The pregnant host is at risk for any of the viral diseases her nonpregnant counterpart acquires. Additionally, pregnancy heightens our concerns regarding specific viral diseases be cause of their potential for enhanced adverse effects on both maternal and fetal well-being. All too often the obstetrician relinquishes responsibility for the management of the gravida infected by a viral pathogen, and those expert in infectious diseases are confounded by the influence of pregnancy on these conditions. A major goal of this textbook is to narrow the gap between the two aforementioned management dichotomies in the virally infected pregnant woman. Weare at the infancy of our understanding of viral infections in pregnancy. The current and anticipated advancements are due in large part to a burgeoning oftechnological achievements in the areas of immunodiagnostics, molecular biology, and pharmacotherapeutics. Our in utero diagnostic capabilities, both invasive and noninvasive, have also allowed us new opportunities to study the effects of various maternal infectious disease processes on the developing fetus. New insights have been recognized pertaining to the maternal-fetal interface, the placenta, in that this structure is now acknowledged to function as both a mechanical and an immunological barrier to vertical transmission of infection. These observations suggest that there will be an outpouring of new data in the next several years that clinicians will need to master to maintain an appropriate level of expertise in the care of their patients.

The discovery of adenoviruses naturally induced a new interest in viruses of the human upper respiratory tract since previously unknown viruses infecting this portion of the human body had not been identified in 20 years, and their unique characteristics stimulated investigations into the biochemical events essential for replication of animal viruses. Indeed, the field of molecular virology has evolved during the period since their dis covery, and adenoviruses have played a major role in this development. The exciting discoveries made with adenoviruses have had such a pro found effect on knowledge in basic virology, molecular biology, viral ge netics, human and animal infections, and cell transformation that this seemed a propitious time to have some of the major contributors review this field. This volume pays tribute to the late Wallace Rowe, Robert Huebner, and Maurice Hilleman whose initial discoveries of adenoviruses have tremendously enriched virology. Harold S. Ginsberg vii Contents Chapter 1 An Overview 1 Harold S. Ginsberg Chapter 2 The Architecture of Adenoviruses M. V. Nermut I. Introduction ................................... . 5 II. Chemical and Physical Properties ................... . 6 III. Virus Capsid: Composition and Organization .......... . 7 A. Hexon ..................................... . 10 B. Penton .................................... . 12 C. Other Virus Polypeptides Associated with the Capsid 13 D. Organization of the Capsid ..................... . 14 IV. Virus Core .................................... . 15 A. Evidence for the Core Shell ..................... . 17 B. Organization of the DNA-Protein Complex (Nucleoc- sid) ....................................... . 18 C. Tentative Model of the Adenovirus Nucleocapsid ... . 22 V. Model of the Adenovirion ......................... . 29 32 References .......................................... ."

Endotoxins are potentially toxic compounds produced by Gram-negative bacteria including some pathogens. Unlike exotoxins, which are secreted in soluble form by live bacteria, endotoxins are comprised of structural components of bacteria. Endotoxins can cause a whole-body inflammatory state, sepsis, leading to low blood pressure, multiple organ dysfunction syndrome and death. This book brings together contributions from researchers in the forefront of these subjects. It is divided into two sections. The first deals with how endotoxins are synthesized and end up on the bacterial surface. The second discussed how endotoxins activate TLR4 and, in turn, how TLR4 generates the molecular signals leading to infectious and inflammatory diseases. The way endotoxins interact with the host cells is fundamental to understanding the mechanism of sepsis, and recent research on these aspects of endotoxins has served to illuminate previously undescribed functions of the innate immune system. This volume presents a description of endotoxins according to their genetic constitution, structure, function and mode of interaction with host cells.

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.

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.

