobic [alpha],[omega]-DichloroalkaneDegrading Bacterium. by Wischnak C, Loffler FE, Li J, Urbance JW, Muller R.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106756

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Pseudomonas syringae Phytotoxins: Mode of Action, Regulation, and Biosynthesis by Peptide and Polyketide Synthetases. by Bender CL, Alarcon-Chaidez F, Gross DC.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98966

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Purification and Characterization of Gentisate 1,2-Dioxygenases from Pseudomonas alcaligenes NCIB 9867 and Pseudomonas putida NCIB 9869. by Feng Y, Khoo HE, Poh CL.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91127

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Purification and properties of 2,3-dihydroxybiphenyl dioxygenase from polychlorinated biphenyl-degrading Pseudomonas pseudoalcaligenes and Pseudomonas aeruginosa carrying the cloned bphC gene. by Furukawa K, Arimura N.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211873

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Quantification of Chemotaxis to Naphthalene by Pseudomonas putida G7. by Marx RB, Aitken MD.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91427

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Quantitative Selective PCR of 16S Ribosomal DNA Correlates Well with Selective Agar Plating in Describing Population Dynamics of Indigenous Pseudomonas spp. in Soil Hot Spots. by Johnsen K, Enger O, Jacobsen CS, Thirup L, Torsvik V.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91253

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Quinolobactin, a New Siderophore of Pseudomonas fluorescens ATCC 17400, the Production of Which Is Repressed by the Cognate Pyoverdine. by Mossialos D, Meyer JM, Budzikiewicz H, Wolff U, Koedam N, Baysse C, Anjaiah V, Cornelis P.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91853

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Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. by Pesci EC, Milbank JB, Pearson JP, McKnight S, Kende AS, Greenberg EP, Iglewski BH.; 1999 Sep 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18016

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Real-Time Reverse Transcription-PCR Analysis of Expression of Halobenzoate and Salicylate Catabolism-Associated Operons in Two Strains of Pseudomonas aeruginosa. by Corbella ME, Puyet A.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154809

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Reduction of Olive Knot Disease by a Bacteriocin from Pseudomonas syringae pv. ciccaronei. by Lavermicocca P, Lonigro SL, Valerio F, Evidente A, Visconti A.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123734

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Reevaluation, using intact cells, of the exclusion limit and role of porin OprF in Pseudomonas aeruginosa outer membrane permeability. by Bellido F, Martin NL, Siehnel RJ, Hancock RE.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206352

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Regioselectivity of nitroglycerin denitration by flavoprotein nitroester reductases purified from two Pseudomonas species. by Blehert DS, Knoke KL, Fox BG, Chambliss GH.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179628

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Regulation of Alginate Biosynthesis in Pseudomonas syringae pv. syringae. by Fakhr MK, Penaloza-Vazquez A, Chakrabarty AM, Bender CL.; 1999 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93816

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Regulation of ExoS Production and Secretion by Pseudomonas aeruginosa in Response to Tissue Culture Conditions. by Vallis AJ, Yahr TL, Barbieri JT, Frank DW.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96404

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Regulation of rpoS Gene Expression in Pseudomonas: Involvement of a TetR Family Regulator. by Kojic M, Venturi V.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95248

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Regulation of the hemA gene during 5-aminolevulinic acid formation in Pseudomonas aeruginosa. by Hungerer C, Troup B, Romling U, Jahn D.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176757

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Regulatory mutations of the Pseudomonas plasmid alk regulon. by Fennewald M, Shapiro J.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221904

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Removal of Mercury from Chloralkali Electrolysis Wastewater by a MercuryResistant Pseudomonas putida Strain. by von Canstein H, Li Y, Timmis KN, Deckwer WD, Wagner-Dobler I.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91717

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Repression of Phenazine Antibiotic Production in Pseudomonas aureofaciens Strain 30-84 by RpeA. by Whistler CA, Pierson III LS.; 2003 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161564

90

Pseudomonas

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Requirement of Novel Competence Genes pilT and pilU of Pseudomonas stutzeri for Natural Transformation and Suppression of pilT Deficiency by a Hexahistidine Tag on the Type IV Pilus Protein PilAI. by Graupner S, Weger N, Sohni M, Wackernagel W.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99522

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Resistance of Pseudomonas aeruginosa Isolates to Hydrogel Contact Lens Disinfection Correlates with Cytotoxic Activity. by Lakkis C, Fleiszig SM.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87957

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Resistance to Tellurite as a Selection Marker for Genetic Manipulations of Pseudomonas Strains. by Sanchez-Romero JM, Diaz-Orejas R, De Lorenzo V.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106597

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Responses to nutrient starvation in Pseudomonas putida KT2442: analysis of general cross-protection, cell shape, and macromolecular content. by Givskov M, Eberl L, Moller S, Poulsen LK, Molin S.; 1994 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205008

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Rhizoremediation of Trichloroethylene by a Recombinant, Root-Colonizing Pseudomonas fluorescens Strain Expressing Toluene ortho-Monooxygenase Constitutively. by Yee DC, Maynard JA, Wood TK.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124680

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Ribonucleotide Reduction in Pseudomonas Species: Simultaneous Presence of Active Enzymes from Different Classes. by Jordan A, Torrents E, Sala I, Hellman U, Gibert I, Reichard P.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93887

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Risk of cross-colonization and infection by Pseudomonas aeruginosa in a holiday camp for cystic fibrosis patients. by Hoogkamp-Korstanje JA, Meis JF, Kissing J, van der Laag J, Melchers WJ.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227992

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RNA polymerases from Pseudomonas aeruginosa and Pseudomonas syringae respond to Escherichia coli activator proteins. by Gao JG, Gussin GN.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207199

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Role of copper resistance in competitive survival of Pseudomonas fluorescens in soil. by Yang CH, Menge JA, Cooksey DA.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202147

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Role of Fatty Acid De Novo Biosynthesis in Polyhydroxyalkanoic Acid (PHA) and Rhamnolipid Synthesis by Pseudomonads: Establishment of the Transacylase (PhaG)-Mediated Pathway for PHA Biosynthesis in Escherichia coli. by Rehm BH, Mitsky TA, Steinbuchel A.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92987

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Role of Flagella in Pathogenesis of Pseudomonas aeruginosa Pulmonary Infection. by Feldman M, Bryan R, Rajan S, Scheffler L, Brunnert S, Tang H, Prince A.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107856

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Role of phaD in Accumulation of Medium-Chain-Length Poly(3-Hydroxyalkanoates) in Pseudomonas oleovorans. by Klinke S, de Roo G, Witholt B, Kessler B.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92210

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Role of Pseudomonas putida tol-oprL Gene Products in Uptake of Solutes through the Cytoplasmic Membrane. by Llamas MA, Rodriguez-Herva JJ, Hancock RE, Bitter W, Tommassen J, Ramos JL.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166457

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Role of Respiratory Nitrate Reductase in Ability of Pseudomonas fluorescens YT101 To Colonize the Rhizosphere of Maize. by Ghiglione JF, Gourbiere F, Potier P, Philippot L, Lensi R.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92252

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Role of the Alternative Sigma Factor [final sigma]S in Expression of the AlkS Regulator of the Pseudomonas oleovorans Alkane Degradation Pathway. by Canosa I, Yuste L, Rojo F.; 1999 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93572

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Role of the crc Gene in Catabolic Repression of the Pseudomonas putida GPo1 Alkane Degradation Pathway. by Yuste L, Rojo F.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100097

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Role of the Hrp type III protein secretion system in growth of Pseudomonas syringae pv. syringae B728a on host plants in the field. by Hirano SS, Charkowski AO, Collmer A, Willis DK, Upper CD.; 1999 Aug 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22299

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Role of the Multidrug Efflux Systems of Pseudomonas aeruginosa in Organic Solvent Tolerance. by Li XZ, Zhang L, Poole K.; 1998 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107269

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Role of the Pseudomonas aeruginosa oxyR-recG Operon in Oxidative Stress Defense and DNA Repair: OxyR-Dependent Regulation of katB-ankB, ahpB, and ahpC-ahpF. by Ochsner UA, Vasil ML, Alsabbagh E, Parvatiyar K, Hassett DJ.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94625

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Role of the Tat Transport System in Nitrous Oxide Reductase Translocation and Cytochrome cd1 Biosynthesis in Pseudomonas stutzeri. by Heikkila MP, Honisch U, Wunsch P, Zumft WG.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95051

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Roles of N-acetylglutaminylglutamine amide and glycine betaine in adaptation of Pseudomonas aeruginosa to osmotic stress. by D'Souza-Ault MR, Smith LT, Smith GM.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202129

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Roles of Pseudomonas aeruginosa las and rhl Quorum-Sensing Systems in Control of Twitching Motility. by Glessner A, Smith RS, Iglewski BH, Robinson JB.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93554

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Roles of the Carboxy-Terminal Half of Pseudomonas aeruginosa Major Outer Membrane Protein OprF in Cell Shape, Growth in Low-Osmolarity Medium, and Peptidoglycan Association. by Rawling EG, Brinkman FS, Hancock RE.; 1998 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107322

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Selection of Pseudomonas sp. strain HBP1 Prp for metabolism of 2-propylphenol and elucidation of the degradative pathway. by Kohler HP, van der Maarel MJ, KohlerStaub D.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202200

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Self-mobilization and organization of the genes encoding the toluene metabolic pathway of Pseudomonas mendocina KR1. by Wright A, Olsen RH.; 1994 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201294

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Sequence Diversity of rulA among Natural Isolates of Pseudomonas syringae and Effect on Function of rulAB-Mediated UV Radiation Tolerance. by Sundin GW, Jacobs JL, Murillo J.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92439

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Sequence Diversity of the oprI Gene, Coding for Major Outer Membrane Lipoprotein I, among rRNA Group I Pseudomonads. by De Vos D, Bouton C, Sarniguet A, De Vos P, Vauterin M, Cornelis P.; 1998 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107757

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Siderophore receptor PupA as a marker to monitor wild-type Pseudomonas putida WCS358 in natural environments. by Raaijmakers JM, Bitter W, Punte HL, Bakker PA, Weisbeek PJ, Schippers B.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201457

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Siderophore Typing, a Powerful Tool for the Identification of Fluorescent and Nonfluorescent Pseudomonads. by Meyer JM, Geoffroy VA, Baida N, Gardan L, Izard D, Lemanceau P, Achouak W, Palleroni NJ.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123936

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Siderophores and outer membrane proteins of antagonistic, plant-growthstimulating, root-colonizing Pseudomonas spp. by de Weger LA, van Boxtel R, van der Burg B, Gruters RA, Geels FP, Schippers B, Lugtenberg B.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214459

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Single and Combination Antibiotic Susceptibilities of Planktonic, Adherent, and Biofilm-Grown Pseudomonas aeruginosa Isolates Cultured from Sputa of Adults with Cystic Fibrosis. by Aaron SD, Ferris W, Ramotar K, Vandemheen K, Chan F, Saginur R.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139693

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Single-Nucleotide-Polymorphism Mapping of the Pseudomonas aeruginosa Type III Secretion Toxins for Development of a Diagnostic Multiplex PCR System. by Ajayi T, Allmond LR, Sawa T, Wiener-Kronish JP.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179785

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snr-1 Gene Is Required for Nitrate Reduction in Pseudomonas aeruginosa PAO1. by Kerschen EJ, Irani VR, Hassett DJ, Rowe JJ.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95112

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Spatial Physiological Heterogeneity in Pseudomonas aeruginosa Biofilm Is Determined by Oxygen Availability. by Xu KD, Stewart PS, Xia F, Huang CT, McFeters GA.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106596

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Species-Specific Oligonucleotides for Enumeration of Pseudomonas putida F1, Burkholderia sp. Strain JS150, and Bacillus subtilis ATCC 7003 in Biodegradation Experiments. by DuTeau NM, Rogers JD, Bartholomay CT, Reardon KF.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90954

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Specific genomic fingerprints of phytopathogenic Xanthomonas and Pseudomonas pathovars and strains generated with repetitive sequences and PCR. by Louws FJ, Fulbright DW, Stephens CT, de Bruijn FJ.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=201645

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Statistical Analysis of Pseudomonas aeruginosa Biofilm Development: Impact of Mutations in Genes Involved in Twitching Motility, Cell-to-Cell Signaling, and Stationary-Phase Sigma Factor Expression. by Heydorn A, Ersboll B, Kato J, Hentzer M, Parsek MR, Tolker-Nielsen T, Givskov M, Molin S.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123874

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Stringent Response Activates Quorum Sensing and Modulates Cell DensityDependent Gene Expression in Pseudomonas aeruginosa. by van Delden C, Comte R, Bally AM.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95422

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Structural, functional, and evolutionary analysis of moeZ, a gene encoding an enzyme required for the synthesis of the Pseudomonas metabolite, pyridine-2,6bis(thiocarboxylic acid). by Cortese MS, Caplan AB, Crawford RL.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115864

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Structure and regulation of the carAB operon in Pseudomonas aeruginosa and Pseudomonas stutzeri: no untranslated region exists. by Kwon DH, Lu CD, Walthall DA, Brown TM, Houghton JE, Abdelal AT.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205390

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Succession of Indigenous Pseudomonas spp. and Actinomycetes on Barley Roots Affected by the Antagonistic Strain Pseudomonas fluorescens DR54 and the Fungicide Imazalil. by Thirup L, Johnsen K, Winding A.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92707

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Superoxide Dismutase Activity in Pseudomonas putida Affects Utilization of Sugars and Growth on Root Surfaces. by Kim YC, Miller CD, Anderson AJ.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92008

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Survival in Soil of Different Toluene-Degrading Pseudomonas Strains after Solvent Shock. by Huertas MJ, Duque E, Marques S, Ramos JL.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124669

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Survival of GacS/GacA Mutants of the Biological Control Bacterium Pseudomonas aureofaciens 30-84 in the Wheat Rhizosphere. by Chancey ST, Wood DW, Pierson EA, Pierson III LS.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126771

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Survival of rifampin-resistant mutants of Pseudomonas fluorescens and Pseudomonas putida in soil systems. by Compeau G, Al-Achi BJ, Platsouka E, Levy SB.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204279

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Swarming of Pseudomonas aeruginosa Is Dependent on Cell-to-Cell Signaling and Requires Flagella and Pili. by Kohler T, Curty LK, Barja F, van Delden C, Pechere JC.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94731

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The Alternative Sigma Factor RpoN Is Required for hrp Activity in Pseudomonas syringae pv. Maculicola and Acts at the Level of hrpL Transcription. by Hendrickson EL, Guevera P, Ausubel FM.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101944

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The atzABC Genes Encoding Atrazine Catabolism Are Located on a SelfTransmissible Plasmid in Pseudomonas sp. Strain ADP. by de Souza ML, Wackett LP, Sadowsky MJ.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106326

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The Avr (Effector) Proteins HrmA (HopPsyA) and AvrPto Are Secreted in Culture from Pseudomonas syringae Pathovars via the Hrp (Type III) Protein Secretion System in a Temperature- and pH-Sensitive Manner. by van Dijk K, Fouts DE, Rehm AH, Hill AR, Collmer A, Alfano JR.; 1999 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93963

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The Branched-Chain Dodecylbenzene Sulfonate Degradation Pathway of Pseudomonas aeruginosa W51D Involves a Novel Route for Degradation of the Surfactant Lateral Alkyl Chain. by Campos-Garcia J, Esteve A, Vazquez-Duhalt R, Ramos JL, Soberon-Chavez G.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91560

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The CAM-OCT plasmid enhances UV responses of Pseudomonas aeruginosa recA mutants. by McBeth DL.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208603

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The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000. by Buell CR, Joardar V, Lindeberg M, Selengut J, Paulsen IT, Gwinn ML, Dodson RJ, Deboy RT, Durkin AS, Kolonay JF, Madupu R, Daugherty S, Brinkac L, Beanan MJ, Haft DH, Nelson WC, Davidsen T, Zafar N, Zhou L, Liu J, Yuan Q, Khouri H, Fedorova N, Tran B, Russell D, Berry K, Utterback T, Van Aken SE, Feldblyum TV, D'Ascenzo M, Deng WL, Ramos AR, Alfano JR, Cartinhour S, Chatterjee AK, Delaney TP, Lazarowitz SG, Martin GB, Schneider DJ, Tang X, Bender CL, White O, Fraser CM, Collmer A.; 2003 Sep 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193536

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The emerging periplasm-localized subclass of AroQ chorismate mutases, exemplified by those from Salmonella typhimurium and Pseudomonas aeruginosa. by Calhoun DH, Bonner CA, Gu W, Xie G, Jensen RA.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55327

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The Global Posttranscriptional Regulator RsmA Modulates Production of Virulence Determinants and N-Acylhomoserine Lactones in Pseudomonas aeruginosa. by Pessi G, Williams F, Hindle Z, Heurlier K, Holden MT, Camara M, Haas D, Williams P.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95500

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The PalkBFGHJKL Promoter Is under Carbon Catabolite Repression Control in Pseudomonas oleovorans but Not in Escherichia coli alk + Recombinants. by Staijen IE, Marcionelli R, Witholt B.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93552

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The Periplasmic Nitrate Reductase in Pseudomonas sp. Strain G-179 Catalyzes the First Step of Denitrification. by Bedzyk L, Wang T, Ye RW.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93722

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The Pseudomonas aeruginosa Lectins PA-IL and PA-IIL Are Controlled by Quorum Sensing and by RpoS. by Winzer K, Falconer C, Garber NC, Diggle SP, Camara M, Williams P.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94786

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The Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3Oxododecanoyl)Homoserine Lactone Contributes to Virulence and Induces Inflammation In Vivo. by Smith RS, Harris SG, Phipps R, Iglewski B.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134808

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The Pseudomonas aeruginosa rhlAB Operon Is Not Expressed during the Logarithmic Phase of Growth Even in the Presence of Its Activator RhlR and the Autoinducer NButyryl-Homoserine Lactone. by Medina G, Juarez K, Soberon-Chavez G.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141836

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The Pseudomonas aeruginosa rhlG Gene Encodes an NADPH-Dependent [beta]Ketoacyl Reductase Which Is Specifically Involved in Rhamnolipid Synthesis. by Campos-Garcia J, Caro AD, Najera R, Miller-Maier RM, Al-Tahhan RA, Soberon-Chavez G.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107453

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The Pseudomonas syringae pv. tomato HrpW Protein Has Domains Similar to Harpins and Pectate Lyases and Can Elicit the Plant Hypersensitive Response and Bind to Pectate. by Charkowski AO, Alfano JR, Preston G, Yuan J, He SY, Collmer A.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107559

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The Sigma Factor AlgU (AlgT) Controls Exopolysaccharide Production and Tolerance towards Desiccation and Osmotic Stress in the Biocontrol Agent Pseudomonas fluorescens CHA0. by Schnider-Keel U, Lejbolle KB, Baehler E, Haas D, Keel C.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93360

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The ssu Locus Plays a Key Role in Organosulfur Metabolism in Pseudomonas putida S-313. by Kahnert A, Vermeij P, Wietek C, James P, Leisinger T, Kertesz MA.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101997

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The Sulfur-Regulated Arylsulfatase Gene Cluster of Pseudomonas aeruginosa, a New Member of the cys Regulon. by Hummerjohann J, Laudenbach S, Retey J, Leisinger T, Kertesz MA.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101934

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The Transcriptional Regulator AlgR Is Essential for Pseudomonas aeruginosa Pathogenesis. by Lizewski SE, Lundberg DS, Schurr MJ.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130412

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The Two-Component Regulators GacS and GacA Influence Accumulation of the Stationary-Phase Sigma Factor [final sigma]S and the Stress Response in Pseudomonas fluorescens Pf-5. by Whistler CA, Corbell NA, Sarniguet A, Ream W, Loper JE.; 1998 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107767

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The Viable-but-Nonculturable State Induced by Abiotic Stress in the Biocontrol Agent Pseudomonas fluorescens CHA0 Does Not Promote Strain Persistence in Soil. by Mascher F, Hase C, Moenne-Loccoz Y, Defago G.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92038

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Thermoregulated Expression and Characterization of an NAD(P)H-Dependent 2Cyclohexen-1-one Reductase in the Plant Pathogenic Bacterium Pseudomonas syringae pv. glycinea. by Rohde BH, Schmid R, Ullrich MS.; 1999 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93447

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Three distinct quinoprotein alcohol dehydrogenases are expressed when Pseudomonas putida is grown on different alcohols. by Toyama H, Fujii A, Matsushita K, Shinagawa E, Ameyama M, Adachi O.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176903

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Towards a Biocatalyst for (S)-Styrene Oxide Production: Characterization of the Styrene Degradation Pathway of Pseudomonas sp. Strain VLB120. by Panke S, Witholt B, Schmid A, Wubbolts MG.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106275

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Transcriptional Control of the Hydrogen Cyanide Biosynthetic Genes hcnABC by the Anaerobic Regulator ANR and the Quorum-Sensing Regulators LasR and RhlR in Pseudomonas aeruginosa. by Pessi G, Haas D.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94819

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Transcriptional Organization and Dynamic Expression of the hbpCAD Genes, Which Encode the First Three Enzymes for 2-Hydroxybiphenyl Degradation in Pseudomonas azelaica HBP1. by Jaspers MC, Schmid A, Sturme MH, Goslings DA, Kohler HP, Roelof van der Meer J.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94875

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Transcriptional Organization of the Pseudomonas putida tol-oprL Genes. by Llamas MA, Ramos JL, Rodriguez-Herva JJ.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141831

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Twitching Motility Contributes to the Role of Pili in Corneal Infection Caused by Pseudomonas aeruginosa. by Zolfaghar I, Evans DJ, Fleiszig SM.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187331

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Two Distinct Alcohol Dehydrogenases Participate in Butane Metabolism by Pseudomonas butanovora. by Vangnai AS, Arp DJ, Sayavedra-Soto LA.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134940

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Two-Component Transcriptional Regulation of N-Acyl-Homoserine Lactone Production in Pseudomonas aureofaciens. by Chancey ST, Wood DW, Pierson LS III.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91339

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Type II Topoisomerase Mutations in Ciprofloxacin-Resistant Strains of Pseudomonas aeruginosa. by Mouneimne H, Robert J, Jarlier V, Cambau E.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89021

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Type II Topoisomerase Mutations in Fluoroquinolone-Resistant Clinical Strains of Pseudomonas aeruginosa Isolated in 1998 and 1999: Role of Target Enzyme in Mechanism of Fluoroquinolone Resistance. by Akasaka T, Tanaka M, Yamaguchi A, Sato K.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90640

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Unusual Integrase Gene Expression on the clc Genomic Island in Pseudomonas sp. Strain B13. by Sentchilo V, Ravatn R, Werlen C, Zehnder AJ, van der Meer JR.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165761

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Uptake of Pyocin S3 Occurs through the Outer Membrane Ferripyoverdine Type II Receptor of Pseudomonas aeruginosa. by Baysse C, Meyer JM, Plesiat P, Geoffroy V, Michel-Briand Y, Cornelis P.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93868

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Use of a Genetic Approach To Evaluate the Consequences of Inhibition of Efflux Pumps in Pseudomonas aeruginosa. by Lomovskaya O, Lee A, Hoshino K, Ishida H, Mistry A, Warren MS, Boyer E, Chamberland S, Lee VJ.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89275

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Use of an Intergenic Region in Pseudomonas syringae pv. Syringae B728a for SiteDirected Genomic Marking of Bacterial Strains for Field Experiments. by Hirano SS, Willis DK, Clayton MK, Upper CD.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93081

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Use of Subtractive Hybridization To Identify a Diagnostic Probe for a Cystic Fibrosis Epidemic Strain of Pseudomonas aeruginosa. by Parsons YN, Panagea S, Smart CH, Walshaw MJ, Hart CA, Winstanley C.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154653

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Use of ureidopenicillins for selection of plasmid vector transformants in Pseudomonas aeruginosa and Pseudomonas putida. by Day DL, Yasinow D, McDonough J, Shuster CW.; 1984 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215350

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Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion. by Kadurugamuwa JL, Beveridge TJ.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177130

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Virulence of the Phytopathogen Pseudomonas syringae pv. Maculicola Is rpoN Dependent. by Hendrickson EL, Guevera P, Penaloza-Vazquez A, Shao J, Bender C, Ausubel FM.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101941

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Zinc Eluted from Siliconized Latex Urinary Catheters Decreases OprD Expression, Causing Carbapenem Resistance in Pseudomonas aeruginosa. by Conejo MC, Garcia I, Martinez-Martinez L, Picabea L, Pascual A.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161826

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 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

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

A clinical index predicting mortality with Pseudomonas aeruginosa bacteraemia. Author(s): Aliaga L, Mediavilla JD, Cobo F. Source: Journal of Medical Microbiology. 2002 July; 51(7): 615-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12132781

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A liposome model to treat pseudomonas in lungs of cystic fibrosis and immune compromised patients. Author(s): Yatvin MB. Source: Cellular & Molecular Biology Letters. 2002; 7(2): 304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097974

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A mathematical model of partial-thickness burn-wound infection by Pseudomonas aeruginosa: quorum sensing and the build-up to invasion. Author(s): Koerber AJ, King JR, Ward JP, Williams P, Croft JM, Sockett RE. Source: Bulletin of Mathematical Biology. 2002 March; 64(2): 239-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926116

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A preliminary study on metallo-beta-lactamase producing Pseudomonas aeruginosa in hospitalized patients. Author(s): Navaneeth BV, Sridaran D, Sahay D, Belwadi MR. Source: The Indian Journal of Medical Research. 2002 December; 116: 264-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807154

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A simple alfalfa seedling infection model for Pseudomonas aeruginosa strains associated with cystic fibrosis shows AlgT (sigma-22) and RhlR contribute to pathogenesis. Author(s): Silo-Suh L, Suh SJ, Sokol PA, Ohman DE. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 26; 99(24): 15699-704. Epub 2002 Nov 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426404

journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A wound-isolated Pseudomonas aeruginosa grows a biofilm in vitro within 10 hours and is visualized by light microscopy. Author(s): Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz PM. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 June; 29(6): 631-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786708

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Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomonal activity. Author(s): Paramythiotou E, Lucet JC, Timsit JF, Vanjak D, Paugam-Burtz C, Trouillet JL, Belloc S, Kassis N, Karabinis A, Andremont A. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 March 1; 38(5): 670-7. Epub 2004 February 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14986251

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Activation of the Pseudomonas aeruginosa type III secretion system requires an intact pyruvate dehydrogenase aceAB operon. Author(s): Dacheux D, Epaulard O, de Groot A, Guery B, Leberre R, Attree I, Polack B, Toussaint B. Source: Infection and Immunity. 2002 July; 70(7): 3973-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065547

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Acute mastoiditis in children: Pseudomonas aeruginosa as a leading pathogen. Author(s): Butbul-Aviel Y, Miron D, Halevy R, Koren A, Sakran W. Source: International Journal of Pediatric Otorhinolaryngology. 2003 March; 67(3): 27781. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633928

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Adherence of Pseudomonas aeruginosa strains to solid surfaces. Author(s): Wolska K, Sowka A, Bukowski K, Jakubczak A. Source: Acta Microbiol Pol. 2001; 50(3-4): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11931000

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Adhesion of Pseudomonas aeruginosa strains to untreated and oxygen-plasma treated poly(vinyl chloride) (PVC) from endotracheal intubation devices. Author(s): Triandafillu K, Balazs DJ, Aronsson BO, Descouts P, Tu Quoc P, van Delden C, Mathieu HJ, Harms H. Source: Biomaterials. 2003 April; 24(8): 1507-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12527292

100 Pseudomonas

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Ambler class A extended-spectrum beta-lactamases in Pseudomonas aeruginosa: novel developments and clinical impact. Author(s): Weldhagen GF, Poirel L, Nordmann P. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2385-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878494

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An outbreak of carbapenem-resistant Pseudomonas aeruginosa in a urology ward. Author(s): Pena C, Dominguez MA, Pujol M, Verdaguer R, Gudiol F, Ariza J. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 938-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616682

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An outbreak of conjunctivitis caused by multiresistant Pseudomonas aeruginosa in a Brazilian newborn intensive care unit. Author(s): Brito DV, Oliveira EJ, Matos C, Abdallah VO, Gontijo Filho PP. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2003 August; 7(4): 234-5. Epub 2003 December 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533982

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An outbreak of multidrug-resistant Pseudomonas aeruginosa associated with increased risk of patient death in an intensive care unit. Author(s): Bukholm G, Tannaes T, Kjelsberg AB, Smith-Erichsen N. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 August; 23(8): 441-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186209

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An outbreak of Pseudomonas aeruginosa infections associated with flexible bronchoscopes. Author(s): Srinivasan A, Wolfenden LL, Song X, Mackie K, Hartsell TL, Jones HD, Diette GB, Orens JB, Yung RC, Ross TL, Merz W, Scheel PJ, Haponik EF, Perl TM. Source: The New England Journal of Medicine. 2003 January 16; 348(3): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529462

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Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. Author(s): Hassett DJ, Cuppoletti J, Trapnell B, Lymar SV, Rowe JJ, Yoon SS, Hilliard GM, Parvatiyar K, Kamani MC, Wozniak DJ, Hwang SH, McDermott TR, Ochsner UA. Source: Advanced Drug Delivery Reviews. 2002 December 5; 54(11): 1425-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458153

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101

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Analysis of the two common alpha-1-antitrypsin deficiency alleles PiMS and PiMZ as modifiers of Pseudomonas aeruginosa susceptibility in cystic fibrosis. Author(s): Meyer P, Braun A, Roscher AA. Source: Clinical Genetics. 2002 October; 62(4): 325-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372062

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Analysis of transmission pathways of Pseudomonas aeruginosa between patients and tap water outlets. Author(s): Reuter S, Sigge A, Wiedeck H, Trautmann M. Source: Critical Care Medicine. 2002 October; 30(10): 2222-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394948

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Antibacterial activity of 2,4-diacetylphloroglucinol produced by Pseudomonas sp. AMSN isolated from a marine alga, against vancomycin-resistant Staphylococcus aureus. Author(s): Isnansetyo A, Cui L, Hiramatsu K, Kamei Y. Source: International Journal of Antimicrobial Agents. 2003 November; 22(5): 545-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602377

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Antibacterial activity of intraocularly used liquids against two strains of Pseudomonas aeruginosa. Author(s): Economou-Stamatelopoulou C, Roussopoulos GP, Prouskas JC, Apostolopoulos M. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 November-December; 217(6): 426-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573977

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Antibiotic sensitivity patterns of Pseudomonas aeruginosa strains isolated from various clinical specimens. Author(s): Shenoy S, Baliga S, Saldanha DR, Prashanth HV. Source: Indian Journal of Medical Sciences. 2002 September; 56(9): 427-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12710338

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Antimicrobial susceptibility of imipenem-resistant Pseudomonas aeruginosa. Author(s): Higgins PG, Fluit AC, Milatovic D, Verhoef J, Schmitz FJ. Source: The Journal of Antimicrobial Chemotherapy. 2002 August; 50(2): 299-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161417

102 Pseudomonas

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Antimicrobial susceptibility testing of carbapenems: multicenter validity testing and accuracy levels of five antimicrobial test methods for detecting resistance in Enterobacteriaceae and Pseudomonas aeruginosa isolates. Author(s): Steward CD, Mohammed JM, Swenson JM, Stocker SA, Williams PP, Gaynes RP, McGowan JE Jr, Tenover FC. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 351-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517872

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Antineutrophil cytoplasmic antibodies directed against bactericidal/permeabilityincreasing protein detected in children with cystic fibrosis inhibit neutrophilmediated killing of Pseudomonas aeruginosa. Author(s): Sediva A, Bartunkova J, Bartosova J, Jennette C, Falk RJ, Jethwa HS. Source: Microbes and Infection / Institut Pasteur. 2003 January; 5(1): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593970

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Apoptosis induced by Pseudomonas aeruginosa in antigen presenting cells is diminished by genetic modification with CD40 ligand. Author(s): Worgall S, Martushova K, Busch A, Lande L, Crystal RG. Source: Pediatric Research. 2002 November; 52(5): 636-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409507

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Apoptotic response of Chang cells to infection with Pseudomonas aeruginosa strains PAK and PAO-I: molecular ordering of the apoptosis signaling cascade and role of type IV pili. Author(s): Jendrossek V, Fillon S, Belka C, Muller I, Puttkammer B, Lang F. Source: Infection and Immunity. 2003 May; 71(5): 2665-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704141

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Application of proteomics to Pseudomonas aeruginosa. Author(s): Nouwens AS, Walsh BJ, Cordwell SJ. Source: Adv Biochem Eng Biotechnol. 2003; 83: 117-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12934928

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Association of Pseudomonas aeruginosa and Serratia marcescens with extended-wear soft contact lenses in asymptomatic patients. Author(s): Ahanotu EN, Ahearn DG. Source: The Clao Journal : Official Publication of the Contact Lens Association of Ophthalmologists, Inc. 2002 July; 28(3): 157-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12144237

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103

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Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. Author(s): Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA, Coquillette S, Fieberg AY, Accurso FJ, Campbell PW 3rd; Macrolide Study Group. Source: Jama : the Journal of the American Medical Association. 2003 October 1; 290(13): 1749-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519709

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Bacteria killing their own kind: novel bacteriocins of Pseudomonas and other gamma-proteobacteria. Author(s): Parret AH, De Mot R. Source: Trends in Microbiology. 2002 March; 10(3): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11864811

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Bactericidal properties of group IIa secreted phospholipase A(2) against Pseudomonas aeruginosa clinical isolates. Author(s): Dubouix A, Campanac C, Fauvel J, Simon MF, Salles JP, Roques C, Chap H, Marty N. Source: Journal of Medical Microbiology. 2003 December; 52(Pt 12): 1039-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614061

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Beekeeper's arthritis caused by Pseudomonas aeruginosa. Author(s): Montes I, Torresano M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 June 15; 34(12): 1662. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032911

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Biosurfactant production by a new Pseudomonas putida strain. Author(s): Tuleva BK, Ivanov GR, Christova NE. Source: Z Naturforsch [c]. 2002 March-April; 57(3-4): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064740

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blaVIM-7, an evolutionarily distinct metallo-beta-lactamase gene in a Pseudomonas aeruginosa isolate from the United States. Author(s): Toleman MA, Rolston K, Jones RN, Walsh TR. Source: Antimicrobial Agents and Chemotherapy. 2004 January; 48(1): 329-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693560

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Blocking of Pseudomonas aeruginosa lectins by human milk glycans. Author(s): Lesman-Movshovich E, Lerrer B, Gilboa-Garber N. Source: Canadian Journal of Microbiology. 2003 March; 49(3): 230-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12795411

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Capillary electrophoresis study of outer membrane proteins of Pseudomonas strains upon antibiotic treatment. Author(s): Kustos T, Kustos I, Gonda E, Kocsis B, Szabo G, Kilar F. Source: J Chromatogr A. 2002 December 6; 979(1-2): 277-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498259

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Carbapenemase-producing Pseudomonas aeruginosa and ciprofloxcacin use in neonatal intensive care units. Author(s): Toraman ZA, Yakupogullari Y. Source: The Journal of Hospital Infection. 2003 June; 54(2): 164-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818594

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Cefepime, piperacillin/tazobactam, gentamicin, ciprofloxacin, and levofloxacin alone and in combination against Pseudomonas aeruginosa. Author(s): Burgess DS, Nathisuwan S. Source: Diagnostic Microbiology and Infectious Disease. 2002 September; 44(1): 35-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376029

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Cerebrospinal fluid-cutaneous fistula and pseudomonas meningitis complicating thoracic epidural analgesia. Author(s): Abaza KT, Bogod DG. Source: British Journal of Anaesthesia. 2004 March; 92(3): 429-31. Epub 2004 January 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742337

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Characterization of Pseudomonas aeruginosa isolates from patients with urinary tract infections during antibiotic therapy. Author(s): Horii T, Muramatsu H, Morita M, Maekawa M. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Summer; 9(2): 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820809

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Characterization of the onset and consequences of pneumonia due to fluoroquinolone-susceptible or -resistant Pseudomonas aeruginosa. Author(s): Paladino JA, Sunderlin JL, Forrest A, Schentag JJ. Source: The Journal of Antimicrobial Chemotherapy. 2003 September; 52(3): 457-63. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888598

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Chimeric ecotropic MLV envelope proteins that carry EGF receptor-specific ligands and the Pseudomonas exotoxin A translocation domain to target gene transfer to human cancer cells. Author(s): Erlwein O, Wels W, Schnierle BS. Source: Virology. 2002 October 25; 302(2): 333-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441077

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105

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Chromosomally-encoded resistance mechanisms of Pseudomonas aeruginosa: therapeutic implications. Author(s): Lister PD. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. 2002; 2(4): 235-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12421094

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Chronic postoperative endophthalmitis due to pseudomonas oryzihabitans. Author(s): Yu EN, Foster CS. Source: American Journal of Ophthalmology. 2002 October; 134(4): 613-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383826

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Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates from keratitis. Author(s): Lomholt JA, Kilian M. Source: The British Journal of Ophthalmology. 2003 October; 87(10): 1238-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507757

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c-Jun NH2-terminal kinase-mediated signaling is essential for Pseudomonas aeruginosa ExoS-induced apoptosis. Author(s): Jia J, Alaoui-El-Azher M, Chow M, Chambers TC, Baker H, Jin S. Source: Infection and Immunity. 2003 June; 71(6): 3361-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12761120

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Class 1 integron containing metallo-beta-lactamase gene blaVIM-2 in Pseudomonas aeruginosa clinical strains isolated in Japan. Author(s): Yatsuyanagi J, Saito S, Harata S, Suzuki N, Ito Y, Amano K, Enomoto K. Source: Antimicrobial Agents and Chemotherapy. 2004 February; 48(2): 626-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742222

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Clinical and bacteriological characteristics of IMP-type metallo-beta-lactamaseproducing Pseudomonas aeruginosa. Author(s): Hirakata Y, Yamaguchi T, Nakano M, Izumikawa K, Mine M, Aoki S, Kondoh A, Matsuda J, Hirayama M, Yanagihara K, Miyazaki Y, Tomono K, Yamada Y, Kamihira S, Kohno S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 26-32. Epub 2003 June 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830405

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Clinical strain of Pseudomonas aeruginosa carrying a bla(TEM-21) gene located on a chromosomal interrupted TnA type transposon. Author(s): Dubois V, Arpin C, Noury P, Quentin C. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3624-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384376

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Clinical study to assess the immunogenicity and safety of a recombinant Pseudomonas aeruginosa OprF-OprI vaccine in burn patients. Author(s): Mansouri E, Blome-Eberwein S, Gabelsberger J, Germann G, von Specht BU. Source: Fems Immunology and Medical Microbiology. 2003 July 15; 37(2-3): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832120

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Community-acquired Pseudomonas aeruginosa sepsis in previously healthy infants and children: analysis of forty-three episodes. Author(s): Huang YC, Lin TY, Wang CH. Source: The Pediatric Infectious Disease Journal. 2002 November; 21(11): 1049-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442028

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Comparative analysis of type III effector translocation by Yersinia pseudotuberculosis expressing native LcrV or PcrV from Pseudomonas aeruginosa. Author(s): Broms JE, Sundin C, Francis MS, Forsberg A. Source: The Journal of Infectious Diseases. 2003 July 15; 188(2): 239-49. Epub 2003 Jul 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854079

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Comparative studies on the activity of basil--an essential oil from Ocimum basilicum L.--against multidrug resistant clinical isolates of the genera Staphylococcus, Enterococcus and Pseudomonas by using different test methods. Author(s): Opalchenova G, Obreshkova D. Source: Journal of Microbiological Methods. 2003 July; 54(1): 105-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732427

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Comparative study of antimicrobial resistance of Pseudomonas aeruginosa strains isolated from urinary tract infection in patients from Caracas and Lima. Author(s): Rodriguez CN, Molina N, Garcia A, Nino C RA, Rodriguez AJ, Meijomil P. Source: International Journal of Antimicrobial Agents. 2002 December; 20(6): 476-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12458146

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Comparison of four antimicrobial susceptibility testing methods to determine the in vitro activities of piperacillin and piperacillin-tazobactam against clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa. Author(s): Karlowsky JA, Weaver MK, Thornsberry C, Dowzicky MJ, Jones ME, Sahm DF. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3339-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843088

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Compromised host defense on Pseudomonas aeruginosa biofilms: characterization of neutrophil and biofilm interactions. Author(s): Jesaitis AJ, Franklin MJ, Berglund D, Sasaki M, Lord CI, Bleazard JB, Duffy JE, Beyenal H, Lewandowski Z. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 October 15; 171(8): 4329-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530358

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Conservation of genome content and virulence determinants among clinical and environmental isolates of Pseudomonas aeruginosa. Author(s): Wolfgang MC, Kulasekara BR, Liang X, Boyd D, Wu K, Yang Q, Miyada CG, Lory S. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 8; 100(14): 8484-9. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815109

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Constitutive high expression of chromosomal beta-lactamase in Pseudomonas aeruginosa caused by a new insertion sequence (IS1669) located in ampD. Author(s): Bagge N, Ciofu O, Hentzer M, Campbell JI, Givskov M, Hoiby N. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3406-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12384343

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Contamination of a milk bank pasteuriser causing a Pseudomonas aeruginosa outbreak in a neonatal intensive care unit. Author(s): Gras-Le Guen C, Lepelletier D, Debillon T, Gournay V, Espaze E, Roze JC. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 September; 88(5): F434-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937053

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Corneal response to Pseudomonas aeruginosa infection. Author(s): Hazlett LD. Source: Progress in Retinal and Eye Research. 2004 January; 23(1): 1-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766315

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Cross infection of cystic fibrosis patients with Pseudomonas aeruginosa. Author(s): Pitt TL. Source: Thorax. 2002 November; 57(11): 921. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403869

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Cross-reactivity between related sequences found in Acinetobacter sp., Pseudomonas aeruginosa, myelin basic protein and myelin oligodendrocyte glycoprotein in multiple sclerosis. Author(s): Hughes LE, Smith PA, Bonell S, Natt RS, Wilson C, Rashid T, Amor S, Thompson EJ, Croker J, Ebringer A. Source: Journal of Neuroimmunology. 2003 November; 144(1-2): 105-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597104

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Cross-sectional analysis of clinical and environmental isolates of Pseudomonas aeruginosa: biofilm formation, virulence, and genome diversity. Author(s): Head NE, Yu H. Source: Infection and Immunity. 2004 January; 72(1): 133-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688090

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Current and future perspectives for levofloxacin in severe Pseudomonas aeruginosa infections. Author(s): Marchetti F, Viale P. Source: J Chemother. 2003 August; 15(4): 315-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962358

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Cystic fibrosis airway epithelial cell polarity and bacterial flagellin determine host response to Pseudomonas aeruginosa. Author(s): Hybiske K, Ichikawa JK, Huang V, Lory SJ, Machen TE. Source: Cellular Microbiology. 2004 January; 6(1): 49-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678330

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Decisions facing the cystic fibrosis clinician at first isolation of Pseudomonas aeruginosa. Author(s): Bush A. Source: Paediatric Respiratory Reviews. 2002 March; 3(1): 82-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065187

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Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic. Author(s): Armstrong DS, Nixon GM, Carzino R, Bigham A, Carlin JB, Robins-Browne RM, Grimwood K. Source: American Journal of Respiratory and Critical Care Medicine. 2002 October 1; 166(7): 983-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359658

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Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients. Author(s): Favre-Bonte S, Pache JC, Robert J, Blanc D, Pechere JC, van Delden C. Source: Microbial Pathogenesis. 2002 March; 32(3): 143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11855945

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Determination of quorum-sensing signal molecules and virulence factors of Pseudomonas aeruginosa isolates from contact lens-induced microbial keratitis. Author(s): Zhu H, Thuruthyil SJ, Willcox MD. Source: Journal of Medical Microbiology. 2002 December; 51(12): 1063-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466404

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Development of a diagnostic PCR assay that targets a heat-shock protein gene (groES) for detection of Pseudomonas spp. in cystic fibrosis patients. Author(s): Clarke L, Moore JE, Millar BC, Garske L, Xu J, Heuzenroeder MW, Crowe M, Elborn JS. Source: Journal of Medical Microbiology. 2003 September; 52(Pt 9): 759-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909651

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Development of a high throughput Pseudomonas aeruginosa epithelial cell adhesion assay. Author(s): Swanson B, Savel R, Szoka F, Sawa T, Wiener-Kronish J. Source: Journal of Microbiological Methods. 2003 March; 52(3): 361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531505

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Development of a rapid assay for screening point mutations associated with quinolone resistance in the Pseudomonas aeruginosa parC gene. Author(s): Deguchi T, Yamaha M, Nakano M, Yasuda M, Nishino Y, Ishihara S, Kawada Y. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2000 March; 6(1): 26-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810527

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Development of resistance in Pseudomonas aeruginosa obtained from patients with cystic fibrosis at different times. Author(s): Spencker FB, Staber L, Lietz T, Schille R, Rodloff AC. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 May; 9(5): 370-9. Erratum In: Clin Microbiol Infect. 2003 July; 9(7): 759-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848749

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Differential interactions within the Caenorhabditis elegans-Pseudomonas aeruginosa pathogenesis model. Author(s): Ruiz-Diez B, Sanchez P, Baquero F, Martinez JL, Navas A. Source: Journal of Theoretical Biology. 2003 December 21; 225(4): 469-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615205

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Differential proteinase expression by Pseudomonas aeruginosa derived from chronic leg ulcers. Author(s): Schmidtchen A, Wolff H, Hansson C. Source: Acta Dermato-Venereologica. 2001 November-December; 81(6): 406-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11859942

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Distinct fates of monocytes and T cells directly activated by Pseudomonas aeruginosa exoenzyme S. Author(s): Epelman S, Neely GG, Ma LL, Gjomarkaj M, Pace E, Melis M, Woods DE, Mody CH. Source: Journal of Leukocyte Biology. 2002 March; 71(3): 458-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11867683

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DNA restriction is a barrier to natural transformation in Pseudomonas stutzeri JM300. Author(s): Berndt C, Meier P, Wackernagel W. Source: Microbiology (Reading, England). 2003 April; 149(Pt 4): 895-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686632

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DNA vaccines against chronic lung infections by Pseudomonas aeruginosa. Author(s): Staczek J, Gilleland LB, van der Heyde HC, Gilleland HE. Source: Fems Immunology and Medical Microbiology. 2003 July 15; 37(2-3): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832118

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Doxycycline in the management of pseudomonas corneal melting: two case reports and a review of the literature. Author(s): McElvanney AM. Source: Eye & Contact Lens. 2003 October; 29(4): 258-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555906

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DsbA of Pseudomonas aeruginosa is essential for multiple virulence factors. Author(s): Ha UH, Wang Y, Jin S. Source: Infection and Immunity. 2003 March; 71(3): 1590-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595484

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Ecthyma gangrenosum arising from Pseudomonas aeruginosa dacryocystitis. Author(s): Watson A, Sloan B. Source: Clinical & Experimental Ophthalmology. 2003 August; 31(4): 366-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12880468

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Effect of basic amino acids on susceptibility to carbapenems in clinical Pseudomonas aeruginosa isolates. Author(s): Muramatsu H, Horii T, Morita M, Hashimoto H, Kanno T, Maekawa M. Source: International Journal of Medical Microbiology : Ijmm. 2003 June; 293(2-3): 191-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868655

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Effect of siliconized latex urinary catheters on the activity of carbapenems against Pseudomonas aeruginosa strains with defined mutations in ampC, oprD, and genes coding for efflux systems. Author(s): Conejo MC, Martinez-Martinez L, Garcia I, Picabea L, Pascual A. Source: International Journal of Antimicrobial Agents. 2003 August; 22(2): 122-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927951

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Effect of Varidase (streptodornase) on biofilm formed by Pseudomonas aeruginosa. Author(s): Nemoto K, Hirota K, Murakami K, Taniguti K, Murata H, Viducic D, Miyake Y. Source: Chemotherapy. 2003 June; 49(3): 121-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815204

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Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia. Author(s): Chamot E, Boffi El Amari E, Rohner P, Van Delden C. Source: Antimicrobial Agents and Chemotherapy. 2003 September; 47(9): 2756-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12936970

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Effector ExoU from the type III secretion system is an important modulator of gene expression in lung epithelial cells in response to Pseudomonas aeruginosa infection. Author(s): McMorran B, Town L, Costelloe E, Palmer J, Engel J, Hume D, Wainwright B. Source: Infection and Immunity. 2003 October; 71(10): 6035-44. Erratum In: Infect Immun. 2003 December; 71(12): 7240. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500525

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Effects of erythromycin on Pseudomonas aeruginosa adherence to collagen and morphology in vitro. Author(s): Tsang KW, Ng P, Ho PL, Chan S, Tipoe G, Leung R, Sun J, Ho JC, Ip MS, Lam WK. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 March; 21(3): 401-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661992

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Effects of nitric oxide on Pseudomonas aeruginosa infection of epithelial cells from a human respiratory cell line derived from a patient with cystic fibrosis. Author(s): Darling KE, Evans TJ. Source: Infection and Immunity. 2003 May; 71(5): 2341-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704103

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Effects of some plant extracts and antibiotics on Pseudomonas aeruginosa isolated from various burn cases. Author(s): Al-Saimary IE, Bakr SS, Jaffar T, Al-Saimary AE, Salim H, Al-Muosawi R. Source: Saudi Med J. 2002 July; 23(7): 802-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12174229

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Effects of subinhibitory concentrations of macrolide antibiotics on Pseudomonas aeruginosa. Author(s): Wozniak DJ, Keyser R. Source: Chest. 2004 February; 125(2 Suppl): 62S-69S; Quiz 69S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872002

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Elastase-producing Pseudomonas aeruginosa degrade plasma proteins and extracellular products of human skin and fibroblasts, and inhibit fibroblast growth. Author(s): Schmidtchen A, Holst E, Tapper H, Bjorck L. Source: Microbial Pathogenesis. 2003 January; 34(1): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620384

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Emergence of ciprofloxacin-resistant pseudomonas in pediatric otitis media. Author(s): Jang CH, Park SY. Source: International Journal of Pediatric Otorhinolaryngology. 2003 April; 67(4): 313-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663100

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Emergence of nosocomial Pseudomonas aeruginosa colonization/infection in pregnant women with preterm premature rupture of membranes and in their neonates. Author(s): Casetta A, Audibert F, Brivet F, Boutros N, Boithias C, Lebrun L. Source: The Journal of Hospital Infection. 2003 June; 54(2): 158-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818591

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Emerging Pseudomonas aeruginosa resistance: implications in clinical practice. Author(s): Ong CT, Kuti JL, Nightingale CH, Nicolau DP. Source: Conn Med. 2004 January; 68(1): 11-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752913

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Endophthalmitis caused by Pseudomonas aeruginosa. Author(s): Eifrig CW, Scott IU, Flynn HW Jr, Miller D. Source: Ophthalmology. 2003 September; 110(9): 1714-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13129867

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Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa. Author(s): Price BM, Barten Legutki J, Galloway DR, von Specht BU, Gilleland LB, Gilleland HE Jr, Staczek J. Source: Fems Immunology and Medical Microbiology. 2002 June 3; 33(2): 89-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052563

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Epidemiological typing of imipenem-resistant Pseudomonas aeruginosa. Author(s): Muller-Premru M, Lejko-Zupanc T. Source: International Journal of Antimicrobial Agents. 2002 November; 20(5): 380-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431874

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Epidemiology of Pseudomonas aeruginosa and risk factors for carriage acquisition in an intensive care unit. Author(s): Thuong M, Arvaniti K, Ruimy R, de la Salmoniere P, Scanvic-Hameg A, Lucet JC, Regnier B. Source: The Journal of Hospital Infection. 2003 April; 53(4): 274-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660124

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Epidemiology of Pseudomonas aeruginosa in cystic fibrosis in British Columbia, Canada. Author(s): Speert DP, Campbell ME, Henry DA, Milner R, Taha F, Gravelle A, Davidson AG, Wong LT, Mahenthiralingam E. Source: American Journal of Respiratory and Critical Care Medicine. 2002 October 1; 166(7): 988-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359659

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Evaluation of media available for testing the susceptibility of Pseudomonas aeruginosa by BSAC methodology. Author(s): Andrews J, Walker R, King A. Source: The Journal of Antimicrobial Chemotherapy. 2002 October; 50(4): 479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356791

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Evaluation of MicroScan Autoscan for identification of Pseudomonas aeruginosa isolates from cystic fibrosis patients. Author(s): Saiman L, Burns JL, Larone D, Chen Y, Garber E, Whittier S. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 492-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517904

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Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-beta-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp. Author(s): Lee K, Lim YS, Yong D, Yum JH, Chong Y. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4623-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532193

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Evaluation of the Merlin, Micronaut system for automated antimicrobial susceptibility testing of Pseudomonas aeruginosa and Burkholderia species isolated from cystic fibrosis patients. Author(s): Haussler S, Ziesing S, Rademacher G, Hoy L, Weissbrodt H. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 August; 22(8): 496500. Epub 2003 July 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898284

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Evaluation of the Osiris expert system for identification of beta-lactam phenotypes in isolates of Pseudomonas aeruginosa. Author(s): Bert F, Ould-Hocine Z, Juvin M, Dubois V, Loncle-Provot V, Lefranc V, Quentin C, Lambert N, Arlet G. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3712-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904380

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Evaluation of the polymorphisms associated with tandem repeats for Pseudomonas aeruginosa strain typing. Author(s): Onteniente L, Brisse S, Tassios PT, Vergnaud G. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 4991-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605129

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Evidence against transmission of Pseudomonas aeruginosa by hands and stethoscopes in a cystic fibrosis unit. Author(s): Kerr JR, Martin H, Chadwick MV, Edwards A, Hodson ME, Geddes DM. Source: The Journal of Hospital Infection. 2002 April; 50(4): 324-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12014913

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Evidence for spread of a clonal strain of Pseudomonas aeruginosa among cystic fibrosis clinics. Author(s): Armstrong D, Bell S, Robinson M, Bye P, Rose B, Harbour C, Lee C, Service H, Nissen M, Syrmis M, Wainwright C. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2266-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734299

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Evolving resistant pseudomonas to ciprofloxacin in malignant otitis externa. Author(s): Berenholz L, Katzenell U, Harell M. Source: The Laryngoscope. 2002 September; 112(9): 1619-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352675

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Exogenous Pseudomonas endophthalmitis: a cause of lens enucleation. Author(s): Gaili H, Woodruff GH. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 May; 86(3): F204-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978756

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Expression stability of six housekeeping genes: A proposal for resistance gene quantification studies of Pseudomonas aeruginosa by real-time quantitative RT-PCR. Author(s): Savli H, Karadenizli A, Kolayli F, Gundes S, Ozbek U, Vahaboglu H. Source: Journal of Medical Microbiology. 2003 May; 52(Pt 5): 403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12721316

