This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

This book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism. Special attention will be paid to methods of oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. This book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

Essentials of Mucosal Immunology presents basic concepts as well as new and exciting advances in mucosal immunology and inflammation, the development of mucosal vaccines, and the role of the immune system in mucosal disease. Specific chapters highlight novel approaches to the treatment of autoimmune disease, including the use of oral tolerance; approaches to and vectors for new vaccines; and current concepts in mucosal inflammation and its role in inflammatory bowel disease and ulcer disease.
Key Features
* Contains the most current research on mucosal immunology and is comprehensive in scope
* Includes ideal coverage of both the basic and clinical aspects of the mucosal immune system
* Provides an understanding of the mucosal immune system with regard to new treatments and preventative methods, including vaccine development
* Includes contributions from an international team of experts

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

Of the many special roles played by proteolytic enzymes in immune reactions, this study addresses different aspects of membrane peptidases, signal transduction via ligation of membrane peptidases (especially of dipeptidyl peptidase IV/CD26 and aminopeptidase N/CD13), and regulation of membrane peptidases in vivo and in vitro. A number of newly discovered peptidases (including cathepsin F, W and X, carboxypeptidase X, attractin) are described, with special emphasis given to the role of peptidases in immune and defense reactions and in the pathogenesis of inflammatory and other diseases, including rheumatoid arthritis, pancreatitis, multiple sclerosis, Alzheimer's disease and tumours of various origins. The focus on the involvement of a selection of proteolytic enzymes in immune reactions and diseases is a useful feature of this multifaceted work , which combines biochemical, immunological and clinical research reports with literary reviews of the field.

In the post genomic era, understanding of the innate immune system is enriched by findings on the specificity of innate immune reactions as well as to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation. This volume covers natural killer cells, mast cells, phagocytes, toll-like receptors, complement, host defense in plants and invertebrates, evasion strategies of microorganisms, pathophysiology, protein structures, design of therapeutics, and experimental approaches.

The once-dreaded scourge of smallpox has been eradicated through barrier immunization. The eminent scientist Edward Jenner (1749-1823) was a pioneer in demonstrating that vaccination was an effective means of preventing smallpox. In the three groundbreaking treatises contained in this volume, originally published between 1798 and 1800, Jenner summarizes his evidence in favor of vaccination and describes individual cases.

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics. While these products have certainly established recombinant biologics as a major pharmaceutical growth sector, the continued interest in this class of drugs arises from the fact that today we have a far better understanding of the human immune response, both at a cellular and molecular level. This has resulted in a more methodical characterisation of these factors which has given clinical researchers an opportunity to plan Phase 1 clinical trials that can provide substantial information on the activity of the cytokine in humans. Currently, a great deal of effort is also being channelled into identifying cytokines from the various DNA databases. Our major objective for this book is to profile cytokines that have been recently identified. The therapeutic potential of these cytokines based on their known properties will be discussed by the authors. The main aim of this book is to provide...

Signaling through antigen receptor initiates a complex series of events resulting in the activation of genes that regulate the development, proliferation and differentiation of lymphocytes. During the past few years, rapid progress has been made in understanding the molecular basis of signaling pathways mediated by antigen and cytokine receptors. These pathways involve protein tyrosine kinases which are coupled to downstream regulatory molecules, including small guanine nucleotide binding proteins (e. g. p21'OS), serine threonine kinases (e. g. , members of the ERK family), and a large group of transcription factors. More recently, there have been breakthroughs in elucidating the genetic defects underlying three X-linked primary immunodeficiency diseases in humans. This volume surveys aspects of these rapidly developing areas of research. The book is divided into 5 different sections. Section I deals with signaling pathways in B lymphocytes. It includes a contemporary assessment of B cell antigen receptor structures, and discussion of the role of Ig-a/lg-B polypeptides in linking the antigen receptor to intracellular signal transduction pathways. The role of accessory molecules in the regulation of signaling by the B cell antigen receptor is also considered. Section II adopts a similar approach to the analysis of the antigen receptor on T lymphocytes. The importance of specialized signaling motifs in the CD3 polypeptides, mechanisms whereby these motifs may interact with the lymphocyte-specific protein tyrosine kinases, and the downstream consequences of these interactions are reviewed. In addition, the role of antigen-induced apoptosis in the generation of immunological tolerance is discussed.

