Three days in Madison have thoroughly modified my view on clostridial neurotoxins. While still realizing the numerous activating, modifying and protective inputs, I cannot judge the meaningfulness of the meeting impartially. Neither may the reader expect a complete summary of all presentations. Collected in this volume, they speak for themselves without requiring an arbiter. Instead I shall write down my very personal opinions as a researcher who has studied clostridial neurotoxins for nearly 25 years. Comparable conferences have been rare during this time. A comprehensive symposium 4 on C. botulinum neurotoxins has been organized at Ft. Detrick. International conferences on tetanus have been held regularly under the auspices of the Wodd Health Organization. One or maximally two days of these meetings have been devoted to tetanus toxin and its actions whereas the sponsor and the majority of the participants have been interested mainly in epidemiology, prevention and treatment of tetanus as a disease (see refs. 5,6). Some aspects of clostridial neurotoxins have been addressed in the context of bacterial toxins, in particular in the biennial European workshops. 1-3,7,8 The Madison meeting differed from the previous ones in three aspects. First, it covered both tetanus and botulinum neurotoxins. The fusion was justified because of their huge similarities in primary structure, in their mode of action and in their cellular targets. Second, the meeting was not limited to toxins but drew some lines on which modern neurobiology might proceed.

Filarial nematodes constitute and important group of human pathogens in tropical regions of the world. Diseases associated with these worms are generally separated into two categories: filariasis, caused by infections of lymphatic dwelling parasites and onchocerciasis, or river blindness, caused by infections of Onchocerca volvulus. Other filariae specifically infect humans and it is likely that zoonotic filarial infections may alter the outcome of infections with human parasites. The chapters in this book will cover concepts that, in most instances, overlap all of these parasites as well as focus on new and emerging ideas. The Filaria, volume five of World Class Parasites, is written for researchers, students and scholars who enjoy reading research that has a major impact on human health, or agricultural productivity, and against which we have no satisfactory defense. It is intended to supplement more formal texts that cover taxonomy, life cycles, morphology, vector distribution, symptoms and treatment. It integrates vector, pathogen and host biology and celebrates the diversity of approach that comprises modern parasitological research.

This book is the result of an international symposium held at the Institute of Virology and Immunobiology of the-University of WUrzburg, Germany, in October 1980. The intent of this symposium was to provide an opportunity to compare the data on coronavirus structure and replica tion as well as to discuss mechanisms of pathogenesis. For over a decade coronaviruses have been recognized as an important group of viruses which are responsible for a variety of diseases of clinical importance in animals and man. Recently new and interesting data on the molecular biology and pathogenesis of coronaviruses have become available and this led us to organize this meeting. The uniformity and diversity in this virus group was evaluated from a molecular point of view and the replication of coronaviruses appears to involve aspects which may be unique for this virus group. Additionally, in contrast to other positive strand RNA viruses it became clear that coronaviruses readily establish persistent infections in the host, a phenomenon which may lead to the different subacute or chronic disorders manifested during coronavirus infection. This volume presents a series of articles based upon the scientific presentation given at the symposium. In addition, there are two articles by B. W. J. Mahy and D. A. J. Tyrrell which summarize the current state of art concerning the biochemistry and biology of coronaviruses, respective ly. We believe this book will be of interest to all virologists and particularly to both established workers and newcomers to this field. V."

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and num bering, has probably reached that stage at which relatively few new truly new-viruses will be discovered. Triggered by the intellectual probes and techniques of molecular biology, genetics, biochemical cytology, and high-resolution microscopy and spectroscopy, the field has experienced a genuine information explosion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 22 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an invalua ble reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere, but which also provides a logical progression of developing facts and integrated concepts."

the discovery of the "splicing" of the gene transcripts, the list would include the whole molecular genetics of the lambda bacteriophage, the notions of "promotor," "repressor," and "integration," the discovery of the reverse flow of genetic information, the very existence of oncogenes, the S'-terminal "cap" struc ture of eukaryotic mRNAs, ... Electronmicroscopy, ultracentrifugation and tissue culture were the landmarks on the way of the young science. During the past few years, however, a major (and not so silent) revolution took place: recombinant DNA technology with all its might entered in our laboratories, and restriction mapping of cloned genomes and sequencing gels have replaced plaque counting and sucrose gradients. The new techniques have made it possible to "dissect" the entire genome of a virus at the molecular level, and studies that would have been dreamt of just in the mid-seventies became the everyday experiments of our days. With new insight into the structure of viral genomes, and a deeper understanding of the mechanisms that regulate their expression, our view of viruses was bound to change: this volume bears witness to this impressive advance."