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First isolation of a carbapenem-hydrolyzing beta-lactamase in Pseudomonas aeruginosa in Spain. Author(s): Prats G, Miro E, Mirelis B, Poirel L, Bellais S, Nordmann P. Source: Antimicrobial Agents and Chemotherapy. 2002 March; 46(3): 932-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11850292

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FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action. Author(s): Fujine K, Abe F, Seki N, Ueda H, Hino M, Fujii T. Source: J Antibiot (Tokyo). 2003 February; 56(2): 62-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715862

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Frequency of Pseudomonas aeruginosa serotypes in burn wound infections and their resistance to antibiotics. Author(s): Estahbanati HK, Kashani PP, Ghanaatpisheh F. Source: Burns : Journal of the International Society for Burn Injuries. 2002 June; 28(4): 340-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052372

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Gene islands integrated into tRNA(Gly) genes confer genome diversity on a Pseudomonas aeruginosa clone. Author(s): Larbig KD, Christmann A, Johann A, Klockgether J, Hartsch T, Merkl R, Wiehlmann L, Fritz HJ, Tummler B. Source: Journal of Bacteriology. 2002 December; 184(23): 6665-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426355

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Genetic analysis of Pseudomonas aeruginosa isolates from the sputa of Australian adult cystic fibrosis patients. Author(s): Anthony M, Rose B, Pegler MB, Elkins M, Service H, Thamotharampillai K, Watson J, Robinson M, Bye P, Merlino J, Harbour C. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 2772-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149328

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Genetic and phenotypic variations of a resistant Pseudomonas aeruginosa epidemic clone. Author(s): Hocquet D, Bertrand X, Kohler T, Talon D, Plesiat P. Source: Antimicrobial Agents and Chemotherapy. 2003 June; 47(6): 1887-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760863

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Genetic features of Pseudomonas aeruginosa isolates from cystic fibrosis patients compared with those of isolates from other origins. Author(s): Lanotte P, Watt S, Mereghetti L, Dartiguelongue N, Rastegar-Lari A, Goudeau A, Quentin R. Source: Journal of Medical Microbiology. 2004 January; 53(Pt 1): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663109

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Genetically programmed autoinducer destruction reduces virulence gene expression and swarming motility in Pseudomonas aeruginosa PAO1. Author(s): Reimmann C, Ginet N, Michel L, Keel C, Michaux P, Krishnapillai V, Zala M, Heurlier K, Triandafillu K, Harms H, Defago G, Haas D. Source: Microbiology (Reading, England). 2002 April; 148(Pt 4): 923-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932439

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Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis. Author(s): Ernst RK, D'Argenio DA, Ichikawa JK, Bangera MG, Selgrade S, Burns JL, Hiatt P, McCoy K, Brittnacher M, Kas A, Spencer DH, Olson MV, Ramsey BW, Lory S, Miller SI. Source: Environmental Microbiology. 2003 December; 5(12): 1341-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641578

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Genotypic and phenotypic analysis of type III secretion system in a cohort of Pseudomonas aeruginosa bacteremia isolates: evidence for a possible association between O serotypes and exo genes. Author(s): Berthelot P, Attree I, Plesiat P, Chabert J, de Bentzmann S, Pozzetto B, Grattard F; Groupe d'Etudes des Septicemies a Pseudomonas aeruginosa. Source: The Journal of Infectious Diseases. 2003 August 15; 188(4): 512-8. Epub 2003 July 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898437

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Geographic variations in activity of broad-spectrum beta-lactams against Pseudomonas aeruginosa: summary of the worldwide SENTRY Antimicrobial Surveillance Program (1997-2000). Author(s): Jones RN, Kirby JT, Beach ML, Biedenbach DJ, Pfaller MA. Source: Diagnostic Microbiology and Infectious Disease. 2002 July; 43(3): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12106958

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Global genomic analysis of AlgU (sigma(E))-dependent promoters (sigmulon) in Pseudomonas aeruginosa and implications for inflammatory processes in cystic fibrosis. Author(s): Firoved AM, Boucher JC, Deretic V. Source: Journal of Bacteriology. 2002 February; 184(4): 1057-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807066

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Glycosylation of Pseudomonas aeruginosa 1244 pilin: glycan substrate specificity. Author(s): DiGiandomenico A, Matewish MJ, Bisaillon A, Stehle JR, Lam JS, Castric P. Source: Molecular Microbiology. 2002 October; 46(2): 519-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406226

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Guess what! Pseudomonas aeruginosa sepsis. Author(s): Bugatti L, Nicolini M, Filosa A, Filosa G. Source: European Journal of Dermatology : Ejd. 2002 May-June; 12(3): 291-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978576

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Haemophagocytic syndrome following Pseudomonas septicaemia. Author(s): Ermis B, Gardas F, Ceviz N, Ors R, Karakelleoglu C. Source: The Lancet Infectious Diseases. 2003 May; 3(5): 287. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12726977

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Heterogeneity in interleukin-13 receptor expression and subunit structure in squamous cell carcinoma of head and neck: differential sensitivity to chimeric fusion proteins comprised of interleukin-13 and a mutated form of Pseudomonas exotoxin. Author(s): Joshi BH, Kawakami K, Leland P, Puri RK. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 June; 8(6): 1948-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060640

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High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux. Author(s): Chuanchuen R, Karkhoff-Schweizer RR, Schweizer HP. Source: American Journal of Infection Control. 2003 April; 31(2): 124-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665747

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Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. Author(s): Haussler S, Ziegler I, Lottel A, von Gotz F, Rohde M, Wehmhohner D, Saravanamuthu S, Tummler B, Steinmetz I. Source: Journal of Medical Microbiology. 2003 April; 52(Pt 4): 295-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12676867

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High-molecular-weight polyethylene glycol prevents lethal sepsis due to intestinal Pseudomonas aeruginosa. Author(s): Wu L, Zaborina O, Zaborin A, Chang EB, Musch M, Holbrook C, Shapiro J, Turner JR, Wu G, Lee KY, Alverdy JC. Source: Gastroenterology. 2004 February; 126(2): 488-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762786

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Hospital mortality for patients with bacteremia due to Staphylococcus aureus or Pseudomonas aeruginosa. Author(s): Osmon S, Ward S, Fraser VJ, Kollef MH. Source: Chest. 2004 February; 125(2): 607-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769745

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Hospital outbreak of multiple clones of Pseudomonas aeruginosa carrying the unrelated metallo-beta-lactamase gene variants blaVIM-2 and blaVIM-4. Author(s): Pournaras S, Maniati M, Petinaki E, Tzouvelekis LS, Tsakris A, Legakis NJ, Maniatis AN. Source: The Journal of Antimicrobial Chemotherapy. 2003 June; 51(6): 1409-14. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716773

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Hospital-acquired, native valve endocarditis caused by Pseudomonas aeruginosa. Author(s): Bicanic TA, Eykyn SJ. Source: The Journal of Infection. 2002 February; 44(2): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076074

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Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Author(s): Grassme H, Jendrossek V, Riehle A, von Kurthy G, Berger J, Schwarz H, Weller M, Kolesnick R, Gulbins E. Source: Nature Medicine. 2003 March; 9(3): 322-30. Epub 2003 February 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12563314

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Hot tub-associated necrotizing pneumonia due to Pseudomonas aeruginosa. Author(s): Crnich CJ, Gordon B, Andes D. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 February 1; 36(3): E55-7. Epub 2003 January 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12539092

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Human targets of Pseudomonas aeruginosa pyocyanin. Author(s): Ran H, Hassett DJ, Lau GW. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 November 25; 100(24): 14315-20. Epub 2003 Nov 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605211

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Identification and characterization of interleukin-13 receptor in human medulloblastoma and targeting these receptors with interleukin-13-pseudomonas exotoxin fusion protein. Author(s): Joshi BH, Leland P, Puri RK. Source: Croatian Medical Journal. 2003 August; 44(4): 455-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950150

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Identification and susceptibility testing of Enterobacteriaceae and Pseudomonas aeruginosa by direct inoculation from positive BACTEC blood culture bottles into Vitek 2. Author(s): Bruins MJ, Bloembergen P, Ruijs GJ, Wolfhagen MJ. Source: Journal of Clinical Microbiology. 2004 January; 42(1): 7-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715724

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Identification of airborne dissemination of epidemic multiresistant strains of Pseudomonas aeruginosa at a CF centre during a cross infection outbreak. Author(s): Jones AM, Govan JR, Doherty CJ, Dodd ME, Isalska BJ, Stanbridge TN, Webb AK. Source: Thorax. 2003 June; 58(6): 525-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775867

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Identification of PSE and OXA beta-lactamase genes in Pseudomonas aeruginosa using PCR-restriction fragment length polymorphism. Author(s): Bert F, Branger C, Lambert-Zechovsky N. Source: The Journal of Antimicrobial Chemotherapy. 2002 July; 50(1): 11-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12096001

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Identification of the Pseudomonas aeruginosa 1244 pilin glycosylation site. Author(s): Comer JE, Marshall MA, Blanch VJ, Deal CD, Castric P. Source: Infection and Immunity. 2002 June; 70(6): 2837-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010970

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Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa. Author(s): de Chial M, Ghysels B, Beatson SA, Geoffroy V, Meyer JM, Pattery T, Baysse C, Chablain P, Parsons YN, Winstanley C, Cordwell SJ, Cornelis P. Source: Microbiology (Reading, England). 2003 April; 149(Pt 4): 821-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686625

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IL-10 controls Aspergillus fumigatus- and Pseudomonas aeruginosa-specific T-cell response in cystic fibrosis. Author(s): Casaulta C, Schoni MH, Weichel M, Crameri R, Jutel M, Daigle I, Akdis M, Blaser K, Akdis CA. Source: Pediatric Research. 2003 February; 53(2): 313-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538792

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Imipenem-EDTA disk method for differentiation of metallo-beta-lactamaseproducing clinical isolates of Pseudomonas spp. and Acinetobacter spp. Author(s): Yong D, Lee K, Yum JH, Shin HB, Rossolini GM, Chong Y. Source: Journal of Clinical Microbiology. 2002 October; 40(10): 3798-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354884

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Immunisation with non-integral OMPs promotes pulmonary clearance of Pseudomonas aeruginosa. Author(s): Thomas LD, Kyd JM, Bastin DA, Dunkley ML, Cripps AW. Source: Fems Immunology and Medical Microbiology. 2003 July 15; 37(2-3): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832119

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Immunotoxins containing Pseudomonas exotoxin A: a short history. Author(s): Pastan I. Source: Cancer Immunology, Immunotherapy : Cii. 2003 May; 52(5): 338-41. Epub 2003 March 06. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700949

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IMP-12, a new plasmid-encoded metallo-beta-lactamase from a Pseudomonas putida clinical isolate. Author(s): Docquier JD, Riccio ML, Mugnaioli C, Luzzaro F, Endimiani A, Toniolo A, Amicosante G, Rossolini GM. Source: Antimicrobial Agents and Chemotherapy. 2003 May; 47(5): 1522-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709317

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Impact of inhaled corticosteroids on the risk of early Pseudomonas aeruginosa acquisition in cystic fibrosis. Author(s): Minicucci L, Severi G, Cresta L, Giannattasio A, Lorini R, Haupt R. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 June; 92(6): 684-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856978

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Impact of large chromosomal inversions on the adaptation and evolution of Pseudomonas aeruginosa chronically colonizing cystic fibrosis lungs. Author(s): Kresse AU, Dinesh SD, Larbig K, Romling U. Source: Molecular Microbiology. 2003 January; 47(1): 145-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492860

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In vitro evaluation of the activity of two doses of Levofloxacin alone and in combination with other agents against Pseudomonas aeruginosa. Author(s): Burgess DS, Hall RG, Hardin TC. Source: Diagnostic Microbiology and Infectious Disease. 2003 June; 46(2): 131-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812717

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In vitro identification of two adherence factors required for in vivo virulence of Pseudomonas fluorescens. Author(s): de Lima Pimenta A, Di Martino P, Le Bouder E, Hulen C, Blight MA. Source: Microbes and Infection / Institut Pasteur. 2003 November; 5(13): 1177-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623013

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In vitro interaction of colistin and rifampin on multidrug-resistant Pseudomonas aeruginosa. Author(s): Giamarellos-Bourboulis EJ, Sambatakou H, Galani I, Giamarellou H. Source: J Chemother. 2003 June; 15(3): 235-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868548

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Incidence and molecular epidemiology of Pseudomonas aeruginosa bacteremias in patients with acute leukemia: analysis by pulsed-field gel electrophoresis. Author(s): Fanci R, Paci C, Anichini P, Pecile P, Marra G, Casini C, Nicoletti P. Source: New Microbiol. 2003 October; 26(4): 353-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596346

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Incidence of Pseudomonas aeruginosa in recreational and hydrotherapy pools. Author(s): Moore JE, Heaney N, Millar BC, Crowe M, Elborn JS. Source: Commun Dis Public Health. 2002 March; 5(1): 23-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12070972

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Increased treatment requirements of patients with cystic fibrosis who harbour a highly transmissible strain of Pseudomonas aeruginosa. Author(s): Jones AM, Dodd ME, Doherty CJ, Govan JR, Webb AK. Source: Thorax. 2002 November; 57(11): 924-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403871

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Increasing prevalence of antimicrobial resistance among Pseudomonas aeruginosa isolates in Latin American medical centres: 5 year report of the SENTRY Antimicrobial Surveillance Program (1997-2001). Author(s): Andrade SS, Jones RN, Gales AC, Sader HS. Source: The Journal of Antimicrobial Chemotherapy. 2003 July; 52(1): 140-1. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775681

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Infection-associated hemophagocytic syndrome due to Pseudomonas aeruginosa in preterm infants. Author(s): Aygun C, Tekinalp G, Gurgey A. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 August; 25(8): 665-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902926

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Inflammatory markers in cystic fibrosis patients with transmissible Pseudomonas aeruginosa. Author(s): Jones AM, Martin L, Bright-Thomas RJ, Dodd ME, McDowell A, Moffitt KL, Elborn JS, Webb AK. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 September; 22(3): 503-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516142

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Influence of wear and overwear on surface properties of etafilcon A contact lenses and adhesion of Pseudomonas aeruginosa. Author(s): Bruinsma GM, Rustema-Abbing M, de Vries J, Stegenga B, van der Mei HC, van der Linden ML, Hooymans JM, Busscher HJ. Source: Investigative Ophthalmology & Visual Science. 2002 December; 43(12): 3646-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454031

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Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Author(s): Cheer SM, Waugh J, Noble S. Source: Drugs. 2003; 63(22): 2501-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609360

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Integration of population pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate a rational empiric dosing strategy for cefepime against Pseudomonas aeruginosa. Author(s): Tam VH, Louie A, Lomaestro BM, Drusano GL. Source: Pharmacotherapy. 2003 March; 23(3): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627925

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Inter- and intraclonal diversity of the Pseudomonas aeruginosa proteome manifests within the secretome. Author(s): Wehmhoner D, Haussler S, Tummler B, Jansch L, Bredenbruch F, Wehland J, Steinmetz I. Source: Journal of Bacteriology. 2003 October; 185(19): 5807-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13129952

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Interleukin-4-Pseudomonas exotoxin chimeric fusion protein for malignant glioma therapy. Author(s): Kawakami M, Kawakami K, Puri RK. Source: Journal of Neuro-Oncology. 2003 October; 65(1): 15-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14649882

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Interspecies communication between Burkholderia cepacia and Pseudomonas aeruginosa. Author(s): Lewenza S, Visser MB, Sokol PA. Source: Canadian Journal of Microbiology. 2002 August; 48(8): 707-16. Erratum In: Can J Microbiol. 2002 September; 48(9): 855. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381027

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Iron acquisition and its control in Pseudomonas aeruginosa: many roads lead to Rome. Author(s): Poole K, McKay GA. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 May 1; 8: D661-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700066

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Isolation of labradorins 1 and 2 from Pseudomonas syringae pv. coronafaciens. Author(s): Pettit GR, Knight JC, Herald DL, Davenport R, Pettit RK, Tucker BE, Schmidt JM. Source: Journal of Natural Products. 2002 December; 65(12): 1793-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502316

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Lack of efflux mechanism in a clinical isolate of Pseudomonas aeruginosa highly resistant to beta-lactams and imipenem. Author(s): Kadry AA. Source: Folia Microbiol (Praha). 2003; 48(4): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533486

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Left-sided endocarditis caused by Pseudomonas aeruginosa: successful treatment with meropenem and tobramycin. Author(s): Gavin PJ, Suseno MT, Cook FV, Peterson LR, Thomson RB Jr. Source: Diagnostic Microbiology and Infectious Disease. 2003 October; 47(2): 427-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522517

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Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma. Author(s): Weber FW, Floeth F, Asher A, Bucholz R, Berger M, Prados M, Chang S, Bruce J, Hall W, Rainov NG, Westphal M, Warnick RE, Rand RW, Rommell F, Pan H, Hingorani VN, Puri RK. Source: Acta Neurochir Suppl. 2003; 88: 93-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531567

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Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. Author(s): Lambert PA. Source: Journal of the Royal Society of Medicine. 2002; 95 Suppl 41: 22-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12216271

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Mechanisms of beta-lactam resistance in Pseudomonas aeruginosa: prevalence of OprM-overproducing strains in a French multicentre study (1997). Author(s): Cavallo JD, Plesiat P, Couetdic G, Leblanc F, Fabre R; Groupe d'Etude de la Resistance de Pseudomonas aeruginosa aux Betalactamines (GERPB). Source: The Journal of Antimicrobial Chemotherapy. 2002 December; 50(6): 1039-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12461030

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Metallo-beta-lactamase VIM-2 in clinical isolates of Pseudomonas aeruginosa from Portugal. Author(s): Cardoso O, Leitao R, Figueiredo A, Sousa JC, Duarte A, Peixe LV. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Summer; 8(2): 93-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118523

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Metalloproteases from Pseudomonas aeruginosa degrade human RANTES, MCP-1, and ENA-78. Author(s): Leidal KG, Munson KL, Johnson MC, Denning GM. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2003 June; 23(6): 307-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859857

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MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides. Author(s): Hocquet D, Vogne C, El Garch F, Vejux A, Gotoh N, Lee A, Lomovskaya O, Plesiat P. Source: Antimicrobial Agents and Chemotherapy. 2003 April; 47(4): 1371-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654672

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Modification of dienes mutual inhibition test for epidemiological characterization of Pseudomonas aeruginosa isolates. Author(s): Munson EL, Pfaller MA, Doern GV. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409411

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Modification of Pseudomonas aeruginosa interactions with corneal epithelial cells by human tear fluid. Author(s): Fleiszig SM, Kwong MS, Evans DJ. Source: Infection and Immunity. 2003 July; 71(7): 3866-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819071

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Modulation of cytosolic Ca(2+) concentration in airway epithelial cells by Pseudomonas aeruginosa. Author(s): Jacob T, Lee RJ, Engel JN, Machen TE. Source: Infection and Immunity. 2002 November; 70(11): 6399-408. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379720

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Modulation of Pseudomonas aeruginosa gene expression by host microflora through interspecies communication. Author(s): Duan K, Dammel C, Stein J, Rabin H, Surette MG. Source: Molecular Microbiology. 2003 December; 50(5): 1477-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651632

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Molecular epidemiology of extended-spectrum beta-lactamases produced by clinical isolates in a university hospital in Greece: detection of SHV-5 in Pseudomonas aeruginosa and prevalence of SHV-12. Author(s): Neonakis IK, Scoulica EV, Dimitriou SK, Gikas AI, Tselentis YJ. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Summer; 9(2): 161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820801

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Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. Author(s): Pirnay JP, De Vos D, Cochez C, Bilocq F, Pirson J, Struelens M, Duinslaeger L, Cornelis P, Zizi M, Vanderkelen A. Source: Journal of Clinical Microbiology. 2003 March; 41(3): 1192-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624051

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Molecular epidemiology of Pseudomonas aeruginosa. Author(s): Speert DP. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 October 1; 7: E35461. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165481

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Mucin degradation mechanisms by distinct Pseudomonas aeruginosa isolates in vitro. Author(s): Aristoteli LP, Willcox MD. Source: Infection and Immunity. 2003 October; 71(10): 5565-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500475

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Mucosal vaccination with a recombinant OprF-I vaccine of Pseudomonas aeruginosa in healthy volunteers: comparison of a systemic vs. a mucosal booster schedule. Author(s): Gocke K, Baumann U, Hagemann H, Gabelsberger J, Hahn H, Freihorst J, von Specht BU. Source: Fems Immunology and Medical Microbiology. 2003 July 15; 37(2-3): 167-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832121

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Multicentre surveillance of Pseudomonas aeruginosa susceptibility patterns in nosocomial infections. Author(s): Van Eldere J. Source: The Journal of Antimicrobial Chemotherapy. 2003 February; 51(2): 347-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562701

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Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: analysis of trends in prevalence and epidemiology. Author(s): Tacconelli E, Tumbarello M, Bertagnolio S, Citton R, Spanu T, Fadda G, Cauda R. Source: Emerging Infectious Diseases. 2002 February; 8(2): 220-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897080

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Multidrug-resistant Pseudomonas aeruginosa isolated from the urine of patients with urinary tract infection. Author(s): Takeyama K, Kunishima Y, Matsukawa M, Takahashi S, Hirose T, Kobayashi N, Kobayashi I, Tsukamoto T. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 March; 8(1): 59-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11957121

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Multidrug-resistant Pseudomonas aeruginosa producing PER-1 extended-spectrum serine-beta-lactamase and VIM-2 metallo-beta-lactamase. Author(s): Docquier JD, Luzzaro F, Amicosante G, Toniolo A, Rossolini GM. Source: Emerging Infectious Diseases. 2001 September-October; 7(5): 910-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11747713

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Multidrug-resistant Pseudomonas aeruginosa strains harbouring R-plasmids and AmpC beta-lactamases isolated from hospitalised burn patients in a tertiary care hospital of North India. Author(s): Shahid M, Malik A, Sheeba. Source: Fems Microbiology Letters. 2003 November 21; 228(2): 181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638422

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Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Author(s): Livermore DM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 March 1; 34(5): 634-40. Epub 2002 January 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823954

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Multiple surface properties of worn RGP lenses and adhesion of Pseudomonas aeruginosa. Author(s): Bruinsma GM, Rustema-Abbing M, de Vries J, Busscher HJ, van der Linden ML, Hooymans JM, van der Mei HC. Source: Biomaterials. 2003 April; 24(9): 1663-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559826

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Multiresistant Pseudomonas aeruginosa in a pediatric cystic fibrosis center: natural history and implications for segregation. Author(s): Davies G, McShane D, Davies JC, Bush A. Source: Pediatric Pulmonology. 2003 April; 35(4): 253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629620

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Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa. Author(s): Higgins PG, Fluit AC, Milatovic D, Verhoef J, Schmitz FJ. Source: International Journal of Antimicrobial Agents. 2003 May; 21(5): 409-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727072

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Mycotic aneurysm of the descending thoracic aorta caused by Pseudomonas aeruginosa in a solid organ transplant recipient: case report and review. Author(s): Feltis BA, Lee DA, Beilman GJ. Source: Surgical Infections. 2002 Spring; 3(1): 29-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593697

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N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. Author(s): Yates EA, Philipp B, Buckley C, Atkinson S, Chhabra SR, Sockett RE, Goldner M, Dessaux Y, Camara M, Smith H, Williams P. Source: Infection and Immunity. 2002 October; 70(10): 5635-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12228292

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Necrotizing stomatitis: report of 3 Pseudomonas aeruginosa-positive patients. Author(s): Barasch A, Gordon S, Geist RY, Geist JR. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 August; 96(2): 136-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12931084

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Nosocomial infections caused by multidrug-resistant isolates of pseudomonas putida producing VIM-1 metallo-beta-lactamase. Author(s): Lombardi G, Luzzaro F, Docquier JD, Riccio ML, Perilli M, Coli A, Amicosante G, Rossolini GM, Toniolo A. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4051-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409373

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Nosocomial infections due to Pseudomonas aeruginosa in neonates. Author(s): Bilikova E, Hafed BM, Kovacicova G, Koprnova J, Svetlansky I, Chovancova D, Huttova M, Kremery V. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 June; 9(2): 191-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872782

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Nosocomial infectious potency of imipenem-resistant Pseudomonas aeruginosa isolated from obstetric and gynecologic infections. Author(s): Yin XH, Mikamo H, Tamaya T. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 March; 9(1): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673417

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Nosocomial outbreak of carbapenem-resistant Pseudomonas aeruginosa with a new bla(IMP) allele, bla(IMP-7). Author(s): Gibb AP, Tribuddharat C, Moore RA, Louie TJ, Krulicki W, Livermore DM, Palepou MF, Woodford N. Source: Antimicrobial Agents and Chemotherapy. 2002 January; 46(1): 255-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11751148

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Nosocomial spread of the integron-located veb-1-like cassette encoding an extendedpectrum beta-lactamase in Pseudomonas aeruginosa in Thailand. Author(s): Girlich D, Naas T, Leelaporn A, Poirel L, Fennewald M, Nordmann P. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 March 1; 34(5): 603-11. Epub 2002 January 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807680

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Novel 3-N-aminoglycoside acetyltransferase gene, aac(3)-Ic, from a Pseudomonas aeruginosa integron. Author(s): Riccio ML, Docquier JD, Dell'Amico E, Luzzaro F, Amicosante G, Rossolini GM. Source: Antimicrobial Agents and Chemotherapy. 2003 May; 47(5): 1746-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709352

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Novel variant (bla(VIM-4)) of the metallo-beta-lactamase gene bla(VIM-1) in a clinical strain of Pseudomonas aeruginosa. Author(s): Pournaras S, Tsakris A, Maniati M, Tzouvelekis LS, Maniatis AN. Source: Antimicrobial Agents and Chemotherapy. 2002 December; 46(12): 4026-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435718

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Nucleotides and heteroduplex DNA preserve the active conformation of Pseudomonas aeruginosa MutS by preventing protein oligomerization. Author(s): Pezza RJ, Smania AM, Barra JL, Argarana CE. Source: The Biochemical Journal. 2002 January 1; 361(Pt 1): 87-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742532

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O-antigen serotypes and type III secretory toxins in clinical isolates of Pseudomonas aeruginosa. Author(s): Faure K, Shimabukuro D, Ajayi T, Allmond LR, Sawa T, Wiener-Kronish JP. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2158-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734267

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Occurrence of a multidrug-resistant Pseudomonas aeruginosa clone in different hospitals in Rio de Janeiro, Brazil. Author(s): Pellegrino FL, Teixeira LM, Carvalho Md Mda G, Aranha Nouer S, Pinto De Oliveira M, Mello Sampaio JL, D'Avila Freitas A, Ferreira AL, Amorim Ed Ede L, Riley LW, Moreira BM. Source: Journal of Clinical Microbiology. 2002 July; 40(7): 2420-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089256

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Oral administration of specific yolk antibodies (IgY) may prevent Pseudomonas aeruginosa infections in patients with cystic fibrosis: a phase I feasibility study. Author(s): Kollberg H, Carlander D, Olesen H, Wejaker PE, Johannesson M, Larsson A. Source: Pediatric Pulmonology. 2003 June; 35(6): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746939

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Orbital cellulitis, panophthalmitis, and ecthyma gangrenosum in an immunocompromised host with pseudomonas septicemia. Author(s): Maccheron LJ, Groeneveld ER, Ohlrich SJ, Hilford DJ, Beckingsale PS. Source: American Journal of Ophthalmology. 2004 January; 137(1): 176-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700664

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Orthokeratology lens-related Pseudomonas aeruginosa infectious keratitis. Author(s): Young AL, Leung AT, Cheung EY, Cheng LL, Wong AK, Lam DS. Source: Cornea. 2003 April; 22(3): 265-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658097

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Outbreak of pseudomonas aeruginosa by multiple organ transplantation from a common donor. Author(s): Kumar D, Cattral MS, Robicsek A, Gaudreau C, Humar A. Source: Transplantation. 2003 April 15; 75(7): 1053-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698099

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Outbreak of Pseudomonas aeruginosa folliculitis associated with a swimming pool inflatable. Author(s): Tate D, Mawer S, Newton A. Source: Epidemiology and Infection. 2003 April; 130(2): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729186

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Outbreak of Pseudomonas aeruginosa infections caused by commercial piercing of upper ear cartilage. Author(s): Keene WE, Markum AC, Samadpour M. Source: Jama : the Journal of the American Medical Association. 2004 February 25; 291(8): 981-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982914

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Pacemaker endocarditis caused by Pseudomonas aeruginosa treated successfully. Author(s): Chacko ST, Chandy ST, Abraham OC, Swaminathan S, Varghese GM, Priscilla R, Mathai D. Source: J Assoc Physicians India. 2003 October; 51: 1021-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719599

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PcrH of Pseudomonas aeruginosa is essential for secretion and assembly of the type III translocon. Author(s): Broms JE, Forslund AL, Forsberg A, Francis MS. Source: The Journal of Infectious Diseases. 2003 December 15; 188(12): 1909-21. Epub 2003 Dec 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673772

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Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas aeruginosa in the HAART era. Author(s): Allen SH, Brennan-Benson P, Nelson M, Asboe D, Bower M, Azadian B, Gazzard B, Stebbing J. Source: Postgraduate Medical Journal. 2003 December; 79(938): 691-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707245

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Presence of Pseudomonas putida strains harboring plasmids bearing the metallobeta-lactamase gene bla(IMP) in a hospital in Japan. Author(s): Yomoda S, Okubo T, Takahashi A, Murakami M, Iyobe S. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4246-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958252

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Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors. Author(s): Sampson JH, Akabani G, Archer GE, Bigner DD, Berger MS, Friedman AH, Friedman HS, Herndon JE 2nd, Kunwar S, Marcus S, McLendon RE, Paolino A, Penne K, Provenzale J, Quinn J, Reardon DA, Rich J, Stenzel T, Tourt-Uhlig S, Wikstrand C, Wong T, Williams R, Yuan F, Zalutsky MR, Pastan I. Source: Journal of Neuro-Oncology. 2003 October; 65(1): 27-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14649883

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Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. Author(s): Rosenfeld M, Ramsey BW, Gibson RL. Source: Current Opinion in Pulmonary Medicine. 2003 November; 9(6): 492-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534401

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Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection. Author(s): Song Z, Wu H, Ciofu O, Kong KF, Hoiby N, Rygaard J, Kharazmi A, Mathee K. Source: Journal of Medical Microbiology. 2003 September; 52(Pt 9): 731-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909647

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Pseudomonas aeruginosa and Burkholderia cepacia cannot be detected by PCR in the breath condensate of patients with cystic fibrosis. Author(s): Vogelberg C, Hirsch T, Rosen-Wolff A, Kerkmann ML, Leupold W. Source: Pediatric Pulmonology. 2003 October; 36(4): 348-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950050

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Pseudomonas aeruginosa and cystic fibrosis: correlation between exoenzyme production and patient's clinical state. Author(s): Lanotte P, Mereghetti L, Lejeune B, Massicot P, Quentin R. Source: Pediatric Pulmonology. 2003 November; 36(5): 405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520723

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Pseudomonas aeruginosa and the oropharyngeal ecosystem of tube-fed patients. Author(s): Leibovitz A, Dan M, Zinger J, Carmeli Y, Habot B, Segal R. Source: Emerging Infectious Diseases. 2003 August; 9(8): 956-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967493

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Pseudomonas aeruginosa bacteremia: risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Author(s): Kang CI, Kim SH, Kim HB, Park SW, Choe YJ, Oh MD, Kim EC, Choe KW. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 745-51. Epub 2003 August 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955633

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Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response. Author(s): Ciofu O. Source: Apmis. Supplementum. 2003; (116): 1-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692154

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Pseudomonas aeruginosa endocarditis associated with endophthalmitis caused by arteriovenous fistula and graft infection. Author(s): Hsu KH, Ben RJ, Shiang JC, Feng NH. Source: J Chin Med Assoc. 2003 October; 66(10): 617-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703280

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Pseudomonas aeruginosa expresses a lethal virulence determinant, the PA-I lectin/adhesin, in the intestinal tract of a stressed host: the role of epithelia cell contact and molecules of the Quorum Sensing Signaling System. Author(s): Wu L, Holbrook C, Zaborina O, Ploplys E, Rocha F, Pelham D, Chang E, Musch M, Alverdy J. Source: Annals of Surgery. 2003 November; 238(5): 754-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578740

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Pseudomonas aeruginosa lectin PA-IIL as a powerful probe for human and bovine milk analysis. Author(s): Lesman-Movshovich E, Gilboa-Garber N. Source: Journal of Dairy Science. 2003 July; 86(7): 2276-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12906043

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Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. Author(s): Smith RS, Iglewski BH. Source: The Journal of Clinical Investigation. 2003 November; 112(10): 1460-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617745

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Pseudomonas aeruginosa septic shock secondary to “gripe water” ingestion. Author(s): Sas D, Enrione MA, Schwartz RH. Source: The Pediatric Infectious Disease Journal. 2004 February; 23(2): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872189

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Pseudomonas aeruginosa urosepsis from use of a hot-water spa. Author(s): McNeil AC. Source: The American Journal of Medicine. 2003 November; 115(7): 592-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599651

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Pseudomonas aeruginosa-specific IgG1 and IgG2 subclasses in enhancement of pulmonary clearance following passive immunisation in the rat. Author(s): Dunkley ML, Rajyaguru S, McCue A, Cripps AW, Kyd JM. Source: Fems Immunology and Medical Microbiology. 2003 October 24; 39(1): 37-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556994

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Pseudomonas cross-infection from cystic fibrosis patients to non-cystic fibrosis patients: implications for inpatient care of respiratory patients. Author(s): Robinson P, Carzino R, Armstrong D, Olinsky A. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5741. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662972

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Pseudomonas infections in the thermally injured patient. Author(s): Tredget EE, Shankowsky HA, Rennie R, Burrell RE, Logsetty S. Source: Burns : Journal of the International Society for Burn Injuries. 2004 February; 30(1): 3-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693082

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Pseudomonas keratitis associated with continuous wear silicone-hydrogel soft contact lens: a case report. Author(s): Lee KY, Lim L. Source: Eye & Contact Lens. 2003 October; 29(4): 255-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555905

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Pseudomonas pneumonia in infants: an autopsy study. Author(s): Bonifacio SL, Kitterman JA, Ursell PC. Source: Human Pathology. 2003 September; 34(9): 929-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562290

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Pseudomonas surgical-site infections linked to a healthcare worker with onychomycosis. Author(s): Mermel LA, McKay M, Dempsey J, Parenteau S. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 October; 24(10): 749-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587936

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Quality control for beta-lactam susceptibility testing with a well-defined collection of Enterobacteriaceae and Pseudomonas aeruginosa strains in Spain. Author(s): Canton R, Loza E, Del Carmen Conejo M, Baquero F, Martinez-Martinez L; MENSURA Collaborative Group. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1912-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734226

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Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways. Author(s): Guina T, Purvine SO, Yi EC, Eng J, Goodlett DR, Aebersold R, Miller SI. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 4; 100(5): 2771-6. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601166

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Quorum sensing in Pseudomonas aeruginosa: yet another player. Author(s): Sperandio V. Source: Trends in Microbiology. 2002 March; 10(3): 118. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11864819

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Reappraisal of attributable mortality in critically ill patients with nosocomial bacteraemia involving Pseudomonas aeruginosa. Author(s): Blot S, Vandewoude K, Hoste E, Colardyn F. Source: The Journal of Hospital Infection. 2003 January; 53(1): 18-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495681

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Recalcitrant otorrhea due to Pseudomonas biofilm. Author(s): Bothwell MR, Smith AL, Phillips T. Source: Otolaryngology and Head and Neck Surgery. 2003 November; 129(5): 599-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595288

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Recent advances in cross-infection in cystic fibrosis: Burkholderia cepacia complex, Pseudomonas aeruginosa, MRSA and Pandoraea spp. Author(s): Jones AM, Webb AK. Source: Journal of the Royal Society of Medicine. 2003; 96 Suppl 43: 66-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12906328

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Recognition of mucin components by Pseudomonas aeruginosa. Author(s): Ramphal R, Arora SK. Source: Glycoconjugate Journal. 2001 September; 18(9): 709-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386456

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Recurrent facial pain due to Pseudomonas aeruginosa sinusitis. Author(s): Danielides V, Nousia CS, Gesouli E, Papakostas V, Milionis HJ, Skevas A. Source: Rhinology. 2002 December; 40(4): 226-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526255

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Regulation of expression of the cyanide-insensitive terminal oxidase in Pseudomonas aeruginosa. Author(s): Cooper M, Tavankar GR, Williams HD. Source: Microbiology (Reading, England). 2003 May; 149(Pt 5): 1275-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724389

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Repeated relapses in a meropenem-treated Pseudomonas aeruginosa meningitis. Author(s): Esen S, Leblebicioglu H, Sunbul M, Eroglu C, Leblebcioglu H. Source: J Chemother. 2002 October; 14(5): 535-6. No Abstract Available. Erratum In: J Chemother. 2002 December; 14(6): 642. Leblebcioglu H [corrected to Leblebicioglu H]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462436

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Respiratory infections with Pseudomonas aeruginosa in children with cystic fibrosis: early detection by serology and assessment of risk factors. Author(s): West SE, Zeng L, Lee BL, Kosorok MR, Laxova A, Rock MJ, Splaingard MJ, Farrell PM. Source: Jama : the Journal of the American Medical Association. 2002 June 12; 287(22): 2958-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052125

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Risk factors for imipenem-resistant Pseudomonas aeruginosa among hospitalized patients. Author(s): Harris AD, Smith D, Johnson JA, Bradham DD, Roghmann MC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 February 1; 34(3): 340-5. Epub 2001 December 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11774081

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Risk factors for initial acquisition of Pseudomonas aeruginosa in children with cystic fibrosis identified by newborn screening. Author(s): Maselli JH, Sontag MK, Norris JM, MacKenzie T, Wagener JS, Accurso FJ. Source: Pediatric Pulmonology. 2003 April; 35(4): 257-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629621

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Risk factors for piperacillin-tazobactam-resistant Pseudomonas aeruginosa among hospitalized patients. Author(s): Harris AD, Perencevich E, Roghmann MC, Morris G, Kaye KS, Johnson JA. Source: Antimicrobial Agents and Chemotherapy. 2002 March; 46(3): 854-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11850272

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Risk factors for Pseudomonas aeruginosa bacteremia in Thai patients. Author(s): Siripassorn K, Santiprasitkul S, Udompanthurak S, Thamlikitkul V. Source: J Med Assoc Thai. 2002 October; 85(10): 1095-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12501901

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Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. Author(s): Weber F, Asher A, Bucholz R, Berger M, Prados M, Chang S, Bruce J, Hall W, Rainov NG, Westphal M, Warnick RE, Rand RW, Floeth F, Rommel F, Pan H, Hingorani VN, Puri RK. Source: Journal of Neuro-Oncology. 2003 August-September; 64(1-2): 125-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952293

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Segregation and use of nonshared care settings reduce the risk of multiresistant P. aeruginosa infection. Re: Davies et al., “Multiresistant Pseudomonas aeruginosa in a pediatric cystic fibrosis center: natural history and implications for segregation,” Pediatr Pulmonol 2003;35:253-256. Author(s): Festini F, Ballarin S, Loganes C. Source: Pediatric Pulmonology. 2003 August; 36(2): 171; Author Reply 172. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12833499

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Selective early production of CCL20, or macrophage inflammatory protein 3alpha, by human mast cells in response to Pseudomonas aeruginosa. Author(s): Lin TJ, Maher LH, Gomi K, McCurdy JD, Garduno R, Marshall JS. Source: Infection and Immunity. 2003 January; 71(1): 365-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12496186

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Sequencing of the Pseudomonas aeruginosa and Burkholderia cepacia genomes and their applications in relation to cystic fibrosis. Author(s): Miller DA, Mahenthiralingam E. Source: Journal of the Royal Society of Medicine. 2003; 96 Suppl 43: 57-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12906327

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Sequential genotyping of Pseudomonas aeruginosa from upper and lower airways of cystic fibrosis patients. Author(s): Jung A, Kleinau I, Schonian G, Bauernfeind A, Chen C, Griese M, Doring G, Gobel U, Wahn U, Paul K. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 December; 20(6): 1457-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503704

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Serial granulocyte transfusions as a treatment for sepsis due to multidrug-resistant Pseudomonas aeruginosa in a neutropenic patient. Author(s): Lin YW, Adachi S, Watanabe K, Umeda K, Nakahata T. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4892-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532253

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Serovar determination, drug resistance patterns and plasmid profiles of Pseudomonas aeruginosa isolated from burn patients at two hospitals of Tehran (IRAN). Author(s): Shahcheraghi F, Feizabadi MM, Yamin V, Abiri R, Abedian Z. Source: Burns : Journal of the International Society for Burn Injuries. 2003 September; 29(6): 547-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927978

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Simple microdilution test for detection of metallo-beta-lactamase production in Pseudomonas aeruginosa. Author(s): Migliavacca R, Docquier JD, Mugnaioli C, Amicosante G, Daturi R, Lee K, Rossolini GM, Pagani L. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4388-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409438

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Single and combination antibiotic susceptibilities of planktonic, adherent, and biofilm-grown Pseudomonas aeruginosa isolates cultured from sputa of adults with cystic fibrosis. Author(s): Aaron SD, Ferris W, Ramotar K, Vandemheen K, Chan F, Saginur R. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4172-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409393

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Single-nucleotide-polymorphism mapping of the Pseudomonas aeruginosa type III secretion toxins for development of a diagnostic multiplex PCR system. Author(s): Ajayi T, Allmond LR, Sawa T, Wiener-Kronish JP. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3526-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904350

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Spread of integron-associated VIM-type metallo-beta-lactamase genes among imipenem-nonsusceptible Pseudomonas aeruginosa strains in Greek hospitals. Author(s): Giakkoupi P, Petrikkos G, Tzouvelekis LS, Tsonas S, Legakis NJ, Vatopoulos AC; WHONET Greece Study Group. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 822-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574292

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Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Author(s): Mitchell E, Houles C, Sudakevitz D, Wimmerova M, Gautier C, Perez S, Wu AM, Gilboa-Garber N, Imberty A. Source: Nature Structural Biology. 2002 December; 9(12): 918-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415289

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Structural revision of sulfated polysaccharide B-1 isolated from a marine Pseudomonas species and its cytotoxic activity against human cancer cell lines. Author(s): Matsuda M, Yamori T, Naitoh M, Okutani K. Source: Marine Biotechnology (New York, N.Y.). 2003 January-February; 5(1): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925914

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Subcellular localization of Pseudomonas pyocyanin cytotoxicity in human lung epithelial cells. Author(s): O'Malley YQ, Abdalla MY, McCormick ML, Reszka KJ, Denning GM, Britigan BE. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 February; 284(2): L420-30. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12414438

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Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide. Author(s): Bufler P, Schmidt B, Schikor D, Bauernfeind A, Crouch EC, Griese M. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 February; 28(2): 249-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540493

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Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001. Author(s): Karlowsky JA, Draghi DC, Jones ME, Thornsberry C, Friedland IR, Sahm DF. Source: Antimicrobial Agents and Chemotherapy. 2003 May; 47(5): 1681-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709340

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Survey of resistance of Pseudomonas aeruginosa from UK patients with cystic fibrosis to six commonly prescribed antimicrobial agents. Author(s): Pitt TL, Sparrow M, Warner M, Stefanidou M. Source: Thorax. 2003 September; 58(9): 794-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947141

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Susceptibility of multi-drug-resistant Pseudomonas aeruginosa in intensive care units: results from the European MYSTIC study group. Author(s): Goossens H. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 980-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616692

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Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis. Author(s): Smith AL, Fiel SB, Mayer-Hamblett N, Ramsey B, Burns JL. Source: Chest. 2003 May; 123(5): 1495-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740266

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Synergic activity of cephalosporins plus fluoroquinolones against Pseudomonas aeruginosa with resistance to one or both drugs. Author(s): Fish DN, Choi MK, Jung R. Source: The Journal of Antimicrobial Chemotherapy. 2002 December; 50(6): 1045-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12461031

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Tertiary structure of thiopurine methyltransferase from Pseudomonas syringae, a bacterial orthologue of a polymorphic, drug-metabolizing enzyme. Author(s): Scheuermann TH, Lolis E, Hodsdon ME. Source: Journal of Molecular Biology. 2003 October 24; 333(3): 573-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556746

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The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. Author(s): Garrity-Ryan L, Shafikhani S, Balachandran P, Nguyen L, Oza J, Jakobsen T, Sargent J, Fang X, Cordwell S, Matthay MA, Engel JN. Source: Infection and Immunity. 2004 January; 72(1): 546-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688136

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The Drosophila melanogaster toll pathway participates in resistance to infection by the gram-negative human pathogen Pseudomonas aeruginosa. Author(s): Lau GW, Goumnerov BC, Walendziewicz CL, Hewitson J, Xiao W, MahajanMiklos S, Tompkins RG, Perkins LA, Rahme LG. Source: Infection and Immunity. 2003 July; 71(7): 4059-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819096

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The dual roles of AlgG in C-5-epimerization and secretion of alginate polymers in Pseudomonas aeruginosa. Author(s): Jain S, Franklin MJ, Ertesvag H, Valla S, Ohman DE. Source: Molecular Microbiology. 2003 February; 47(4): 1123-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581364

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The effect of an antimicrobial restriction program on Pseudomonas aeruginosa resistance to beta-lactams in a large teaching hospital. Author(s): Regal RE, DePestel DD, VandenBussche HL. Source: Pharmacotherapy. 2003 May; 23(5): 618-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12741436

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The effects of some formulation factors used in ophthalmic preparations on thiomersal activity against Pseudomonas aeruginosa and Staphylococcus aureus. Author(s): Abuqaddom AI, Darwish RM, Muti H. Source: Journal of Applied Microbiology. 2003; 95(2): 250-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859755

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The glycosylation of airway mucins in cystic fibrosis and its relationship with lung infection by Pseudomonas aeruginosa. Author(s): Roussel P, Lamblin G. Source: Advances in Experimental Medicine and Biology. 2003; 535: 17-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714886

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The in-vitro antimicrobial effect of non-antibiotics and putative inhibitors of efflux pumps on Pseudomonas aeruginosa and Staphylococcus aureus. Author(s): Hendricks O, Butterworth TS, Kristiansen JE. Source: International Journal of Antimicrobial Agents. 2003 September; 22(3): 262-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678831

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The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin, ExoU. Author(s): Sato H, Frank DW, Hillard CJ, Feix JB, Pankhaniya RR, Moriyama K, FinckBarbancon V, Buchaklian A, Lei M, Long RM, Wiener-Kronish J, Sawa T. Source: The Embo Journal. 2003 June 16; 22(12): 2959-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12805211

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The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Author(s): Tateda K, Ishii Y, Horikawa M, Matsumoto T, Miyairi S, Pechere JC, Standiford TJ, Ishiguro M, Yamaguchi K. Source: Infection and Immunity. 2003 October; 71(10): 5785-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500500

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The Pseudomonas aeruginosa genome: how do we use it to develop strategies for the treatment of patients with cystic fibrosis and Pseudomonas infections? Author(s): Erwin AL, VanDevanter DR. Source: Current Opinion in Pulmonary Medicine. 2002 November; 8(6): 547-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394165

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The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells. Author(s): O'Malley YQ, Reszka KJ, Rasmussen GT, Abdalla MY, Denning GM, Britigan BE. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 November; 285(5): L1077-86. Epub 2003 July 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871859

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The transcriptional regulator AlgR is essential for Pseudomonas aeruginosa pathogenesis. Author(s): Lizewski SE, Lundberg DS, Schurr MJ. Source: Infection and Immunity. 2002 November; 70(11): 6083-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379685

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To the editor: Re: A-Rahman, Pedler S, Bray R, The effect of anesthetic gases on the growth of Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus, Pediatr Pulmonol 2002;34:226-227. Author(s): Kerr JR. Source: Pediatric Pulmonology. 2003 May; 35(5): 414; Author Reply 415. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687602

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Toll-like receptor 5-mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa flagellin. Author(s): Zhang J, Xu K, Ambati B, Yu FS. Source: Investigative Ophthalmology & Visual Science. 2003 October; 44(10): 4247-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507868

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Towards “molecular Esperanto” or the Tower of Babel? (the need for harmonization of techniques for genotyping clinical isolates of Pseudomonas aeruginosa isolated from patients with cystic fibrosis). Author(s): Moore JE, Goldsmith CE, Elborn JS, Murphy PG, Gilligan PH, Fanning S, Hogg G. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5347-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605202

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Transmission pathways of Pseudomonas aeruginosa in intensive care units: don't go near the water. Author(s): Bonten MJ, Weinstein RA. Source: Critical Care Medicine. 2002 October; 30(10): 2384-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394977

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Two different mechanisms are involved in the extremely high-level benzalkonium chloride resistance of a Pseudomonas fluorescens strain. Author(s): Nagai K, Murata T, Ohta S, Zenda H, Ohnishi M, Hayashi T. Source: Microbiology and Immunology. 2003; 47(10): 709-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605437

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Type III secretion-mediated killing of endothelial cells by Pseudomonas aeruginosa. Author(s): Saliba AM, Filloux A, Ball G, Silva AS, Assis MC, Plotkowski MC. Source: Microbial Pathogenesis. 2002 October; 33(4): 153-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385743

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Typing of Pseudomonas aeruginosa strains in Turkish cystic fibrosis patients. Author(s): Yagci A, Ciragil P, Over U, Sener B, Erturan Z, Soyletir G. Source: New Microbiol. 2003 January; 26(1): 109-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12578318

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Understanding Pseudomonas aeruginosa. Author(s): Reynolds P. Source: Nurs Times. 2000 June 8; 96(23 Suppl): 6-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11963422

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Unusual nosocomial infection due to Pseudomonas aeruginosa. Author(s): Kanellopoulou M, Horiaropoulou M, Paraskevopoulos I, Lambropoulos S, Legakis NJ, Papafrangas E. Source: The Journal of Hospital Infection. 2002 March; 50(3): 239. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886208

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Use of DNA fingerprinting in decision making for considering closure of neonatal intensive care units because of Pseudomonas aeruginosa bloodstream infections. Author(s): Schutze GE, Gilliam CH, Jin S, Cavenaugh CK, Hall RW, Bradsher RW, Jacobs RF. Source: The Pediatric Infectious Disease Journal. 2004 February; 23(2): 110-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872174

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Use of parenteral colistin for the treatment of serious infection due to antimicrobialresistant Pseudomonas aeruginosa. Author(s): Linden PK, Kusne S, Coley K, Fontes P, Kramer DJ, Paterson D. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 December 1; 37(11): E154-60. Epub 2003 October 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614688

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Use of real-time PCR with multiple targets to identify Pseudomonas aeruginosa and other nonfermenting gram-negative bacilli from patients with cystic fibrosis. Author(s): Qin X, Emerson J, Stapp J, Stapp L, Abe P, Burns JL. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4312-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958262

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Use of subtractive hybridization to identify a diagnostic probe for a cystic fibrosis epidemic strain of Pseudomonas aeruginosa. Author(s): Parsons YN, Panagea S, Smart CH, Walshaw MJ, Hart CA, Winstanley C. Source: Journal of Clinical Microbiology. 2002 December; 40(12): 4607-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454160

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Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis. Author(s): Miyata S, Casey M, Frank DW, Ausubel FM, Drenkard E. Source: Infection and Immunity. 2003 May; 71(5): 2404-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704110

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VIM- and IMP-type metallo-beta-lactamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean hospitals. Author(s): Lee K, Lee WG, Uh Y, Ha GY, Cho J, Chong Y; Korean Nationwide Surveillance of Antimicrobial Resistance Group. Source: Emerging Infectious Diseases. 2003 July; 9(7): 868-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890331

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VIM-4 in a carbapenem-resistant strain of Pseudomonas aeruginosa isolated in Sweden. Author(s): Giske CG, Rylander M, Kronvall G. Source: Antimicrobial Agents and Chemotherapy. 2003 September; 47(9): 3034-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12937022

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Whole genome fingerprinting and genotyping of multiple drug resistant (MDR) isolates of Pseudomonas aeruginosa from endophthalmitis patients in India. Author(s): Ahmed N, Bal A, Khan AA, Alam M, Kagal A, Arjunwadkar V, Rajput A, Majeed AA, Rahman SA, Banerjee S, Joshi S, Bharadwaj R. Source: Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2002 May; 1(3): 237-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798020

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

Finding Nutrition Studies on Pseudomonas 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 “pseudomonas” (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 “pseudomonas” (or a synonym): •

Antifungal efficacy of bacteria isolated from marine sedentary organisms. Author(s): Regional Research Lab., Orissa (India). Forest and Marine Products Div. Source: Mohapatra, B.R. Bapuji, M. Sree, A. Folia-Microbiologica (Czech Republic). (February 2002). volume 47(1) page 51-55.

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Experiences in the molecular ecology of the rhizosphere with microbial releases. Author(s): University Coll., Cork (Ireland) Source: Lohrke, S. Moeenne Loccoz, Y. McCarthy, J. Powell, J. Higgins, P. Joyce, H. O'Gara, F. JIRCAS-International-Symposium-Series (Japan). (November 1997). (no.5) page 91-100.

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Toxoflavin is an essential factor for virulence of Burkholderia glumae causing rice [Oryza sativa] seedling rot disease. Author(s): Meiji Univ., Kawasaki, Kanagawa (Japan). Faculty of Agriculture Source: Yoneyama, K. Kono, Y. Yamaguchi, I. Horikoshi, M. Hirooka, T. Annals-of-thePhytopathological-Society-of-Japan (Japan). (April 1998). volume 64(2) page 91-96.