Infection of the lower respiratory tract is a major determinant of the course of cystic fibrosis. Although numerous efforts have been made to elucidate the specific mechanisms predisposing the respiratory mucosa of cystic fibrosis patients to infection, so far no clinically relevant procedures for completely effective prevention or control of infection have resulted. Hence, in dealing with infections in cystic fibrosis, we continue to rely mainly on antimicrobials. Antiinfective measures are inseparably correlated with microbiology, and the quality of antiinfec tive therapy directly reflects the quality of microbial monitoring. Vali dated guidelines for microbiologic testing and antiinfective use need to be developed and made available to all health providers and their cystic fibrosis patients. Several years ago, the editors cochaired a symposium at the Interna tional Congress of Chemotherapy on the Global Perspectives of Micro biological and Clinical Infectious Diseases in Patients with Cystic Fibrosis. During this half-day symposium, the editors heard reports from several countries around the world with an alarming range of survival for patients with cystic fibrosis. This sent a dramatic message to us that the understanding of this disease, its diagnosis, management and prevention was different in various countries and that patients may be inconsistently served. That is how our journey began."

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having only recently passed through its descriptive phase of naming and num bering, has probably reached that stage at which relatively few new truly new-viruses will be discovered. Triggered by the intellectual probes and techniq ues of molecular biology, genetics, biochemical cytology, and high-resolution microscopy and spectroscopy, the field has experienced a genuine information explosion. Few serious attempts have so far been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 22 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed and scattered throughout a wide literature. I n this way, we hope to place the entire field in perspective as well as to develop an invaluable reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere but which also provides a logical progression of developing facts and integrated concepts."

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.

This volume contains the presentations of the principal speakers at the NATO Advanced Study Institute held at Porto Portese, Italy,23 August - 2 September, 1982. This meeting was the third in a series devoted to the molecular biology of plants. The initial meeting was held in Strasbourg, France in 1976 (J. Weil and L. Bogorad, organizers), and the second in Edinburgh, Scotland in 1979 (C. Leaver, organizer). As in these previous meetings, we have attempted to cover the major topics of plant molecular biology so as to promote the integration of information emerging at an accelerating rate from the various sub-disciplines of the field. In addition, we have introduced several topics, unique to higher plants, that have not yet been approached with the tools of molec ular biology, but that should present new and important aspects of plants amenable to study in terms of DNA -+ RNA -+ Protein. This meeting also served to inaugerate the new International Society for Plant Molecular Biology. The need for this society is, like the NATO meetings themselves, an indication of the growth, vitalitv and momentum of this field of research."

It has been said that the development of vaccines against a variety of infectious diseases is among the greatest triumphs of immunology. Indeed, several pathogens have lost their horror through the availability of effective vaccination measures. Unfortunately, this does not hold true for the pathogens dealt within this volume. Malaria, schistosomiasis, leishmaniasis, leprosy, and tuberculosis together are prevalent in more than 100 countries, and over 400 million persons suffer from these diseases. It is becoming increasingly clear that the failure to control these infections in a satisfactory way is directly related to the complexity oftheir interactions with the immune system. These agents have lived with their hosts for long enough to give both-host and parasite-ample opportunity to develop a highly sophisticated interrelationship. The central role of T lymphocytes both in acquired resistance to and pathogenesis of these microbes is well appreciated. In the beginning it may have been thought that acq uired resistance against infectious agents is nothing but another aspect of the immune response, studied with soluble and particulate antigens. This simple concept has gradually changed, and it has become clear that the viability not only of the immune cells but also of the 'antigens' adds another dimension to the game. Several achievements in cellular immunology and molecular biology have now made it possible to better understand at least some mechanisms in this intricate interplay.

