I assume that you already know a good deal of microbiology. In this book, I frequently use the word "we" by which I mean "you and I." Together we are going to consider bacteriology from a broader perspective and we will think our way through the important biological problems that are frequently just skipped over in every microbiology course. My most important reason for writing this book is to make accessible the relevant thinking from fields of science other than microbiology that are important to microbiology. The book is written for people that have already have a fascination with bacteria, but can see that their background for understanding is far complete. This book consists of topics that are largely omitted from microbiology textbooks and includes some mathematics, physics, chemistry, and evolutionary biology. It contains a good deal of my own work, both experimental and theoretical, together with a lot of speculation. If ten times bigger, it would be a full text book on microbial physiology. A third of the microbial physiology is covered by the recent is no longer treated even in textbook by White (2000). Another third current specialized tests and is greatly underrepresented in text books.

Staphylococcus aureus is now acknowledged as being the most important bacterial pathogen of humans. It usually produces localized disease but can be rapidly invasive, spreading through the tissues, invading bone, and seeding the bloodstream to produce a fulminant picture of septic shock, disseminated intravascular coagulation, and rapid death. Moreover, most strains of staph infections are becoming resistant to most antibiotics, thus posing a significant problem for hospitals and health care facilities. This book, a volume in the Infectious Agents and Pathogenesis series, presents chapters by the major researchers in the field.

International specialists in Microbiology, Infectious Diseases, Internal Medicine, Cardiology Immunology, Pneumonology, Neurology and Epidemiology gathered to this workshop to discuss and enhance interdisciplinary knowledge on the possible etiological role of Chlamydia pneumoniae, a widespread human respiratory infection, in the pathogenesis of chronic inflammatory diseases with major public health impact such as atherosclerosis, cardiovascular disease, adult-onset asthma bronchiale, chronic obstructive pulmonary diseases, reactive arthritis, morbus Alzheimer and multiple sclerosis. Current deficits and goals in the standardisation of diagnostic tools, basic and applied research, design of epidemiological and monitoring of therapy studies were identified. A special feature of this book is the comprehensive collection of state-of-the-art review articles in the various fields with many references.

Although there have been many books on HIV and AIDS, surprisingly little has been published that focuses on the immunology of retroviral infections in general, and HIV in particular. Retroviral Immunology: Immune Response and Restoration is the first book of its kind to address the most important aspects of the immunology of retroviruses, including not only the virus-specific immune responses, but also genetic and virologic factors modulating these responses. The book also deals directly with the emerging concept of immune restora tion in retroviral infections, a particularly important subject to the thousands of clinicians who deal with this problem on a daily basis. With the advent of highly effective antiviral drug regimens to slow down the replication of HIV and the progression of AIDS, new challenges and opportunities are arising. Restoration of general immune function has brought with it not only complica tions of immune restoration-mediated disease, but also the realistic hope for meaningful restoration of the ability to control HIV replication with the immune system. Leading scientists in the field have summarized the most current informa tion regarding experimental and clinical aspects of retroviral infections. Retroviral Immunology: Immune Response and Restoration should prove an impor tant point of reference for basic scientists and clinicians in this area of research. We are indebted to all of our authors for their excellent contributions."

The term "muscular dystrophy" (MD) describes a group of primary genetic disorders of muscle that often have a distinctive and recognizable clinical p- notype, accompanied by characteristic, but frequently not pathognomonic, pathological features. Research into the molecular basis of the MDs by a c- bination of positional cloning and candidate gene analysis has provided the basis for a reclassification of these disorders, with genetic and protein data augmenting traditional clinically based nomenclature. These findings have brought insights into the molecular pathogenesis of MD, with an increasing number of potential pathways involved in arriving at a dystrophic phenotype. Some common themes can be recognized, however, including the involvement of five members of the dystrophin-associated complex (dystrophin and four sarcoglycans) in different types of MD, and the involvement of two nuclear envelope proteins in producing an Emery-Dreifuss MD phenotype. Other d- ease-associated genes appear to cause MD in a completely unrelated way, such as the involvement of calpain 3 in a form of limb-girdle muscular dystrophy. Section 1 of Muscular Dystrophy: Methods and Protocols reviews tra- tional strategies used to identify MDs. Meantime, techniques developed as a result of the research strategies described previously have become an integral part of the management of many patients with MD and their families, and these techniques are addressed in Sections 2 (DNA-based tests) and 3 (p- tein-based analyses). The continued effort to translate this enhanced und- standing into a molecular cure or treatment for MD is reviewed in Section 4.