Additional physician-oriented references include: •

1 alpha,25-Dihydroxyvitamin D3 inhibits pro-inflammatory cytokine and chemokine expression in human corneal epithelial cells colonized with Pseudomonas aeruginosa. Author(s): Cooperative Research Centre For Eye Research and Technology, School of Optometry, University of New South Wales, Sydney, New South Wales, Australia. Source: Xue, M L Zhu, H Thakur, A Willcox, M Immunol-Cell-Biol. 2002 August; 80(4): 340-5 0818-9641

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Accumulation of poly(3-hydroxybutyrate) from octanoate in different pseudomonas belonging to the rRNA homology group I. Author(s): Unite de Biodiversite des Bacteries Pathogenes Emergentes, Institut National de la Sante et de la Recherche Medicale U389, Institut Pasteur, Paris, France. Source: Diard, S Carlier, J P Ageron, E Grimont, P A Langlois, V Guerin, P Bouvet, O M Syst-Appl-Microbiol. 2002 August; 25(2): 183-8 0723-2020

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Bioaccumulation of yttrium in Pseudomonas fluorescens and the role of the outer membrane component(s). Author(s): Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada. Source: Appanna, V D Hamel, R D Pankar, E Puiseux Dao, S Microbios. 2001; 106(413): 19-29 0026-2633

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Bioavailability of solid and non-aqueous phase liquid (NAPL)-dissolved phenanthrene to the biosurfactant-producing bacterium Pseudomonas aeruginosa 19SJ. Author(s): Instituto de Recursos Naturales y Agrobiologia, CSIC, Apartado 1052, E41080 Seville, Spain. Source: Garcia Junco, M De Olmedo, E Ortega Calvo, J J Environ-Microbiol. 2001 September; 3(9): 561-9 1462-2912

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Bioremediation of toxic chromium from electroplating effluent by chromate-reducing Pseudomonas aeruginosa A2Chr in two bioreactors. Author(s): School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi, India. Source: Ganguli, A Tripathi, A K Appl-Microbiol-Biotechnol. 2002 March; 58(3): 416-20 0175-7598

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Biotransformation kinetics of Pseudomonas putida for cometabolism of phenol and 4-chlorophenol in the presence of sodium glutamate. Author(s): Department of Chemical and Environmental Engineering, The National University of Singapore, Singapore. Source: Wang, S J Loh, K C Biodegradation. 2001; 12(3): 189-99 0923-9820

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Characterization of the eugenol hydroxylase genes (ehyA/ehyB) from the new eugenol-degrading Pseudomonas sp. strain OPS1. Author(s): Institut fur Mikrobiologie der Westfalischen Wilhelms-Universitat Munster, Germany. Source: Brandt, K Thewes, S Overhage, J Priefert, H Steinbuchel, A Appl-MicrobiolBiotechnol. 2001 September; 56(5-6): 724-30 0175-7598

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Cloning, characterization and comparison of the Pseudomonas mendocina polyhydroxyalkanoate synthases Phac1 and PhaC2. Author(s): Institut fur Mikrobiologie der Westfalischen Wilhelms-Universitat Munster, Germany. Source: Hein, S Paletta, J R Steinbuchel, A Appl-Microbiol-Biotechnol. 2002 February; 58(2): 229-36 0175-7598

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Co-metabolic degradation of chlorinated hydrocarbons by Pseudomonas sp. strain DCA1. Author(s): Department of Agrotechnology and Food Sciences, Wageningen University, The Netherlands. [email protected] Source: Hage, J C Kiestra, F D Hartmans, S Appl-Microbiol-Biotechnol. 2001 November; 57(4): 548-54 0175-7598

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Constitutive activation of jasmonate signaling in an Arabidopsis mutant correlates with enhanced resistance to Erysiphe cichoracearum, Pseudomonas syringae, and Myzus persicae. Author(s): School of Biological Sciences, University of East Anglia, Norwich, UK. Source: Ellis, C Karafyllidis, I Turner, J G Mol-Plant-Microbe-Interact. 2002 October; 15(10): 1025-30 0894-0282

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Effect of outer-membrane permeabilizers on the activity of antibiotics and plant extracts against Pseudomonas aeruginosa. Author(s): Biochemistry Division, Regional Research Laboratory, Jorhat 785 006, Assam, India. Source: Guha, A Choudhury, A Unni, B G Roy, M K Folia-Microbiol-(Praha). 2002; 47(4): 379-84 0015-5632

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Effectiveness of mupirocin and polymyxin B in experimental Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis. Author(s): Department of Microbiology, Immunology, and Parasitology, LSU Health Sciences Center, New Orleans, LA 70112, USA. Source: Moreau, J M Conerly, L L Hume, E B Dajcs, J J Girgis, D O Cannon, B M Thibodeaux, B A Stroman, D W O'Callaghan, R J Cornea. 2002 November; 21(8): 807-11 0277-3740

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Effects of nutritional factors on production of tabtoxin, a phytotoxin, by Pseudomonas syringae pv. tabaci. Author(s): Institut National de la Recherche Agronomique d'Algerie, UR, Setif 19000, Algeria. Source: Dehbi, F Harzallah, D Larous, L Meded-Rijksuniv-Gent-Fak-LandbouwkdToegep-Biol-Wet. 2001; 66(2a): 241-7 1373-7503

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Effects of surfactant protein A and NaCl concentration on the uptake of Pseudomonas aeruginosa by THP-1 cells. Author(s): Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. Source: Khubchandani, K R Oberley, R E Snyder, J M Am-J-Respir-Cell-Mol-Biol. 2001 December; 25(6): 699-706 1044-1549

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Evaluation of carbazole degradation by Pseudomonas rhodesiae strain KK1 isolated from soil contaminated with coal tar. Author(s): Research Institute for Basic Sciences, Cheju National University, Jeju 690-756, Korea. Source: Yoon, B J Lee, D H Kang, Y S Oh, D C Kim, S I Oh, K H Kahng, H Y J-BasicMicrobiol. 2002; 42(6): 434-43 0233-111X

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Functional analysis of a chromosomal arsenic resistance operon in Pseudomonas fluorescens strain MSP3. Author(s): Department of Experimental Radiation Oncology, University of Texas-MD Anderson Cancer Center, Houston 77030, USA. [email protected] Source: Prithivirajsingh, S Mishra, S K Mahadevan, A Mol-Biol-Repage 2001; 28(2): 63-72 0301-4851

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GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: identification of novel pyoverdine biosynthesis genes. Author(s): Department of Microbiology, Campus Box B-175, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. Source: Ochsner, U A Wilderman, P J Vasil, A I Vasil, M L Mol-Microbiol. 2002 September; 45(5): 1277-87 0950-382X

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Induction of systemic resistance to Botrytis cinerea in tomato by Pseudomonas aeruginosa 7NSK2: role of salicylic acid, pyochelin, and pyocyanin. Author(s): Laboratory of Phytopathology, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Belgium. Source: Audenaert, K Pattery, T Cornelis, P Hofte, M Mol-Plant-Microbe-Interact. 2002 November; 15(11): 1147-56 0894-0282

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Induction of the halobenzoate catabolic pathway and cometabolism of orthochlorobenzoates in Pseudomonas aeruginosa 142 grown on glucose-supplemented media. Author(s): Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain. Source: Corbella, M E Garrido Pertierra, A Puyet, A Biodegradation. 2001; 12(3): 149-57 0923-9820

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Metal chelating properties of pyridine-2,6-bis(thiocarboxylic acid) produced by Pseudomonas spp. and the biological activities of the formed complexes. Author(s): Environmental Biotechnology Institute, University of Idaho, Moscow 838441052, USA. Source: Cortese, M S Paszczynski, A Lewis, T A Sebat, J L Borek, V Crawford, R L Biometals. 2002 June; 15(2): 103-20 0966-0844

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Method for qualifying microbial removal performance of 0.1 micron rated filters. Part III: bacterial challenge tests on 0.2/0.22 and 0.1 micron rated filter cartridges with Hydrogenophaga (formerly Pseudomonas) pseudoflava. Author(s): Pall Corporation, Scientific and Laboratory Services Department, Port Washington, NY, USA. [email protected] Source: Sundaram, S Eisenhuth, J Lewis, M Howard, G Jr Brandwein, H PDA-J-PharmSci-Technol. 2001 Nov-December; 55(6): 393-416 1079-7440

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Preliminary examinations for applying a carbazole-degrader, Pseudomonas sp. strain CA10, to dioxin-contaminated soil remediation. Author(s): Biotechnology Research Center, The University of Tokyo, Japan. Source: Habe, H Ide, K Yotsumoto, M Tsuji, H Hirano, H Widada, J Yoshida, T Nojiri, H Omori, T Appl-Microbiol-Biotechnol. 2001 September; 56(5-6): 788-95 0175-7598

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Pseudomonas aeruginosa biofilms react with and precipitate toxic soluble gold. Author(s): Department of Microbiology, College of Biological Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Source: Karthikeyan, S Beveridge, T J Environ-Microbiol. 2002 November; 4(11): 667-75 1462-2912

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Pseudomonas salomonii sp. nov., pathogenic on garlic, and Pseudomonas palleroniana sp. nov., isolated from rice. Author(s): UMR 077 de Pathologie Vegetale INRA-INH-Universite, BP 57, 42 rue G. Morel, 49071 Beaucouze , France. [email protected] Source: Gardan, L Bella, P Meyer, J M Christen, R Rott, P Achouak, W Samson, R Int-JSyst-Evol-Microbiol. 2002 November; 52(Pt 6): 2065-74 1466-5026

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Pseudomonas sp. strain KC represents a new genomovar within Pseudomonas stutzeri. Author(s): Department of Microbiology and National Science Foundation Center for Microbial Ecology, Michigan State University, East Lansing 48823, USA. [email protected] Source: Sepulveda Torres, L C Zhou, J Guasp, C Lalucat, J Knaebel, D Plank, J L Criddle, C S Int-J-Syst-Evol-Microbiol. 2001 November; 51(Pt 6): 2013-9 1466-5026

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Rapid flow cytometry--Nile red assessment of PHA cellular content and heterogeneity in cultures of Pseudomonas aeruginosa 47T2 (NCIB 40044) grown in waste frying oil. Author(s): Department de Microbiologia i Parasitologia Sanitaries, Facultat de Farmacia, Universitat de Barcelona, Spain. Source: Vidal Mas, J Resina Pelfort Haba, E Comas, J Manresa, A Vives Rego, J AntonieVan-Leeuwenhoek. 2001 October; 80(1): 57-63 0003-6072

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Regiospecific effect of 1-octanol on cis-trans isomerization of unsaturated fatty acids in the solvent-tolerant strain Pseudomonas putida S12. Author(s): Department of Bioconversion, ATO, Wageningen UR, The Netherlands. [email protected] Source: Heipieper, H J de Waard, P van der Meer, P Killian, J A Isken, S de Bont, J A Eggink, G de Wolf, F A Appl-Microbiol-Biotechnol. 2001 November; 57(4): 541-7 01757598

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Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism. Author(s): Institute of Microbiology, Technical University Braunschweig, Spielmannstrasse 7, D-38106 Braunschweig, Germany.

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Source: Frere, Frederic Schubert, Wolf Dieter Stauffer, Frederic Frankenberg, Nicole Neier, Reinhard Jahn, Dieter Heinz, Dirk W J-Mol-Biol. 2002 July 5; 320(2): 237-47 00222836 •

Subinhibitory bismuth-thiols reduce virulence of Pseudomonas aeruginosa. Author(s): CardioPulmonary Research Institute, Division of Pulmonary and Critical Care Medicine, Winthrop-University Hospital, SUNY School of Medicine at Stony Brook, Mineola, New York 11501, USA. Source: Wu, Chieh Liang Domenico, Philip Hassett, Daniel J Beveridge, Terry J Hauser, Alan R Kazzaz, Jeffrey A Am-J-Respir-Cell-Mol-Biol. 2002 June; 26(6): 731-8 1044-1549

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Tetrachloroethylene, trichloroethylene, and chlorinated phenols induce toluene-oxylene monooxygenase activity in Pseudomonas stutzeri OX1. Author(s): Department of Chemical Engineering, University of Connecticut, Storrs 06269-3222, USA. Source: Ryoo, D Shim, H Arenghi, F L Barbieri, P Wood, T K Appl-Microbiol-Biotechnol. 2001 August; 56(3-4): 545-9 0175-7598

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Treatment of post-burns bacterial infections by bacteriophages, specifically ubiquitous Pseudomonas spp. notoriously resistant to antibiotics. Author(s): Department of Life Sciences, Nottingham Trent University, Nottingham, England. [email protected] Source: Ahmad, S I Med-Hypotheses. 2002 April; 58(4): 327-31 0306-9877

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

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

•

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

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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/

•

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/

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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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CHAPTER 3. DISSERTATIONS ON PSEUDOMONAS Overview In this chapter, we will give you a bibliography on recent dissertations relating to pseudomonas. 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 “pseudomonas” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on pseudomonas, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Pseudomonas 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 pseudomonas. 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: •

4-deoxy-4-fluoro-d-glucose a Novel Membrane Probe in Pseudomonas Putida by D'Amore, Tony; PhD from University of Windsor (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK62052

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A Study of an Aldehyde Dehydrogenase from Pseudomonas Aeruginosa by Tigerstrom, Richard G. C. von; ADVDEG from The University of British Columbia (Canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02400

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Alkaline Phosphatase and the Cell Envelope of Pseudomonas Aeruginosa by Day, Donal F; PhD from Mcgill University (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK18188

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Amino Acid Transport and Pool Formation in Pseudomonas Aeruginosa by Kay, William Wayne; ADVDEG from The University of British Columbia (Canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02373

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Amino Acid Transport in Catabolic and Cryptic Mutants of Pseudomonas Fluorescens by Hechtman, Peter; ADVDEG from Mcgill University (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06396

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An Examination of Some Aspects of the Structure, Function and Synthesis of the Extracellular Slime Produced by Cystic Fibrosis Isolates of Pseudomonas Aeruginosa in Relation to the Microcolony Mode of Growth by Chan, Chiu-Yeung Raphael; PhD from University of Calgary (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK51240

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An Examination of Some Immunological and Structural Aspects of the Outer Membrane of Pseudomonas Aeruginosa Strain Pa01 (h103) by Lam, Joseph Sui-Lung; PhD from University of Calgary (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK66213

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Angular Leaf Spot (Pseudomonas Syringae Pv. Lachrymans) Control, Detection and Pathogenicity on Cucurbits, and Control of Bacterial Leaf Spot of Pumpkin (Xanthomonas cucurbitae) with Chemical Seed Treatments by Ozdemir, Zahide; PhD from Cornell University, 2003, 125 pages http://wwwlib.umi.com/dissertations/fullcit/3075845

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Biochemical, Molecular and Physiological Characterization of 1-butanol Dehydrogenases of Pseudomonas Butanovora in Butane and 1-butanol Metabolism by Vangnai, Alisa S.; PhD from Oregon State University, 2003, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3061924

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Biocontrol of Fusarium in Wheat: Introducing Bacteria to a System of Complex Interactions (Pseudomonas) by Johansson, Petra Maria; Fildr from Sveriges Lantbruksuniversitet (Sweden), 2003, 74 pages http://wwwlib.umi.com/dissertations/fullcit/f12209

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Biosynthesis of Phenazines by Pseudomonas Aeruginosa by Chang, Pin-Chuan; ADVDEG from Mcgill University (Canada), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK01903

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Biosynthesis of the Pseudomonas Aeruginosa Siderophore Pyochelin: Peptide Synthesis and Tailoring by Patel, Hiten M.; PhD from Harvard University, 2003, 201 pages http://wwwlib.umi.com/dissertations/fullcit/3091655

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Characterization of the Pilus of Pseudomonas Aeruginosa Demonstration of an Epithelial Binding Domain Within the Pilin by Doig, Peter Clifford; PhD from University of Toronto (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL54462

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Characterization of Type III Effectors of Pseudomonas Syringae Pv. Tomato by Shan, Libo; PhD from Kansas State University, 2003, 123 pages http://wwwlib.umi.com/dissertations/fullcit/3090385

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Chloramphenicol Effects on Growth, Enzymatic Activities and Metabolism of the Parental and a Resistant Strain of Pseudomonas Aeruginosa by Mahmourides, George; PhD from McGill University (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK66595

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Chloramphenicol Resistance in Pseudomonas Aeruginosa by Irvin, Jean E; PhD from McGill University (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK66574

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Cloning and Characterization of the OPRF Gene for Protein F from Pseudomonas Aeruginosa by Woodruff, Wendy Anne; PhD from The University of British Columbia (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL47048

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Colonization of Model and Meat Surfaces by Pseudomonas Fragi and Pseudomonas Fluorescens by Delaquis, Pascal J; PhD from The University of Saskatchewan (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL53080

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Construction of a Pseudomonas Aeruginosa Dihydroorotase Mutant and the Discovery of a Novel Link between Pyrimidine Biosynthetic Intermediates and the Ability to Produce Virulence Factors by Brichta, Dayna Michelle; PhD from University of North Texas, 2003, 246 pages http://wwwlib.umi.com/dissertations/fullcit/3106866

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Contributions of the Hrp/hrc Cluster and Conserved Effector Locus to the Pathogenicity of Pseudomonas Syringae Pv. Tomato Dc3000 by Badel, Jorge Luis; PhD from Cornell University, 2003, 250 pages http://wwwlib.umi.com/dissertations/fullcit/3075894

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Conversion of Gdp-mannose into Various GDP-deoxyhexoses in Gram-negative Bacteria (Actinobacillus actinomycetemcomitans, Pseudomonas aeruginosa, Helicobacter pylori) by Maki, Minna; PhD from Helsingin Yliopisto (Finland), 2003, 63 pages http://wwwlib.umi.com/dissertations/fullcit/f59009

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Degradation of Trichloroethylene by Pseudomonas Putida F1 Grown on Toluene and Its Degradation Product Benzyl Alcohol by Begonia, Micahel Tejada; MS from Mississippi State University, 2003, 54 pages http://wwwlib.umi.com/dissertations/fullcit/1414576

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D-gluconate Transport and Metabolism in Membrane Vesicles of Pseudomonas Putida (ATCC 12633) by Moses, Godfrey Cornelius; PhD from University of Windsor (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK49235

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DNA Synthesis and Modification in OW-14-Infected Pseudomonas Acidovorans by Maltman, Kirk Lee; PhD from The University of British Columbia (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK56670

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Functional Analysis of ALKB Genes in a Pseudomonas Aeruginosa Strain: Basis for Different Alkane Chain Length Utilization Capabilities by Sotsky, Julie B.; PhD from University of Louisville, 2003, 190 pages http://wwwlib.umi.com/dissertations/fullcit/3089521

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Functional Characterization of the P-Nitrophenol Gene Cluster in Pseudomonas Sp. Strain ENV2030 by Jackson, Michael Gary; PhD from Rutgers the State University of New Jersey - New Brunswick, 2003, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3105456

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Genetics of Resistance to Bacterial Speck Caused by Pseudomonas Syringae Pv. Tomato in Field Tomatoes by Pitblado, Ronald E; PhD from University of Guelph (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK63432

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Host Defense Mechanisms in the Crayfish: The Effect of Injection with Live or Killed Bacteria (Procambarus clarkii, Pseudomonas) by Goins, Kimberly Renee; MS from East Tennessee State University, 2003, 37 pages http://wwwlib.umi.com/dissertations/fullcit/1413431

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Identification and Characterization of a CRP/VFR Homologue in Pseudomonas Putida and the Determination of Its Role in the Expression of PCA Genes by Farag, Bothina Ahmed Kamel; PhD from Georgia State University, 2003, 192 pages http://wwwlib.umi.com/dissertations/fullcit/3097487

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Immunochemistry of Pseudomonas Aeruginosa Outer Membrane Proteins by Mutharia, Lucy Muthonl; PhD from The University of British Columbia (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK22432

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Interactions between Pseudomonas Aeruginosa and Airway Epithelia in Cystic Fibrosis by Hybiske, Kevin James; PhD from University of California, Berkeley, 2003, 232 pages http://wwwlib.umi.com/dissertations/fullcit/3105247

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Investigating Activities of the Pseudomonas Syringae Type III Effector AVRRPT2 in Promoting Disease on Arabidopsis Thaliana by Chen, Zhongying; PhD from Washington University, 2003, 276 pages http://wwwlib.umi.com/dissertations/fullcit/3105942

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Investigating the Role of Salicylic Acid in the Age-Related Resistance Response of the Arabidopsis Thaliana-Pseudomonas Syringae Pv. Tomato System by Zaton, Kasia Katherine; MSc from University of Toronto (Canada), 2003, 142 pages http://wwwlib.umi.com/dissertations/fullcit/MQ78500

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Investigation of the R Protein-Autoinducer Interaction in the Pseudomonas Aeruginosa Quorum Sensing System by Smith, Kristina Marie; PhD from State University of New York at Buffalo, 2003, 149 pages http://wwwlib.umi.com/dissertations/fullcit/3089120

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Investigations Related to the Delta(5)-3-Ketoisomerase of Pseudomonas Testosteroni by Gordon, Keith David; PhD from University of Toronto (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK15393

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Localization and Characterization of a Cell-Associated Precursor to Exocellular Protease 1 of Pseudomonas Aeruginosa by Fecycz, Irene Tekla; PhD from University of Alberta (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK56832

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Macrophage Interaction with Pseudomonas Aeruginosa by Kluftinger, Janet Louise; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50838

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Mechanisms of Streptomycin and Tetracycline Resistance in Pseudomonas Aeruginosa by Tseng, Jui-Teng; PhD from University of Alberta (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15369

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Microbial Interactions: Effect of Pseudomonas Aeruginosa and Pyocyanine on the Growth of Salmonella Thompson by McDonald, Malcolm Sterling; PhD from McGill University (Canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK33668

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Molecular Mutational Characterization of NAHR and Mating Pair Formation (MPF) Genes in Naphthalene-Degrading Pseudomonas Putida: Implications for Survival in

Dissertations 159

Soil and Plasmid Transfer by Park, Wodjun; PhD from Cornell University, 2003, 207 pages http://wwwlib.umi.com/dissertations/fullcit/3087039 •

Molecular Studies of the Nmephe Pilin of Pseudomonas Aeruginosa by Pasloske, Brittan L; PhD from University of Alberta (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL55637

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Nucleic Acid Metabolism in Uninfected and Bacteriophage [PHI]W-14 Infected Pseudomonas Acidovorans by Kelln, R. A; PhD from The University of British Columbia (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK17194

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Optimization of Cultural Factors Influencing the Production of Extracellular Vesicles and Proteinase by Pseudomonas FRAGI ATCC 4973 by Myhara, Robert Michael; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50738

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Paclobutrazol and Acibenzolar-S-Methyl Induced Tomato Seedling Growth Response and Resistance to Bacterial Speck (Pseudomonas Syringae Pv. Tomato) (Pseudomonas Syringae) by Mahesaniya, Akbarali Alimahammad; MSc from University of Guelph (Canada), 2003, 100 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76091

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Pathway of Phloroglucional Degradation by a Pseudomonas Sp MAC 451 by Hang, Yong Deng; ADVDEG from McGill University (Canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02801

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Pharmacokinetics/Pharmacodynamics of Beta-Lactams Alone and in Combination with Beta-Lactamase Inhibitors against Beta-Lactamase-Inducible Pseudomonas Aeruginosa by Li, Chonghua; PhD from The University of Connecticut, 2003, 131 pages http://wwwlib.umi.com/dissertations/fullcit/3101700

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Phosphate Transport across the Outer Membrane of Pseudomonas Aeruginosa by Poole, Raymond Keith; PhD from The University of British Columbia (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL34853

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Physiological Basis of Polyhydroxyalkanoate Metabolism in Pseudomonas Putida by De Roo, Guy; Drscnat from Eidgenoessische Technische Hochschule Zuerich (Switzerland), 2003, 146 pages http://wwwlib.umi.com/dissertations/fullcit/f70001

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Pseudomonas Aeruginosa Lipopolysaccharide : Interaction with Isolated Mitochondria and Some Endotoxin Properties by Greer, G. Gordon; PhD from Queen's University at Kingston (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK26260

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Pseudomonas Oxalaticus (OX 1) and Its Formate Dehydrogenase: A Study by Tan, Thiam Yong; PhD from The University of Manitoba (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK26382

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Pseudomonas Putida 06909 Genes Expressed during Colonization on Mycelial Surfaces and Phenotypic Characterization of Mutants by Ahn, Sang-Joon; PhD from University of California, Riverside, 2003, 167 pages http://wwwlib.umi.com/dissertations/fullcit/3096757

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Regulation of Carbohydrate-Catabolizing Enzymes in Pseudomonas Aeruginosa ATCC 9027 by Lynch, William Henry Walter; PhD from The University of British Columbia (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK17202

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Structure and Assembly of Pili Isolated from Pseudomonas Aeruginosa Strains Pak and Pao by Watts, Tania H; PhD from University of Alberta (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK67535

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Structure, Function, and Role in Antibiotic Resistance of Outer Membrane Protein Hl in Pseudomonas Aeruginosa by Bell, Angus; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL55055

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Studies on the Mechanisms of Resistance to Fluoroquinolone Antimicrobial Agents in Pseudomonas Aeruginosa by Chamberland, Suzanne; PhD from University of Calgary (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46567

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Studies Related to the Delta(5)-3-Ketoisomerase of Pseudomonas Testosteroni by Wigfield, Donald Compston; PhD from University of Toronto (Canada), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK13808

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Studies Related to the Mechanism of Action of the Delta 5 Delta(4)-3-Ketosteroid Isomerase of Pseudomonas Testosteroni by Ship, Saul Irving; PhD from University of Toronto (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK25506

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Succinate Metabolism and Tricarboxylic Acid Cycle Activity in Pseudomonas Aeruginosa by Tiwari, Narayan Prasad; ADVDEG from The University of British Columbia (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK03746

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The Endogenous Respiration of Pseudomonas Aeruginosa during Periods of Prolonged Starvation by MacKelvie, R. M; ADVDEG from The University of British Columbia (Canada), 1965 http://wwwlib.umi.com/dissertations/fullcit/NK00182

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The Enzymology of Cell Division in Pseudomonas Aeruginosa by Bhatti, Mohammad Abdul Rashid; PhD from McGill University (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK31712

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The Genome, Transcriptome, and Preliminary Proteome of Pseudomonas Putida Bacteriophage GH-1: a New Member of the T7 Family of Bacterial Viruses. Computational Analyses of Genomes of Various Bacteriophages and Their Hosts by Kovalyova, Irina Vladimirovna; PhD from Queen's University at Kingston (Canada), 2003, 248 pages http://wwwlib.umi.com/dissertations/fullcit/NQ81003

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The Isolation and Characterization of a Bacteriophage Specific for the Lipopolysaccharide of Rough Derivatives of Pseudomonas Aeruginosa Strain Pao by Jarrell, Kenneth F; PhD from Queen's University at Kingston (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK46360

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The Isolation and Characterization of Aryl-Sulphatase Isoenzymes of Pseudomonas Aeruginosa by Delisle, Gloria Jean (Lougheed); ADVDEG from Queen's University at Kingston (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK07592

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The Isolation and Characterization of Endoglucanase Genes from Pseudomonas Sp. 8634 and Pseudomonas Fluorescens Subs. Cellulosa by Wolff, Bruce R; PhD from University of Waterloo (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL43026

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The Metabolism of 4-deoxy-4-fluoro-d-glucose in Pseudomonas Putida by Sbrissa, Diego; PhD from University of Windsor (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50530

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The Purification, Modification and Characterization of an Intracellular ExonucleasePhosphatase from Pseudomonas Aeruginosa by Bryan, L. E.; ADVDEG from University of Alberta (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06691

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The Role of Ethylene Response Factors in Plant-Pseudomonas Syringae Interactions by He, Ping; PhD from Kansas State University, 2003, 102 pages http://wwwlib.umi.com/dissertations/fullcit/3090358

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The Transport of Citrate and Other Tricarboxylic Acids in Pseudomonas Fluorescens by Lawford, Hugh Gibson; PhD from University of Toronto (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK17788

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Transcription in Pseudomonas Aeruginosa by Allan, Brenda J; PhD from Queen's University at Kingston (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL42294

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Transfer and Behavior of N Plasmids in Pseudomonas Aeruginosa by Tardif, Ginette; PhD from University of Toronto (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK66723

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Transferable Antibiotic Resistance in Clinical Isolates of Pseudomonas Aeruginosa by Dillon, Jo-Anne R; PhD from Queen's University at Kingston (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20237

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Transport of 2-Keto-D-Gluconate and L-Malate in Pseudomonas Putida by Agbanyo, Francisca Roseline Akuvi; PhD from University of Windsor (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65525

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

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

Role of Toxins in Lung Infections Caused by Pseudomonas Aeruginosa Condition(s): Pseudomonas Infection; Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Some bacteria that cause disease can produce toxic substances that may worsen the disease. Pseudomonas aeruginosa is a bacteria that can produce a variety of toxins and is of special interest for patients with cystic fibrosis and repeated long term lung infections. The goal of this study is to determine whether specific toxins produced by Pseudomonas aeruginosa may be important in the disease process of chronic lung infections of patients with cystic fibrosis. This study will attempt to measure bacterial production of toxins in blood and sputum and immune system response to toxins in the blood. Researchers plan to study 4 effector proteins (toxins). 1. exotoxin A 2. Exo S 3. Exo U 4. Pcr V Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027183

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Benefits and Risks of Newborn Screening for Cystic Fibrosis Condition(s): Cystic Fibrosis; Lung Disease; Pseudomonas Infections

8

These are listed at www.ClinicalTrials.gov.

164 Pseudomonas

Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Research Resources (NCRR) Purpose - Excerpt: Although cystic fibrosis (CF) is the most common, life-threatening autosomal recessive genetic disorder of the white population, there are often delays in diagnosis and hence start of treatment. Advances of the past two decades have made CF screening feasible using routinely collected neonatal blood specimens and measuring an enzyme level followed by CF mutation DNA analysis. Our overall goal of the study is to see if early diagnosis of CF through neonatal screening will be medically beneficial without major risks. ''Medically beneficial'' refers to better nutrition and/or pulmonary status, whereas '' risks'' include laboratory errors, miscommunication or misunderstanding, and adverse psychosocial consequences. Specific aims include assessment of the benefits, risks, costs, quality of life, and cognitive function associated with CF neonatal screening and a better understanding of the epidemiology of CF. A comprehensive, randomized clinical trial emphasizing early diagnosis as the key variable has been underway since 1985. Nutritional status has been assessed using height and weight measurements and biochemical methods. The results have demonstrated significant benefits in the screened (early diagnosis) group. We are now focusing on the effect of early diagnosis of CF on pulmonary outcome. Pulmonary status is measured using chest radiographs, chest scans using high resolution computerized tomography, and pulmonary function tests. Other factors that we are looking at include risk factors for the acquisition of respiratory pathogens such as Pseudomonas aeruginosa, quality of life and cognitive function of children with CF who underwent early versus delayed diagnosis, as well as the cost effectiveness of screening and the costs of diagnosis and treatment of CF throughout childhood. If the questions underlying this study are answered favorably, it is likely that neonatal screening using a combination of enzyme level (immunoreactive trypsinogen) and DNA test will become the routine method for identifying new cases of CF not only in the State of Wisconsin, but throughout the country. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014950 •

Phase II Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Mucoid Exopolysaccharide Pseudomonas Aeruginosa Immune Globulin for Cystic Fibrosis Condition(s): Cystic Fibrosis; Bacterial Infections Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Vanderbilt University Medical Center Purpose - Excerpt: Objectives: I. Assess the efficacy of monthly intravenous mucoid exopolysaccharide Pseudomonas aeruginosa immune globulin (MEP IGIV) given over 1 year in reducing the frequency of acute pulmonary exacerbation in patients with cystic fibrosis, mild to moderate pulmonary disease, and mucoid P. aeruginosa colonization. II. Assess the effect of MEP IGIV on FEV1, sputum density of mucoid P. aeruginosa, and the quality of life in these patients. III. Assess the safety of monthly MEP IGIV. IV. Assess population-based MEP IGIV pharmacokinetics during chronic therapy. Phase(s): Phase II

Clinical Trials 165

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004747

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “pseudomonas” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

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

•

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

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

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

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

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

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

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

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

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

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

166 Pseudomonas

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

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

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

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

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CHAPTER 5. PATENTS ON PSEUDOMONAS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “pseudomonas” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on pseudomonas, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Pseudomonas By performing a patent search focusing on pseudomonas, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

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

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example of the type of information that you can expect to obtain from a patent search on pseudomonas: •

Alkylpolyglucosides containing pseudomonas microorganism

disinfectant

compositions

active

against

Inventor(s): Gluck; Bruno Anthony (North Gosford, AU) Assignee(s): Novapharm Research (australia) Pty. (rosebery, Au) Patent Number: 6,531,434 Date filed: March 23, 2000 Abstract: An antiseptic cleansing composition comprising an antimicrobial agent, an effective amount of an alkylpolysaccharide surfactant, at least one alkyl alcohol and at least on aryl alcohol. Suitable surfactant alkylpolysaccharides may contain one or more sugar units selected from the group consisting of maltose, arabinose, xylose, mannose, galactose, gulose, idose, talose, allose, altrose, sucrose, fructose, sorbose, levulose, lactose, allulose, tagatose, alloheptulose, sedoheptulose, glucoheptulose, mannoheptulose, guloheptulose, idoheptulose, galactoheptulose, taloheptulose and derivatives thereof. Suitable antimicrobial agents include chlorohexidine, chlorohexidine salt, chlorophenol derivative, octenidindihydrochloride (CH.sub.3 -(CH.sub.2).sub.7 --NHOH--(CH.sub.2).sub.10 --NO--NH(CH.sub.2).sub.7 --CH.sub.3) or any salt thereof, and quaternary ammonium compounds. Excerpt(s): This invention relates to a disinfectant cleansing composition. It is known that infection is spread via skin contact through the transmission of pathogenic microorganisms. Hitherto, in order to reduce the presence of such organisms it has been known to scrub the skin with a solution containing a surfactant followed by application of an antiseptic. In recent years it has been suggested that it would be desirable to combine the washing and disinfectant actions in a single operation by providing a composition comprising both an antimicrobial agent and a surfactant. It has been found however that many antimicrobial agents such as chlorhexidine [N,N'-bis(4chlorophenyl)-3,12-diimino 2,4,11,13-tetraazatetradecanediimidamide]digluconate and other chlorhexidine salts are incompatible with anionic surfactants, and are reduced in their antimicrobial activity by nonionic surfactants, thus requiring addition of more antimicrobial agent in order to retain sufficient biocidal activity at the amount of surfactant required for satisfactory foam formation. Web site: http://www.delphion.com/details?pn=US06531434__ •

Aqueous disinfectant Inventor(s): Arata; Andrew B. (Lake City, FL) Assignee(s): Innovative Medical Services () Patent Number: 6,583,176 Date filed: March 2, 2001 Abstract: A non-toxic environmentally friendly aqueous disinfectant is disclosed for specific use as prevention against contamination by potentially pathogenic bacteria and virus. The aqueous disinfectant is formulated by electrolytically generating silver ions in water in combination with a citric acid. The aqueous disinfectant may include a suitable alcohol and/or a detergent. The aqueous disinfectant has been shown to be very

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effective at eliminating standard indicator organisms such as staphylococcus aureus, salmonella cholerasuis and pseudomonas aeruginosa. Excerpt(s): This invention relates to disinfectants and more particularly to an environmentally friendly, non-toxic aqueous disinfectant for specific use against pathogenic bacteria and viruses. The prior art has demonstrated that the presence of copper and silver ions in an aqueous solution is useful as a disinfectant. Many in the prior art have used copper and silver ions in an aqueous solution as a disinfectant in water systems such as cooling towers, swimming pools, hot water systems in hospitals, potable water systems, spa pools and the like. Typically, copper and silver electrodes were connected to a direct current power supply. When the direct current was applied to the copper and silver electrodes, copper and silver ions were generated by an electrolysis process from the copper and silver ions within the water. In one example of the prior art, water was passed continuously through an ion chamber having copper and silver electrodes. The water emanating from the ion chamber contained the copper and silver ions generated by copper and silver electrodes within the ion chamber. The water emanating from the ion chamber containing the copper and silver ions was used as a disinfectant in water systems such as cooling towers, swimming pools, hot water systems in hospitals, potable water systems, spa pools and the like. The copper and silver ions within the water systems acted as a disinfectant for controlling algae, viruses, bacteria and the like. Web site: http://www.delphion.com/details?pn=US06583176__ •

Bacteria mixture having heavy oil degrading ability and method of treating oil components Inventor(s): Fujita; Tokio (Nara, JP) Assignee(s): Technology Licensing Organization Inc. (osaka, Jp) Patent Number: 6,649,400 Date filed: March 3, 2000 Abstract: A bacteria strain FERMBP-7046 belonging to the genus Acinetobacter, a strain FERMBP-7049 belonging to the genus Acinetobacter, a strain FERMBP-7047 belonging to the genus Pseudomonas, and a strain FERMBP-7048 belonging to the genus Alcaligenes are caused to act on an object of treatment, either individually or in a bacteria mixture including at least one of the foregoing strains. Thus it is possible to provide heavy oil degrading bacteria and a heavy oil degrading bacteria mixture which are inexpensively prepared, which simplify degradation and removal operations, and which can be stored and shipped simply, and to provide a nurturing composition for such bacteria, a method of degrading heavy oil using such bacteria, and building and civil engineering materials containing a substance obtained by heavy oil degradation treatment. Excerpt(s): The present invention relates to a novel strain of bacteria for use in heavy oil degradation, a bacteria mixture, a composition for nurturing heavy oil degrading bacteria, a formulation containing that composition, a method of treating oil components, and building and civil engineering materials containing a substance treated by that method. Recent years have seen worsening of ocean pollution throughout the world due to heavy oil or crude oil leaks from supertanker accidents, submarine oil field development, etc., and this is one cause of damage to the global environment. Conventionally, oils, such as heavy oil and crude oil, leaked into the ocean

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are removed through degradation by microorganisms capable of degrading chiefly hydrocarbons contained in the oils. Specifically, microorganisms which can metabolize and degrade oil components such as saturated hydrocarbons, aromatic hydrocarbons, etc. are screened from the natural world, and the screened microorganisms are isolated and grown, after which a culture solution is prepared for use in degradation of the leaked oil. Web site: http://www.delphion.com/details?pn=US06649400__ •

Bacterial cleavage of only organic C-N bonds of carbonaceous materials to reduce nitrogen content Inventor(s): Kilbane, II; John J. (Woodstock, IL), Linhares; Monica Moreira (Rio de Janeiro, BR), Ribeiro; Claudia Maria Soares (Rio de Janeiro, BR) Assignee(s): Petroleo Brasileiro S.a.-petrobras (rio DE Janeiro, Br) Patent Number: 6,541,240 Date filed: November 30, 1999 Abstract: A microbial process is provided for selective cleavage of only organic C--N bonds while leaving C--C bonds intact which may be used for reducing the nitrogen content of nitrogen-containing organic carbonaceous materials. Microorganisms of Pseudomonas ayucida have been found which have the ability of selective cleavage of organic C--N bonds. A particularly preferred microorganism is Pseudomonas ayucida strain ATCC No PTA-806. Other microorganisms useful in the cleavage of organic C--N bonds are Aneurinibacillus sp, Pseudomonas stutzeri, Yokenella sp. and Pseudomonas nitroreducens. Excerpt(s): The present invention relates to a process for microbial cleavage of organic C--N bonds and biodenitrogenation of nitrogen-containing organic carbonaceous material thereby. More specifically, total nitrogen from a hydrocarbon-containing medium may be reduced, as well nitrogen may be removed from the hydrocarbon molecule or from a fossil fuel. Microorganisms which have the ability of selective cleavage of organic C--N bonds, particularly microorganisms such as Pseudomonas ayucida strain No PTA-806 can be used in the process that is the subject of this invention. The process of the invention is particularly useful in removal of organic nitrogen from fossil fuels, such as nitrogen-containing coal, petroleum oil, lignite and derived synthetic fuels while retaining the calorific value of the fuel. The quality of petroleum is progressively deteriorating as the highest quality petroleum deposits are preferentially produced. Consequently, the concern about the concentration of compounds/contaminants such as sulfur, nitrogen, and metals in petroleum will intensify. These contaminants are not only contributors to environmental pollution resulting from the combustion of petroleum, but also interfere with the processing of petroleum by poisoning catalysts and contributing to corrosion. The selective removal of contaminants from petroleum while retaining the fuel value is a difficult technical challenge. The selective removal of sulfur from dibenzothiophene with the aid of a bacterium useful for cleaving C--S bonds is taught in U.S. Pat. No. 5,002,888. Web site: http://www.delphion.com/details?pn=US06541240__

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Bacterial plasmid having genes encoding enzymes for the degradation of aromatic compounds Inventor(s): Bramucci; Michael G. (Folsom, PA), Chen; Mario W. (Chadds Ford, PA), Nagarajan; Vasantha (Wilmington, DE) Assignee(s): E. I. DU Pont DE Nemours and Company (wilmington, De) Patent Number: 6,548,292 Date filed: November 20, 2000 Abstract: A bacterial plasmid has been isolated from Pseudomonas CT14 comprising genes encoding enzymes implicated in aromatic ring cleavage. Additionally, the novel genes encoding proteins involved in mercury tolerance and plasmid stability and replication have been identified. The strain from which the plasmid was isolated is useful in a variety of methods including methods for the degradation of aromatic compounds, particularly catechols. Excerpt(s): This invention is in the field of bacterial plasmids. More specifically, a bacterial plasmid has been isolated which contains genes necessary for plasmid maintenance and for degrading aromatic compounds to small aliphatic molecules. It is well known that bacterial genes are sometimes located on plasmids (Actis et al., Front. Biosci. 4:D43-62 (1999); del Solar et al., Microbiol. Mol. Biol. Rev. 62:434-464 (1998)). Plasmids are not necessary for routine "housekeeping" functions in bacteria (e.g., DNA synthesis and protein synthesis). However, the genes on plasmids are often important in specialized environments. Antibiotic resistance genes and heavy metal resistance genes are examples of genes commonly found on plasmids. Although plasmids are similar in function to chromosomes as carriers of genes, plasmids can be distinguished from chromosomes. Plasmids are smaller than chromosomes and encode functions that are dedicated to plasmid replication. Each type of plasmid has a distinct ori sequence and rep gene(s) for initiation of replication. These sequences constitute the minimum requirements for a functional, replicating plasmid. Fu et al. (Mol Gen Genet 250:699-704 (1996); Plasmid 38:141-147 (1997)) has reported RepA protein that has replication initiation and transcription repression function. The genetic information for degradation of aromatic chemicals is also frequently located on plasmids in bacteria (Assinder and Williams, Adv. Microb. Physiol. 31:2-69 (1990)). The well-characterized TOL plasmid pWWO is typical of many bacterial plasmids that have genes for degradation of aromatic compounds (Assinder and Williams, Adv. Microb. Physiol. 31:2-69 (1990)). Plasmid pWWO is 117 kb in size, is transmissible, and belongs to the broad host range IncP-9 incompatibility group of plasmids. The pWWO xyl genes encode enzymes for metabolism of toluene, m-xylene, and p-xylene. Web site: http://www.delphion.com/details?pn=US06548292__

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Biocontrol agents for take-all Inventor(s): Cook; R. James (Pullman, WA), Raaijmakers; Jos M. (Pullman, WA), Thomashow; Linda S. (Pullman, WA), Weller; David M. (Pullman, WA) Assignee(s): The United States of America AS Represented by the Secretary of Agriculture (washington, Dc) Patent Number: 6,447,770 Date filed: September 14, 1999

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Abstract: Fluorescent Pseudomonas spp. are described which are effective for the control of diseases caused by the soil-borne fungus, Gaeumannomyces graminis (Gg), such as take-all, in small grain crops or turf grass. The subject biocontrol strains have a unique genotype as shown by a characteristic banding pattern, and exhibit rootcolonizing ability which is characterized by both higher population density on roots and extended colonizing activity compared to known Gg-suppressive strains. A further property is the ability of a strain to duplicate the level of biocontrol obtained naturally in a take-all decline soil. Methods for isolation and identification of the strains and their use to control diseases caused by Gg are provided. In particular, strains of P. fluorescens NRRL B-21806 and NRRL B-21807. Excerpt(s): The present invention relates to biocontrol of diseases caused by the soilborne fungus Gaeumannomyces graminis. In particular, the invention relates to strains of fluorescent Pseudomonas species (spp.) which have unique root-colonizing ability for small grain crops and biocontrol activity for diseases caused by Gaeumannomyces graminis in small grain crops and take-all patch in turf grass. The invention further relates to isolation and identification of the unique strains, and application thereof to control plant diseases caused by Gaeumannomyces graminis. Widespread diseases of small grain crops and turf grass are caused by the soil-borne fungus Gaeumannomyces graminis (Gg), and result in significant economic losses due to reductions in crop yield. Take-all, a disease caused by Gaeumannomyces graminis var. tritici (Ggt) occurs in all wheat-growing regions of the world and is the most important root disease of wheat. Symptoms of wheat take-all include dark longitudinal lesions on roots; in severe cases, the entire root may become blackened with disease with the fungus migrating to the crown of the wheat plant (where the crown roots originate) and the tillers (stems). Severely infected wheat plants are identified in the field by their white heads which result when infection of the crown by the fungus cuts off water transport to upper plant parts causing the plant to die prematurely. Yield losses can be considerable up to 50% of the potential wheat yield. There are no resistant wheat cultivars and registered fungicides perform inconsistently. Further, growers are being increasingly challenged to grow wheat with minimum or no tillage to reduce soil erosion. These practices increase the severity of take-all and other root diseases. Although wheat is particularly susceptible to the take-all fungus, many other Gramineae such as barley, rye, and triticale can also be infected. Traditionally, take-all has been controlled by a combination of crop rotation and tillage, practices which reduce the inoculum potential of the pathogen. However, because long rotations are often not economically feasible and tillage contributes to soil erosion, the trend in cereal production is toward less tillage and two or three wheat crops before a break. Both of these practices exacerbate take-all. There is no known source of genetic resistance in wheat against take-all, and methods of chemical control are limited. The need for agriculture to become more sustainable and less dependent on chemical pesticides has necessitated the development of alternative approaches to control take-all and other soil-borne diseases. Web site: http://www.delphion.com/details?pn=US06447770__

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Biological agent and methods for inhibiting plant pathogens Inventor(s): Mienie; Nicolaas Johannes Jacobus (393 Kaberoe Avenue, Magalieskruin, Pretoria, ZA 0150) Assignee(s): None Reported Patent Number: 6,491,911 Date filed: March 5, 2001 Abstract: A biological agent and methods for inhibiting plant pathogens are provided. More particularly, this invention provides the use of Pseudomonas resinovorans in the biological control of inter alia: Ralstonia solanacearum, Verticillium dahliae and Phytophthora infestans. This invention further relates to a biological combination agent for inibiting Colletotrichum coccodes, in addition to the above pathogens. Excerpt(s): This invention relates to a biological agent and methods for inhibiting plant pathogens. More particularly, this invention relates to the use of Pseudomonas resinovorans (R. resinovorans) in the biological control of inter alia: Ralstonia solanacearum (R. solanacearum), Verticillium dahliae (V. dahliae) and Phytophthora infestans (P. infestans). This invention further relates to a biological combination agent for inhibiting Colletotrichum coccodes, in addition to the above pathogens. For the purposes of this specification, a bacterium is deemed to be characterised by the bacterium deposited at the Centraalbureau voor Schimmelcultures under deposit number 100189, if there is a similarity of more than 85% between the other bacterium and the deposited bacterium, according to the BIOLOG identification system, of Biolog, Inc, 3938 Trust Way, Hayward, Calif. 94545, USA. R. solanacearum (previously known as Pseudomonas solanacearum) is a soil-borne, pathogenic bacterium which causes bacterial wilt in plants and which is of substantial economic importance because it is endemic in most if not all the tropical and subtropical countries of the world. R. solanacearum colonises the roots of plants and penetrates the xylem and multiply within the vascular tissue of plants. Furthermore, it has a wide host range and the measures for controlling the disease are still limited. Web site: http://www.delphion.com/details?pn=US06491911__

•

Biologically pure culture of bacteria which suppresses diseases caused by pathogens in chickpea crops and a culture of bacteria comprising a strain of Pseudomonas fluorescens Inventor(s): Nautiyal; Chandra Shekhar (Lucknow, IN) Assignee(s): Council of Scientific & Industrial Research (new Delhi, In) Patent Number: 6,495,362 Date filed: July 10, 1997 Abstract: A simple sand-live soil assay method for large scale screening of the rhizosphere-competent bacteria, effective in suppressing plant pathogens has been developed. Screening for chickpea rhizosphere competitive bacteria having biological control property was conducted at three different stages: development of screening method for large scale initial selection of bacteria isolates from chickpea rhizosphere, testing of biocontrol activity under in vitro conditions and screening of antibiotic resistant mutants for rhizosphere competence in nonsterile field soil, which assay is used to disclose one Pseudomonas fluorescens NBRI 1303 (ATCC 55939) which is

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effective in suppressing plant pathogens, including Fusarium oxysporum f. sp. ciceri, Rhizoctonia bataticola and Phthium sp. in chickpeas and the purified bacterial strain can be used as active agent for biocontrol compositions and can also be used for enhancement of chickpea plant growth and yield, as well as for the production of antibiotics directed towards phytopathogenic fungal diseases. Excerpt(s): This invention relates to a novel bacteria strain of Pseudomonas fluorescens designated as ATCC 55939 and a method for large scale screening of native rhizosphere microflora, to identify and characterize naturally occurring rhizosphere-competent biocontrol bacteria from non-sterilized soil, which could effectively colonize plant roots. The present invention relates more specifically to the use of a novel strain of Pseudomonas fluorescens as a biocontrol agent for controlling plant fungal disease particularly those diseases caused by fungus of the genus Fusarium sp., Rhizoctonia sp. and Pythium sp. The fungal pathogens play a major role in the development of diseases on many important field and horiculture crops which often results in the poor plant yields. Considering the cost of chemical pesticides and hazard involved, biological control of plant diseases is now increasingly capturing the imagination of plant microbiologists. Frequent failure of the added microorganisms to become established is not surprising because the biological associations and antagonisms within the ecosystem determine the composition of the microflora, the climax population being a reflection of the physical and chemical characteristics of the habitat. A major factor in the unsuccessful commercialization of rhizosphere bacteria has been the inconsistency of field test results. Reasons for the reported variability include nonpersistence on seed before it is planted and poor bacterial establishment on seed and roots, please refer Burr, T, J., and A. Caesar, Crit. Rev. Plant Sci. 2: 1-20 (1984); Gaskins, M. H. et al. Ecosystems Environ. 12: 99-116 (1985); Liang, L. et al. Appl. Environ. Microbiol. 44: 708-714 (1982); O'Sullivan, D. J., and F. O'Gara, Micrbiol. Rev. 56: 662-676 (1992); Schrotk, M. N., and J. G. Hancock. Disease suppressive soil and root colonizing bacteria. Science 216: 13761381 (1981); Weller, D. M., Ann. Rev. Plant Pathol. 26: 379-407 (1988). The introduced microorganism must colonize plant roots and demonstrate rhizosphere competence before its further utilization as biological control and/or, plant growth promoting agent. When the proper bacterial strain is used, plant roots are extensively colonized by the introduced strain, which suggests a close bacteria-plant association that allows for beneficial plant growth or disease protection, see for example, Schmidt, E. L., Ann. Rev. Microbiol. 33: 355-376 (1979). Web site: http://www.delphion.com/details?pn=US06495362__ •

Detection of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients Inventor(s): Deretic; Vojo (San Antonio, TX), Martin; Daniel W. (Palo Alto, CA) Assignee(s): Board of Regents, the University of Texas System (austin, Tx) Patent Number: 6,426,187 Date filed: June 30, 2000 Abstract: Compositions and methods for detecting the conversion to mucoidy in Pseudomonas aeruginosa are disclosed. Chronic respiratory infections with mucoid Pseudomonas aeruginosa are the leading cause of high mortality and morbidity in cystic fibrosis. The initially colonizing strains are nonmucoid but in the cystic fibrosis lung they invariably convert into the mucoid form causing further disease deterioration and poor prognosis. Mucoidy is a critical P. aeruginosa virulence factor in cystic fibrosis

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that has been associated with biofilm develoment and resistance to phagocytosis. The molecular basis of this conversion to mucoidy is also disclosed. The present invention provides for detecting the switch from nonmucoid to mucoid state as caused by either frameshift deletions and duplications or nonsense changes in the second gene of the cluster, mucA. Inactivation of mucA results in constitutive expression of genes, such as algD, dependent on algU for transcription. Also disclosed is a novel alginate biosynthesis heterologous expression system for use in screening candidate substances that inhibit conversion to mucoidy. Excerpt(s): Cystic Fibrosis (CF) is the most common inheritable lethal disease among Caucasians. There are approximately 25,000 CF patients in the U.S.A. The frequency of CF in several other countries (e.g., Canada, United Kingdom, Denmark) is high (ranging from 1 in 400 to 1 in 1,600 live births). There are numerous CF centers in the U.S.A. and Europe--specialized clinical facilities for diagnosing and treating children and adolescents with CF. Chronic respiratory infections caused by mucoid Pseudomonas aeruginosa are the leading cause of high morbidity and mortality in CF. The initially colonizing P. aeruginosa strains are nonmucoid but in the CF lung they inevitably convert into the mucoid form. The mucoid coating composed of the exopolysaccharide alginate leads to the inability of patients to clear the infection, even under aggressive antibiotic therapies. The emergence of the mucoid form of P. aeruginosa is associated with further disease deterioration and poor prognosis. The microcolony mode of growth of P. aeruginosa, embedded in exopolysaccharide biofilms in the lungs of CF patients (Costerton et al., 1983), among other functions, plays a role in hindering effective opsonization and phagocytosis of P. aeruginosa cells (Pier et al., 1987; Pier 1992). Although CF patients can produce opsonic antibodies against P. aeruginosa antigens, in most cases phagocytic cells cannot effectively interact with such opsonins (Pressler et al., 1992; Pier et al., 1990; Pier 1992). Physical hindrance caused by the exopolysaccharide alginate and a functionally important receptor-opsonin mismatch caused by chronic inflammation and proteolysis are contributing factors to these processes (Pedersen et al., 1990; Tosi et al., 1990; Pier, 1992). Under such circumstances, the ability of P. aeruginosa to produce alginate becomes a critical persistence factor in CF; consequently, selection for alginate overproducing (mucoid) strains predominates in the CF lung. Web site: http://www.delphion.com/details?pn=US06426187__ •

Genes encoding denitrification enzymes Inventor(s): Bedzyk; Laura Anne (Odessa, DE), Ye; Rick Weizhang (Hockessin, DE) Assignee(s): E. I. DU Pont DE Nemours and Company (wilmington, De) Patent Number: 6,429,003 Date filed: February 15, 2000 Abstract: This invention relates to the isolation of nucleic acid fragments from Pseudomonas sp. strain G-179 that encode periplasmic nitrate reductase and nitric oxide reductase enzymes. The enzymes are useful in denitrification reactions and for the identification of other denitrifying bacteria. In addition, this invention also relates to the construction of chimeric genes encoding all or a substantial portion of a bacterial nitric oxide reductase or a bacterial periplasmic nitrate reductase enzymes, in sense or antisense orientation, wherein the expression of the chimeric genes results in production of altered levels of the nitric oxide reductase or periplasmic nitrate reductase in a transformed host cell.

