The understanding of the role of dendritic cells (DCs) in immune responses has come a long way since Steinmann and colleagues described these cells in 1972. - tensive research during the intervening period has provided a good understanding of the complexity of the DC system and its pivotal role in immunity. It is also now clearer how different subsets of DCs interact and regulate each other and how DC populations affect the function of other cells of the immune system. The improved understanding of their role in immune response has led to the idea that modulation of DC functions by, for example, pharmacological agents could be used as a pot- tial therapeutic approach in some pathological conditions. The actual applicability and therapeutic potential of all these approaches is yet to be fully demonstrated but nonetheless, animal models of human diseases are proving to be very helpful in the evaluation of manipulated DCs as a new treatment in diseases like cancer, auto- munity or asthma. DCs are integral to the initiation and regulation of immune response (Banchereau et al. 2000). The outcome of antigen presentation by DCs is determined by their maturation status, which can be induced by their interaction with danger signals. To recognise a wide array of pathogen-associated molecular patterns (PAMP), DCs express a number of pattern recognition receptors (PRR) such as Toll-like rec- tors (TLRs) and C-type lectin receptors (CLR) that recognise structural components of pathogens and discriminate between self and non-self molecules.

R. VANFURTH Infection is an inseparable part of communal life, and infections are more common and more severe in hospital communi ties because the sick are more easily infected than the healthy. However, even though progress in the medical sciences has meant that many more patients suftering from relatively severe diseases can be helped at present, the use of more sophisticated and complex treatment leads to impairment of the defence mechanisms in more patients than was the case ten to twenty years ago, and these patients are also more prone to develop an infection. Two questions are particularly relevant in this context. 1) Under what conditions do hospital infections occur? Defects of host defence mechanisms are of great importance in this respect. Such defects can be due to the disease or to the treatment given to the patient. 2) Which of the host defence mechanisms can be affected by a stay in the hospital? Among the factors involved in the host defence against infections (Table I), a number are especially important in this respect. For instance, venepuncture, indwelling catheters, and surgery all cause a breach in the surface structures. Anaesthesia causes temporary impairment of mechanical factors. Vascularization may be defective -- especial ly in the aged and patients with diabetes mellitus -- and this may complicate the healing of wounds in the skin and mucous membranes after surgery."

The clinical microbiology laboratory is often a sentinel for the detection of drug resistant strains of microorganisms. Standardized protocols require continual scrutiny to detect emerging phenotypic resistance patterns. The timely notification of clinicians with susceptibility results can initiate the alteration of antimicrobial chemotherapy and improve patient care. It is vital that microbiology laboratories stay current with standard and emerging methods and have a solid understanding of their function in the war on infectious diseases. Antimicrobial Susceptibility Testing Protocols clearly defines the role of the clinical microbiology laboratory in integrated patient care and provides a comprehensive, up-to-date procedural manual that can be used by a wide variety of laboratorians. The authors provide a comprehensive, up-to-date procedural manual including protocols for bioassay methods and molecular methods for bacterial strain typing. Divided into three sections, the text begins by introducing basic susceptibility disciplines including disk diffusion, macro and microbroth dilution, agar dilution, and the gradient method. It covers step-by-step protocols with an emphasis on optimizing the detection of resistant microorganisms. The second section describes specialized susceptibility protocols such as surveillance procedures for detection of antibiotic-resistant bacteria, serum bactericidal assays, time-kill curves, population analysis, and synergy testing. The final section is designed to be used as a reference resource. Chapters cover antibiotic development; design and use of an antibiogram; and the interactions of the clinical microbiology laboratory with the hospital pharmacy, and infectious disease and control. Unique in its scope, Antimicrobial Susceptibility Testing Protocols gives laboratory personnel an integrated resource for updated lab-based techniques and charts within the contextual role of clinical microbiology in modern medicine.

