Sendai virus (SeV) is not just a mouse pathogen but is evolving into a cutting-edge component of biotechnology. SeV reverse genetics originating from a pure academic need to settle long-held questions in the biology and pathogenicity of nonsegmented negative strand RNA viruses (Mononegavirales) is about to bear the impressive fruit of multipurpose cytoplasmic (non-integrating) RNA vectors. This book brings together in one source the SeV biology revealed by conventional approaches and reverse genetics, the methods to construct the first-generation SeV vector and to generate safer versions, and the applications in medical settings that have left or are about to leave the laboratory bench. The applications, which already are diverse and have high medical impact, include use as vaccine vectors against AIDS and respiratory virus infections, creation of BioKnife to resect malignant tumors, induction of "footprint (transgene) free" pluripotent stem cells, and gene therapy for peripheral arterial disease. These achievements-which are just a few of many examples-were attainable only after rigorously incorporating the rich knowledge of SeV biology that has accumulated during the several decades since the discovery of the virus. Application of SeV vector is certain to expand greatly because of its extremely high performance in transgene expression and its remarkable target cell breadth.

Immunology of Infection, 2nd Edition, edited by two leading experts in the field, presents the most appropriate up-to-date experimental approaches in the detail required for modern microbiological research. Focusing on the methods most useful for the Microbiologist interested in analysing host-pathogen relationships, this volume will be essential reading for all researchers working in microbiology, immunology, virology, mycology and parasitology.
This new edition of Immunology of Infection provides ready-to-use "recipes," and the latest emerging techniques as well as novel approaches to the tried and tested, established methods included in the successful first edition.
Methods in Microbiologyis the most prestigious series devoted to techniques and methodology in the field. Established for over 30 years, Methods in Microbiology will continue to provide you with tried and tested, cutting edge protocols to directly benefit your research.
Key Features:
* Includes techniques for genome-wide expression profiling of both the pathogen and host and of the host response to infection
* Cytometric analysis of cytokine secretion by immune cells
* Describes tetramer technology for the quantitative analysis of antigen specific T cell responses
* analysis of host cells and pathogens involved in the host-microbe interplay
* Covers techniques useful for the analysis of human and murine systems
* Includes techniques for the prediction and determination of MHC ligands and T cell epitopes
* Covers the fundamentals and practice of DNA vaccines
* Describes methods for the isolation and propagation of human dendritic cells

In Vivo EPR (ESR) is a textbook on this relatively new subject in biomedical electron spin resonance. While a few chapters have appeared in special topics volumes in this series, this book covers the principles and theory, instrumentation as well as the latest applications at the time of its writing. The authors are world-renowned experts and pioneers in their fields. This book is divided into two major sections dealing with theory and instrumentation, and aspects of biochemistry, in vitro and in vivo applications. A significant amount of detail is devoted to clinical applications and the problems and pitfalls encountered in in vivo spectroscopy and imaging.
Key Features:

-History of In Vivo EPR,
-Principles of Imaging-Theory and Instrumentation,
-Time-domain Radio Frequency EPR Imaging,
-The Measurement of Oxygen In Vivo Using In Vivo EPR Techniques,
-Potential Medical (Clinical) Applications of EPR,
-Combining NMR and EPR/ESR for In Vivo Experiments.

Provides the latest QMRA methodologies to determine infection risk cause by either accidental microbial infections or deliberate infections caused by terrorism - Reviews the latest methodologies to quantify at every step of the microbial exposure pathways, from the first release of a pathogen to the actual human infection - Provides techniques on how to gather information, on how each microorganism moves through the environment, how to determine their survival rates on various media, and how people are exposed to the microorganism - Explains how QMRA can be used as a tool to measure the impact of interventions and identify the best policies and practices to protect public health and safety - Includes new information on genetic methods - Techniques use to develop risk models for drinking water, groundwater, recreational water, food and pathogens in the indoor environment

Dendritic cells are vital to induce potent anti-viral immune responses. It will become clear to the reader that dendritic cells often play a dual role during viral infections. On the one hand they are able to mount potent antiviral immune responses, and on the other hand several viruses, including HIV-1, use DC as a vector to be transferred from the periphery to the lymph nodes where they infect their prime target.

Vaccines represent the greatest achievements of one area of science for increasing our health and well-being. This collection of papers represents the latest advances in bacterial vaccine research. The papers presented at this symposium illustrate the increasing potential and need for continuing research into disease pathogenesis, host resistance mechanisms, and vaccine development. Further, the study of bacterial vaccines provides an important method for characterizing pathogenic mechanisms and natural and induced host resistance mechanisms.

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.

The aberrant replication pathway of foamy viruses distinguishes them from all other retroviruses. Many details have been accumulated over the past ten or so years. Most of the findings on foamy viruses were obtained by research on a single virus isolate previously called "human foamy virus", which appeared to be the first to be investigated on a molecular level. However, to the editor's knowledge, genuine human foamy viruses do not exist, but several trans-species transmissions of different simian foamy viruses from monkeys and apes to human hosts.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the Western world. It is also the prototype of B-cell chronic lymphoid malignancies and of their ramifications within the fields of hematology, immunology and oncology. For a long time the Cinderella of lymphoid malignancies CLL has now become the focus of major interest and an increasing number of investigators from different areas, including genetics, molecular biology, basic and applied immunology are becoming actively engaged in the investigation of CLL. Clinicians are considering CLL as a very interesting target of many projects which aim at translating the new and exciting developments of basic science into effective new approaches to the patient.

