It is with great pleasure and, much interest that I accepted to write the foreword to this book by Paul Doury, Yves Dirheimer, and Serge Pattin on the subject of "algodystrophy." First, because I know the extent of their personal experience, from which they have selected the best for this book. Second, because it seemed to me that their detailed analysis of the numerous works on the subject, works which have been published all over the world and which provide diverse physiopathologic interpretations, would provide a comprehensive study meeting a real need. Algodystrophy, to adopt the term used by the authors, merits rheumatolog ists' careful attention. It is indeed a frequent condition and, as is now well known, occurs in the most varied etiologic circumstances; it is not solely posttraumatic, a notion on which diagnosis had long been based. This variable etiology suggests the complexity of algodystrophy's pathogenic mechanism."

The skin allograft has been used as the test tool since the beginning of investiga tions of the fate of skin transplanted between two individuals of ordinary genetic diversity. This monograph is designed to furnish the transplantation work er with a review of the significant papers in which skin allografts and xeno grafts, applied to experimental animals and man, have played a role in acquiring a body of knowledge concerning the behavior and fate of these transplants and the reaction of the body to their presence. Skin, an essential organ for survival, a barrier between the "milieu inte rieur" of Claude Bernard and the "milieu exterieur," will remain the most frequently used transplant in transplantation research. Because it is highly antigenic, the final solution of the problem of acceptance of allografts of various tissues and organs will probably depend upon the achievement of a permanent survival of skin allografts. My personal interest in transplantation, which originated during my surgi cal training, was rekindled when I met Peter Medawar (today Sir Peter) in England during World War II. I had joined, in 1940, an American Volunteer Surgical Unit (The American Hospital in Britain), organized and headed by Dr."

During the last years the heat shock response has been stu- died as a model system to analyze control mechanisms regula- ting the synthesis of heat shock proteins providing impor- tant general insight into the regulation of gene expression. But the major revelation, which has sparked interest from all quarters of biology, is the discovery that heat shock proteins play major roles in an extraordinary variety of normal cellular processes. They are the focus of investiga- tions in many areas of cell biology, including protein traf- ficking, signal transduction, DNS replication, transcrip- tion, protein synthesis, and in the assembly of di- verse protein structures. These aspects are thoroughly trea- ted in the book, as are the implications in immunology, in- fec- tious diseases, chronic degeneration, hyperthermia, and can- cer research.

The pathology caused by baculoviruses in insect popula- tions was described centuries ago, notably in the larvae of insects such as the silkworm (Bombyx mori) which has been appreciated for the quality and beauty of its products. In the 1940s baculoviruses and their structure and physiolo- gy were intensively investigated, particularly by Bergold's group in Tiibingen. The following decades saw excellent progress, laying a solid virological base for later investiga- tions on the system. Further studies mushroomed in the 1970s with the advent of tissue culture systems for insect cells which eventually facilitated the molecular biological approach that came to the fore in the 1980 s. One of the reasons for pursuing research on the baculo- virus system was the prospect of eventually using these vi- ruses as insect pest control agents. While this practical as- pect may appeal to many, molecular biologists had addi- tional reasons to be interested in baculoviruses. Here was a large DNA viral genome, probably fraught with problems of replication and regulation that hopefully would open inroads into the molecular biology of interesting insect cell systems. In the days when genetechnology promises laurels, and after several virus systems had been skilfully exploited as highly efficient eukaryotic expression vectors, it came as no surprise that baculoviruses were also investigated in that respect. Indeed, the Autographa californica nuclear po- lyhedrosis virus became a good vector. Insect cells also seem to collaborate in modifying and processing the gene- technologically synthesized polypeptides.

