Especially the past two decades have seen renewed interest in the vasculitides. In this volume an international expert group presents the current state of knowledge and concentrates on principles of immune modulating therapy. Drawing from their work in rheumatology, nephrology, internal medicine, connective tissue disease and clinical immunology, they present new concepts in classificiation, diagnosis and pathophysiology of the vasculitides. Evidence from experimental and clinical trials is reviewed, as well as the outlook for further research.

This work is concerned with a group of proteins which were originally consid ered to be an esoteric phenomenon but which have now been shown to play critical roles both in normal and stressed cells as well as being involved in a variety of human diseases. It is the purpose of this work to give a comprehen sive view of these proteins and their various aspects. After an introductory chapter providing an overview of these proteins, the work is divided into four main sections each of which deals with one important aspect of these proteins. Thus, the first section contains a series of chapters which describe individual stress proteins and their roles in particular biological phenomena. Evidently, the induction of these proteins by elevated tempera ture or other stresses is their defining feature and the second section of this book therefore considers the regulation of stress protein gene expression both by stressful stimuli such as elevated temperature or ischaemia and by non stressful stimuli such as cytokines.

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

In this volume, a distinguished international group of contributors present the latest molecular, organismal, and epidemiological research on arenaviruses. Their work will broaden both the clinician's and the researcher's knowledge of basic mechanisms of immunological tolerance, viral immunosuppression, the nature of protective immune responses to vaccination, and viral effects on cell functions.

This volume is based on the program of the Second International Conference on Drugs of Abuse, Immunity and AIDS, held in Clearwater Beach, FL in June 1992. The Conference was supported in part by the University of South Florida College of MediCine with financial assistance from the National Institute on Drug Abuse. The focus of this conference was the effects of drugs of abuse on immunity. It is now widely recognized that psychoactive drugs of abuse, including marijuana, cocaine, and opiates, as well as alcohol, have marked effects in an individual, including effects on their nervous system and behavior. In the past two decades, the scope of studies concerning the effects of some drugs of abuse have also involved investigations of alterations of various physiologic parameters including effects on the immune system. and the influence of such immune alterations on normal physiological responses. In this regard, participants in this Second International Conference provided newer information concerning both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiencies. In this regard, advances have been made in recent years concerning the nature and mechanisms whereby the immune system is regulated and the possible mechanisms by which drugs of abuse influence such immune systems. In particular, the emergence of psychoneuroimmunology as a new discipline the last decade has heightened interest in the immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving both clinical and basic scientists, including microbiologists, immunologists, physiologists, psychiatrists, oncologists, psychologists, etc.

The seventh Annual Pezcoller Symposium entitled, Cancer Genes: Functional As- pects, was held in Trento, Italy, June 14-16, 1995 and was focused on oncogenes func- tion, tumor suppressor gene function, transcription regulation, cell cycle progression regulation and apoptosis, and the clinical implications of oncogene function and regula- tion for prevention and therapy of cancer. With presentations at the cutting edge of pro- gress and stimulating discussions, this Symposium addressed issues related to the mechanisms of control of cell growth and death by certain genes such as c-myc, src, fyns, bcl2, the function of cdk inhibitors, the functions of p53 and WTI, the mechanisms of transcriptional activation of specific oncogenes, the genetic characterization of certain he- matological malignancies, the interference with specific sites along signal transduction and the genetic alterations of tumor immunity. We wish to thank the participants in the Symposium for their substantial contribu- tions and their participation in the spirited discussions which followed. We would also like to thank Drs. Jane Azizkhan, Paolo Comoglio, Giulio Draetta~ David M. Livingston and Alex Matter for their essential input as members of the Program Committee, and Ms. A. Toscani for her invaluable assistance. The aid of the Bank Cassa di Risparmio di Trento and Rovereto, and the Municipal, Provincial and Regional Administrations in sup- porting this Symposium through the Pezcoller Foundation are also acknowledged with deep appreciation. Finally, we wish to thank the staff of Plenum Publishing Corporation for their efficient cooperation in the production of these Proceedings.