This book covers the state-of-the-art research on molecular biology assays and molecular techniques enabled or enhanced by microfluidic platforms. Topics covered include microfluidic methods for cellular separations and single cell studies, droplet-based approaches to study protein expression and forensics, and microfluidic in situ hybridization for RNA analysis. Key molecular biology studies using model organisms are reviewed in detail. This is an ideal book for students and researchers in the microfluidics and molecular biology fields as well as engineers working in the biotechnology industry. This book also: Reviews exhaustively the latest techniques for single-cell genetic, epigenetic, metabolomic, and proteomic analysis Illustrates microfluidic approaches for inverse metabolic engineering, as well as analysis of circulating exosomes Broadens readers' understanding of microfluidics convection-based PCR technology, microfluidic RNA-seq, and microfluidics for robust mobile diagnostics

This book provides readers with information on the factors underlying the emergence of infectious diseases originating in animals and spreading to people. The One Health concept recognizes the important links between human, animal, and environmental health and provides an important strategy in epidemic mitigation and prevention. The essential premise of the One Health concept is to break down the silos among the different health professions and promote transdisciplinary collaborations. These concepts are illustrated with in-depth analyses of specific zoonotic agents and with examples of the successes and challenges associated with implementing One Health. The book also highlights some of the challenges societies face in confronting several specific zoonotic diseases. A chapter is included on comparative medicine to demonstrate the broad scope of the One Health concept. Edited by a team including the One Health Initiative pro bono members, the book is dedicated to those studying zoonotic diseases and comparative medicine in both human and veterinary medicine, to those involved in the prevention and control of zoonotic infections and to those in the general public interested in the visionary field of One Health.

V Pentostam, an uncharacterized complex of Sb and carbohydrate derived from gluconic acid, is concentrated by Leishmania amastigotes via protein binding. Biochemical consequences of the interaction of amastigotes with Pentostam are inhibition of parasite bioenergetics and inhibition of ATP synthesis. REFERENCES 1. J.C. Mottram and G.H. Coombs. Enzyme activities of amastigotes and promastigotes and their inhibition by antimonials and arsenicqls. Exper. Parasitol. 59:151 (1985). 125 2. S.L. Croft, K.D. Neame and C.A. Homewood. Accumulation of [ Sb] sodium stibogluconate by Leishmania mexicana amazonensis and Leishmania donovani in vitro. Compo Biochem. Physiol. 68c:95 (1981). 3. J.D. Berman, J.V. Gallalee, and B.D. Hansen. Leishmania mexicana: uptake of sodium stibogluconate (Pentostam) and pentamidine by parasite and macrophages. Exper. Parasitol. 64:127 (1987). 4. J.D. Berman, D. Waddell and B.D. Hanson. Biochemical meChanisms of the antileishmanial activity of sodium stibogluconate. Antimicrobial Agents Chemotherapy. 27:916 (1985). 5. J.D. Berman, J.V. Gallalee, and J.M. Best. Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid B-oxidation in Leishmania mexicana amastigotes. Biochem. Pharmacol. 36:197 (1987). 6. D.T. Hart and G.H. Coombs. Leishmania mexicana: Energy metabolism of amastigotes and promastigotes. Exper. Parasitol. 54:397 (1982). 478 EFFECTS OF SINEFUNGIN ON CELLULAR AND BIOCHEMICAL EVENTS IN PROMASTIGOTES OF LEISHMANIA d. donovani Fran~oise Lawrence, and MaIka Robert-Cero Institut de Chimie des Substances Naturelles C.N.R.S.

New Bacterial Vaccines focuses upon unfulfilled needs for bacterial vaccines. The increase in drug resistance among many bacterial species has increased the need for new bacterial vaccines. This book serves as a comprehensive reference on the major aspects of developing new bacterial vaccines. The distinctive feature of this book is that it focuses upon new vaccines now under development by reviewing key issues for each vaccine target and new technologies being applied to developing new vaccines.
This book should prove useful for students in the life sciences, scientists, developers of vaccines and biotechnology products, clinicians, regulators, and health-care practitioners.

This volume thoroughly covers HIV-1 antiretrovirals currently in clinical use, together with their advantages and limitations. HIV-1 inhibitor resistance is discussed in detail, and critical assessments as to what will be required of future antiretrovirals in order to halt viral replication, reduce viral resistance, and alter the state of viral latency are presented. Experts at the forefront of HIV-1 research provide overviews of approaches from the fields of virology, chemical biology and structural biology for obtaining small molecule inhibitors that target viral regulatory and structural components at multiple points in the viral lifecycle. The individual chapters will appeal to scientists and clinicians alike.