M. B. A. OLDSTONE Viruses are generally studied either because they cause significant human, animal or plant disease or for their utility as materials to probe a basic phenomenon in biology, chemistry, genetics or molecular biology. Arenaviruses are unusually interesting in that they occupy both of these categories. Arenaviruses cause severe human diseases known primarily as the hemor rhagic fevers occurring in South and Latin America (Bolivia: Machupo virus and Argentina: Junin virus) and in Africa (Lassa virus). Because such viruses produce profound disability and may kill the persons they infect, they are a source of economic hardship in the countries where they are prevalent. Further, they provide new problems for health care personnel owing to the narrowing of the world as visitors from many countries increasingly travel to and from these endemic areas. In addition, lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling than those elicited by other arenaviruses. Yet LCMV is likely of greater concern to non-arena-virologists and experimentalists using tissue culture or animals, i. e. , workers in molecular biology, cancer research, virology, immunobiology, etc. , because normal appearing cultured cells or tissues and animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and transmit that infection to laboratory workers (reviewed OLDSTONE and PETERS 1978). For example, HINMAN et al.

Although upstaged by the tragic appearance of the human immunodeficiency virus, herpes simplex viruses (HSV) types 1 and 2 continue to be major human pathogens against which we lack acceptable vaccines or other means of immunological control. The virus is large and complex, coding for 70 or more proteins. Although many mysteries remain to be unraveled, our knowledge base regarding genomic organization, gene expression and regulation, pathogenesis, and immune recog nition of component parts is quite considerable. Indeed, meet ings devoted entirely to herpesviruses are conspicuous by their frequency and excellent, yet sometimes exclusive, attendance. The purpose of this volume is to compile in a single book a series of reviews by leading investigators that deal with various aspects of virus-host interactions and which hopefully will pro vide clues as to how to best manage HSV from an immunobio logical perspective. Ultimately, one anticipates that a full under standing of virus-host interaction will lead to strategies useful for the prevention and control of HSV. The state of current progress with conventional vaccines is presented, as is a chapter on intracellular immunization. This latter novel approach to virus infections comes at approximately the bicentenary of Jenner's introduction of a successful conventional immunization strategy."

The last decade has witnessed rapid progress in our under standing of the mechanisms of protein export and secretion in both prokaryotic and eukaryotic cells. Studies of protein secretion across the membranes of the rough endoplasmic reticulum have led to the formulation of the now-classic signal hypothesis, which has stimulated many discussions and new ideas, and the identification of the signal recogni tion particle as an organelle in the initiation of the export process. However, more recent work pertaining to intrage nic information related to targeting specific proteins for either secretion or membrane localization, the energetics of protein secretion, the timing of synthesis versus the initia tion of export, structural requirements for the processing of precursor proteins, and the identification of the proces sing enzymes (signal peptidases), has been the result of a combined biochemical and genetic approach to the study of protein localization in bacteria. While reviews on the biochemistry and genetics of pro tein secretion have appeared frequently in recent years, this book attempts to summarize the current status and the future perspectives of this rapidly moving field in a single volume. Topics covered in this book include the genetics of protein secretion in E. coli, biochemical analysis of pro tein export in vitro, signal peptidases, excretion of colicins and hemolysin in E. coli, protein secretion in Bacillus, and protein secretion cloning vectors."

Over the last few years, many new observations have profoundly changed our concepts of the immune competence of the newborn. For the immune system, as for other systems and functions, the neonatal age represents a crucial transition period. In fact the immune characteristics of the fetus are likely to result fro- or be conditioned by - several often contradictory physiological requirements. On the one hand, it would certainly be an advantage for the fetus to acquire a complete immunocompetence as soon as possible in order to be able to cope with the eventual transplacental passage of pathogenic microorganisms and possibly also in order to reject maternal cells occasionally crossing the placental nd barrier. This is actually what occurs, at least in part, during the 2 and Jfd month of gestation when the fetus begins to acquire his biological individuality and at the same time the role of a "biological ego" resulting from the attain ment by the immune system of the capacity to discriminate between self and nonself."

those who deal with infectious diseases on a daily This two volume work stems from the belief of the Editors that infectious diseases are not only very basis. much with us today but, more importantly, that they There are several excellent textbooks dealing will continue to playa significant global role in mor with medical microbiology, and there are equally well-recognized books devoted to infectious dis bidity and mortality in all people. A continuing need for an informed and knowledgeable community of eases. The Editors of this work, on the other hand, laboratory scientists is fundamental. Data describing were persuaded that there was a need for a publica the global impact of infectious diseases are difficult tion that would bring together the most pertinent and to come by. Fortunately, a recent thoughtful and relevant information on the principles and practice of provocative publication by Bennett et al. (1987) pro the laboratory diagnosis of infectious diseases and vides us with data derived from several consultants include clinical relationships. While this two volume that clearly delineate the impact of infectious dis text is directed toward the role of the laboratory in eases on the United States today."