Development and Implications of Antimicrobial Resistance One of the most ominous trends in the field of antimicrobial chemotherapy over the past decade has been the increasing pace of development of antimicrobial resistance among microbial pathogens. The hypothesis that man can discover a magic bullet to always cure a particular infection has proved false. Physicians are now seeing and treating patients for which there are few therapeutic alternatives, and in some cases, none at all. Until recently there was little concern that physicians might be losing the war in our ability to compete with the evolving resistance patterns of microbial pathogens. Now the general public is very aware of the threat to them if they become infected, thanks to cover story articles in major magazines such as Time, Newsweek, newspapers, and other news sources. Antimicrobial resistance is not a novel problem. Shortly after the widespread introduction of penicillin in the early 1940s, the first strains of penicillin-resistant staphylococci were described. Today it is an uncommon event for a clinical laboratory to isolate an S. aureus that is sensitive to penicillin. Other gram-positive strains of bacteria have become resistant, including the exquisitely sensitive Streptococcus pneumoniae. Sensitivity to vancomycin was once so uniform that it was used in routine clinical laboratories as a surrogate marker for whether an organism should be classified as a gram-positive. That criterion can no longer be relied upon because of emerging resistance among some species. Gram-negative bacteria, viruses, fungi, and parasites all have succeeded in developing resistance.

The hypothesis that cancer of the cervix is infectious was raised more than 150 years ago (Rigoni-Stern 1842). The first cell-free transmissions of papillomas were reported 95 years ago (McFadyan and Hobday 1898). A report of cell- free trans-mission of human warts was published in 1907 (Ciuffo). Thus, since these initial discoveries papillomavirus research has had to go a long way before it became possible to link these infections to cancer of the cervix (Durst et al. 1983; Boshart et al. 1984). Table 1 lists a selection of the publications that form the basis for our present understand- ing of the role of human pathogenic papillomaviruses (H PV) in human cancers. The identification of specific H PV types in cervical cancer in 1983, 1984 and in subsequent years substantially boosted activities in papillomavirus research. In part this is because cancer of the cervix ranks first in cancer incidence in develop- ing countries and is an important cause of cancer death in affluent societies (Parkin etal. 1984; I.A.R.C. 1989). Premalignant cervical lesions, particularly in affluent soci- eties, also contribute considerably to morbidity. Moreover, the availability of cell lines harboring H PV DNA and the identification of H PV genes as oncogenes have permitted in vitro analyses of H PV genome persistence, gene expression, and gene functions.

Viruses are the smallest of organisms, yet given that they account for at least a third of presentations in the doctor's clinic, they must be well understood by medical students and practitioners alike. Collier and Oxford's "Human Virology" presents this complex and rapidly evolving subject with notable clarity and topicality. The first part of the text deals with the general principles of virology, including the properties of viruses, replication and genetics, along with disease and resistance. This is followed by chapters dedicated to specific groups of viruses, then special syndromes associated with susceptible groups. The final part of the book is reserved for practical aspects of virology, including diagnosis, control measures and anti-viral therapies. The author's intent is not to turn their readers into virologists, but rather to provide them with enough knowledge of the nature of viruses and viral infections to serve as an essential foundation for clinical involvement with the subject. By providing a concise but comprehensive account of the fascinating subject of virology, this text is ideal for students of medicine, dentistry, microbiology, nursing and the biological sciences. This latest edition has been extensively updated and incorporates many new diagrams, accompanied by the introduction of full color presentation. The importance of viruses has demanded a fresh appreciation in recent years, providing opportunity for this edition to include coverage of: The emergence of SARS; Latest research in the study of prion diseases; An exploration of the debate regarding MMR versus single vaccination; Progress in the study and treatment of HIV/AIDS; Recent advances in diagnostic virology and antiviral therapy; and Greater emphasis on the antiviral precautions required of healthcare professionals.

