Herpesviruses, classified in the family Herpesviridae, are important human and animal pathogens that can cause primary, latent or recurrent infections and even cancer. The major interest in research on herpesviruses today focuses on understanding the organization of the DNA genome, as well as on characterizing the viral genes in regard to their control and function. Modern techniques have allowed the viral DNA to become a molecular tool in the study of gene function, since it is now possible to implant the DNA into eukaryotic cells. This book contains original studies on the structure and organization of the DNA of human and animal herpes viruses. The various chapters acquaint the reader with the organization of the viral DNA, the mRNA transcripts, the replicative intermediates of the viral DNA, defective DNA genomes and their mode of synthesis, analyses of the viral DNA sequences in transformed cells, and the relationship between the presence of viral DNA fragments in the cancer cells and the transformed state of the cells."

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."

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."

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."

Over the last few years, bacterial adhesion has become a more and more important and active scientific area, but the field lacks communication and scientific exchange between medical and microbiology researchers who work with the relevant biological systems, and biochemists, structural biologists and physicists, who know and understand the physical methods best suited to investigate the phenomenon at the molecular level. The field consequently would benefit from a cross-disciplinary conference enabling such communication. This book tries to bridge the gap between the disciplines.

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."

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.

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 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 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.

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.

This volume is based on a FEMS Symposium entitled "Bacterial Growth and Lysis: Metabolism and Structure of the Bacterial Sacculus" held at the Monastery of Lluc (Mallorca, Spain) on 5-10 April, 1992. The goals of the symposium were to assess the present state of knowledge on the structure and physiology of the bacterial murein sacculus, and to develop new hypotheses and strategies to promote further development of the field. Consequently, the contributions compiled in this volume include broadly different approaches, from the introduction of new analytical methods to the presentation of provocative models for cell wall growth and division. Structural, biochemical, and genetic aspects are widely covered with special emphasis on the enzymology and regulation of murein hydrolases (autolysins). Comprehensive reviews on bacterial S layers and yeast cell walls are included to stimulate conceptual cross-feeding with these closely related topics. We believe that this book will provide the reader with a useful and up-to-date review of the topic. We would feel deeply rewarded by any positive influence this book may have on the future progress of the field, whereby all the scientific credit for it should be given to the authors of the excellent contributions presented.

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."

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

Experts in microbiology and autoimmunity examine the association between microorganisms and the development of specific categories of autoimmune diseases. The opening chapters explore the bacterial induction of diseases considered autoimmune in nature. Subsequent chapters describe the role of viruses in the induction of these diseases and of diseases with an autoimmune component. Specific topics include: the role of streptococcal infection in rheumatic fever and the role of Klebsiella in the development of ankylosing spondylitis.

It is now just 20 years since Gomatos and his co-workers at the Rocke feller University showed that the nucleic acid in reovirus particles is double-stranded RNA (dsRNA). This discovery created great excitement, for dsRNA was at that time under intense investigation as the replicative form of viral genomes consisting of single-stranded RNA. An equally interesting and important finding followed soon after: it was found that the reovirus genome consists, not of a single nucleic acid molecule, but of 10 discrete "segments," each with its specific sequence content and each transcribed into its own messenger RNA. It is clear now that these segments are genes. Not surprisingly, the availability of a viral genome 10 unlinked genes has permitted some unique lines of in consisting of vestigation in molecular biology. Mammalian and avian reoviruses proved to be but the first of several viruses recognized as sharing Similarity in size and morphology and ge nomes consisting of 10, II, or 12 separate genes. These viruses are dis tributed throughout living organisms; among the natural hosts of mem bers of this virus family are vertebrates, Insects, and plants. Members of the Reoviridae family differ widely in the virulence that they exhibit toward their hosts . . For example, the first discovered mam malian reovirus literally is, as the name signifies, a "respiratory enteric orphan" virus, that is, a virus unassociated with disease."

No other area of biology has grown as fast and become as relevant over the last decade as virology. It is with no little amount of amaze ment, that the more we learn about fundamental biological questions and mechanisms of diseases, the more obvious it becomes that viruses perme ate all facets of our lives. While on one hand viruses are known to cause acute and chronic, mild and fatal, focal and generalized diseases, on the other hand, they are used as tools for gaining an understanding of the structure and function of higher organisms, and as vehicles for carrying protective or curative therapies. The wide scope of approaches to different biological and medical virological questions was well rep resented by the speakers that participated in this year's Symposium. While the epidemic by the human immunodeficiency virus type 1 continues to spread without hope for much relief in sight, intriguing questions and answers in the area of diagnostics, clinical manifestations and therapeutical approaches to viral infections are unveiled daily. Let us hope, that with the increasing awareness by our society of the role played by viruses, not only as causative agents of diseases, but also as models for better understanding basic biological principles, more efforts and resources are placed into their study. Luis M. de la Maza Irvine, California Ellena M."

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.

Biotechnology is a word that was originally coined to describe the new processes which could be derived from our ability to manipulate, in vitro, the genetic material common to all organisms. I t has now become a generic term encompassing all "applications" of living systems, including the more traditional fermentation and agricultural industries. Recombinant DNA technology has opened up new opportunities for the exploitation of microorganisms and animal and plant cells as producers or modifiers of chemical and biological products. This series of handbooks deals exclusively with microorganisms which are at the forefront of the new technologies and brings together in each of its volumes the background information necessary to appreciate the historical development of the organisms making up a particular genus, the degree to which molecular biology has opened up new opportunities, and the place they occupy in today's biotechnology industry. Our aim was to make this primarily a practical approach, with emphasis on methodology, combining for the first time information which has largely been spread across a wide literature base or only touched upon briefly in review articles. Each handbook should provide the reader with a source text, from which the importance of the genus to his or her work can be identified, and a practical guide to the handling and exploitation of the organisms included.

Thousands of different microbial species colonize the human body, and are essential for our survival. This book presents a review of the current understanding of human microbiomes, the functions that they bring to the host, how we can model them, their role in health and disease and the methods used to explore them. Current research into areas such as the long-term effect of antibiotics makes this a subject of considerable interest. This title is essential reading for researchers and students of microbiology.

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.

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