Immunopharmacology represents the boundary between the immune system and chemical mediators of the inflammatory and neuroendocrine responses. The subject as applied to the respiratory system embraces most of the common non-malignant lung diseases of which asthma and allied disorders are the most prevalent. An understanding of the underlying mechanisms of the disorders provides rationale for prevention and drug treatment as well as creating opportunities for novel drug development. This volume embraces all of these principles and should enable the reader to become rapidly updated in an area of medical importance.
*
* Focuses on aspects of disease pathogenesis that are common to a variety of lung disorders.
* Includes coverage of the mechanisms of asthma - origin, progression, and novel therapeutic interventions.
* This volume is another in the "Systems" section of the Handbook of Immunopharmacology.

Neutrophils, the most abundant white cells in humans, serve as the primary cellular defense against infection. Neutrophil Methods and Protocols, Second Edition provides a concise set of protocols written by leading researchers in the field for assessing basic neutrophil functions, investigating specialized areas in neutrophil research, and completing step diagnostic assays of common neutrophil disorders. Topics covered include an overview of neutrophils and their role in host defense and inflammation; methods most commonly used for isolating neutrophils from humans and other animal species; procedures for subcellular fractionation of human neutrophils, analysis of in vivo transmigrated neutrophils, generation of mature neutrophils from induced pluripotent stem cells and analysis of neutrophil gene expression; methods for investigating priming, oxidant production, phagocytosis, bactericidal activity and extracellular trap formation and protocols for investigating neutrophil adhesion, chemotaxis and outside-in signaling via integrins. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Neutrophil Methods and Protocols, Second Edition is a comprehensive source for detailed explanations and applications of the most modern methodological advances in neutrophil biology. Both basic scientists and clinicians will find a collection of this caliber to be an invaluable aid in their work with neutrophils.

Autoimmunity, characterized by autoreactive lymphocytes and autoantibodies, is the consequence of a failure to discriminate between self and non-self, and autoimmune diseases are an increasing threat to people living in the industrialized countries. Autoimmune disorders are treatable, but not curable, and patients can face disability at later stages of the disease. Thus, there is a medical and economic need for new concepts and treatments in autoimmune disorders. New concepts and treatments can only be achieved by an interdisciplinary approach bringing together expertise, technologies, and clinical experience. The workshop focused on multiple sclerosis, rheumatoid arthritis and type I diabetes, and discussed conventional drug therapies, gene therapy, cell and tissue transplantation therapies, and first treatments using blood stem cells for reprogramming the patients' immune system.

Immunofluorescence, a suitable laboratory method for the microscopic demonstration of antigens and antibodies in biological materials, useable, for example, to provide evidence for the pathogenesis of disease in histological or cytological preparations and for tumour cell differentiation. For this reason immunofluorescence has a decisive role as the method of choice for the diagnosis of auto-immune diseases. This primer on immunofluorescence techniques, which first appeared in 1979, is a richly illustrated handbook suitable for everyday practical work in the laboratory, useable as both an introduction to the subject as well as an atlas. In hardly any other area of medicine are there so many new findings to report. The second edition of this book is concerned not only with the detection methods which now form an essential and established part of diagnostic techniques, but also with the most recent research results such as the discovery of antibodies against Auerbach's plexus and against podocytes...

The rapid progress in clinical and experimental immunological research, in addition to the radical change in immunological concepts in recent years, has been accompanied by similar developments in the technical vocabulary, and, as a consequence, frequent widespread confusion. The fourth edition of The Dictionary of Immunology will satisfy the needs of any biologist, clinician or biochemist who requires easy reference to current immunological usage.
This well-established work has been completely revised and updated to include key terms arising from new discoveries in the fast-developing fields of molecular and cellular immunology. The Dictionary of Immunology contains brief descriptions of the most commonly used immunological techniques, as well as definitions, useful in clinical immunology, of immunodeficiency states and autoimmune diseases. Clear illustrations and tables have been added to complement the text, and extensive cross-referencing is used to inform an integrated view.
The Dictionary will serve equally as a handy reference, a companion to other reference texts, or a spelling and fact checker for students, research scientists and those engaged in ancillary activities such as science journalists, and the curious lay reader.
* Special Features:
* Radical revision, including addition of 30% new terms.