In eukaryotic cells, the nuclear genome and its transcriptional apparatus is separated from the site of protein synthesis by the nuclear envelope. Thus, a constant flow of proteins and nucleic acids has to cross the nuclear envelope in both directions. This transport in and out of the nucleus is mediated by nuclear pore complexes (NPCs) and occurs in an energy and signal-dependent manner. Thus, nucleocytoplasmic translocation of macro molecules across the nuclear envelope appears to be a highly specific and regulated process. Viruses that replicate their genome in the cell nucleus are therefore forced to develop efficient ways to deal with the intracellulZlr host cell transport machinery. Historically, investigation of Polyomavirus replication allowed identification ofsequences that mediate nuclear import, which led subsequently to our detailed understanding of the cellular factors that are involved in nuclear import. Transport ofmacromolecules in the opposite direction, however, is less well understood. The investigation of retroviral gene expression in recent years pro vided the first insights into the cellular mechanisms that regulate nuclear export. In particular, the detailed dissection of the function of the human immunodeficiency virus type I (HIV-I) Rev trans-activator protein identified CRMI, as a hona fide nuclear export receptor. CRM I appears to be involved in the nucleocytoplasmic translocation of the vast majority of viral and cellular proteins that have subsequently been found to contain a Rev-type leucine-rich nuclear export signal (NES)."

The discovery of Epstein-Barr virus (EBV) by Epstein, Achong, and Barr, reported in 1964 (Lancet 1:702-703), was stimulated by Denis Burkitt's rec- nition of a novel African childhood lymphoma and his postulation that an infectious agent was involved in the tumor's etiology (Nature194:232-234, 1962). Since then, molecular and cellular biological and computational technologies have progressed by leaps and bounds. The advent of recombinant DNA technology opened the possibilities of genetic research more than most would have realized. Not only have the molecular tools permitted the analyses of viral mechanisms, but, importantly, they have formed the basis for discerning viral presence and, subsequently, viral involvement in an increasing number of diseases. Though in every field of science the search for further knowledge is likely to be a limitless phenomenon, the distinct goal in EBV research, namely, to gain sufficient insight into the viral-host interaction to be able to intercept the pathogenic process, is beginning to be realized. Epstein-Barr virus research has effectively entered the postgenomic era that began with the sequencing of the first strains, cloned in the mid to late 1980s.

Hantaviruses are found world-wide and are associated with two severe disease syndromes, hemorrhagic fever and hantavirus pulmonary syndrome. The recent studies in this volume provide a basis for understanding the high human pathogenicity of theses viruses and their continued maintenance and transmission within rodent populations.

Corepressors are newly discovered assemblies of proteins that play essential roles in eukaryotic gene regulation. Recent discoveries about corepressors have provided new insights into the molecular basis of gene regulation, and have established surprising connections between the mechanisms of action of a wide variety of transcriptional regulators. The reviews in this volume critically discuss the nature, mechanisms of action, and physiological roles of corepressors in a diverse assortment of biological systems. Both basic and clinical investigators will be able to find relevant information. The comprehensive nature of the compilation, and the breadth of the reviews, are intended to provide the reader with an excellent introduction to the newly emergent and rapidly-growing field of corepressor research. A valuable and detailed reference guide.

Der Zyklus der Tropenchirurgischen Symposien wurde am 21. Marz 1992 in Ulm eroffnet. Dieser Impuls setzt sich erfreulicherweise mit zunehmender Dynamik in jahrlichen Folgeveranstaltungen fort. Das lO-jahrige Jubilaum im Jahr 2000 wird im tropen chirurgischen Epizentrum Homburg/Saar stattfinden und damit einen neuen Hohepunkt markieren. Beschrankten sich die ersten Symposien in Ulm (1992 und 1993) und in Wurzburg (1994) noch auf jeweils zwei tropenchirurgische Schwerpunkte, so offnete sich 1995 in Bonn erstmals das thematische Spektrum. Dieser Gewinn an inhaltlicher Breite wurde begleitet durch eine offizielle Internationalisierung der Veranstaltung. Das IV. Tropenchirurgische Symposium war damit gleichzeitig zum ersten "International Meeting" der "German Society for Tropical Surgery" geworden. Das V. Tropenchirurgische Symposium 1996, erneut in Ulm, konzentrierte sich wie- derum auf zwei wichtige Themenkomplexe: Septische Chirurgie und Abdominalchirur- gie. Wahrend das Treffen 1997 in Wolfratshausen dem Bonner Vorbild folgte (,,2nd International Meeting"), war die Deutsche Gesellschaft fur Tropenchirurgie (DTC) 1998 erstmals bei einer der grossen chirurgischen Fachgesellschaften, der Deutschen Gesellschaft fur Unfallchirurgie (DGU), in Berlin zu Gast. Die thematischen Schwer- punkte waren dementsprechend unfallchirurgisch ausgerichtet: "Minenverletzungen" und "Angepasste Frakturbehandlung". Wir freuen uns uber die mittlerweile gewon- nene Eigendynamik der tropenchirurgischen Symposien, die sich in den kommenden Veranstaltungen 1999 in Jena und im Jahr 2000 in Homburg widerspiegeln wird. Der vorliegende Band der" Tropenchirurgie III" vereint die wichtigsten Vortrage der Symposien 1994 in Wurzburg und 1996 in Ulm, erganzt durch herausragende Bei- trage der Symposien 1995 und 1997 sowie durch weitere geladene Manuskripte.