This volume focuses on blocking disease transmission and the ecological perspective of pathogens and pathogenic processes. The chapters on blocking transmission cover the environmental safety of space flight, biocides and biocide resistance, as well as infection control in healthcare facilities. The book also offers insights into the ecological aspects of infectious disease, introducing the reader to the role of indigenous gut microbiota in maintaining human health and current discussions on environmentally encountered bacterial and fungal pathogens including species that variously cause the necrotizing skin disease Buruli ulcer and coccidioidomycosis. Further, it explores the influenza A virus as an example for understanding zoonosis. It is a valuable resource for microbiologists and biomedical scientists alike.

This book provides an essential update on the startling array of novel insecticidal toxins and drugs produced by the fascinating bacterium Photorhabdus. The respective chapters describe everything from the detailed molecular biology of the 'Toxin complexes' or Tc's to the complexity of insect immune response in relation to both the bacterium and its nematode vector. The volume covers both primary (toxin production and regulation) and secondary (natural product synthesis and regulation) metabolism and emphasises the potential use of toxins and drugs in both agriculture and medicine. It also discusses in detail two totally novel quorum sensing mechanisms and the likely role of LuxR solos in sensing the presence of different bacterial hosts. Lastly, the book explores the unique case of P. asymbiotica, which seems to have evolved the ability to infect both insects and humans. This synthesis proves that Photorhabdus truly does offer a 'gold mine' for the discovery of novel insecticidal proteins and novel natural products with potential uses in agriculture and medicine alike.

Recently, there has been an upsurge in microbial infections. Extensive and inappropriate usage of antimicrobial drugs in treating infections has led to the evolution of a resistant strain of microorganisms and irreversible immunosuppression in humans. Medical institutions and hospitals require solutions to combat these contagions in order to avoid future epidemics. Strategies to Overcome Superbug Invasions: Emerging Research and Opportunities highlights current research and potential strategies to prevent the emergence and re-emergence of drug-resistant pathogenic microbial strains. The content within this publication examines biosensing, global initiatives, nanomaterials, and alternative therapies. It is designed for microbiologists, biotechnologists, pharmacists, pharmacologists, virologists, formulation scientists, infectious disease specialists, government officials, policymakers, healthcare practitioners, doctors, nurses, hospital directors, researchers, surgeons, and academicians who are seeking research on innovative solutions for multi-drug-resistant infections.

This volume on enzootic bovine leukosis (EBL) and bovine leukemia virus (BLV) is the second in our series "Developments in Veterinary Virology." Each book in this series is devoted to a major virus disease of agricultural significance. The chapters in each volume are planned to supply information on a range of subjects from pathogenesis of the causative virus to vaccination, eradication, and rules regarding disease control. The present volume on enzootic bovine leukosis and bovine leukemia virus updates the reader on the disease and its causative agent and includes the nucleotide sequence of the BLV genome as well as data on its integration into the DNA of the tumor cell. Insights into diagnosis, veterinary legislation, and the economic aspects of EBL are also provided. Intense research conducted on EBL and BLV during the course of a decade is presented in a most concise and in-depth manner, so as to provide the reader with a comprehensive overview of this economically important disease of cattle. I wish to thank the editors, A. Burny and M. Mammerickx, as well as all the authors, for making this excellent book available at a stage when the knowledge on bovine leukemia virus will also contribute to our understanding of the virus causing human AIDS.

Any branch of biology depends for its progress on the development of new concepts and to a lesser, but sometimes crucial, extent on the elimination of erroneous notions. Understanding the roles of bacteria required first the observation that such minute creatures existed, and subsequently the exper imental demonstrations that their presence was necessary for the occurrence of particular phenomena. In this first volume, the authors review the development of scientific understanding of the role of microbes as agents of diverse natural processes. Notably absent is a separate review of the history of microbes as agents of disease, a his tory available in many other publications. Regrettably absent is a review of the his tory of microbes as agents of inorganic transformations, a serious omission that resulted from the illness of the prospective author late in the preparation of this volume. The topic will of course be treated in later volumes, although not predominantly in a historical manner. Otherwise, the emphasis in this volume is on the history of understanding interrelationships between modes of bacterial existence and the inanimate environment. These relationships were established long be fore multicellular, differentiated or ganisms appeared as potential microbial habitats, and their recognition and elucidation contributed greatly to the widened appreciation of bacterial di versity and the importance of these simpler creatures to the physiochemical conditions of the biosphere."

