The growing concern about where energy rich chemicals for the future will come from has stimulated a resurgence of interest in the potentialities of microbial fermentations to assist in meeting anti cipated demands for fuels and chemicals. While much attention has been given recently to the early deployment of alcohol production plants and similar currently available technologies, the potential future developments have received much less attention. One of the intentions of the present symposium was to look ahead and try to perceive some of the prospects for future fermentation technology. In order to accomplish this, a symposium program of sizable diversity was developed with workers giving a representative cross section of their particular specialty as an indicator of the status of basic information in their area. In addition, an attempt was made to elicit from the various participants the types of fundamental infor mation which should be generated in the coming years to enable new fermentation technology to proceed expeditiously. In organizing the symposium particular effort was made to involve workers from the academic, industrial and governmental scientific communities."

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 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, bio chemical cytology, and high resolution microscopy and spec troscopy, 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 18 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."

This book is a festschrift to mark the career of ogy, immunology and clinical aspects of each Dr David Tyrrell, eminent virologist and group. There are also more general chapters physician. Almost all of the contributors have overviewing the clinical manifestations, treat been colleagues or students at some time ment and pathophysiology of respiratory during his career. Unlike most festschrifts, virus infections. In addition, chapters in however, the essays have been integrated to which psychological aspects and the ethical produce a comprehensive book that covers use of human volunteers are discussed will be the entire field of non-bacterial infections of of interest to all those involved with respira the human respiratory tract. This is a measure tory infectious agents. of the breadth of interest of the research We hope also that this book serves as a undertaken by David, spanning a period of fitting tribute to a man who is a true poly over 40 years. math: a physician, researcher, teacher, We hope that this book will be of interest mentor, linguist and ambassador for science, to microbiologists, virologists and in particu among other things. To those of us who have lar, to physicians. All the major virus groups contributed to this book, he is even more: a are covered, as well as chlamydial and friend.

'You damn sadist/said mr cummings 'you try to make people think. ' -Ezra Pound (Canto 89) What makes herpesviruses unique? It is certainly not the size of their genomes or the individual features of their reproductive cycle, although in toto striking features that are exclusive to the herpesviruses abound. Unquestionably, the pre-eminent feature is the relationship of herpes viruses with their natural hosts. As described in preceding volumes, all herpesviruses seem to be able to colonize and to remain in a latent, nonproductive form for life of their hosts. Once established in the host, the relationship is best described as that of an armed truce. What happens when this truce breaks down or when the host encounters the virus for the first time is the subject of this volume. We have focused primarily on the five human herpesviruses herpes simplex virus 1 (HSV-l), herpes simplex virus 2 (HSV-2), cytomegalovirus (CMV), varicella zoster virus (VZV) and Epstein-Barr virus (EBV)] because much more is known about them than about any other herpesviruses, and because it is of interest to compare both the diversity of manifestations of infections with human herpesviruses and the spectrum of human responses to these viruses. This volume summarizes the current knowledge of the pathogenesis and immunobiology of herpesvirus infections in man and describes new and developing approaches to prophylaxis and treatment. It contains con tributions from distinguished research scientists presently engaged at the forefront of these scientific investigations."

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.

The first volume of the series entitled Comprehensive Virology was pub lished in 1974 and the last is yet to appear. We noted in 1974 that virology as a discipline has passed through its descriptive and phenomenological phases and was joining the molecular biology revolution. The volumes published to date were meant to serve as an in-depth analysis and standard reference of the evolving field of virology. We felt that viruses as biological entities had to be considered in the context of the broader fields of mo lecular and cellular biology. In fact, we felt then, and feel even more strongly now, that viruses, being simpler biological models, could serve as valuable probes for investigating the biology of the far more complex host cell. During the decade-long compilation of a series of books like Comprehensive Virology, some of the coverage will obviously not remain up-to-date. The usual remedy to this aspect of science publishing is to produce a second edition. However, in view of the enormous increase in knowledge about viruses, we felt that a new approach was needed in covering virology in the 1980s and 1990s. Thus we decided to abandon the somewhat arbitrary subgrouping of the subject matter of Compre hensive Virology under the titles Reproduction, Structure and Assembly, Regulation and Genetics, Additional Topics, and Virus-Host Interac tions. Instead we have organized a new series entitled The Viruses."