This monograph is intended to compile the lectures presented at the 4th Annual Symposium "Cardiac Surgery:1992" held at the Frenchman's Reef Beach Resort, St. Thomas, US Virgin Islands, November 7-10, 1991. This symposium was organized by the Division of Cardiothoracic Surgery and the School of Cardiovascular Perfusion, Cooper Hospital/University Medical Center, Camden, New Jersey and sponsored by the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Philadelphia Academy of Cardiovascular Perfusion and the American Society of Extracorporeal Technology -Region II. The symposium was devoted to cardiothoracic surgeons, cardiologists, cardiovascular perfusionists, and nurses involved in the management of the cardiac surgical patient. Therefore, the context of the book represents the multidisciplinary nature of cardiac surgery at its present level of development. The contributors to this book have critically examined their experience and discussed controversial issues regarding cardiac pathophysiology, surgical indications, operative techniques, and long term care and outcome. The co-editors wish to express their gratitude for the contributors' efforts in the production of this manuscript. We would also like to thank the members of the Organizing Committee, Jane V. Stewart MSN, RN, CCRN, Roger A. Vertrees BA, CCP, Rosemary Volosin, MSN, RN, Rosemary Morrone and Paul R. Cappola BS, CCP, who have greatly contributed to the success of the symposium."

Since the first edition of Complement in Health and Disease was published in 1986, significant advances have been made. The cDNAs for all of the components and some of the receptors have been cloned and sequenced. The chromosomal localization and the structural organization of a number of these genes have now been determined. These advances are now facilitating research into the structure of the complement proteins, the nature of the complement deficiency syndromes, the regulation of complement gene expression and the role of complement in different diseases. This edition contains contributions from both basic and clinical scientists in a format which we hope will appeal to both immunologists and physicians who wish to know more about this fascinating and important host defence system. The introductory chapter by John Weiler presents a historical background to research on the complement system and describes the biochemical events occurring during activation of the system. In Chapter 2 Alastair Dodds and Tony Day discuss the phylogeny and evolution of the complement system. The techniques of protein chemistry and molecular biology have provided powerful insights into the modular structure of complement proteins and the evolution of the complement system. The structure and organisation of the complement genes is described in Chapter 3 by Ken Reid and Duncan Campbell. This chapter describes the modular structure of the complement proteins and some of the mutations which are responsible for deficiencies of individual components.

During the past decade, the rapid growth of molecular and cellular knowledge of macrophages, as a specialized host defense and homeostatic system, has begun to offer attractive targets for therapeutic intervention. Macrophages play a central role in a wide range of disease processes, from genetically determined lysosomal storage diseases, to acute sepsis, chronic inflammation and repair, tissue injury and cell death. Under- or overactivity of macrophage clearance, immune effector functions and responses to metabolic abnormalities contribute to common disorders such as autoimmunity, atherosclerosis, Alzheimer s disease and major infections including AIDS and Tuberculosis. Whilst the goals of therapeutic intervention based on improved understanding of macrophage functions and their contribution to pathogenesis may seem self evident, there are considerable difficulties in producing useful new agents.

The present volume covers a range of subjects and provides opportunities for a more focused macrophage-targeted approach. The individual chapters review selected topics briefly, to place cellular processes and molecular targets in perspective. Overall, the volume should provide a broad sample of the state of the art. Useful reviews and references in the literature are cited within individual chapters."

