This comprehensive text provides a much-needed review of a disease that is currently garnering the interest of molecular biologists, translational scientists, and clinicians. The volume includes emerging developments in the molecular genetics of endometrial carcinoma. In addition to covering the basic genetics of endometrial carcinoma, chapters also cover a wide range of signaling pathways implicated in endometrial carcinoma. A section of the book includes a number of genetically engineered mouse models, which contribute to understanding the role of various genetic alterations in the development and progression of endometrial carcinoma. These models also provide preclinical models for developing effective targeted therapeutic approaches. Endometrial carcinoma is the most common malignancy of the female genital tract in the United States and the number of cases continues to increase around the world. This book is a meant to serve as a resource for a wide range of scientists, from molecular geneticists to signal transduction biologists, as well as to both clinicians and scientists interested in developing targeted therapeutic approaches for women with endometrial carcinoma.

Prokaryotic Toxins - Antitoxins gives the first overview of an exciting and rapidly expanding research field. Toxin - antitoxin (TA) genes were discovered on plasmids 30 years ago. Since then it has become evident that TA genes are highly abundant in bacterial and archaeal chromosomes. TA genes code for an antitoxin that combine with and neutralize a cognate toxin. When activated, the toxins inhibit protein synthesis and cell growth and thereby induce dormancy and multidrug tolerance (persistence). Remarkably, in some species, the TA gene families have undergone dramatic expansions. For example, the highly persistent major human pathogen Mycobacterium tuberculosis has "100 TA loci. The large expansion of TA genes by some organisms is a biological mystery. However, recent observations indicate that TA genes contribute cumulatively to the persistence of bacteria. This medically important phenomenon may thus for the first time become experimentally tractable at the molecular level.

This comprehensive work, aimed at both students and researchers alike, systematically covers all aspects of prion diseases (transmissible spongiform encephalopathies), from their history, microbiology and pathology to their transmissibility and prevention. The book describes diseases such as Creutzfeldt-Jakob disease, kuru, mad cow disease (BSE), chronic wasting disease and scrapie, highlighting their biochemical, molecular biological, genetic, and clinical aspects. A detailed presentation of the impact of prion diseases in fields such as pharmaceutics, blood products, disinfection, surgical instruments and epidemiology concludes with a discussion of preventive measures. A renowned editorial team, representing the fields of medicine, veterinary medicine and molecular biology, brought together 80 internationally respected authors for this translation and new edition of the successful German publication, not only from relevant research fields, but also from industry and public health institutions. The book includes chapters by, among many other notable scientists, William J. Hadlow, who discovered the relationship between the human and animal forms of prion diseases and Michael P. Alpers, with 45 years of experience in Papua New Guinea investigating the first known human epidemic form, kuru, transmitted by endocannibalism. Further contributions from Gerald A. H. Wells, a veterinary pathologist who described BSE and recognised its similarity to scrapie, thus recording the first cases in 1986 of the most important animal epidemic of modern times, and Robert G. Will, a medical neurologist and epidemiologist who discovered the emergence of the variant form of Creutzfeldt-Jakob disease in 1996, underscore the strength of this author team. Carefully edited with numerous illustrations, this work offers a systematic approach committed to a clear presentation of the current knowledge of prion diseases. It aims to inspire and stimulate interdisciplinary cooperation, innovative research ideas and effective prevention.

A study of mast cells and basophils, designed for the use of immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

In the past, many tropical and parasitic infections were confined to tropical areas of the world located between the Tropic of Cancer and the Tropic of Capricorn. However, with the increase in air travel and tourism and the changing patterns of immigration, an increasing number of individuals are coming into contact with these infectious agents and transmission across the world has been enhanced.

Tropical and Parasitic Infections in the Intensive Care Unit provides an international perspective on this topic and an overview of those infections that may cause critical illness.

Charles Feldman, MB BCh., PhD, FRCP, FCP (SA) is a Professor of Pulmonology, Chief Physician and Head, Pulmonology Division of the University of the Witwatersrand Medical School in Johannesburg, South Africa.