Recent progress in the fields of pharmacology and immunology has provided us with new possibilities for treating dermatological diseases. This book reviews the most important immunosuppressive and immunostimulatory drugs and gives helpful, practical information on the treatment of various dermatoses, including autoimmundiseases, atopic dermatitis, psoriasis, vasculitis, contact dermatitis, pyoderma gangrenosum, infectious diseases, and neoplasms of the skin - in particular, malignant melanoma.

This volume documents our growing understanding of the human major histocompatibility complex. The application of this information is ever more important as the limits of transplantation continue to be reduced, including the recent success of bone marrow transplantation between unrelated but closely matched individuals. In addition, the need to transfuse platelets in the face of immunologic barriers continues to challenge transfusion services. Thus, the serologic information summarized in this volume is essential for optimal patient care. At the same time, recombinant DNA technology has led to a revolution in our understanding of many aspects of basic biology. Among the advances has been the initial characterization of the structure of some HLA loci. While this will ultimately improve clinical services, constant reference to serologic data is essential so that the powerful new techniques can be applied in the most effective ways. The timing of the First Red Cross International Histocompatibility Workshop is fortunate as it brings together experts from around the world to address the state of the art. We are all grateful to Dr. John Lee and his colleagues for organizing the workshop, and for bringing together in this volume the material to be presented in Beijing during October 17-23, 1990. Leon W. Hoyer, M.D.

There is no doubt among experts that the prevalence of allergic diseases has increased in many industrialized countries in recent years. The rea sons for this increase are unknown; only suppositions exist. Many people focus on environmental influences. However, the assumption that air pollution alone is responsible for this increase seems to be too simple: many other influences, including the genetic predisposition of individual patients, allergen exposure, and possibly socioeconomic factors, also have to be taken into consideration. Although our understanding of the complex mechanisms of allergic diseases has considerably improved thanks to the progress made in ex perimental immunology and allergology, we still have a long way to go before this scientific knowledge is translated into new therapeutic mo dalities. For this reason, the scientific community welcomed the gathering of scientists from very different disciplines and different parts of the world at an international symposium, "New Trends in Allergy IV" together with "Environmental Allergy and Allergotoxicology III" in Hamburg in 1995. This volume contains the invited papers, covering a wide range from basic science to practical clinical diagnosis and therapy. A further unique feature of this event was the concomitant first official workshop of the Environmental Pollution and Allergy Committee of the International Association of Allergy and Clinical Immunology (IAACI), at which the state of scientific knowledge in this field was defined and formulated."

Vaccines have historically been considered to be the most cost-effective method for preventing communicable diseases. It was a vaccine hat enabled global eradication of the dreaded disease smallpox. Mass immunization of children forms the anchor of the strategy of the World Health Organization (WHO) to attain "health for all" status by the year 2000. Vaccinology is undergoing a dimensional change with the advances that have taken place in immunology and genetic engineering. Vaccines that confer short or inadequate immunity or that have side effects are being replaced by better vaccines. New vaccines are being developed for a variety of maladies. Monoclonal antibodies and T cell clones have been employed to delineate the immunodeterminants on microbes, an approach elegantly complemented by computer graphics and molecular imaging techniques. Possibilities have opened for obtaining hitherto scarce antigens of parasites by the DNA recombinant route. Better appreciation of the idiotypic network has aroused research on anti-idiotypic vaccines. Solid-phase synthesis of peptides is leading to an array of synthetic vaccines, an approach that is expected to attain its full potential once the sequences activating suppressor cells are discovered and the rules for presentation of antigens to T and B cells are better worked out. A new breed of vaccines is on the horizon that seeks to control fertility.

