Although there are a number of excellent current reviews on one or another aspect of cytomegalovirus, the last comprehensive treatment of this subject was that of Krech et al. (197la). In view of the amazing advances in the virological, epidemiologic, and clinical knowledge of cytomegaloviruses, an up-to-date book is needed. Such a work should cover many areas of expertise and a voluminous technical literature. Each area might have been reviewed and analyzed by workers more expert than myself. However, I have embarked on the entire venture alone in order to attain unity and continuity in this book, characteristics that are not easily achieved in the more popular multiauthored works. I have tried to review the Iiterature and provide a critical summary for each area discussed. To do this, I provide as much of the primary data of the relevant works as needed and not just the qualitative conclusions. Inevitably, the flow of the narrative may be interrupted by dry facts and figures. However, such information is essential to make this a meaningful reference work. But for those not interested in such details, I have provided at what I hope are crucial points critiques and summaries. This book is not an exhaustive review of all the literature. This is probably no Ionger possible or even desirable. By selection, however, one runs the risk of having missed or ignored important papers. I am keenly aware of this, and I wish to apologize for such oversight, if that is possible.

The world needs clean and renewable energy and hydrogen represents an almost ideal resource. Hydrogen is the simplest and most abundant molecule in the universe, yet one that is a challenge to produce from renewable resources. Biohydrogen, or hydrogen produced from renewable resources such as water or organic wastes by biological means, is a goal worthy of increased global attention and resources. The purpose of BioHydrogen '97 was to bring together leaders in the biological p- duction of hydrogen from the United States, Japan, Europe, and elsewhere to exchange scientific and technical information and catalyze further cooperative programs. Parti- pants came from at least different countries representing academia, industry, and g- ernment. Especially important participants were young research scientists and engineers: the next generation of contributors. The conference consisted of plenary presentations, topical sessions, posters, and mini-workshop discussions on key areas of biohydrogen. It was designed to maximize - formation exchange, personal interaction among participants, and formulate new inter- tional initiatives. BioHydrogen '97 was an outgrowth of an international workshop convened by the Research Institute of Innovative Technology for the Earth (RITE) and was held in Tokyo, Japan, November 24-25, 1994. The RITE workshop was highly successful but largely l- ited to traditional biochemical and biological studies and not engineering research topics.

The papers contained in this book were presented at a NATO Advanced Research Workshop (ARW) held at Cape Sounion, Athens, Greece, 19-24 May, 1991. The twenty-eight more comprehensive papers represent the key subjects of the ARW covered by invited speakers. The thirty-four short papers pre sented in a research format are contributions of those invited to participate in the ARW. There was a total of 70 participants from 21 countries. The objectives of the ARW were as follows: to review current knowledge of biological control of plant diseases and plant parasitic nematodes, with emphasis on mechanisms at the molecular, cellular, organismal, and ecosystem level; to examine and expand on current concepts and synthesize new concepts; to identify and prioritize limitations in the use of biological control for plant diseases and nematodes and the scientific research needed to overcome these limitations; and to develop strategies for biological control through management of resident agents or introduction of natural or modified agents."

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.

Volume 3 is devoted to the latest diagnostic technology for virus diseases, particularly molecular methodologies.

Biomedical scientists widely acknowledge that individuals' immune respon siveness is important in resistance to infections by microorganisms, including fungi. Because of the devastating acquired immunodeficiency syndrome (AIDS) epidemic, caused by the human immunodeficiency retrovirus, it is now accepted that suppressed immune responses, especially cellular immu nity, are important contributors to increased individual susceptibility to opportunistic infections-including infections caused by fungi which were at one time thought to be very lowly or nonpathogenic. Within the last few years, there has been an almost explosive increase in interest and studies concerning the nature and mechanisms of the immune response to fungal infections. Many immunologists who are not well versed in mycology have begun to study the nature and mechanisms of antifungal immunity using a wide variety of newer as well as more conventional immunologic technologies, both in vivo and in vitro. Up to the 1980s, however, there was little interest among basic immunologists concerning fungal immunity. This situation has changed dramatically in the past half decade, mainly because of AIDS.