This fascinating intellectual history is the first critical study of the work of Elie Metchnikoff, the founding father of modern immunology. Metchnikoff authored and championed the theory that phagocytic cells actively defend the host body against pathogens and diseased cells.

In this scientific biography, Tauber and Chernyak explore Metchnikoff's development as an embryologist, showing how it prepared him to propose his theory of host-pathogen interaction. They discuss the profound impact of Darwin's theory of evolution on his progress, and the influence of 19th century debates on vitalism, teleology, and mechanism. As a case study of scientific discovery, this work offers lucid insight into the process of creative science and its dependence on cultural and philosophic sources.

The OHOLO conferences are sponsored by the Israel Institute for Biological Research and take their name from the site of the ?rst meeting on the shores of Lake Kinnereth. The purpose of these meetings is, as it was at their inception over 50 years ago, "to foster interdisciplinary communication between scientists in Israel, and to provide added stimulus by the participation of invited scientists from abroad". The core of the organizers of the OHOLO conferences are scientists from the Israel Institute for Biological Research. From time to time a particular OHOLO conference cooperates with an international scienti?c organization. The present 46th OHOLO Conference marks the resumption of the OHOLO tradition after 8 years of interruption caused by events beyond our control. It is my belief that our uncomp- mising commitment to excellence in research and development in the various areas of science in Israel is essential to our survival in this troubled region. The OHOLO conference tradition is a re?ection of this conviction. The present 46th OHOLO Conference entitled: The Challenge of Highly Pathogenic Microorganisms - Mechanisms of Virulence and Novel Medical Countermeasures intends to address the unique virulence features and ho- pathogen interactions of microorganisms constituting emerging biothreat with emphasis on Y. pestis, B. anthracis, F. tularensis and Orthopox viruses. Accordingly we selected classical microbiological as well as genomic, proteomic & transcr- tomic approaches towards developments of novel prophylactic and post-exposure treatment, as well as updated strategies of diagnostics and bioforensics.

The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney. A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are associated with these diseases. Mutations have been identified in the fluid phase alternative pathway regulator Factor H and the membrane regulator Membrane Cofactor Protein MCP (CD46). The functional characterization of the mutant proteins allows to define the pathophysiological events on a molecular level. These new concepts and data on disease mechanisms already allowed to establish new diagnostic and novel promising therapeutic approaches for several human kidney diseases.

Why sex matters

Among human and nonhuman animals, the prevalence and intensity of infection typically is higher in males than females and may reflect differences in exposure as well as susceptibility to pathogens. Elevated immunity among females is a double-edged sword in which it is beneficial against infectious diseases but is detrimental in terms of increased development of autoimmune diseases.

The present book critically reviews the evolutionary origin and the functional mechanisms responsible for sexual dimorphism in response to infection. It emphasizes the value of examining responses in both males and females to improve our understanding about host-pathogen interactions in both sexes.

The contributors are experts in their specific disciplines which range from microbiology and immunology to genetics, pathology, and evolutionary biology.

The book aims at bringing insight to the treatment and management of infectious diseases; it delineates areas where knowledge is lacking and highlights future avenues of research.

The field of DNA vaccines has undergone explosive growth in the last few years. As usual, some historical precursors of this approach can be d- cerned in the scientific literature of the last decades. However, the present state of affairs appears to date from observations made discreetly in 1988 by Wolff, Malone, Felgner, and colleagues, which were described in a 1989 patent and published in 1990. Quite surprisingly, they showed that genes carried by pure plasmid DNA and injected in a saline solution, hence the epithet "naked DNA," could be taken up and expressed by skeletal muscle cells with a low but reproducible frequency. Such a simple methodology was sure to spawn many applications. In a separate and important line of experimentation, Tang, De Vit, and Johnston announced in 1992 that it was indeed possible to obtain humoral immune responses against proteins encoded by DNA delivered to the skin by a biolistic device, which has colloquially become known as the "gene gun. " The year 1993 saw the publication of further improvements in the me- ods of naked DNA delivery and, above all, the first demonstrations by several groups of the induction of humoral and cytotoxic immune responses to viral antigens expressed from injected plasmid DNA. In some cases, protection against challenge with the pathogen was obtained. The latter result was - questionably the touchstone of a method of vaccination worthy of the name.