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Excerpt(s): This invention is in the field of microbial denitrification. More specifically, this invention pertains to nucleic acid fragments encoding new bacterial nitric oxide reductase and bacterial periplasmic nitrate reductase enzymes. In practical applications, microbial denitrification has been widely used for water purification (Mateju et al., Enzyme Microb. Technol. 14:172-183 (1992)). On the other hand, nitrous oxide (N.sub.2 O) has been shown to have detrimental effect on the stratospheric ozone layer (de Boer et al., Eur. J. Biochem. 242:592-600 (1996)). NOx, along with carbon monoxide and hydrocarbons can lead to an increase in the amount of stratospheric ozone. Thus, the production of N.sub.2 O and nitric oxide (NO) due to incomplete denitrification is of concern. It will be useful therefore to devise new and better methods for denitrification of industrial waste streams to effect complete denitrification. The identification of genes encoding proteins responsible for key denitrification reactions will be essential for the development of improved denitrification methods. Two of the essential genes in the bacterial denitrification pathway are those encoding nitric oxide reductase (nor) and nitrate reductase (nap). Genes encoding these enzymes have been identified in both denitrifying bacteria as well as non-denitrifyers. For example, Bartnikas et al., J. Bacteriol. 179:3534-3540 (1997) teach the identification and sequencing of a gene cluster required for the expression of nitric oxide reductase in Rhodobacter sphaeroidesi and de Boer et al., (Eur. J. Biochem. 242:592-600 (1996)) describe a nor gene cluster isolated from Paracoccus denitrificans. Genes encoding periplasmic nitrate reductase have been characterized from Thiosphaera pantotropha (Berks et al., Biochem J., (1995), 309, 983) and from Rhodobacter sphaeroides (Reyes et al., Biochem J., (1998), 331, 897). Finally Grove et al., (Mol. Microbiol. 19:467-481 (1996)) describe the identification of a gene encoding a periplasmic nitrate reductase from the non-denitrifying E. coli K-12. Web site: http://www.delphion.com/details?pn=US06429003__ •

IL-13 receptor specific chimeric proteins and uses thereof Inventor(s): Debinski; Waldemar (Hummelstown, PA), Obiri; Nicholas (N. Potomac, MD), Pastan; Ira (Potomac, MD), Puri; Raj K. (North Potomac, MD) Assignee(s): The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,518,061 Date filed: February 17, 1998 Abstract: The present invention provides a method and compositions for specifically delivering an effector molecule to a tumor cell bearing an IL-13 receptor. The method involves providing a chimeric molecule that comprises an effector molecule attached to a circularly permuted IL-13 ("cpIL-13") that specifically binds an IL-13 receptor and contacting the tumor cell with the chimeric molecule. The compositions include chimeric molecules comprising effector molecules such as modified Pseudomonas exotoxin attached to a cpIL-13. The invention further provides vectors encoding the chimeric molecules. Excerpt(s): This invention relates to methods of specifically delivering an effector molecule to a tumor cell. In particular this invention relates to chimeric molecules that specifically bind to IL-13 receptors and their use to deliver molecules having a particular activity to tumors overexpressing IL-13 receptors. In a chimeric molecule, two or more molecules that exist separately in their native state are joined together to form a single molecule having the desired functionality of all of its constituent molecules. Frequently, one of the constituent molecules of a chimeric molecule is a "targeting molecule". The

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targeting molecule is a molecule such as a ligand or an antibody that specifically binds to its corresponding target, for example a receptor on a cell surface. Thus, for example, where the targeting molecule is an antibody, the chimeric molecule will specifically bind (target) cells and tissues bearing the epitope to which the antibody is directed. Another constituent of the chimeric molecule may be an "effector molecule". The effector molecule refers to a molecule that is to be specifically transported to the target to which the chimeric molecule is specifically directed. The effector molecule typically has a characteristic activity that is desired to be delivered to the target cell. Effector molecules include cytotoxins, labels, radionuclides, ligands, antibodies, drugs, liposomes, and the like. Web site: http://www.delphion.com/details?pn=US06518061__ •

Immobilized microbial consortium useful for rapid and reliable BOD estimation Inventor(s): Kumar; Rita (Delhi, IN), Makhijani; Santosh Dayaram (Delhi, IN), Manoharan; A. (Delhi, IN), Rastogi; Shikha (Delhi, IN), Sharma; Alka (Delhi, IN) Assignee(s): Council of Scientific and Industrial Research (new Delhi, In) Patent Number: 6,511,822 Date filed: October 18, 2001 Abstract: An immobilized microbial consortium is formulated which comprises of a synergistic mixture of isolated bacteria namely, Aeromonas hydrophila, Pseudomonas aeruginosa, Yersinia enterocolitica, Serratia liquefaciens, Pseudomonas fluoresces, Enterobacter cloaca, Klebsiella oxytoca, Citrobacter amalonaticus and Enterobacter sakazaki. The formulated microbial consortium is immobilized on charged nylon membrane. The said immobilized microbial consortium is attached to dissolved oxygen probe for the preparation of electrode assembly. The prepared electrode assembly is used for rapid and reliable BOD estimation. The prepared electrode assembly is used for monitoring of BOD load of synthetic samples such as Glucose-Glutamic acid (GGA) used as a reference standard in BOD analysis and industrial effluents; covering a range from low to high biodegradable organic matter. Excerpt(s): The present invention relates to an immobilized microbial consortium and a process for the preparation of the said immobilized microbial consortium, useful for rapid and reliable BOD estimation. Rapid analytical devices have attracted tremendous interest and attention in science and technology for their wide range of possible application as an alternative to conventional analytical techniques. Analytical devices are sensitive to biological parameters and consist of a biological sensing element such as microbes, enzymes, etc., in close contact with a physico-chemical transducer such as an electrode, which converts biological signal to a quantitative response. These devices have several unique features such as compact size, simple to use, one step reagent-less analysis, low cost and quick real time results. Rapid analytical devices, termed as biosensors, have the potential for a major impact in the human health care, environmental monitoring, food analysis and industrial process control. Among these, microbial biosensors (the devices using microbes as biological component), have great potential in environmental monitoring. Recent trends in biotechnology suggest that monitoring and control of pollutant by means of microbial biosensors may be of crucial importance. Such microbial sensors, constructed by entrapping the required microorganisms in suitable polymeric matrices and attached to a transducer, function on the basis of assimilatory capacity of the micro-organisms. In addition, microbial biosensors are more stable and inexpensive for the determination of compounds of interest as

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compared to enzyme-based biosensors; where enzymes employed in enzyme-based biosensors require costly extraction and purification prior to use as biocatalysts. Further, micro-organisms employed in microbial biosensors show a high degree of stability as compared to enzymes. Web site: http://www.delphion.com/details?pn=US06511822__ •

Immobilizing lipase by adsorption from a crude solution onto nonpolar polyolefin particles Inventor(s): Friedrich; Thomas (Darmstadt, DE), Sturmer; Rainer (Rodersheim-Gronau, DE) Assignee(s): Basf Aktiengesellschaft (ludwigshafen, De) Patent Number: 6,596,520 Date filed: July 6, 2000 Abstract: Immobilized lipase is prepared by adsorbing lipase from a crude lipase solution onto polyolefin particles such as polypropylene particles which are nonpolar. The crude solution may be a cell-free culture broth. Lipase sources include Pseudomonas burkholderia and Pseudomonas aeruginosa. Uses of the immobilized lipase include enantioselective conversion of substrates such as enantioselective acylating or hydrolyzing. Excerpt(s): The present invention relates to a process for preparing immobilized lipase, to the immobilized lipase itself and to a process for enzyme-catalyzed conversion in the presence of the immobilized lipase. Lipases can be used in solution as enzymatic catalysts for converting substrates. Immobilized lipases are distinguished from free lipases by having an increased stability and useful life on carrying out the reaction continuously and batchwise, and by easy recovery of the catalytically active species in batchwise reactions. It is known to immobilize lipases by adsorption onto a solid support. It is also known to prepare immobilized lipases by contacting polyolefin particles with an aqueous solution of a purified lipase. Web site: http://www.delphion.com/details?pn=US06596520__

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Inhalable dry powder aztreonam for treatment and prevention of pulmonary bacterial infections Inventor(s): Montgomery; Alan Bruce (Seattle, WA) Assignee(s): Salus Pharma, Inc. (seattle, Wa) Patent Number: 6,660,249 Date filed: December 20, 2001 Abstract: A method and a composition for treatment of pulmonary bacterial infections caused by gram-negative bacteria suitable for treatment of infection caused by Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Haemophilus influenzae, Proteus mirabilis, Enterobacter species, Serratia marcescens as well as those caused by Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa, using a concentrated formulation of aztreonam, or a pharmaceutically acceptable salt thereof, delivered as an aerosol or dry powder formulation.

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Excerpt(s): The current invention concerns a novel, safe, nonirritating and physiologically compatible inhalable aztreonam formulation suitable for treatment of pulmonary bacterial infections caused by gram negative bacteria, such as Escherichia coli, Enterobacteria species, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans. In particular, the invention concerns the inhalable formulation comprising aztreonam or a pharmaceutically acceptable salt thereof suitable for treatment and prophylaxis of acute and chronic pulmonary bacterial infections, particularly those caused by gram-negative bacteria Burkholderia cepacia, Stenotrophomonas maltophlia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa which are resistant to treatment with other antibiotics. The inhalable formulation is delivered as an aerosol or as an inhalable dry powder. For aerosolization, about 1 to about 250 mg of aztreonam is dissolved in about 1 to about 5 ml of saline or other aqueous solution having a pH between 4.5 and 7.5, delivered to the lung endobronchial space in an aerosol having mass medium average diameter particles predominantly between 1 to 5.mu. using a nebulizer able to atomize the aztreonam solution into particles of required sizes. The aerosol formulation has a small volume yet delivers a therapeutically efficacious dose of aztreonam to the site of the infection in amounts sufficient to treat bacterial pulmonary infections. A combination of the novel formulation with the atomizing nebulizer permits about 50% delivery of the administered dose of aztreonam into airways. For delivery of dry inhalable powder, aztreonam is milled or spray dried to particle sizes between about 1 and 5.mu. The dry powder formulation or a reconstituted aztreonam solid for aerosolization have a long shelf-life and storage stability. A wide variety of gramnegative bacteria cause severe pulmonary infections. Many of these bacteria are or become resistant to commonly used or specialty antibiotics and require treatment with new types of antibiotics. The pulmonary infections caused by gram-negative bacteria are particularly dangerous to patients who have decreased immunoprotective responses, such as for example cystic fibrosis and HIV patients, patients with bronchiectasis or those on mechanical ventilation. Therefore, the bacterial respiratory infections caused by organisms resistant to antibiotics continues to be a major problem, particularly in immunocompromised or hospitalized patients, as well as in patients assisted by mechanical ventilation, as described in Principles and Practice of Infectious Diseases, Eds. Mandel, G. L., Bennett, J. E., and Dolin, R., Churchill Livingstone Inc., New York, N.Y., (1995). Web site: http://www.delphion.com/details?pn=US06660249__ •

Method for bioremediating undetonated explosive device Inventor(s): Badger; Farrell G. (Mapleton, UT), Bahr; Lyman G. (Payson, UT), Richards; Dean F. (Pleasant Grove, UT), Thomas; Ronald D. (Woodland Hills, UT), Welch; Brendan M. (Farmington, CT) Assignee(s): The Ensign-bickford Company (simsbury, Ct) Patent Number: 6,644,200 Date filed: September 19, 2000 Abstract: Technology for in situ remediation of undetonated explosive material. An explosive apparatus contains an explosive material in close proximity with microorganisms. An explosive mixture capable of self remediation in the form of an explosive material is intermixed with microorganisms. The microorganisms are either

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mobile or temporarily deactivated by freeze drying until rehydrated and remobilized. The microorganisms are capable of metabolizing the explosive material. Examples of such microorganisms include Pseudomonas spp., Escherichia spp., Morganella spp., Rhodococcus spp., Comamonas spp., and denitrifying microorganisms. A bioremediation apparatus that contains microorganisms and prevents contact between the microorganisms and explosive material is joined with an explosive apparatus that houses a charge of explosive material. A barrier is actuated by mechanical, electrical or chemical mechanisms to release the microorganisms into the explosive assembly to enable the microorganisms to begin metabolizing the explosive material, when the explosive apparatus is joined with the bioremediating apparatus. If the explosive material fails to detonate, the explosive is remediated by the action of the microorganisms. Remediation includes both disabling of the explosive material and detoxification of the resulting chemical compositions. Excerpt(s): The present invention is directed to systems, apparatus, and methods for remediating explosives. More particularly, the present invention is directed to the remediation of explosives which have not detonated. Explosive charges are inherently dangerous in a number of respects. Inadvertent detonation poses risks of severe personal injury or death, as well as of substantial property destruction and consequential losses. Explosive charges are, in addition, comprised of material substances, which even when not consolidated in a shape capable of performing as a detonatable explosive charge, may be toxic and thus potentially injurious to human health and to complex as well as simple plant and animal life. Web site: http://www.delphion.com/details?pn=US06644200__ •

Method for conversion of a halogenated hydrocarbon using a pseudomonas sp Inventor(s): Criddle; Craig S. (Okemos, MI), Dybas; Michael J. (Lansing, MI), Tatara; Gregory M. (Lansing, MI) Assignee(s): Board of Trustees of Michigan State University (east Lansing, Mi) Patent Number: 6,613,558 Date filed: June 7, 1995 Abstract: A method of remediating an environment containing soil or water contaminated with a halogenated hydrocarbon, particularly carbon tetrachloride, by introducing a Pseudomonas sp. into the environment. In particular, the method converts carbon tetrachloride in the soil or water into carbon dioxide and a non-volatile water soluble fraction, rather than into a toxic chlorinated hydrocarbon with a lesser number of chlorines. Further, pH adjustment in a particular area provides a niche advantage for the Pseudomonas sp in the soil or water for the conversion. Excerpt(s): The present invention relates to the use of Pseudomonas sp. for the bioremediation of soil and/or water containing other resident microorganisms and contaminated with halogenated hydrocarbons. In particular, the present invention relates to bioaugmentation of the Pseudomonas sp in situ by the use of pH adjustment to cause suppression of the resident organisms in the soil and/or water so as to convert the halogenated hydrocarbon to carbon dioxide. Pseudomonas have been well characterized with regard to their ability to dehalogenate various halogenated hydrocarbon compounds in nature. It has been recognized that this activity can potentially be exploited for in situ bioremediation of contaminated groundwater and soil.

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Web site: http://www.delphion.com/details?pn=US06613558__ •

Method for the production of.rho.-Hydroxybenzoate in species of pseudomonas and agrobacterium Inventor(s): Ben-Bassat; Arie (Newark, DE), Cattermole; Monica (Newark, DE), Gatenby; Anthony A. (Wilmington, DE), Gibson; Katharine J. (Wilmington, DE), Ramos; Juan (Granada, ES), Ramos-Gonzalez; M. Isabel (Granada, ES), Sariaslani; Sima (Newark, DE) Assignee(s): North Carolina State University (raleigh, Nc) Patent Number: 6,586,229 Date filed: June 1, 2000 Abstract: Bacterial strains transformed with the pcu genes are useful for the production of para-hydroxybenzoate (PHBA). Applicant has provided the p-cresol utilizing (pcu) and tmoX gene sequences from Pseudomonas mendocina KR-1, the proteins encoded by these sequences, recombinant plasmids containing such sequences, and bacterial host cells containing such plasmids or integrated sequences. Method for the use of these materials to produce PHBA are also disclosed. Excerpt(s): The present invention relates to the fields of molecular biology and microbiology, and to the use of genetic techniques to introduce a modified pathway for the production of desired compounds. More specifically, this invention describes genetically engineered biocatalysts possessing an enhanced, or new, ability to transform p-cresol or toluene to p-hydroxybenzoate. p-Hydroxybenzoate (PHBA) is used as a monomer for synthesizing Liquid Crystal Polymers (LCP). LCP's are used in electronic connectors and in telecommunication and aerospace applications. LCP resistance to sterilizing radiation suits these materials for use in medical devices as well as in chemical, and food packaging applications. Esters of PHBA also are used as backbone modifiers in other condensation polymers (i.e., polyesters), and are also used to make parabens preservatives. Chemical synthesis of PHBA is known. For example, JP 05009154 teaches a chemical route using the Kolbe-Schmidt process from tar acid and CO.sub.2 involving 1) the extraction of tar acid from a tar naphthalene oil by an aqueous potassium hydroxide, 2) adding phenol to the extracted tar acid potassium salt, 3) removing H.sub.2 O, and 4) reacting the resultant slurry with CO.sub.2. Alternative methods of chemical synthesis are known (see, for example, U.S. Pat. No. 5,399,178; U.S. Pat. No. 4,740,614; and U.S. Pat. No. 3,985,797). Web site: http://www.delphion.com/details?pn=US06586229__

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Methods for making oligonucleotide probes for the detection and/or quantitation of non-viral organisms Inventor(s): Hogan; James John (San Diego, CA), Kop; Jo Ann (San Marcos, CA), McDonough; Sherrol Hoffa (San Diego, CA), Smith; Richard Dana (San Diego, CA) Assignee(s): Gen-probe Incorporated (san Diego, Ca) Patent Number: 6,512,105 Date filed: June 30, 2000 Abstract: A method for preparing probes, as well as several probes for use in qualitative or quantitative hybridization assays are disclosed. The method comprises constructing

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an oligonucleotide that is sufficiently complementary to hybridize to a region of rRNA selected to be unique to a non-viral organism or group of non-viral organisms sought to be detected, said region of rRNA being selected by comparing one or more variable region rRNA sequences of said non-viral organism or group of non-viral organisms with one or more variable region rRNA sequences from one or more non-viral organisms sought to be distinguished. Hybridization assay probes for Mycobacterium avium, Mycobacterium intracellulare, the Mycobacterium tuberculosis-complex bacteria, Mycoplasma pneumoniae, Legionella, Salmonella, Chlamydia trachomatis, Campylobacter, Proteus mirabilis, Enterococcus, Enterobacter cloacae, E. coli, Pseudomonas group I, Neisseria gonorrhoeae, bacteria, and fungi also are disclosed. Excerpt(s): The inventions described and claimed herein relate to probes and assays based on the use of genetic material such as RNA. More particularly, the inventions relate to the design and construction of nucleic acid probes and hybridization of such probes to genetic material of target non-viral organisms in assays for detection and/or quantitation thereof in test samples of, e.g., sputum, urine, blood and tissue sections, food, soil and water. Two single strands of nucleic acid, comprised of nucleotides, may associate ("hybridize") to form a double helical structure in which the two polynucleotide chains running in opposite directions are held together by hydrogen bonds (a weak form of chemical bond) between pairs of matched, centrally located compounds known as "bases." Generally, in the double helical structure of nucleic acids, for example, the base adenine (A) is hydrogen bonded to the base thymine (T) or uracil (U) while the base guanine (G) is hydrogen bonded to the base cytosine (C). At any point along the chain, therefore, one may find the base pairs AT or AU, TA or UA, GC, or CG. One may also find AG and GU base pairs in addition to the traditional ("canonical") base pairs. Assuming that a first single strand of nucleic acid is sufficiently complementary to a second and that the two are brought together under conditions which will promote their hybridization, double stranded nucleic acid will result. Under appropriate conditions, DNA/DNA, RNA/DNA, or RNA/RNA hybrids may be formed. Broadly, there are two basic nucleic acid hybridization procedures. In one, known as "in solution" hybridization, both a "probe" nucleic acid sequence and nucleic acid molecules from a test sample are free in solution. In the other method, the sample nucleic acid is usually immobilized on a solid support and the probe sequence is free in solution. Web site: http://www.delphion.com/details?pn=US06512105__ •

Methods for microbiological control in aqueous systems Inventor(s): Howarth; Jonathan N. (Baton Rouge, LA), Nalepa; Christopher J. (Baton Rouge, LA), Sanders; Michael J. (Baton Rouge, LA), Shelton; David L. (Baton Rouge, LA) Assignee(s): Albemarle Corporation (richmond, Va) Patent Number: 6,565,868 Date filed: January 18, 2000 Abstract: Microbiological control in water systems is achieved with an amount,of 1,3dibromo-5,5-dimethylhydantoin that is less than the amount of N,N'-bromochloro-5,5dimethylhydantoin required to achieve the same degree of microbiological control. The methods of combating Escherichia coli and/or Enterococcus faecium in an aqueous medium, and biofilms such as formed by Pseudomonas aeruginosa on surfaces contacted by the aqueous medium, involve introducing into the medium a biocidally effective amount of 1,3-dibromo-5,5-dimethylhydantoin. A microbiological control agent

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for use in water in accordance with U.S. Environmental Protection Agency regulations is purveyed in containers of a water control agent comprising 1,3-dibromo-5,5dimethylhydantoin, which containers bear a label having thereon dosage levels pursuant to requirements promulgated by the U.S. Environmental Protection Agency. The 1,3-dibromo-5,5-dimethylhydantoin is used or purveyed either as a product having a large average particle size (e.g., 175 microns or more) or in the form of a compacted product. The compacted product can be formed without using a binder where the average particle size of the 1,3-dibromo-5,5-dimethylhydantoin is about 175 microns or more. Alternatively, the compacted product can be formed using a micronized synthetic polyolefin-based hydrocarbon wax and/or a micronized synthetic polyfluorocarbon wax as a binder, provided the wax is compatible with the 1,3-dibromo-5,5dimethylhydantoin. In this case, the average particle size can be in the range of about 20600 microns. Similarly, the compacted product can be a product formed from 1,3dibromo-5,5-dimethylhydantoin having an average particle size of at least 175 microns, using an amount of a saturated, normally solid, fatty amide as the binder. Excerpt(s): 1,3-Dihalo-5,5-dialkylhydantoins are effective as biocides for aqueous systems such as industrial cooling water, recreational water, and wastewater. Widely used for such purposes are N,N'-bromochloro-5,5-dialkylhydantoins. One of the features emphasized for such materials is that in use, the chlorine released from the biocide regenerates active bromine from inactive bromide species formed during the water treatment operation. In other words, the chlorine atom in the initial N,N'bromochloro-5,5-dialkylhydantoin is in effect regarded as a precursor for additional active bromine for sanitation purposes. As is well known in the art, a deficiency of chlorine, of hypochlorites, and of certain halogenated organic water-treating agents is the formation, during usage, of undesirable disinfection by-products. These by-products are undesirable both from the standpoint of environmental concerns and also from the standpoint of toxicological considerations. Web site: http://www.delphion.com/details?pn=US06565868__ •

Methods of protecting vasculature from damage by pseudomonas toxin-based immunotoxins during therapy

diphtheria

toxin-and

Inventor(s): Hagihara; Naoshi (Saga, JP), Youle; Richard J. (Chevy Chase, MD) Assignee(s): The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,696,064 Date filed: June 19, 2001 Abstract: Vascular damage has proven to be dose limiting in administering immunotoxins into the brain to treat brain tumors. Vascular toxicity of immunotoxins which rely in part on exposure to lowered pH in cellular endosomes and lysosomes can be avoided by administering an endosome pH-raising agent systemically during some or all of the time that the immunotoxin is present in the brain of the organism. Suitable endosome pH-raising agents include lysosomotrophic amines, proton ionophores, and vacuolar H+ ATPase inhibitors. The invention increases the therapeutic window of the immunotoxins and increases the likelihood the treatment will have an effect on the course of the tumor. Excerpt(s): Not applicable. The prognosis of patients with malignant brain tumors is poor. Standard therapy, including surgery, radiation, and chemotherapy has proven

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ineffective in the majority of cases. One attempt to improve this grim clinical outlook has resulted from the discovery that many brain tumors over express the transferrin ("Tf") receptor ("Tf-R"). A Tf-targeted immunotoxin known as Tf-CRM107 (Johnson, V. G. et al., J. Biol Chem., 263:1295-1300 (1988)), a conjugate of transferrin ("Tf") and a mutant diphtheria toxin ("DT") lacking receptor-binding function (Greenfield, L. et al., Science, 238:536-539 (1987), can target and kill cells expressing Tf-R, such as tumor cells The potential of Tf-CRM107 for brain tumor therapy has been explored in vitro (Johnson, V. G. et al., J. Biol Chem., 263:1295-1300 (1988), in animal models (Laske, D. W. et al., J. Neurosurg., 80:520-526 (1994)), and in patients with malignant gliomas (Laske, D. W. et al., Nat. Med., 3:1362-1368 (1997) (hereafter, "Laske 1997"). When delivered by high-flow (4-10.mu.l/min) interstitial microinfusion convection-enhanced delivery ("CED") (Bobo, R. H. et al., Proc. Natl. Acad. Sci. USA, 91:2076-2080 (1994)), intratumoral infusion of Tf-CRM107 in patients with malignant brain tumors produces tumor responses (Laske 1997). When CED is used, Tf-CRM107 (140 kDa) is distributed preferentially into the interstitial space of the tumor and the surrounding brain infiltrated by tumor and circumvents the blood-brain barrier ("BBB"). One factor limiting the success of Tf-CRM107 therapy is the fact that capillary endothelial cells in the brain express low levels of Tf-R (Jeffries, W. A. et al., Nature, 312:162-163 (1984)). A portion of patients receiving high doses of Tf-CRM107 display neurological deficits consistent with endothelial damage. MRI in these patients has revealed changes in the brain consistent with microvascular occlusion and/or petechial hemorrhage (Laske 1997). This vascular damage therefore limits the doses at which Tf-CRM107, and other immunoconjugates using Tf as a targeting agent, can be administered. Web site: http://www.delphion.com/details?pn=US06696064__ •

Microbial strains of pseudomonas, bacillus and enterobacter/in agricultural chemical compositions Inventor(s): Tateishi; Hideaki (Fukushima, JP) Assignee(s): Kureha Chemical Industry Co., Ltd. (tokyo, Jp) Patent Number: 6,565,846 Date filed: March 9, 2000 Abstract: A method for screening a bacterium antagonistic to pathogenic bacteria that emerge during raising of seedlings of gramineous plants utilizing tropolone resistance and tropolone non-producing property as indices, and a microbial pesticide containing as an active ingredient the bacterium that has tropolone resistance and tropolone nonproducing property selected by the screening method or spores thereof. Excerpt(s): The present invention relates to a method for screening microbes antagonistic to pathogenic bacteria that emerge during raising of seedlings of gramineous plants by selection from a plant body, soil, a seed or seed soaking water utilizing tropolone resistance and tropolone non-producing characteristics as indices. Also, the present invention relates to a microbial pesticide containing as an active ingredients a bacterium and spores thereof characterized by having a resistance to tropolone and not producing tropolone and also having a antagonistic activity against pathogenic bacteria that emerge during raising of seedlings of gramineous plants. Diseases that emerge during raising of seedlings of gramineous plants include rice "Bakanae" disease, Helminthosporium leaf spot, and blast typically caused by fungi, rice bacterial gram rot, bacterial seedling blight, bacterial brown stripe, etc. caused by bacteria. To prevent these diseases, seed disinfectants, soil drenching agents, soil drench

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agents, foliage application agents after greening are said to be effective and these are used systematically by using them singly or incombination. For the disease damages by fungi, it has recently become possible to prevent them at high degree with EBI agents having high efficacy. Also, the disease damages caused by bacteria are prevented by use of chemical pesticides. However, chemical pesticides are generally low in their effect when bacterial diseases outburst and so that the problem remains that no sufficient prevention can be obtained. In case bacterial diseases outburst, at present the affected seedlings must be abolished. Therefore, development of a pesticide that can prevent or control the outburst of bacterial diseases has been desired. Under the circumstances, the present inventors have made intensive investigation with view to making a research on bio-controlling material that is superior in controlling effect to chemical pesticides on the bacterial diseases of gramineous plants. Focusing on tropolone, which is a pathogenic toxin of pathogenic bacteria on rice bacterial seedling blight disease, they have searched a bacterium that is resistant to tropolone but does not produce tropolone from rice plants and established a method for screening a antagonistic bacteria to the pathogenic bacteria. Using this screening method, they have made an extensive search for microbial materials that can be used for controlling bacterial diseases. As a result, they have been successful in isolating antagonistic bacteria from rice seedlings that are antagonistic to the pathogenic bacteria. Web site: http://www.delphion.com/details?pn=US06565846__ •

Microorganisms useful in a method of producing.alpha.-halo-.alpha.,.beta.-saturated carbonyl compounds Inventor(s): Esaki; Nobuyoshi (Shiga, JP), Kamachi; Harumi (Chiba, JP), Kamachi; Motoaki (Chiba, JP), Yoneda; Tadashi (Chiba, JP) Assignee(s): Showa Denko Kabushiki Kaisha (tokyo, Jp) Patent Number: 6,645,752 Date filed: September 26, 2001 Abstract: A method of producing an.alpha.-halo-.alpha.,.beta.-saturated carbonyl compound from an.alpha.-halocarbonyl compound having an.alpha.,.beta.-carboncarbon double bond by reducing said.alpha.,.beta.-carbon-carbon double bond using a microorganism belonging to any one of the genera Acetobacter, Actinomyces, Acinetobacter, Agrobacterium, Aeromonas, Alcaligenes, Arthrobacter, Azotobacter, Bacillus, Brevibacterium, Burkholderia, Cellulomonas, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Gluconobacter, Halobacteium, Halococccus, Klebsiella, Lactobacillus, Microbacterium, Micrococcus, Micropolyspora, Mycobacterium, Nocardia, Pseudomonas, Pseudonocardia, Rhodococcus, Rhodobacter, Serratia, Staphylococcus, Streptococcus and Streptomyces, Xanthomonas, or a microbial product thereof. Pseudomonas sp. SD810, SD811 and SD812, Burkholderia sp. SD 816, and mutants thereof having an activity of reducing the.alpha.,.beta.-carbon-carbon double bond of an.alpha.-halocarbonyl compound having an.alpha.,.beta.-carbon-carbon double bond. Excerpt(s): The present invention relates to a method of producing a corresponding.alpha.-halo-.alpha.,.beta.-saturated carbonyl compound from an.alpha.halocarbonyl compound having an.alpha.,.beta.-carbon-carbon double bond by hydrogenating the.alpha.,.beta.-carbon-carbon double bond using a microorganism belonging to the genus Acetobacter, Actinomyces, Acinetobacter, Agrobacterium, Aeromonas, Alcaligenes, Arthrobacter, Azotobacter, Bacillus, Brevibacterium,

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Burkholderia, Cellulomonas, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Gluconobacter, Halobacteium, Halococccus, Klebsiella, Lactobacillus, Microbacterium, Micrococcus, Micropolyspora, Mycobacterium, Nocardia, Pseudomonas, Pseudonocardia, Rhodococcus, Rhodobacter, Serratia, Staphylococcus, Streptococcus, Streptomyces or Xanthomonas, preferably a microorganism belonging to the genus Pseudomonas or Burkholderia, more preferably Pseudomonas sp. SD810, Pseudomonas sp. SD811, Pseudomonas sp. SD812 or Burkholderia sp. SD816, or a microbial product thereof. The present invention also relates to novel microorganisms belonging to the genera Pseudomonas and Burkholderia, particularly Pseudomonas sp. SD810, Pseudomonas sp. SD811, Pseudomonas sp. SD812 and Burkholderia sp. SD816. Furthermore, the present invention relates to a method of producing a corresponding.alpha.-halo-.alpha.,.beta.-saturated carbonyl compound as an S form compound with respect to the.alpha.-position from an.alpha.-halocarbonyl compound having an.alpha.,.beta.-carbon-carbon double bond by hydrogenating the carbon-carbon double bond. This method can be used in the production of optically active carbonyl compounds such as various optically active (having an absolute S form configuration at the.alpha.-position) saturated carboxylic acids or amides. The optically active carbonyl compounds are a highly valuable chiral building block which is difficult to prepare by classical chemical processes, and are materials useful particularly as a raw material of medical or agricultural chemicals. In recent years, a method of producing various compounds, particularly optically active substances, by the reduction of a carbon--carbon double bond using a microorganism is drawing attention. To this effect, various methods of producing a corresponding.alpha.,.beta.-saturated carbonyl compound having a substituent at the.alpha.-position from a carbonyl compound having an.alpha.,.beta.-carbon-carbon double bond and having a substituent at the.alpha.-position by microbially reducing the carbon--carbon double bond have been reported (see, H. Simon, et al., Hoppe-Seyler's Z. Physiol. Chem., 362, 33 (1981), H. Giesel, et al., Arch. Microbiol., 135, 51 (1983), H. G. W. Leuenberger, et al., Helv. Chim. Acta., 62, 455 (1979), R. Matsuno, et al., J. Ferm. Bioeng., 84, 195 (1997)). However, for example, according to the method of using bacteria as the microorganism, an anaerobe such as Clostridium kluyveri (DSM-555) or Clostridium sp. La-1 (DSM-1460) is used. Therefore, the growing rate of the microorganism is slow, it is difficult to increase the cell concentration and accordingly, the reaction rate is not satisfactorily high. Thus, these methods have a problem in profitability and operability. Web site: http://www.delphion.com/details?pn=US06645752__ •

Nucleic acid and amino acid sequences relating to pseudomonas aeruginosa for diagnostics and therapeutics Inventor(s): Bush; David (Somerville, MA), Deloughery; Craig (Medford, MA), Nolling; Jork (Ouincy, MA), Rubenfield; Marc J. (Framingham, MA) Assignee(s): Genome Therapeutics Corporation (waltham, Ma) Patent Number: 6,551,795 Date filed: February 18, 1999 Abstract: The invention provides isolated polypeptide and nucleic acid sequences derived from Pseudomonas aeruginosa that are useful in diagnosis and therapy of pathological conditions; antibodies against the polypeptides; and methods for the production of the polypeptides. The invention also provides methods for the detection, prevention and treatment of pathological conditions resulting from bacterial infection.

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Excerpt(s): The invention relates to isolated nucleic acids and polypeptides derived from Pseudomonas aeruginosa that are useful as molecular targets for diagnostics, prophylaxis and treatment of pathological conditions, as well as materials and methods for the diagnosis, prevention, and amelioration of pathological conditions resulting from bacterial infection. Incorporated herein by reference in its entirety is a Sequence Listing, comprising SEQ ID NO: 1 to SEQ ID NO: 33,142. The Sequence Listing is contained on a CD-ROM, three copies of which are filed, the Sequence Listing being in a computerreadable ASCII file named "Path9904.pto", created on Oct. 20, 2000 and of 68,982,000 bytes in size, in IBM-PC Windows.RTM.NT v4.0 format. Pseudomonas aeruginosa (P. aeruginosa) is an aerobic, motile, gram-negative, rod. P. aeruginosa normally inhabits soil, water, and vegetation. Although it seldom causes disease in healthy people, P. aeruginosa is an opportunistic pathogen which accounts for.about.10% of all nosocomial infections (National Nosocomial Infection Survey report-Data Summary from October 1986-April 1996). P. aeruginosa is the most common pathogen affecting Cystic Fibrosis patients with 61% of the specimens culturing positive (Govan, J. R. W. and V. Deretic, 1996, Microbiol. Reviews, 60(3):530-574) as well as one of the two most common pathogens observed in intensive care units (Jarvis, W. R. et al., 1992, J. Antimicrob. Chemother., 29(a supp.):19-24). Mortality from some P. aeruginosa infections can be as high as 50%. Presently, P. aeruginosa infection can still be effectively controlled by antibiotics particularly using a combination of drugs. However, resistance to several of the common antibiotics has been shown and is particularly problematic in ICUs (Archibald, L. et al., 1997, Clin. Infectious Dis., 24(2):211-215; Fish, D. N., et al., 1995, Pharmacotherapy, 15(3):279-291). In addition, P. aeruginosa has already demonstrated mechanisms for acquiring plasmids containing antibiotic resistance genes (Jakoby, G. A. (1986), The bacteria, Vol. X, The biology of Pseudomonas, pp. 265-294, J. R. Sokach (ed.) Academic Press, London) and at present thare are no approved vaccines for Pseudomonas infection. Web site: http://www.delphion.com/details?pn=US06551795__ •

PNA probes, probe sets, methods and kits pertaining to the detection of microorganisms Inventor(s): Coull; James M. (Westford, MA), Hyldig-Nielsen; Jens J. (Holliston, MA) Assignee(s): Boston Probes, Inc. (bedford, Ma) Patent Number: 6,664,045 Date filed: June 18, 1999 Abstract: This invention is related to novel PNA probes, probe sets, methods and kits pertaining to the detection of microorganisms. The probes, probe sets, methods and kits of this invention can be used to detect, identify or quantitate one or more organisms in a sample wherein the organisms are selected from the group consisting of E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepatia, Pseudomonas fluorescens or organisms of a bacterial genus including the Salmonella genus, Bacillus genus or Pseudomonas genus. The preferred probing nucleobase sequence of the PNA probes used to detect the bacteria listed above are TCA-ATG-AGC-AAA-GGT (E. coli); GCT-TCT-CGT-CCG-TTC (Staphylococcus aureus); CTG-AAT-CCA-GGA-GCA and AAC-TTG-CTG-AAC-CAC (Pseudomonas aeruginosa); CCA-TCG-CAT-CTA-ACA (Pseudomonas cepatia); TCT-AGT-CAG-TCA-GTT (Pseudomonas fluorescens); CCGACT-TGA-CAG-ACC and CCT-GCC-AGT-TTC-GAA (Salmonella genus); CTT-TGTTCT-GTC-CAT (Bacillus genus); GCT-GGC-CTA-GCC-TTC, GTC-CTC-CTT-GCG-GTT

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and TTC-TCA-TCC-GCT-CGA (Pseudomonas genus). The PNA probes, probe sets, methods and kits of this invention are particularly well suited for use in multiplex PNAFISH assays. Excerpt(s): This invention is related to the field of probe-based detection, analysis and quantitation of microorganisms. More specifically, this invention relates to novel PNA probes, probe sets, methods and kits pertaining for the detection of microorganisms. The PNA probes, probe sets, methods and kits of this invention can be used to detect, identify or quantitate one or more organisms in a sample wherein the organisms of interest may include E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepatia, Pseudomonas fluorescens or organisms of a bacterial genus including the Salmonella genus, Bacillus genus or Pseudomonas genus. Nucleic acid hybridization is a fundamental process in molecular biology. Probe-based assays are useful in the detection, quantitation and analysis of nucleic acids. Nucleic acid probes have long been used to analyze samples for the presence of nucleic acid from bacteria, fungi, virus or other organisms and are also useful in examining genetically-based disease states or clinical conditions of interest. Nonetheless, probe-based assays have been slow to achieve commercial success. This lack of commercial success is, at least partially, the result of difficulties associated with specificity, sensitivity and reliability. Hybridization assays hold promise as a means to screen large numbers of samples for conditions of interest. In practice, however, it is often difficult to multiplex a hybridization assay given the requirement that each of the many very different probes in the assay must exhibit a very high degree of specificity for a specific target nucleic acid under the same or similar conditions of stringency. Given the difficulties in specificity, sensitivity and reliability of nucleic acid probes in assays designed to detect a single target nucleic acid, sensitive and reliable methods for the multiplex analysis of samples has been particularly elusive. Web site: http://www.delphion.com/details?pn=US06664045__ •

Polycondensation of organic silicon compounds Inventor(s): Friedrich; Thomas (Darmstadt, DE) Assignee(s): Basf Aktiengesellschaft (ludwigshafen, De) Patent Number: 6,617,411 Date filed: November 22, 2000 Abstract: A process is described for the polycondensation of organic silicon compounds at from pH 6 to 8 in the presence of a lipase which is, where appropriate, immobilized on a carrier composed of polymer materials. Suitable organic silicon compounds capable of polycondensation are (RO)(R.sup.1 O)(R.sup.2 O)(R.sup.3 O)Si, (RO)(R.sup.1 O)(R.sup.2 O)SiR.sup.3, (RO)(R.sup.1 O)Si (R.sup.2)(R.sup.3) and (RO) SiR.sup.1 R.sup.2 R.sup.3, where R, R.sup.1, R.sup.2 and R.sup.3 are independently of one another C.sub.1 - to C.sub.10 -alkyl, C.sub.3 - to C.sub.10 -cycloalkyl, C.sub.4 - to C.sub.20 alkylcycloalkyl, aryl, C.sub.6 - to C.sub.16 -alkylaryl, the alkyl groups being linear or branched. It is advantageous and possible to obtain the lipase on a large scale relatively simply by fermentation processes. Preference is given to employing lipases from Pseudomonas species. Excerpt(s): The invention relates to a process for polycondensation of organic silicon compounds in the presence of an enzyme. Silicones and silicates are of industrial-scale importance. Silicates are employed, for example, as phase material in chromatography.

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There are numerous processes for their preparation. Processes leading to amorphous silicates, for example, start from orthosilicic acid which is condensed in aqueous solution with acid or base catalysis (A. F. Holleman, E. Wiberg, Lehrbuch der Anorganischen Chemie [Textbook of Inorganic Chemistry], Walter de Gruyter Verlag, Berlin N.Y. 1985, 91st-100th edition, pp. 757-764). Silicones can be prepared by condensation of silanols, silanediols and silanetriols (A. F. Holleman, E. Wiberg, Lehrbuch der Anorganischen Chemie, Walter de Gruyter Verlag, Berlin N.Y. 1983, 91st100th edition, pp.786-788). In novel processes developed in the last few years it is possible to condense organic silicon compounds under mild conditions. Enzymes are employed as catalysts. The reactions can be carried out at from pH 6 to pH 8. In 1998 a suitable enzyme has been isolated for the first time from a marine sponge, as described in J. N. Cha, K. Shimizu, Y. Zhou, S. C. Christiansen, B. F. Chmelka, G. D. Stucky, D. E. Morse, Proc. Natl. Acad. Sci. USA 1999, 96, 361-365. The enzyme is composed of three subunits, the so-called silicateins. Extracting the enzyme is relatively costly. Besides polycondensation in buffer solution, the organic silicon compounds (EtO).sub.4 Si and (EtO).sub.3 SiPh have been converted directly using air-dried enzyme. Moreover, WO 00/35993 describes employing synthetic homopolymers composed of cysteine and block polypeptides composed of lysine and cysteine for polycondensation of silicon alkoxides, metal alkoxides and derivatives thereof into silicates, polysiloxanes and polymetaloxanes. It is an object of the present invention to provide a further process for the polycondensation of organic silicon compounds, which can be carried out at from pH 6 to 8, and to find a suitable catalyst for this reaction. Web site: http://www.delphion.com/details?pn=US06617411__ •

Polyhydroxyalkanoate synthase and gene encoding the same enzyme Inventor(s): Honma; Tsutomu (Atsugi, JP), Imamura; Takeshi (Chigasaki, JP), Suda; Sakae (Atsugi, JP), Yano; Tetsuya (Atsugi, JP) Assignee(s): Canon Kabushiki Kaisha (tokyo, Jp) Patent Number: 6,485,951 Date filed: March 30, 2001 Abstract: A novel polyhydroxyalkanoate (PHA) synthase derived from a microorganism capable of producing a PHA having a novel side-chain structure and a DNA encoding the amino acid sequence for the synthase are provided. Two PHA synthase proteins (SEQ ID Nos. 1 and 3) derived from Pseudomonas jessenii P161 (FERM BP-7376) and PHA synthase genes encoding these PHA synthases are provided, respectively (SEQ ID Nos. 2 and 4). A recombinant microorganism is endowed with a PHA producing ability. Excerpt(s): This invention relates to a polyhydroxyalkanoate (hereinafter, referred to as a "PHA") synthase, a gene encoding the PHA synthase, a recombinant vector containing the gene, a transformant capable of expressing the PHA synthase which has been transformed by the recombinant vector, a process for producing the PHA synthase utilizing the transformant, and a process for preparing the PHA utilizing the transformant. In particular, this invention relates to a microorganism-derived PHA synthase capable of producing a polyhydroxyalkanoate and a gene encoding the PHA synthase utilized for expressing the PHA synthase by transformation. There have been reported a number of microorganisms producing poly-3-hydroxybutyric acid (PHB) or another PHA and storing it therein ("Biodegradable Plastic Handbook", edited by Biodegradative Plastic Research Society, NTS Co. Ltd., p.178-197). These polymers may be, as conventional plastics, used for producing a variety of products by, for example,

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melt-processing. Since they are biodegradable, they have an advantage that they can be completely degraded by microorganisms in the natural environment, and they do not cause pollution due to remaining in the natural environment like many conventional polymer compounds. Furthermore, they are excellently biocompatible, and thus are expected to be used in applications such as a medical soft member. It is known that a composition and a structure of such a PHA produced by a microorganism may considerably vary depending on the type of a microorganism used for the production, a culture-medium composition and culturing conditions. Investigations have been, therefore, mainly focused on controlling such a composition or structure for the purpose of improving physical properties of a PHA. Web site: http://www.delphion.com/details?pn=US06485951__ •

Process for producing burkholderia cepacia in the presence of tert-butanol or tertamyl alcohol, the inoculum produced, and a process for degrading said alcohols Inventor(s): Fayolle; Fran.cedilla.oise (Clamart, FR), Monot; Frederic (Nanterre, FR), Pivetau; Pascal (Rueil Malmaison, FR) Assignee(s): Institut Francais DU Petrole (rueil-malmaison Cedex, Fr) Patent Number: 6,632,649 Date filed: November 8, 2000 Abstract: The growth of the bacterium, Burkholderia cepacia (ex Pseudomonas cepacia) CIP 1-2052 is substantially increased when it is supplied with tert-butanol (TBA) or tertamyl alcohol (TAA) as the sole source of carbon and energy in the presence of at least one cobalt salt, at a concentration of 0.01 to 4 mg/l of medium. The bacterium is degraded to CO.sub.2 in the presence of oxygen. The inoculom produced by the process and the degradation process for these alcohols are useful for water treatment applications. Excerpt(s): The invention relates to a process for producing microorganisms, Burkholderia cepacia (ex Pseudomonas cepacia), CIP I-2502, to the inoculum produced, and to its application in a process for degrading the alcohols produced, for example during degradation of ethers known as ether fuels when they are contained in aqueous effluents. The ethers are as follows: ethyl tert-butyl ether, hereinafter termed ETBE, methyl tert-butyl ether, hereinafter termed MTBE, and tert-amyl methyl ether, hereinafter termed TAME. The alcohols produced during their degradation are tertbutanol, hereinafter termed TBA or tert-amyl alcohol, hereinafter termed TAA. Its particular industrial application is to water treatment. The prior art is illustrated by the document: "Transformation of carbon tetrachloride by Pseudomonas sp; strain KC under denitrification conditions", Appl. Environ. Microbiol., vol 56, No. 11, Nov, 1990 (1990-11), p. 3240-3246, and by European patent EP-A-0 237 002 and French patents FRA-2 735 497 and FR-A-2 766 478. Web site: http://www.delphion.com/details?pn=US06632649__

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Process for the preparation of cell beads BOD sensor useful for instant BOD estimation Inventor(s): Kumar; Rita (Delhi, IN), Rastogi; Shikha (Delhi, IN), Saxena; Tushya Kumar (New Delhi, IN), Sharma; Alka (Delhi, IN) Assignee(s): Council of Scientific & Industrial Research (new Delhi, In) Patent Number: 6,709,853 Date filed: April 3, 2001 Abstract: Immobilized cell beads incorporating formulated microbial consortium comprising a synergistic mixture of the following bacterial strains namely, Enterobacter sakazaki, Pseudomonas aeruginosa and Aeromonas sobria selected from the following isolated bacterial strains namely, Yersinia enterocolitica, Aeromonas sobria, Klebsiella pneumoniae, Serratia liquefaciens, Enterobacter sakazaki, Citrobacter amalonaticus, Pseudomonas fluorescens, Pseudomonas aeruginosa, Enterobacter cloaca, Acinetobacter calcoaceticus are prepared, the formulated microbial consortium is immobilized in an appropriate immobilizing agent resulting in the formation of beads and the beads are used for instant BOD estimation using an electronic device and the formulated cell beads are reusable and are capable of assimilating most of the organic matter present in varied industrial effluents. Excerpt(s): The present invention relates to a process for the preparation of cell beads BOD sensor useful for instant BOD estimation. The cell beads comprise of a formulated, synergistic, immobilized microbial consortium. The problem of water pollution is increasing day by day with industrial development and urbanization. Many toxic and recalcitrant chemical compounds are being released in increasing amounts in the aquatic environment without proper treatment. The multitude of industries are by far the largest pollution creating units, whose discharges require a great degree of detoxification before they are released into the aquatic environment. Before diverting the industrial effluents for treatment, their monitoring is crucial. Monitoring is an essential tool for waste-water management, for it details the ambient or background pollution level. Till date, classical chemical or spectrophotometric methods, requiring long reaction time and complicated procedures are used for monitoring of parameters/compounds of environmental interest such as Biochemical Oxygen Demand (BOD), heavy metals, pesticides, phenols, etc. Web site: http://www.delphion.com/details?pn=US06709853__

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Production of vanillin Inventor(s): Gasson; Michael John (Norfolk, GB), Narbad; Arjan (Norfolk, GB), Rhodes; Michael John Charles (Norfolk, GB), Walton; Nicholas John (Norfolk, GB) Assignee(s): Plant Bioscience Limited (norwich, Gb) Patent Number: 6,664,088 Date filed: December 7, 2000 Abstract: A method of producing vanillin comprising the steps of: (1) providing transferulic acid or a salt thereof; and (2) providing trans-ferulate: CoASH ligase activity (enzyme activity I), trans-feruloyl ScoA hydratase activity (enzyme activity II), and 4hydroxy-3-methoxyphenyl-.beta.-hydroxy-propionyl SCoA (HMPHP SCoA) cleavage activity (enzyme activity III). Conveniently the enzymes are provided by Pseudomonas

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fluorescens Fe3 or a mutant or derivative thereof. Polypeptides with enzymes activities II and III and polynucleotides encoding the polypeptides. Use of the polypeptides or the polynucleotides in a method for producing vanillin is also provided. Excerpt(s): The present invention relates principally to the production of vanillin (4hydroxy-3-methoxybenzaldehyde), particularly to the production of vanillin other than by extraction from the Vanilla pod. Vanillin is an important food and drink flavouring agent and a major flavour component of natural vanilla from the Vanilla pod. The use of natural vanilla is limited by its high price. Synthetic vanillin, commonly derived from sulphite liquors produced during the processing of wood pulp for paper manufacture, is frequently used as a low-cost vanilla substitute. Alternative biological processes for the production of natural vanillin and allied flavourings would have considerable industrial value and utility, most particularly if such processes could facilitate the production of vanillin and/or allied flavourings directly in a fermented food or beverage. The mechanism of vanillin biosynthesis in Vanilla remains substantially uncharacterised. M. H. Zenk (Anal. Z. Pflanzenphysiol 53, 404-414 (1965)) showed that vanillin was derived from trans-ferulate (4-hydroxy-3-methoxy-trans-cinnamate) and proposed a mechanism analogous to the classical.beta.-oxidation of fatty acids, with cleavage of a.beta.-keto thioester to produce acetyl SCoA and vanilloyl SCoA (4hydroxy-3-methoxybenzoyl SCoA) and subsequent reduction and CoASH release to generate vanillin. C. Funk and P. E. Brodelius (Plant Physiol. 94, 95-101; 102-108 (1990); 99, 256-262 (1992)), proposed a different route, in which the 4-hydroxy group of trans-ferulate became successively methylated and demethylated during the pathway of vanillin biosynthesis; however, the detailed enzymology was not elucidated. In potato tubers and in the fungus, Polyporus hispidus (C. J. French, C. P. Vance and G. H. N. Towers, Phytochemistry 15, 564-566 (1976)), in cell cultures of Lithospermum erythrorhizon (K. Yazaki, L. Heide and M. Tabata, Phytochemistry 30, 2233-2236 (1991)) and in cell cultures of carrot (J.-P. Schnitzler, J. Madlung, A. Rose and H. U. Seitz, Planta 188, 594-600 (1992)), evidence was obtained from in vitro studies that the corresponding analogue of vanillin, 4hydroxybenzaldehyde, was an intermediate in the formation of 4-hydroxybenzoate from 4-coumarate (4-hydroxy-trans-cinnamate). There was no requirement for ATP or CoASH, thus apparently ruling out a.beta.-oxidation mechanism. Further studies with cell-free extracts of Lithospermum erythrorhizon, however, have in contrast recently established the presence of a.beta.-oxidation route for the conversion of 4-coumarate to 4-hydroxybenzoate (R. Loscher and L. Heide, Plant Physiol. 106, 271-279 (1994)); in this case, the conversion was dependent on ATP, Mg.sup.2+ ions and NAD.sup.+ and proceeded via 4-hydroxybenzoyl SCoA, without the intermediate formation of 4hydroxybenzaldehyde. Web site: http://www.delphion.com/details?pn=US06664088__ •

Protease-activatable pseudomonas exotoxin A-like proproteins Inventor(s): Fitzgerald; David J. (Rockville, MD), Pastan; Ira (Potomac, MD), Reiter; Yoram (Ness Ziona, IL) Assignee(s): The United States of America AS Represented by the Secretary of the (washington, Dc) Patent Number: 6,426,075 Date filed: July 30, 1999 Abstract: This invention provides protease-activatable Pseudomonas exotoxin A-like ("PE-like") proproteins. The proproteins comprise (1) a cell recognition domain of

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between 10 and 1500 amino acids that binds to a cell surface receptor; (2) a modified PE translocation domain comprising an amino acid sequence sufficiently homologous to domain II of PE to effect translocation to a cell cytosol upon proteolytic cleavage, wherein the translocation domain comprises a cysteine-cysteine loop that comprises a protease activatable sequence cleavable by a protease and wherein the cysteine-cysteine loop is substantially un-activatable by furin; (3) optionally, a PE Ib-like domain comprising an amino acid sequence up to 1500 amino acids; (4) a cytotoxicity domain comprising an amino acid sequence substantially homologous to domain III of PE, the cytotoxicity domain having ADP-ribosylating activity; and (5) an endoplasmic reticulum ("ER") retention sequence. The invention also provides methods of using these proproteins for killing target cells. Excerpt(s): Methods and compositions relating to Pseudomonas exotoxin proproteins modified for selective toxicity. The exotoxin is modified to be activated by a desired protease by insertion of a protease activatable sequence in the domain II loop. Activation of the proprotein results in formation of the cytotoxic Pseudomonas exotoxin. Pseudomonas Exotoxin (PE), which binds and enters mammalian cells by receptor-mediated endocytosis, depends on proteolytic cleavage to generate a Cterminal active fragment which translocates to the cell cytosol, ADP-ribosylates elongation factor 2 and inhibits protein synthesis. Mutant versions of PE which cannot be processed appropriately by cells are non-toxic. Furin has been identified as the intracellular protease responsible for this cleavage. Cleavage occurs between arginine 279 and glycine 280 in an arginine-rich loop located in domain II of the toxin. In biochemical experiments, furin-mediated cleavage is evident only under mildly acidic conditions (pH 5.5). Recently, Garten et al., (EMBO J, 14(11):2424-35 (1995)) have proposed that sequences in the cytoplasmic tail of furin are responsible for its cycling to the cell surface and re-entry through the endosomal compartment. Since PE enters cells via the alpha 2-macroglobulin receptor/Low density lipoprotein receptor-related protein (LRP), it is likely that this receptor delivers PE to an acidic endosomal compartment where it is cleaved by furin. PE is broadly cytotoxic because most mammalian cells and tissues express both LRP and furin. In vivo, the injection of native PE produces profound liver toxicity. The existing strategy for targeting the cell-killing activity of PE to cancer cells is to delete the DNA encoding the cell binding domain and replace it with cDNAs encoding binding ligands or antibody fragments that recognize cancer-related cell surface determinants. Surface binding then mediates the internalization of PE-immunotoxins to a furin-containing compartment where the appropriate C-terminal fragment is generated. Since most cancer cells express furin, this cleavage-activation step does not contribute to the selectivity of immunotoxin action. Web site: http://www.delphion.com/details?pn=US06426075__ •