Background Cancer is a variety of malignancies generally associated with aging. As the overall health technology and health care delivery improved with the advances made in medicine and science in the United States, the life expectancy of the population also increased. The average life expectancy in the U. S. A. has increased from 49 years at the end of 1900 to 75 years today in 1990 (1-3). The population of 65 years and older that constituted 25. 5 million or 11. 3% of the total U. S. population in 1980(4) has now increased to 31. 1 million or 12. 5% of the population according to the 1990(5) census. As cancer diagnosis and treatment have improved, cancer mortality among patients under 55 has been significantly reduced within recent years *1; however, cancer incidence under 55 is still increasing at about 0. 4% per year (as compared to 1. 0% for all ages or 0. 6% for < 65) according to the 1990 review of the 15 year trends in the Cancer Statistics Review 1973-1987, published by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). In contrast, both cancer incidence and mortality have been increasing among the population 65 and over*2 at a rate of 1. 4% and 1. 0% respectively per year between 1973-1987(6).

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

This volume represents a series of papers presented at the Second International Workshop on HPV Immunology held at the University of Cambridge July 5-7 1993. This Workshop and its predecessor held in Amsterdam in May 1992 were two of the major activities of the European Concerted Action "Immunology of Human Papillomavirus and Vaccine Development." The Concerted Action (CA) was supported by grants from the Commission of the European Communities (EC), the French Association for Cancer Research (ARC) and the European Association for Medical Research (EAMR). Twenty two laboratories throughout Europe and Scandinavia were members of the CA, the objectives of which were to develop collaborations, implement scientific exchanges and co-operate in a collective effort to develop vaccination strategies for HPV. HPV's are ubiquitous pathogens and evidence which has been accumulated over the past decade leaves little doubt that infection with certain HPV types (the so called "oncogenic HPV's" 16, 18 and their relatives) is the major risk factor in the development of cancer of the uterine cervix in women. Since an infectious agent, a virus, is implicated as the main aetiologic factor in this disease, the possibility is raised that if one could prevent HPV infection or treat established infections this would be an effective anti-cancer strategy against what is the commonest cancer in women worldwide."

The purpose of this volume in the Progress in Inflammation Research series is to provide the biomedical and clinical researcher with a state-of-the-art insight in the role of cytokines in joint inflammation and joint destruction. This is of relevance for better understanding of key processes in diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). Apart from the impact of old and novel cytokines on joint tissues, the various chapters address the issue of targeted therapy with biological response modifiers and future interventions with carefully designed inhibitors. Spe cial attention is given to elements of synovial cell activation, cell-cell interaction, cytokine interplay as well as mechanisms of cartilage destruction and bone erosion. In addition to an outline of the role of established cytokines, such as TNF, IL-l and IL-6, new information is given on the novel cytokines IL-15, IL-17 and IL-18 and their positioning in the complex cytokine interplay. Cytokine regulation of destructive enzymes, RANKL, the endogenous inhibitor OPG and their crucial roles as central players in joint erosion are highlighted. Together, the chapters provide a complete and balanced view on pivotal cytokines and joint pathology.

1. 1. Invasive versus Non-Invasive Clinical Measurements in Medicine Clinical measurement has become an essential complement to traditional physical diagnosis. An ideal clinical measurement should be quantitative, have a high level of reliability and accuracy, be safe, acceptable to the patient, easy to perform and non-invasive. The latter demands that the technique should not break the skin or the lining epithelium and should be devoid of effects on the tissues of the body by the dissipation of energy or the introduction of infection [1]. It is therefore logical that for a given measurement, a non-invasive test will be preferred if it provides the same information with the same accuracy and precision. In the following sections, we will discuss the role of various non-invasive or relatively non-invasive methods to assess airway inflammation in asthma and concentrate on the only direct method of induced sputum examination. 1. 2. Why Is Assessment of Airway Inflammation Important in Asthma? Inflammation is a localized protective response elicited by injury or destruc tion of tissues which serves to destroy, dilute or wall off both the injurious agent and the injured tissue [2]. The role of inflammation in asthma was rec ognized long ago. In his textbook The Principles and Practice of Medicine, in 1892, Sir William Osler described "bronchial asthma . . . in many cases is a spe cial form of inflammation of the smaller bronchioles . . .