This treatise is focused on early aspects of fungal pathogenesis in plant and animal hosts. Our aim in choosing the topics and contributors was to demonstrate common approaches to studies of fungal-plant and fungal-animal interactions, particularly at the biochemical and molecular Ievels. For example, the initial events of adh"sion of fungal spores to the exposed surface tissues of the host are essential for subsequent invasion of the plant or animal and establishment of pathogenesis. A point of consensus among investigators who have directed their attention to such events in plants, insects, and vertebrates isthat spore adhesion to the host cuticle or epithelium is more than a simple binding event. lt is a complex and potentially pivotal process in fungal-plant interactions which "may involve the secretion of ftuids that prepare the infection court for the development of morphological stages of the germling" and subsequent invasion of the host (Nicholson and Epstein, Chapter 1). The attachment of the fungal propagule to the arthropod cuticle is also "mediated by the chemical components present on the outer layer of the spore wall and the epicuticle . . . . Initial attachment may be reinforced further by either the active secretion of adhesive materials or the modification of spore wall materiallocated at the [fungal spore arthropod] cuticle interface (Boucias and Pendland, Chapter 5).

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.

In this translation of the Italian second edition, the authors provide a comprehensive account of the current knowledge on antibiotics. They concisely describe how various scientific disciplines are involved in antibiotics research, development, and use. Their work also discusses the industrial and clinical development of new antibiotics, as well as the questions and controversies related to the function of antibiotics in nature. Antibiotics is richly illustrated with clear chemical structures, drawings, diagrams, and synoptical tables.

In this volume we aim to present an easy-to-read account of the genus Saccharomyces that we hope will be of value to all students and researchers wishing to exploit this important genus, be it for academic or commer cial purposes. Individual chapters have been commissioned to cover specific aspects of the biology of Saccharomyces species: growth, genetics, and metabolism, with the emphasis on methodology. Basic principles are discussed without an over-detailed, step-by-step breakdown of specific techniques, and lengthy discussions of standard molecular, biological, and biochemical techniques (e. g., polyacrylamide gel electrophoresis, protein purification, DNA sequencing) have been avoided. We hope the volume will provide a quick reference to the current status of a wide range of Saccharomyces-specific methodologies without focusing ex clusively on recent developments in molecular techniques which can be found in the ever increasing numbers of "cloning manuals. " By necessity, much of what is described in this volume concentrates on one particular species of Saccharomyces, namely Saccharomyces cerevisiae. This is not just a reflection of the authors' interests, but indicates the extent to which this simple eukaryote has been studied by biologists from all walks of life, for all sorts of reasons. If this volume can provide a broader knowledge base to the experienced yeast researcher, or ease the path of someone just starting work with Saccharomyces, then we will have achieved our aim."

The literature in microbial ecology is growing rapidly. Journals in many countries dealing with microbiology, ecology, environmental sciences, and environmental technology are publishing an ever-increasing number of papers, and these reports are providing microbial ecologists with a wealth of information. This body of data is now so large and the research is published in so many journals and mono graphs that maintaining an overview of the development of the field grows more difficult. The role of Advances in Microbial Ecology thus becomes more obvious with time. The articles in the present volume encompass an array of topics appropriate to the development of the discipline of microbial ecology. Both terrestrial and aquatic ecosystems are subjects of attention, and a variety of microbiological groups come under review. Furthermore, methodological problems and ap proaches are not overlooked. The ecology of protozoa, constraints on their populations, and their role in nutrient cycling and energy flow are considered by J. D. Stout. A unique micro environment is discussed by B. Norkrans, the surface microlayer of aquatic eco systems, and Dr. Norkrans presents information on a field that has blossomed in the last few years. The subject of the review by H. S. Lowendorf is the genus Rhizobium, a group of bacteria whose importance has grown as the cost of fuel for production of nitrogen fertilizers and ultimately for protein production has increased.