Proteins involved in the synthesis and assembly of core lipopolysaccharide of Pseudomonas aeruginosa Inventor(s): Burrows; Lori L. (1299 Griffith Pl., Oakville, Ontario, CA), De Kievit; Teresa R. (674 Whispering Pines Cir., Rochester, NY 14612), Lam; Joseph S. (2 Bridlewood Drive, Guelph, Onatario, CA), Matewish; Mauricia (139-78 College Ave., Guelph, Ontario, CA), Walsh; Andrew (223 Terraview Cr., Guelph, Ontario, CA) Assignee(s): None Reported Patent Number: 6,444,804 Date filed: November 2, 1999

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Abstract: Novel nucleic acid molecules encoding proteins involved in the synthesis and assembly of core lipopolysaccharide in P. aeruginosa; and novel proteins encoded by the nucleic acid molecules are described. Methods are disclosed for detecting P.aeruginosa in a sample by determining the presence of the proteins or a nucleic acid molecule encoding the proteins in the sample. Excerpt(s): The invention relates to novel nucleic acid molecules encoding proteins involved in the synthesis and assembly of core lipopolysaccharide of P. aeruginosa, the novel proteins encoded by the nucleic acid molecules; and, uses of the proteins and nucleic acid molecules. Gram negative bacterial infections account for a significant number of hospital-acquired infections. The majority of hospital-acquired infections are due to gram negative organisms such as Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Gram negative infections are particularly common among individuals receiving chemotherapy, and immunocompromised individuals. These individuals often develop resistance to antibiotics over the long course of the infection making conventional treatment difficult. Many virulence factors have been identified in the pathogenesis of gram negative bacteria, including lipopolysaccharide. The lipolypolysaccharide of gram negative bacteria is composed of O-antigen, usually tri- or tetrasaccharide repeating units, which is immunodominant and responsible for serotype specificity. The O-antigen is attached to a core oligosaccharide composed of hexoses and octoses, which is itself attached to lipid A (endotoxin) embedded in the cell membrane. The core lipopolysaccharide structure, particularly the inner core region, appears to be widely shared among diverse gram negative bacterial genera. Web site: http://www.delphion.com/details?pn=US06444804__ •

Pseudomonas exotoxin-myelin basic protein chimeric proteins Inventor(s): Beraud; Eveline (Marseille, FR), Lorberboum-Galski; Haya (Jerusalem, IL), Marianovsky; Irina (Jerusalem, IL), Steinberger; Ida (Jerusalem, IL), Yarkoni; Shai (KfarSaba, IL) Assignee(s): Yissum Research Development Company of the Hebrew University of Jerusalem (il) Patent Number: 6,531,133 Date filed: January 27, 1999 Abstract: A chimeric protein comprising a Pseudomonas aeruginosa exotoxin (PE) moiety linked to a myelin basic protein (MBP) moiety is disclosed. The MBP moiety is selected from the group comprising: (a) MBP; (b) amino acids 69-88 of guinea-pig myelin basic protein or an antigenic portion thereof; (c) amino acids 84-102 of human myelin basic protein or an antigenic portion thereof; (d) amino acids 143-168 of human myelin basic protein or an antigenic portion thereof; and (e) an amino acid sequence in which one or more amino acids have been deleted, added, substituted or mutated in the amino acid sequences of (a), (b), (c) or (d), the modified sequence of (e) retaining at least 75% homology with the amino acid sequences of (a), (b), (c) or (d), respectively. Each of the MBP moieties of (b), (c) and (d) are linked to the PE moiety by a pentapeptide linker repeated 1-3 times. The chimeric protein is useful in treating autoimmune diseases, and especially multiple sclerosis. Excerpt(s): The present invention relates to antigen-toxin chimeric proteins useful in the targeted immunotherapy of autoimmune diseases, and particularly of multiple sclerosis. The development of selective immunosuppressive agents is one of the major goals in the

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treatment of autoimmune diseases. In the ignorance of the identity of the specific antigen involved, treatment has until now been oriented toward nonspecific killing of rapidly dividing cells by means of cytotoxic agents, as well as inhibiting the action of mediators of inflammation with anti inflammatory agents. More recently, specific and selective agents for the therapy of disorders of the immune response have been developed, based on our increased understanding of the immune response, advances in genetic engineering and improved models of autoimmune diseases. Web site: http://www.delphion.com/details?pn=US06531133__ •

Solid-chemical composition for sustained release of organic substrates and complex inorganic phosphates for bioremediation Inventor(s): Hince; Eric Christian (Campbell Hall, NY) Assignee(s): Geovation Technologies, Inc. (florida, Ny) Patent Number: 6,620,611 Date filed: January 6, 2001 Abstract: A slow-release solid chemical composition for environmental bioremediation is provided. The composition comprises a source of soluble organic substrates which include sugars, soluble organic polymers and mixtures of them in an amount of 7% to 90%, insoluble organic substrates an amount of 10% to 70%, complex inorganic phosphates in an amount of 0.5% to 7% and soluble organic salts in an amount of 2% to 70%. The insoluble organic substrates include fibrous plant materials, starches, cellulosic materials and mixtures of these substrates. The complex inorganic phosphates include ringed metaphosphates, linear polyphosphates and mixtures. The organic salts include lactates, formates, acetates, citrates, etc. Also the composition further comprises microorganisms which include Bacillus spp., Rhizobium spp., Bradyrhibzobium spp., Fibrobacter spp., Clostridium spp., Pseudomonas. spp., Geobacter spp., Arthrobacter spp., Nocardia, spp., aspergillus spp., Trichoderma spp., Candida spp., Yarrowia spp. and combinations of these microorganisms. The composition can be prepared in various forms, including granules, briquettes, pellets, tablets or capsules. Excerpt(s): This invention discloses advanced solid-chemical compositions which provide balanced, sustained-release sources of soluble and insoluble organic substrates and complex inorganic phosphates, as well as other beneficial agents, which when used as intended, promote the bioremediation of contaminated environmental media. Specifically, the present invention was developed to provide a relatively simple and inexpensive means of enhancing the anaerobic bioremediation and dehalogenation of halogenated organic contaminants, such as trichloroethene (TCE), as well as the biologically mediated chemical reduction of oxidized forms of certain inorganic contaminants, such as chromium (VI), uranium (VI), and arsenate-based pesticides. Either alone or in combination with other liquid- and solid-chemical compositions, it is the inventor's belief that the present invention also has the potential for the remediation of the gasoline additive methyl tertiary butyl ether (MTBE). The disclosed solidchemical compositions of the present invention provide improved means for (1) creating, enhancing, and maintaining anaerobic if not anoxic conditions by facilitating the biologically mediated removal of the available oxygen from the media; and (2) creating and maintaining reducing conditions (i.e., negative Eh values) and near neutral to slightly acidic pH conditions (6.ltoreq.pH.ltoreq.8) which favor anaerobic, biologically mediated chemical-reduction reactions, e.g., the reductive dehalogenation of halogenated organic contaminants and the reduction of the oxidized forms of certain

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metals. The disclosed solid-chemical compositions also provide means for maintaining the aforementioned conditions for sufficiently long periods of time to enable the biologically mediated degradation, transformation, and/or detoxification reactions to proceed to the extent that the concentrations and/or toxicity of the contaminants are reduced to acceptable levels. Soil and ground-water pollution caused by chemical contaminants released into the environment is a well documented, world-wide problem. Such chemical contamination is associated with many different types of industrial activities over the last two centuries. Common environmental contaminants include several different types and forms of petroleum hydrocarbons, halogenated organic compounds including solvents (e.g., tetra- and trichloroethene, methylene chloride), organochlorine pesticides (e.g., DDT and toxaphene), polychlorinated biphenyls (i.e., PCBs), and heavy metals and other inorganic contaminants such as cyanides. The available toxicological data indicates that many of these contaminants, in particular many of the halogenated organic compounds, are toxic, carcinogenic or potentially carcinogenic to humans, animals and other environmental receptors. In addition, the available environmental and ecological data have shown that many of these contaminants tend to persist in the environment for long time periods. The long-term stability and extremely slow degradation of many such environmental contaminants presents a substantial, long-term hazard to human health and the environment throughout the industrialized world. Web site: http://www.delphion.com/details?pn=US06620611__ •

Topical compositions containing extracellular products of Pseudomonas lindbergii and Emu oil Inventor(s): Farmer; Sean (La Jolla, CA) Assignee(s): Ganeden Biotech, Inc. (san Diego, Ca) Patent Number: 6,645,506 Date filed: August 26, 1999 Abstract: The present invention discloses compositions derived from an isolated Bacillus species, spores, or an extracellular product of Bacillus coagulans comprising a supernatant or filtrate of a culture of said Bacillus coagulans strain, suitable for topical application to the skin or mucosal membranes of a mammal, which are utilized to inhibit the growth of bacterium, yeast, fungi, virus, and combinations thereof. The present invention also discloses methods of treatment and therapeutic systems for inhibiting the growth of bacterium, yeast, fungi, virus, and combinations thereof, by topical application of therapeutic compositions which are comprised, in part, of isolated Bacillus species, spores, or an extracellular product of Bacillus coagulans comprising a supernatant or filtrate of a culture of said Bacillus coagulans strain. In addition, the present invention also discloses compositions, methods of treatment, and therapeutic systems for inhibiting the growth of bacterium, yeast, fungi, virus, and combinations thereof, comprising an extracellular product of Pseudomonas lindbergii comprising a supernatant or filtrate of a culture of said Pseudomonas lindbergii strain. Excerpt(s): The present invention relates to the utilization of a probiotic, viable Bacillus bacteria, spores, and extracellular supernatant products in therapeutic compositions as a topical agent. More specifically, the present invention relates to the use of therapeutic compositions derived from Bacillus coagulans for the prevention and/or control of infections caused by bacterium, fungi, yeast, and virus, and combinations thereof The present invention also relates to the use of extracellular product of Pseudomonas

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lindbergii comprising a supernatant or filtrate of a culture of said Pseudomonas lindbergii strain for the prevention and/or control of infections caused by bacterium, fungi, yeast, and virus, and combinations thereof. Probiotic microorganisms are those which confer a benefit when grow in a particular environment, often by inhibiting the growth of other biological organisms in the same environment. Examples of probiotic organisms include bacteria and bacteriophages which possess the ability to grow within the gastrointestinal tract, at least temporarily, to displace or destroy pathogenic organisms, as well as providing other benefits to the host. See e.g., Salminen et al, 1996. Antonie Van Leeuwenhoek 70: 347-358; Elmer et al, 1996. JAMA 275: 870-876; Rafter, 1995. Scand. J. Gastroenterol. 30: 497-502; Perdigon et al, 1995. J. Dairy Sci. 78: 1597-1606; Gandi, Townsend Lett. Doctors & Patients, pp. 108-110, January 1994; Lidbeck et al, 1992. Eur. J. Cancer Prev. 1: 341-353. The majority of previous studies on probiosis have been observational rather than mechanistic in nature, and thus the processes responsible for many probiotic phenomena have yet to be quantitatively elucidated. Some probiotics are members of the normal colonic microflora and are not viewed as being overtly pathogenic. However, these organisms have occasionally caused infections (e.g., bacteremia) in individuals who are, for example, immunocompromised. See e.g., Sussman, J. et al., 1986. Rev Infect. Dis. 8: 771-776; Hata, D. et al., 1988. Pediatr. Infect. Dis. 7: 669-671. Web site: http://www.delphion.com/details?pn=US06645506__ •

Use of bacterial phage associated lysing enzymes for treating dermatological infections Inventor(s): Fischetti; Vincent (West Hempstead, NY), Loomis; Lawrence (Columbia, MD) Assignee(s): New Horizons Diagnostics Corp (columbia, Md) Patent Number: 6,432,444 Date filed: September 28, 2000 Abstract: A bandage for treating a bacterial infection of skin is disclosed wherein the bandage contains a composition produced by the method of obtaining an effective amount of at least one lytic enzyme genetically coded for by a specific bacteriophage specific for a bacteria infecting the skin, wherein the bacteria to be treated is selected from the group consisting of Staphylococcus, Pseudomonas, Streptococcus, and combinations thereof. This lytic enzyme is specific for and has the ability to digest a cell wall of one of the bacteria and is coded for by the same bacteriophage capable of infecting the bacteria being digested. The enzyme produced is mixed with a topical carrier. Excerpt(s): The present invention discloses a method and composition for the treatment of bacterial infections by the use of a lysing enzyme blended with an appropriate carrier suitable for the treatment of the infection. In the past, antibiotics have been used to treat various infections. The work of Selman Waksman in the introduction and production of Streptomycetes, Dr. Fleming's discovery of penicillin, are well known as well as the work of numerous others in the field of antibiotics. Over the years, there have been additions and chemical modifications to the "basic" antibiotics in attempts to make them more powerful, or to treat people allergic to these antibiotics. Others have found new uses for these antibiotics. U.S. Pat. No. 5,260,292 (Robinson et al.) discloses the topical treatment of acne with aminopenicillins. The method and composition for topically treating acne and acneiform dermal disorders includes applying an amount of an

198 Pseudomonas

antibiotic selected from the group consisting of ampicillin, amoxicillin, other aminopenicillins, and cephalosporins, and derivatives and analogs thereof, effective to treat the acne and acneiform dermal disorders. U.S. Pat. No. 5,409,917 (Robinson et al.) discloses the topical treatment of acne with cephalosporins. Web site: http://www.delphion.com/details?pn=US06432444__ •

Use of emu oil and its various fractions as a carrier for antifungal, antibacterial, and antiviral medications and preparations Inventor(s): Farmer; Sean (La Jolla, CA) Assignee(s): Ganeden Biotech, Inc. (san Diego, Ca) Patent Number: 6,531,126 Date filed: May 7, 2001 Abstract: An animal-derived lipid is disclosed that is useful as a carrying agent for antimicrobial formulations. Pharmaceutical and other preparations including Emu Oil are also described as profoundly useful components in anti-bacterial, anti-fungal, and antiviral treatments. This lipid material is extracted from the Emu (Dromais NovaeHollandiae), an indigenous bird of Australia and New Zealand. The present invention also discloses therapeutic compositions comprising Emu Oil in combination with an extracellular product of Bacillus coagulans or Pseudomonas lindbergii strain, comprising a supernatant or filtrate of said culture suitable for topical application to the skin or mucosal membranes of a mammal, which are utilized to inhibit the growth of bacterium, yeast, fungi, virus, and combinations thereof. Additionally, the aforementioned therapeutic composition may also include an anti-microbial, antimycotic, and/or anti-viral agent. The present invention also discloses methods of treatment and therapeutic systems for inhibiting the growth of bacterium, yeast, fungi, virus, and combinations thereof, by topical application of therapeutic compositions comprising Emu Oil in combination with an extracellular product of Bacillus coagulans or Pseudomonas lindbergii strain suitable for topical application to the skin or mucosal membranes of a mammal. Similarly, the aforementioned method may also employ a therapeutic composition additionally containing an anti-microbial, anti-mycotic, and/or anti-viral agent. Excerpt(s): The present invention relates to compositions and methods of use for the treatment of bacterial, fungal, and viral infections of the dermis and cuticle. More specifically, the present invention relates to compositions and methods of use of Emu Oil, and it various associated fractions, in combination with the appropriate medicaments, in the treatment of bacterial, fungal, and viral infections of the dermis and cuticle. The present invention also relates to the utilization of therapeutic compositions comprised of Emu Oil in combination with a probiotic, viable Bacillus bacteria, spores, and extracellular supernatant products, as well as the extracellular product of Pseudomonas lindbergii, as a topical agent for the prevention and/or control of infections caused by bacterium, fungi, yeast, and virus, and combinations thereof. Emu Oil, is an animal-derived lipid composition, extracted from the Emu (Dromais NovaeHollandiae), a flightless bird part of a group called ratites (which also includes the ostrich and the kiwi), indigenous to Australia and New Zealand. Emu Oil is extracted from a thick fat-pad on the back of the bird which putatively functions to protect the animal from the extreme temperatures in its Australian homeland. The fat is carefully extracted to prevent the formation of trans-fatty acids, wherein approximately 100 pounds of fat produces approximately 50 to 90 pounds of unrefined, pale yellow oil. The

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chemical composition and characteristics of Emu Oil has been quantitatively ascertained and is set forth below in Table I. Web site: http://www.delphion.com/details?pn=US06531126__

Patent Applications on Pseudomonas As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to pseudomonas: •

Alcohol dehydrogenase and use thereof Inventor(s): Altenbuchner, Josef; (Nufringen, DE), Bornscheuer, Uwe; (Greifswald, DE), Hildebrandt, Petra; (Weitenhagen, DE), Riermeier, Thomas; (Floersheim, DE) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030171544 Date filed: March 13, 2002 Abstract: The invention relates to a novel alcohol dehydrogenase (ADHF1) from Pseudomonas fluorescens (DSM 50106) and to functional variants thereof and to a process for selective reduction of ketones to the corresponding alcohols by using such alcohol dehydrogenases. Excerpt(s): The invention relates to a novel alcohol dehydrogenase (ADH) from Pseudomonas fluorescens and also to a process for selective reduction of ketones to the corresponding alcohols by using such alcohol dehydrogenases. The alcohol dehydrogenases (EC 1.1.1.1) belong to the group of oxidoreductases. Alcohol dehydrogenases catalyze a multiplicity of biological reactions in which alcohol substrates are oxidized to the corresponding ketones or aldehydes or in which the opposite reduction from aldehyde or ketone to alcohol is catalyzed. Alcohol dehydrogenase-mediated biological processes include such important reactions as the last step of alcoholic fermentation, i.e. conversion of glucose into ethanol in yeasts, the reduction of all-trans retinal to all-trans retinol (vitamin A.sub.1) in the retina or the degradation of blood alcohol in the liver. The reactions described are normally reversible and take place in the presence of nicotinamide adenine dinucleotide (NAD.sup.+/NADH) or nicotinamide adenine dinucleotide phosphate (NADP.sup.+/NADPH) as coenzyme. In most alcohol dehydrogenases, zinc to which the substrate oxygen atom can coordinate serves as the catalytic center. Apart from the crucial importance of alcohol dehydrogenases in biological processes, there are attempts to make use of these enzymes for organochemical synthesis to prepare alcohols, ketones or aldehydes. Of particular interest from a technical point of view is the enantioselective synthesis of optically active alcohols by catalytic reduction of the corresponding ketones. Up to now, especially alcohol dehydrogenases from horse liver, yeast (YADH) or from Thermoanaerobium brockil have been used in organic synthesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

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

200 Pseudomonas

•

AMINO ACID SEQUENCES AND METHOD FOR ISOLATING BACTERIES FROM THE TYPE GENUS PSEUDOMONAS Inventor(s): BERGHOF, CORNELIA; (BERLIN, DE), BRAEUER, ANJA; (BERLIN, DE), GASCH, ALEXANDER; (BERLIN, DE), GROENEWALD, CORDT; (BERLIN, DE), ROLFS, ARNDT; (ROSTOCK, DE), WILBORN, FREIMUT; (BERLIN, DE) Correspondence: Ronald R Santucci; Pitney Hardin Kipp & Szuch; 711 Third Avenue 20th Floor; New York; NY; 10017; US Patent Application Number: 20030082656 Date filed: May 8, 2000 Abstract: The present invention relates to a nucleic acid molecule or molecules and to a process for the detection of bacteria of the Pseudomonas genus, especially Pseudomonas aeruginosa. The invention relates also to a test kit or kits for carrying out the said detection processes. Excerpt(s): The invention relates to nucleic acid molecules for detecting Pseudomonas, to a kit and to uses thereof. The gram-negative bacterium Pseudomonas aeruginosa is a widespread bacterium that is pathogenic for humans and that constitutes a major health risk especially to neonates and to people having weakened resistance. Besides its major clinical significance, the antibiotic resistances that are frequently present and the formation of toxins, especially the highly toxic exotoxin A (Woods, D. E. and Iglewski, B. H., Rev. Infect. Dis. 5, 714-722 (1983), Pseudomonas aeruginosa is one of the most important bacterial causes of cases of food poisoning. Conventional processes require at least 4 days for the detection of Pseudomonas aeruginosa. There is therefore an urgent need for the development of rapid processes for detecting Pseudomonas aeruginosa in food and in clinical samples. In recent years, a number of new methods have been developed for routine use in detecting particular microorganisms. These include immunological processes based on the use of polyvalent or monoclonal antibodies and processes in which nucleic acid probes are used for detection by means of hybridisation to organism-specific nucleic acids. Further methods that have been described are those processes which are based on a specific nucleic acid amplification, with or without a subsequent confirmation reaction by nucleic acid hybridisation. Processes used for the amplification of nucleic acids are, for example, the polymerase chain reaction (PCR) [U.S. Pat. Nos. 4,683,195; 4,683,202; and 4,965,188], the ligase chain reaction [WO Publication 89/09835], "self-sustained sequence replication" [EP 329,822], the "transcription based amplification system" [EP 310,229] and the Q.beta. RNA-replicase system [U.S. Pat. No. 4,957,858]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Antimicrobial agent Inventor(s): Elsser, Dieter; (Bargum, DE), Morgan, Andrew John; (Vedbaek, DK), Thomas, Linda Valerie; (Dorset, GB), Yu, Shukun; (Malmoe, SE) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20030203963 Date filed: March 25, 2003

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Abstract: The present invention provides an antimicrobial composition for use against a micro-organism selected for Listeria, Salmonella, Bacillus, Saccharomyces, Pseudomonas, Clostridium, Lcatobacillus, Brochothrix, Micrococcus, Yersinia, Enterobacter and Zygosaccharomyces, said composition comprising a cyclic compound having Formula (I), or a derivative thereof, wherein R.sup.1 and R.sup.2 are independently selected from --OH,.dbd.O, and OR', wherein R' is H or --COR", and R" is C.sub.1-10 alkyl; wherein R.sup.3 is a substituent comprising an OH-group, wherein R.sup.4 and R.sup.5 are each independently selected from a hydrocarbyl group, H, OH or.dbd.O, or represent a bond with an adjacent atom on the ring of the cyclic compound. The invention further relates to a process preventing and/or inhibiting the growth of, and/or killing, micro-organisms in a material, and the use of a cyclic compound having Formula (I). Excerpt(s): This application is a Continuation-in-Part of PCT/GB01/04328, filed on Sep. 27, 2001, designating the U.S., published on Apr. 4, 2002 as WO 02/26060 A1 and claiming priority from GB 0023687.7 filed on Sep. 27, 2000 and GB 0023686.9 filed on Sep. 27, 2000. All of the above-mentioned applications, as well as all documents cited herein and documents referenced or cited in documents cited herein, are hereby incorporated by reference. The present invention relates to antimicrobial agents. More specifically, the invention relates to the antimicrobial activity of a series of anhydrofructose derivatives. Food degradation from various sources is recognised in the literature and individual chemicals are known which will inhibit one aspect or another of degradation derived from a single source. Degradation, and the loss of colour or flavour of freshly cut plant parts are known to be caused by oxidation, enzymes, microbes, and metal ions. For example, acidulants are known to prevent microbial degradation by maintaining a relatively low pH environment but their effectiveness is only temporary. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bacterial isolates from organisms that respire at least partially through their skin and biologically active extracts derived therefrom Inventor(s): Austin, Richard M. JR.; (Demorest, GA) Correspondence: Kent A. Herink, ESQ.; The Financial Center; Suite 2500; 666 Walnut Street; Des Moines; IA; 50309; US Patent Application Number: 20030072829 Date filed: January 4, 2002 Abstract: Extracts including a biologically active compound or combination of compounds derived from microorganisms isolated from mucus-producing organisms that respire at least partially through their skin. Rod-shaped bacteria isolated from the skin of salamanders and frogs are found to produce compound(s) which have antiviral, antitumor, antibacterial and antifungal properties. These compound(s) have an inhibitory effect on opportunistic human pathogens, including Candida sp., Microsporum sp., Staphylococcus sp., Pseudomonas sp., Escherichia sp, and Enterococcus sp, as well as on HIV strains and tumor cell lines. Excerpt(s): This application claims priority to provisional application Serial No. 60/260,022, filed Jan. 5, 2001. All amphibians respire, to varying degrees, cutaneously. As such, their integument must serve as a gas permeable barrier to their external environment (Lilleywhite, H. B., and P. F. A. Maderson. 1988. The structure and

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permeability of the integument. American Zoologist 28:945-962). Moisture is requisite for skin to be utilized as a respiratory organ (Fox, H. 1994. Structure of the integument. Cpt. 1 in "Amphibian Biology, Vol 1, The Integument", ed by H. Heatwole and G. T. Barthalmus, Surrey Beatty and Sons, Chipping Norton). This necessary moisture is achieved through the production of mucus via mucus-producing glands associated with the integument (Duellman, W. E., and L. Trueb. 1986. Biology of Amphibians. McGraw Hill, New York, N.Y., U.S.A.; Fox 1994). The primary component of mucus in amphibians is a mucopolysaccharide (glycoprotein) (Duellman and Trueb 1986). Glycoproteins contain one or more carbohydrate chains covalently linked to a polypeptide backbone (Schaechter, M., and I. Brockhausen. 1989. The biosynthesis of branched O-glycans. In Mucus and related topics. E. Chantler and N. A. Ratcliffe (eds). Symposia of the Society for Experimental Biology, no. XLIII, University of Cambridge, Cambridge). The mucus is rich in carbon, a necessary element to support microbial growth and synthesis of most, if not all, cellular compounds (Guirard, B. M., and E. E. Snell. 1962. Nutritional requirements of microorganisms. Pp. 33-93. In I. C. Gunsalis and R. Y. Staneir (Eds.), The Bacteria. A Treatise on Structure and Function. Vol. IV: The Physiology of Growth. Academic Press, New York, N.Y., U.S.A.). Thus, the mucus layer necessarily produced by amphibians in order to accomplish cutaneous respiration represents a nutrient rich habitat for microorganisms (Austin, Jr., R.M. 2000. Cutaneous microbial flora and antibiosis in Plethodon ventralis: inferences for parental care in the Plethodontidae. Pp. 451-461. In R. C. Bruce, R. G. Jaeger and L. D. Houck (Eds.), The Biology of Plethodontid Salamanders, Kluwer Academic/Plenum Pub., New York, N.Y., U.S.A.). The majority of microorganisms in most ecosystems are attached to surfaces (Wimpenny, J. W. T., S. L. Kinniment, and M. A. Scourfield. 1993. The physiology and biochemistry of biofilms. Pp. 274-318. In S. Denyer, P. Gorman, and M. Sussman, (Eds.), Microbial Biofilms: Formation and Control. Blackwell Scientific Publications, London, U.K.), and the integuments of animals often serve as suitable habitats for the development of microbial communities (Alexander, M. 1971. Microbial Ecology. John Wiley and Sons, New York, N.Y., U.S.A.). These microcommunities often exhibit the same types of community-level interactions that communities of larger organisms (macrocommunities) exhibit. Members of microcommunities compete for limited resources and form intimate, and, at times, ammensalistic relationships (Atlas, R. M., and R. Bartha. 1993. Microbial Ecology. Fundamentals and Applications, 3rd ed. Benjamin Cummings, New York, N.Y., U.S.A.; Bull, A. T., and J. H. Slater. 1982. Microbial Interactions and Communities. Vol. 1. Academic Press, New York, N.Y., U.S.A.; Frederickson, A. G., and G. Stephanopoulos. 1981. Microbial competition. Science 213:972-979). Such amensalistic strategies include, but are not limited to, the production of antibiotics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Biocontrol for plants sporobolomyces roseus

with

bacillus

subtilis,

pseudomonas

putida,

and

Inventor(s): Bergstrom, Gary C.; (Ithaca, NY), Corio da Luz, Wilmar; (Passo Fundo, RS, BR) Correspondence: Michael L. Goldman, ESQ.; Nixon Peabody Llp; Clinton Square, P.O. Box 31051; Rochester; NY; 14603-1051; US Patent Application Number: 20030082792 Date filed: September 10, 2002

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Abstract: The present invention is directed to isolated Bacillus subtilis, Pseudomonas putida, and Sporobolomyces roseus which are useful as a biocontrol agent. These organisms are useful in a method of imparting to plants protection against plant pathogens by applying them to plants, plant seeds, or soil surrounding plants under conditions effective to impart disease protection to the plants or plants produced from the plant seeds. The biocontrol agents are also useful in a method of enhancing plant growth which involves applying them to plants, plants seeds, or soil surrounding plants under conditions effective to enhance growth in the plants or plants produced from the plant seeds. Excerpt(s): This application claims benefit of U.S. Provisional Patent Application Serial No. 60/053,310, filed Jul. 22, 1997, and is a continuation-in-part of U.S. patent application Ser. No. 09/118,656, filed Jul. 17, 1998. The present invention relates to biocontrol for plants with Bacillus subtilis, Pseudomonas putida, and Sporobolomyces roseus. There are approximately 40 biocontrol products commercially available for the control of plant diseases worldwide. Biocontrol products are available to control many diverse pathogens, as recently reviewed by Fravel, et al., "Availability and Application of Biocontrol Products," Biological and Culture Tests for Control of Plant Diseases, 11: 17 (1996). At least 27 genera of fungi, 3 genera of bacteria, and 4 genera of nematodes are targeted for control by these products. More than half of these products control soilborne fungi. The biocontrol agents themselves are also diverse and include at least 9 genera of fungi, 4 genera of bacteria, and one actinomycete. Biocontrol products are used on a great variety of crops including greenhouse crops, row crops, field crops, perennial field crops, and trees and wood, as well as in special cropping systems such as mushroom cultivation. The products are applied in many ways. They may be sprayed onto plants or harvested fruits, drenched on harvested fruit or on plants, incorporated into the soil, applied as root dips, used to treat seeds, or inserted into trees or wood products. Biocontrol products currently on the market in the U.S. include Aspire, AQ-10, Galltrol A, Norbac 84C, Bio-Save 10, Bio-Save 11, Blightban A506, Victus, Epic, Kodiak, Deny, Mycostop, Binab-T and W, T-22G and T-22HB, and SoilGard. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Degradation of polycyclic aromatic hydrocarbons by microorganisms Inventor(s): Boonchan, Sudarat; (Choncuri, TH), Britz, Margaret; (Victoria, AU), Stanley, Grant; (Victoria, AU) Correspondence: Greer, Burns & Crain; 300 S Wacker DR; 25th Floor; Chicago; IL; 60606; US Patent Application Number: 20040023362 Date filed: April 21, 2003 Abstract: The invention relates to isolated microorganisms useful for the biodegradation of polycylic aromatic hydrocarbons (PAHs). Specifically, the invention relates to isolated Stenotrophomonas maltophilia VUN 10,010, Pseudomonas fluorescens VUN 10,011, Burkholderia sp. VUN 10,013 and Penicillium janthinellum. The invention further relates to a bacterial consortium having the ability to degrade PAHs. Excerpt(s): This invention relates to methods and compositions for degradation of polycyclic aromatic hydrocarbons. In particular, the invention relates to microorganisms which are able to degrade polycyclic aromatic hydrocarbons, and to methods and compositions which utilise these microorganisms. In a preferred embodiment, the

204 Pseudomonas

invention relates to a composition which is able to degrade polycyclic aromatic hydrocarbons completely to carbon dioxide and water. The microorganisms, compositions and methods of the invention are useful in the bioremediation of materials contaminated with polycyclic aromatic hydrocarbons, such as soils, sediments and liquid effluents. Polycyclic aromatic hydrocarbons (PAHs) are hydrophobic organic compounds which are commonly found in the environment through the disposal of coal processing wastes, petroleum sludges, asphalt, creosote and other wood preservative wastes (Wilson and Jones, 1993). The decontamination of PAH-polluted sites is of major importance because many PAH compounds are either known or suspected carcinogens and mutagens (Wright, 1980). Most low molecular weight PAHs are biodegradable in the presence of suitable microbial populations, and a number of bioremediation programs have had some success in the decontamination of PAH-contaminated sites. However, the extent and rate of PAH biodegradation are restricted by the limited bioavailability of these compounds, which is due to their low aqueous solubilities and strong adsorptive capacity to soil and sediments (McElroy et al, 1989). Indeed, the mass transfer rate of naphthalene and phenanthrene into the aqueous phase was shown to be the rate-limiting step in their biodegradation (Bury and Miller, 1993; Grimberg et al, 1996; Volkering et al, 1995). Human exploitation of fossil fuel reserves and the production of novel synthetic compounds have introduced many pollutants into the environment. In recent years there has been an increasing awareness and concern regarding the disposal and accumulation of polycyclic aromatic hydrocarbons (PAHs) in the ecosystem. Many low molecular weight PAHs are acutely toxic, with some having effects on the reproduction and mortality rates of aquatic animals, and most high molecular weight PAHs are mutagenic and carcinogenic. Owing to their hydrophobic nature, most PAHs in aquatic and terrestrial ecosystems become associated with particulates and are bound to soil and sediments, rendering them less available for biological uptake. There is also a potential for the bioaccumulation of PAHs into food chains (Morehead et al, 1986). Because of their toxicity, carcinogenicity, recalcitrance and ubiquitous distribution, the U.S Environment Protection Agency has listed sixteen PAH compounds as priority pollutants to be monitored in industrial effluents (Keith and Telliard, 1979). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Disinfectant and method of making Inventor(s): Arata, Andrew B.; (Lake City, FL) Correspondence: Frijouf, Rust & Pyle, P.A.; 201 East Davis Boulevard; Tampa; FL; 33606; US Patent Application Number: 20030198689 Date filed: May 9, 2003 Abstract: A non-toxic environmentally friendly aqueous disinfectant is disclosed for specific use as prevention against contamination by potentially pathogenic bacteria and virus. The aqueous disinfectant is formulated by electrolytically generating silver ions in water in combination with a citric acid. The aqueous disinfectant may include a suitable alcohol and/or a detergent. The aqueous disinfectant has been shown to be very effective at eliminating standard indicator organisms such as staphylococcus aureus, salmonella cholerasuis and pseudomonas aeruginosa. Excerpt(s): This application claims benefit of U.S. Patent Provisional application serial No. 60/128,212 filed Apr. 7, 1999. All subject matter set forth in provisional application

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serial No. 60/128,212 is hereby incorporated by reference into the present application as if fully set forth herein. This invention relates to disinfectants and more particularly to an environmentally friendly, non-toxic aqueous disinfectant for specific use against pathogenic bacteria and viruses. The prior art has demonstrated that the presence of copper and silver ions in an aqueous solution is useful as a disinfectant. Many in the prior art have used copper and silver ions in an aqueous solution as a disinfectant in water systems such as cooling towers, swimming pools, hot water systems in hospitals, potable water systems, spa pools and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Disruption of PQS synthesis using precursor analogs Inventor(s): Coleman, James P.; (Farmville, NC), Pesci, Everett C.; (Greenville, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20040002130 Date filed: June 27, 2002 Abstract: The present invention concerns methods of detecting bacterial infections as well as methods of treating such infections with compounds such as methyl anthranilate. The detection and treatment of Pseudomonas is particularly preferred. Excerpt(s): The present invention concerns methods of detecting PQS and bacterial cells producing the same, as well as methods of treating bacterial infections in a subject in need thereof. Cell-to-cell signaling by Pseudomonas aeruginosa occurs through a complex circuitry of interconnected, regulatory systems that controls over 70 different genes (Pesci and Iglewski (1997) Trends in Micro. 5:132-135; Whiteley, et al. (1999) Proc. Nail. Acad. Sci. USA 96:13904-13909). The signaling systems of P. aeruginosa are necessary for virulence in multiple infectious disease model systems (de Kievet and Iglewski (2000) Infect. Immun. 68:4839-4848). P. aeruginosa produces two cell-to-cell signals from the acyl homoserine lactone family [N-3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone], and a third, unique cell-to-cell Pseudomonas quinolone signal, referred to as PQS (Pesci, et al. (1999) Proc. Natl. Acad. Sci. USA 96:11229-11234; Pearson, et al. (1994) Proc. Nat. Acad. Sci. USA 91:197-201; Pearson, et al. (1995) Proc. Nat. Acad. Sci. USA 92:1490-1494). PQS, which induces the expression of virulence factors elastase and rhlI (encodes the N-butyryl-L-homoserine lactone synthase), is the only quinolone compound known to act as a cell-to-cell signal (Pesci, et al. (1999) Proc. Natl. Acad. Sci. USA 96:11229-11234; McKnight, et al. (2000) J. Bacteriol. 182:2702-2708). Although the role of this signal in the pathogenesis of human infections is not known, it is clearly important for P. aeruginosa virulence in a nematode killing assay (Gallagher and Manoil (2001) J. Bacteriol. 183:6207-6214). Also important to note, is that PQS signaling is regulated differently from acyl homoserine lactone signaling. Acyl homoserine lactone signals are produced at a time of rapid population growth, but PQS is produced maximally in the late stationary phase of growth (McKnight, et al. (2000) J. Bacteriol. 182:2702-2708). This suggests that PQS signaling is important when P. aeruginosa cells are under stressful conditions, such as those which would occur during a chronic infection in the lungs of cystic fibrosis (CF) patients. As an opportunistic pathogen, P. aeruginosa has found a specialized niche in the lungs of CF patients (Gilligan (1991) Clin. Microbiol. Rev. 4:35-51). Due to poor pulmonary clearance, P. aeruginosa chronically infects the lungs of a vast majority of CF patients at a young age (Welsh, et al. In: The Metabolic and Molecular Basis of Inherited Disease Vol. III (eds. Scriver, et al.) 3799-3876 (McGraw-Hill, New York, 1995)). These infections

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are difficult to treat and persist for the life of the patient, causing progressive lung damage that eventually leads to respiratory failure (Koch and Hoiby (1993) Lancet 341:1065-1069). Hence, as P. aeruginosa can have devastating effects on individuals suffering from CF or other infections and can rapidly develop antibiotic resistance there is a need in the art for novel therapeutic agents to combat P. aeruginosa infections. Intercellular signals and their synthetic pathways have been suggested as starting points for novel therapeutic targets (Govan and Deretic (1996) Microbiol. Rev. 60:539-547; Calfee, et al. (2001) Proc. Natl. Acad. Sci. USA 98:11633-11637). In fact, earlier work has shown that PQS is required for virulence in an insect model of infection (Gallagher & Manoil (2001) J. Bacteriol. 183:6207-6214). In addition, the use of a PQS precursor analog was found to interfere with PQS synthesis and inhibit the production of elastase, a PQScontrolled virulence factor (Calfee, et al. (2001) Proc. Natl. Acad. Sci. USA 98:1163311637). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Enhanced plant growth using alkane biostimulation Inventor(s): DiCesare, George A.; (Norwood, MA), Perriello, Felix A.; (Norwood, MA), Perriello, Jeanne M.; (Norwood, MA) Correspondence: Robert P. Lenart; Pietragallo, Bosick & Gordon; One Oxford Centre, 38th Floor; 301 Grant Street; Pittsburgh; PA; 15219; US Patent Application Number: 20030084609 Date filed: October 29, 2002 Abstract: A method of enhancing plant growth comprises the step of introducing an alkane into a location adjacent to a plant. The alkane can be introduced intermittently, and can be combined with another gas and/or nutrients. The alkane preferably comprises a butane substrate. The butane substrate can stimulate the growth of butaneutilizing bacteria, such as Aeromonas caviae, Stenotrophomonas maltophilia, Micrococcus varians, Aureobacterium esteroaromaticum, Aureobacterium barkeri, Rhodococcus fascians, Nocardia paradoxus, Comamonas acidovorans and Pseudomonas aeruginosa. The alkane can increase the amount of heterotrophic bacteria in the location adjacent to the plant, and thereby accelerate a heterotrophic nitrification process. The butane substrate can also stimulate the growth of butane-utilizing fungi. The method can also enhance the growth protists and/or prokaryotes. A system for enhancing plant growth in accordance with the method is also disclosed. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/334,981, filed Oct. 31, 2001. The present invention provides enhanced plant growth. More particularly, the invention provides methods and apparatus for using alkanes, such as butane, in order to stimulate plant growth. Soil systems contain a variety of microorganisms including bacteria, fungi and algae. Bacterial populations in soil survive and flourish depending on the availability of nutrients and carbon sources. Aerated soils including topsoil typically have the highest population of bacteria. A level of population for each type of bacteria in soil is defined based on the competition among soil bacteria. Competition may be shifted toward a specific type of bacteria due to changes in the availability of growth requirements as well as changes resulting in the alteration of physical or chemical conditions within the subsurface environment. The addition or natural presence of a carbon source becomes a major element affecting the bacterial diversity in an ecosystem. Fungi live in symbiotic relationships with plants among their roots, feeding on organic materials and assisting plants in water and

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mineral uptake. A number of genera of algae live both on the soil surface and within the soil, where they produce oxygen used by aerobes and serve as a food source for other microorganisms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Enzymatic detergent compositions Inventor(s): Bae-Lee, MyongSuk; (Montville, NJ), Ehrnsperger, Eric Charles; (Chestnut Ridge, NY), Hage, Ronald; (Vlaardingen, NL), Klugkist, Jan; (Vlaardingen, NL), Swarthoff, Ton; (Vlaardingen, NL), Van Der Waal, Patrick; (Vlaardingen, NL) Correspondence: Unilever; Patent Department; 45 River Road; Edgewater; NJ; 07020; US Patent Application Number: 20030050211 Date filed: May 20, 2002 Abstract: There is provided an enzymatic detergent composition which comprises:(a) surfactant;(b) 10-20,000 LU per gram of the detergent composition of a lipolytic enzyme obtainable from Humicola lanuginosa, Pseudomonas pseudoalcaligenes, Rhizomucor miehei and(c) a non-cross-bridged polydentate N-donor ligand capable of forming a complex with a transition metal, wherein said complex is capable of catalysing the bleaching of stains on fabrics by means of atmospheric oxygen. Excerpt(s): The present invention generally relates to the field of enzymatic detergent and cleaning compositions. More in particular, the invention is concerned with enzymatic detergent compositions comprising enzymes having lipolytic activity. Various types of enzymes are known as additives for detergent compositions. For example, detergent compositions containing proteases, cellulases, amylases, lipases and various combinations thereof have been described in the literature and several such products have appeared on the market. The present invention is concerned with detergent compositions comprising lipolytic enzymes or lipases. Such enzymes could contribute to the removal of fatty soil from fabrics by hydrolysing one or more of the ester bonds in tri-glycerides. EP-A-214 761 (Novo Nordisk) discloses lipases which are derived from organisms of the species Pseudomonas cepacia, and EP-A-258 068 (Novo Nordisk) discloses lipases which are derived from organisms of the genus Humicola. Both patent applications also describe the use of these lipases as detergent additives. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Enzymatic hydrolysis of a polymer comprising vinyl acetate monomer Inventor(s): Borch, Kim; (Birkerod, DK), Fitzhenry, James William; (Memphis, TN), Lund, Henrik; (Skodsborg, DK), Pedersen, Hanne Host; (Lyngby, DK), Sakaguchi, Hiromichi; (Chiba city, JP), Sharyo, Masaki; (Matsudo-shi, JP) Correspondence: Novozymes North America, INC.; 500 Fifth Avenue; Suite 1600; New York; NY; 10110; US Patent Application Number: 20030051836 Date filed: May 21, 2002 Abstract: The invention relates to the use of certain lipolytic enzymes such as cutinases and lipases in the manufacture of paper and paper products from recycled paper. Examples of such enzymes are derived from strains of Humicola, Candida, Fusarium

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and Pseudomonas. By use of these enzymes, the problems relating to the so-called "stickies" derived from waste paper are reduced. Excerpt(s): This application claims under 35 U.S.C. 119 priority from or the benefit of Danish application No. PA 2001 00813 filed May 21, 2001, and U.S. Provisional No. 60/294,539 filed May 30, 2001, the contents of which are fully incorporated herein by reference. This invention relates to the use of certain lipolytic enzymes in the manufacture of paper and paper products from recycled paper. By use of these enzymes, the problems relating to the so-called stickies derived from waste paper are reduced. Polymers comprising vinyl acetate are very commonly used as an adhesive and coating material throughout industrial sectors (paper, textiles etc.). However, because of their adhesive properties these polymers often cause problems at later process stages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Esterase, its DNA, its overexpression and production of optically active aryl propionic acids using the same Inventor(s): Chung, Bong Hyun; (Seo-ku, KR), Hahm, Moon Sun; (Yusung-ku, KR), Lee, Eun Gyo; (Yusung-ku, KR), Lee, Han Seung; (Yusung-ku, KR), Ryu, Yeon Woo; (Seoul, KR) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030170835 Date filed: April 9, 2002 Abstract: The present invention relates to an esterase, its DNA, its overexpression and a method for preparing an optically active aryl propionic acid of formula (1) using the same in high yield, 1wherein R.sub.1 represents an aryl group; and R.sub.2 represents a hydrogen atom.quadrature.SEQ:ID.quadrature.<110>KRIBB<120>Novel esterase, its DNA, overexpression, and production of optically active aryl propionic acids using same<160>8<170>Kopatentln 1.71<210>1<211>1143<212>DNA<213>Pseudomonas sp. BHY-1(KCTC 0688BP)<400>1 1 atgcagattc agggacatta cgagcttcaa ttcgaagcgg tgcgcgaagc tttcgccgca 60 ctgttcgacg atccccagga acgcggcgcc gcgttgtgca tccgggtcgg cggggaaacc 120 gtcctcgacc tctggtccgg caccgccgac aaggacggcg ccgaggcctg gcacagcgac 180<213>Pseudomonas sp. BHY-1(KCTC 0688BP)<400>2 2 Met Gln Ile Gln Gly His Tyr Glu Leu Gln Phe Glu 1 5 10 Ala Val Arg Glu Ala Phe Ala Ala Leu Phe Asp Asp 15 20 Pro Gln Glu Arg Gly Ala Ala Leu 25 30 Excerpt(s): wherein R.sub.1 represents an aryl group; and R.sub.2 represents a hydrogen atom. Indeed, FDA's (Food and Drug Administration's) Policy Statement for Development of New Drugs recommends "that the pharmacokinetic profile of each isomer should be characterized in animals and later compared to the clinical pharmacokinetic profile obtained in Phase I" drug testing. Thus, the demand for racemic switch technologies to produce each pure isomer has been rapidly increased in recent years. Aryl propionic acids are non-steroidal anti-inflammatory drugs and known as profen drugs such as ibuprofen, ketoprofen, naproxen, flurbiprofen, fenoprofen, suprofen and the like. It is generally alleged that the (S)-profens has the higher pharmacological effect of the racemic mixture of profens bearing at least one benzene ring a-position to aliphatic carboxylic function. A method for preparing optically pure

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(S)-profen drugs involves the conversion of a racemic mixture of profen ester to optically active profen carboxylic acid by reacting with a stereoselective chiral enzyme. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Fcepsilon-PE chimeric protein for targeted treatment of allergy responses a method for its production and pharmaceutical compositions containing the same Inventor(s): Fishman, Ala; (Haita, IL), Lorberboumgalski, Haya; (Jerusalem, IL), Yarkoni, Shai; (Kfar-Saba, IL) Correspondence: Lowe Hauptman Gilman And Berner, Llp; 1700 Diagonal Road; Suite 300 /310; Alexandria; VA; 22314; US Patent Application Number: 20030158390 Date filed: March 14, 2002 Abstract: The present invention generally relates to a new approach for thetherapy of allergic responses, based on targeted elimination of cells expressing the Fc.epsilon.RI receptor by a chimeric cytotoxin FC.sub.2'-3-PE.sub.40. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE.sub.40'--a truncated form of PE lacking the cell binding domain. The chimeric protein, produced in E. coli, specifically and efficiently kills mouse mast cell lines expressing the Fc.epsilon.RI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of Fc.epsilon.RI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for Fc.epsilon.RI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxin Pseudomonas exotoxin (PE). This Pseudomonas exotoxin is a product of Pseudomonas aeruginosa. The present invention also relates to a method for the preparation of said protein. This chimeric protein is prepared by genetically fusing the Fc region of the mouse IgE molecule to PE.sub.40, a truncated form of PE lacking the cell binding domain. The present invention also provides pharmaceutical compositions, for the treatment of allergic diseases and for the treatment of hyperplasias and malignancies, comprising as an active ingredient the above mentioned chimeric protein and a conventional adjuvant product. Excerpt(s): The present invention generally relates to a novel approach for the therapy of allergic responses. More specifically the present invention relates to Fc.epsilon.-PE chimeric protein for targeted elimination of Fc.epsilon.RI expressing cells, a method for its production, and pharmaceutical compositions containing the same. This chimeric protein is composed of cell targeting which is a part of IgE molecule linked to cell killing moieties for recognizing and distroying cells overexpressing the specific receptor. The killing moiety used in the chimeric protein of the present invention is the bacterial toxin Pseudomonas exotoxin (PE) (a product of Pseudomonas aeruginosa). About twenty percent of the world population suffers from various allergic diseases such as asthma, allergic rhinitis, food allergies, atopic dermatitis and anaphylaxis. The alarming increase in the prevalence of allergic diseases over the past decade has led to a clear need for more effective treatment. The interaction between IgE and mast cells or basophils is the primary effector pathway in allergic responses. IgE binds to high-affinity receptor (Fc.epsilon.RI) for its constant region, found almost exclusively on the surface of these cells. The binding itself, in spite of the low dissociation rate, does not result in stimulation of the cell. However, cross-linkage of cell surface-bound IgE by multivalent antigen causes receptor aggregation, triggering explosive cellular degranulation

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whereby mediators of allergy such as cellular degranulation whereby mediators of allergy such as histamine and seretonin are released. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Glutaryl cephalosporin amidase from pseudomonas diminuta BS-203 Inventor(s): Franceschini, Thomas J.; (Cicero, NY), Liu, Suo Win; (Manlius, NY), Politino, Michael; (Syracuse, NY), Tonzi, Sean M.; (Skaneateles, NY), Binder, Ross; (Manlius, NY), Brown, Joanne L.; (Dewitt, NY), Burnett, William V.; (Fayetteville, NY) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030143715 Date filed: January 17, 2003 Abstract: The invention provides a glutaryl 7-ACA amidase from Pseudomonas diminuta strain BS-203, which catalyzes the hydrolysis of 7-.beta.-(4-carboxybutanamido)-cephalosporanic acid to 7-aminocephalosporanic acid and glutaric acid. The invention also provides nucleic acid sequences, vectors, and host cells useful in the production of this amidase. The glutaryl 7-ACA amidase can be used for the preparation of 7-aminocephalosporanic acid. Excerpt(s): This application claims the benefit of provisional U.S. Application Serial No. 60/234,532, filed Sep. 22, 2000, which is incorporated herein by reference in its entirety. This invention relates to a novel glutaryl cephalosporin amidase (glutaryl 7-ACA amidase) enzyme from Pseudomonas diminuta BS-203, which catalyzes the hydrolysis of 7-(4-carboxybutanamido)-3-acetoxymethyl-3-cep- hem-4-carboxylic acid (glutaryl 7ACA) to yield 7-aminocephalosporanic acid (7-ACA) and glutaric acid. The invention also relates to nucleic acids having sequences which encode the glutaryl 7-ACA enzyme, including the nucleic acid sequence of the glutaryl 7-ACA amidase gene from P. diminuta BS-203, and to nucleic acid sequences derived therefrom. The invention also relates to vectors and host cells containing these nucleic acid sequences, and methods of producing glutaryl 7-ACA amidase with these vectors and host cells. The invention also relates to a method of preparing 7-ACA by using glutaryl 7-ACA amidase from P. diminuta BS-203. Steps A and B can also be carried out by chemical processes. The chemical processes, which involve the use of large quantities of organic solvents and toxic chemicals, have safety and environmental disadvantages. By using enzymatic processes, on the other hand, 7-ACA is obtained under mild conditions in an aqueous solvent system. Enzymes that catalyze the hydrolysis of glutaryl 7-ACA to 7-ACA (Step B) have been readily available, but enzymes that efficiently catalyze direct hydrolysis of cephalosporin C to 7-ACA (Step C) have not. Consequently, a two-step process has been generally employed, where step A is carried out chemically or enzymatically, and step B is carried out enzymatically. See for example Cambiaghi et al., U.S. Pat. No. 5,424,196, and references therein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Identification of essential genes in microorganisms Inventor(s): Carr, Grant J.; (Escondido, CA), Forsyth, R. Allyn; (San Diego, CA), Haselbeck, Robert; (San Diego, CA), Malone, Cheryl; (Santee, CA), Ohlsen, kari L.; (San Diego, CA), Trawick, John D.; (La Mesa, CA), Wall, Daniel; (San Diego, CA), Wang, Liangsu; (San Diego, CA), Xu, H. Howard; (San Diego, CA), Yamamoto, Robert; (San Diego, CA), Zamudio, Carlos; (La Jolla, CA), Zyskind, Judith W.; (La Jolla, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040029129 Date filed: October 25, 2002 Abstract: The sequences of antisense nucleic acids which inhibit the proliferation of prokaryotes are disclosed. Cell-based assays which employ the antisense nucleic acids to identify and develop antibiotics are also disclosed. The antisense nucleic acids can also be used to identify proteins required for proliferation, express these proteins or portions thereof, obtain antibodies capable of specifically binding to the expressed proteins, and to use those expressed proteins as a screen to isolate candidate molecules for rational drug discovery programs. The nucleic acids can also be used to screen for homologous nucleic acids that are required for proliferation in cells other than Staphylococcus aureus, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nucleic acids of the present invention can also be used in various assay systems to screen for proliferation required genes in other organisms. Excerpt(s): This application claims priority from International Application Number PCT/US02/09107, entitled IDENTIFICATION OF ESSENTIAL GENES IN MICROORGANISMS, filed Mar. 21, 2002, U.S. Provisional Patent Application No. 60/362,699, entitled IDENTIFICATION OF ESSENTIAL GENES IN MICROORGANISMS, filed Mar. 6, 2002, U.S. patent application Ser. No. 10/072,851, entitled METHODS FOR IDENTIFYING THE TARGET OF A COMPOUND WHICH INHIBITS CELLULAR PROLIFERATION, filed Feb. 8, 2002, U.S. Provisional Patent Application No. 60/342,923, entitled STAPHYLOCOCCUS AUREUS ESSENTIAL GENES AND METHODS OF USE, filed Oct. 25, 2001, U.S. patent application Ser. No. 09/948,993, entitled RAPID METHOD FOR REGULATING GENE EXPRESSION, filed Sep. 6, 2001, U.S. patent application Ser. No., 09/815,242, IDENTIFICATION OF ESSENTIAL GENES IN PROKARYOTES, filed Mar. 21, 2001, U.S. Provisional Patent Application No. 60/269,308, entitled IDENTIFICATION OF ESSENTIAL GENES IN STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, KLEBSIELLA PNEUMONIAE, SALMONELLA TYPHIMURIUM, AND ENTEROCOCCUS FAECALIS, filed Feb. 16, 2001, U.S. Provisional Patent Application No. 60/267,636, entitled METHODS FOR IDENTIFYING THE TARGET OF A COMPOUND WHICH INHIBITS CELLULAR PROLIFERATION, filed Feb. 9, 2001, U.S. Provisional Patent Application No. 60/257,931, entitled IDENTIFICATION OF ESSENTIAL GENES IN STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, KLEBSIELLA PNEUMONIAE AND SALMONELLA TYPHIMURIUM, filed Dec. 22, 2000, U.S. Provisional Patent Application No. 60/253,625, entitled IDENTIFICATION OF ESSENTIAL GENES IN STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, KLEBSIELLA PNEUMONIAE AND SALMONELLA TYPHIMURIUM, filed Nov. 27, 2000, U.S. Provisional Patent Application No. 60/242,578, entitled GENES IDENTIFIED AS ESSENTIAL IN STAPHLOCOCCUS AUREUS, filed Oct. 23, 2000, U.S. Provisional Patent Application No. 60/230,347, entitled RAPID PCR METHOD FOR DETERMINATION OF WHETHER A GENE IS ESSENTIAL, filed Sep. 6, 2000, U.S.