Reports of influenza-like illnesses date back to the Middle Ages, and outbreaks of influenza likely afflicted humans long before that. Over the last half century, influenza virus research has led to the development of two classes of antivirals - ion channel and neuraminidase inhibitors. Recently, a method of the artificial generation of an influenza virus was established. This system has been instrumental in the development of novel influenza vaccines and in the understanding of viral pathogenicity and the functions of viral proteins. Influenza Virus: Methods and Protocols summarizes the current techniques that have made this progress possible, ranging from protocols for virus isolation, growth, and subtyping to procedures for the efficient generation of any influenza virus. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Influenza Virus: Methods and Protocols seeks to serve both professionals and novices with the techniques used in numerous laboratories around the world that are, thus, the building blocks that underpin almost all influenza virus research.

Achieving good clinical outcomes with implanted biomaterials depends upon achieving optimal function, both mechanical and biological, which in turn depends upon integrating advances realized in biological science, material science, and tissue engineering. As these advances push back the frontiers of biomaterial medicine , the control and patterning of bio-implant interface reactions will have a tremendous impact on future design and prospects of implant treatments.

Bio-Implant Interface: Improving Biomaterials and Tissue Reactions brings together a remarkable panel of scientists to present the state of the art in our understanding of interactions at the interface between biomaterials and living tissue. Much of the focus is on the importance of the implant surface's topography and chemistry to its interaction with the biological environment. Biomineralization along with the biological content of the interface and its role in directing cellular response along desired pathways also receive particular attention.

The pursuit of new and better designs for improved biocompatibility and patient response to implants continues to challenge clinicians and scientists alike. This book offers a unique opportunity to bring yourself up to date on recent advances in the field and new strategies for controlling the bio-implant interface.

Research on antiviral drugs and their mode of action in infected cells. in animals and in man. has led to a better understanding of the molecular pro cesses involved in virus replication. Screeninq of large numbers of natural and semisynthetic compounds resulted in the characterization of certain sub stances that had a limited efficiency as antiviral druqs. A few chemically synthesized compounds were also found to be effective as antiviral agents in the chemotherapy of human virus diseases. A major difficulty in the develop ment of effective antiviral agents has been the lack of selectivity. and toxicity for uninfected cells. of drugs that effectively inhibited virus replication in vitro. Further understanding of the molecular processes of virus replication in infected cells has resulted in the development of new antivirals directed at virus-coded enzymes or proteins. Recent studies on antivirals that are activated by the herpes simplex virus type l-coded thy midine kinase from a prod rug to an antiviral drug have opened new directions in the development of effective antiviral drugs. The present book deals with a number of antiviral drugs effective against herpes simplex viruses and provides some insight into the molecular aspects of virus replication. It also throws light on the new approaches to the development of antiviral drugs. The molecular basis of the antiviral activity of new and known drugs and their possible use in chemotherapy of viral disease are presented in this book."

This detailed volume presents timely and authoritative content offering a comprehensive overview of the current state of the art in fungal diagnostics. Moreover, it addresses on-going developments expected to provide a basis for targeted treatment strategies resulting in improved outcome of invasive mycoses. The knowledge of host-related predisposing factors and stratified treatment options facilitating timely onset of adequate antifungal therapy are critical for successful clinical management and outcome of invasive fungal disease (IFD), requiring not only rapid diagnosis of a fungal infection and identification of the causative species, but also assessment of pathogen/host factors related to pathogenicity, susceptibility, and response to treatment. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Human Fungal Pathogen Identification: Methods and Protocols serves as an ideal reference for researchers investigating the ever-growing worldwide healthcare problems involving fungal infections.

This book focuses on the envelope of Gram-positive bacteria including its composition, the latest discoveries in the mechanisms behind its assembly, and its role in pathogenesis. Furthermore, new applications in biotechnology and vaccine development involving these bacteria are discussed in detail. This concise volume consists of eleven chapters by prominent experts in the field, which review the latest findings and current state of knowledge on a range of diverse yet interlinked aspects. This book is written for all researchers, clinicians and technicians engaged in basic or applied science projects on Gram-positive bacteria.