"Clostridium difficile" has been recognized as the cause of a broad spectrum of enteric disease ranging from mild antibiotic-associated diarrhea to pseudomembranous colitis. This volume gives new insights into the microbiology, diagnostics and epidemiology of "Clostridium difficile" and describes recent strategies in treatment of diseases caused by this agent. Main parts of the volume are devoted to "Clostridium difficile" toxins A and B which are the major virulence factors. The molecular biology, biochemistry, pharmacology and cell biology of these toxins which are the prototypes of a new family of large clostridial cytotoxins is described in great detail. "Clostridium difficile" toxins act as glucosyltransferases to inactivate small GTP-binding proteins of the Rho family which are involved in regulation of the actin cytoskeleton, cell adhesion and various signaling processes.

The discovery of the human T cell leukemia virus type I in the late 1970s heralded a new era in retrovirology. For the first time, it was demonstrated that a retrovirus could play a role in the development of a human disease, in this case adult T cell leukemia (ATL). Several years later, the acquired immunodeficiency syndrome (AIDS) epidemic began, and it was dem- strated that a retrovirus, originally designated the human T cell lymp- tropic virus type 3, was the causal agent of this syndrome. This virus, later named the human immunodeficiency virus type 1 (HIV-1), has since been extensively studied in terms of its pathogenesis as well as its ability to elicit immune responses. In that time, a tremendous amount of information has been obtained about the virus. Although recent drug regimens have been useful in significantly lowering viral loads and perhaps maintaining an asymptomatic state among individuals infected with HIV-1, an established "cure" for AIDS eludes us. In addition, the effective drug therapies are very expensive, and are not available to infected people in the third world, where greater than 90% of new infections occur. Furthermore, the development of viral resistance against the drug therapies is an additional concern. Despite extensive study, no effective vaccine has been developed. One of the problems in developing an effective vaccine against HIV-1 is the ability of the virus, particularly in the immunogenic envelop glycoprotein, to undergo amino acid hypervariability.

DNA Methods in Clinical Microbiology describes the novel DNA-based technology now used in the diagnosis and management of infectious diseases. It is a concise, yet readable, overview written primarily for clinicians, clinical microbiologists, medical students and undergraduates in medical and veterinary microbiology. The book has two primary aims. First, to explain the principles of these methods at the molecular' level. Second, to provide a clinical perspective by reporting results from actual DNA-based investigations on a range of specimens. Those approaching DNA methods for the first time are assisted by a brief rA(c)sumA(c) of the relevant features of nucleic acids (Chapter 2): this information is essential for an understanding of later chapters. Subsequent text covers detection, characterization and quantification of pathogens by a variety of methods - e.g., target amplification (PCR, LCR, NASBA, TMA and SDA), signal amplification (bDNA) and probe-based techniques; the chapter on typing describes nearly twenty named molecular methods, including spoligotyping and MLST. All chapters include an adequate range of current reference from which, if required, detailed protocols can be obtained. The diagrams are clear, and readers are assisted by a detailed index.

Biology of Parasitism is based on the Biology of Parasitism Course at the Marine Biological Laboratory in Woods Hole, Massachusetts. Having just celebrated its 20th offering, this Course has distinguished itself as the premier, world-renowned training ground for future generations of parasitologists. The primary goal of the Course is to attract and introduce the very best and most promising young researchers to the many unresolved problems in parasitology and prepare them for their future as independent investigators in the field. The rigorous program combines state-of-the-art laboratory research with a program of visiting lecturers who bring together the most current research in the field. Since at this time there are no academic institutions that have enough depth in parasitology research or teaching faculty to provide up-to-date and state-of-the-art training, the Course has become, and will remain, a global resource for providing intensive education in modern parasitology. Biology of Parasitism is intended to present a snapshot of the content and spirit of the Biology of Parasitism Course. By presenting a series of chapters that reflect the formal lectures that students receive on a daily basis, as well as the approaches used during the laboratory section of the Course, the editors hope to share some of the science that occurs there. One part of the book presents the experimental component of the Course, in particular the subject matter of the four two-week sessions covering Immunology, Biochemistry, Cell Biology and Molecular Biology of protozoan and helminth parasites. As in the Course, the experimental part is complemented by a number of review-like chapters solicited from the large number of speakers who lecture during the Course.