Milestones in Current Research is a series of reprint collections dis tinguished from other such publications by new concepts in preparation, presentation, and intent. The aim of each volume is to gather for a given field the seminal contributions that have defined and shaped the trends within the most active areas of current research. The selections for each volume and the structure of the book have been determined with the help of a novel tech nique of bibliographic analysis and have then been presented to an acknowl edged scientific authority for minor adjustments and the writing of an In troduction. These introductions will lend historic perspective to the material selected for each volume. The bibliographic analysis used tends to select papers central to the areas of current research within, roughly, the last decade and is a systematic procedure for depicting, delineating, and covering all such areas over a wide spectrum of scientific research. It is hoped that with this procedure it will be possible to achieve an objectivity, authority, and thoroughness not reached by others and that the timeliness of the volumes will not be limited to just a few years. Each volume should have the permanent value of a historical statement and yet be suf ficiently interesting to active researchers in the field as well as to students exploring the quiet way in which the relentless drama of research unfolds in the journal literature.

Bluetongue viruses (BTV) cause diseases that have serious economic consequences in ruminants (sheep, cattle) in many parts of the world. The incidence of bluetongue disease affects the international movement of animals and germ plasm. Although the etiological agent of the disease was isolated in 1900 and preliminary biochemical characterizations were pub lished as early as in 1969, most of the current understanding of the molecular biology, biochemistry, and genetics of BTV has evolved only recently. Triggered by the modern techniques of molecular biology, genetics, and immunology, BTV research has experienced an information explosion in the past 10 years. However, much of this information is scattered throughout an extensive literature. It is therefore an appropriate time to meld this together into a reference book. This book includes compre hensive information on BTV research provided in articles contributed by researchers from around the world. It covers what is known about the molecular structure of the virus and the current understanding of its biology, evolution, and relationships with its invertebrate and vertebrate hosts (infection, immunity, and pathogenicity)."

Infectious agents have been recognized to involve the heart and vascular system for well over a century. Traditional concepts and teachings of their involvement in the pathogenesis of disease have been by a few established mechanisms. Since the last decade of the 20th century there has been renewed interest in the medical and public media on infectious diseases affecting the cardiovascular and cerebrovascular systems, through their relationship with the development of acceleration of atherosclerosis. This volume highlights and reviews new perspectives of infections on the cardiovascular system as never before. It is a truly valuable resource for scientists, researchers, residents, and fellows in the fields of infectious disease, cardiology, and microbiology.

The viruses of the family Rhabdoviridae have an exceedingly broad host range and are widely distributed throughout the animal and plant king doms. Animal rhabdoviruses infect and often cause disease in insects, fish, and mammals, including man. The prototype rhabdovirus, vesicular stomatitis virus VSV), has been extensively studied and provides perhaps the best model system for studying negative-strand viruses. The popularity of VSV as a model system is to a considerable extent due to its relative simplicity and to its rapid growth, generally to high titer, in many cell types ranging from yeast to human. The nucleocapsids of these viruses also carry transcriptional and replicative functions that are expressed in cell-free systems. The first RNA-dependent RNA poly merase was described in VSV and its G protein provided an early model system for studying the synthesis, processing, and membrane insertion of mammalian glycoproteins. VSV is also highly cytopathogenic and has been studied quite extensively for its capacity to kill cells and to shut off cellular macromolecular synthesis. Even earlier, VSV was discovered to be highly susceptible to the action of interferons and has served ever since as a means for quantitating the activity of interferons. To my way of thinking, the spark that ignited the explosion of re search in this field was struck at the First International Colloquium on Rhabdoviruses, attended by 30 or so participants in Roscoff, France, in June 1972."

''Informative, well-constructed, and readable...The contributors are leaders in their fields and what they have to say is worthwhile.'' --- SGM Quarterly, August 1998

This volume contains the lectures given at the NATO Advanced Study Institute on "Biophysics of Photoreceptors and Photomovements in Microorganisms" held in Tir renia (Pisa), Italy, in September 1990. The Institute was sponsored and mainly funded by the Scientific Affairs Division of NATO; the Physical Science Committee and the Institute of Biophysics of National Research Council of Italy also supported the School and substantially contributed to its success. It is our pleasant duty to thank these institu tions. Scientists from very different backgrounds contributed to the understanding of this fast developing field of research, which has seen considerable progress during the last years. The areas of expertise ranged from behavioral sciences, supported by sophi sticated techniques such as image analysis or laser light scattering, to spectroscopy, ap plied, in different time domains, to the study of the primary photoreactions, to electro physiology, biochemistry or molecular biology, with the aim of analyzing the various steps of the transduction chains and how they control the motor apparatus of the cells. The organisms studied covered a wide range, from bacteria to algae, fungi and other eukaryotes. Thus, the ASI represented a successful opportunity for carrying on and imple menting an interdisciplinary approach to the study of the biophysical basis of photore ception and photosensory transduction in aneural organisms, with special attention to the basic phenomena and the underlying molecular events. We hope that this book has caught the spirit in which the ASI was conceived."