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Provisional Patent Application No. 60/230,335, entitled RAPID REPLACEMENT OF GENOMIC PROMOTERS TO GENERATE STRAINS FOR USE IN A CELL-BASED ASSAY FOR ANTIBIOTICS, filed Sep. 6, 2000, U.S. Provisional Patent Application No. 60/207,727, entitled GENES IDENTIFIED AS ESSENTIAL IN STAPHYLOCOCCUS AUREUS, filed May 26, 2000, U.S. Provisional Patent Application No. 60/206,848, enititled GENES IDENTIFIED AS ESSENTIAL IN STAPHYLOCOCCUS AUREUS, filed May 23, 2000, and U.S. Provisional Patent Application No. 60/191,078, entitled, GENES IDENTIFIED AS REQUIRED FOR PROLIFERATION IN STAPHYLOCOCCUS AUREUS, filed March 21, 2000, the disclosures of which are incorporated herein by reference in their entireties. The present application is being filed along with duplicate copies of a CD-ROM marked "Copy 1" and "Copy 2" containing a Sequence Listing in electronic format. The duplicate copies of the CD-ROM each contain a file entitled 034A_FINAL.ST25.txt created on Oct. 25, 2002 which is 181,323,992 bytes in size. The information on these duplicate CD-ROMs is incorporated herein by reference in its entirety. Table IA is provided in electronic format on duplicate copies of a CD-ROM filed herewith and marked "Tables-Copy 1" and "Tables-Copy 2." The duplicate copies of the CD-ROM each contain a file entitled FINAL_CLONE_LIST created on Feb. 26, 2002 which is 248,535 bytes in size and which contains Table IA. The information on these duplicate CD-ROMs is incorporated herein by reference in its entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Inhalable aztreonam for treatment and prevention of pulmonary bacterial infections Inventor(s): Montgomery, Alan Bruce; (Seattle, WA) Correspondence: Peters, Verny, Jones & Biksa Llp; Suite 6; 385 Sherman Avenue; Palo Alto; CA; 94306; US Patent Application Number: 20030055034 Date filed: December 20, 2001 Abstract: A method and a composition for treatment of pulmonary bacterial infections caused by gram-negative bacteria suitable for treatment of infection caused by Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Haemophilus influenzae, Proteus mirabilis, Enterobacter species, Serratia marcescens as well as those caused by Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa, using a concentrated formulation of aztreonam, or a pharmaceutically acceptable salt thereof, delivered as an aerosol or dry powder formulation. Excerpt(s): This application is based on and claims priority of the Provisional application Ser. No. 60/258,423, filed on Dec. 27, 2000. The current invention concerns a novel, safe, nonirritating and physiologically compatible inhalable aztreonam formulation suitable for treatment of pulmonary bacterial infections caused by gram negative bacteria, such as Escherichia coli, Enterobacteria species, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans. In particular, the invention concerns the inhalable formulation comprising aztreonam or a pharmaceutically acceptable salt thereof suitable for treatment and prophylaxis of acute and chronic pulmonary bacterial infections, particularly those caused by gram-negative bacteria Burkholderia cepacia, Stenotrophomonas maltophlia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa which are resistant to treatment with other antibiotics. The

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inhalable formulation is delivered as an aerosol or as an inhalable dry powder. For aerosolization, about 1 to about 250 mg of aztreonam is dissolved in about 1 to about 5 ml of saline or other aqueous solution having a pH between 4.5 and 7.5, delivered to the lung endobronchial space in an aerosol having mass medium average diameter particles predominantly between 1 to 5.mu. using a nebulizer able to atomize the aztreonam solution into particles of required sizes. The aerosol formulation has a small volume yet delivers a therapeutically efficacious dose of aztreonam to the site of the infection in amounts sufficient to treat bacterial pulmonary infections. A combination of the novel formulation with the atomizing nebulizer permits about 50% delivery of the administered dose of aztreonam into airways. For delivery of dry inhalable powder, aztreonam is milled or spray dried to particle sizes between about 1 and 5.mu. The dry powder formulation or a reconstituted aztreonam solid for aerosolization have a long shelf-life and storage stability. A wide variety of gram-negative bacteria cause severe pulmonary infections. Many of these bacteria are or become resistant to commonly used or specialty antibiotics and require treatment with new types of antibiotics. The pulmonary infections caused by gram-negative bacteria are particularly dangerous to patients who have decreased immunoprotective responses, such as for example cystic fibrosis and HIV patients, patients with bronchiectasis or those on mechanical ventilation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the production of p-hydroxybenzoate in species of Pseudomonas and Agrobacterium Inventor(s): Ben-Bassat, Arie; (Newark, DE), Cattermole, Monica; (Newark, DE), Gatenby, Anthony A.; (Wilmington, DE), Gibson, Katharine J.; (Wilmington, DE), Ramos, Juan L.; (Granada, ES), Ramos-Gonzalez, M. Isabel; (Granada, ES), Sariaslani, Sima; (Newark, DE) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20030207322 Date filed: June 19, 2003 Abstract: Bacterial strains transformed with the pcu genes are useful for the production of para-hydroxybenzoate (PHBA). Applicant has provided the p-cresol utilizing (pcu) and tmoX gene sequences from Pseudomonas mendocina KR-1, the proteins encoded by these sequences, recombinant plasmids containing such sequences, and bacterial host cells containing such plasmids or integrated sequences. Method for the use of these materials to produce PHBA are also disclosed. Excerpt(s): The present invention relates to the fields of molecular biology and microbiology, and to the use of genetic techniques to introduce a modified pathway for the production of desired compounds. More specifically, this invention describes genetically engineered biocatalysts possessing an enhanced, or new, ability to transform p-cresol or toluene to p-hydroxybenzoate. p-Hydroxybenzoate (PHBA) is used as a monomer for synthesizing Liquid Crystal Polymers (LCP). LCP's are used in electronic connectors and in telecommunication and aerospace applications. LCP resistance to sterilizing radiation suits these materials for use in medical devices as well as in chemical, and food packaging applications. Esters of PHBA also are used as backbone modifiers in other condensation polymers (i.e., polyesters), and are also used to make parabens preservatives. Chemical synthesis of PHBA is known. For example, JP 05009154 teaches a chemical route using the Kolbe-Schmidt process from tar acid and

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CO.sub.2 involving 1) the extraction of tar acid from a tar naphthalene oil by an aqueous potassium hydroxide, 2) adding phenol to the extracted tar acid potassium salt, 3) removing H.sub.2O, and 4) reacting the resultant slurry with CO.sub.2. Alternative methods of chemical synthesis are known (see, for example, U.S. Pat. Nos. 5,399,178; 4,740,614; and 3,985,797). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of circulating water in circulatory water tank system and liquid composition for sterilizing and disinfecting circulatory water tank system Inventor(s): Yoshida, Masashi; (Chiba, JP), Yoshida, Shigetoshi; (Chiba, JP) Correspondence: Darby & Darby; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20040029758 Date filed: April 8, 2003 Abstract: Disclosed is a method for circulating water through a circulating tub system, which method gives no harm to human body and no damage to the system, is capable of inhibiting formation of biofilms wherein Legionella inhibit, and circulates water while bacteria such as Legionella, Pseudomonas aeruginosa, and Escherichia coli are effectively sterilized and disinfected, and while foaming is suppressed. The method includes circulating, through water circulation piping of a circulating tub system, water containing a quaternary ammonium salt, 2-phenoxyethanol, and an antifoaming agent, wherein a total concentration of the quaternary ammonium salt and the 2phenoxyethanol is 10 to 100 ppm. Excerpt(s): The present invention relates to a method for circulating water through a circulating tub system having a water or hot water circulation system, such as public baths, household baths, and indoor and outdoor swimming pools, and to a sterilizing, disinfecting liquid composition for a circulating tub system for use in the method. More specifically, the present invention relates to a method for circulating water through a circulating tub system which causes no harm to human body and no damage to the system, which is capable of inhibiting formation of biofilms wherein bacteria of the genus Legionella or the like inhabit, and which enables circulation of water while bacteria such as those of the genus Legionella, Pseudomonas aeruginosa, and Escherichia coli are effectively disinfected or sterilized, and to a sterilizing, disinfecting liquid composition for a circulating tub system for use in the method. Circulating tub systems having a water or hot water circulation system, such as those of public baths, household baths, and indoor and outdoor swimming pools, are usually provided with a device for removing large pollutants, such as prefilters and hair catchers, and a filtering device loaded with a filter medium, in the circulation piping for water purification. In addition, for sterilization and disinfection of the systems, a sodium hypochlorite solution or sodium isocyanurate is usually dissolved at a predetermined concentration in the water or hot water circulating through the systems. Further, ozone, ultraviolet rays, photocatalysts, or chlorinating agents are sometimes used for disinfecting only the bath water. However, even the circulating tub systems subjected to such purification or sterilization are not irrelevant to the recent concerns about the risk of infection with Legionnaire's disease. In the circulating tubs, in particular, whirlpool baths, bubbling baths, and Jacuzzi baths, aerosol is generated, which may be inhaled into the respiratory system of the bathers. Thus the problem of infection needs urgent attention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for production of p-hydroxybenzoate in bacteria Inventor(s): Ben-Bassat, Arie; (US), Duque, Estrella; (US), Godoy, Patricia; (US), Ramos, Juan Luis; (US), Ramos-Gonzalez, Marie Isable; (Granda, ES) Correspondence: E I DU Pont DE Nemours And Company; Legal Patent Records Center; Barley Mill Plaza 25/1128; 4417 Lancaster Pike; Wilmington; DE; 19805; US Patent Application Number: 20030158397 Date filed: October 1, 2001 Abstract: This invention relates to the isolation of a novel tonB operon from Pseudomonas putida. These genes are useful to render the cells more sensitive to antibiotics, toluene, pHBA, aromatic compounds, parabenes, and aromatic amino acids after inactivation with specific mutant allels or more tolerant to these compounds after overexpression with appropriate expression vector. These findings are important in the field of medicine and biotechnology and biocatalysis. In addition a screen to identify pHBA tolerant genes is provided and strains with significant tolerance to pHBA were identified. These strains are important for pHBA production. Excerpt(s): The present invention relates to the fields of molecular biology and microbiology. More specifically, this invention pertains to a novel gene cluster, tonB operon (exbB, exbD, tonB) and its role in tolerance to aromatic compounds, aromatic amino acids, p-hydroxybenzoic acid (pHBA), and bactericidal agents in bacteria. In addition, a method for screening and characterizing pHBA tolerance is provided. By these methods, some strains with particular tolerance to pHBA were identified. Also provided are methods for producing bacterial strains which are more sensitive or tolerant to a variety of chemical compounds. Toxicity of aromatic compounds, antibiotics, organic solvents and bacteriocidic agents to microorganisms presents a major problem in the field of microbiology. In addition, tolerance to pHBA, antibiotics, aromatic compounds, parabenes and aromatic amino acids are of significant importance in various biotechnology areas such as biotransformation, biodegradation, food, pharmaceuticals, and cosmetics. Factors influencing tolerance appear to be varied and not always understood. Increasingly, attention has turned to genetic manipulation to create microbes that are able to thrive in high concentrations of aromatic compounds and organic solvents or to create microbes that are more sensitive to antibiotics and bacteriocidic agents, e.g., parabene preservatives. Among these are microbes that can synthesize monomers that can be used for the ulterior synthesis of added value polymers. One of these products of interest is pHBA that can be synthesized from toluene as described below. para-Hydroxybenzoic acid (pHBA) is a key monomer for production of liquid crystal polymers, (e.g., Zenite.RTM. that are used in board displays of computers and other electronic devices and for parabene preservatives). A current limitation on the biotransformation of toluene into pHBA is the relative toxicity of these compounds for cells (Sikema et al., Microbiol. Rev. 50:201-222 (1995), as well as the toxicity of the product being produced (WO 9856920). One enzymatic pathway of increasing commercial interest for biotransformation is that of toluene degradation through the toluene monooxygenase pathway (TMO pathway). This pathway includes the following steps: toluene is oxidized to p-cresol with toluene monooxygenase, pcresol is progressively oxidized to p-hydroxybenzyl alcohol and phydroxybenzaldehyde with p-cresol methylhydroxylase, and p-hydroxybenzaldehyde is then oxidized to p-hydroxybenzoic acid (pHBA) with p-hydroxybenzaldehyde dehydrogenase and pHBA is further oxidized to protocatechuic acid (PCA) with phydroxybenzoate hydroxylase. PCA is further metabolized to the TCA cycle where it is used for cell biosynthesis or energy metabolism.

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

Microbial consortium for the biodegradation of dithiocarbamates Inventor(s): Gannon, James E.; (Bonner, MT), Standish, Mike; (Rock Spring, GA) Correspondence: Thomas F. Roland; National Starch And Chemical Company; P.O. Box 6500; Bridgewater; NJ; 08807-0500; US Patent Application Number: 20030201224 Date filed: April 24, 2002 Abstract: The invention relates to a method for biodegrading dithiocarbamates or related compounds which are present in a contaminated environment. The method involves contacting the contaminated environment with a microbial consortium comprised of methylotrophic bacteria such as the genera of bacteria: Alcaligenes, Pseudomonas, and Hypomicrobium, and maintaining the microbial consortium in contact with the contaminated environment for a time that is sufficient for the microbial consortium to degrade the dithiocarbamates or related compounds. Other bacterium, such as Thiobacillus may optionally be present as part of the consortium. Excerpt(s): This invention relates to a microbial consortium useful for biodegrading dithiocarbamates. Dithiocarbamates are used in a variety of water treatment applications as metal precipitating agents. Dithiocarbamates provide a cost effective means of removing heavy metals from metal processing wastewater. Dithiocarbamates, however, pose a toxicity problem. In particular, dithiocarbamates have been shown to be inherently toxic to fish and other wildlife. In addition, dithiocarbamates may with time and under certain conditions autocatalytically hydrolyse to carbon disulfide which also poses a toxicity problem. Mounting public concern and increasing environmental legislation have provided the impetus for a safe, effective means to remediate dithiocarbamates contaminated environments. Past methods of disposing of wastewater or soil containing dithiocarbamates have included dumping at specified land-fill areas, isolation in suitable, reinforced containers, land based deep-welling, dumping in deep water at sea and incineration. All of these methods carry some potential for harm to the environment. For example, incineration creates a problem of air pollution and disposal on land risks the possibility that toxic substances will leach into locations where they may threaten aquatic life forms, animals or humans. A more desirable disposal method might incorporate a chemical, enzymatic, or biological degradative process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Microbial process for degradation of PCBs in clophen A-50 using a novel marine microorganism, pseudomonas CH07 Inventor(s): De, Jaysankar; (Goa, IN), Nagappa, Ramaiah; (Goa, IN), Sarkar, Anupam; (Goa, IN) Correspondence: Lackenbach Siegel; One Chase Road; Scarsdale; NY; 10583; US Patent Application Number: 20030054538 Date filed: February 5, 2001 Abstract: A novel marine microorganism (Pseudomonas CH07) capable of degrading different congeners namely coplanar, sterically hindered and other chlorobiphenyls

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present in a technical grade PCBs (Clophen A-50); the aerobic bacterial strain, identified as Pseudomonas CH07 isolated from coastal zone of Arabian sea near Goa, India subjected to intense anthropogenic activity is shown to degrade PCBs of chlorine content (4-7 chlorine atoms per biphenyl). Excerpt(s): The invention relates A novel marine microorganism (Pseudomonas CH07) isolated from the Indian coastal zone near Goa which is capable of biodegradation of PCBs including sterically hindered di and tri-ortho chlorinated biphenyls and coplanar congeners present in a technical grade Clophen A-50 (Bayer, Lot no. 16572) by the novel strain of marine microorganism, Pseudomonas CH07. 1. Coplanar PCBs--those compounds have chlorinated substituents in both para positions, and any/all meta positions. Meta or para chlorine substituents have, by their structure, low steric hindrance with neighboring H, which allows free rotation about the phenyl-phenyl bond. There are 20 coplanar PCBs, out of which three (77, 126, 105) are very toxic. Most importantly, they are non-ortho chlorinated. 2. Mono-ortho chlorinated PCBs-all molecules have one-chloro substitutions in the other positions only. Ortho substituents tend to create rigid bonds due to the large steric interference between C1 and H atoms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microbial SUMO protease homologs Inventor(s): Godzik, Adam; (San Diego, CA), Reed, John C.; (Rancho Santa Fe, CA) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20030203473 Date filed: November 20, 2002 Abstract: The invention provides isolated SUMO-specific protease-like (or "SSP") domain-containing polypeptides from microorganisms, including bacteria, protozoans and yeast, including Eschericia, Salmonella, Pseudomonas, Chlamydia, Plasmodium, Trypanosma, Mesorhizobium, Rickettsia, Cryptosporidium and Candida species, as well as modifications of such polypeptides, functional fragments therefrom, encoding nucleic acid molecules and specific antibodies. Also provided are methods for identifying polypeptides and compounds that associate with or modulate the activity of the SSP domain-containing polypeptides. Further provided are methods of modulating a biological activity in a cell, and treating pathological conditions, using the described nucleic acid molecules, polypeptides and compounds. Excerpt(s): This application claims benefit of the filing date of U.S. Provisional Application No. 60/331,895, filed Nov. 20, 2001, and which is incorporated herein by reference. The invention relates generally to the fields of medicine and cell biology and, more specifically, to the fields of infectious disease and regulation of apoptosis and inflammation. Post-translational modification of proteins is an important means of regulating protein activity, stability or localization. For example, post-translational modification of target proteins by conjugation to the small protein ubiquitin earmarks the target protein for degradation by the 26S proteasome. Recently, several small proteins have been identified with sequence similarity to ubiquitin and which modify target proteins. These ubiquitin-like modifiers (UBLs) include SUMO (small ubiquitinrelated modifier), Rubi (also called Nedd8), Apg8 and Apg12. In mammals, three members of the SUMO family have been described: SUMO-1, also known as PIC-1, sentrin or GMP1, which in humans is a 101 amino acid polypeptide; and the highly

218 Pseudomonas

homologous polypeptides SUMO-2 and SUMO-3. Although SUMO-1 shares only about 18% sequence identity to ubiquitin, both polypeptides share a common threedimensional structure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel carbapenem derivatives Inventor(s): Aihara, Kazuhiro; (Yokohama-Shi, JP), Akiyama, Yoshihisa; (Yokohama-Shi, JP), Ando, Takashi; (Yokohama-Shi, JP), Atsumi, Kunio; (Yokohama-Shi, JP), Ida, Takashi; (Yokohama-Shi, JP), Iwamatsu, Katsuyoshi; (Yokohama-Shi, JP), Kano, Yuko; (Yokohama-Shi, JP), Kitagawa, Hideo; (Yokohama-Shi, JP), Maruyama, Takahisa; (Yokohama-Shi, JP), Sambongi, Yumiko; (Yokohama-Shi, JP), Sasaki, Toshiro; (Yokohama-Shi, JP), Takizawa, Hiromasa; (Yokohama-Shi, JP), Tanabe, Kiyoshi; (Yokohama-Shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030149016 Date filed: August 14, 2002 Abstract: Disclosed is a novel carbapenem derivative having a substituted imidazo[5,1b]thiazole group at the 2-position on the, carbapenem ring have high anti-microbial activities against.beta.-lactamase producing bacteria, MRSA, resistant-Pseudomonas aeruginosa, PRSP, enterococci, and influenza, and high stabilities to DHP-1. According to the present invention, there is provided a compound represented by the formula (I), or a pharmacologically acceptable salt thereof or an ester at the 3-position on the carbapenem ring thereof: 1 Excerpt(s): The present invention relates to a carbapenem compound which has excellent antimicrobial activity and wide range of anti-microbial spectrum, and can be administered not only as an injection but also orally. More particularly, the present invention relates to a novel carbapenem derivative which has a substituted imidazo[5,1b]thiazole group or a salt thereof. Carbapenem derivatives, by virtue of potent antibacterial activity against a wide spectrum of bacteria, have been energetically studied as a highly useful.beta.-lactam agent, and Imipenem, Panipenem, and Meropenem have been clinically used. Both Imipenem and Panipenem, however, are used as a mixture due to instability against renal dehydropeptidase-1 ("DHP-1") in the case of Imipenem and in order to reduce nephrotoxicity in the case of Panipenem. Meropenem which has recently been marketed has a methyl group at the 1.beta.position, so that it has increased stability to DHP-1 and thus can be used alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel proteins involved in the synthesis and assembly of O-antigen in pseudomonas aeruginosa Inventor(s): Burrows, Lori L.; (Guelph, CA), Charter, Deborah; (Guelph, CA), Kievit, Teresa de; (Guelph, CA), Lam, Joseph S.; (Guelph, CA) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030124634 Date filed: August 12, 2002 Abstract: Novel nucleic acid molecules encoding proteins involved in the synthesis and assembly of O-antigen in P. aeruginosa; and novel proteins encoded by the nucleic acid molecules are described. Methods are disclosed for detecting P.aeruginosa in a sample by determining the presence of the proteins or a nucleic acid molecule encoding the proteins in the sample. Excerpt(s): The invention relates to novel nucleic acid molecules encoding proteins involved in the synthesis and assembly of O-antigen in P. aeruginosa; the novel proteins encoded by the nucleic acid molecules; and, uses of the proteins and nucleic acid molecules. The opportunistic pathogen P. aeruginosa remains a problem in the nosicomial infection of immunocompromised individuals. P. aeruginosa infections are particularly a problem in burn patients, people receiving medical implants, and in individuals suffering from cystic fibrosis (Fick, R. B. Jr., 1993). The organism is intrinsically resistant to many antibiotics and capable of forming biofilms which are recalcitrant to treatment. Several virulence factors have been identified in the pathogenesis of P. aeruginosa infections, including proteins such as exotoxin A, proteases, and exopolysaccharides including alginate and lipopolysaccharide (LPS). The LPS of P. aeruginosa is typical of Gram-negative bacteria, composed of lipid A-core oligosaccharide-O antigen repeating units. P. aeruginosa is capable of coexpressing two distinct forms of LPS, designated A-band and B-band LPS, respectively. A-band LPS is a shorter, common form expressed by the majority of P. aeruginosa serotypes, and has a trisaccharide repeating unit of.alpha.-D-rhamnose linked 1.fwdarw.3, 1.fwdarw.3, 1.DELTA.2. B-band LPS is the serotype-specific, O-antigen-containing form, and is a heteropolymer composed of di- to pentasaccharide repeats containing a wide variety of acyl sugars, amino sugars, and uronic acids. Both the A- and B-band repeating units are attached to lipid A-core, but there appear to be differences between them regarding point of attachment to and composition of the outer core region (Rivera et al., 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel regulatory elements of cold-inducible hutU gene from the Antarctic psychrotrophic bacterium Pseudomonas Syringae Inventor(s): Janiyani, Kamala L.; (Hyderabad, IN), Ray, M.K.; (Hyderabad, IN) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030219865 Date filed: January 23, 2003 Excerpt(s): A DNA sequence from the upstream region of cold-inducible hutU gene of the Antarctic Psychrotrophic Bacterium Pseudomonas Syringae, comprising promoter

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elements and other regulatory sequences, with unique `CAAAA` nucleotide sequence at -10 site of multiple transcription start sites and using said promoter to express genes of interest in the said bacterium at temperature as low as 4.degree. C. and using the said bacterium with generation time ranging between two and half to three hours, as a system to produce low temperature labile proteins of pharmaceutical significance. Antarctic bacteria provide a useful model system for studying cold adaptation (15, 17, 31, 36). These organisms are generally represented by the psychrotrophs and psychrophiles, which have the ability to grow at 0.degree. C. They can transcribe at this lower temperature both in vitro and in vivo (31). However, nothing much is known about the nature of promoter and regulatory elements from these bacteria or about the mechanism of transcription at lower temperatures. Most of the transcriptional studies thus far have been carried out with only mesophilic bacterium, and the RNA polymerase from these bacteria, including Escherichia coli, cannot transcribe at 0.degree. C. A recent study from our laboratory has demonstrated that the RNA polymerase of the Antarctic psychrotrophic bacterium Pseudomonas syringae has can transcribe at 0.degree. C. The polymerase from the bacterium was not only active at the low temperature but also could transcribe in vitro preferentially the cold-inducible gene of E. coli cspA from a supercoiled template (43). However, absolutely no information is available with regard to the characteristics of promoter sequence such as the -10 and -35 elements from the bacterium for such low temperature specific transcription. Neither is any information available for the in vivo recognition of promoter sequences by RNA polymerase from the cold-adapted P. syringae. Therefore, we initially attempted to identify the genes from the Antarctic P. syringae that are upregulated at low temperature, with the help of TnJ-mediated random genomic fusions of a prompter-less reporter gene, lacZ (23). One of the fusions that produced at least 10- to 14-fcp,1d more p-galactosida.sc at a low temperature (4.degree. C.) was identified by cloning and sequencing of ca. 450 bp of DNA sequence proximal to the Tn5 insertion site. The fusion was in the hutU gene, which encodes for an enzyme urocanase of the histidine utilization pathway of bacteria (13, 23). A direct assay of urocanase activity from the P. syringae and a few more Antarctic Pseitdomonas species and their comparison with the mesophilic P. putida suggested that the hutU gene is unregulated in the psychrotrophs but not in the mcso-phile. Therefore, it appeared to us that the hutUgene might be a useful model for investigating the mechanism of gene regulation at low temperatures in the Antarctic bacterium. Accordingly, we cloned and sequenced the DNA encompassing the hut if gene, and its upstream and downstream regions and identified different open reading frames (ORFs) in the region. We also examined transcripts from bacterial cells grown at low (4.degree. C.) and high (22.degree. C.) temperatures by Northern and primer extension analyses, and we identified the transcription start sites and other putative regulatory elements of the hutU gene. Additionally, we compare here the deduced amino acid sequences of the urocanase from the psychrotrophic P. syringae and other bacteria, including the mesophilic P. putida, in order to examine the possible amino acid substitutions due to a low-temperature adaptation. The main object of the present invention is to determine the role of promoter and other regulatory elements of antarctic psychotrophic bcterium pseudomonas syringae in expression of proteins under extremely low temperature. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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221

Peptide compositions and methods of producing and using same Inventor(s): Hodges, Robert; (Denver, CO), Lund, Garry; (Edmonton, CA), Malcolm, Andrew J.; (Edmonton, CA), Marcotte, Rita L.; (Edmonton, CA) Correspondence: Bell, Boyd & Lloyd Llc; P.O. Box 1135; Chicago; IL; 60690-1135; US Patent Application Number: 20030228324 Date filed: May 9, 2003 Abstract: Peptide compositions and methods of producing and using same are provided. The peptide compositions are based on pilin peptides derived from Pseudomonas aeruginosa. The compositions include antigens and antibodies immunoreactive against the antigens. The compositions can be utilized in vaccines for treatment purposes, such as to treat or prevent infection associated with Pseudomonas aeruginosa and/or other infectious agents. Further, the compositions can be utilized to produce antibody or monoclonal antibody therapeutic to treat or prevent infection associated with Pseudomonas aeruginosa and/or other infectious agents. Excerpt(s): This patent application is a continuation-in-part of U.S. patent application Ser. No. 10/341,775 filed on Jan. 14, 2003 which is a continuation of U.S. patent application Ser. No. 09/345,624, filed on Jun. 30, 1999 which issued as U.S. Pat. No. 6,541,007 and is a continuation of U.S. patent application Ser. No. 09/306,241, filed on May 6, 1999, now abandoned, the disclosures of which are incorporated herein by reference. The present invention generally relates to peptide compositions. More specifically, the present invention relates to peptide compositions based on pilin peptides derived from Pseudomonas aeruginosa, and includes antigens, antibodies, and methods of producing and using same. Pseudomonas aeruginosa is a serious opportunistic gram-negative bacterial pathogen, which can cause fatal infections in immunocompromised and immunosuppressed patients. See, Irvin, R. T., "Attachment and colonization of Pseudomonas aeruginosa: Role of the surface structures", in PSEUDOMONAS AERUGINOSA AS AN OPPORTUNISTIC PATHOGEN, (Campa, M., M. Bendinelli, and H. Friedman, Eds.), pp 19-42, Plenum Press, New York (1993); Pier, G. B., J. Infect. Dis. 151:575-580 (1985); Rivera, M. and Nicotra, M. B., Am. Rev. Respir. Dis. 126:833-836 (1982); and Todd, T. R. J., et al., Am. Rev. Respir. Dis. 140:15851589 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Plant defense-related genes regulated in response to plant-pathogen interactions and methods of use Inventor(s): Crasta, Oswald R.; (Clinton, CT), Folkerts, Otto; (Guilford, CT), Martin, Gregory B.; (Ithaca, NY), Mysore, Kiran Kumar; (Ardmore, OK), Swirsky, Peter; (Branford, CT) Correspondence: Brown & Michaels, PC; 400 M & T Bank Building; 118 North Tioga ST; Ithaca; NY; 14850; US Patent Application Number: 20040006787 Date filed: January 14, 2003 Abstract: Compositions and methods of use for the expression of plant pathogen defense-related and signaling genes are provided. The compositions include nucleotide sequences identified from tomato that show specific patterns of gene expression

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associated with the Avr-Pto mediated defense response in tomato plants resistant to bacterial speck disease caused by Pseudomonas syringae pathovar tomato [strain T1(A)]. The nucleotide sequences are specific to genes that are up-regulated or downregulated in response to the interaction of AvrPto and Pto in the presence of Prf. These compositions have agricultural utility for increasing resistance to a variety of biotic and abiotic stresses, including plant pathogens. Excerpt(s): This application claims an invention which was disclosed in Provisional Application No. 60/348,792, filed Jan. 14, 2002, entitled "PLANT DEFENSE RELATED GENES AND METHODS OF USE"; and Provisional Application No. 60/390,249, filed Jun. 20, 2002, entitled "PLANT DEFENSE RELATED GENES REGULATED IN RESPONSE TO PLANT-PATHOGEN INTERACTIONS AND METHODS OF USE". The benefit under 35 USC.sctn. 119(e) of the United States provisional applications is hereby claimed, and the aforementioned applications are hereby incorporated herein by reference. The invention pertains to the field of genetic engineering of plants. More particularly, the invention pertains to the genetic manipulation of plants, through transformation and.backslash.or breeding, by expressing or manipulating the regulation of expression of certain polynucleotides that enhance plant disease resistance. Biotic stress is major cause of loss in yield and quality of crop produce. It is caused by infection by plant pathogens, infestation by insects and other pests and parasitism by another organism. Developing plants that can resist or tolerate biotic and/or abiotic stress impacts positively on the quality and yield of crop plants. Understanding of the molecular mechanisms used by plants to resist, tolerate or avoid biotic and/or abiotic stress provides new strategies of crop improvement for stress tolerance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Polyhydroxyalkanoate synthase and gene encoding the same Inventor(s): Honma, Tsutomu; (Kanagawa, JP), Imamura, Takeshi; (Kanagawa, JP), Suda, Sakae; (Ibaraki, JP), Yano, Tetsuya; (Kanagawa, JP) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20030124692 Date filed: September 18, 2002 Abstract: The present invention provides a PHA (polyhydroxyalkanoate) synthase useful in a process for preparing a PHA, a gene encoding the enzyme, a recombinant vector comprising the gene, a transformant transformed by the vector, a process for producing a PHA synthase utilizing the transformant and a process for preparing a PHA utilizing the transformant. A transformant obtained by introducing a PHA synthase gene from Pseudomonas putida P91 strain into a host microorganism is cultured to produce a PHA synthase or PHA. Excerpt(s): This invention relates to a polyhydroxyalkanoate (hereinafter, referred to as a "PHA") synthase, a gene encoding the synthase, a recombinant vector containing the gene, a transformant transformed by the vector, a process for producing the PHA synthase utilizing the transformant, and a process for preparing the PHA utilizing the transformant. There have been reported a number of microorganisms producing poly-3hydroxybutyric acid (PHB) or another PHA and storing it therein ("Biodegradable Plastic Handbook", edited by Biodegradable Plastic Research Society, NTS Co. Ltd., p. 178-197 1995). These polymers may be, as conventional plastics, used for producing a

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variety of products by, for example, melt processing. Since they are biodegradable, they have an advantage that they can be completely degraded by microorganisms in the natural environment, and they do not cause pollution due to remaining in the natural environment like many conventional polymer compounds. Furthermore, they are excellently biocompatible, and thus are expected to be used in applications such as a medical soft member. It is known that a composition and a structure of such a PHA produced by a microorganism may considerably vary depending on the type of a microorganism used for the production, a culture-medium composition and culturing conditions. Investigations have been, therefore, mainly focused on controlling such a composition or structure for the purpose of improving physical properties of a PHA. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pre-emergent biological control agents Inventor(s): Boyetchko, Susan M.; (Saskatoon, CA), Geissler, Jon; (Saskatoon, CA), Sawchyn, Karen; (Saskatoon, CA) Correspondence: Sheldon & Mak, Inc; 225 South Lake Avenue; 9th Floor; Pasadena; CA; 91101; US Patent Application Number: 20030054959 Date filed: March 15, 2002 Abstract: The present invention provides an isolated biocontrol agent, or a biocontrol composition, comprising, at least one Pseudomonas strain that exhibits weed suppressive activity. Preferably, the biocontrol composition comprises an acceptable medium such as a liquid culture medium, a solid culture medium, a seed coating, pesta, peat prill, vermiculite, clay, starch, wheat straw, or any combination thereof. The biocontrol agent or biocontrol composition may be used to suppress the growth of a weed. The weed may be selected from the group consisting of green foxtail (Setaria viridis [L.] Beauv.), foxtail barley (Hordeum jubatum), crabgrass (Digitaria sanguinalis), annual ryegrass (Lolium rigidum), barnyard grass (Echinochloa crusgalli), yellow foxtail (Setaria glauca), Italian rye grass (Lolium multiflorum), Goose grass (Eleusine indica), and wild oat (Avena fatua). Furthermore, the biocontrol agent or composition may be applied to soil before, during or after planting crops in the soil. Excerpt(s): The present Application claims the benefit of U.S. Provisional Patent Application 60/276,413 titled "Pre-Emergent Biological Control Agents," filed Mar. 16, 2001, the contents of which are incorporated in this disclosure by reference in its entirety. The invention relates to biocontrol agents for suppressing weed growth. More specifically the present invention relates to bacterial biocontrol agents for suppression of weed growth. Control of weeds is an important aspect of crop management. Due to several undesirable properties associated with the use of chemical herbicides, alternative weed control practices, including the use of biological herbicides, are desired. For example, rising economic, environmental and social costs associated with agricultural inputs, spray drift, pesticide residues, government legislation for reduced pesticide use, along with the development of herbicide resistance in weeds, make biocontrol agents attractive strategies for weed control. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for preparing (-)- menthol and similar compounds Inventor(s): Brady, Dean; (Midrand, ZA), Chaplin, Jennifer Ann; (San Diego, CA), Evans-Dickson, Melanie Daryle; (Livingstone, ZA), Gardiner, Neil Stockenstrom; (Pretoria, ZA), Marais, Stephanus Francois; (Garsfontein, ZA), Mboniswa, Butana Andrew; (Edenvale, ZA), Mitra, Robin Kumar; (Benoni, ZA), Parkinson, Christopher John; (Modderfontein, ZA), Portwig, Madrie; (Greenside, ZA), Reddy, Shavani; (Edenvale, ZA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W.; Washington; DC; 20005; US Patent Application Number: 20040058422 Date filed: September 9, 2003 Abstract: A process of separating a desired (-) stereoisomer which is selected from (-) menthol or an equivalent (-) compound where the isopropyl group is replaced with an isopropanol or an isopropylene group, from a starting material comprising: 40 to 100 m/m % of a mixture of (-)-menthol and (+)-menthol; up to 30 m/m % of a mixture of (-)isomenthol and (+)-isomenthol; up to 20 m/m % of a mixture of (-)-neomenthol and (+)neomenthol; and up to 10 m/m % of a mixture of (-)-neoisomenthol and (+)neoisomenthol or an equivalent (+) mixture where the isopropyl group is replaced with an isopropanol or an isopropylene group, includes the steps of: contacting the starting material with an esterifying agent and a stereospecific enzyme which is a Pseudomonas lipase enzyme which stereoselectively esterifies the --OH group of the desired (-) steroisomer, for a time sufficient to convert a desired percentage of the desired (-) stereoisomer to a desired (-) esterified compound where the --OH group is converted to a group --O--C(O)--R4, wherein R4 is an alkyl or an aryl group, to give a first reaction product including the desired (-) esterified compound, the organic solvent, the unconverted stereoisomers, excess esterifying agent and by-products of the reaction; and separating the desired (-) esterified compound from the first reaction product. The process is of particular application for the production of (-)-menthol. Excerpt(s): THIS invention relates to a process for producing (-)-menthol and similar compounds. Menthol has been the subject of much research in the flavour industry. The molecule of menthol has three asymmetric carbon atoms, and hence, a total of eight optically active isomers are possible. The eight isomers are (-)-menthol, (+)-menthol, (-)isomenthol, (+)-isomenthol, (-)-neomenthol, (+)-neomenthol, (-)-neoisomenthol and (+)neoisomenthol. Of all of these isomers only (-)-menthol has a strong refreshing character and is widely used in perfumes and medicines. Thus, the isolation of (-)-menthol from the other isomers is industrially important. As previously discussed, reacemic menthol contains four stereoisomeric pairs of menthols. The isolation of (-)-menthol from this isomeric mixture can be performed chemically via crystallisation, freeze-drying or distillation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for preparing hudroxylation

n-substituted

4-hydroxypiperidines

by

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enzymatic

Inventor(s): Chang, Dongliang; (Zurich, CH), Li, Zhi; (Urdorf, CH), Witholt, Bernard; (Zurich, CH) Correspondence: Hoffmann & Baron, Llp; 6900 Jericho Turnpike; Syosset; NY; 11791; US Patent Application Number: 20040029237 Date filed: August 21, 2003 Abstract: A process for the preparation of N-substituted 4-hydroxypiperidine, wherein an oxygen atom is inserted regioselectively into the corresponding N-substituted piperidine, by using as a biocatalyst a bacterium degrading alkanes or alicyclic hydrocarbons, or a prokaryotic host-organism having the gene(s) necessary for the hydroxylation derived from the said bacterium, or an enzyme having hydroxylation activity derived therefrom. The bacterium may be selected from species from, for example, the genera Sphingomonas and Pseudomonas, that are capable of degrading nalkanes having 4 to 20 carbon atoms. Excerpt(s): The present invention relates to a process for preparing N-substituted 4hydroxypiperidines that are useful as intermediates for the preparation of several pharmaceutical products and agricultural chemicals, wherein an oxygen atom is inserted regioselectively into the corresponding N-substituted piperidines by use of biocatalysts. 4Hydroxypiperidine and N-substituted 4-hydroxypiperidines are useful intermediates for the syntheses of several pharmaceuticals, agrochemicals, and the like. In practice it is often advantageous, if not required, to use 4-hydroxypiperidine in its Nprotected form. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for the preparation of pseudomonic acid a antibiotic by microbiological method Inventor(s): Albrecht, Karoly; (Budapest, HU), Balogh, Gabor; (Debrecen, HU), Barta, Istvan; (Budapest, HU), Erdei, Janos; (Debrecen, HU), Gulyas, Eva; (Debrecen, HU), Lang, Ildiko; (Budapest, HU), Mozes Nee Suto, Julianna; (Budapest, HU), Petroczki, Magdolna; (Budapest, HU), Szabo, Istvan M.; (Budapest, HU), Szell, Valeria; (Budapest, HU), Tedges, Aniko; (Budapest, HU) Correspondence: Steve J. Lee; Kenyon & Kenyon; One Broadway; New York; NJ; 10004; US Patent Application Number: 20030100083 Date filed: November 12, 2002 Abstract: A procedure for the preparation of pseudomonic acid A comprising submerged cultivation of a Pseudomonas bacterium strain capable of biosynthesis of the substantially pure pseudomonic acid A in aerated conditions via fermentation; and isolation of the desired compound is disclosed. In particular, the procedure of the present invention comprises cultivation of the Pseudomonas sp. bacterium strain No. 19/26 deposited under accession No. NCAIM(P)B 001235 in the National Collection of the Agricultural and Industrial Microorganisms, Budapest, Hungary, or its pseudomonic acid A-producing mutant or variant, on a medium at a temperature of

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between about 20.degree. C. and 30.degree. C. containing organic nitrogen and carbon sources and, optionally, mineral salts Excerpt(s): The present invention relates to a microbiological method for the manufacture of the antibiotic pseudomonic acid A (mupirocin). Pseudomonic acid A, also known as mupirocin, is an antibiotic that has a growth inhibiting effect mainly against Gram positive bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Klebsiella pneumoniae) and some Gram negative bacteria (e.g. Haemophilus influenzae, Neisseria gonorrhoeae) [A Ward, D M Campoli-Richards, Drugs 32, 425-444 (1986)] and its minimal inhibiting concentration is in the range of 0 020.5 mg/dm.sup.3 Pseudomonic acid A, by inhibiting the isoleucine-tRNA synthase enzyme, affects the peptide synthesis of pathogen bacteria [J Hughes and G Mellows, Biochem. J. 191, 209-219 (1980)]. An advantageous feature of this antibiotic is that it has very low toxicity both for humans and animals and it is negative in the Ames test Pseudomonic acid A is presently used in human therapy, in various formulations, for the treatment of skin infections (e.g. impetigo, pyoderma), nose and external ear infections, acne, burns, eczema, psoriasis, in case of ulceration for treatment of secondary infections, and for prevention of hospital infections. It is known that Pseudomonas fluorescens is able to produce the pseudomonic acid A. According to the British Patent No. 1,395,907, the Pseudomonas fluorescens NCIB 10586 strain is able to biosynthesize the pseudomonic acid complex consisting of pseudomonic acid A and its isomer being a double bond in the cis position between the carbon atoms C.sub.2 and C.sub.3 and pseudomonic acid B. The ratio of the components is 4 5.4 5.1. According to the Japanese patent application No. 52-70083, however, the Pseudomonas fluorescens Y11633 strain is able to biosynthesize the pseudomonic acid complex consisting of the pseudomonic acid A, pseudomonic acid B and further two components with unknown structures in the ratio of 9:0.5.0.5. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pseudomonas Avr and Hop proteins, their encoding nucleic acids, and use thereof Inventor(s): Alfano, James R.; (Lincoln, NE), Buell, C. Robin; (Olney, MD), Collmer, Alan; (Ithaca, NY), Martin, Gregory B.; (Ithaca, NY), Tang, Xiaoyan; (Manhattan, KS) Correspondence: Michael L. Goldman; Nixon Peabody Llp; Clinton Square; P.O. Box 31051; Rochester; NY; 14603-1051; US Patent Application Number: 20030182681 Date filed: April 2, 2002 Abstract: One aspect of the present invention relates to isolated nucleic acid molecules encoding avirulence proteins or polypeptides of Pseudomonas syringae pv. syringae DC 3000, or nucleic acid molecules which are complementary thereto. Expression vectors, host cells, and transgenic plants which include the DNA molecules of the present invention are also disclosed. Another aspect relates to the isolated proteins or polypeptides and compositions containing the same. The nucleic acid molecules and proteins of the present invention can be used to impart disease resistance to a plant. Excerpt(s): This application claims benefit of U.S. Provisional Patent Application Serial Nos. 60/280,918, filed Apr. 2, 2001, and No. 60/356,408, filed Feb. 12, 2002, each of which is hereby incorporated by reference in its entirety. The present invention relates to isolated DNA molecules corresponding to the open reading frames of Pseudomonas syringae pv. tomato DC3000, the isolated avirulence effector proteins and hrp-

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dependent outer proteins encoded thereby, as well as their various uses. The plant pathogenic bacterium Pseudomonas syringae is noted for its diverse and host-specific interactions with plants. A specific strain may be assigned to one of at least 40 pathovars based on its host range among different plant species and then further assigned to a race based on differential interactions among cultivars of the host. In host plants the bacteria typically grow to high population levels in leaf intercellular spaces and then produce necrotic lesions. In nonhost plants or in host plants with race-specific resistance, the bacteria elicit the hypersensitive response (HR), a rapid, defense-associated programmed death of plant cells in contact with the pathogen (Alfano & Collmer, J. Bacteriol. 179:5655-5662 (1997)). The ability to produce either of these reactions in plants appears to be directed by hrp (HR and pathogenicity) and hrc (HR and conserved) genes that encode a type III protein secretion pathway and by avr (avirulence) and hop (Hrpdependent outer protein) genes that encode effector proteins injected into plant cells by the pathway (Alfano & Collmer, J. Bacteriol. 179:5655-5662 (1997)). These effectors may also betray the parasite to the HR-triggering R-gene surveillance system of potential hosts (hence the avr designation), and plant breeding for resistance based on such genefor-gene (avr-R) interactions may produce complex combinations of races and differential cultivars (Keen, Annu. Rev. Genet. 24:447-463 (1990)). hrp/hrc genes are probably universal among necrosis-causing gram-negative plant pathogens, and they have been sequenced in P. syringae pv. syringae (Psy) 61, Erwinia amylovora Ea321, Xanthomonas campestris pv. vesicatoria (Xcv) 85-10, and Ralstonia solanacearum GMI1000 (Alfano & Collmer, J. Bacteriol. 179:5655-5662 (1997)). Based on their distinct gene arrangements and regulatory components, the hrp/hrc gene clusters of these four bacteria can be divided into two groups: I (Pseudomonas and Erwinia) and II (Xanthomonas and Ralstonia). The discrepancy between the distribution of these groups and the phylogeny of the bacteria provides some evidence that hrp/hrc gene clusters have been horizontally acquired and, therefore, may represent pathogenicity islands (Pais) (Alfano & Collmer, J. Bacteriol. 179:5655-5662 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

PSEUDOMONAS EXOTOXIN A-LIKE CHIMERIC IMMUNOGENS ELICITING A SECRETORY IGA-MEDIATED IMMUNE RESPONSE

FOR

Inventor(s): FITZGERALD, DAVID J.; (ROCKVILLE, MD), MRSNY, RANDALL J.; (REDWOOD CITY, CA) Correspondence: Townsend And Townsend And Crew Llp; Two Embarcadero Center; 8th Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030054012 Date filed: May 12, 2000 Abstract: This invention provides methods of eliciting a secretry IgA-mediated immune response in a subject by administering a Pseudomonas exotoxin A-like chimeric immunogens that include a non-native epitope in the Ib domain of Pseudomonas exotoxin. Compositions comprising secretory IgA antibodies that specifically recognize an epitope of HIV-1 also are provided Excerpt(s): This application claims the benefit of the filing date of co-pending application 60/056,924, filed Jul. 11, 1997, the content of which is incorporated herein by reference in its entirety. This invention is directed to the fields of chimeric proteins and immunology. Immunization against infectious disease has been one of the great achievements of modern medicine. Vaccines can be useful only if the vaccine, itself, is

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not significantly pathogenic. Many vaccines are produced by inactivating the pathogen. For example, hepatitis vaccines can be made by heating the virus and treating it with formaldehyde. Other vaccines, for example certain polio vaccines, are produced by attenuating a live pathogen. However, there is concern about producing attenuated vaccines for certain infectious agents whose pathology is not fully understood, such as HIV. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pseudomycins useful against plant diseases Inventor(s): Rodriguez, Michael J.; (Indianapolis, IN), Strobel, Gary A; (Bozeman, MT) Correspondence: Mcdermott Will & Emery; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20040029797 Date filed: August 18, 2003 Abstract: Plants and crops subject to attack by fungal related diseases are protected or treated by the application of Pseudomycin compositions which were originally isolated from Pseudomonas syringae. Excerpt(s): The present invention relates to the use of pseudomycins as effective fungicides against plant and crop diseases, and more particularly relates to the use of pseudomycins against particular classes of fungi which cause diseases in plants and crops. The present invention provides a group of pseudomycins which are particularly useful to protect plants and crops against fungal diseases. It is an object of the present invention to provide a method for the treatment or protection of plants and crops against diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Salicylaldehyde-containing composition having antimicrobial and fragrancing properties and process for using same Inventor(s): White, Michael John Robert; (Amsterdam, NL), De Meijere, Remco Johannes Hendrik; (Huizen, NL), Deans, Stanley G.; (South Ayrshire, GB), Lis-Balchin, Maria Therese; (London, GB), Simpson, Elisabeth J. M.; (South Ayrshire, GB) Correspondence: Joseph F. Leightner, ESQ.; International Flavors & Fragrances INC.; 521 West 57th Street; New York; NY; 10019; US Patent Application Number: 20030156975 Date filed: November 8, 2002 Abstract: Described are synergistic antimicrobial-fragrance compositions including broad spectrum antimicrobial compositions containing salicylaldehyde and at least one organoleptically-compatible antimicrobial synergism cofactor substance. The weight ratio range of salicylaldehyde:synergism cofactors substance is from 1:10 up to 10:1. The cofactor substance is such that the degree of synergism of the resultant mixture is defined according to the IFF Antimicrobial Synergism Test wherein the difference between the actual and expected antimicrobial values of the mixture is greater than or equal to a multiple of (i) 0.05 and (ii) the expected antimicrobial value of the mixture. Cofactor substances include phenolics such as cresol, caravacrol and thymol; ethyl

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vanillin; benzyl alcohol; indol;.beta.-orcinol; and terpinenol-4. Microorganisms against which the synergistic compositions are effective include:Escherichia coli;Enterococcus hirae;Pseudomonas aeruginosa;Staphylococcus aureus; andSaccharomyces cerevisae.The compositions have application in all-purpose cleaning compositions, geltype toilet rim articles, liquid-type toilet rim articles, personal shower cleaning compositions, and body and hair care products including shower gel compositions, shampoo compositions and foam bath compositions. Excerpt(s): The present invention relates to fragrance compositions exhibiting antimicrobial activity with a hedonically acceptable odor. The present invention also relates to antimicrobial-flavor compositions which are capable of eliminating one or more microorganisms from a solid or semisolid surface (e.g., skin) or a three-space inhabited by said microorganisms, which compositions include salicylaldehyde and at least one organoleptically compatible antimicrobial synergism cofactor substance. The prior art, including U.S. Pat. No. 5,965,518 issued on Oct. 12, 1999, the specification for which is incorporated by reference herein, indicates that fragrances having antimicrobial activity may comprise between 3 up to 20% by weight of non-aromatic terpenoids. U.S. Pat. No. 5,965,518 further indicates that the fragrance composition may also, either alternatively or additionally, include essential oils containing phenoic compounds as a major constituent and/or essential oils containing non-aromatic terpenoids as the main constituent. U.S. Pat. No. 5,965,518 further indicates that the fragrance composition further has an odor intensity index of less than 100 and an odor evaluation acceptability index of greater than 50. Fragrances are commonly incorporated in a wide variety of household and industrial items, for example, counterwipes and cleansers, in order to impart a pleasing odor to a solid or semisolid surface or a three-space. A number of fragrances have been reported to have weak bacteria static activity. However, this activity has been ascertained to be too low to be of practical use. To overcome this weak activity and achieve antimicrobial fragrances of practical use either as bacteria static agents and preservatives or as bacteriacidal agents and sanitizers and disinfectants, combinations of fragrance materials with other materials are employed. For example, fragrances have been combined with a cationic phospholipid as taught in U.S. Pat. No. 5,420,104; and fragrances have been combined with a preservative and surface active agent as taught in U.S. Pat. No. 5,306,707. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Specific and universal probes and amplification primers to rapidly detect and identify common bacterial pathogens and antibiotic resistance genes from clinical specimens for routine diagnosis in microbiology laboratories Inventor(s): Bergeron, Michel G.; (Sillery, CA), Ouellette, Marc; (Quebec, CA), Roy, Paul H.; (Loretteville, CA) Correspondence: Quarles & Brady Llp; 411 E. Wisconsin Avenue; Suite 2040; Milwaukee; WI; 53202-4497; US Patent Application Number: 20030180733 Date filed: April 11, 2002 Abstract: The present invention relates to DNA-based methods for universal bacterial detection, for specific detection of the common bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Staphylococcus saprophyticus, Streptococcus pyogenes, Haemophilus influenzae and

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Moraxella catarrhalis as well as for specific detection of commonly encountered and clinically relevant bacterial antibiotic resistance genes directly from clinical specimens or, alternatively, from a bacterial colony. The above bacterial species can account for as much as 80% of bacterial pathogens isolated in routine microbiology laboratories.The core of this invention consists primarily of the DNA sequences from all species-specific genomic DNA fragments selected by hybridization from genomic libraries or, alternatively, selected from data banks as well as any oligonucleotide sequences derived from these sequences which can be used as probes or amplification primers for PCR or any other nucleic acid amplification methods. This invention also includes DNA sequences from the selected clinically relevant antibiotic resistance genes.With these methods, bacteria can be detected (universal primers and/or probes) and identified (species-specific primers and/or probes) directly from the clinical specimens or from an isolated bacterial colony. Bacteria are further evaluated for their putative susceptibility to antibiotics by resistance gene detection (antibiotic resistance gene specific primers and/or probes). Diagnostic kits for the detection of the presence, for the bacterial identification of the above-mentioned bacterial species and for the detection of antibiotic resistance genes are also claimed. These kits for the rapid (one hour or less) and accurate diagnosis of bacterial infections and antibiotic resistance will gradually replace conventional methods currently used in clinical microbiology laboratories for routine diagnosis. They should provide tools to clinicians to help prescribe promptly optimal treatments when necessary. Consequently, these tests should contribute to saving human lives, rationalizing treatment, reducing the development of antibiotic resistance and avoid unnecessary hospitalizations. Excerpt(s): Bacteria are classically identified by their ability to utilize different substrates as a source of carbon and nitrogen through the use of biochemical tests such as the API20E.TM. system. Susceptibility testing of Gram negative bacilli has progressed to microdilution tests. Although the API and the microdilution systems are cost-effective, at least two days are required to obtain preliminary results due to the necessity of two successive overnight incubations to isolate and identify the bacteria from the specimen. Some faster detection methods with sophisticated and expensive apparatus have been developed. For example, the fastest identification system, the autoSCAN-Walk-Away system.TM. identifies both Gram negative and Gram positive from isolated bacterial colonies in 2 hours and susceptibility patterns to antibiotics in only 7 hours. However, this system has an unacceptable margin of error, especially with bacterial species other than Enterobacteriaceae (York et al., 1992. J. Clin. Microbiol. 30:2903-2910). Nevertheless, even this fastest method requires primary isolation of the bacteria as a pure culture, a process which takes at least 18 hours if there is a pure culture or 2 to 3 days if there is a mixed culture. A large proportion (40-50%) of specimens received in routine diagnostic microbiology laboratories for bacterial identification are urine specimens (Pezzlo, 1988, Clin. Microbiol. Rev. 1:268-280). Urinary tract infections (UTI) are extremely common and affect up to 20% of women and account for extensive morbidity and increased mortality among hospitalized patients (Johnson and Stamm, 1989; Ann. Intern. Med. 111:906-917). UTI are usually of bacterial etiology and require antimicrobial therapy. The Gram negative bacillus Escherichia coli is by far the most prevalent urinary pathogen and accounts for 50 to 60% of UTI (Pezzlo, 1988, op. cit.). The prevalence for bacterial pathogens isolated from urine specimens observed recently at the "Centre Hospitalier de 1'Universit Laval (CHUL)" is given in Tables 1 and 2. Conventional pathogen identification in urine specimens. The search for pathogens in urine specimens is so preponderant in the routine microbiology laboratory that a myriad of tests have been developed. The gold standard is still the classical semi-quantitative plate culture method in which a calibrated loop of urine is streaked on plates and incubated for 18-24 hours.