The National Institute of Dental Research sponsored a workshop on "Genetically Engineered Vaccines: Prospects for Oral Disease Prevention," held at the National Institutes of Health (NIH) on November 6-8, 1991. The purpose of the workshop was to convene molecular biologists and immunologists to address the state of the science in vaccine development and to explore the potential of developing vaccines for prevention of oral diseases. The goal was to elicit new research initiatives and recommendations for vaccine development with emphasis on the prevention of oral diseases and diseases affecting the orofacial tissues. The workshop was attended by more than 100 persons who heard 30 presentations, and the speakers provided the papers for this volume. The workshop focused on the following topics: oral diseases and host immune responses, update on vaccines and vaccine development, vaccines and the mucosal immune system, optimizing mucosal and systemic immune responses, delivery systems and immune analysis, target antigen selection and vaccine development, immunological correlates of protection and future direc tions/recommendations. Three key areas were identified: Optimizing the Mucosal Immune Response, Antigen Delivery Systems, and Target Antigens and Immunological Correlates of Protection. The summary and recommendations from these deliberations is included at the end of this volume."

Assembling the latest research by an international group of contributors, this volume covers the epidemiology, pathogenesis, clinical features, and control measures of this elusive microorganism. It will provide a deeper understanding of the pathogen to physicians and surgeons caring for patients infected, or at risk of becoming infected, with Pseudomonas Aeruginosa.

Since the discovery of the bone morphogenetic proteins (BMPs) more than 15 years ago, there has been an unpredicted explosion of both basic scientific discoveries and clinical reports on their use from institutions all over the world. The potent effica cy of BMPs in almost all crucial developmental events as well as during regenera tion of various organs such as bone, kidney, brain, liver, heart etc. , has positioned BMPs at the center of scientific interest. Many of these aspects are covered in this new PIR volume. Their role in development, biology, signal transduction, kidney regeneration, eNS functions, craniofacial skeleton reconstruction, joint and carti lage repair, long bone non-unions and acute fractures, and spinal fusion is reviewed by experts in the field. For the first time, the role of BMPs in carcinogenesis has been reviewed to provide a rationale for applying their biology in patients with bone tumors. The optimism resulting from safe and successful treatment with BMPs for various skeletal malformations of more than 10,000 patients worldwide has opened new avenues for exploring other indications for their use. The next big challenge for bringing BMPs to the benefit ofmankind is in regenerating articular cartilage defects and rescuing patients with acute and chronic renal failure. The volume editors thank all authors for the rapid preparation of their chapters in order that the book remains up-to-date for readers with specific interest in the field of regenerative medicine. The important contribution of Mrs. Morana and Mr.

This book is based upon a series of papers originally presented at a NATO Advanced Studies Workshop of the same title held at the study Center HI Cappuccini," a converted monastery in San Miniato, a small village located between Pisa and Florence, Italy, in October 1991. Authors were asked to submit their completed chapters by the following February; these were then scanned onto computer disks, edited and returned to the authors for final revision, and updating, with a final deadline of February 1993. The authors were encouraged to make whatever modifications they wanted, especially regarding updating their chapters, with an eye to making the final product both comprehensive and current. In this we succeeded beyond our expectations, with most chapters extensively altered and many completely re-written and significantly expanded. Thus, although the original meeting was held in 1991, the chapters in this volume may be regarded as current from at least February, 1993, with some of the final updated revisions received as late as July, 1993. This book, as agreed in our original contract, has been delivered to the publisher "camera-ready. " This means that all of the scanning, editing, proofing and typesetting were done here, by the office of the Department of Dermatology at the New Jersey Medical School. We essentially produced the book, which the publisher, for the most part, then photocopied. This has been an enormous burden, borne mainly by my colleague in this division, Robert A.