Introduction and Perspectives This volume is based on the proceedings of the 7th annual symposium on the topic Neuroimmune Circuits, Infectious Diseases and Drugs of Abuse, Bethesda, Maryland, Oc- ber 7-9, 1999. This symposium, as in the past, focused on newer knowledge concerning the relationship between the immune and nervous systems with regards to the effects of drugs of abuse and infections, including AIDS, caused by the immunodeficiency virus. Presentations discussed the brain-immune axis from the viewpoint of drugs of abuse rather than from the subject of the brain or immunity alone. The major aim of this series of conferences has been to clarify the consequences of immunomodulation induced by drugs of abuse in regards to susceptibility and pathogenesis of infectious diseases, both in man and in various animal model systems. The recreational use of drugs of abuse such as morphine, cocaine, and marijuana by large numbers of individuals in this country and around the world has continued to arouse serious concerns about the consequences of use of such drugs, especially on the normal physiological responses of an individual, including immune responses. Much of the recent data accumulated by investigators show that drugs of abuse, especially opioids and cannabinoids, markedly alter immune responses in human populations as well as in experimental animals, both in vivo and in vitro.

Integrating recent research on the physiology and modelling of bioreactions and bioreactors, the authors present a comprehensive, unified introduction to the principles and practices of the field. The work features nearly 100 detailed design examples and problems, many of which are suitable for hands-on demonstrations on a personal computer or for expanded research. The text will serve as a highly instructive guide for students in bioengineering and biotechnology, as well as biochemical, chemical, and environmental engineering.

This book examines aspects of paediatric infectious diseases written by leading authorities in the field. It is based on a lecture given at the seventh 'Infection and Immunity in Children' (IIC) course held at the end of June 2009 at Keble College, Oxford.

The symposium, "Microbial Diversity in Time and Space," was held in the Sanjo Conference Hall, University of Tokyo, Tokyo, Japan, October 24-26, 1994. The symposium was organized under the auspices of the Japanese Society of Microbial Ecology and co-sponsored by the International Union of Biological Sciences (IUBS), International Union of Microbiological Societies (IUMS), International Committee on Microbial Ecology (ICOME), and the Japanese Society of Ecology. The aim of the symposium was to stress the importance of the global role of microorganisms in developing and maintaining biodiversity. Twenty-four speakers from seven countries presented papers in the symposium and in the workshop, "Microbial Diversity and Cycling of Bioelements," that followed the symposium. Papers presented at the symposium are published in this proceedings. Discussions of the workshop, which were energetic and enthusiastic, are also summarized in this proceedings. The symposium provided an opportunity to address the role of microorganisms in global cycles and as the basic support ofbiodiversity on the planet. Previously unrecognized as both contributing to and sustaining biodiversity, microorganisms are now considered to be primary elements of, and a driving force in, biodiversity. Financial support was provided for the symposium by the CIBA GEIGY Foundation for the Promotion of Science, Naito Foundation, and the Uchida Foundation of the Ocean Research Institute, University of Tokyo. Support from these foundations is gratefully acknowledged. CONTENTS Microbial Biodiversity-Global Aspects ................................. 1 Rita R. Colwell 2. Importance of Community Relationships in Biodiversity ...................

The discovery and concept that Helicobacter pylori is associated with gastric disease including gastric cancer which is one of the most common and frequently lethal forms of malignancy, heralded a new and rapidly expanding field recognizing the emergence of many new pathogens and disease syndromes in clinical medicine, as well as basic infectious disease research. There is now an extensive and widely known literature of how H. pylori is involved in a wide variety of disease syn dromes. As summarized in the introductory chapter of this volume, many major advances have been made in diagnosis, both serologic and endoscopic in time of the involvement of this organism in patients with upper GI ailments as well as its presence in those who are not clinically ill. The Introduction describes the rapid development of understanding the role of this organism in disease. The basic bacteriology of H. pylori is then described in the second chapter. Diagnostic tests for detecting H. pylori infection is then highlighted, as well as the role of such infection in gastric cancer. Current knowledge concerning risk factors and peptic ulcer pathology associated with H. pylori is then described. Newer information concerning therapy of H. pylori infection and colonization is described in a subsequent chapter as well as one concerning the effects of anti biotics on H. pylori infection. The extensive literature on natural substances with anti-H.