The third edition of this volume expands upon the previous two editions with new and up-to-date methods and protocols. Chapters include step-by-step procedures involved in quantifying cell growth, baculovirus infection and cell metabolism, methods to isolate new cell lines and develop your own serum-free medium, and routine maintenance and storage of insect cell lines and baculoviruses, small- and large-scale recombinant protein production with the BEVS in both insect and mammalian cell culture and in insect larvae, production and characterization of baculoviruses, green fluorescent protein, tubular reactors and RNAi, and baculovirus/insect cell system to study apoptosis and generating envelop-modified baculovirus for gene delivery into mammalian cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Baculovirus and Insect Cell Expression Protocols, Third Edition aims to not only aid the user in successfully completing the tasks described, but also stimulate the development of improved techniques and new applications of baculoviruses and insect cell culture.

The development of proteomic analyses using advanced mass spectrometry techniques has revolutionized the way proteins are studied, namely, as individual molecules within a complex system. HIV-1 Proteomics: From Discovery to Clinical Application comprehensively covers protein analysis from the early classic experimental days to current state-of-the-art HIV-1 proteomics in a clear informative style that brings expert-level understanding to the novice. Discussion of important clinical applications and future directions for the field also make this an ideal read for the expert. After finishing this book, the reader will have a complete and functional understanding of protein analysis from traditional biochemistry to modern proteomics.

Metabolic engineering has been developed over the past 20 years to become an important tool for the rational engineering of industrial microorganisms. This book has a particular interest in the methods and applications of metabolic engineering to improve the production and yield of a variety of different metabolites. The overall goal is to achieve a better understanding of the metabolism in different microorganisms, and provide a rational basis to reprogram microorganisms for improved biochemical production.

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.

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.

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

The enormous advances in molecular biology that have been witnessed in . Not recent years have had major impacts on many areas of the biological sciences least of these has been in the field of clinical bacteriology and infectious disease . Molecular Bacteriology: Protocols and ClinicalApplications aims to provide the reader with an insight into the role that molecular methodology has to play in modern medical bacteriology. The introductory chapter ofMolecular Bacteriology: ProtocolsandCli- cal Applications offers a personal overview by a Consultant Medical Microbio- gist of the impact and future potential offered by molecular methods. The next six chapters comprise detailed protocols for a range of such methods . We believe that the use of these protocols should allow the reader to establish the various methods described in his or her own laboratory. In selecting the methods to be included in this section, we have concentrated on those that, arguably, have greatest current relevance to reference clinical bacteriology laboratories; we have deliberately chosen not to give detailed protocols for certain methods, such as multilocus enzyme electrophoresis that, in our opinion, remain the preserve of specialist la- ratories and that are not currently suited for general use. We feel that the methods included in this section will find increasing use in diagnostic laboratories and that it is important that the concepts, advantages, and limitations of each are th- oughly understood by a wide range of workers in the field .

Volume 3 of "Advances in Antiviral Drug Design" is keeping up with the recent progress made in the field of antiviral drug research and highlights five specific directions that have opened new avenues for the treatment of virus infections.
"First," the use of lamivudine (3TC) for the treatment of HIV infections, and its more recent introduction for the treatment of hepatitis B virus (HBV) infections, has heralded the transition of D- to L-nucleosides in the antiviral nucleoside drug design, and it is likely that the future will provide more nucleosides of the L-configuration, such as (-)FFC (emtricitabine) and L-FMAU, as will be described by J.-C.G. Graciet and R.F. Shinazi.
"Second," the acyclic purine nucleoside phosphonates, i.e. PMEA (adefovir and PMPA (tenofovir), offer great potential as both anti-HIV and anti-HBV agents, and both compounds have been the subject of advanced clinical trials in their oral produrg form (adefovir dipivoxil and tenofovir disoproxyl), as mentioned by M.N. Arimilli, J.P. Dougherty, K.C. Cundy, and N. Bischofberger.
"Third," with the advent of nevirapine, delavirdine, and efavirenz, the NNRTIs have definitely come of age. Emivirine (MKC-442), a derivative of the original HEPT analog that was described in 1989 has now proceeded through pivotal clinical studies, and how this class of compounds evolved is presented in the account of H. Tanaka and his colleagues.
"Fourth," at the end of 1999, anticipating on the next winter influenza offensive, we should have at end two compounds that specifically inhibit influenza A and B virus infections: zanamivir (by the intranasal route) and oseltamivir (by the oral route). Both compounds have proved effective in the prophylaxis and treatment of influenza A and B virus infections and act through the same mechanism; that is by blocking the viral neuraminidase (or sialidase), a key enzyme that allows the virus to spread from one cell to another (within the respiratory mucosal tract). The design of these sialidase inhibitors will be presented by M. von Itzstein and J.C. Dyason.
"Fifth," the discovery (in 1996) of the chemokine receptors CXCR4 and CCR5 as essential coreceptors (in addition to the CD4 receptor) for HIV entry into the cells, has boosted an enormous interest in potential antagonists of these receptors. The bicyclams represent the first low-molecular-weight compounds targeted at CXCR4, the coreceptor used by the more pathogenic, T-lymphotropic, HIV strains, to enter the cells. They will be addressed by G.J. Bridger and R.T. Skerlj.
The five topics covered in this third volume of "Advances in" "Antiviral Drug Design" are in the front line of the present endeavors towards the chemotherapy of virus infections. They pertain to the combat against three of the most important virus infections of current times: HIV, HBV, and influenza virus.

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.

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.

"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.

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.

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

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

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.