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Colonies are then counted to determine the total number of colony forming units (CFU) per liter of urine. A bacterial UTI is normally associated with a bacterial count of.gtoreq.10.sup.7 CFU/L in urine. However, infections with less than 10.sup.7 CFU/L in urine are possible, particularly in patients with a high incidence of diseases or those catheterized (Stark and Maki, 1984, N. Engl. J. Med. 311:560-564). Importantly, close to 80% of urine specimens tested are considered negative (<10.sup.7 CFU/L; Table 3). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Th1 inducing natural adjuvant for heterologous antigens Inventor(s): Baetselier, Patrick De; (Berchem, BE), Cornelis, Pierre; (Elsene, BE), Revets, Hilde; (Meise, BE) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030059439 Date filed: August 16, 2002 Abstract: The present invention relates to the use of the major OprI lipoprotein of Pseudomonas aeruginosa to elicit a Type-1 immune response towards a heterologous antigen. The invention relates specifically to the use of OprI--antigen fusion proteins to elicit the Type-1 response. More particularly, the present invention is directed to pharmaceutical formulations comprising OprI and/or OprI fusion proteins, optionally together with a suitable excipient, to stimulate the Th1 dependent, cellular immune response. Excerpt(s): This patent application is a continuation of International Application Number PCT/EP01/01673, filed on Feb. 18, 2000 designating the United States of America, corresponding to International Publication No. WO 01/60404 (Aug. 23, 2001), published in English, the contents of the entirety of which is incorporated by this reference. Upon T-Cell Receptor (TCR) ligation, ThO cells differentiate into distinct subsets characterized by their functions and cytokine production profiles (Mosmann and Coffinan, 1989). Th1 lymphocytes, characterized by the production of IL-2, IFN.gamma. and TNF-.beta., contribute to cellular immunity whereas Th2 lymphocytes, producing IL-4, IL-5 and IL-10, are mainly involved in humoral immunity. The generation of cell-mediated immunity against many infectious pathogens relies on the induction of the innate immune system, which in turn generates appropriate signals for adaptive immune responses (Fearon and Locksley, 1996). Bacterial lipoproteins are, among others, molecules that stimulate cells of the innate immune system to produce cytokines such as TNF-.alpha. (Radolf et al., 1991; Vidal et al., 1998) and IL-12 (Brightbill et al., 1999). Hereby, bacterial lipoproteins activate innate immune cells via Toll-like receptors (Brightbill et al., 1999; Aliprantis et al., 1999) and their signaling activity resides in the NH2-terminal triacylated lipopeptide region (Erdile et al., 1993; Weis et al., 1994). The potent capacity of bacterial lipoproteins and/or lipopeptides to induce the production of IL-12 (Brightbill et al., 1999), a key signal of the innate immune system, may in turn trigger the development of adaptive immune responses. Numerous examples ofthe consequences on disease outcome of skewed Th1 to Th2 ratios have been reported. Polarized Th2 responses have been implicated in pathological situations, such as Leishmania major infection (Heinzel et al., 1991; Nabors et al., 1995), tuberculosis (TBC) (de Jong et al., 1997), human leprosy (Yamamura et al., 1991) and mycotic infections (Murphy et al., 1994). The contribution of Th1 cells relative to Th2 cells to the developing autoimmune response determines for a larger part whether or not this response leads to clinical disease (Racke et al., 1994; Racke et al., 1995; Leonard et al.,

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1995). In allergic asthma, a predominant Th2-type response has been noted (Vogel, 1997). Also the chronic autoimmune graft-versus-host disease, which develops after the administration of mismatched lymphoid cells, can be prevented by switching a Th2 response to a Th1 response through administration of IFN-.gamma. at the time of cellular transfer (Donckier et aL, 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of Emu Oil and its various fractions as a carrier for antifungal, antibacterial, and antiviral medications & preparations Inventor(s): Farmer, Sean; (La Jolla, CA) Correspondence: Mintz, Levin, Cohn, Ferris, Glovsky; And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030170334 Date filed: March 10, 2003 Abstract: An animal-derived lipid is disclosed that is useful as a carrying agent for antimicrobial formulations. Pharmaceutical and other preparations including Emu Oil are also described as profoundly useful components in anti-bacterial, anti-fungal, and antiviral treatments. This lipid material is extracted from the Emu (Dromais NovaeHollandiae), an indigenous bird of Australia and New Zealand. The present invention also discloses therapeutic compositions comprising Emu Oil in combination with an extracellular product of Bacillus coagulans or Pseudomonas lindbergii strain, comprising a supernatant or filtrate of said culture suitable for topical application to the skin or mucosal membranes of a mammal, which are utilized to inhibit the growth of bacterium, yeast, fungi, virus, and combinations thereof. Additionally, the aforementioned therapeutic composition may also include an anti-microbial, antimycotic, and/or anti-viral agent. The present invention also discloses methods of treatment and therapeutic systems for inhibiting the growth of bacterium, yeast, fungi, virus, and combinations thereof, by topical application of therapeutic compositions comprising Emu Oil in combination with an extracellular product of Bacillus coagulans or Pseudomonas lindbergii strain suitable for topical application to the skin or mucosal membranes of a mammal. Similarly, the aforementioned method may also employ a therapeutic composition additionally containing an anti-microbial, anti-mycotic, and/or anti-viral agent. Excerpt(s): The present invention relates to compositions and methods of use for the treatment of bacterial, fungal, and viral infections of the dermis and cuticle. More specifically, the present invention relates to compositions and methods of use of Emu Oil, and it various associated fractions, in combination with the appropriate medicaments, in the treatment of bacterial, fungal, and viral infections of the dermis and cuticle. The present invention also relates to the utilization of therapeutic compositions comprised of Emu Oil in combination with a probiotic, viable Bacillus bacteria, spores, and extracellular supernatant products, as well as the extracellular product of Pseudomonas lindbergii, as a topical agent for the prevention and/or control of infections caused by bacterium, fungi, yeast, and virus, and combinations thereof. Emu Oil, is an animal-derived lipid composition, extracted from the Emu (Dromais NovaeHollandiae), a flightless bird part of a group called ratites (which also includes the ostrich and the kiwi), indigenous to Australia and New Zealand. Emu Oil is extracted from a thick fat-pad on the back of the bird which putatively functions to protect the animal from the extreme temperatures in its Australian homeland. The fat is carefully

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extracted to prevent the formation of trans-fatty acids, wherein approximately 100 pounds of fat produces approximately 50 to 90 pounds of unrefined, pale yellow oil. The chemical composition and characteristics of Emu Oil has been quantitatively ascertained and is set forth below in Table I. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vaccine for Pseudomonas aeruginosa Inventor(s): Cachia, Paul J.; (Edmonton, CA), Hodges, Robert S.; (Edmonton, CA), Irvin, Randall T.; (Sherwood Park, CA) Correspondence: Bell, Boyd & Lloyd Llc; P.O. Box 1135; Chicago; IL; 60690-1135; US Patent Application Number: 20030211114 Date filed: January 14, 2003 Abstract: A C-terminal pilin peptide vaccine for immunizing or treating a patient for infection by a Pseudomonas aeruginosa (PA) infection is disclosed. The peptide comprises the peptide identified as SEQ ID NOS. 3-6; and a carrier protein conjugated to the peptide. Also disclosed is a pilin peptide C-terminal PA pilin peptide having the amino acid sequence identified as SEQ ID NO: 3, and analogs thereof having one of residues T, K, or A at position 130, D, T, or N at position 132, Q, A, or V at position 133, E, P, N, or A at position 135, Q, M, or K at position 136, and I, T, L, or R at position 138, excluding SEQ ID NOS: 1, 2, 9, 10, and 11, and the ability to cross-react with antibodies against the corresponding C-terminal peptides from PA strains PAK and PAO. Excerpt(s): The present application claims priority to U.S. provisional application 60/084,444, filed May 6, 1998, and U.S. patent application Ser. No. 09/306,241, filed May 6, 1999, which are hereby incorporated by reference. The present invention relates to a vaccine for Pseudomonas aeruginosa, and in particular to novel vaccine peptides. 1. Irvin, R. T., "Attachment and colonization of Pseudomonas aeruginosa: Role of the surface structures", in PSEUDOMONAS AERUGINOSA AS AN OPPORTUNISTIC PATHOGEN, (Campa, M., M. Bendinelli, and H. Friedman, Eds.), pp 19-42, Plenum Press, New York (1993). 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 pseudomonas, 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 “pseudomonas” (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 pseudomonas. You can also use this procedure to view pending patent applications concerning pseudomonas. 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 PSEUDOMONAS Overview This chapter provides bibliographic book references relating to pseudomonas. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on pseudomonas 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: 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 “pseudomonas” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “pseudomonas” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “pseudomonas” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Bacterial Wilt: The Disease and Its Causative Agent, Pseudomonas Solanacearum by A. C. Hayward (Editor), et al; ISBN: 085198875X; http://www.amazon.com/exec/obidos/ASIN/085198875X/icongroupinterna

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Bakterii roda Pseudomonas by V. V. Smirnov; ISBN: 5120016103; http://www.amazon.com/exec/obidos/ASIN/5120016103/icongroupinterna

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Characteristics of IS401, a new member of the IS3 family implicated in plasmid rearrangements in pseudomonas cepacia (SuDoc EP 1.23/6:600/J-94/447) by Armando M. Byrne; ISBN: B00010NQ7S; http://www.amazon.com/exec/obidos/ASIN/B00010NQ7S/icongroupinterna

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COM (97) 15 Final, Brussels, 29.01.1997 - 97/0025 (CNS): 03 - Agriculture, Silviculture and Fisheries: Proposal for a Council Directive on the Control of Pseudomonas Solanacearum (Smith) Smith (COM (97) 15 Final, Brussels, 29.01.1997 - 97/0025 (CNS));

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ISBN: 9278150428; http://www.amazon.com/exec/obidos/ASIN/9278150428/icongroupinterna •

Genetics and Biochemistry of Pseudomonas by Patricia H. Clarke, Mark H. Richmond; ISBN: 0471158968; http://www.amazon.com/exec/obidos/ASIN/0471158968/icongroupinterna

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Molecular Biology of Pseudomonads by Teruko Nakazawa (Editor), et al; ISBN: 1555811043; http://www.amazon.com/exec/obidos/ASIN/1555811043/icongroupinterna

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Multiple replicons constituting the genome of pseudomonas cepacia 17616 (SuDoc EP 1.23/6:600/J-94/446) by Hai-Ping Cheng; ISBN: B00010NPOW; http://www.amazon.com/exec/obidos/ASIN/B00010NPOW/icongroupinterna

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Physiological properties and substrate specificity of a pentachlorophenol-degrading Pseudomonas species (SuDoc EP 1.23/6:600/J-94/444) by Sol M. Resnick; ISBN: B00010NK9W; http://www.amazon.com/exec/obidos/ASIN/B00010NK9W/icongroupinterna

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Pseudomonas by Thomas C. Montie (Editor); ISBN: 0306458497; http://www.amazon.com/exec/obidos/ASIN/0306458497/icongroupinterna

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Pseudomonas by Juan-Luis Ramos (Editor); ISBN: 0306483750; http://www.amazon.com/exec/obidos/ASIN/0306483750/icongroupinterna

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Pseudomonas diagnostic assay patent application (SuDoc NAS 1.71:NPO-17653-1-CU) by NASA; ISBN: B00010DZTM; http://www.amazon.com/exec/obidos/ASIN/B00010DZTM/icongroupinterna

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Pseudomonas Infection and Alginates: Biochemistry, Genetics, and Pathology by P. Gacesa, N.J. Russell (Editor); ISBN: 0412358409; http://www.amazon.com/exec/obidos/ASIN/0412358409/icongroupinterna

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Pseudomonas: Biotransformations, Pathogenesis, and Evolving Biotechnology by Simon Silver, et al; ISBN: 1555810195; http://www.amazon.com/exec/obidos/ASIN/1555810195/icongroupinterna

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Pseudomonas: Molecular Biology and Biotechnology by Enrica Galli, et al; ISBN: 1555810519; http://www.amazon.com/exec/obidos/ASIN/1555810519/icongroupinterna

•

Pulmonary exposure of mice to "engineered" pseudomonads influences intestinal microbiota populations (SuDoc EP 1.23/6:600/J-94/036) by U.S. Environmental Protection Agency; ISBN: B00010J14K; http://www.amazon.com/exec/obidos/ASIN/B00010J14K/icongroupinterna

•

The Bacteria: A Treatise on Structure and Function: The Biology of Pseudomonas by L. Nicholas Ornston, et al; ISBN: 0123072107; http://www.amazon.com/exec/obidos/ASIN/0123072107/icongroupinterna

•

The Pseudomonas Group (Patterns of Progress) by N.J. Palleroni; ISBN: 0904095282; http://www.amazon.com/exec/obidos/ASIN/0904095282/icongroupinterna

Chapters on Pseudomonas In order to find chapters that specifically relate to pseudomonas, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search

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to book chapters and pseudomonas 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 “pseudomonas” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on pseudomonas: •

Oral Bacterial Infections Source: in Eisen, D. and Lynch, D.P. Mouth: Diagnosis and Treatment. St. Louis, MO: Mosby, Inc. 1998. p. 92-107. Contact: Available from Harcourt Health Sciences. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St. Louis, MO 63146-9988. Website: www.mosby.com. PRICE: $79.95 plus shipping and handling. ISBN: 0815131054. Summary: More than 300 different bacteria, including Staphylococcus aureus, coliform bacteria, Kelsiella, and Pseudomonas, reside in the oral cavity and comprise what is regarded as normal oral flora. When a species of bacteria increases in number or when the host defense threshold is exceeded, disease arises. Two of the most common bacterial diseases that afflict humans are dental caries and periodontal disease. This chapter on oral bacterial infections is from a textbook on the mouth that offers information to primary care physicians and to many specialists in medicine and dentistry. Topics include gingivitis and periodontitis, necrotizing gingivostomatitis, tuberculosis, oral cutaneous fistulas, gonorrhea, syphilis, actinomycosis, parulis, and miscellaneous infections, including scarlet fever, diphtheria, tularemia, granuloma inguinale, leprosy, suppurative infection of the salivary glands, and noma. For each condition, the authors describe symptoms, identification, complications, and treatment. The chapter is illustrated with numerous full color photographs of the conditions under discussion. 19 figures. 46 references.

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

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

Human enzyme produced by Pseudomonas aeruginosa Source: Reuters Industry Breifing Date: February 03, 2004

•

Pseudomonas outbreak linked to bronchoscope defect Source: Reuters Medical News Date: January 15, 2003

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Monoclonal antibody increases survival from Pseudomonas in mice Source: Reuters Medical News Date: July 16, 2002

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Antimicrobial peptide active against Pseudomonas-infected burn wounds Source: Reuters Medical News Date: May 21, 2002

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DNase I prevents formation of Pseudomonas biofilm Source: Reuters Medical News Date: February 21, 2002

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Downregulated gene in Pseudomonas biofilm increases tobramycin resistance Source: Reuters Medical News Date: October 24, 2001

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Cystic fibrosis patients are susceptible to pseudomonas cross-infection Source: Reuters Medical News Date: August 16, 2001

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Outbreak of "Pseudomonas hot-foot syndrome" traced to wading pool Source: Reuters Medical News Date: August 02, 2001

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Pseudomonas aeruginosa often present by age 3 in children with CF Source: Reuters Medical News Date: February 12, 2001

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Pseudomonal coverage key in preventing fulminant late-onset neonatal sepsis Source: Reuters Medical News Date: December 12, 2000

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Pseudomonas aeruginosa genome surprisingly large and complex Source: Reuters Medical News Date: September 05, 2000

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Pseudomonas pneumonia increases in hospitalized HIV-infected patients Source: Reuters Medical News Date: May 08, 2000

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Clavulanate antagonizes ticarcillin in clinical isolates of Pseudomonas aeruginosa Source: Reuters Medical News Date: May 04, 1999

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Immunization technique may succeed against Pseudomonas aeruginosa Source: Reuters Medical News Date: March 31, 1999

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Genome Therapeutics Sequences Pseudomonas Aeruginosa Source: Reuters Medical News Date: March 30, 1998 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

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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 “pseudomonas” (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 “pseudomonas” (or synonyms). If you know the name of a company that is relevant to pseudomonas, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “pseudomonas” (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 “pseudomonas” (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 pseudomonas:

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•

Body Piercing and Branding Are the Latest Fads Source: Skin and Allergy News. 30(12): 27. December 1999. Contact: Available from Skin and Allergy News, Circulation. 12230 Wilkins Avenue, Rockville, MD 20852. (301) 816-8796. Summary: This newsletter article provides health professionals with information on the safety of body piercing and branding. One dermatologist who has studied various forms of body decorations for over 35 years believes that most people who have body art do not experience any problems. Nickel allergy does occur but is not all that common. Bacterial infections from Staphylococcus aureus and Streptococcus seem to cause most problems. Another type of infection common in patients who have body piercings is Pseudomonas. Colonization of this bacteria can liquify ear cartilage and may require treatment with intravenous antibiotics. Candidal infections commonly affect piercings of the navel. Infections are more likely to occur in moist areas such as the genitalia and the nose, mouth piercings rarely become infected. Umbilicus piercings are more prone to infection if exposed to friction. Infections can also occur from trauma-induced tears. Problems are more likely to arise if the piercing is done by an unqualified person. The newest symbols of teenage rebellion are branding and scarification. The latter involves cutting a design into the skin and placing sand or another agent in the wound to promote the formation of a keloid. Branding is performed using a branding iron with initials or some other design on a tip that is heated using an acetylene torch. 6 figures.

Academic Periodicals covering Pseudomonas Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to pseudomonas. In addition to these sources, you can search for articles covering pseudomonas that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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

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

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to pseudomonas by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “pseudomonas” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

Researching Medications 245

marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for pseudomonas: •

Mucoid esopolysaccharide Pseudomonas hyperimmune g (trade name: MEPIG) http://www.rarediseases.org/nord/search/nodd_full?code=166

•

Tobramycin for inhalation (trade name: TOBI) http://www.rarediseases.org/nord/search/nodd_full?code=62

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

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

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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/

11

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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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.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

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

•

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

•

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

•

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

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

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

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

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

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

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

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “pseudomonas” (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 62358 165 890 280 317 64010

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “pseudomonas” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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 pseudomonas 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 pseudomonas. 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 pseudomonas. 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 “pseudomonas”:

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Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Cystic Fibrosis http://www.nlm.nih.gov/medlineplus/cysticfibrosis.html Immune System and Disorders http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html Phenylketonuria http://www.nlm.nih.gov/medlineplus/phenylketonuria.html Sepsis http://www.nlm.nih.gov/medlineplus/sepsis.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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “pseudomonas” (or synonyms). The following was recently posted: •

ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery Source: American Society of Health-System Pharmacists - Professional Association; 1999 September 15; 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2182&nbr=1408&a mp;string=pseudomonas

•

Care of the contact lens patient Source: American Optometric Association - Professional Association; 2000; 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2603&nbr=1829&a mp;string=pseudomonas

•

Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2002 October; 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3484&nbr=2710&a mp;string=pseudomonas

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Guideline for the management of intravascular catheter-related infections Source: American College of Critical Care Medicine - Professional Association; 2001 May; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2790&nbr=2016&a mp;string=pseudomonas

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Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients Source: American Society for Blood and Marrow Transplantation - Professional Association; 2000 October 20; 126 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2573&nbr=1799&a mp;string=pseudomonas

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Guidelines for the management of leg ulcers in Ireland Source: Smith and Nephew, Ltd. - Private For Profit Organization; 2002; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3616&nbr=2842&a mp;string=pseudomonas

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Guidelines for the prevention of intravascular catheter-related infections Source: American Academy of Pediatrics - Medical Specialty Society; 1996 (revised 2002 August 9); 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3387&nbr=2613&a mp;string=pseudomonas

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Infection control in physicians' offices Source: American Academy of Pediatrics - Medical Specialty Society; 2000 June; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2769&nbr=1995&a mp;string=pseudomonas

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Practice guidelines for the management of community-acquired pneumonia in adults Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 February; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2665&nbr=1891&a mp;string=pseudomonas 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

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in some way to pseudomonas. 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

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

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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

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

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WebMDHealth: http://my.webmd.com/health_topics

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

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To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “pseudomonas” (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 “pseudomonas”. 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 “pseudomonas” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “pseudomonas” (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.22

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

22

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)23: •

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)

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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

23

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

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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

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

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

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

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

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

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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

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

•

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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PSEUDOMONAS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinobacillus: A genus of Pasteurellaceae described as gram-negative, nonsporeforming, nonmotile, facultative anaerobes. Most members are found both as pathogens and commensal organisms in the respiratory, alimentary, and genital tracts of animals. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine

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derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [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] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] 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] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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] Agrobacterium: A genus of gram-negative, aerobic, rod-shaped bacteria found in soil, plants, and marine mud. With the exception of Agrobacterium radiobacter, members of this genus invade the crown, roots, and stems of plants, via wounds, causing the transformation of the plant cells into proliferating tumor cells (plant tumors). [NIH] Agrochemicals: Chemicals used in agriculture. These include pesticides, fumigants, fertilizers, plant hormones, steroids, antibiotics, mycotoxins, etc. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure

Dictionary 271

and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alcaligenes: A genus of gram-negative, aerobic, motile bacteria that occur in water and soil. Some are common inhabitants of the intestinal tract of vertebrates. These bacteria occasionally cause opportunistic infections in humans. [NIH] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [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,

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magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]

Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Compounds: Inorganic and organic compounds that contain the hypothetical radical NH4. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH]

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Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amylases: A group of amylolytic enzymes that cleave starch, glycogen, and related alpha1,4-glucans. (Stedman, 25th ed) EC 3.2.1.-. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH]

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Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Anthropogenic: Of human origin or influence. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiosis: A property of microorganisms which enables one microorganism to kill, injure, or inhibit the growth of a different microorganism. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms

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without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord.

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Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Aztreonam: A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with grampositive organisms. [NIH] 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] Bacillus subtilis: A species of gram-positive bacteria that is a common soil and water saprophyte. [NIH] Bacteraemia: The presence of bacteria in the blood. [EU] 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 Adhesion: Physicochemical property of fimbriated and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. [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] Bacterial Translocation: The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal

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sepsis. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriocins: Substances elaborated by specific strains of bacteria that are lethal against other strains of the same or related species. They are protein or lipopolysaccharide-protein complexes used in taxonomy studies of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [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] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Baths: The immersion or washing of the body or any of its parts in water or other medium for cleansing or medical treatment. It includes bathing for personal hygiene as well as for medical purposes with the addition of therapeutic agents, such as alkalines, antiseptics, oil, etc. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Lactam Resistance: Nonsusceptibility of an organism to the action of the beta-lactam

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antibiotics. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] 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] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of

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bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] Bombesin: A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. [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

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of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] 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] 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] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchoscope: A thin, lighted tube used to examine the inside of the trachea and bronchi, the air passages that lead into the lungs. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burkholderia: A genus of gram-negative, aerobic, rod-shaped bacteria. Organisms in this genus had originally been classified as members of the Pseudomonas genus but overwhelming biochemical and chemical findings indicated the need to separate them from other Pseudomonas species, and hence, this new genus was created. [NIH] Burkholderia cepacia: A species of Burkholderia considered to be an opportunistic human pathogen. It has been associated with various types of infections of nosocomial origin. [NIH]

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Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] 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] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbapenems: A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. [NIH]

Carbenicillin: Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carbon Disulfide: A colorless, flammable, poisonous liquid, CS2. It is used as a solvent, and is a counterirritant and has local anesthetic properties but is not used as such. It is highly toxic with pronounced CNS, hematologic, and dermatologic effects. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU]

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Carcinogenicity: The ability to cause cancer. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiotoxicity: Toxicity that affects the heart. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [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] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell 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 Movement: The movement of cells from one location to another. [NIH]

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Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [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] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] 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 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]

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Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] Chlorobenzoates: Benzoic acid or benzoic acid esters substituted with one or more chlorine atoms. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] 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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chorismate Mutase: An isomerase that catalyzes the conversion of chorismic acid to prephenic acid. EC 5.4.99.5. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from

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the small intestines to the tissues. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cicatrix, Hypertrophic: An elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [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] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Claviceps: A genus of ascomycetous fungi, family Clavicipitaceae, order Hypocreales, parasitic on various grasses. The sclerotia contain several toxic alkaloids. Claviceps purpurea on rye causes ergotism. [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, prevention, diagnosis, or treatment of a disease. [NIH] Cloaca: The common chamber into which the intestinal, urinary, and genital tracts discharge in birds, reptiles, amphibians and many fishes; also a phylogenetically related embryonic structure in mammals. [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]

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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] 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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coal Tar: A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed). [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Coliphages: Viruses whose host is Escherichia coli. [NIH] Colistin: Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU]

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Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] 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] 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 Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU]

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Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [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] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [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] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH]

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Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corrosion: Irreversible destruction of skin tissue. [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] Cross Infection: Any infection which a patient contracts in a healthcare institution. [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] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cutaneous Fistula: An abnormal passage or communication leading from an internal organ to the surface of the body. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cyst: A sac or capsule filled with fluid. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH]

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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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]

Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] 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

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protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Instruments: Hand-held tools or implements especially used by dental professionals for the performance of clinical tasks. [NIH] Dental Materials: Materials used in the production of dental bases, restorations, impressions, prostheses, etc. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]

Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desmosine: 4-(4-Amino-4-carboxybutyl)-1-(5-amino-5-carboxypentyl)-3,5-bis(3-amino-3carboxypropyl)pyridinium. A rare amino acid found in elastin, formed by condensation of four molecules of lysine into a pyridinium ring. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH]

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Dilator: A device used to stretch or enlarge an opening. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] 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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] 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

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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] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH]

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Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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]

Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroretinography: Recording of electric potentials in the retina after stimulation by light. [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] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Emus: Members of the Casuariiformes, an order of flightless, running birds. The Emu is the only surviving member of the family Dromeidae. They naturally inhabit forests, open plains, and grasslands in Australia. [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]

Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] 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] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph

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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] Endotoxin: Toxin from cell walls of bacteria. [NIH] Endotracheal intubation: Insertion of an airtube into the windpipe. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enterobacter: Gram-negative gas-producing rods found in feces of man and other animals, sewage, soil, water, and dairy products. [NIH] Enucleation: Removal of the nucleus from an eucaryiotic cell. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental Monitoring: The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment or workplace by measuring the amounts of these toxicants in the bodies of people and animals in that environment, among other methods. It also includes the measurement of environmental exposure. Levels in humans and animals are used as indicators of toxic levels of undesirable chemicals. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] 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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH]

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Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] 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]

Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [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] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [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] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor.

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[NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] 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] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [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 non-

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identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flagellin: A protein with a molecular weight of 40,000 isolated from bacterial flagella. At appropriate pH and salt concentration, three flagellin monomers can spontaneously reaggregate to form structures which appear identical to intact flagella. [NIH] Flatus: Gas passed through the rectum. [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 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] 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] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Food Chain: The sequence of transfers of matter and energy from organism to organism in

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the form of food. Food chains intertwine locally into a food web because most organisms consume more than one type of animal or plant. Plants, which convert solar energy to food by photosynthesis, are the primary food source. In a predator chain, a plant-eating animal is eaten by a larger animal. In a parasite chain, a smaller organism consumes part of a larger host and may itself be parasitized by smaller organisms. In a saprophytic chain, microorganisms live on dead organic matter. [NIH] Food Packaging: Containers, packaging, and packaging materials for processed and raw foods and beverages. It includes packaging intended to be used for storage and also used for preparation of foods such as microwave food containers versus cooking and eating utensils. Packaging materials may be intended for food contact or designated non-contact, for example, shipping containers. Food labeling is also available. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] Fosfomycin: An antibiotic produced by Streptomyces fradiae. [NIH] Fossil Fuels: Any hydrocarbon deposit that may be used for fuel. Examples are petroleum, coal, and natural gas. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [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] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] 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] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental

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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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene 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 Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors,

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transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic 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] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] 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] Geographic Locations: All of the continents and every country situated within, the United States and each of the constituent states arranged by region, Canada and each of its provinces, Australia and each of its states, the major bodies of water and major islands on both hemispheres, and selected major cities. Although the geographic locations are not printed in index medicus as main headings, in indexing they are significant in epidemiologic studies and historical articles and for locating administrative units in education and the delivery of health care. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [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] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH]

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Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

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] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerol Kinase: An enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol. Dihydroxyacetone and L-glyceraldehyde can also act as acceptors; UTP and, in the case of the yeast enzyme, ITP and GTP can act as donors. It provides a way for glycerol derived from fats or glycerides to enter the glycolytic pathway. EC 2.7.1.30. [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] Glycopeptides: Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH]

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Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gramicidin: Antibiotic mixture that is one of the two principle components of tyrothricin from Bacillus brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D, etc., seem to be linear polypeptides. The mixture is used topically for gram-positive organisms. It is toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Inguinale: Anogenital ulcers caused by Calymmatobacterium granulomatis as distinguished from lymphogranuloma inguinale (see lymphogranuloma venereum) caused by Chlamydia trachomatis. Diagnosis is made by demonstration of typical intracellular Donovan bodies in crushed-tissue smears. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanine: One of the four DNA bases. [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]

Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hairy cell leukemia: A type of chronic leukemia in which the abnormal white blood cells appear to be covered with tiny hairs when viewed under a microscope. [NIH]

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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] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Hazardous Substances: Substances which, upon release into the atmosphere, water, or soil, or which, in direct contact with the skin, eyes, or mucous membranes, or as additives to food, cause health risks to humans or animals through absorption, inhalation, or ingestion. The concept includes safe handling, transportation, and storage of these substances. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala, nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH]

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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]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH]

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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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydration: Combining with water. [NIH] Hydrocarbons, Aromatic: Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]

Hydrogen Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain

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collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imagination: A new pattern of perceptual or ideational material derived from past experience. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is

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deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunoconjugates: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as immunoglobulins, monoclonal antibodies or antigens. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of drugs and radioisotopes in the chemotherapy and radioimmunotherapy of certain cancers. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive 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] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impetigo: A common superficial bacterial infection caused by staphylococcus aureus or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incineration: High temperature destruction of waste by burning with subsequent reduction to ashes or conversion to an inert mass. [NIH] Incision: A cut made in the body during surgery. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH]

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Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Industrial Waste: Worthless, damaged, defective, superfluous or effluent material from industrial operations. It represents an ecological problem and health hazard. [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH]

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Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-13: T-lymphocyte-derived cytokine that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature Blymphocytes. It appears to play a role in regulating inflammatory and immune responses. [NIH]

Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH]

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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] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. [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] Isocitrate Lyase: A key enzyme in the glyoxylate cycle. It catalyzes the conversion of isocitrate to succinate and glyoxylate. EC 4.1.3.1. [NIH] Isodesmosine: 2-(4-Amino-4-carboxybutyl)-1-(5-amino-5-carboxypentyl)-3,5-bis(3-amino-3carboxypropyl)pyridinium. A rare amino acid found in elastin, formed by condensation of four molecules of lysine into a pyridinium ring. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isopropyl: A gene mutation inducer. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]

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Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactates: Salts or esters of lactic acid containing the general formula CH3CHOHCOOR. [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] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] 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] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Legionella: Gram-negative aerobic rods, isolated from surface water, mud, or thermally polluted lakes or streams. It is pathogenic for man and it has no known soil or animal sources. [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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lethal: Deadly, fatal. [EU] 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]

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Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] 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] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligase Chain Reaction: A DNA amplification technique based upon the ligation of oligonucleotide probes. The probes are designed to exactly match two adjacent sequences of a specific target DNA. The chain reaction is repeated in three steps in the presence of excess probe: (1) heat denaturation of double-stranded DNA, (2) annealing of probes to target DNA, and (3) joining of the probes by thermostable DNA ligase. After the reaction is repeated for 20-30 cycles the production of ligated probe is measured. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU]

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Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] 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] Lubricants: Oily or slippery substances. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphogranuloma Venereum: Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. but is more widespread in developing countries. It is distinguished from granuloma venereum (granuloma inguinale), which is caused by Calymmatobacterium granulomatis. [NIH]

Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in

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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] 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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannans: Polysaccharides consisting of mannose units. [NIH] Mannoheptulose: A 7-carbon keto sugar having the mannose configuration. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastoiditis: Inflammation of the cavity and air cells in the mastoid part of the temporal bone. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Mediastinal Emphysema: Presence of air in the mediastinal tissues due to leakage of air from the tracheobronchial tree, usually as a result of trauma. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [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]

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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] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Menthol: An alcohol produced from mint oils or prepared synthetically. [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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyl Parathion: The methyl homolog of parathion. An effective, but highly toxic, organothiophosphate insecticide and cholinesterase inhibitor. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH]

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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] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]

Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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]

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Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] 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] Mupirocin: A topically used antibiotic from a strain of Pseudomonas fluorescens. It has shown excellent activity against gram-positive staphylococci and streptococci. The antibiotic is used primarily for the treatment of primary and secondary skin disorders, nasal infections, and wound healing. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Mycotoxins: Toxins derived from bacteria or fungi. [NIH]

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Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myristate: Pharmacological activator of protein kinase C. [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] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]

Nebulizer: A device used to turn liquid into a fine spray. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Screening: The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic. [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] 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] Neuropeptide: A member of a class of protein-like molecules made in the brain.

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Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [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]

Nitrofurantoin: A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and longterm suppression. [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] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]

Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [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

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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] Novobiocin: An antibiotic drug used to treat infection. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclease Protection Assays: Techniques for measuring specific nucleic acid interaction with another nucleic acid or with a protein by digestion of the non-interacting nucleic acid by various nucleases. After all non-interacting regions are eliminated by nuclease digestion, the protected nucleic acid that remains is analyzed. DNA footprinting utilizes this technique to analyze the DNA contact sites of DNA-binding proteins. [NIH] 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] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] 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

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codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] 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] Orofacial: Of or relating to the mouth and face. [EU] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [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

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localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Ostriches: Flightless birds of the order Struthioniformes which naturally inhabit open, low rainfall areas of Africa. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otorrhea: A discharge from the ear, especially a purulent one. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [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] 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] Panophthalmitis: Acute suppurative inflammation of the inner eye with necrosis of the sclera (and sometimes the cornea) and extension of the inflammation into the orbit. Pain may be severe and the globe may rupture. In endophthalmitis the globe does not rupture. [NIH]

Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in

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different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitism: A) The mode of life of a parasite; b) The relationship between an organism (parasite) that derives benefits from, and at the expense of, another organism (host). [NIH] Parathion: A highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide. [NIH] Paratuberculosis: An infectious disease caused by Mycobacterium paratuberculosis. Characteristics include chronic debilitation and weight loss. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Particle Accelerators: Devices which accelerate electrically charged atomic or subatomic particles, such as electrons, protons or ions, to high velocities so they have high kinetic energy. [NIH] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentachlorophenol: An insecticide and herbicide that has also been used as a wood preservative. Pentachlorphenol is a widespread environmental pollutant. Both chronic and acute pentachlorophenol poisoning are medical concerns. The range of its biological actions is still being actively explored, but it is clearly a potent enzyme inhibitor and has been used as such as an experimental tool. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [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] Perennial: Lasting through the year of for several years. [EU]

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Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] 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 stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Periplasm: The space between the inner and outer membranes of a cell that is shared with the cell wall. [NIH] Pesticide Residues: Pesticides or their breakdown products remaining in the environment following their normal use or accidental contamination. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] 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] Pharyngitis: Inflammation of the throat. [NIH] 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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] 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]

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Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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] Phosphorus Compounds: Inorganic compounds that contain phosphorus as an integral part of the molecule. [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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Phytotoxin: A substance which is toxic for plants. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Piperacillin: Semisynthetic, broad-spectrum, ampicillin-derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. [NIH]

Piperacillin-tazobactam: A combination of drugs used to fight infections in people who have cancer. Piperacillin is a synthetic penicillin; tazobactam enhances the effectiveness of piperacillin. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Diseases: Diseases of plants. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid

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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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH]

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Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. [NIH] Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] 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] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polyphosphates: Linear polymers in which orthophosphate residues are linked with energy-rich phosphoanhydride bonds. They are found in plants, animals, and microorganisms. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Polyvinyl Alcohol: A polymer prepared from polyvinyl acetates by replacement of the acetate groups with hydroxyl groups. It is used as a pharmaceutic aid and ophthalmic lubricant as well as in the manufacture of surface coatings artificial sponges, cosmetics, and other products. [NIH]

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Population Density: Number of individuals in a population relative to space. [NIH] Population Growth: Increase, over a specific period of time, in the number of individuals living in a country or region. [NIH] Porphobilinogen Synthase: An enzyme that catalyzes the formation of porphobilinogen from two molecules of 5-aminolevulinic acid. EC 4.2.1.24. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] 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] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle

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(shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [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] Progeny: The offspring produced in any generation. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propionic Acids: 3-carbon saturated monocarboxylic acids. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH]

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Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteobacteria: A class of bacteria consisting of the purple bacteria and their relatives which form a branch of the eubacterial tree. This group of predominantly gram-negative bacteria is classified based on homology of equivalent nucleotide sequences of 16S ribosomal RNA or by hybridization of ribosomal RNA or DNA with 16S and 23S ribosomal RNA. [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] Proteome: The protein complement of an organism coded for by its genome. [NIH] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [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] Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. [NIH] Pseudomonas Infections: Infections with bacteria of the genus Pseudomonas. [NIH] Pseudomonas putida: A species of gram-negative, aerobic bacteria isolated from soil and

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water as well as clinical specimens. Occasionally it is an opportunistic pathogen. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary 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] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU]

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Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring systems. [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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] Ratites: A grouping of flightless birds consisting of four orders: the Apterygiformes, which includes kiwis; the Casuariiformes, which includes emus; the Rheiformes, or rheas; and the Struthioniformes, or ostriches. [NIH]

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Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell. [NIH] Recessive gene: A gene that is phenotypically expressed only when homozygous. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] 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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [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] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheas: Members of the Rheiformes, a South American order of large, long-necked, longlegged, flightless birds, sometimes called American ostriches, though in a separate order from true ostriches. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve

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impulses to the brain. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]

Salicylic: A tuberculosis drug. [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] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Saprophyte: A saprophytic (= whose nutrition involves uptake of dissolved organic material from decaying plant or animal matter) organism. [EU] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and

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pharyngitis. An erythematous rash is commonly present. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Self-Sustained Sequence Replication: An isothermal in-vitro nucleotide amplification process. The process involves the concomitant action of a RNA-directed DNA polymerase, a ribonuclease, and a DNA-directed RNA polymerase to synthesize large quantities of sequence-specific RNA and DNA molecules. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] 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] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found

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in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] 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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Compounds: Inorganic compounds that contain silicon as an integral part of the molecule. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Silver Sulfadiazine: Antibacterial used topically in burn therapy. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] 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 Behavior: Any behavior caused by or affecting another individual, usually of the same species. [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] Sodium Glutamate: L-Glutamic acid, sodium salt. An additive used to impart meat flavor to foods, and to enhance other natural food flavors. Medically it has been used to reduce blood ammonia levels in ammoniacal azotemia, therapy of hepatic coma, in psychosis, and mental retardation. [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] Spasmogenic: Capable of producing convulsions. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of

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a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincters: Any annular muscle closing an orifice. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sputa: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Staphylococcal Infections: Infections with bacteria of the genus Staphylococcus. [NIH] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH]

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Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stethoscopes: An instrument used for the detection and study of sounds within the body that conveyed to the ears of the observer through rubber tubing. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] 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] 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]

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Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [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] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superinfection: A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. Experimental challenge and in vitro models are sometimes used in virulence and infectivity studies. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. [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]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH]

Dictionary 343

Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [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] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH]

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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] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Ticarcillin: An antibiotic derived from penicillin similar to carbenicillin in action. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH]

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Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transposons: Discrete genetic elements capable of inserting, in a non-permuted fashion, into the chromosomes of many bacteria. [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] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichloroethylene: A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment. [NIH] Triclosan: A diphenyl ether derivative used in cosmetics and toilet soaps as an antiseptic. It has some bacteriostatic and fungistatic action. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH]

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Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Tropolone: A seven-membered aromatic ring compound. It is structurally related to a number of naturally occurring antifungal compounds. [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, Oral: Tuberculosis of the mouth, tongue, and salivary glands. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor 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] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyrocidine: An antibiotic mixture produced by Bacillus brevis which may be separated into three components, tyrocidines A, B, and C. It is the major constituent (40-60 per cent) of tyrothricin, gramicidin accounting for the remaining 10-20 per cent active material. It is a topical antimicrobial agent, that is very toxic parenterally. [NIH] Tyrothricin: A polypeptide antibiotic mixture obtained from Bacillus brevis. It consists of a mixture of three tyrocidines (60%) and several gramicidins (20%) and is very toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. It is used topically. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. [NIH]

Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those ionophores that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH]

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Urbanization: The process whereby a society changes from a rural to an urban way of life. It refers also to the gradual increase in the proportion of people living in urban areas. [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] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [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] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] 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

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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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [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] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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]

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Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] 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] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xanthomonas: A genus of Pseudomonadaceae whose cells produce a yellow pigment (Gr. xanthos - yellow). It is pathogenic to plants. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

351

INDEX A Abdomen, 269, 280, 310, 314, 340, 341 Aberrant, 11, 50, 269 Acatalasia, 269, 282 Acceptor, 269, 323, 345 Acetylcholine, 269, 320 Acne, 197, 226, 269, 335 Acremonium, 269, 283 Acrylonitrile, 269, 336 Actin, 29, 269 Actinobacillus, 157, 269 Actinomycosis, 237, 269 Acute leukemia, 122, 269 Acute renal, 269, 304 Acyl, 37, 39, 84, 96, 128, 205, 219, 269 Adaptability, 14, 269, 282 Adaptation, 91, 121, 220, 269, 318 Adenine, 182, 199, 269, 332 Adenosine, 269, 326 Adjustment, 180, 269, 270 Adjuvant, 209, 231, 270, 300 Adrenal Medulla, 270, 296, 320 Adsorption, 178, 270 Adsorptive, 204, 270 Adverse Effect, 270, 338, 348 Aerobic, 61, 67, 81, 88, 187, 217, 270, 271, 280, 307, 312, 317, 323, 331 Aerobic Metabolism, 88, 270, 323 Aerobic Respiration, 81, 270, 323 Aerosol, 7, 50, 178, 179, 212, 213, 214, 270, 320, 348 Affinity, 11, 13, 33, 56, 57, 209, 270, 276, 313, 339 Agrobacterium, 181, 185, 213, 270 Agrochemicals, 225, 270 Airway, 11, 20, 30, 31, 35, 37, 48, 50, 51, 60, 108, 126, 141, 158, 270 Albumin, 270, 327 Alcaligenes, 88, 169, 178, 179, 185, 212, 216, 271 Alcohol Dehydrogenase, 66, 96, 199, 271 Aldehydes, 199, 271 Alfalfa, 62, 98, 271 Algorithms, 24, 271, 278 Alimentary, 269, 271, 324 Alkaline, 85, 155, 271, 272, 281 Alkaloid, 271, 326 Alkylating Agents, 33, 271, 346

Alleles, 101, 271 Allergen, 271, 337 Allergic Rhinitis, 209, 271, 304 Alloys, 271, 286 Alpha Particles, 271, 333 Alpha-1, 101, 271, 273 Alpha-Defensins, 271, 290 Alternative medicine, 241, 271 Aluminum, 272, 349 Alveoli, 272, 332, 348 Amber, 272, 308 Ambulatory Care, 272 Amine, 272, 305 Amino Acid Motifs, 272, 288 Amino Acid Sequence, 17, 186, 189, 193, 194, 220, 233, 272, 274, 288, 301 Amino Acid Substitution, 220, 272 Aminolevulinic Acid, 89, 272, 329 Ammonia, 272, 302, 339, 342 Ammonium Compounds, 168, 272 Amoxicillin, 198, 272 Ampicillin, 4, 198, 272, 326 Amplification, 67, 200, 229, 230, 273, 313, 337 Amylases, 207, 273 Anaerobic, 38, 67, 96, 100, 195, 273, 307, 336, 340 Anaesthesia, 104, 273, 309 Anal, 192, 273, 295, 298 Analgesic, 273, 307, 312, 319, 320, 342 Analog, 44, 206, 273 Analogous, 9, 192, 273, 293, 345 Anaphylatoxins, 31, 273, 287 Anaphylaxis, 209, 273 Anatomical, 273, 284, 294, 308, 337 Anemia, 43, 273, 286 Anergy, 273, 342 Anesthesia, 270, 273, 345 Aneurysm, 128, 273 Angina, 273, 320 Angioedema, 52, 273 Angiogenesis, 56, 273, 315 Animal model, 10, 17, 21, 35, 42, 184, 273 Anionic, 168, 273 Anions, 271, 273, 311, 338, 342 Annealing, 274, 313, 328 Anthrax, 28, 52, 274 Anthropogenic, 217, 274

Pseudomonas

Antibacterial, 20, 26, 51, 67, 101, 198, 201, 218, 232, 274, 292, 307, 320, 338, 339, 347 Antibiosis, 202, 274 Antibiotic, 6, 9, 10, 14, 16, 17, 22, 23, 24, 41, 42, 49, 55, 57, 59, 61, 69, 77, 81, 83, 89, 92, 100, 101, 104, 124, 131, 133, 138, 140, 160, 161, 171, 173, 175, 187, 198, 200, 206, 225, 226, 229, 230, 272, 274, 276, 280, 285, 286, 296, 299, 303, 318, 319, 321, 324, 326, 328, 336, 339, 341, 344, 346 Anticoagulant, 274, 331 Antifungal, 75, 80, 148, 198, 201, 232, 274, 346 Antigen-Antibody Complex, 274, 287 Anti-infective, 274, 281, 284, 306, 320, 339 Anti-inflammatory, 32, 35, 45, 52, 208, 274, 307, 312, 319, 342 Antineoplastic, 271, 274 Antineoplastic Agents, 271, 274 Antipruritic, 274, 281, 286 Antipyretic, 274, 312, 319, 342 Antiseptic, 168, 274, 282, 345 Antiviral, 198, 201, 232, 275, 324 Aorta, 128, 275 Apolipoproteins, 275, 313 Apoptosis, 13, 36, 55, 102, 105, 142, 217, 275, 282 Arachidonic Acid, 53, 275, 313, 330 Archaea, 275, 317 Arginine, 28, 193, 273, 275, 320 Aromatic, 53, 58, 63, 67, 80, 83, 84, 171, 203, 215, 229, 275, 281, 341, 346 Arterial, 275, 284, 312, 320, 331 Arteries, 275, 279, 289, 314, 316, 343 Arterioles, 275, 279, 281 Arteriovenous, 133, 275 Arteriovenous Fistula, 133, 275 Artery, 273, 275, 279, 289, 332 Aspergillus, 45, 120, 195, 275 Asphyxia, 275, 320 Aspirate, 56, 275 Assay, 29, 43, 72, 109, 173, 182, 188, 205, 211, 220, 236, 275, 336, 346 Astringent, 275, 282 Astrocytes, 275, 305 Asymptomatic, 102, 269, 276 Atopic, 209, 276 Auditory, 5, 276 Autoimmune disease, 43, 194, 276, 318 Autoimmunity, 4, 42, 276 Autonomic, 269, 276, 301, 320 Autopsy, 134, 276

352

Azotemia, 276, 339 Aztreonam, 65, 178, 179, 212, 276 B Bacillus, 5, 23, 37, 93, 184, 185, 187, 188, 195, 196, 198, 201, 202, 203, 230, 232, 274, 276, 286, 303, 328, 346 Bacillus subtilis, 93, 202, 203, 276 Bacteraemia, 98, 135, 276 Bacteremia, 111, 117, 118, 133, 137, 197, 276, 336 Bacterial Adhesion, 31, 276 Bacterial Physiology, 269, 276 Bacterial toxin, 209, 276 Bacterial Translocation, 40, 276 Bactericidal, 45, 51, 52, 102, 103, 215, 277, 296, 320, 346 Bacteriocins, 103, 277 Bacteriophage, 10, 47, 159, 160, 197, 277, 327, 336, 345, 348 Bacteriophage lambda, 47, 277 Bacteriostatic, 277, 296, 345 Base, 8, 27, 151, 182, 189, 269, 277, 281, 290, 299, 301, 311, 327, 343, 346 Base Sequence, 277, 299, 301 Basement Membrane, 277, 297 Basophils, 209, 277, 303, 313 Baths, 214, 277 Benzene, 208, 277 Benzoic Acid, 277, 284 Benzyl Alcohol, 157, 229, 277 Beta-Defensins, 60, 277, 290 Beta-Lactam Resistance, 125, 277 Beta-Lactamases, 100, 126, 127, 276, 278, 307 Bile, 278, 300, 306, 314 Binding Sites, 11, 57, 60, 76, 278 Bioassay, 51, 278 Bioavailability, 4, 38, 148, 204, 278 Biodegradation, 65, 93, 149, 150, 203, 204, 215, 216, 217, 278 Biogenesis, 59, 87, 278 Bioluminescence, 14, 278 Biomarkers, 37, 278 Biopsy, 278, 296 Bioreactors, 149, 278 Biotechnology, 20, 44, 60, 97, 139, 149, 150, 151, 177, 215, 236, 241, 251, 278 Bioterrorism, 17, 278 Biotic, 12, 222, 279, 346 Biotin, 279, 321 Biotransformation, 65, 82, 149, 215, 279 Biphasic, 14, 279

353

Bismuth, 152, 279 Bladder, 4, 25, 276, 279, 289, 318, 330, 334, 347 Blood Coagulation, 279, 281, 336, 343 Blood pressure, 279, 317, 339 Blood vessel, 273, 279, 280, 283, 284, 294, 295, 304, 314, 325, 326, 339, 341, 343, 347 Blood-Brain Barrier, 184, 279 Blot, 135, 279, 321 Body Fluids, 278, 279, 281, 293, 339, 346 Bolus, 21, 279 Bolus infusion, 279 Bolus injection, 21, 279 Bombesin, 22, 279 Bone Marrow, 7, 209, 269, 277, 279, 280, 301, 303, 307, 314, 318, 339 Bone Marrow Transplantation, 7, 280 Bone scan, 280, 336 Bowel, 273, 280, 291, 309, 310 Bowel Movement, 280, 291 Bradykinin, 280, 320, 327 Branch, 25, 27, 265, 280, 314, 324, 331, 332, 339, 343 Breakdown, 34, 37, 280, 291, 300, 322, 325 Breeding, 222, 227, 280 Broad-spectrum, 23, 117, 272, 280, 281, 283, 326, 344 Bromine, 183, 280 Bronchi, 280, 296, 345 Bronchial, 280, 305 Bronchiectasis, 37, 73, 179, 213, 280 Bronchioles, 272, 280, 332 Bronchoalveolar Lavage, 31, 51, 280 Bronchoalveolar Lavage Fluid, 31, 51, 280 Bronchoscope, 239, 280 Buccal, 280, 341 Burkholderia cepacia, 24, 37, 123, 132, 135, 137, 178, 179, 190, 212, 280 Burns, 42, 62, 68, 103, 114, 115, 116, 134, 138, 140, 144, 152, 226, 281 Burns, Electric, 281 Bypass, 12, 281 C Calcium, 73, 281, 285, 287, 315, 331, 338 Camphor, 27, 281 Canonical, 182, 281 Capillary, 104, 184, 280, 281, 348 Capsular, 32, 281 Capsules, 195, 281, 300 Carbapenems, 102, 111, 281 Carbenicillin, 281, 344

Carbohydrate, 11, 54, 160, 202, 281, 302, 328 Carbon Dioxide, 180, 204, 281, 290, 298, 300, 335 Carbon Disulfide, 216, 281 Carboxy, 91, 281 Carboxylic Acids, 186, 281 Carcinogen, 27, 281 Carcinogenic, 196, 204, 271, 277, 281, 286, 309, 321, 330, 346 Carcinogenicity, 204, 282 Carcinoma, 13, 281, 282 Cardiac, 282, 293, 294, 296, 313, 319 Cardiotoxicity, 282, 345 Carotene, 282, 335 Carrier Proteins, 282, 327 Case report, 110, 128, 134, 282 Caspase, 55, 282 Catalase, 49, 61, 64, 65, 72, 142, 269, 282 Catechol, 53, 282 Catheter, 4, 16, 257, 282, 311 Cations, 282, 311 Causal, 282, 295, 337, 343 Cause of Death, 11, 54, 282 Cell Adhesion, 109, 282, 310 Cell Communication, 89, 282 Cell Death, 275, 282 Cell Differentiation, 14, 282, 338 Cell Division, 160, 276, 282, 283, 315, 317, 326, 330, 337 Cell membrane, 194, 282, 286, 291, 317, 325, 328 Cell Movement, 32, 282 Cell Polarity, 29, 108, 283 Cell proliferation, 56, 283, 310, 338 Cell Respiration, 270, 283, 317, 323, 335 Cell Size, 283, 298 Cellulitis, 130, 283 Cellulose, 283, 299, 326 Central Nervous System, 269, 277, 283, 300, 302, 304, 313, 318, 322 Cephalosporins, 140, 198, 278, 283 Ceramide, 7, 119, 283 Cerebral, 279, 283, 296 Cerebrovascular, 5, 283 Cerebrum, 283 Character, 224, 283, 290 Chemical Warfare, 28, 283, 290 Chemical Warfare Agents, 28, 283, 290 Chemokines, 8, 20, 31, 49, 283 Chemotactic Factors, 283, 287 Chemotaxis, 33, 67, 84, 88, 283