George Sarosi, MD is the Chief, Medical Service at Roudebush VA Medical Center and Professor of Medicine, Department of Internal Medicine at the Indiana University School of Medicine in Indianapolis, Indiana.

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.

"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.

Gene expression studies have revealed diagnostic profiles and upregulation of specific pathways in many solid tumors. The explosion of new information in gene expression profiling could potentially lead to the development of tailored treatments in many solid tumors. In addition many studies are ongoing to validate these signatures also in predicting response to hormonal, chemotherapeutic and targeted agents in breast cancer as well as in other tumors. Diagnostic, Prognostic and Therapeutic Value of Gene Signatures provides readers a useful and comprehensive resource about the range of applications of microarray technology in oncological diseases. Topics covered include gene signatures and soft tissue sarcomas, prognostic relevance of breast cancer signatures, gene expression profiling of colorectal cancer and liver metastasis, gene signatures in GISTs, CNVs and gene expression profiles in pancreatic cancer, and gene signatures in head/neck, lung and gastric tumors. Diagnostic, Prognostic and Therapeutic Value of Gene Signatures will be of great value to residents and fellows, physicians, pathologists and medical oncologists.

Pathology and Pathogenesis of Human Viral Disease is a comprehensive reference that examines virus-induced clinical disease of humans in the context of the responsible virus and its epidemiology. Encompassing everything from cold and flu viruses to sexually transmitted diseases, this important resource describes the cellular and tissue pathological changes attributable to infection in the context of the pathogenic mechanisms involved. The author provides a comprehensive review of the older and contemporary literature, considering both the common and much rarer complications of infection.
Pathology and Pathogenesis of Human Viral Disease is written from the unique perspective of the clinical pathologist. It will help clinicians and pathologists gain a better understanding of changes that occur in viral infected cells, tissues, and organs. It will also serve as a pathology source book for virologists, internists, and pediatricians.
Key Features
* Provides a comprehensive, worldwide perspective of viral disease pathology
* Bridges the fields of pathology and virology; integrating clinical disease with cell and tissue pathology
* Addresses topics from the perspective of the clinical pathologist
* Illustrates unique, viral induced pathological lesions
* Considers common and uncommon complications of infection

This book focuses on host-pathogen interactions at the metabolic level. It explores the metabolic requirements of the infectious agents, the microbial metabolic pathways that are dedicated to circumvent host immune mechanisms as well as the molecular mechanisms by which pathogens hijack host cell metabolism for their own benefit. Finally, it provides insights on the possible clinical and immunotherapeutic applications, as well as on the available experimental and analytical methods. The contributions break new ground in understanding the metabolic crosstalk between host and pathogen.

In recent decades, cytopathology has assumed an increasing role in the primary diagnosis of mass lesions owing to its ability to deliver rapid, non-invasive, and timely information. This book provides a comprehensive overview of the role of cytology at various body sites. The diagnostic details covered are abbreviated in comparison with those in pathology texts. Instead, a more clinical approach is taken, with the focus on the advantages and limitations of techniques and the key features of entities that are important to clinicians. Pathological-clinical correlation is highlighted throughout the book, ensuring that it will be highly relevant for clinicians. In particular, physicians who deal with oncology patients will find it to be a rich source of guidance on how to use and understand cytopathology in the diagnosis and exclusion of malignancy.

A collection of state-of-the-art molecular methods for studying antifungal resistance, for discovering and evaluating both new and existing antifungal drugs, and for understanding the host response and immunotherapy of such agents. The protocols follow the successful Methods in Molecular Medicine (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Antifungal Agents: Methods and Protocols offers clinician-scientists, microbiologists and molecular biologists the productive tools they need today to understand and successfully develop new therapeutic agents for yeast, mold, and fungal infections.

