In order to survive, bacteria must constantly monitor their structure and physiology. Adaptive behaviours are established by using environmental sensors and response regulators. These communication modules regulate a wide variety of signals including host detection and invasion, cell cycle, metabolite utilization, starvation and many others. The purpose of this volume is to give an overview of the various systems and to introduce recent advances in understanding selected systems of pathogenic bacteria.

Dubos's classic biography of Louis Pasteur, originally published in 1960 and for several years out of print is once again made available in this new and expanded hardcover edition. The original work has been enlarged by more than forty illustrations and tables, a new biographical sketch of Dubos, a glossary of technical terms and a chronological outline of Pasteur's career. The book's enduring appeal is a tribute both to its subject and to its author. Few scientists so captured the public imagination as Louis Pasteur, and fewer still had such a dramatic effect on everyday life. Dubos, a Pulitzer prize winner, was a modern biographer almost ideally suited to the task. A distinguished French-born microbiologist of broad culture, Dubos had a deep appreciation for the power and enduring significance of Pasteur's scientific work. To the more personal dimensions of the biographer's task, Dubos brought his keen insight into the wellsprings of human action, behavior, and personality. He thus appreciated the full range of Pasteur's life, including its philosophical, religious, and political dimensions. Finally, Dubos' graceful writing style allowed him to convey the excitement and significance of even the most technical aspects of Pasteur's work.

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.

Nearly thirty years ago, in 1974, the volume on Angiotensin edited by Irvine H.Page and F. Merlin Bumpus expanded the Handbook of Experimental Pharmacology. Even after two decades the multiplicity of its actions appears not to have been fully discovered. To call attention to its many functions is one of the purposes of this book. This new edition of the volume on Angiotensin attempts to provide an updated account of the knowledge and findings accumulated since the complexity of angiotensin was so accurately recognized.

rope it was mainly the states of the northern and centrat European areas which succeeded in achieving the extermi nation or at least the regression of brucellosis. (The origi nal plan to present the conditions in Asia and Oceania, in cluding Australia, in maps as weil, and thereby to achieve a comprehensive worldwide review of the known and as certainable distribution of brucellosis, was not, however, practicable. ) Information available from these parts of the world, especially from Asia, is so fragmentary that the great expense required for the compilation of the map did not seem justified. On the other hand it seemed desirable to collate and document these data which had been ac quired as a basis for future research. It is tobe hoped that, at a later date, when more comprehensive data become available, the Heidelberg Academy will be able to decide to support a cartographic presentation of the occurrence of brucellosis in these parts of the world as weil. Last, but not least, the intensive research carried out by bacteriologists had led to the discovery of new species of Brucella, such as B. ovis, B. canis and B. neotomae. Further types - such as Type 4 of B. suis which occurs in reindeer and caribou - were identified. Though these new species and types, which are undoubtedly to be classed with the brucellae, have achieved regional significance in places, the three dassie species B. melitensis, B. abortus and B."

Microsporidia: Pathogens of Opportunity provides a systematic overview of the biology of this important pathogen. Written by leading experts in the field, the book combines background and basic information on microsporidia with descriptive methods and resources for working with the pathogen.Newly revised and updated for its second edition, Microsporidia will continue to be the standard text reference for these pathogenic protists, and is an indispensable research resource for biologists, physicians and parasitologists. The first edition of this book was published in 1999 and was the first systematic review of information that had accumulated on these pathogens since the publication of a 2 monograph series in Comparative Pathobiology in 1977. In the last decade there have been tremendous strides in our understanding of the biology of the Microsporidia. This has included the development of new information on genomics and proteomics of this organism as well as a new understanding of the population biology and genetic diversity of this organism. The new edition of this publication will provide systematic reviews of the biology of this pathogen by leading experts in the field. This will be combined with descriptions of the methods and resources for working with this pathogen.

Viral Vaccines Joseph L. Melnick As with history in general, the history of vaccines needs to be reexamined and updated. My task is to look back to see what has been successful and to look forward to see what remains to be accomplished in the prevention of viral diseases by vaccines. Also, I shall refer to the pertinent material discussed at two recent conferences of the Institute of Medicine, National Academy of Sciences, on virus vaccines under development and their target populations in the United States (1985b) and in developing countries (1986). These reports, plus a third on Vaccine Supply and Innovation (1985a), should be required reading for all those in both the public and the private sector who have a responsibility or interest in vaccines for the prevention of human disease. It has been through the development and use of vaccines that many viral diseases have been brought under control. The vaccines consist either of infectious living attenu ated viruses or of noninfectious killed viruses or subviral antigens. When we look at the record, it is the live vaccines that have given the great successes in controlling diseases around the world. Examples are smallpox, yellow fever, poliomyelitis, measles, mumps, and rubella."

