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

In recent years increased scientific attention has been given to immediate defense mechanisms based on non-clonal recognition of microbial components. These mechanisms constitute the innate immunity arm of the body s defense. Identification of pathogens by these mechanisms involves primarily receptors recognizing sugar moieties of various microorganisms. Innate immunity based mechanisms are essential for the existence of multicellular organisms. They are evolutionarily conserved and designed to provide immediate protection against microbial pathogens to eradicate infection. Activation of innate immunity is crucial for transition to specific immunity and for its orientation, and to assist the specific immune response in the recognition of pathogens and their destruction. Innate immunity is regularly involved in the arrest of bacterial, mycotic, viral and parasitic infections, giving the specific immune response time to become effective. It becomes critically essential in immunocompromised patients who fail to mount specific immune responses due to congenital or acquired immunodeficiencies as a result of chemotherapy, dialysis, immunosuppressive drugs, or HIV infection. The Innate Immunity arsenal constitutes polymorphonuclear and mononuclear phagocytes, mast cells, the complement system, Natural Killer cells, antimicrobial peptides, and presumably a subset of T lymphocytes with TCRl receptors.

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."

It would have been difficult at the beginning of the 80's to have predicted that by the end of the decade, Medical Virology would have become one of the most important topics in the area of both basic and clinical research. Although we were expecting a progressive increase in awareness of the role played by viruses in different diseases, we did not expect the outbreak of a fatal disease that was going to shake the roots of our society. The appearance of the human immunodeficiency virus (HIV-1) in the early 80's, has prompted a unique re search impetus in the area of Medical Virology. The knowledge that we are gaining in our attempt to understand the biology of HIV-1 and the immuno logical response to this virus should not only help us control the spread of this virus, but should also help us to better understand other viral infections. Let us hope that during the 1990's we can learn how to control HIV-1 infections so that by the end of the decade, no more human lives succumb to an infection with this virus. Luis M. de la Maza Irvine, California Ellena M. Peterson March, 1990 v ACKNO EDGEMENTS We would like to thank all the speakers that came to San Francisco and shared their knowledge during the lectures and for writing the chapters in this book."

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.

The recent sequencing of mycoplasma genomes has marked a turning point in the molecular genetic analysis of these microorganisms. Transcriptome and proteome analyses promise to provide the first definition of the total protein complement of a cell. The mycoplasma group includes the smallest known self-replicating organisms carrying the smallest number of genes. No wonder, therefore, that mycoplasmas have a special appeal to those interested in deciphering the minimal set of genes essential for life. Mycoplasma genomics facilitated better understanding of mycoplasma pathogenesis. Most impressive are the findings concerning the interaction of mycoplasmas with the immune system, macrophage activation, cytokine induction, mycoplasma cell components acting as superantigens, and autoimmune manifestations. The molecular definition of mycoplasmal adhesins responsible for mycoplasma attachment to host cells and evasion of the host immune system by antigenic variation of mycoplasmal surface components are other 'hot' subjects of research.Demonstration of the ability of mycoplasmas to enter host cells, cause fusogenic, apoptotic and oncogenic effects, as well as the possible association of mycoplasmas with arthritis, had their share in intensifying research on mycoplasma pathogenesis, bringing more researchers into the circle of those interested in this group of organisms. The present book is a comprehensive, up-to-date, multi-authored treatise.

This is the third volume of Advances in Microbial Ecology to be produced by the current editorial board. I would, therefore, like to take this opportunity to thank my co-editors for all their efforts, particularly in maintaining a balance of subject matter and geographical distribution of the contributions. Volume 15 is no exception in that we have a balance between the prokaryo tic and eukaryotic organisms and a range of subject matter from applied ecology through process ecology to ecological theory. The response from our readers has been encouraging in the sense that the breadth of coverage is much appreciated, particularly by teachers and postgraduate/postdoctoral researchers. However, we still strive to improve our coverage and particularly to move wider than the North America/Europe axis for contributions. Similarly, we would like to see coverage of the more unusual microbes, perhaps a chapter devoted to the ecology of a particular species or genus. There must exist many ecological notes on "rarer" organisms that have not found their way into the standard textbooks or taxonomic volumes; properly compiled these could provide valuable information for the field ecologist. Ecological theory has, until recently, been the domain of the "macroecolo gist. " Recent advances in molecular techniques will ensure that the microbial ecologist will playa more significant role in the development of the subject. We shall not, therefore, change our policy of encouraging our contributors to specu late, permitting them sufficient space to develop their ideas.

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."

Study of the phenomena of bacterial adhesion to surfaces has accelerated considerably over the past 10 to 15 years. During this period, microbiologists have become increasingly aware that attachment to a substratum influences considerably the activities and structures of microbial cells. Moreover, in many cases attached communities of cells have important effects on their substratum and the surrounding environment. Such phenomena are now known to be important in plant and animal hosts, water and soil ecosystems, and man-made structures and industrial processes. Much work on microbial adhesion in the early 1970s was descriptive. Those studies were important for detecting and describing the phenomena of bacterial adhesion to substrata in various environments; the findings have been presented in numerous recently published, excellent books and reviews. In some studies, attempts were made to elucidate some funda mental principles controlling adhesion processes in different environments containing a variety of microorganisms. Common threads have been observed occasionally in different studies. Taken as a whole, however, the information has revealed that many disparate factors are involved in adhesion processes. Whether a particular microorganism can adhere to a certain substratum depends on the properties of the microbial strain itself and on charac teristics of the substratum and of the environment.

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.

Whereas plant and insect infections are commonly caused by fungi, only a small minority of the vast diversity of fungal species is pathogenic to humans. Despite this, fungal infections cause considerable morbidity and mortality worldwide. This volume is dedicated to the biology, clinical presentation and management of invasive fungal infections. Major pathogenic fungi are introduced by world-leading experts and the basic principles of fungal virulence are reviewed in the light of new results and experimental technologies that offer unprecedented insights into invasive infections caused by Aspergillus, Candida, Cryptococcus, Pneumocystis and Mucorales. In parallel, the clinical presentation of invasive fungal infections and current approaches to their diagnosis and treatment are summarized to provide an overview of human pathogenic fungi, linking pathogen biology to the clinical presentation of disease.

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 meeting that provided the material for this book was the 58th Symposium of the Federation of European Microbiological Societies (FEMS) entitled MOLECULAR PATHOGENESIS OF GASTROINTESTINAL INFECTIONS which was held in Helsingor, Denmark from 2nd to 4th September, 1990. The aim of this meeting was to bring together scientists from a range of discipline- microbiology, cell biology, molecular biology and immunology - to consider how microbes, including parasites, colonize and infect the gastrointestinal tract. The programme was designed to focus particular attention on the range of strategies whereby enterovirulent bacteria and parasites colonize the gastrointestinal mucin layer, how they adhere to and penetrate the epithelial layer by entering the cells or passing between them, and how various protein toxins may facilitate these processes. Speakers were especially encouraged to highlight the recent expansion in our knowledge of the molecular mechanisms by which enterotoxigenic and enteropathogenic Escherichia coli, shigellae, salmonellae and Yersinia enterocolitica cause intestinal disease. There were also discussions of recently-discovered gastrointestinal pathogens such as Clostridium difficile and Helicobacter pylori as well as accounts of how virulent determinants can be used to develop new diagnostic methods based on DNA gene probes and the polymerase chain reaction (PCR). These presentations provided the basis for the chapters in this book.

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."