This volume provides researchers with the most updated understanding of the basics of West Nile Virus (WNV). Chapters focus on the biology, virology, epidemiology, pathogenesis, as well as the step-by-step molecular, cellular, and statistical methods to study WNV infection in cell culture, mosquitos, animal models, and human clinical specimen. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, West Nile Virus: Methods and Protocols aims to be a valuable resource for all researchers interested in learning more about this important and developing field.

This book was written during a period when the technologies of genetic engineering were being applied to the study of animal viruses and when the organization and function of individual virus genes were being elucidated. This book, which uses human and animal viruses as models, aims to under stand the developments in molecular virology during the last 20 years. Al though molecular virology could also be taught by means of bacteriophages or plant viruses, the advantage of using animal viruses is in their ability to cause human and animal diseases as well as to transform cells, a primary problem in medicine. For the sake of clarity and convenience, not all the individual contributors to the various aspects of molecular virology were cited in the text. Instead, the reader is referred to review articles or key papers that list the numerous excel lent publications that have contributed to clarification of the various molecular processes. Thus the end-of-chapter bibliographies will guide the reader to the publications in which the original contributing authors are quoted. References given under the heading Recommended Reading are intended to assist those interested in pursuing a given subject further. I hope that this book will fulfill the purpose for which it is designed, and I urge readers to contact me if errors are found or updating is required."

This volume focuses on apoptotic and non-apoptotic programmed cell death, including necroptosis, pyroptosis, and ferroptosis, and presents recent findings in the field. It discusses the crucial role that apoptotic and non-apoptotic cell death play in various pathological conditions, such as skin diseases, inflammatory bowel diseases, and virus infections. Further, it highlights the mechanisms underlying the recognition and clearance of dead cells, and the subsequent biological responses triggered by phagocytosed macrophages and factors released from dying cells. Offering insights into cell death, it is a valuable resource for researchers and clinicians developing novel strategies to treat various diseases that are closely associated with cell death.

The successful prophylaxis and treatment of ubiquitous respiratory infections is essential for the enhancement of public health. The chapters provide new insights into the biology of causative pathogens, tackle the epidemiological aspects, and present an update on diagnostics, prevention and therapy of infections. The emerging new pathogens and antibiotic resistance of the old ones are discussed. Novel markers of the severity of community acquired pneumonia, which bears high morbidity and mortality, also are presented.

depth overview of the retrovirus family. I have greatly enjoyed and learned from this experience. Each chapter is an excellent introduction to the topic covered and provides a good foundation for further work in the field. Jay A. Levy University of California School of Medicine San Francisco, California REFERENCES Brown, E. W., Yuhki, N., Packer, C., and O'Brien, S. J., 1994, A lion lentivirus related to feline immunodeficiency virus: Epidemiologic and phylogenetic aspects, ,. Viral. 68:5953-5968. Merza, M., Larsson, E., Steen, M., and Morein, B., 1994, Association of a retrovirus with a wasting condition in the Swedish moose, Virology 202:956-961. Contents Chapter 1 The Human Immunodeficiency Viruses Edward Barker, Susan W Barnett, Leonidas Stamatatos, and Jay A. Levy I. Introduction .................................................... 1 TI. Description of Agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 A. Virus Structure .............................................. 2 B. Genetic Organization and Gene Function ...................... 2 TIL Transmission.................................................... 7 A. General Observations ........................................ 7 B. HIV Transmission by Blood and Blood Products ................ 8 C. HIV Transmission by Genital Fluids ........................... 10 D. HIV Transmission by Other Body Fluids ....................... 12 E. Mother-to-Child Transmission ................................ 12 IV. HIV Infection of the Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . . . . A. Introduction ................................................. 13 B. HIV-Cell Interaction............ ............... .............. 15 C. CD4-Induced gp120 Conformational Changes .................. 16 D. Soluble CD4-Induced gp120-gp41 Dissociation..... ............ 16 E. gp120 Proteolytic Cleavage ................................... 17 F. pH-Independent Membrane Fusion ............................ 19 G. Transmission of HIV by Cell-to-Cell Fusion.................... 19 H. Additional Cell Surface Receptors for HIV ..................... 20 I. The Envelope Region and Cell Tropism ........ . . . . . . . . . . . . 21 . . . .