The rapid and continuous upsurge of interesting data in the subject of tumor immunology necessitates the publication of an annual series to furnish the updated materials to the students, researchers, and clinicians in this rapidly advancing field. Concepts and methodologies are ever changing. Also, current research in tumor immunology promises to offer breakthroughs in the future. Important is the need to communicate to the right people the exact role of immunodiagnostic methods and immunolog ical intervention in cancer prevention and treatment. The role of immuno therapy in combination with conventional modalities of treatment needs in its proper perspective. Oncogene, interferon, lympho to be understood kines, monoclonal antibodies, natural killer cells, platelet-mediated cyto toxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell function, ab rogation of plasma-blocking factors, etc., are some of the areas that are continually advancing. Progress in these areas will have implication in cancer therapy. Further, it is already understood that if immunocompe tence of the host can be maintained at a reasonably good level, there exists the potential to increase the therapeutic indexes of conventional modalities of treatment. This series will attempt to present updated infor mation in all these areas based on contributed and solicited articles. P. K."

During the past decade, there have been numerous direct and indirect scientific contributions to both the etiology and therapy of aplastic anemia and related bone marrow failure syndromes. Clinical observations, such as autologous bone marrow recovery after conditioning with immunosup pressive agents for bone marrow transplantation; failure to achieve en graftment in some identical twins without prior immunosuppressive ther apy; and hematologic response to immunosuppressive agents, have led to the concept of immune-mediated etiology of acquired aplastic anemia. Such a concept was further strengthened by laboratory findings, implicat ing the role of activated cytotoxic T lymphocytes and abnormal produc tion of inhibitory lymphokines. The immunologic mechanisms may also apply to the idiosyncratic bone marrow aplasias associated with drugs, toxic chemicals, and viruses. These agents may alter normal cellular recog nition sites by interacting with cellular components and result in loss of self tolerance. Immunologic mechanisms have long been advocated in many other organ failures, and the hemopoietic organ is no exception. It is of interest that parallel clinical and laboratory investigations in juvenile diabetes mellitus type I and in rodent models of this disease have yielded results compatible with the same pathogenic mechanisms. The infiltration of pancreatic islets by activated T lymphocytes, functional and morphological alterations of islet cells upon incubation with lymphokines such as gamma interferon and tumor necrosis factor, and clinical response to cyclosporine are a few examples."

Fibronectins comprise a class of high molecular weight glycoproteins present both in extracellular matrices and in soluble form in body fluids. Although they have been studied for about forty years, their real significance emerged only during the past decade. Intensive research has focused on their role in platelet function, cell migration, the cytoskeleton, reticuloendothelial function, and on alterations in fibronectin distribution during development and disease. Fibronectins have emerged as glycoproteins with a very interesting set of properties generally involving adhesion of cells to cells or to extracellular material. In more recent years, the complete sequences of several fibronectin molecules and their genes were determined, the relation between structure and function was understood and much has been learned about cell surface receptors for fibronectins and other adhesive ligands. Having been at the forefront of all these exciting developments, the author has synthesized the entire field and with all the latest information at hand for the first time given it a clear perspective.

CURRENT TOPICS IN MEDICAL MYCOLOGY, VOLUME 4, like the pre- ceding three volumes in the series, is intended to summarize current research advances inmedical mycology. Topics ex- plored in this volume include skin kinetics of azole anti- fungal drugs; killer system interactions; fusarium-caused hyalohyphamycosis; molecular technique for epidemiologic ty- ping of Candida species; and the need for a mycoses-repor- ting system.