Species of aspergilli are common in man's environment and are responsible for a wide spectrum of human and animal disease, ranging in animals from mycotic abortion to aflatoxicosis and in humans from localized colonization of the ear or skin to life-threatening systemic infection of neutropenic patients. In recent times, invasive aspergillosis has become increasingly important as a cause of morbidity and death, initially in patients receiving immunosuppression prior to organ transplantation, and latterly in haematologic patients rendered neutropenic by underlying disease or chemotherapy. In some centres, the condition has been recorded in more than 40% of patients dying with acute leukaemia. Laboratory diagnostic procedures are not always helpful and the diagnosis depends largely on clinical parameters. The clinician is faced with yet another problem, that of management. At present, antifungal therapy of invasive aspergillosis can be largely ineffectual, and the mortality rate remains unacceptably high. Since Aspergillus fumigatus was first described almost 125 years ago, several other pathogenic species have been recognized. The marked biosynthetic abilities and varied mechanisms of gene recombination of aspergilli have long commanded attention in food technology and genetics. Their equally varied abilities to cause disease have attracted the interest of toxicologists, allergists and physicians concerned with infectious diseases.

Retroviruses have been of great importance to biomedical science for the past half century. Initially, studies on oncogenic animal retroviruses provided important insights into molecular processes in carcinogenesis - most notably the existence and mechanisms of action of oncogenes and proto-oncogenes. Moreover, several human diseases are caused by retroviruses, including AIDS, adult T-cell leukemia and the neurological disease HAM/TSP. The topic of this volume is a relatively unknown animal retrovirus, jaagsiekte sheep retrovirus, the causative agent of transmissible lung cancer in sheep -ovine pulmonary adenocarcinoma. The disease was first documented in South Africa in the 1800s, it has a wide geographical distribution, and it is of economic importance in high endemic regions. However, until very recently the nature of the etiologic agent was unclear, and relatively few laboratories actively studied the disease.

The genus Bacillw; has a long history of importance, both from an economic point of view and as a source of experimental microorganisms. This volume critically reviews aspects of identification, molecular biology, and growth that are of impor tance for the current and anticipated future exploitation of members of this group. In addition, the volume includes a chapter on taxonomy, as the importance of good taxonomy is often not fully appreciated; on sporulation, since so many important products are produced concomitantly with this process and we are beginning to understand the mechanisms by which the process is controlled; and, finally, on the cell envelope, as we are only just beginning to appreciate the significance of dif ferences between the cell walls of gram-positive and gram-negative bacteria for productivity and processing. The commercial importance of Bacillus lies mainly in the area of enzyme pro duction for the food, drink, and detergent markets. Increasingly, however, the ability of Bacillus to secrete proteins, coupled with its regulatory acceptability, has resulted in strenuous efforts to develop species of Bacillus as hosts for the produc tion of value-added heterologous proteins. Difficulties have often been encoun tered, indicating a need to divert more resources to improving our understanding of the molecular biology of members of this grou p. Experience with Escherichia coli, a far from ideal organism from a commercial point of view, suggests that an in creased investment in Bacillus is likely ultimately to be productive.

This is the introductory volume of a new series to be issued under our general editorship. With the development of an unpre cedented increase in interest in comparative pathobiology, we are of the opinion and intent that Comparative PathobioZogy should become the focal point for the publication of definitive reviews and the proceedings of significant symposia in this area of modern biomedical science. Although the term is now in common use, the question is still sometimes raised as to what "pathobiology" includes. This broad area of modern biology includes but extends beyond traditional pathology. It also encompasses studies directed at understanding the biology, chemistry, and physics of infectious agents, in cluding how they contact and invade the effected organism; the reactions of hosts to such agents, as well as to abiotic invaders; the ecologic parameters which facilitate infection; and the development of tools essential for the understanding of hast pathogen interactions. In other words, pathobiology is inter disciplinary and incorporates all of those aspects of biology, chemistry, and physics which directly or indirectly permit greater understanding of the nature of infectious and noninfectious diseases and the possible implications of such in biomedicine, agriculture, and environmental science. By "comparative" is meant an analytical and critical evaluation of comparable processes as they apply to all categories of animals, invertebrates as well as poikilothermic and homeothermic verte brates."

