Clostridium difficile, a major nosocomial pathogen shown to be a primary cause of antibiotic-associated disease, has emerged as a highly transmissible and frequently antibiotic-resistant organism, causing a considerable burden on health care systems worldwide. In Clostridium difficile: Methods and Protocols, expert researchers bring together the most recently developed methods for studying the organism, including techniques involving isolation, molecular typing, genomics, genetic manipulation, and the use of animal models. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes highlighting tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Clostridium difficile: Methods and Protocols serves as an ideal guide for scientists now in a position to gain an in-depth understanding of how this organism is transmitted and how it causes disease.

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.

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.

This is a pocket book to assist in the interpretation of routine biochemical results. It contains comprehensive tests of causes of abnormalities and associated algorithms, that is, an aide-memoire plus flow charts to assist in diagnosis. The material is based on the author's vast experience in teaching hospitals and in providing services to general practitioners.This book, which covers all routine bichemical tests, is aimed at medical students, house officers and general practitioners.

Patients with advanced breast or prostate cancers usually develop bone metastases. The principal complications resulting from metastatic bone disease are pain, spinal cord compression, pathologic fractures and bone marrow suppression. Improving the management of bone metastases is crucial to quality of life for patients with breast and prostate cancer.

Advances in understanding of the molecular mechanisms underlying the pathophysiology of bone metastasis are driving the development of new therapeutic strategies.

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.

1 The Genetics of Paramyxoviruses.- I. Introduction: The Genome Strategy of the Paramyxoviruses.- II. Genome Organization.- A. Genome Structure and function.- B. Coding Potential.- III. Genetic Interactions.- A. Absence of Genetic Recombination.- B. Complementation Analysis with Conditional Lethal Mutants.- C. Other Mutants.- IV. Analysis of Gene function.- A. Transport and Glycosylation of the G Glycoprotein of Respiratory Syncytial Virus.- B. Membrane Interactions of the F1 Polypeptide of SV5.- C. Gene-Specific Hypermutation in Measles Virus.- V Prospects.- VI. References.- 2 The Molecular Biology of the Paramyxovirus Genus.- I. Introduction.- A. History.- B. General Properties.- II. Virus Structure.- A. Morphology.- B. Virion Envelope and Envelope-Associated Proteins.- C. Internal Virion and Nonstructural Proteins.- III. Viral Replication.- A. Adsorption, Penetration, and Uncoating.- B. Molecular Organization of the Genome.- C. Transcription.- D. Genome Replication.- IV References.- 3 The Molecular Biology of the Morbilliviruses.- I. Introduction.- II. Genome Structure and Replication Strategy.- III. Genetic Relationships among the Morbilliviruses.- A. Nucleocapsid Protein Gene.- B. The Phosphoprotein Gene.- C. Matrix Protein Gene.- D. Fusion Protein Gene.- E. The Hemagglutinin Protein Gene.- F. The L Protein Gene.- IV. Function of the 5? and 3? Untranslated Regions.- V. Diagnosis Using Molecular Techniques.- VI. Morbillivirus Vaccines.- VII. Conclusions.- VIII. References.- 4 The Molecular Biology of Human Respiratory Syncytial Virus (RSV) of the Genus Pneumovirus.- I. Introduction.- II. Structures of the RSV Virion, RNAs, and Proteins.- A. Virion Structure.- B. Overview: Identification of Genomic RNA (vRNA), mRNAs, and Proteins.- C. Genetic Map of Strain A2.- D. Structures of the mRNAs.- E. Sequence Diversity among RSV Strains: Antigenic Subgroups.- F. Structures of the RSV Proteins.- III. RSV Replication.- A. Attachment, Penetration, and Growth Cycle.- B. vRNA Transcription.- C. vRNA Replication.- D. Virion Morphogenesis.- IV. Evolutionary Relationships.- A. RSV Antigenic Subgroups.- B. Relationships with Other Paramyxoviruses.- V. Conclusions.- VI. References.- 5 Evolutionary Relationships of Paramyxovirus Nucleocapsid-Associated Proteins.- I. Introduction.- A. Paramyxovirus Nucleocapsid Structure.- B. Functions of Nucleocapsid-Associated Proteins.- II. Sequence Analyses of Nucleocapsid Proteins.- A. NP Proteins.- B. L Proteins.- C. P Proteins.- III. Conclusions.- IV. References.- 6 The Nonstructural Proteins of Paramyxoviruses.- I. Introduction.- II. Paramyxovirus C Proteins.- A. Identification in Infected Cells.- B. The P and C Proteins are Encoded in Overlapping Reading Frames.- C. Multiple Initiation Codons on One mRNA.- D. Initiation Codon Consensus Sequences and the Scanning Hypothesis.- E. Subcellular Localization and Possible Function of Sendai Virus C Proteins.- F. When is a Nonstructural Protein a Structural Protein?.- G. Identification of C Proteins of Parinfluenza Virus 3, Measles Virus, and CDV.- III. Paramyxovirus Cysteine-Rich Proteins.- A. Identification of the Polypeptide and Its Gene in SV5.- B. Assignment of Coding Regions.- C. Strategy by Which P and V are Encoded.- D. Mechanism for the Addition of Extra Nucleotides to mRNAs.- E. Conservation of the Cysteine-Rich Region of Protein V in Paramyxoviruses.- F. Prediction of Cysteine-Rich Polypeptides and mRNAs with Extra Nucleotides in All Paramyxoviruses.- G. Identification of the Nonstructural Protein V and Its mRNAs in Other Paramyxoviruses.- H. Function of the Paramyxovirus Cysteine-Rich Protein V?.- IV. Paramyxovirus Small Hydrophobic (SH) Proteins.- A. Identification of the Polypeptide and Its Gene in SV5.- B. The SH Gene of Mumps Virus.- V Sendai Virus Nonstructural Polypeptide B: Intracellularly Phosphorylated Matrix Protein.- VI. Prospects.- VII. References.- 7 Paramyxovirus RNA Synthesis and P Gene Expression.- I. Paramyxovirus RNA Synthesis...