HIV and the New Viruses presents cutting-edge reviews of persistent human virus infections as a coherent collection for the first time. These cover recently discovered viruses such as HHV-6, HHV-8 and HCV, as well as the latest research on HIV.
This comprehensive and updated reference includes an in-depth study of the major issues in the epidemiology, pathogenicity, molecular virology, host responses and management of conditions associated with those viruses. Information on new pharmaceuticals and vaccine developments is also included.
Edited by the leading experts in the field, HIV and the New Viruses will be essential reading for postgraduates, clinicians and researchers in virology, immunology, cancer, molecular biology and the pharmaceutical industry.
Key Features
* Presents cutting-edge reviews of persistent human virus infections as a coherent collection for the first time
* Includes an in-depth study of the major issues in the epidemiology, pathogenicity, molecular virology, host responses, and management of conditions associated with those viruses

Mammalian reovirus had been the major focus for molecular understanding of the Reoviridae and has served as a model system for the other members of the family. Indeed, most of our initial understanding of molecular biology and processes involved in virus replication and pathogenesis for the members of the family was generated from reovirus studies. With this platform two other members of the family causing disease in human and/or animals have gained in prominence and the molecular interactions from a structural level through to host-virus interactions as well as the function of the structural and non-structural proteins in the virus life cycle has been investigated in detail.

This book reviews our current understanding of Reoviridae entry, disassembly/assembly and egress in addition to updating high resolution structures of virus proteins and capsids from three different genera of the family.

In May 1993, a cluster of cases of a lethal disease among healthy young people brought the attention of the world to the southwestern deserts. A previously unknown disease was killing up to 80% of the people it infected.
The reaction in the area and across the nation mixed fear, lack of information, and the struggles of doctors to save the victims of an unknown killer with hard science and the age old rhythmns of the desert. What came out was the story of a virus that had been killing since man arrived in the American continents, Hantavirus, with deadly relatives across the Americas and across the world. This book explains why and how the virus kills, and why it is still killing today. Why all of the science aimed at a virus identified back in 1993 has not brought a vaccine or a cure is part of the story, as is how that killer virus fits into the story of "new" diseases across the world.
The story of hantavirus disease, what has happened since that first outbreak, and what the real risks are is laid out by an experienced scientist and an award winning journalist living and working in the area of the 1993 outbreak.
Key Features
* Covers the full story of the recent hantavirus outbreak
* Includes interviews with survivors, and local reaction
* Presents the science in lay terms
* Places the event in the broader context of emerging diseases worldwide
* The only account which takes the reader beyond the initial outbreak in 1993-1994, bringing them up to late 1998
* Discusses hantavirus disease in the U.S., Argentina, and Canada

Handbook of Animal Models of Infection is a complete revision of a three-volume text that was published in 1986. It incorporates the major advances in the field during the past decade, in particular those concerning molecular biological procedures and new models that have been developed. It focuses on both methods and techniques, which makes it an essential and comprehensive reference as well as a benchtop manual. The Handbook will help investigators save time and effort in formulating an approach to test a new potential therapeutic agent or combination of agents for "in vivo" efficacy and to position the therapy for specific infections where it may have therapeutic promise. The book is divided into five sections; the first covering the general methodologies, followed by sections describing experimental bacterial, mycotic, parasitic, and viral infections.
Key Features
* Discusses ethical and safety aspects in an introductory background section
* Covers principles of animal care and current techniques appropriate for the use of animal models of infection
* Details a wide range of animals including rodents, rabbits, cats, and primates
* Provides hands-on descriptions of how to set up the model
* Discusses the major advantages and limitations of each model
* Ensures full coverage of bacterial, fungal, viral, and parasitic infections

Microbial cell wall structures play a significant role in maintaining cells' shape, as protecting layers against harmful agents, in cell adhesion and in positive and negative biological activities with host cells. All prokaryotes, whether they are bacteria or archaea, rely on their surface polymers for these multiple functions. Their surfaces serve as the indispensable primary interfaces between the cell and its surroundings, often mediating or catalyzing important interactions.

"Prokaryotic Cell Wall Compounds" summarizes the current state of knowledge on the prokaryotic cell wall. Topics concerning bacterial and archaeal polymeric cell wall structures, biological activities, growth and inhibition, cell wall interactions and the applications of cell wall components, especially in the field of nanobiotechnology, are presented.