Rapid advances continue to be made in all areas of immunology, not least the biology of the immunoglobulins. This knowledge has resulted in a better understanding of antibody responses and helped to clarify pathogenic mechanisms in many diseases, particularly autoimmune and allergic diseases, as well as expand our comprehension of antibody deficiency diseases and mechanisms in therapeutic immunization. In addition, the recognition that diverse disease states may result in abnormalities of the amount of immunoglobulins in body fluids has resulted in the use of immunoglobulin assays for disease diagnosis and management. The aim of this book has been to condense both the established and recent aspects of this knowledge, particularly that pertaining to clinical immunology. The contributions of different authors hopefully provide a comprehensive review of their particular field of interest as well as a discussion of how this information can be applied to clinical medicine. Immunological terms and concepts have been explained where appropriate so that the book can be read by those with only a basic knowledge of immunology. In producing a book on this one area of immunology some duplication of information has been accepted so that topics can be considered in different contexts. I hope the book will be of value to those in training or already pursuing a career in clinical or laboratory medicine by providing a basic and short text on immunoglobulins. M.A.H.F.

It has been a challenge for us to edit this volume of Endocrinology and Metabo lism: Progress in Research and Clinical Practice. The topic of the pathogenesis of insulin-dependent, type I diabetes mellitus is particularly appropriate for this series, since advances in this area have been made, to a large extent, by applying state-of-the-art laboratory techniques to clinical samples. Over the last several years, a number of lines of evidence have been gathered, suggesting that classic type I diabetes mellitus results from the autoimmune des truction of pancreatic beta-cells in genetically susceptible individuals. This hypothesis is particularly appealing because it offers a rational approach to the prevention of diabetes by immunosuppression. We have tried to present a balanced, authoritative summary of the information currently available to support the autoimmune hypothesis for the pathogenesis of human type I diabetes, to place this information in historical perspective, to include relevant information from animal models of type I diabetes in which more invasive experimentation is ethical, and, finally, to update the reader on the current status of attempts to intervene in the progression of diabetes with immunosuppressive drugs. New York, New York Fredda Ginsberg-Fellner Robert C. McEvoy Contents Preface.. . . .. .. .. . . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . .. . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . 1. The Autoimmune Hypothesis of Insulin-Dependent Diabetes: 1965 to the Present . . . . . . . . . . . . ..................... . . . . . .

Vaccines have historically been considered to be the most cost-effective method for preventing communicable diseases. It was a vaccine that en abled global eradication of the dreaded disease smallpo. ."

The human leukocyte antigen (HLA) or tissue types are the products of a rapidly developing field of knowledge within the last 20 years. In the early stages of the research many investigators suspected the existence of a complex series of transplantation antigens, but it was widely believed that these antigens would not be well-defined even in this century. Yet in the last two decades as many as 124 different HLA antigens determined by at least 7 very closely linked genes located on the short arm of chromosome 6 have been identified and subsequently agreed upon by an international nomenclature committee. 1 Extensive international collaboration fueled by the potential clinical application of these antigens to clinical transplantation has advanced the field rapidly. There were nine inter national histocompatibility workshops held during this period. Although iden tification of HLA antigens was of primary clinical importance in transplantation 2 and of great basic interest in human genetics and anthropology, a rather un expected bonus has been the determination that HLA antigens are associated with disease susceptibility to a greater extent than any other known genetic marker in man. In the past, many genetic polymorphisms have been suspected to be associated with diseases. The most extensively studied markers are blood groups, enzymes, and serum proteins. A comprehensive account of published studies, totalling approximately 1,000, of these markers is available in a book by Mourant et al."

Oral tolerance is a major immunological property of the gastrointestinal mucosa. It plays a critical role in immune defence by preventing inflammatory and allergic responses to dietary and non pathogenic microbial antigens. The interest in oral tolerance has been renewed in the recent years, due to novel insights on its cellular mechanisms and potential clinical applications in the treatment of autoimmune diseases. Oral Tolerance: Cellular and Molecular Basis, Clinical Aspects, and Therapeutic Potential, has been designed as a concise yet comprehensive overview of the newest fundamental and clinical advances in the field. Based on the outstanding contribution of world experts, this book will be helpful to students, clinicians, and researchers working in mucosal immunology and gastroenterology. The first part of this volume describes the structure and functions of the gastrointestinal mucosa and the fundamental features and mechanisms of oral tolerance, including the role of T cells, cytokines, IgA antibodies, and bacterial antigens. The second part explores the clinical implications of the disruption of oral tolerance in Inflammatory Bowel Diseases, food and milk allergies, and coeliac disease in particular. The final chapter focuses on the clinical potential of oral tolerance as a promising therapeutic tool.