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.

Hematopathology: Genomic Mechanisms of Neoplastic Diseases will keep physicians abreast of the rapid and complex changes in genomic medicine, as exemplified by the molecular pathology of hematologic malignancies. This timely volume will update physicians on the complexities of genomic lesions, as well as offer an integrated framework encompassing molecular diagnosis, the new WHO classification of hematologic neoplasms with focus on molecular pathology, prognostic value of molecular tests, and molecular monitoring of response to gene-targeted therapy. As such, it will be of great value to hematologists, oncologists, pathologists, internal medicine and pediatric specialists, as well as bioscientific staff and laboratorians in private hospitals and academic institutions.

One of the most exciting developments in the field of bacterial pathogenesis in recent years is the discovery that many pathogens utilize complex nanomachines to deliver bacterially encoded effector proteins into eukaryotic and prokaryotic target cells to modulate a variety of cellular functions for the pathogen's benefit. These protein-delivery machines include the type III secretion system (T3SS), which is widespread in nature and encoded not only by bacteria pathogenic to vertebrates or plants, but also by bacteria that are symbiotic to plants or insects. Because they are essential virulence factors for many important human pathogens, these systems are emerging as a prime target for the development of new-generation, anti-infective drugs. This book reviews our current understanding of these intriguing injection machines as well as of the closely related T3SS that serves in flagella assembly. Individual chapters focus on regulation, assembly, structure, and function of the type III secretion machine and on the evolution of the secreted effector proteins. Given its scope, this book will appeal to a broad readership, including researchers and teachers in the fields of infectious diseases, host pathogen interactions, plant and animal pathogenesis, and symbiosis.

Advances in Parasitology, Volume 118, the latest release in this ongoing series, includes medical studies of parasites of major influence, along with reviews of more traditional areas, such as zoology, taxonomy and life history. New chapters in this release cover topics such as Parasitic and infectious diseases of African wildlife: The Big Five and Improving Translational Power for Antischistosomal Drug Discovery.

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.

The book "Parasitic Zoonoses" emphasizes a veterinary and public health perspective of zoonotic parasites. This book is suitable for higher undergraduate and graduate students of zoonoses and public health, veterinary parasitology, parasite epidemiology; public health workers; public health veterinarians; field veterinarians, medical professionals and all others interested in the subject. More than 15 protozoa and 50 other parasitic diseases are zoonotic in nature and all these diseases have been discussed in detail. The first chapter is concerned with classification of zoonotic parasites, food borne, vector borne and occupation related zoonotic parasites. The remaining chapters cover etiology, epidemiology, life cycle, transmission, clinical signs, diagnosis, prevention and control of zoonotic parasites. The text is illustrated with a large number of coloured figures. An alphabetical bibliography for every disease has also been included so that readers have access to further information.

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.

Megaplasmids are extrachromosomal genetic elements in the size range of 100 kb and larger. They are found in physiologically and phylogenetically diverse groups of bacteria and archaea. By definition, megaplasmids are not essential for the viability of their hosts under all growth conditions, but paradoxically many megaplasmids carry the genetic information for the defining and characteristic traits of the organism in which they reside.

Microbial Megaplasmids reviews our knowledge of the extensively studied representatives, such as the catabolic plasmids of the pseudomonads, the rhizobial Sym plasmids, the Ti plasmids of the genus Agrobacterium and the giant enterobacterial virulence plasmids. It also presents snapshots of more recently discovered megaplasmids. The contribution of megaplasmids to the biology of their hosts is described, highlighting the interactions between megaplasmid and chromosomal genes.

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 .

Smoking and Lung Inflammation is the first book directly related to chronic lung inflammation of its kind in several respects. First, the it focuses on both basic and clinical research on COPD, and the inflammatory mechanisms that function in these diseases. Second, it is unique with respect to scope of the discussion of the unusual characteristics of the immune response which occurs in these patients. Third, it includes knowledge being gained from translational research conducted through clinical trials at several Medical Schools in the United States. Not only is this research providing information about novel drugs and therapies, but it is also advancing our understanding of the genetics of these diseases. This work will illuminate the molecular basis for these diseases, and hopefully will permit us to individualize the therapies for these diseases.

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

Only recently have we begun to appreciate the role of microbiome in health and disease. Environmental factors and change of life style including diet significantly shape human microbiome that in turn appears to modify gut barrier function affecting nutrient & electrolyte absorption and inflammation. Approaches that can reverse the gut dysbiosis represent as reasonable and novel strategies for restoring the balance between host and microbes. In the book, we offer summary and discussion on the advances in understanding of pathophysiological mechanisms of microbial host interactions in human diseases. We will not only discuss intestinal bacterial community, but also viruses, fungi and oral microbiome. Microbiome studies will facilitate diagnosis, functional studies, drug development and personalized medicine. Thus, this book will further highlight the microbiome in the context of health and disease, focusing on mechanistic concepts that underlie the complex relationships between host and microbes.

"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.

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.

Oxidation is any reaction in which electrons are removed from a molecule, thus increasing the number of binding sites on the molecule that are able to react with other atoms and molecules.;This volume addresses oxidant-reduction or redox and antioxidant sensitive molecular mechanisms and how they are implicated in different disease processes. Recent work in this area has revealed that these mechanisms may be linked with different disease processes, such as immune response, cell proliferation, inflammation, metabolism, ageing and cell death. Possible strategies to pharmacologically and/or nutritionally manipulate such redox-sensitive molecular responses are emphasized.

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.