This book describes antibiotic resistance amongst pathogenic bacteria. It starts with an overview of the erosion of the efficacy of antibiotics by resistance and the decrease in the rate of replacement of redundant compounds. The origins of antibiotic resistance are then described. It is proposed that there is a large bacterial resistome which is a collection of all resistance genes and their precursors in both pathogenic and non-pathogenic bacteria. Ongoing resistance surveillance programs are also discussed, together with the perspective of a clinical microbiologist. The book then turns to specific themes such as the most serious area of resistance in pathogens, namely in Gram-negative organisms. The role of combinations of antibiotics in combating resistance emergence is discussed, particularly in the tuberculosis field, and then the importance of non-multiplying and persistent bacteria which are phenotypically resistant to antibiotics and prolong the duration of therapy of antibiotics which leads to poor compliance and resistance emergence. The role of anti-microbial compounds in textiles is covered, with its potential to exacerbate the spread of resistance. Then, efflux pumps are discussed. The final chapter describes the compounds which are in late stage clinical development, illustrating the paucity of the antibiotic pipeline, especially for Gram-negative bacteria.

There is a widespread consensus that use of antioxidants as a therapeutic approach may counteract free radical mediated pathologies. However, the role of antioxidants in normal physiology and redox signaling is still in its infancy. Since oxidative stress is related to various diseases and pathologies, scientists are eager to study the disease in humans, but it is not always ethical to study all the aspects of the disease in humans. Thus, it becomes mandatory to study the disease process and the mechanisms behind it through experimental models which generally involve animals, in vitro/cell culture studies, primates and even humans to a certain extent. Studies on Experimental Models contains data on the experimental models or review of such models of oxidative stress in various diseases. It is structured into six sections, which are as follows: diabetes, cardiovascular, neurology, ocular diseases, toxicology/environmental and in vitro/tissue culture. Each section presents a sketch of models in humans, animals and in vitro methods. Taken together, they comprise a valuable reference for basic and clinical scientists, one aimed at contributing to the advancement of oxidative stress research using appropriate animal models.

Alessandro Condivilla of Bologna first attempted a resection of the head of the pan creas in 1898, but several decades of further trial-and-error attempts ensued before the prototype procedure of pancreatoduodenectomy (PD) was established by Whipple in 1935. In the half-century following that landmark, refinements of surgical technique, including pancreatico-and bilio-entero anastomosis as well as develop ment of new technology to support perioperative management and patient care have contributed to the decrease in mortality and morbidity rates for obstructive jaundice and pancreatic fistula. The improvement in mortality and morbidity rates associated with PD has led to an increase in the number of patients undergoing the procedure and in the number of institutions performing it. Indications for PD have also been expanded. In the early years after PD was established as a viable procedure, periampullary carcinoma was the most common indication; now PD is indicated for a number of benign and malignant diseases. Some surgeons believe that PD is the procedure of choice for certain types of chronic pancreatitis, pancreatico-biliary maljunction, and pancreatic and duodenal trauma. Other surgeons have reported the necessity of PD for lymph node dissection of gallbladder carcinoma. Consequently, the basic procedure has been greatly modi fied to accommodate the specific conditions of each disease. For patients with malig nancy, extended procedures have been developed to improve the curative resection rate and ensure complete lymph node dissection.

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.

This book examines the current state of probiotic research and in particular focuses on the future potential of this important and exciting area. Probiotics and Prebiotics contains state-of-the-art commentaries on all aspects of the intestinal microflora and probiotics and provides an authoritative review of important aspects of probiotic research. Written by leading experts in the field, each chapter affords a critical insight to a particular topic, reviews current research, discusses future direction and stimulates discussion. Topics covered include the genomics of probiotic microorganisms, the developing technologies for analysis of gut microorganisms, evaluation and future potential of prebiotic substances, and the potential for disease prevention in the host by probiotic organisms. This book is an essential text for all microbiologists, health professionals, biotechnologists, pharmaceutical companies, and dairy and food scientists.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.