For over 50 years, the mission of the National Institute of Allergy and Infectious Diseases (NIAID) has been to conduct and support basic and applied research to better understand, treat, and prevent infectious, immunologic, and allergic diseases with the ultimate goal of improving the health of individuals in the United States and around the world. As part of its mission to foster biomedical discovery and to reduce the burden of human disease, NIAID is committed to encouraging the accelerated translation of biomedical discoveries into effective clinical care and public health practice throughout the world. In pursuit of this goal and its disease-specific scientific objectives, NIAID seeks to broaden research opportunities and collaborations involving scientists and institutions outside the United States. National Institute of Allergy and Infectious Diseases, NIH: Volume 1, Frontiers in Research contains presentations given at the 2006 NIAID Research Conference held in Opatija, Croatia which brought internationally known researchers from the United States and Central and Eastern Europe to focus together on shared interests in microbiology, infectious disease, HIV/AIDS, and basic and clinical immunology. Some of the topics covered include emerging and re-emerging infections, the development of infectious disease prophylactics and therapeutics, drug resistance, and various topics in immunomodulation, autoimmunity, infections and immunity, and the development of vaccines.

Extensive and in-depth, National Institute of Allergy and Infectious Diseases, NIH: Volume 1, Frontiers in Research is a valuable, comprehensive guide to the state of research today.

Recognizing the clinician's need for quick access to a comprehensive and immediately useful presentation of evidence-based material, the authors and editors have condensed the research on the most common otorhinolaryngological complaints into this indispensable volume. Their unique approach color-codes the level of research backing each set of evidence in order to make assessment of the evidence as quick and useful as possible. Each clinical problem is presented with a "color key," letting the physician know the level of evidence available: green (high-level evidence), yellow (low-moderate levels of evidence), or red (major disagreement or only minimal low-level evidence). The content of each chapter is structured in the same manner so the reader quickly becomes accustomed to finding precisely the information needed for each new case.

Featuring sections on general otolaryngology, head and neck surgery, pediatrics, and otology, Evidence-Based Otolaryngology not only presents the research, but gives the clinician immediately applicable recommendations for patient treatment.

lnflammatory reactions are generated in response to extemal and intemal stimuli, such as infection, trauma, clinical insult or dysregulation of the umnune system. The int1ammatory responses may bc antigen-specific or non-specific, local or systemic, chronic or rapid and severe, characterized by a massive release of mediators, often lethal. The aim of this book is to review selectcd aspects associated with the mechanism of the pathology of int1ammatory processes of ditlerent origin and to evaluate therapeutic strategies aimed at combating various inflamma- tory diseases. The introductory article describcs the inmlllnological status of patients with severe sepsis, with particular attention paid to the roJe of circulating neutrophils. Intcgrin activation and chemokine receptor expression and the roles of IL-15, prostaglandins and leukotriens in inflmmnation and immunity are the subjects of next articles. Subsequent reviews are focused on allergic diseases involving mast cells and Th2 type cytokines, in particular the mech- anisms of atopic dennatitis and signaling hy IL-13. The intlmmnatory responscs elicited by Mycobacterium tuberculosis and Mvcobacferium nviwn are also analyzed with special interest paid to the mechanisms which allow the bacteria to escape the host' s immune reactions. The thcrapeutic potential of IL- I 0 in infection and inflammation and thc possible factors contributing to the devclopment of idiopathic pulmonary fibrosis are rcvicwed in the next articles. The final report demonstrates the advantages of bacteriophage ther- apy in thc context of the aggravating problem of hactcrial resistance to antibi- otics.