The papers assembled in this collection comprise a majority of the oral presentations as well as several poster presentations given at the 22nd Annual Symposium arranged by the Bastern Pennsylvania Branch of the American Society for MicrobioloS)'. The symposium would not be possible without the generous support of the many sponsors (see sponsor list) or without the concerted effort of a11 the Committee members. This Symposium series has evolved into an annual Bastern Pennsylvania Branch ASM event that attracts participants from a wide geographie area. It should be noted that one of the hallmarks of these symposia involves interaction between the presenters and those in attendance. Several authors have altered their by the participants. Therefore, the manuscript that manuscripts based on comments fo11ows should be viewed as a group effort of both the participants and presenters. J ames Poupard Lori Walsh Bruee Kleger ix CONTENTS 1 Introduction 1: CURRENT METHODS The Evolution of Antimicrobial Susceptibility Testing Methods . . . . . . . . . . . . . . . 3 James A. Poupard, Stephen F. Rittenhouse, and Lori R. Walsh Antimicrobial Susceptibility Tests: Testing Methods and Interpretive Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Patrick R. Murray Clinician Utilization of Rapid Antibiotic Susceptibility Data: A Prospective Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Franklin P. Koontz SESSION 2: CONTEMPORARY ISSUES IN SUSCEPTIBILITY TESTING When We Should Be Testing, How Often and What to Report . . . . . . . . . . . . . . . 35 Raymond C. Bartlett Areas of Recent Emphasis of the National Committee for Clinical Laboratory Standards Subcommittee on Antimicrobial Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . 61 James H. Jorgensen Non-Traditional Approaches for Quality Control of Antimicrobial Susceptibility Tests . . . . . . . . . . . . . . . . . . . . . . . . .

To the uninitiated, the genus Clostridium is likely more to be associated with disease than biotechnology. In this volume, we have sought to remedy this misconception by compiling aseries of chapters which, together, provide a practically-oriented handbook of the biotechnologie potential of the genus. Clostridium is a broad grouping of organisms that together undertake a myriad of biocatalytic reactions. In the first two chapters, the reader is introduced to this diversity, both taxonomically and physiologically. In the following chapter, the current state of genetic analysis of members of the genus is reviewed. The remaining chapters concentrate on specific, exploit able aspects of individual Clostridium species-highlighting their range of unique capabilities (of potential or recognized industrial value), particu larly in the areas of biotransformation, enzymology, and the production of chemical fuels. Fittingly, the final chapter demonstrates that even the most toxic of the clostridia can be of therapeutic value. The contributors to this volume reflect the trans national interest in Clostridium, and we are indebted to each of them for making this volume possible. We particularly wish to acknowledge the contributions, both to this volume and to microbiology in general, of Dr. Elizabeth Cato, who, sadly, died shortly be fore publication ofthis volume. Finally, we would like to join the authors in recommending closer and wider consideration of the attributes and capabilities of this genus.

Hepatitis A virus (HAV) is responsible for around half of the total number of hepatitis infections diagnosed worldwide. HAV infection is mainly propagated via the fecal-oral route, and as a consequence of globalization, transnational outbreaks of foodborne infections are reported with increasing frequency. Therefore, in this review, state-of-the-art information on the molecular procedures for HAV detection in food, and the efficacy of common food manufacturing processes are compiled. The purpose of this Brief is to consolidate basic information on various aspects of HAV and to provide a guideline for its prevention and control across the food supply chain from pre-harvest to manufacturing. "

In the last fifteen years, substantial progress has been made in identifying why some people are particularly susceptible to specific infectious diseases. Extensive evidence has accumulated that host genes are important determinants of the outcome of infection for many common pathogens. This book summarises advances that have been made in understanding the complexity of host genetic susceptibility. The diseases covered include those of great public health importance such as malaria and HIV, and those of topical interest such as Creutzfeldt-Jakob disease. Many different techniques have been used to identify host genes involved in infectious disease susceptibility. Each chapter describes how these discoveries were made and the book is therefore useful to anyone planning genetic studies on a multi-factorial disease, regardless of whether it has an infectious etiology.

This book is about the adhesion of bacteria to their human hosts. Although adhesion is essential for maintaining members of the normal microflora in/on their host, it is also the crucial first stage in any infectious disease. It is important, therefore, to fully understand the mechanisms underlying bacterial adhesion so that we may be able to develop methods of maintaining our normal (protective) microflora, and of preventing pathogenic bacteria from initiating an infectious process. These topics are increasingly important because of the growing prevalence of antibiotic-resistant bacteria and, consequently, the need to develop alternative approaches for the prevention and treatment of infectious diseases. This book describes the bacterial structures responsible for adhesion and the molecular mechanisms underlying the adhesion process. It also deals with the consequences of adhesion for both the adherent bacterium and the host cell/tissue to which it has adhered.

