Starting in 1986, the European School of Oncology has expanded its activities in post graduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meet ings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminat ing the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It was decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a com mon problem in medical literature: that of the material being outdated even before publication. Umberto Veronesi Chairman, Scientific Committee European School of Oncology Position Paper on the Application of Human Tumour Xenografts as a Model for Preclinical Phase" Studies in the Evaluation of New Anticancer Compounds Outcome of a seminar on Human Tumour Xenografts organised by the European School of Oncology, Milan, 26th-27th May, 1986.

Diabetes mellitus represents one of the most frequent and serious clinical syn dromes in contemporary medicine. Since the end of the nineteenth century, the endocrine pancreas has been implicated in the pathogenesis of this disease. Several pathologists of the twentieth century detected various lesions and mor phologic alterations in the pancreatic islets of diabetic patients, but the patho physiologic basis of their findings remained long obscure. The systematic mi croscopic work of WILLY GEPTS clarified the views and related the variety in histopathology to differences in origin, duration and clinical expression of the disease. Over the past two decades, the concept of a multifactorial origin of diabetes has become widely accepted. Various agents and mechanisms have been identified which can lead to a quantitative or qualitative deficit in pancre atic B-cells. The purpose of this book is to bring an update on the many path ways which may induce an absolute or relative insufficiency in insulin release and hence a diabetic state. Rather than bringing a complete account on all re search relevant to the understanding of the pathology of the diabetic pancreas, the authors of the various chapters of this volume have focussed on selected processes which can impair B-cell function, survival or regeneration.

The papers in this book were presented at the 6th Workshop on Mechanisms in B-Cell Neoplasia, held in Bethesda, March 23-25, 1988. On alternate years this meeting is sponsored by the . ;. Basel Institute of Immunology in Basel, Switzerland and by the National Cancer Institute in Bethesda, and is attended by 100 to 150 parti cipants. This 6th workshop, like the preceding five, was characterized by intense and enthusiastic discussion which reflects, we think, the exciting growth and development of this field. It is quite clear, however, that despite many general advances an understanding of the precise underlying mechanisms in B-cell tumor development is not yet defined. Probably, there is no single mechanism for all the various forms of B-cell neo plastic development. Many different forms of B-cell neoplasms are known, and these are distinguished by several characteristics: 1) the stage of development attained by the tumor stem cells; 2) mode of growth (slow or fast); 3) association with natural or inductive etiologic agents and 4) specific and consistent mutational mechanisms such as retroviral insertion, chromosomal rearrangement. Those charac teristic forms which arise naturally in relatively high frequency or those tumors with hallmark properties which can be induced consistently are the models most frequently studied, e. g. , endemic Burkitt's lymphoma, follicular lymphoma, acute and chronic lymphocytic leukemia and mUltiple myeloma in man; bursal lymphoma in chickens; Abelson virus induced pre B cell lymphomas and plasmacytomas in mice and immunocytomas in rats. Each model system, has special problems and advantages.

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper- function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self- constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

From the preface: "The importance of the lymphatic system has been known for a long time. It was therefore surprising to learn that the status of dermal lymphatics, under both normal and pathological conditions of man, had been largely neglected to date, particularly with respect to their ultrastructure. Moreover, the existing information is incomplete, relating only to narrow segments of the skin, and it is controversial. This monograph represents an effort to overcome some of the existing deficiencies in the area of the structure (with emphasis on ultrastructure) of lymphatic capillaries. It is an account of our experience in the evaluation of dermal lymphatics in normal, edematous, and some other pathological conditions in man and in experimental animals. It is hoped that this information will prove useful for other investigators as a basis for evaluation of the structural and functional status of dermal lymphatics under a wide variety of pathological conditions."

Aromas are an integral part of our civilised society. They are not only used in fine perfumes, but also in numerous other articles with which we have daily contact. Another new development has been the agricultural use of aromas as a "biological weapon" to combat insects and other pests. In the field of dermatology, aromas are today among the most frequent sensitizers and may trigger allergic contact eczemas. This volume presents numerous aspects of the topic for the first time in comprehensive form. In an introduction, the chemistry of frequently used aroma components is described, together with the art of perfume composition that has been refined over the centuries. In a chapter on neuropharmacology, the mechanisms of scent recognition are described in detail.