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

The interest of investigators across a broad spectrum of scientific dis- plines has been steadily stimulated by the field of bacterial toxin research, an area that makes use of a large variety of biological, chemical, physicochemical, and medically oriented approaches. Researchers studying bacterial toxins need to be acquainted with all these disciplines in order to work effectively in the field. To date, there has been no published collection offering detailed descr- tions of the techniques and methods needed by researchers operating across the field'sdiverse areas. The present volume Bacterial Toxins: Methods and Pro- cols, is intended to fill this gap. Bacterial Toxins: Methods and Protocols consists of two sections: one on protein toxins (15 chapters) and one on endotoxins (5 chapters). Each s- tion is introduced by an overview article (Chapters 1 and 16). The protocols collected represent state-of-the-art techniques that each have high impact on future bacterial toxin research. All methods are described by authors who have regularly been using the protocol in their own laboratories. Included in each chapter is a brief introduction to the method being described.

James Gray and Ulrich Desselberger have assembled a comprehensive collection of established and cutting-edge methods for studying and illuminating the structure, molecular biology, pathogenesis, epidemiology, and prevention in animal models of infection with rotaviruses, an important cause of infant morbidity and mortality. Presented by experts in the fields of animal and human rotavirus infections and rotavirus vaccine research, these readily reproducible methods detail molecular and other modern techniques, and include relevant background information and various notes to ensure reproducible and robust results. Authoritative and up-to-date, Rotaviruses: Methods and Protocols offers researchers today's benchmark compendium of experimental methods for the investigation of this medically significant virus.

John Sinclair and a panel of expert investigators present a comprehensive collection of cellular and molecular techniques for the analysis of cytomegalovirus (CMV) biology and its pathogenetic mechanisms. The methods-all described in step-by-step detail with ready reproducibility in mind-range from basic virus culture to complex molecular analysis of CMV structure and function. Included are methods for CMV detection using both immunological and biological techniques, methods for analyzing fundamental aspects of the CMV infection cycle, and methods for analyzing T cell response to cytomegalovirus infection in the human host. Comprehensive and state-of-the-art, Cytomegalovirus Protocols provides investigators with a collection of the key methods that are illuminating not only the basic biology of this complex and intriguing human herpesvirus, but also its significant role in human infectious diseases and their emergent therapies.

This book presents a series of papers on a special group of antifungal agents - the hydroxypyridones (e.g. Ciclopirox, Rilopirox, and Piroctone) given by international experts at conferences in Vancouver and Sydney. The action of this group of agents is unique. Hydroxypyridones are not only active against all relevant fungi, but they are active against dermato- phytes, yeasts, moulds as well as gram positive and gram negative bacteria. They have an inhibitory effect on the lipoxygenase and cyclo-oxygenase path- ways and, in vitro, exhibit fungicidal and even sporicidal activity. Ciclopirox is particularly able to penetrate keratin. These properties facilitate the treatment not only of tinea pedis caused by fungi but also of infections by gram negative bacteria. The special ability of Ciclopirox to penetrate keratin opens the door to an efficacious topical treat- ment for onychomycosis, with a transungual drug delivery system specially adapted to infections of the nail organ. The absence of drug interactions and systemic side effects of this formulation is an appreciable advantage over the newer systemic therapies for onychomycosis. Papers are presented covering the mode of action, antimicrobial spectrum, pharmacological properties, penetration potential, clinical efficacy and the various indications for this group of drugs. They will enable the reader to as- sess the advantage and disadvantage of this new therapeutic modality.