By 1977 it was clear that the thermophilic campylobacters were a major cause of acute bacterial enteritis. In response to that observation an international workshop was convened in Reading, England, and attracted over 130 participants. Many of these individuals resolutely returned for the eighth in the series of biennial international workshops, this time held in Win chester, England, in July 1995. All were surprised at the continued, and even expanding, re search effort in this narrow microbiological field. Such a lasting interest is undoubtedly a reflection of a consistent rise in the incidence of infection, the growing number of closely re lated organisms and disease associations, and an ever-increasing awareness by the public and government agencies of public health and food safety issues. The second workshop in Brussels in 1983 was a forum that demonstrated the growing awareness in the campylobacter community of the existence of campylobacter-like organisms and provided the platform for presentations describing the association of these organisms, now classified in the genus Helicobacter. with gastroduodenal disease. The clinical aspects of the research into helicobacters is now thoroughly covered in several other meetings, and the remit of the international workshop has been expanded to provide a forum for the presentation of the basic microbiological research carried out on these bacteria. In a continuation of this ap proach the remit of the workshop has been further extended to other related organisms, reflect ing that there are many other campylobacter-like organisms still to identify and characterize."

Fenner and White's Medical Virology, Fifth Edition provides an integrated view of related sciences, from cell biology, to medical epidemiology and human social behavior. The perspective represented by this book, that of medical virology as an infectious disease science, is meant to provide a starting point, an anchor, for those who must relate the subject to clinical practice, public health practice, scholarly research, and other endeavors. The book presents detailed exposition on the properties of viruses, how viruses replicate, and how viruses cause disease. These chapters are then followed by an overview of the principles of diagnosis, epidemiology, and how virus infections can be controlled. The first section concludes with a discussion on emergence and attempts to predict the next major public health challenges. These form a guide for delving into the specific diseases of interest to the reader as described in Part II. This lucid and concise, yet comprehensive, text is admirably suited to the needs of not only advanced students of science and medicine, but also postgraduate students, teachers, and research workers in all areas of virology.

In response to the field's need for an introductory text, the authors have distilled the vast and scattered literature relating to the biotechnology of microbial secondary metabolites. General biology, biosynthesis, the search for novel metabolites, and techniques for strain improvement are all discussed to provide undergraduate and graduate students with a concise, readable overview of the field.

The formation of atmospheric nitrogen gas by denitrifying bacteria may represent a significant nutrient sink in natural ecosystems. The rate of denitrification has often been difficult to measure in situ, however, and new methodologies should stimulate research on distribution of activity in space and time. The load of fertilizer nitrogen in modem agriculture has led to increasing nutrient reservoirs in recipient subsoils, aquifers, inland waters and coastal seas. By its conversion of nitrate to atmospheric nitrogen, bacterial denitrification is the only biological process to potentially reduce the impact of increasing nutrient loadings by fertilizer nitrogen in the environment. As part of a scientific program set up by the Danish Ministry of Environment to study environment cycling of nitrogen, phosphorous and organic matter (NPO program) in the light of agricultural, domestic and industrial activities, a symposium on DENITRIFICATION IN SOIL AND SEDIMENT was held at the University of Aarhus, Denmark from 6-9 June 19i\9. On the basis of lectures given at the symposium, this book contains a number of invited contributions on the regulation of denitrification activity (control of enzyme synthesis and activity) and measurement of in situ rates of denitrification in terrestrial and aquatic environments (control factors, diel and seasonal variations, etc). Emphasis has been placed on including the recent improvements in methodologies and current understanding of process regulation, however the book also contains examples of integrated research on the significance of denitrification in environmental nutrient cycling.