The prevention and control of infectious diseases represents, even today, an important public health problem for responsible national and international authorities. Newly emerging p.athogens such as human immunodeficiency virus (HIV), legionella, and bovine spongiform encephalopathy (BSE) have captured current public awareness. Despite significant success against smallpox, polio myelitis, mumps, and measles, the vast majority of infectious diseases are yet to be satisfactorily controlled. Limited efficacy of some vaccines, e. g., against influenza viruses, or their nonavailability have hampered an effective control of many infections. A meaningful reduction of the health risks posed by microbial pathogens is of crucial importance. Increased efforts need to be exerted in areas of active and passive immunization as well as in stimulation of enhanced nonspecific resistance .. Progress in the field of infectious diseases can be accelerated when a generation of new improved vaccines are developed. These vaccines should be capable of activat ing the cellular and the humoral immune responses as well as inducing persistent immunological memory. Development of novel regimens for enhancing natural resistance against infections is also progressively gaining in importance. The urgency increases as chemotherapy against viral and other infections further continues to be plagued by a carousel of a limited number of licensed drugs, problems of side effects, and development of drug resistance. It is becoming expedient that future strategies embrace a policy directed towards triggering mechanisms capable of inducing specific and nonspecific host defences."

Allergic Contact Dermatitis presents all up-to-date chemical and physio-chemical concepts for the study and understanding of allergic contact dermatitis (ACD). The book covers all aspects of ACD - skin penetration and metabolism, identification of sensitizers and hapten-protein interaction, including new concepts of increasing importance such as molecular recognition and quantitative structure-activity relationships. In addition, comprehensive references are provided, making this the most complete available text-book for dermatologists.
Allergic Contact Dermatitis reaches an equilibrium between fundamental concepts and clinical applications and thus presents an essential guideline to dermatologists, allergologists, biochemists and toxicologists.

For a long time, immunology has been dominated by the idea of a simple linear cause-effect relationship between the exposure to an antigen and the production of specific antibodies against that antigen. Clonal selection was the name of the theory based on this idea and it has provided the main concepts to account for the known features of the immune response. More recently, immunologists have discovered a wealth of new facts, in the form of different regulatory cells (helpers, suppressors, antigen presenting cells), genetic determinations of immune responses such as those involved in graft re jections, different molecular structures responsible for intercellular interactions such as interleukins, cytokins, idiotype-antiidiotype recognition and others. While furthering our understanding of the local interactions (molecular and cellular) in volved in the immune response, these discoveries have led to a questioning of the simplicities of the classical clonal selection theory. It is clear today that every single immune response is a cooperative phenomenon involving several different molecular and cellular interactions taking place in a coupled manner. In addition, cross reactivity to different antigens has shown that responses of the whole im mune system to different antigens are not completely isolated from one another and that the history of encounters with different antigens plays a crucial role in the maturation of the whole system. Thus, problems of complexity, generation of di versity and self-organization have entered the field of immunology.

Many bacteria, such as certain Neisseria and Haemophilus or Escherichia coli, are able to withstand the bactericidal activity of complement and phagocytes. This bacterial self protection is brought about by encapsulation. Bacterial capsules thus enable the pathogenic bacteria to survive in the host by counter action or evasion of the nonspecific host defense in the early pre immune phase of an infection. It is only in the late immune phase of the infection, when specific anticapsular antibodies are formed and enforce the host's defense system, that this protective action is overcome. Encapsulated bacteria are then killed and eliminated. Interestingly, some capsules can not or only inefficiently be handled by the immune system. The ensuing lack of antibody formation results in a prolonged susceptibility of the host to the pathogenic bacteria exhibiting such capsules. It was found that bacterial capsules consist of acidic poly saccharides. From this it followed that the role of the capsules in the interaction of encapsulated bacteria with the host may be due to the chemistry of the capsular polysaccharides. This led to intensive studies of capsular polysaccharides in many laboratories. Our increasing knowledge of the structural features of capsular polysaccharides prompted not only immuno chemical studies analyzing the interactions of these poly saccharide antigens and characterizing the epitopes, but also investigations into their biosynthesis. These studies were complemented and supported by genetic analyses. Today many interdisciplinary investigations of capsular polysaccharides are in progress.

The diversity of antigen-binding structures of antibody molecules is so vast that every conceivable antigen can be bound by an antibody molecule within the immune system. This is true even for the antigen binding sites of antibodies called idiotypes, which are bound by complementary bind ing sites of other antibodies called anti-idiotypes. Thus, anti-idiotypes are structural homologues of antigens. These idiotypic-anti-idiotypic interactions constitute a network within the immune system. Since one lymphocyte produces only one type of antibody molecule, this network is in fact a network of cells. We expect that the network is functional: the appearance of antigen will disturb the equilibrium of the network at the point where it competes with the anti idiotypic lymphocyte for binding to the idiotypic lympho cyte. It has been known for quite some time that anti idiotypic antibody can be used to prime the immune system for memory to an antigen that it has never seen. This phe nomenon is now being explored for possible use in immuni zation against viruses, bacteria, parasites and tumors as well as for the modulation of autoimmunity. The ability of anti-idiotypes to mimic, both antigenically and function ally, the corresponding biologically active molecules seen by an idiotypic antibody was first demonstrated for the hormone insulin and is now being observed in many other systems. The papers assembled in this volume. bring the reader to the cutting edge of the potential practical applica tions of the network theory of the immune system."