Organisms are constantly being bombarded by stimuli in their envi ronment (and also by internal stimuli), and a common way of responding is by movement. This is an aspect of irritability, or excitability, or behaviour. Response to stimuli by movement is found in all organisms: it represents one of the universalities of biology. Yet at the molecular level it is one of the least understood of biological phenomena. Micro-organisms are no exception. If motile, they respond to stimuli by active movement (taxis); if sessile, they respond by growth movements (tropisms). Responses by movement are known among micro-organisms to such stimuli as chemicals, electric current, gravity, light, temperature, touch, and vibrations. The behaviour of micro-organisms is an exciting subject, first of all for its own sake, but in addition because it may reveal facts and concepts that are applicable to understanding behaviour in more complicated organisms (even us) and because it may, help to understand the movement of cells and tissues during differentiation and development of higher plants and animals.

The meeting on "Microbial Surface Components and Toxins in Relation to Pathogenesis" was held on May 15-19, 1989, in the Mitzpe Rachel guesthouse of Kibbutz Ramat Rachel in Israel. Four major topics formed the basis for the meeting: adhesion and colonization; cell invasion and intracellular multipli cation; evasion of host defenses; toxins and systemic effects. The presentations clearly show that our understanding of the pathology, pathogenesis and bacteria-host cell inter-action has greatly advanced over the last few years. The contributions to our knowledge on the biogenesis of adhesins and their molecular organization, as well as on the mechanism of adherence to infected target tissue by pathogenic bacteria, have been particularly impressive. significant progress has been made in defining the nature of pathogenic and cytotoxic factors produced by bacteria, and much has been learned about the biochemical and antigenic modifications occurring in diverse types of host cells upon infection. The discussions of poly saccharide capsules, bacterial endotoxins and secreted toxins illustrated the challenge and the possibilities for vaccine development."

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having only recently passed 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 so far 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 as well as to develop an invaluable 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."

American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite, Trypanosoma cruzi. Sixteen to eighteen million people are currently infected with this organism, and 45,000 deaths are attributed to the disease each year. Infection with T. cruzi is life-long, and 10-30% of persons who harbor the parasite chronically develop cardiac and gastrointestinal problems associated with the parasitosis. Although major progress has been made in recent years in reducing vector-borne and transfusion-associated transmission of T. cruzi, the burden of disability and death in persons chronically infected with the organism continues to be enormous. Eight to ten million persons born in countries in which Chagas disease is endemic currently reside in the United States, and epidemiologic and census data suggest that 50,000-100,000 are chronically infected with T. cruzi. The presence of these infected persons poses a risk of transmission of the parasite in the USA through blood transfusion and organ transplantation and several such cases have now been documented. American Trypanosomiasis, volume seven of World Class Parasites is written for students of tropical medicine, parasitology and public health, for researchers and practitioners alike who wish to bring themselves abreast of the status quo with respect to this disease. It is intended to supplement formal textbooks, in order to broaden and illuminate current areas of scientific and public health concern. Uniquely for T. cruzi, this book addresses parasite, vector and host biology, the pathogenesis of Chagas disease and current and prospective therapeutics and control strategies in a single volume.

This volume is the third in the series devoted to Antibiotics initiated by Springer Verlag in 1967. The first two volumes were devoted to the Mode of Action of Antibiotics and Biogenesis, respectively and were received graciously. During the intervening years these two works have been used often by research workers and students alike and have been quoted extensively. Although a number of other excellent treatises on antibiotics have appeared, the Springer series has set a standard for thoroughness and quality that meets the need of the scientific community. It is against this background that the present Editors set about the preparation of a third volume in the Series on Antibiotics. Since the appearance of Volume I, also dealing with Mechanism of Action, tremendous strides have been made in the depth and breadth of our knowledge of molecular biology, microbial chemistry and molecular pharmacology and of their direct application to studies on the mode of action of drugs. The field of molecular biology itself was in its relative infancy during the preceding decade and the unique role played by many anti biotics in the development of our understanding of nucleic acid synthesis and function and its relationship to protein synthesis and cell physiology has led rapidly to a very precise, understanding of how many of these same antibiotics inhibit susceptible cells."