The genus Pseudomonas represents a large group of medically and envi ronmentally important bacteria. Interest in these bacteria is reflected in the extensive number of publications devoted to original research, re views, and books on this subject. In this volume selected areas of Pseu domonas research are presented in depth by persons who have been active in their fields over many years. The extensive reviews presented are an effort to provide a balanced perspective in a number of areas not readily available in the current literature. In the style of the previous Biotechnology Handbooks most of these topics have not been reviewed at all, and several are also presented from a new direction. For example, in addition to structural and compositional aspects, the chapter on lipids provides shifts in lipid parameters that result from environmental changes. This information will be invaluable to a cross section of Pseu domonas researchers in pathogenesis and bioremediation. The chapters presented include basic aspects of plasmid biology and carbohydrate metabolism and regulation. A major emphasis is placed on the Pseudomonas aeruginosa cell surface. Chapters cover lipo polysaccharide, capsular polysaccharide and alginate, the outer mem brane, transport systems, and the flagellum. Uptake of iron is also neces sarily an important portion of the chapter on iron metabolism.

The 1st International Workshop on Acinetobacter was held on 6th September, 1986, in Manchester, England, in association with the 14th International Congress of Microbiology. That occasion was so well attended and productive that there were soon discussions about how, when and where the next meeting should be held. This time, however, there was sufficient confidence to think of a more substantial meeting and to plan for the proceedings to be published. It emerged that there was wide agreement that the time was ripe to take stock of the entire biology of Acinetobacter: its occurrence and taxonomy; its molecular biology, biochemistry and physiology; its clinical importance and its industrial and commercial applications. The 2nd International Workshop on Acinetobacter took place from 6th to 7th September, 1990, at the Institut Pasteur, Paris, and was sponsored by the Federation of European Microbiological Societies. There were about 100 participants from 19 countries. The backbone of the meeting consisted of 23 plenary lectures. There were 28 posters and the meeting closed with a general discussion which went on long after the official finishing time despite all the counter-attractions of a sunny Parisian Friday afternoon. Indeed discussions continued while cruising along the Seine and while dining at the top of the Tour Montparnasse. However, the vitality and usefulness of even the most successful meeting is difficult to transmit by the printed word.

Coronaviruses were recognized as a group of enveloped, RNA viruses in 1968 and accepted by the International Committee on the Taxonomy of Viruses as a separate family, the Coronaviridae, in 1975. By 1978, it had become evident that the coronavirus genomic RNA was infectious (i. e. , positive strand), and by 1983, at least the framework of the coronavirus replication strategy had been per ceived. Subsequently, with the application of recombinant DNA techniques, there have been remarkable advances in our understanding of the molecular biology of coronaviruses, and a mass of structural data concerning coronavirus genomes, mRNAs, and pro teins now exists. More recently, attention has been focused on the role of essential and accessory gene products in the coronavirus replication cyde and a molecular analysis of the structure-function relation ships of coronavirus proteins. Nevertheless, there are still large gaps in our knowledge, for instance, in areas such as the genesis of coronavirus subgenomic mRNAs or the function of the coronavirus RNA-dependent RNA polymerase. The diseases caused by coronaviruses have been known for much longer than the agents themselves. Possibly the first coronavirus-related disease to be recorded was feline infectious peritonitis, as early as 1912. The diseases associ ated with infectious bronchitis virus, transmissible gastroenteritis virus, and murine hepatitis virus were all well known before 1950.

The recent developments in modern vaccinology are mainly based on: (i) cloning of microbial genes into recombinant vectors containing genetic information for expression of desired neutralizing immunogens; (ii) alternatives of attenuated vectors with deleted genes permitting the insertion of several foreign genes expressing antigens exposed to the host immune system during the abortive replication of such vectors; (iii) combined vaccines with the aim to protect against many diseases with a limited number of administrations; (iv) evidence demonstrating the ability of animals to respond serologically to DNA injections considered as a potential method of vaccination; (v) the possibility to manipulate the immune system with new and improved immunomodulators enhancing the immune response; and (vi) new microcarrier systems for particular immunogens or immunomodulators delivery, either in a single dose or sustained release, and presentation to the immune system for a relevant response. New vaccines being developed are mainly based on viral, bacterial or other vectors modified with genetic engineering technology, to possess and express desired antigens for vaccination against single or multiple infections. Existing combined vaccines like diphtheria, tetanus, pertussis (DTP) are also experimented with new additional components like recombinant hepatitis B virus surface antigen, inactivated poliovirus, and Haemophilus inJluenzae type b immunogens, in order to produce multivalent vaccines. Such types of vaccines permitting the reduction of multiple medical visits is of particular interest to pediatric immuni zation programs, and would benefit especially the developing countries assuring better vaccine compliance with immunization schedules.