The idea for this volume was conceived during a discussion in the hallway at a conference in early 1990. "What is the best way to detect and define pluripotent hematopoietic stem cells?" was the question posed by Dr. Fritz Melchers. After discussing the pros and cons of the available assays for quite some time, it became apparent that this topic required a wider expertise and merited a larger forum. Thus, we decided to extend the discussion and to compile the results in this volume. Much to our delight. many of the pioneers of recent experimental and theoretical developments in stem cell research agreed to contribute their expertise to answer the question. These authors review both past findings and present insights, thus providing an overview of the evolution that has been and is occurring in the field of stem cell research. In the light of recent trailblazing developments in both experimental models and in clinical application it is indeed time to reevaluate our knowledge about stem cells. Trans plantation of hematopoietic stem cells has become more and more prevalent as a curative therapy in a variety of acquired and genetic diseases, including cancer, radiation accident, as an agent for gene therapy, and perhaps even as treatment for autoimmune diseases. Stem cells are now derived not only from bone marrow but also from peripheral blood, cord blood, and fetal liver, greatly increasing their availability for human transplantation and in some cases (fetal tissues) obliterating the need to match donors and hosts."

The third component of complement, C3, is one of the most versatile proteins and an important participant in immune surveillance and immune response pathways. Its multifunctio nality is based on its ability to interact specifically with multiple serum complement proteins, cell surface receptors, and mem brant;-associated regulatory proteins. One of its most intriguing strategies of interaction with cell surfaces is the covalent binding of activated C3 through the internal thioester. The field has expanded over the past 10 years and a wealth of information has accumulated. C3 from various species and many of the human C3 binding proteins have been cloned and expressed. Numerous cellular responses mediated by the diffe rent fragments of C3 have been described. The findings that C3 interacts in a ligand-receptor-like fashion with proteins of nonself origin such as the gC of herpes simplex virus, a 70-kDa protein from Candida albicans, proteins from Epstein-Barr virus, etc. has opened a new field of investigation. The papers assembled in this volume summarize the wealth of data on the various aspects of the C3 interactions; together they bring to the reader new information on the chemistry, molecular gene tics, biology, and pathophysiology of C3 and C3-binding proteins. Emphasis is given to structural features as they relate to functions. Spring 1989 JOHN D. LAMBRIS, HANS J. MULLER-EBERHARD Table of Contents J. E. VOLANAKIS: Participation of C3 and Its Ligands in Complement Activation . . . . . . . . . . . 1 S. R. BARNUM, G. FEY, and B. F. TACK: Biosynthesis and Genetics of C3 . . . . . . . . . . . . .

African and South American trypanosomiases are notable features of clinical and veterinary practice in their respective endemic areas and, as such, are of considerable economic importance. Scientifically, however, their importance ex tends beyond their clinical significance, as the trypano somes are intriguing and easily manipulated models for the study of the control of gene expression, membrane chemistry, proliferation and differentiation. It is clear from the scientific press that the rate of advance has "hotted" up in these areas of trypanosome research over the past 5 years and so a single-topic volume within the scope of the present series seemed timely. As ever, the final admix ture of review topics was a compromise between what was appropriate and what was available - fortunately with the former in vast excess. I should like to highlight two omissions, made for en tirely different reasons. The first is a detailed treatment of the molecular biology of the variant surface glycopro teins of the African trypanosomes (in particular Trypano soma brucei and T. equiperdum). This topic has been the subject of several reviews, for example, BORST and CROSS (1982)1 and TURNER (1982)2, and so was excluded from the present volume. The second omission is a review of the first-class work on genetic recombination from the group of Dr. Leo Jenni at the Schweizerisches Tropeninsti tut, Basel. This group has used isoenzyme markers to show that T."