It has been 10 years since Plenum included a series of reviews on bacte riophages, in Comprehensive Virology. Chapters in that series contained physical-genetic maps but very little DNA sequence information. Now the complete DNA sequence is known for some phages, and the se quences for others will soon follow. During the past 10 years two phages have come into common use as reagents: A phage for cloning single copies of genes, and Ml3 for cloning and DNA sequencing by the dideoxy termi nation method. Also during that period the use of alternative sigma fac tors by RNA polymerase has become established for SPOl and T4. This seems to be a widely used mechanism in bacteria, since it has been implicated in sporulation, heat shock response, and regulation of nitro gen metabolism. The control of transcription by the binding of A phage CII protein to the -35 region of the promoter is a recent finding, and it is not known how widespread this mechanism may be. This rapid progress made me eager to solicit a new series of reviews. These contributions are of two types. Each of the first type deals with an issue that is exemplified by many kinds of phages; chapters of this type should be useful in teaching advanced courses. Chapters of the second type provide comprehensive pictures of individual phage families and should provide valuable information for use in planning experiments."

Scientists from 24 countries who participated in the ~ Symposium on Candida and Candidamycosis, 24-28 April 1989, Antalya, Turkey, have made important contributions to a better understanding of Candida and its infections - by their presence, presentations and discussions in the meeting. The Turkish Microbiological Society, organizing the Symposium in the name of the Federation of European Microbiological Societies (FEMS), thanks all participants for realising this important meeting on such an important subject. In this book the full manuscripts of invited and free papers of the meeting are presented. The Editors extend their sincere thanks to all contributors of papers; to FEMS for encouraging and undertaking the arrangements for publication; to Ege University Publishing House for printing; to Plenum Publishing Company for publishing; and to all colleagues and friends who with their help contributed to this book. The Editors wish that this volume would contribute to a better understanding of Candida and its infections by colleagues working and/or interested in mycology and mycotic diseases.

All too often the fruits of modern medicine are blighted by avoidable infection when patients on whom technical skills have been lavished die or lose a benefit they might otherwise have enjoyed. Although such a loss is expensive both in terms of human tragedy and of wasted time and resources, scant attention is paid to its prevention compared with that which goes into the development and use of the advanced techniques which so often bring infections in their train. The intravascular route for biochemical. pharmacological, nutritional and other physiological support and monitoring necessary to patients undergoing many of the demanding modern medical procedures opens a channel through which infection all too easily finds a way. When it does it may be unsuspected and un detected until too late by those whose attention is fixed on the end they seek while forgetting that the means they use can produce preventable disease. The largest medical use of the intravascular route is for 'intravenous therapy'. Lip-service is paid to the idea that this carries a significant morbidity and mortality, but surprisingly little has been done to measure its incidence or design measures to avoid it. In the early 1970s, the medical and pharmaceutical professions, and the lay public, were startled by the realization of the microbiological threat to patients infused with products which had been subject to manufacturing error in their design or pro duction."

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.

Advances in Microbial Ecology was established by the International Com mittee on Microbial Ecology (ICOME) as a vehicle for the publication of critical reviews selected to reflect current trends in the ever-expanding field of microbial ecology. Most of the chapters found in Advances in Microbial Ecology have been solicited by the Editorial Board. Individuals are encouraged, however, to submit outlines of unsolicited contributions to any member of the Editorial Board for consideration for inclusion in a subsequent volume of Advances. Contributions are expected to be in depth, even provocative, reviews of topical interest relating to the ecology of microorganisms. With the publication of Volume 8 of Advances we welcome to the panel of contributors Martin Alexander, the founding editor of this series, who discusses the range of natural constraints on nitrogen fixation in agri cultural ecosystems. Ecological aspects of cellulose degradation are dis cussed by L. G. Ljungdahl and K. -E. Eriksson, and of heavy metal responses in microorganisms by T. Duxbury. In his chapter, A. Lee con siders the gastrointestinal tract as an ecological system, and comments on the possibility of manipulating this system. The complex interactions among aerobic and anaerobic sulfur-oxidizing bacteria are discussed in terms of natural habitats and chemostat culture by J. G. Kuenen, L. Rob ertson, and H. van Gemerden. Finally, J. A. Robinson presents the advantages and limitations in the use of nonlinear regression analysis in determining microbial kinetic parameters in ecological situations. K. C. Marshall, Editor R. M. Atlas B. B."

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 invalu able 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."

