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."

The First International Symposium on the Interface between Analytical Chemistry and Microbiology: Applications of Chromatography and Mass Spectrometry was held June 1987 at the University of South Carolina, Columbia, SC, U.S.A. The purpose of the "Interface" meeting was to forge connections between analytical chemists and microbiologists that are using chromatography and mass spectrometry to solve common problems. The goals were admirably fulfilled. Nearly a hundred participants from seven European countries, Japan, and the United States participated in hearing twenty-three plenary talks and thirty-six submitted papers and posters. The papers and discussions displayed the breadth and depth of current research applications and revealed future directions. This book "Analytical Microbiology Methods: Chromatography and Mass Spectrometry" is loosely based on some of the presentations and discussions at the meeting. Each chapter describes specific methodology and applications in the context of the relevant scientific background. The present book continues the theme of an earlier book, "Gas Chromatography/Mass Spectrometry Applications in Microbiology", edited by G. Odham, L. Larsson, and P-A. Mardh, published by Plenum Press in 1984.

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."

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.

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.

Presenting the basic concepts and clinical implications of respiratory infection, with special emphasis on the role of the immune system, the field's leading researchers contribute detailed chapters on most of the major pathogenic and opportunistic bacteria, fungi, and viruses. Their work will stimulate new research by microbiologists and immunologists, teach clinicians the interaction between microorganisms and the host, and provide health professionals with information necessary to evaluate public health procedures.

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.

This SpringerBrief on Spx reviews the investigations that led to the discovery of Spx and its orthologs and ties together the results of various studies that have explored the function and control of spx in Gram-positive organisms. Spx of "Bacillus subtilis" has been extensively studied, but very little has been published about it. This book incorporates a number of studies that have been conducted in other Gram positive bacteria, which examined the role of Spx orthologs in stress response, bacterial development and virulence.

The book contains an overview that will introduce the protein and its orthologous forms, its association with RNA polymerase, the species of Gram-positive bacteria in which it is found, and the conditions in which it is abundant and active. Spx is a member of a large group of proteins belonging to the ArsC/Spx protein family, so the review touches upon the bioinformatic support for the protein family composition and its meaning with regard to protein structure/function.

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.

This fifth volume in the series The Plant Viruses, dealing with viruses with bipartite genomes, completes the coverage of viruses with isometric parti cles and genomes consisting of single-stranded, positive-sense RNA: viruses that have tripartite and monopartite genomes of this kind were dealt with in Volumes 1 and 3, respectively. How close are the affinities among the viruses within the groupings distinguished in this way? All those with tripartite genomes are considered to be sufficiently closely related to be included in the family Bromoviridae, whereas the monopartite-genome viruses covered in Volume 3 clearly are a much more diverse collection. Affinities among the viruses with bipartite genomes are considered in Chapter 1 of this volume, along with the possible origins, advantages, and disadvantages of these ge nomes. The conclusion reached from this assessment is that the bipartite genome viruses fall into four categories, those within each category having closer affinities with viruses not included in this book than with viruses in the other categories. No evidence was found that possession of a bipartite genome gives a virus overwhelming advantages over viruses of other sorts. More probably, any advantages are largely balanced by disadvantages, and bipartite genomes may be best considered simply as an alternative design for the hereditary material of a virus.

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."

In this comprehensive reference, leading researchers examine the biology, molecular biology, and diseases of the Bunyaviridae, and provide up-to-date information on the genetic characterization and variations of this virus group. Chapters deal with the molecular biology of five genera: Bunyavirus, Hantavirus, Nairovirus, Phlebovirus, and Tospovirus. Chapters examine Bunyaviridae assembly and intracelluar protein transport as well as Bunyaviridae genetics. Contributors discuss the Bunyaviridae diseases, including the hantavirus pulmonary syndrome.

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.

Vector transmission of pathogens affecting human, animal, and plant health continues to plague mankind both in industrialized and Third World coun tries. The diseases caused by these pathogens cost billions of dollars an nually in medical expenses and lost productivity. Some cause widespread of food-and fiber-producing plants and animals, whereas others destruction present direct and immediate threats to human life and further development in Third World countries. During the past 15 years or so, we have witnessed an explosive increase in interest in how vectors acquire, carry, and subsequently inoculate dis ease agents to human, animal, and plant hosts. This interest transcends the boundaries of anyone discipline and involves researchers from such varied fields as human and veterinary medicine, entomology, plant pa thology, virology, physiology, microbiology, parasitology, biochemistry, molecular biology, genetic engineering, ultrastructure, biophysics, bio systematics, biogeography, ecology, behavioral sciences, and others. Ac companying and perhaps generating this renewed interest is the realization that fundamental knowledge of pathogen-vector-host interrelationships is a first and necessary step in our quest for efficient, safe methods of disease control."

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."