Pseudomonas

Chemotherapeutic agent, 24, 284 Chimeric Proteins, 176, 194, 227, 284 Chin, 133, 284, 316 Chlorhexidine, 168, 284 Chlorine, 183, 217, 284 Chlorobenzoates, 150, 284 Chlorophyll, 43, 284, 299 Cholera, 9, 284, 337, 348 Cholesterol, 278, 284, 313, 314 Cholesterol Esters, 284, 313 Chorismate Mutase, 94, 284 Choroid, 284, 335, 347 Chromatin, 55, 275, 284, 295 Chromium, 149, 195, 284 Chromosomal, 7, 48, 52, 57, 61, 65, 67, 80, 106, 107, 121, 133, 150, 273, 284, 327 Chromosome, 47, 68, 284, 288, 304, 313, 337, 345 Chronic, 4, 5, 6, 7, 11, 15, 16, 20, 21, 29, 35, 41, 42, 48, 49, 51, 52, 58, 73, 105, 110, 133, 163, 164, 174, 175, 179, 205, 212, 232, 284, 292, 303, 309, 312, 324, 332, 338, 341, 344, 347, 349 Chronic Disease, 4, 284 Chronic leukemia, 284, 303 Chylomicrons, 284, 313 Cicatrix, 285, 312 Cicatrix, Hypertrophic, 285, 312 Cilastatin, 285, 307 Ciprofloxacin, 6, 96, 104, 105, 112, 115, 285 CIS, 48, 80, 151, 226, 285, 335 Citric Acid, 168, 204, 285 Citrus, 285 Clamp, 19, 285 Clathrin, 285, 286, 294 Claviceps, 285, 336 Clear cell carcinoma, 285, 291 Cleave, 51, 273, 285 Clinical Medicine, 285, 329 Clinical trial, 7, 13, 38, 163, 165, 251, 285, 333 Cloaca, 177, 191, 285 Clone, 19, 33, 50, 73, 75, 84, 109, 116, 126, 130, 285 Cloning, 11, 47, 68, 78, 80, 83, 87, 149, 157, 220, 278, 285, 313 Clot Retraction, 286, 327 Coagulation, 52, 279, 286, 305, 327 Coal, 150, 170, 204, 277, 286, 299 Coal Tar, 150, 286 Coated Vesicles, 285, 286, 294 Cobalt, 190, 286

354

Codons, 286, 301, 322 Coenzyme, 33, 199, 286 Cofactor, 53, 228, 229, 286, 331, 343 Coliphages, 277, 286 Colistin, 121, 144, 286 Colitis, 52, 286, 309 Collagen, 112, 272, 277, 286, 297, 298, 300, 312, 315, 327, 330 Collapse, 273, 280, 286 Colloidal, 270, 286, 294, 338 Colon, 286, 287, 309, 312 Commensal, 269, 287 Complement, 9, 15, 32, 34, 45, 52, 273, 287, 301, 310, 327, 337 Complement Activation, 45, 52, 273, 287 Computational Biology, 251, 287 Computed tomography, 38, 287, 336 Computerized tomography, 47, 164, 287 Concomitant, 287, 337 Cones, 287, 335 Conjugated, 32, 277, 287, 288, 289 Conjugation, 32, 217, 279, 288 Conjunctiva, 288, 309, 345 Conjunctivitis, 100, 288, 304 Connective Tissue, 45, 280, 283, 286, 288, 291, 298, 300, 312, 314, 335 Connective Tissue Cells, 288 Consciousness, 273, 288, 292 Consensus Sequence, 57, 272, 288 Conserved Sequence, 272, 288 Consumption, 19, 38, 288, 300, 323 Contamination, 44, 107, 168, 196, 204, 288, 325 Contraindications, ii, 288 Conventional therapy, 288 Conventional treatment, 194, 288 Coordination, 23, 288, 318 Cornea, 130, 149, 288, 289, 312, 323, 337 Corneal Ulcer, 16, 64, 289 Coronary, 289, 316, 320 Coronary Thrombosis, 289, 316 Corrosion, 170, 289 Cortex, 289, 323 Corticosteroids, 121, 289 Cross Infection, 120, 289 Crossing-over, 289, 334 Crowns, 289, 291 Crystallization, 59, 289 Cues, 46, 289 Curative, 289, 343 Cutaneous, 104, 202, 237, 274, 289 Cutaneous Fistula, 104, 237, 289

355

Cyanide, 76, 136, 289 Cyclic, 74, 87, 201, 282, 286, 289, 303, 320, 329, 330 Cyst, 275, 289 Cystitis, 4, 289 Cytochrome, 27, 55, 81, 91, 289 Cytokine, 7, 10, 32, 43, 125, 148, 231, 289, 310 Cytoplasm, 275, 277, 282, 290, 295, 318, 336 Cytosine, 182, 290, 333 Cytoskeleton, 29, 36, 39, 290, 310 Cytotoxic, 10, 42, 90, 139, 193, 195, 290, 308, 333, 338 Cytotoxicity, 139, 193, 290 Cytotoxins, 46, 177, 290 D Dairy Products, 290, 295 Decarboxylation, 59, 290, 305 Decision Making, 144, 290 Decontamination, 29, 204, 290 Defense Mechanisms, 158, 290, 310 Defensins, 12, 271, 277, 290 Degenerative, 7, 290, 305, 322 Dehydration, 55, 284, 290 Deletion, 31, 47, 69, 275, 290 Delivery of Health Care, 290, 301, 304 Denaturation, 290, 313, 328 Density, 14, 25, 50, 93, 164, 193, 290, 298, 313, 321, 328 Dental Abutments, 290, 291 Dental Caries, 237, 290 Dental Instruments, 23, 291 Dental Materials, 23, 291 Dentures, 5, 291 Depolarization, 291, 338 Dermal, 197, 291 Dermatitis, 209, 291, 293 Dermatologist, 242, 291 Dermis, 198, 232, 273, 291, 312, 342 DES, 41, 117, 148, 273, 291 Desmosine, 37, 291 Detergents, 286, 291 Detoxification, 28, 180, 191, 196, 291 Deuterium, 33, 291, 306 Diagnostic procedure, 167, 241, 291 Diarrhea, 52, 291 Dietary Fats, 291, 313 Digestion, 271, 278, 280, 291, 310, 313, 314, 321, 341, 347 Digestive system, 166, 291 Digestive tract, 291, 339, 340

Dihydrotestosterone, 291, 334 Dilatation, 273, 280, 291, 330, 332 Dilator, 292, 320 Diphtheria, 183, 184, 237, 292 Diphtheria Toxin, 183, 184, 292 Diploid, 292, 327 Direct, iii, 21, 23, 33, 39, 48, 49, 57, 119, 169, 210, 220, 282, 283, 285, 292, 304, 306, 334 Discrete, 36, 292, 345 Disease Progression, 37, 292 Disinfectant, 168, 169, 204, 205, 284, 292, 296 Disinfection, 90, 183, 214, 292 Dissection, 18, 292 Dissociation, 33, 209, 270, 292, 311 Dissociative Disorders, 292 Distal, 292, 293, 331, 332 Dose-dependent, 51, 292 Drive, ii, vi, 18, 36, 147, 193, 237, 292 Drug Delivery Systems, 44, 292 Drug Design, 17, 244, 245, 292 Drug Interactions, 244, 293 Drug Resistance, 17, 57, 104, 125, 126, 138, 293 Drug Tolerance, 293, 344 Duct, 293, 336, 342 Dura mater, 293, 316, 323 Dyes, 277, 293, 298 Dysmenorrhea, 293, 319 E Ecosystem, 64, 81, 133, 174, 204, 206, 293 Eczema, 226, 293 Edema, 28, 53, 273, 293 Effector cell, 60, 293, 334 Efficacy, 13, 17, 18, 20, 22, 23, 32, 49, 84, 113, 148, 164, 185, 292, 293, 307 Elastic, 293, 342 Elastin, 37, 52, 286, 291, 293, 297, 311 Elective, 137, 293 Electrocoagulation, 286, 293 Electrode, 177, 293 Electrolysis, 89, 169, 273, 282, 293, 294 Electrolyte, 294, 329, 339 Electrophoresis, 8, 41, 104, 122, 294 Electroplating, 149, 282, 294 Electroretinography, 35, 294 Embryo, 282, 294, 309 Emollient, 294, 302 Empiric, 123, 294 Emulsion, 294, 298 Emus, 294, 333

Pseudomonas

Enamel, 290, 294 Encapsulated, 32, 294 Endemic, 173, 284, 294 Endocarditis, 66, 119, 124, 131, 133, 294 Endocardium, 294 Endocytosis, 193, 294 Endogenous, 46, 160, 279, 293, 294, 331, 346 Endophthalmitis, 105, 113, 115, 133, 145, 294, 323 Endosomes, 183, 294 Endothelial cell, 88, 143, 184, 279, 294, 343 Endothelium, 295, 320, 327 Endothelium-derived, 295, 320 Endotoxin, 83, 159, 194, 295, 346 Endotracheal intubation, 99, 295 Enteric Nervous System, 21, 295 Enterobacter, 177, 178, 182, 184, 185, 186, 191, 201, 212, 295 Enucleation, 115, 295 Environmental Exposure, 295 Environmental Health, 19, 250, 252, 295 Environmental Monitoring, 177, 295 Enzymatic, 40, 156, 178, 207, 210, 215, 216, 225, 272, 281, 282, 287, 290, 295, 305, 328, 335 Enzyme, 7, 17, 22, 29, 33, 37, 40, 44, 53, 59, 84, 93, 96, 97, 140, 164, 176, 178, 188, 189, 191, 197, 207, 209, 210, 220, 222, 224, 225, 226, 239, 271, 272, 278, 282, 286, 292, 293, 295, 297, 301, 302, 303, 305, 311, 313, 314, 316, 323, 324, 327, 328, 329, 331, 334, 336, 338, 341, 342, 343, 345, 349 Enzyme Inhibitors, 295, 327 Eosinophils, 295, 303, 313 Epidemic, 73, 75, 97, 116, 120, 144, 295 Epidemiologic Studies, 295, 301 Epidemiological, 73, 82, 113, 125, 295 Epidermis, 291, 295, 332 Epidermoid carcinoma, 295, 340 Epidural, 104, 296 Epinephrine, 296, 320 Epithelial Cells, 11, 25, 29, 30, 36, 46, 48, 49, 60, 74, 88, 111, 112, 125, 126, 139, 142, 148, 277, 296, 305 Epithelium, 12, 50, 277, 295, 296 Epitope, 177, 227, 296 Ergot, 296, 336 Erythrocytes, 273, 279, 296, 334, 337 Erythromycin, 112, 296 Esophageal, 5, 296

356

Esophagus, 291, 296, 325, 341 Ethanol, 199, 271, 296, 297 Ether, 190, 195, 275, 296, 345 Eukaryotic Cells, 36, 49, 59, 296, 321, 322, 346 Excipient, 231, 296 Excisional, 21, 42, 296 Excitation, 296, 298, 320 Exogenous, 115, 270, 279, 293, 294, 296, 300, 331 Expiration, 296, 334 Extensor, 296, 332 Extracellular Matrix, 33, 34, 51, 52, 288, 297, 298, 310, 315 Extracellular Matrix Proteins, 297, 315 Extracellular Space, 297 Extraction, 4, 178, 181, 192, 214, 297 Extremity, 297, 312 Eye Infections, 12, 297 F Facial, 136, 297 Facial Pain, 136, 297 Family Planning, 251, 297 Fat, 198, 232, 275, 279, 282, 283, 297, 313, 318, 328, 335, 339, 342 Fatty acids, 76, 151, 192, 198, 233, 271, 281, 297, 330, 339, 343 Feces, 295, 297 Fermentation, 188, 199, 225, 271, 297, 336 Fertilizers, 270, 297 Fibril, 33, 297 Fibrin, 279, 286, 297, 327, 343 Fibrinogen, 297, 327, 343 Fibroblasts, 112, 288, 298 Fixation, 32, 298, 337 Flagellin, 68, 69, 108, 142, 298 Flatus, 298, 300 Flow Cytometry, 151, 298 Fluorescence, 18, 72, 298 Fluorescent Dyes, 298 Fold, 9, 42, 46, 298, 316 Follicles, 298 Folliculitis, 131, 298 Food Chain, 204, 298 Food Packaging, 181, 213, 299 Food Technology, 299, 316 Fosfomycin, 23, 87, 299 Fossil Fuels, 33, 170, 299 Fovea, 298, 299 Frameshift, 175, 299, 346 Frameshift Mutation, 299, 346 Free Radicals, 292, 299

357

Freeze Drying, 180, 299 Friction, 242, 299 Fructose, 168, 299, 302 Fungistatic, 277, 299, 345 Fungus, 75, 172, 174, 192, 283, 296, 299, 318, 336 G Gallbladder, 291, 300 Ganglia, 269, 295, 300, 319 Gangrenous, 300, 337 Gas, 33, 201, 206, 272, 281, 284, 295, 298, 299, 300, 306, 318, 320, 332, 335, 347, 348 Gas exchange, 300, 335, 348 Gasoline, 195, 277, 300 Gastric, 272, 279, 281, 300, 305 Gastroenteritis, 280, 300, 336 Gastrointestinal, 197, 276, 280, 285, 296, 300, 313, 320, 341, 346, 348 Gastrointestinal tract, 197, 276, 296, 300, 313, 346 Gelatin, 300, 302, 343 Gels, 11, 14, 300 Gene Expression, 24, 26, 43, 45, 63, 65, 69, 75, 89, 93, 97, 111, 116, 126, 221, 300 Gene Expression Profiling, 26, 300 Gene Fusion, 51, 300 Gene Library, 300, 301 Gene Targeting, 51, 300 Gene Therapy, 7, 20, 48, 300 Genetic Code, 301, 321 Genetic Engineering, 55, 195, 222, 278, 285, 301 Genetic testing, 301, 328 Genetic transcription, 301, 330 Genetics, 7, 12, 26, 28, 30, 38, 47, 53, 56, 76, 101, 145, 157, 236, 288, 301 Genital, 269, 285, 301, 347 Genomic Library, 25, 300, 301 Genomics, 36, 55, 105, 301 Genotype, 30, 172, 301, 325 Geographic Locations, 69, 301 Gingivitis, 237, 301 Gland, 270, 301, 314, 315, 323, 330, 337, 341, 342 Glioma, 13, 123, 124, 137, 301 Glossopharyngeal Nerve, 297, 301 Glucans, 273, 302 Glucose, 150, 155, 161, 177, 199, 283, 284, 302, 304 Glutamic Acid, 302, 320, 330 Glutamine, 21, 81, 302 Glycerol, 54, 302, 325

Glycerol Kinase, 54, 302 Glycine, 91, 193, 272, 277, 302, 320, 337 Glycogen, 273, 302 Glycopeptides, 11, 302 Glycoprotein, 108, 202, 297, 302, 318, 343, 346 Glycoside, 302, 306 Glycosylation, 11, 30, 68, 117, 120, 141, 302 Gonorrhea, 9, 237, 302 Gout, 302, 319 Governing Board, 302, 329 Gp120, 302, 324 Grade, 217, 302 Graft, 133, 232, 303, 305, 308 Graft Rejection, 303, 308 Graft-versus-host disease, 232, 303 Gramicidin, 39, 303, 346 Gram-Negative Bacteria, 54, 178, 179, 212, 221, 303, 331, 335, 344 Gram-positive, 23, 26, 51, 55, 276, 303, 307, 318, 320, 340, 341 Gram-Positive Bacteria, 51, 276, 303 Granule, 303, 336 Granulocyte, 138, 303 Granuloma, 237, 303, 314 Granuloma Inguinale, 237, 303, 314 Growth, 9, 12, 17, 24, 26, 32, 41, 45, 49, 56, 62, 63, 66, 76, 77, 78, 84, 85, 87, 91, 92, 93, 95, 97, 112, 128, 132, 142, 156, 158, 159, 174, 175, 190, 196, 197, 198, 201, 202, 203, 205, 206, 223, 226, 232, 273, 274, 275, 277, 279, 282, 283, 297, 299, 303, 310, 315, 319, 322, 326, 346, 347, 348 Guanine, 182, 303, 332 Guanylate Cyclase, 303, 320 Gyrase, 39, 303, 320 H Habitat, 174, 202, 303, 320 Habitual, 283, 303 Hair follicles, 291, 298, 303, 340, 349 Hairy cell leukemia, 13, 303 Haploid, 304, 326 Haptens, 270, 304 Hay Fever, 271, 304 Hazardous Substances, 57, 304 Headache, 304, 309, 346 Health Care Costs, 21, 304 Health Expenditures, 304 Helminths, 304, 309 Hematogenous, 6, 304 Heme, 25, 26, 27, 43, 53, 272, 289, 304, 323, 329

Pseudomonas

Hemoglobin, 273, 296, 304, 311, 329 Hemoglobinopathies, 301, 304 Hemolytic, 52, 87, 304, 308 Hemorrhage, 184, 293, 304, 341 Hemostasis, 305, 310 Heparan Sulfate Proteoglycan, 56, 305 Hepatic, 34, 271, 305, 329, 339 Hepatitis, 228, 305 Hepatocytes, 305 Herbicide, 223, 305, 324 Hereditary, 52, 302, 305 Heredity, 25, 300, 301, 305 Heterodimers, 305, 310 Heterogeneity, 13, 77, 92, 118, 151, 270, 305 Heterotrophic, 206, 299, 305 Histamine, 210, 273, 305 Histamine Release, 273, 305 Histidine, 220, 305 Homeostasis, 45, 305 Hormonal, 27, 305 Hormone, 278, 289, 291, 296, 305, 316, 335, 338, 343 Horseradish Peroxidase, 12, 305 Housekeeping, 115, 171, 305 Humoral, 133, 231, 303, 306 Humour, 306 Hybrid, 39, 57, 59, 69, 285, 306, 321, 336 Hybridization, 25, 71, 72, 97, 144, 181, 182, 188, 230, 306, 321, 331, 341 Hybridoma, 22, 306 Hydration, 23, 306 Hydrocarbons, Aromatic, 170, 306 Hydrogel, 15, 90, 134, 306 Hydrogen Bonding, 306, 321 Hydrogen Cyanide, 49, 67, 96, 306 Hydrogen Peroxide, 64, 65, 72, 282, 306, 342 Hydrogenation, 306, 333 Hydrolases, 28, 306, 326 Hydrolysis, 207, 210, 278, 279, 306, 324, 325, 326, 331 Hydrophilic, 291, 306 Hydrophobic, 204, 291, 306, 313 Hydroxylation, 27, 225, 306 Hydroxylysine, 286, 306 Hydroxyproline, 272, 286, 307 Hyperoxia, 31, 56, 307 Hyperplasia, 31, 307 Hyperreflexia, 307, 343 Hypersensitivity, 83, 271, 273, 307, 313, 335, 337

358

Hypertrophy, 307 Hypoxia, 31, 307 Hypoxic, 31, 307 I Ibuprofen, 208, 307, 312, 342 Id, 24, 34, 153, 256, 257, 258, 264, 266, 307 Imagination, 174, 307 Imipenem, 101, 113, 114, 120, 124, 129, 136, 139, 218, 285, 307 Immersion, 277, 307 Immune function, 307, 308 Immune Sera, 307 Immunization, 8, 32, 227, 240, 307, 308, 337 Immunocompromised, 29, 34, 50, 130, 179, 194, 197, 219, 221, 307 Immunocompromised Host, 130, 307 Immunoconjugates, 184, 308 Immunodeficiency, 308 Immunogen, 57, 308 Immunoglobulin, 274, 308, 310, 318 Immunologic, 21, 283, 307, 308 Immunosuppressant, 39, 271, 308 Immunosuppressive, 115, 194, 308 Immunosuppressive Agents, 194, 308 Immunosuppressive therapy, 308 Immunotherapy, 121, 194, 308 Immunotoxin, 183, 184, 193, 308 Impairment, 8, 38, 44, 297, 308, 316, 332, 345 Impetigo, 226, 308 In situ, 179, 180, 308 In vivo, 13, 21, 29, 32, 40, 42, 43, 46, 48, 51, 57, 59, 121, 193, 220, 301, 308, 343 Incineration, 216, 308 Incision, 308, 311 Incubated, 230, 308 Indicative, 235, 309, 324, 347 Indolent, 46, 309 Induction, 8, 19, 32, 55, 56, 76, 87, 150, 231, 309 Industrial Waste, 176, 309 Infancy, 47, 49, 309 Infarction, 289, 309, 316 Infertility, 309, 347 Infestation, 222, 309 Inflammatory bowel disease, 4, 309 Influenza, 15, 37, 218, 309 Infusion, 184, 279, 309 Ingestion, 134, 274, 304, 309, 328 Inhalation, 245, 270, 304, 309, 316, 328, 345

359

Initiation, 30, 39, 43, 46, 47, 171, 309, 330, 341 Inner ear, 309, 347 Inoculum, 172, 190, 309 Inorganic, 79, 189, 195, 272, 309, 318, 325, 326, 338 Inpatients, 36, 309 Insecticides, 310, 325 Insight, 27, 37, 40, 41, 51, 54, 55, 310 Insulator, 310, 318 Integrins, 21, 310 Intensive Care, 57, 64, 99, 100, 104, 107, 113, 140, 143, 144, 187, 310 Intensive Care Units, 99, 104, 140, 143, 144, 187, 310 Interleukin-1, 118, 119, 310 Interleukin-13, 118, 119, 310 Interleukin-2, 310 Interleukins, 308, 310 Intermittent, 44, 310 Interstitial, 184, 280, 297, 310 Intestinal, 21, 46, 52, 118, 133, 236, 271, 276, 282, 285, 310 Intestinal Mucosa, 276, 310 Intestine, 46, 280, 310, 312, 341 Intoxication, 31, 310 Intracellular, 26, 30, 42, 48, 83, 161, 193, 283, 285, 303, 309, 310, 316, 320, 329, 330, 338 Intracellular Membranes, 310, 316 Intramuscular, 15, 311, 324 Intraocular, 12, 294, 311 Intravascular, 257, 311 Intravenous, 5, 14, 21, 164, 242, 279, 309, 311, 324 Intrinsic, 8, 50, 52, 57, 80, 87, 270, 277, 311 Introns, 301, 311 Intubation, 311 Invasive, 42, 307, 311, 315 Involuntary, 311, 319, 339, 344 Ion Channels, 31, 276, 311 Ionization, 41, 80, 311 Ionizing, 271, 295, 311, 315, 346 Ionophores, 183, 311, 346 Ions, 30, 73, 168, 169, 192, 201, 204, 205, 277, 292, 294, 306, 311, 324, 331 Isocitrate Lyase, 37, 311 Isodesmosine, 37, 311 Isoleucine, 226, 311 Isopropyl, 224, 311 J Joint, 285, 311, 322

K Kb, 47, 171, 250, 311 Keloid, 242, 285, 312 Keratitis, 8, 12, 16, 105, 109, 130, 134, 149, 312 Keratolytic, 291, 312 Keto, 161, 192, 312, 315 Ketoprofen, 208, 312 Kidney stone, 4, 312 Kinetic, 22, 23, 35, 40, 53, 311, 312, 324 L Labile, 220, 287, 312 Laceration, 312, 343 Lactates, 195, 312 Large Intestine, 291, 310, 312, 334, 339 Larynx, 312, 345 Latent, 312, 329 Lectin, 46, 133, 312, 316 Leg Ulcer, 110, 257, 312 Legionella, 4, 182, 214, 312 Lens, 15, 64, 90, 102, 109, 110, 115, 130, 134, 256, 281, 312, 334, 349 Leprosy, 231, 237, 312 Lethal, 5, 11, 28, 30, 41, 46, 52, 118, 133, 175, 276, 277, 289, 292, 312 Leucocyte, 271, 312 Leukemia, 301, 313 Leukocytes, 277, 279, 283, 295, 310, 313, 318, 346 Leukotrienes, 275, 313 Levofloxacin, 104, 108, 121, 313 Library Services, 264, 313 Lidocaine, 277, 313 Life cycle, 279, 299, 313 Life Expectancy, 37, 313 Ligands, 20, 21, 104, 177, 193, 310, 313 Ligase, 191, 200, 313 Ligase Chain Reaction, 200, 313 Ligation, 44, 53, 231, 313 Linkage, 33, 209, 313 Lipase, 70, 77, 81, 85, 178, 188, 224, 313 Lipid, 7, 30, 76, 194, 198, 219, 232, 275, 302, 311, 312, 313, 314, 318 Lipophilic, 313, 328 Lipopolysaccharide, 30, 35, 58, 63, 73, 139, 159, 160, 193, 194, 219, 277, 303, 313 Lipoprotein, 92, 193, 231, 303, 313, 314, 348 Liposome, 98, 314 Liver Neoplasms, 314, 348 Liver scan, 314, 336 Localization, 13, 55, 139, 158, 217, 314

Pseudomonas

Localized, 5, 42, 94, 273, 290, 292, 294, 298, 309, 314, 323, 326, 327, 343, 346, 347 Locomotion, 314, 326 Loop, 193, 230, 314 Low-density lipoprotein, 313, 314 Lubricants, 314, 325 Luciferase, 36, 314 Lymph, 276, 294, 295, 306, 314 Lymph node, 276, 314 Lymphatic, 295, 309, 314, 339, 340, 344 Lymphatic system, 314, 339, 340, 344 Lymphocyte, 274, 310, 314 Lymphogranuloma Venereum, 303, 314 Lymphoid, 21, 43, 232, 274, 289, 312, 314, 315 Lymphoma, 13, 315 Lysine, 42, 189, 291, 306, 311, 315 Lytic, 197, 315, 348 M Macrophage, 137, 158, 310, 315 Magnetic Resonance Imaging, 315, 336 Malignant, 5, 13, 115, 123, 124, 132, 137, 183, 274, 315 Malnutrition, 47, 271, 315 Man-made, 38, 282, 315 Mannans, 299, 315 Mannoheptulose, 168, 315 Mastitis, 82, 315, 337 Mastoiditis, 99, 315 Matrix metalloproteinase, 34, 37, 315 Maximum Tolerated Dose, 28, 293, 315 Meat, 157, 291, 315, 339 Mechanical ventilation, 179, 213, 315 Mediastinal Emphysema, 4, 315 Mediate, 20, 48, 54, 57, 58, 315 MEDLINE, 251, 315 Medulloblastoma, 119, 315 Meiosis, 315, 318, 342 Membrane Proteins, 54, 92, 104, 158, 316 Meninges, 276, 283, 293, 303, 316, 346 Meningitis, 104, 136, 316 Mental, iv, 6, 166, 250, 252, 284, 292, 316, 332, 339 Mental Disorders, 166, 316, 332 Mental Health, iv, 6, 166, 250, 252, 316, 332 Mental Processes, 292, 316, 332 Mental Retardation, 316, 339 Menthol, 224, 316 Mentors, 38, 316 Mercury, 24, 42, 73, 82, 89, 171, 298, 316 Mesenteric, 276, 316

360

Metabolite, 93, 279, 316 Metastasis, 315, 316 Methionine, 316, 342 Methyl Parathion, 81, 316 Methylene Chloride, 196, 316 Methyltransferase, 140, 316 MI, 70, 80, 180, 267, 316 Microbe, 56, 149, 150, 317, 344 Microbiological, 8, 30, 106, 109, 182, 225, 226, 317 Micronutrients, 35, 317 Microorganism, 17, 19, 168, 170, 174, 185, 189, 216, 217, 222, 223, 274, 286, 317, 324, 349 Micro-organism, 177, 201, 290, 293, 317, 326, 337 Microscopy, 9, 99, 277, 305, 317, 321 Microvilli, 39, 317 Migration, 13, 317 Mineralization, 33, 317 Mitochondria, 159, 317, 322 Mitosis, 275, 317 Mitosporic Fungi, 275, 317 Mobilization, 92, 317 Modeling, 9, 11, 35, 293, 317 Modification, 29, 82, 102, 125, 157, 161, 217, 272, 301, 317, 333 Modulator, 81, 111, 317 Monitor, 51, 72, 92, 317, 321 Monoclonal, 22, 32, 57, 200, 221, 240, 308, 318 Monoclonal antibodies, 57, 200, 308, 318 Monocytes, 45, 110, 310, 313, 318 Mononuclear, 53, 303, 318, 346 Morphological, 83, 294, 299, 318 Morphology, 64, 112, 275, 318 Motility, 10, 17, 33, 59, 83, 91, 93, 96, 116, 318 Mucins, 11, 15, 141, 318, 336 Mucociliary, 318, 338 Mucolytic, 280, 318 Mucosa, 318, 341 Mucus, 11, 201, 202, 318 Multidrug resistance, 19, 57, 318 Multiple sclerosis, 108, 194, 318 Multivalent, 209, 318 Mupirocin, 149, 226, 318 Mutagen, 318 Mutagenic, 69, 204, 271, 318, 346 Myalgia, 309, 318 Mycosis, 318, 321 Mycotic, 128, 198, 231, 232, 318

361

Mycotoxins, 270, 318 Myelin, 108, 194, 318, 319 Myeloma, 306, 319 Myocarditis, 292, 319 Myocardium, 316, 319 Myristate, 45, 319 N Naive, 18, 21, 319 Naproxen, 208, 319 Narcotic, 316, 319, 320 Nasal Mucosa, 309, 319 Natural selection, 278, 319 NCI, 1, 165, 249, 285, 319 Nebramycin, 319, 344 Nebulizer, 179, 213, 319 Neonatal, 42, 46, 104, 107, 115, 144, 164, 240, 319 Neonatal Screening, 46, 164, 319 Neoplastic, 297, 315, 319 Nerve, 28, 273, 284, 295, 301, 318, 319, 322, 329, 335, 337, 341, 344, 345 Nervous System, 283, 319, 320, 341, 342, 347 Neural, 306, 319 Neuromuscular, 269, 319, 328 Neuropeptide, 21, 319 Neurotransmitter, 269, 270, 272, 279, 280, 282, 302, 305, 311, 320, 338, 341 Neutrons, 271, 320, 333 Neutrophil, 10, 20, 21, 35, 37, 49, 50, 51, 87, 102, 107, 320 Niche, 3, 36, 180, 205, 320 Nitric Oxide, 84, 112, 175, 176, 320 Nitrofurantoin, 3, 320 Nitrogen, 170, 226, 230, 271, 272, 297, 298, 302, 306, 320, 346 Nitroglycerin, 89, 320 Nitrous Oxide, 84, 91, 176, 320 Norepinephrine, 46, 320 Norfloxacin, 3, 320 Nosocomial, 9, 14, 20, 46, 56, 72, 84, 112, 127, 129, 135, 143, 187, 280, 321, 331 Novobiocin, 39, 321 Nuclear, 6, 35, 286, 288, 296, 315, 321, 346 Nuclease Protection Assays, 49, 321 Nuclei, 271, 288, 301, 311, 315, 317, 320, 321, 322, 331 Nucleic Acid Hybridization, 182, 306, 321 Nucleic Acid Probes, 182, 188, 200, 321 Nucleolus, 321, 336 Nucleotidases, 306, 321

Nucleus, 55, 64, 275, 277, 284, 289, 290, 291, 295, 296, 315, 318, 320, 321, 330, 331, 341 O Ocular, 8, 12, 15, 34, 321 Odour, 275, 321 Oligonucleotide Probes, 181, 313, 321 Oncogenic, 310, 321 Onychomycosis, 135, 321 Opacity, 290, 321 Open Reading Frames, 47, 220, 226, 321 Operon, 48, 57, 62, 71, 75, 84, 85, 91, 93, 95, 99, 150, 215, 322, 330, 334 Ophthalmic, 141, 322, 328 Ophthalmology, 101, 105, 111, 113, 123, 130, 142, 298, 322 Opportunistic Infections, 257, 271, 322 Opsin, 322, 335 Optic Nerve, 322, 323, 335, 337 Orbit, 322, 323 Organ Culture, 322, 344 Organ Transplantation, 131, 322 Organelles, 10, 59, 285, 290, 318, 322, 327 Orofacial, 32, 297, 322 Osmolality, 46, 322 Osmoles, 322 Osmosis, 322 Osmotic, 35, 91, 95, 270, 322, 338 Osteoarthritis, 312, 322 Osteomyelitis, 5, 6, 322 Ostriches, 323, 333, 335 Otitis, 5, 73, 112, 115, 323 Otitis Media, 112, 323 Otorrhea, 135, 323 Outpatient, 323 Overexpress, 51, 56, 323 Oxidation, 22, 38, 53, 68, 70, 86, 192, 201, 269, 279, 289, 323, 346 Oxidation-Reduction, 38, 279, 323 Oxidative metabolism, 270, 313, 323 Oxygen Consumption, 323, 335 Oxygenase, 26, 27, 80, 87, 323 Oxygenation, 56, 323 P Pachymeningitis, 316, 323 Palate, 301, 323, 341 Palliative, 323, 343 Pancreas, 278, 279, 291, 313, 323, 346 Panophthalmitis, 130, 323 Paranasal Sinuses, 323, 338 Parasite, 227, 299, 324 Parasitic, 285, 304, 309, 324

Pseudomonas

Parasitism, 222, 324 Parathion, 316, 324 Paratuberculosis, 4, 324 Parenteral, 140, 144, 324 Particle Accelerators, 315, 324 Patch, 172, 324 Pathologic, 56, 275, 278, 289, 307, 324, 332 Pathologic Processes, 275, 324 Pathophysiology, 132, 324 Penicillin, 78, 197, 272, 281, 324, 326, 344 Pentachlorophenol, 236, 324 Peptide, 20, 28, 30, 39, 41, 57, 66, 87, 88, 156, 221, 226, 233, 240, 272, 306, 324, 331, 342 Peptide Hydrolases, 306, 324 Peptide T, 20, 324 Perennial, 203, 324, 345 Perfusion, 278, 307, 325 Perineum, 325, 340 Periodontal disease, 237, 325 Periodontitis, 237, 301, 325 Peripheral stem cells, 303, 325 Periplasm, 94, 325 Pesticide Residues, 223, 325 Pesticides, 28, 172, 174, 185, 191, 195, 270, 278, 310, 325 Petroleum, 65, 170, 196, 204, 299, 300, 325 Phagocytosis, 83, 175, 325 Phallic, 298, 325 Pharmacodynamics, 159, 325 Pharmacokinetic, 208, 325 Pharmacologic, 273, 325, 344 Pharyngitis, 325, 337 Pharynx, 309, 325 Phenotype, 13, 30, 34, 46, 47, 73, 78, 325 Phenyl, 217, 325 Phorbol, 45, 325 Phosphates, 195, 325 Phospholipases, 325, 338 Phospholipids, 297, 313, 325 Phosphoric Monoester Hydrolases, 306, 326 Phosphorus, 38, 281, 326 Phosphorus Compounds, 38, 326 Phosphorylated, 41, 286, 326 Phosphorylation, 40, 49, 60, 326, 346 Photocoagulation, 286, 326 Photodynamic therapy, 42, 326 Photosensitizer, 42, 326 Phylogeny, 24, 26, 227, 326 Physical Examination, 6, 326 Physiologic, 317, 326, 330, 334

362

Physiology, 139, 142, 202, 326, 342 Phytotoxin, 76, 150, 326 Pigments, 282, 286, 326, 327, 335 Piperacillin, 104, 107, 137, 326 Piperacillin-tazobactam, 107, 137, 326 Piperidines, 225, 326 Plague, 326, 346 Plant Diseases, 172, 174, 203, 228, 326 Plaque, 284, 327 Plasma cells, 274, 319, 327 Plasma protein, 112, 270, 327, 331, 338 Plasmid, 14, 23, 24, 36, 47, 64, 73, 74, 84, 86, 89, 94, 97, 121, 138, 159, 171, 235, 327, 347 Plasmin, 52, 327 Plasminogen, 327 Plasminogen Activators, 327 Plastids, 322, 327 Platelet Activation, 327, 338 Platelet Aggregation, 273, 320, 327, 343 Platelets, 320, 327 Platinum, 314, 327 Pneumonia, 10, 15, 21, 29, 34, 36, 55, 57, 62, 104, 119, 131, 134, 240, 257, 288, 327, 346 Pneumonitis, 29, 327 Point Mutation, 109, 327 Poisoning, 170, 200, 296, 300, 310, 316, 324, 328, 336, 337 Polychlorinated Biphenyls, 69, 196, 328 Polyesters, 181, 213, 328 Polyethylene, 118, 328 Polymerase, 19, 86, 200, 220, 328, 330, 334, 337 Polymerase Chain Reaction, 200, 328 Polymers, 141, 181, 189, 195, 208, 213, 215, 222, 278, 328, 331, 341 Polymorphic, 140, 328 Polymorphism, 63, 92, 120, 138, 328 Polymyxin, 80, 149, 286, 328 Polyneuritis, 292, 328 Polyphosphates, 195, 328 Polysaccharide, 14, 22, 32, 61, 63, 87, 139, 274, 283, 328 Polyvalent, 200, 328 Polyvinyl Alcohol, 21, 328 Population Density, 14, 172, 329 Population Growth, 205, 329 Porphobilinogen Synthase, 151, 329 Porphyria, 44, 329 Porphyrins, 329 Postoperative, 105, 329

363

Postsynaptic, 329, 338 Post-translational, 10, 41, 217, 329 Potassium, 181, 214, 329, 339 Potassium hydroxide, 181, 214, 329 Potentiates, 310, 329, 334 Potentiation, 329, 338 Practice Guidelines, 252, 256, 329 Preclinical, 60, 329 Precursor, 43, 50, 158, 183, 205, 206, 275, 293, 295, 320, 327, 329, 331, 346 Predisposition, 50, 329 Prevalence, 30, 87, 122, 125, 126, 127, 209, 230, 329 Primitive neuroectodermal tumors, 315, 329 Probe, 34, 72, 97, 133, 144, 155, 177, 181, 182, 187, 188, 313, 321, 330 Progeny, 288, 330 Progression, 273, 330 Progressive, 5, 20, 30, 37, 49, 206, 282, 289, 293, 303, 322, 327, 330 Projection, 290, 320, 322, 330 Proline, 71, 81, 87, 286, 307, 330 Promoter, 48, 49, 76, 78, 87, 94, 219, 330 Promotor, 56, 330 Prone, 242, 330 Prophase, 318, 330, 342 Prophylaxis, 3, 179, 187, 212, 256, 320, 330, 335, 347 Propionic Acids, 208, 330 Proportional, 322, 330 Prostaglandin, 330, 342, 343 Prostate, 278, 330, 346 Protease, 28, 43, 52, 61, 81, 85, 158, 192, 193, 217, 331 Protein Binding, 10, 331 Protein C, 10, 27, 32, 132, 194, 233, 271, 272, 275, 277, 286, 301, 313, 331, 348 Protein Conformation, 27, 272, 331 Protein S, 10, 55, 73, 76, 91, 94, 171, 193, 227, 278, 288, 292, 296, 301, 331, 336, 341 Proteobacteria, 103, 331 Proteolytic, 28, 37, 45, 52, 56, 80, 193, 271, 287, 298, 327, 331 Proteome, 87, 123, 160, 331 Prothrombin, 331, 343 Protons, 271, 306, 311, 324, 331, 333 Protozoa, 278, 288, 317, 331, 340 Proximal, 27, 220, 292, 331 Pruritic, 293, 331 Pseudomonas Infections, 163, 326, 331 Psoriasis, 226, 286, 332, 335

Psychiatry, 298, 332, 348 Psychic, 316, 332 Psychology, 292, 332 Psychosis, 332, 339 Public Health, 10, 16, 18, 122, 252, 332 Public Policy, 251, 332 Pulmonary Edema, 284, 332 Pulmonary Emphysema, 45, 332 Pulmonary Ventilation, 332, 335 Pulse, 317, 332 Purifying, 15, 291, 332 Purines, 277, 332, 337 Purulent, 294, 323, 332, 333 Pustular, 308, 332 Pyoderma, 226, 333 Pyogenic, 322, 333, 337 Pyrimidines, 277, 333, 337 Q Quality of Life, 47, 164, 333 Quaternary, 168, 214, 331, 333 Quinolones, 4, 333 R Race, 208, 227, 317, 333 Racemic, 208, 333 Radiation, 69, 92, 150, 181, 183, 213, 295, 298, 299, 308, 311, 315, 333, 336, 349 Radioactive, 280, 290, 306, 311, 314, 315, 318, 321, 333, 336, 343, 346 Radiography, 6, 333 Radioimmunotherapy, 308, 333 Radioisotope, 321, 333, 345 Radiolabeled, 13, 333 Radiology, 47, 128, 333 Radiopharmaceutical, 6, 333 Randomized, 47, 103, 164, 293, 333 Randomized clinical trial, 47, 164, 333 Ratites, 198, 232, 333 Reaction Time, 191, 334 Reagent, 177, 284, 314, 334 Receptor, 20, 21, 26, 28, 30, 31, 50, 58, 74, 75, 84, 92, 97, 104, 118, 119, 142, 175, 176, 177, 184, 193, 209, 231, 269, 274, 302, 324, 334, 338, 342 Receptor Aggregation, 209, 334 Recessive gene, 46, 164, 334 Recombinant, 7, 27, 35, 51, 70, 85, 86, 90, 106, 126, 132, 181, 189, 213, 222, 278, 334, 347 Recombination, 47, 288, 300, 301, 334 Rectum, 280, 287, 291, 298, 300, 309, 312, 330, 334 Recurrence, 4, 334

Pseudomonas

Red blood cells, 296, 304, 323, 334 Reductase, 40, 55, 71, 79, 81, 84, 91, 95, 96, 175, 176, 334 Refer, 1, 174, 280, 287, 298, 299, 314, 319, 320, 321, 332, 333, 334, 344 Refraction, 334, 339 Refractory, 50, 132, 293, 334 Regimen, 293, 334 Regulon, 57, 75, 89, 95, 334 Reliability, 188, 334 Remission, 334 Renal Circulation, 279, 334 Renal pelvis, 312, 334 Repressor, 49, 57, 322, 334 Resolving, 57, 334 Respiration, 71, 160, 202, 281, 317, 334 Respirator, 315, 335, 348 Respiratory failure, 11, 206, 335, 348 Respiratory Physiology, 112, 122, 138, 335, 348 Respiratory System, 214, 318, 335 Retina, 199, 284, 287, 294, 312, 322, 335, 336, 349 Retinal, 34, 107, 199, 322, 335 Retinoids, 335 Retinol, 34, 199, 335 Retroviral vector, 300, 335 Reversion, 335, 346 Rhamnose, 219, 335 Rheas, 333, 335 Rheumatism, 307, 335 Rheumatoid, 4, 312, 319, 335 Rheumatoid arthritis, 312, 319, 335 Rhinitis, 335, 338 Rhodopsin, 322, 335 Ribonuclease, 43, 336, 337 Ribosome, 76, 336, 345 Rigidity, 326, 336 Risk factor, 47, 113, 133, 136, 137, 164, 295, 336 Ristocetin, 336, 347 Rod, 187, 201, 270, 276, 277, 280, 285, 331, 336 Rodenticides, 325, 336 Rubber, 33, 269, 336, 341 Rye, 172, 223, 285, 296, 336 S Salicylic, 63, 150, 158, 336 Saliva, 336 Salivary, 237, 291, 336, 346 Salivary glands, 237, 291, 336, 346

364

Salmonella, 18, 25, 26, 44, 57, 94, 158, 169, 182, 187, 188, 201, 204, 211, 217, 300, 336 Sanitation, 183, 336 Saprophyte, 276, 336 Scans, 38, 164, 336 Scarlet Fever, 237, 336 Sclera, 284, 288, 323, 337 Sclerosis, 318, 337 Screening, 29, 46, 109, 136, 163, 164, 173, 174, 175, 184, 215, 285, 319, 337 Sebaceous, 291, 337, 349 Sebaceous gland, 291, 337, 349 Secretory, 21, 37, 63, 84, 130, 142, 227, 271, 337 Sedentary, 148, 337 Segregation, 128, 137, 334, 337 Self-Sustained Sequence Replication, 200, 337 Semisynthetic, 272, 281, 307, 326, 337 Sensitization, 21, 337 Sensor, 191, 337 Sepsis, 44, 46, 106, 117, 118, 138, 240, 256, 277, 337 Septic, 21, 134, 337 Septicaemia, 117, 337 Septicemia, 130, 337 Sequence Homology, 17, 324, 337 Sequencing, 47, 68, 77, 84, 137, 176, 220, 328, 337 Serine, 51, 52, 61, 85, 127, 337 Serology, 136, 337 Serotypes, 64, 84, 115, 117, 130, 219, 337 Serum, 13, 15, 43, 270, 272, 273, 287, 307, 314, 337, 338, 346 Serum Albumin, 13, 338 Shedding, 56, 338 Shock, 93, 109, 134, 273, 338, 345 Side effect, 243, 245, 270, 338, 344 Signal Transduction, 7, 40, 41, 70, 338 Silicon, 188, 338 Silicon Compounds, 188, 338 Silicon Dioxide, 338 Silver Sulfadiazine, 126, 338 Sinusitis, 136, 338 Skeletal, 285, 338 Skeleton, 269, 311, 330, 338 Skin graft, 338, 340 Skull, 322, 338, 343 Small intestine, 21, 285, 305, 310, 339 Smooth muscle, 31, 273, 279, 288, 305, 320, 339, 341 Sneezing, 338, 339

365

Soaps, 339, 345 Social Behavior, 32, 339 Social Environment, 333, 339 Sodium, 149, 214, 302, 319, 339, 342 Sodium Glutamate, 149, 339 Soft tissue, 6, 42, 279, 338, 339 Solid tumor, 273, 339 Solvent, 79, 80, 83, 91, 93, 151, 210, 224, 277, 281, 296, 302, 316, 322, 339, 345 Somatic, 301, 306, 315, 317, 339 Spasmogenic, 273, 339 Specialist, 258, 339 Specificity, 39, 54, 58, 63, 87, 188, 194, 270, 339 Spectroscopic, 23, 27, 53, 339 Spectrum, 4, 51, 59, 63, 72, 80, 82, 85, 100, 126, 127, 218, 228, 307, 320, 339, 346 Sperm, 284, 340 Sphincters, 44, 340 Spinal cord, 275, 283, 284, 293, 295, 296, 316, 319, 323, 340 Spirochete, 340, 342 Spleen, 276, 306, 314, 340 Spores, 19, 184, 196, 198, 232, 309, 340 Sputa, 92, 116, 138, 340 Sputum, 7, 37, 163, 164, 182, 340 Squamous, 118, 295, 340 Squamous cell carcinoma, 118, 295, 340 Squamous cells, 340 Stabilization, 6, 340 Staging, 6, 336, 340 Staphylococcal Infections, 4, 340 Steady state, 23, 33, 340 Steel, 285, 340 Stents, 44, 340 Sterilization, 23, 214, 341 Steroids, 270, 289, 341 Stethoscopes, 114, 341 Stimulant, 305, 341 Stimulus, 292, 293, 296, 311, 334, 341, 343 Stomach, 291, 296, 300, 305, 325, 339, 340, 341 Stomatitis, 128, 341 Strand, 182, 328, 341 Streptococci, 308, 318, 336, 341 Streptomycin, 72, 158, 341 Stress, 9, 46, 72, 91, 95, 96, 222, 300, 329, 335, 336, 341, 347 Stringency, 188, 341 Stroke, 166, 250, 341 Styrene, 33, 61, 86, 96, 336, 341 Subacute, 6, 309, 314, 338, 341

Subclinical, 309, 341 Subcutaneous, 4, 28, 273, 283, 293, 300, 324, 341 Subspecies, 339, 341 Substance P, 296, 316, 336, 337, 341 Substrate, 29, 33, 40, 53, 54, 64, 117, 199, 206, 236, 295, 306, 341, 342 Substrate Specificity, 40, 53, 54, 117, 236, 342 Sulfur, 55, 85, 95, 170, 281, 297, 316, 342 Superantigens, 4, 342 Superinfection, 276, 342 Superoxide, 49, 88, 93, 342 Superoxide Dismutase, 49, 88, 93, 342 Suppression, 10, 48, 78, 90, 180, 223, 320, 342 Suppressive, 4, 172, 174, 223, 342 Suprofen, 208, 342 Surfactant, 85, 94, 139, 150, 168, 207, 342 Sweat, 291, 342 Sweat Glands, 291, 342 Sympathomimetic, 296, 320, 342 Symptomatic, 4, 342 Synaptic, 320, 338, 342 Synergistic, 177, 191, 228, 342, 344 Syphilis, 237, 342 Systemic, 13, 62, 126, 150, 273, 275, 276, 279, 292, 296, 309, 337, 341, 342, 345 T Tachycardia, 276, 343 Tachypnea, 276, 343 Technetium, 6, 343 Teichoic Acids, 303, 343 Temporal, 5, 9, 14, 315, 343 Teratogenic, 271, 343 Testicular, 44, 343 Testis, 343 Testosterone, 334, 343 Tetani, 343 Tetanic, 343 Tetanus, 52, 343 Therapeutics, 12, 17, 20, 28, 54, 57, 186, 240, 244, 343 Thermal, 292, 320, 328, 343 Thoracic, 104, 128, 343, 349 Threonine, 61, 324, 337, 343 Threshold, 50, 237, 343 Thrombin, 21, 297, 327, 331, 343 Thrombomodulin, 331, 343 Thrombosis, 310, 331, 341, 343 Thromboxanes, 275, 343 Thymus, 45, 307, 314, 344

Pseudomonas

Tic, 46, 164, 344 Ticarcillin, 67, 240, 344 Ticks, 309, 344 Tinnitus, 323, 344 Tissue Culture, 36, 89, 344 Tobramycin, 62, 123, 124, 240, 245, 344 Tolerance, 73, 80, 81, 91, 92, 95, 171, 215, 222, 269, 344 Tomography, 287, 336, 344 Tonsillitis, 336, 344 Tooth Preparation, 269, 344 Topical, 21, 196, 197, 198, 232, 275, 284, 286, 296, 306, 339, 344, 346 Toxicity, 13, 28, 38, 183, 193, 196, 204, 215, 216, 226, 282, 293, 315, 316, 336, 344, 348 Toxicology, 58, 252, 344 Toxin, 13, 28, 39, 183, 185, 193, 194, 292, 295, 343, 344 Trace element, 284, 286, 338, 344 Tracer, 35, 305, 345 Trachea, 48, 280, 312, 325, 345 Traction, 285, 345 Transduction, 41, 338, 345 Transfection, 278, 301, 345 Transfer Factor, 307, 345 Transferases, 302, 345 Translation, 272, 296, 345 Translational, 217, 345 Translocating, 276, 345 Translocation, 36, 39, 91, 104, 106, 193, 276, 296, 345 Transmitter, 269, 276, 311, 320, 345 Transplantation, 131, 257, 307, 345 Transposons, 57, 345 Trauma, 6, 21, 242, 304, 315, 344, 345, 349 Treatment Failure, 4, 345 Trees, 203, 272, 336, 345 Trichloroethylene, 90, 152, 157, 345 Triclosan, 118, 345 Trigeminal, 297, 345 Trimethoprim-sulfamethoxazole, 4, 346 Tropolone, 184, 346 Tryptophan, 286, 346 Tuberculosis, Oral, 237, 346 Tularemia, 237, 346 Tumor marker, 278, 346 Tumor Necrosis Factor, 8, 346 Typhimurium, 25, 44, 94, 211, 346 Tyrocidine, 39, 346 Tyrothricin, 303, 346 U Ubiquitin, 217, 346

366

Ulcer, 283, 346, 347 Ulceration, 226, 312, 346 Ultraviolet Rays, 214, 346 Unconscious, 290, 307, 346 Uncoupling Agents, 311, 346 Uracil, 182, 333, 346 Uranium, 195, 343, 346 Urbanization, 191, 347 Ureters, 312, 347 Urethra, 330, 347 Urinary, 3, 4, 14, 24, 42, 44, 97, 104, 106, 111, 127, 230, 285, 289, 320, 331, 347 Urinary tract, 4, 24, 42, 104, 106, 127, 230, 320, 331, 347 Urinary tract infection, 4, 25, 42, 104, 106, 127, 230, 320, 331, 347 Urine, 25, 37, 127, 182, 230, 279, 312, 320, 334, 347 Urogenital, 302, 347 Urology, 100, 347 Urticaria, 273, 347 Uvea, 294, 347 V Vaccination, 14, 57, 126, 347 Vaccine, 10, 15, 48, 57, 69, 72, 106, 113, 126, 227, 233, 270, 347 Vacuoles, 294, 322, 347 Vagina, 291, 347 Valves, 44, 347 Vancomycin, 59, 101, 347 Varicose, 312, 347 Varicose Ulcer, 312, 347 Vascular, 34, 44, 173, 183, 184, 273, 279, 284, 291, 295, 309, 320, 327, 347 Vasodilator, 280, 305, 347 VE, 55, 347 Vector, 97, 189, 215, 222, 345, 347 Vegetative, 32, 347 Vein, 273, 275, 311, 321, 348 Venereal, 342, 348 Venoms, 290, 348 Venous, 44, 275, 312, 320, 331, 347, 348 Ventilation, 179, 348 Ventilator, 57, 315, 335, 348 Venules, 279, 281, 348 Vertigo, 323, 348 Veterinary Medicine, 251, 348 Vibrio, 9, 14, 52, 284, 348 Vibrio cholerae, 9, 284, 348 Vinyl Chloride, 99, 348 Viral, 20, 48, 181, 182, 198, 232, 289, 309, 321, 345, 348

367

Viral vector, 48, 348 Virion, 277, 348 Virulent, 17, 36, 59, 348 Virus, 15, 168, 188, 196, 198, 204, 228, 232, 277, 301, 302, 327, 335, 345, 348 Vitreous, 312, 335, 349 Vitreous Body, 335, 349 Vitro, 13, 21, 29, 35, 42, 43, 44, 46, 49, 51, 57, 58, 59, 79, 99, 107, 112, 115, 121, 126, 141, 173, 184, 192, 220, 301, 308, 328, 336, 337, 342, 344, 349 Vivo, 22, 40, 42, 43, 51, 79, 95, 220, 349 Vulgaris, 85, 349 W War, 283, 349

White blood cell, 274, 303, 308, 313, 314, 315, 318, 319, 320, 327, 349 Windpipe, 295, 325, 349 Wound Healing, 36, 285, 310, 315, 318, 349 Wound Infection, 98, 115, 349 X Xanthomonas, 93, 156, 185, 186, 227, 349 Xenograft, 273, 349 X-ray, 9, 17, 22, 23, 27, 40, 59, 287, 298, 315, 318, 321, 333, 336, 346, 349 Y Yeasts, 199, 299, 325, 349 Yttrium, 148, 349 Z Zygote, 288, 349 Zymogen, 331, 349

Pseudomonas

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