The plant world represents a vast renewable resource for production of food, chemicals and energy. The utilization of this resource is frequently limited by moisture, temperature or salt stress. The emphasis of this volume is on the molecular basis of osmoregulation, adaptation to salt and water stress and applica tions for plant improvement. A unified concept of drought, salt, thermal and other forms of stress is proposed and discussed in the publication. The volume developed from a symposium entitled "Genetic Engi neering of Osmoregulation: Impact on Plant Productivity for Food, Chemicals and Energy," organized by D. W. Rains and R. C. Valentine in cooperation with Brookhaven National Laboratory and directed by D. W. Rains and A. Hollaender. The program was supported by a grant from the National Science Founda~ion, Division of Problem Focused Research, Problem Analysis Group, and the Department of Energy. This symposium is one of several in the past and pending which deal with potential applications of genetic engineering in agri culture. Since the question was raised several times during the meeting it is perhaps a convenient time to attempt to define gene tic engineering in the context of the meeting. * Genetic engineering of osmoregulation is simply the application of the science of genetics toward osmo tically tolerant microbes and plants. * Recombinant DNA is regarded as just another tool along with conventional genetics to be utilized for improvement of microbes and plants.

Phagocytic cells and complement are probably the most important components of host defense against bacteria which, after overcoming the mucosal and epithelial barriers, multiply in the subepithelial tissue and may threaten to disseminate and invade the blood stream and different organs. Questions concerning the factors which regulate the interactions of the bacterial cell with host defenses are a challenge to research and lead to practical applications for the prevention, treatment and diagnosis of infectious diseases. The questions of expression and regulation of virulence related bacterial genes and gene products, the specific mechanisms of defence reactions by complement and phagocytic cells, their mutual interactions with bacteria and especially bacterial surfaces are focused. Considerations on how to translate this knowledge into the management of infectious diseases are also included.

Infectious agents have been recognized to involve the heart and vascular system for well over a century. Traditional concepts and teachings of their involvement in the pathogenesis of disease have been by a few established mechanisms. Since the last decade of the 20th century there has been renewed interest in the medical and public media on infectious diseases affecting the cardiovascular and cerebrovascular systems, through their relationship with the development of acceleration of atherosclerosis. This volume highlights and reviews new perspectives of infections on the cardiovascular system as never before. It is a truly valuable resource for scientists, researchers, residents, and fellows in the fields of infectious disease, cardiology, and microbiology.

In recent years there has been an explosion in research on the papillo- maviruses. The viral nature of human warts was first suggested 80 years ago by Ciuffo, who demonstrated transmission using cell-free filtrates. Shope described the first papillomavirus over 50 years ago as the etiologic agent in infectious papillomatosis in rabbits. Subsequent studies by Rous established that benign rabbit papillomas induced by this virus could progress to carcinomas when treated with specific nonviral cofactors. Despite these rich beginnings, the papillomavirus field lay virtually dor- mant until the late 1970s because no one was able to propagate these viruses in culture successfully. In the late 1970s the molecular cloning of the papillomavirus genomes permitted investigators to partially cir- cumvent this obstacle to their progress. The cloning of the viral genomes permitted the standardization of viral reagents and provided sufficient material to begin a systematic evaluation of the biology of this group of viruses.

This volume of the series The Plant Viruses is devoted to viruses with rod-shaped particles belonging to the following four groups: the toba moviruses (named after tobacco mosaic virus), the tobraviruses (after to bacco rattle), the hordeiviruses (after the latin hordeum in honor of the type member barley stripe mosaic virus), and the not yet officially rec ognized furoviruses (fungus-transmitted rod-shaped viruses, Shirako and Brakke, 1984). At present these clusters of plant viruses are called groups instead of genera or families as is customary in other areas of virology. This pe culiarity of plant viral taxonomy (Matthews, 1982) is due to the fact that the current Plant Virus Subcommittee of the International Committee of Taxonomy of Viruses is deeply split on what to call the categories or ranks used in virus classification. Some plant virologists believe that the species concept cannot be applied to viruses because this concept, according to them, necessarily involves sexual reproduction and genetic isolation (Milne, 1984; Murant, 1985). This belief no doubt stems from the fact that these authors restrict the use of the term species to biological species. According to them, a collection of similar viral isolates and strains does constitute an individ ual virus, i. e., it is a taxonomy entity separate from other individual viruses."