This SpringerBrief will a comprehensive account of the functions and effects of the Epstein-Barr virus (EBV) EBNA1 protein that relate to EBV-associated cancers and evidence for EBNA1 contributions to these cancers. EBNA1 was the first EBV protein detected and the most critical for EBV latent infection. EBNA1 fulfills multiple functions at EBV genomes which have been described in many (sometimes confusing) reports over the last 28 years. While these were initially thought to be the only roles of EBNA1, many reports in recent years have shown that EBNA1 also directly affects cellular processes in ways that would be expected to contribute to oncogenesis. However, the degree to which EBNA1 promotes cell survival and oncogenesis in various types of human tumours is not entirely clear and a matter of debate. This Brief would offer a current synopsis of EBNA1 functions in EBV latency, including functions in DNA replication, mitotic segregation and transcription. Mechanisms of these EBNA1 functions will also be discussed as well as implications for tumourigenesis. In addition, the many cellular effects of EBNA1 will be reviewed, including how EBNA1 manipulates specific cellular proteins and relationships to EBV-associated lymphomas and carcinomas.

Three days in Madison have thoroughly modified my view on clostridial neurotoxins. While still realizing the numerous activating, modifying and protective inputs, I cannot judge the meaningfulness of the meeting impartially. Neither may the reader expect a complete summary of all presentations. Collected in this volume, they speak for themselves without requiring an arbiter. Instead I shall write down my very personal opinions as a researcher who has studied clostridial neurotoxins for nearly 25 years. Comparable conferences have been rare during this time. A comprehensive symposium 4 on C. botulinum neurotoxins has been organized at Ft. Detrick. International conferences on tetanus have been held regularly under the auspices of the Wodd Health Organization. One or maximally two days of these meetings have been devoted to tetanus toxin and its actions whereas the sponsor and the majority of the participants have been interested mainly in epidemiology, prevention and treatment of tetanus as a disease (see refs. 5,6). Some aspects of clostridial neurotoxins have been addressed in the context of bacterial toxins, in particular in the biennial European workshops. 1-3,7,8 The Madison meeting differed from the previous ones in three aspects. First, it covered both tetanus and botulinum neurotoxins. The fusion was justified because of their huge similarities in primary structure, in their mode of action and in their cellular targets. Second, the meeting was not limited to toxins but drew some lines on which modern neurobiology might proceed.

Familiarity with nitric oxide is essential to a modern understanding of pathophysiologic mechanisms of infectious disease. Recent research has established nitric oxide and related reactive nitrogen intermediates to be important molecular mediators of diverse physiologic processes such as control of vascular tone, regulation of the immune system, and microbial and tumor cell growth. This book contains chapters by the leading researchers in the field and examines the biology and biochemistry of nitric oxide and its role in a variety of specific infections ranging from sepsis, tuberculosis and malaria to viral myocarditis, influenza, and AIDS.

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

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

This book, originally published in 2004, is concerned with the links between human evolution and infectious disease. It has long been recognised that an important factor in human evolution has been the struggle against infectious disease and, more recently, it was revealed that complex genetic polymorphisms are the direct result of that struggle. As molecular biological techniques become more sophisticated, a number of breakthroughs in the area of host-pathogen evolution led to an increased interest in this field. From the historical beginnings of J. B. S. Haldane's original hypothesis to more recent research, this book strives to evaluate infectious diseases from an evolutionary perspective. It provides a survey of information regarding host-pathogen evolution related to major infectious diseases and parasitic infections, including malaria, influenza and leishmaniasis. Written by leading authorities in the field, and edited by a former pupil of Haldane, Infectious Disease and Host-Pathogen Evolution will be valuable for those working in related areas of microbiology, parasitology, immunology and infectious disease medicine, as well as genetics, evolutionary biology and epidemiology.

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