Many of the fundamental concepts of animal virology originated from the study of the variola-cowpox-vaccinia virus system with vaccinia virus serving as the type species (Fen- nerand Burnet 1957; Burnet 1959; Fenner 1976a, b). The importance of the Poxviridae(Fen- ner 1979) for the study of viruses as biologic entities and in defIning the events which occur in virus-infected cells are exemplifIed by investigations which: (a) described the epidemiology of a virus disease in an animal population (Fenner1949, 1959b); (b) em- ployed electron microscopy to study virion structure (Peters 1956, Nagington and Home 1962, Dales and Siminovitch 1961) and to derme the morphologic stages of virion develop- ment in infected cells (Morgan et al. 1954, Dales 1963); (c) dermed and elaborated on the mechanism of nongenetic reactivation for an animal virus (Joklik et al. 1960a, Fenner and Woodroofe 1960, Hanafusa 1960); (d) described the intracellular uncoating of a viral genome (Joklik 1964a, b); (e) studied the antigenic structure and complexity of poxvirions (Loh and Riggs 1961, Woodroofe and Fenner 1962, Appleyard et al. 1964, Appleyard and Westwood 1964); (1) described the use of chemotherapy to treat viral infec- tions (Bauer et al. 1963); (g) fIrst demonstrated the presence of virion-coded enzymes encapsulated within virions (Kates and McAuslan 1967, Munyon et al. 1967); and (h) established the H -2 restriction of cytotoxic T-cell killing of virus-infected cells in the murine system (Doherty et al. 1976).

Leading researchers present contemporary treatment of in situ hybridization applied to current issues in animal virus pathogenesis. The most recent methods are given for locating viral genes in whole animal section and for defining the number and type of cells surrounded by viruses. The genetic programs played out in these cells and the newer methods of hybridization at the electron microscopic level provide valuable insight into the complexities of virus-host interaction.

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.

When I entered the field of allergy in the early 1970s, the standard textbook was a few hundred pages, and the specialty was so compact that texts were often authored entirely by a single individual and were never larger than one volume. Compare this with Allergy Frontiers: Epigenetics, Allergens, and Risk Factors, the present s- volume text with well over 150 contributors from throughout the world. This book captures the explosive growth of our specialty since the single-author textbooks referred to above. The unprecedented format of this work lies in its meticulous attention to detail yet comprehensive scope. For example, great detail is seen in manuscripts dealing with topics such as "Exosomes, naturally occurring minimal antigen presenting units" and "Neuropeptide S receptor 1 (NPSR1), an asthma susceptibility gene." The scope is exemplified by the unique approach to disease entities normally dealt with in a single chapter in most texts. For example, anaphylaxis, a topic u- ally confined to one chapter in most textbooks, is given five chapters in Allergy Frontiers. This approach allows the text to employ multiple contributors for a single topic, giving the reader the advantage of being introduced to more than one vi- point regarding a single disease.

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.

This key work in the field draws on a broad spectrum of molecular biologic, biochemical, and immunogenetic approaches in combination with human and murine in vitro cell culture and in vivo model systems to address questions in mucosal immunity. Humans produce more immunoglobulin A (IgA) than all other antibody isotypes combined. This book is designed to serve as a concise reference of the present knowledge of the biology of IgA.

Allergy is one of the major health problems of most modern societies. Although allergic diseases are well-known for almost two hundred years, their prevalence has increased dramatically over the last decades. Allergic reactions manifest in various organs, most commonly in the skin and mucous membranes, the frontier surfaces where the contact between the individual and the environment takes place. In a very concise and practical way this book covers all aspects of allergic reactions from pathophysiology to diagnosis, therapy and prevention with a strong focus on relevant aspects for the everyday work of the practising dermatologist and allergist in the hospital or office. This book reflects the rich personal experience of a German allergist with international training and reputation, who is active in immunology and allergy research and practice for almost 30 years. In this book, not only IgE-mediated allergic reactions are covered but all other kinds of allergies such as atopic eczema, contact dermatitis, drug eruptions, anaphylaxis and food allergies are equally represented as well as psychosomatic aspects and problems of environmental intolerances.

Irritant dermatitis is a common condition, accounting for a significant proportion of occupational skin disease. The recent advent of non-invasive skin bioengineering technology has accelerated dermatology research in this field. This book comprises an exhaustive reference text on irritant contact dermatitis, covering all aspects of the condition: clinical features, epidemiology, prevention and therapy, prognosis, mechanisms, pathology and regulatory issues. The book also presents novel in vitro and in vivo research techniques and findings. As irritant dermatitis affects multiple specialties, the audience for this book is wide, including clinical and investigative dermatologists, allergists, toxicologists, pharmaceutical scientists, occupational and environmental physicians, public health physicians, cosmetologists and skin bioengineers.