To stem the tide of foodborne illness, it is important to understand the source of the problem. This volume examines pathogenic bacteria, viruses, protozoan parasites, moulds, and mycotoxins in food. It also discusses food-associated antimicrobial resistance and lessons learned from an actual foodborne outbreak. The book also explores clinical aspects of foodborne illness. It is intended for students within the medical field but is also ideal as a reference book for scientists, technologists, and inspectors in public health-related fields who regularly contend with issues related to food microbiology, foodborne infections and intoxications, and food safety.

The purpose of this book is to illustrate a selection of biological prop erties of bacteria that reveal them as important living beings. We have primarily addressed readers who have had some previous educa tion in the natural sciences, and we have assumed a modest under standing of elementary chemical and biological principles. Our aim is to provide abrief survey of bacterial forms and structures, placing special emphasis on the activities of bacteria in their environment and some important interrelations within it. Bacterial ecobiology is the study of those aspects of bacteria that influence, and are in fluenced by, environmental phenomena. Some material traditionally covered in standard texts-such as medi cal bacteriology and immunology, applied bacteriology, and bacterial classification-will not be found here, because it is our opinion that these are peripheral to the idea of ecobiology and because numerous excellent treatments of this material are readily available. There is also no formal presentation ofbacterial genetics or of molecular biology per se in this book. However, mention of phenomena involved in these subjects is made where considered appropriate.

Course covers topics in infectious diseases in children and is intended for Pediatric Infectious disease trainees, trainers, and all those who manage children with infections.

Each of the chapters in this book is based on a lecture given at the sixth "Infection and Immunity in Children" course, held at the end of June 2008 at Keble College, Oxford.

Thus, it is the sixth book in a series that provides succinct and readable updates on just about every aspect of the discipline of Pediatric Infectious Diseases.

Bluetongue viruses (BTV) cause diseases that have serious economic consequences in ruminants (sheep, cattle) in many parts of the world. The incidence of bluetongue disease affects the international movement of animals and germ plasm. Although the etiological agent of the disease was isolated in 1900 and preliminary biochemical characterizations were pub lished as early as in 1969, most of the current understanding of the molecular biology, biochemistry, and genetics of BTV has evolved only recently. Triggered by the modern techniques of molecular biology, genetics, and immunology, BTV research has experienced an information explosion in the past 10 years. However, much of this information is scattered throughout an extensive literature. It is therefore an appropriate time to meld this together into a reference book. This book includes compre hensive information on BTV research provided in articles contributed by researchers from around the world. It covers what is known about the molecular structure of the virus and the current understanding of its biology, evolution, and relationships with its invertebrate and vertebrate hosts (infection, immunity, and pathogenicity)."

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and num bering, has probably reached that stage at which relatively few new-truly new-viruses will be discovered. Triggered by the intellectual probes and techniques of molecular biology, genetics, bio chemical cytology, and high resolution microscopy and spec troscopy, the field has experienced a genuine information explosion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 18 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an invalua ble reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere, but which also provides a logical progression of developing facts and integrated concepts."

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

At this congress there were again numereous reports of progress in immunology. The new technologies are continuing to have an immense impact: gene isolation, mutation, transfection and expression, protein structure andpeptide synthesis, cell cloning, hybridization and monoclonal antibodies, CD serology, SCID and transgenic mice, modern immunomodulation and vaccines. A trmendous mass of data has accumulated over the last years. The reports are up-to-date and outstanding, to a degree no journal will ever achieve, and the results are presented in a concise and lucid way. This report will serve as a guideline for the years to came, because it is a treasure trove of explorations, making it exciting reading. This progress presents outstanding contributions. Immunology is exhibited at its best: an exciting research area and a rewarding subject to study for the benefit of mankind - today more than ever.