Coronaviruses represent a major group of viruses of both molecular biological interest and clinical significance in animals and humans. During the past two decades, coronavirus research has been an expanding field and, since 1980, an international symposium was held every 3 years. We organized the yth symposium for providing an opportunity to assess important progresses made since the last symposium in Cambridge (U. K. ) and to suggest areas for future investigations. The symposium, held in September 1992, in Chantilly, France, was attended by 120 participants representing the majOlity of the laboratories engaged in the field. The present volume collects 75 papers which were presented during the yth symposium, thus providing a comprehensive view of the state of the art ofCoronavirology. The book is divided into 7 chapters. The first chapters gather reports dealing with genome organization, gene expression and structure-function relationships of the viral polypeptides. New sequence data about as yet poorly studied coronaviruses - canine coronavirus CCY and porcine epidemic diarrhoea virus PEDY - are presented. Increasing efforts appear to be devoted to the characterization of products of unknown function, encoded by various open reading frames present in the coronavirus genomes or delived from the processing of the large polymerase polyprotein. Due to the extreme size of their genome, the genetic engineering ofcoronavi\'uses through the production of full length cDNA clones is presently viewed as an unachievahle task.

The nine chapters presented in this book provide contemporary reviews of research on defective RNAs, satellite RNA viruses, and dependent RNA viruses that require the presence of a helper virus in order to establish productive infections. Since their initial identification nearly four decades ago, fundamental analyses of pathogenic and interdependent interactions involving these agents have contributed enormously to our appreciation of virus structure, RNA replication, and processes leading to disease. Findings arising from these studies have also advanced numerous ancillary areas, including structure and function of nucleic acids and proteins, nucleoprotein interactions, translational mechan isms, RNA processing, macromolecular evolution, and a plethora of other specialty topics. Research on these subviral pathogens is continuing to illuminate various aspects of biology, chemistry, and biotechnology, so the book is intended to provide a current treatment that will be useful for readers with interests in topics related to these areas. Observations in the early I 960s first revealed that a defective virus, satellite tobacco necrosis virus (STNV), is associated with and depends on the presence of a hel per virus, tobacco necrosis virus (TNV), for its multiplication. This finding ushered in a new era in virology that soon resulted in a more profound apprecia tion of the relationships of viruses and their interactions with each other."

Structure-Function Relationships of Human Pathogenic Viruses provides information on the mechanisms by which viruses enter the cell, replicate, package their DNA into capsids and mature into new virions. The relation between structural features and the pathogenicity and oncogenicity of some of the most relevant human viral pathogens are demonstrated and the acquisition of defense mechanisms through virus-host interactions are presented. In contrast to textbooks, this volume combines timely research data to provide a holistic view of viral pathogenesis. Furthermore Structure-Function Relationships of Human Pathogenic Viruses illustrates in a single volume the fundamental processes involved in viral life cycles using up-to-date information from research laboratories around the world. Knowledge of these processes is crucial to develop rationales for the design of future drugs. The timeliness of the data and the comprehensive yet concise approach this book takes in order to present the world of viral pathogens should make it a frontrunner in higher education and R&D.

Mounting evidence in the past decade indicates that innate immunity mediates functions above and beyond first-line defense against infection. It is now appreciated that innate immune mechanisms are critically involved in the development of adaptive immunity and, moreover, the regulation of diverse physiological and homeostatic processes. The latter explains why deregulation of innate immunity may lead to pathological disorders that are not necessarily or directly related to host defense. This Volume compiles the latest advances in this rapidly evolving field as presented by eminent scientists at the 7th International Aegean Conference on Innate Immunity in Rhodes, Greece. It includes topics related to the biology and function of Toll-like and other pattern-recognition receptors, complement and its crosstalk with other physiological systems, inflammatory mechanisms and diseases, natural killer cells, and the cooperative interplay between innate and adaptive immune cells. This book is an excellent source of information for researchers and clinicians with interests in immunology, host-microbe interactions, and infectious and inflammatory diseases.

Lyme Borreliosis is a worldwide infectious disease causing a multisystem illness with considerable morbidity, particularly in North America and Europe. The causative agent is the spirochaete Borrelia burgdorferi, which is usually transmitted by the ixodid tick from animal reservoirs. This book is formed by contributions from the Second European Symposium on Lyme Borreliosis, held at St George's Hospital Medical School, London in 1993, which reviewed the current state of knowledge of the condition with regard to clinical manifestations, diagnosis, treatment, ecology, epidemiology, biology and immunopathogenesis. In this book, important data is reviewed concerning the clinical manifestations of Lyme Borreliosis. It seems that strain variation of the spirochaete is the main cause of regional differences seen in the clinical presentation of patients. One striking example of this, is the relatively high incidence of Lyme arthritis in the USA and apparent rarity of this manifestion in some areas of Europe. These important studies open the way for exciting new research that focuses on the immunological and molecular mechanisms that result in disease. A full insight into the ecology of Borrelia burgdorferi is essential to a balanced understanding of the disease and a number of excellent reviews on this subject are included. Significant advances with regard to the biology of Borrelia burgdorjeri and the immunopathogenic mechanisms that result in disease have been made, enabling the role of the Band T lymphocytes in disease to be established and the development of sophisticated phenotyping methods, improved diagnostic tests and effective vaccines.