The topicS in this book represent the presentations given at the Fifth Annual Meeting entitled "Cardiac Surgery: Current Issues" held at the Frenchman's Reef Beach Resort. St. Thomas. U.S. Virgin Islands. November 11-14. 1992. This symposium was sponsored by the Division of Cardiothoracic Sur gery. the School of Cardiovascular Perfusion and the Department of Nursing Education and QUality Assurance of Cooper Hospital/University Medical Center. the University of Medicine and Dentistry of New Jersey. Robert Wood Johnson Medical School. Camden. New Jersey. as well as the Academy of Medicine of New Jersey. Chapter authors were charged with the task of writing brief overviews of major issues related to the field of cardiac surgery. The book is specifically tailored to the needs of cardiothoracic surgeons. cardiovascular perfusionists. allied health professionals and nursing personnel involved in all phases of caring for the cardiac surgical patient. Although intended as a reference source with emphasis on up-dated approaches applied in cardiac surgery. it is hoped that the discussion of these topics will compliment other texts and manuscripts. Obviously.';ibook of this length cannot cover the whole multidiSciplinary and complex field of cardiac surgery. However. co-editors are certain that the annual appearance of this text will highlight comprehensive. new and interesting approaches to the field of cardiac surgery."

In recent years rapid progress has been made in the areas of T cell and B cell biology, cell-cell and cell-matrix/stroma interactions. The use of isolated subunits of the T cell receptor invariant chains has been instrumental in defining their role in signal transduction and tyrosine phosphorylation. A role of src family phosphotyrosine kinases in T cell activation has been demonstrated and several phosphotyrosine kinase substrates have been identified and their functions characterized. Homologous recombinant techniques have led to the development of murine strains that lack CD4 or CD8 expression. These models are likely to be instrumental in studying the role of T cell subsets in autoimmune disorders, tissue transplant rejection and tumor rejection. A role of major histocompatibility complex I in the development of T cell subsets and NK cells has been defined. Recent data suggest a role of interaction between plasma membrane molecules of activated T helper cells and B cells, B cells primed with plasma membrane of activated T helper cells and cytokines, and interaction between bone marrow stromal cells and B cell progenitors and precursors, in the B cell development, proliferation, and differentiation. The structure and functions of adhesion molecules, especially with regard to signal transduction and homing events, are better defined.

Gastrointestinal diseases present a considerable problem in human medicine in terms of both morbidity and mortality. The aim of this book is to cover the different immunological disorders of the gut with special reference to immunopathological and protective mechanisms. It will be of general interest to clinicians, scientists and students concerned with the gastrointestinal tract. Topics covered include: the current status of research into toxin-secreting pathogens, Campylobacter, Giardia and HIV; the immunological features of idiopathic inflammatory gut diseases such as Crohn's disease and intractable diarrhoea; the genesis of the flat mucosa; the iatrogenic diseases of the gut such as graft-versus-host disease and small bowel allografts; the immune mechanisms and lesions in the gut of patients with parasitic nematode infections (very important in the tropics). Basic background on the immune apparatus in the intestine is also discussed, as are the effects of inflammation on intestinal permeability.

Corona- and related viruses are important human and animal pathogens that also serve as models for other viral-mediated diseases. Interest in these pathogens has grown tremendously since the First International Symposium was held at the Institute of Virology and Immunobiology of the University of Wiirzburg, Germany. The Sixth International Symposium was held in Quebec City from August 27 to September I, 1994, and provided further understanding of the molecular biology, immunology, and pathogenesis of corona-, toro-, and arterivirus infections. Lectures were given on the molecular biology, pathogenesis, immune responses, and development of vaccines. Studies on the pathogenesis of coronavirus infections have been focused mainly on murine coronavirus, and mouse hepatitis virus. Neurotropic strains ofMHV (e.g., JHM, A59) cause a demyelinating disease that has served as an animal model for human multiple sclerosis. Dr. Samuel Dales, of the University of Western Ontario, London, Canada, gave a state-of-the-art lecture on our current under standing of the pathogenesis of JHM-induced disease.