In ancient times foods fermented with lactic acid bacteria already constituted an important part of the human diet. From then on, lactic acid bacteria have played an essential role in the preservation of food raw materials and have contributed to the nutritional, organoleptic and health properties of human food products and animal feed. The important function that lactic acid bacteria still have in the production of foods all over the world has resulted in a growing scientific interest in these micro-organisms by academic research groups as well as by industry. During the last 15 years, this research has been stimulated by major internationally coordinated funding efforts that have resulted in a variety of important scientific breakthroughs and have led to new applications. Written by international experts in the field, this issue of Antonie van Leeuwenhoek documents these developments with respect to genetics, metabolism and the application of lactic acid bacteria for industrial and potential medical applications. In this book the first complete genome of a lactic acid bacterium is presented. The book will serve as a reference source and also as an indispensable source of information for further development and exploration of the field.

This latest addition to the Methods in Molecular Medicine series, Anti- ral Methods and Protocols, is opportune because there is an increasing int- est in discovering compounds that are effective against both chronic and acute viral infections. A number of the methods described in the volume are unp- lished and their inclusion indicates the speed at which this field is moving. This volume is not a review but each chapter contains methods validated by the experts who have spent time in developing the protocols. The hallmark of this series is the comprehensive way in which the me- ods are described, which includes a list of all the reagents needed for each protocol. Of importance is the section on tips and pitfalls that the authors have discovered while developing their protocols. The manual itself is designed to be used by researchers in universities and industry who are familiar with a range of biological techniques but who want to set up quickly a novel assay system. We encourage a dialog between readers and authors, which may also result in useful collaborations.

It has been estimated that there are more microbial cells inhabiting the human body than there are eukaryotic cells of which it is made up. This normal microflora usually co-exists relatively peacefully with the host and does not cause infection. The mechanisms by which this co-existence is achieved are still not properly understood and the interaction between the normal microflora and the host is far from simple. For a variety of reasons, however, this interaction can be disturbed and often results in the microflora becoming pathogens. The study of the diseases then caused is important both in terms of treatment and in terms of contributing to our understanding of the mechanisms by which the normal microflora usually interacts with the host. This title brings together an international list of contributors, all of whom have active research interests in the normal microflora. Each of the chapters reviews current knowledge about a specific group or organism within the microflora and the diseases they can cause. Microflora of the skin, respiratory tract, oral cavity, gastrointestinal system and genital tract are all discussed and the impact of molecular methods on our understanding of the normal microflora is emphasised throughout the book. Medical microbiologists, dental specialists, infectious disease specialists, nutritionists and gastroenterologists will all find this book of immense interest and value, as will epidemiologists, dermatologists and general microbiologists.

The accurate and reliable diagnosis of transmissible diseases is the most powerful weapon available to ensure their control, and in some cases eradication. The detection of parasites in clinical cases, companion and farm animals, and in the environment is relatively easy since many of them are visible to the naked eye, and those that are not are readily detected by light microscopy. Fungal infections can similarly be determined. Bacteria are somewhat harder to detect. Although their presence can frequently be detected by light microscopy, differential diagnosis, beyond their gross morphology, is almost always impossible. However, most bacterial pathogens can be cultured in the laboratory and can be accurately identified by combinations of a series of simple tests such as morphology, staining, antibiotic sensitivity, biochemical analyses, nutrient dependence, and phage sensitivity. Viruses, however, have proved much more difficult; their size and absolute dependence of the host cell for propagation have rendered useless the methods traditionally used for other microorganisms. Until the development of tissue culture in the middle of this century, diagnosis was entirely dependent on the skill and experience of the clinician. But this was an unreliable process since many of the common virus infections exhibit similar clinical symptoms, such as coryza, exanthema, vomiting, diarrhea, neuralgia, and lethargy. Indeed many viral infections display clinical signs that are indistinguishable from bacterial or parasitic infections.

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both."

Is cancer a contagious disease? In the late nineteenth century this idea, and attending efforts to identify a cancer "germ," inspired fear and ignited controversy. Yet speculation that cancer might be contagious also contained a kernel of hope that the strategies used against infectious diseases, especially vaccination, might be able to subdue this dread disease. Today, nearly one in six cancers are thought to have an infectious cause, but the path to that understanding was twisting and turbulent. A Contagious Cause is the first book to trace the century-long hunt for a human cancer virus in America, an effort whose scale exceeded that of the Human Genome Project. The government's campaign merged the worlds of molecular biology, public health, and military planning in the name of translating laboratory discoveries into useful medical therapies. However, its expansion into biomedical research sparked fierce conflict. Many biologists dismissed the suggestion that research should be planned and the idea of curing cancer by a vaccine or any other means as unrealistic, if not dangerous. Although the American hunt was ultimately fruitless, this effort nonetheless profoundly shaped our understanding of life at its most fundamental levels. A Contagious Cause links laboratory and legislature as has rarely been done before, creating a new chapter in the histories of science and American politics.