The consequences of diseases involving the immune system such as AIDS, and chronic inflammatory diseases such as bronchial-asthma, rheumatoid arthritis and atherosclerosis, now account for a considerable economic burden to governments worldwide. In response there has been an enormous research effort investigating the basic mechanisms underlying such diseases, and a tremendous drive to identify novel therapeutic applications for their prevention and treatment. Though a plethora of immunological studies have been published in recent years, little has been written about the implications of such research for drugs development. As a consequence, this area has not gained the prominence of other fields such as molecular pharmacology or neuropharmacology, and a focul information source for the many pharmacologists interested in diseases of the immune system remains unpublished.
The Handbook of Immunopharmacology series provides such a source through the commissioning of a comprehensive collection of volumes on all aspects of immunopharmacology. Editors have been sought after for each volume who are not only active in their respective areas of expertise, but who also have a distinctly pharmacological bias to their research.
The series follows three main themes, each represented by volumes on individual component topics. The first covers each of the major cell types and classes of inflammatory mediators ("cells and mediators"). The second covers each of the major organ systems and the diseases involving the immune and inflammatory responses that can effect them ("systems"). The third covers different classes of drugs currently used to treat these diseases as well as those under development ("drugs").
This volume provides a comprehensive overview of the adhsion molecules, processes and concepts that govern both inflammatory and infectious diseases, and also deals in detail with the specific in vivo pathways involved.
The first chapter introduces some of the molecules that mediate leukocyte adhesion and ranges from their discovery using monoclonal antibodies and a congenital adhesion deficiency, to their antagonism in preliminary clinical trials as novel therapeutics. An in-depth analysis of the structure, distribution and function of the cell surface glycoproteins that regulates lymphocyte (specific immune response), granulocyte (acute inflammatory response) and metastatic cell (malignant processes) adhesions respectively is provided by the next three chapters. Chapters 5 and 7 detail the molecular structure, intracellular pathways, specificty of carbohydrate interactions, and signalling of the molecules that regulate leukocyte-leukocyte and leukocyte-mesenchymal cell interactions.
There follows an exploration into the contributions of specific molecules in inflammatory diseases in various organs from chapters 8-11. The concluding part is unique to this volume by reviewing the comparable, and in some cases same, cell surface molecules that mediate virus, bacteria and parasite interactions with host cells.
The research is far from complete, but Adhesion Molecules is extremely comprehensive and will be a valuable resource for many a year to come.

The incidence of insulin-dependent diabetes mellitus (100M) varies dramatically across racial groups and countries, with annual age-adjusted rates of approximately 40/100,000 per year in Finland, but only 0.51100,000 per year in China. Although reasons for these marked geographic differences are unknown, it is likely that genetic variations across populations play a m or role. To determine the contribution of genetic factors to the global patterns of 100M incidence, international comparative studies are now being undertaken as part of the WHO Multinational Project for Childhood Oiabetes, known as the DIAMOND Project. It is, therefore, necessary to develop and implement epidemiologic standards for these investigations which can be applied across populations. This will ensure that comparable data are obtained in all countries, and that relevant scientific questions can be properly addressed. The development of standards for molecular epidemiologic studies of 100M is the of the NATO Advanced Research Workshop. During this meeting at the objective University of Pittsburgh, scientists from across the world convened to discuss issues relating to the standardization of: 1. the collection of family history data to assess the risk of 100M in first degree relatives, 2. case-control molecular epidemiology studies of 100M susceptibility, 3. HLA family studies, 4. laboratory methods and ONA technology transfer for genetic marker evaluations.