It is widely accepted that vaccination still renains the best answer to ITDst infectious diseases. Recently, vaccine developnent has been greatly facilitated by advances in ITDlecular and cell biology which have laid the foundations of a new generation of vaccines. '!hese are exemplified by submit vaccines produced through gene cloning and synthetic peptides mimicking snall regions of proteins on the outer coat of viruses and capable of eliciting virus neutralizing antibodies. However, submit and peptide vaccines are only weakly or non-inmmogenic in the absence of immunological adjuvants. The latter are a diverse array of agents that augment specific cell-mediated immune responses to the antigens and the formation of protective antibodies. '!his book contains the proceedings of the 3rd NATO Advanced Studies Institute (ASI) "New-Generation vaccines: '!he Role of Basic Irrmmology" held at Cape Sounion Beach, Greece, during 24 June-5 July, 1992. It deals with recent developnents in the understanding of inmmity at the ITDlecular and cellular levels and the application of such knowledge in the search for novel inmmological adjuvants and the fonnulation of new-generation vaccines for experimental and clinical use. We express our appreciation to Professor K. Dalsgaard and H. Snippe for their cooperation in planning the ASI and to Mrs. Concha Perring for her excellent production of the manu- scripts. '!he ASI was held tmder the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SrnithKline Beecham Pharmaceuticals (Fhiladelp,. ia). Financial assistance was also provided by Pasteur Merieux (Marcy L'Etoile), British Biotechnology Ltd.

This volume summarizes the proceedings of the Eighth International Symposium on the Immunobiology of Proteins and Peptides which was held on November 16-20 in Rio Rico, Arizona. The articles represent papers by invited speakers as well as papers selected by the Scientific Council, from among those submitted by the participants, on the basis of quality and timeliness. This symposium series was established in 1976 for the purpose of bringing together, once every two or three years, active investigators in the forefront of contemporary immunology, to present their findings, discuss their significance in the light of current concepts and identify important new directions of investigation. The founding of the symposium was stimulated by the achievement of major breakthroughs in the understanding of the immune recognition of proteins and peptides. We believed that these breakthroughs would lead to the creation of a new generation of peptide reagents, which could have enormous potential in biological, therapeutic, and basic applications. This anticipated explosion has since occurred and many applications ofthese peptides are now being realized. The eighth symposium focused on the manipulation or modulation of the immune response. This volume broadly covers the areas of adjuvants, cytokines, vaccines, and the use of intravenous immunoglobulins for disease management. There is a clear need to identify methods for improving vaccine efficacy and guiding the host to respond with a particular type of immune response.

These Proceedings contain the contributions of the partIcIpants of the Third International Symposium on Dendritic Cells that was held in Annecy, France, from June 19 to June 24, 1994. This symposium represented a follow-up of the first and second international symposia that were held in Japan in 1990 and in the Netherlands in 1992. Dendritic cells are antigen-presenting cells, and are found in all tissues and organs of the body. They can be classified into: (1) interstitial dendritic cells of the heart, kidney, gut, and lung;(2) Langerhans cells in the skin and mucous membranes; (3) interdigitating dendritic cells in the thymic medulla and secondary lymphoid tissue; and (4) blood dendritic cells and lymph dendritic cells (veiled cells). Although dendritic cells in each of these compartments are all CD45+ leukocytes that arise from the bone marrow, they may exhibit differences that relate to maturation state and microenvironment. Dendritic cells are specialized antigen-presenting cells for T lymphocytes: they process and present antigens efficiently in situ, and stimulate responses from naive and memory T cells in the paracortical area of secondary lymphoid organs. Recent evidence also demonstrates their role in induction of tolerance. By contrast, the primary and secondary B-cell follicles contain follicular dendritic cells that trap and retain intact antigen as immune complexes for long periods of time. The origin of follicular dendritic cells is not clear, but most investigators believe that these cells are not leukocytes.