Virus diseases continue to represent serious health problems in most parts of the world. In spite of the fact that diseases such as polio myelitis and measles have been controlled in the industrialized countries by vaccination, vaccines now in use in tropical countries have proved not to be optimal. Further research is needed to develop new vaccines that will be effective in all countries. To do so we need to understand better the immune response to different viruses so that we may be able to maxi mize the protective response of new vaccines and minimize their potential immunopathologic effect. An exciting new discovery which is now being further developed is the possibility of being able to use some viruses (e.g. vaccinia, adenoviruses, etc.), as carriers for other antigens. This may open up the way for the production of vaccines that will be inexpensive and that will confer long lasting immunity after only one injection. This meeting has also served to review our present knowledge of virus diseases which are still of great importance such as hepatitis, dengue and influenza."

The Streptomycetes are industrially widely used microorganisms due to their ability to produce numerous different chemical compounds. These show very varied effects upon other living systems, and result from profound and subtle biochemical and morphological differentiation during the streptomycete life cycle. It is therefore not surprising that research on the genetics of antibiotic biosynthesis and differentiation in this group is currently progressing rapidly in many countries. Intimately connected with the production of antibiotics is resistance to them; analysis of this is giving further information about the origin and evolution of this class of genes and their hypothesized spread among other microorganisms. Another interesting feature of the Streptomyces group is their mycelial growth. Also, their ecologically important utilization of high molecular weight compounds requires enzymes to be transported outside the cell to hydrolyze non-diffusible substrates. Finally, we have as yet limited understanding of the various mechanisms of genome rearrangement observed in some of these species; deletions and/or amplifications of enormous amounts of DNA can occur without seriously affecting the viability of the organism under laboratory conditions. The present volume, which includes contributions addressing the above subjects and others, originates from a meeting on "Genetics and Product Formation in Streptomyces" sponsored by the Federation of European Microbiological Societies in Erfurt on May 1-6 1990. Compared to previous ones of this kind held in 1979, 1983 and 1987 in Weimar, one can point to impressive progress in the study and applications of Streptomyces genetics.

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having only recently passed 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 so far 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 as well as to develop an invaluable 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 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 invalu able 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 fIrst reports on the tropism of the human immunodefIciency virus (HIV), then called human T-celilymphotrophic virus type ill (HTLY- ill) or lymphadenopathy associated virus (LA V), indicated an almost absolute specifIcity of the virus for T4 (helper/inducer) lymphocytes. It became apparent a few years later that macrophages were also infectable by HIV. The common cellular receptor for the virus on these cell types was CD4. A remarkable series of studies by fIve different groups, four of which were published in the same issue of~, showed that recombinant soluble CD4 could inhibit the infectivity of the virus. Subsequent studies began to reveal, however, that cells not expressing CD4 could also be infected, thus raising the possibility that almost any cell in the body could act as a latent reservoir for the virus. Recent observations that the infectivity of patient isolates is not inhibited at the low concentrations of rsCD4 that inhibit laboratory strains, also indicate the importance of CD4-independent mechanisms. The mechanisms of fusion of my with cellular membranes are under investigation by a large number of laboratories. These studies range from the determination of the oligomeric structure of the envelope glycoproteins, to the analysis of the function of various regions of the proteins by site-directed mutagenesis, to the fluorimetric monitoring of membrane fusion. This book originated as the proceedings of a Workshop on the Mechanisms and Specificity of HIV Entry into Host Cells, held at the University of California, San Francisco in June 1989.

This volume is based on the program of the International Conference on Drugs of Abuse, Immunity and Immunodeficiency held in Clearwater Beach, Florida. It was sponsored by the University of South Florida College of Medicine with the support of the National Institute on Drug Abuse. During the past few decades, drugs of abuse, including marijuana, cocaine, opiates and alcohol, have been studied by biomedical scientists in terms of the systemic effects of the drugs as well as alterations in neurophysiology and the psychology. More recently, the scope of such investigations has been broadened to include alterations within the immune system, and the influence of altered immunity on physiological and psychological consequences of drug abuse. In this regard, participants in the Clearwater Beach conference provided new information concern ing both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiency. Advances have been made in recent years in understanding the nature and mechanisms regulating the immune response and the mechanisms by which drugs may influence immune responses. In particular, the emergence of psychoneuroimmunology as a new discipline has heightened interest in immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving clinical and basic scientists including microbiologists, immu nologists, physiologists, psychiatrists, oncologists and others. The recreational use of the above mentioned drugs by large numbers of individuals has aroused serious concern about the consequences of this activity.