The intestinal protozoan Giardia was first described over 300 years ago in 1681 by Leeuwenhoek, from his own stools. In his description of Giardia, he noted the size, movement, and morphology of the organism, and associated its presence with the diarrheic nature of his stools and his dietary habits. This truly remarkable account contains the first description of Giardia in morphologic, pathogenic, and epidemiologic terms. Our knowledge of the organisms in the genus Giardia has advanced tremendously in the past two decades. With the advent of new tech nologies, including techniques in electron microscopy, biochemistry, immunochemistry, tissue culture, and physiology, a tidal wave of information has appeared on the organization and function of this parasitic protozoan and its interaction with its host. The purpose of this book is to celebrate the tricentennial discovery of Giardia by Leeuwenhoek by presenting the above-mentioned advances in our knowledge of Giardia and giardiasis. In the first section of this book, the dominant theme is the biology of the organism and the correlation of structure-function relationships."

Methane and its oxidation product, methanol, have occupied an important position in the chemical industry for many years: the former as a feedstock, the latter as a primary chemical from which many products are produced. More recently, the role played by methane as a potent "greenhouse" gas has aroused considerable attention from environmentalists and clima tologists alike. This role for C compounds has, of course, been quite 1 incidental to the myriad of microorganisms on this planet that have adapted their life-styles to take advantage of these readily available am bient sources. Methane, a renewable energy source that will always be with us, is actually a difficult molecule to activate; so any microorganism that can effect this may point the way to catalytic chemists looking for con trollable methane oxidation. Methanol, formed as a breakdown product of plant material, is also ubiquitous and has also encouraged the growth of prokaryotes and eukaryotes alike. In an attempt to give a balanced view of how microorganisms have been able to exploit these simple carbon sources, we have asked a number ofleading scientists (modesty forbids our own inclusion here) to contribute chapters on their specialist areas of the subject.

HepatitisE (HEV) is a viral infectious disease that infects humans and domestic, wild, and synanthropic animals alike. In developing countries, the disease often presents as an epidemic, transmitted primarily through the fecal-oral route. In recent years, sporadic cases have also been documented in industrial countries, including Europe. The identification and characterization of animal strains of HEV from pigs, wild boar, and deer, and the demonstrated ability of cross-species infection by these animal strains raise potential public health concerns for foodborne and zoonotic transmission of the virus. This Brief will provide a thorough overview of HEV. It will discuss the epidemiology and pathogenesis of the virus in both humans and animals, review detection methods, and provide methods for its control and prevention."

Vaccination is one of the most efficient and cost effective methods of promoting human health and has been in clinical use for at least 200 years. Nevertheless, infectious diseases continue to constitute a constant threat to the well being of humanity. Common pathogens, once believed to be under control, acquire increased virulence and resistance to drugs, while exotic microorganisms emerged from hidden reservoirs to cause yet incurable diseases in humans. These changes, together with epidemic outbreaks related to political and socio-economic instabilities, increase the needs for the development of new, advanced vaccines. In this volume, devoted to the proceedings of the 39th OHOLO Conference, we present some of the recent strategies for the design and production of novel vaccines. The advent of recombinant DNA technology has stimulated the production of several subunit vaccines. In spite of the obvious advantages to this approach, the limited immuno genicity of many subunit candidates has hindered their development. Strategies to enhance the immunogenicity of subunit vaccines is therefore critical. Several approaches toward this goal, including design of novel adjuvants and delivery systems as well as design of advantageous carriers, are presented here. Among the carriers evaluated here are polypep tides (flagellin, HBV core antigen, J3-galactosidase), attenuated virions (Vaccinia, Sindbis), and nonpathogenic licensed bacteria (Salmonella)."

Leading experts provide the only comprehensive book examining all aspects of immune response and immune-based treatments for HIV infection. Contributions, divided into three sections, discuss basic mechanisms, immunopathogenesis of HIV infection, and immune-based therapies. Researchers thoroughly review vaccine-including prospects of T cell vaccine-and gene therapy for HIV infection. Additional topics include organization of HIV genes, the role of co-receptors in signaling of lymphocytes, and biological response modifiers. This reference is designed for basic and clinical researchers, internists, pediatricians, infectious disease specialists, neuropathologists, oncologists, and rheumatologists.

Proceedings of a symposium held in Canterbury, United Kingdom, April 5-8, 1993.