Contents: The Use of Immunohistochemistry: Present and Future - The Expression of Vimentin in Epithelial Neoplasms - Morphologic Manifestations of Malignant Lymphomas in the Spleen. A Histologic and Immunohistochemical Study of 500 Biopsy Cases - Demonstration of Epstein-Barr Viral Genomes in Routine Paraffin Sections of Lymphoproliferative and Epithelial Lesions by in Situ Hybridization - Carcinoma of the Lung;Changing Sex Distribution and Histopathologic Cell Types - Pulmonary Pathology in Lung Transplant Patients - Bronchiolitis Obliterans with Organizing Pneumonia and Constrictive Bronchiolitis: Comparative Analysis ofTwo Distinct Entities - Lymphoid Interstitial Pneunomia in HIV Infected Individuals. Long-Term Clinicopathologic Observations in 52 Patients and Pathogenesis - Genital Human Papillomavirus (HPV) Infections and Their Associations with Squamous Cell Cancer: Reappraisal of the Morphologic, Epidemiologic and DNA Data - Central and Peripheral Bronchial Carcinoids Possess Distinct Peptide Immunostaining Patterns - Diagnosis of Rhabdomyosarcomas with Particular Reference to Immunohistochemical Markers - Borderline Lesionsof the Gastric Epithelium: New Indicators of Cancer Risk and Clinical Implications - The Pathology of Secondary Human Yolk Sac in Spontaneous Abortion: Findings in 103 Cases

Challenging Cases in Allergic and Immunologic Diseases of the Skin offers clinicians a wide range of challenging cases that are certain to provide hours of thoughtful and instructive review. Using a case study format and including excellent quality color images, Challenging Cases in Allergic and Immunologic Diseases of the Skin consists of five parts and 20 chapters. The chapters cover such areas as allergic rhinitis, allergic diseases of the eye, drug-induced urticaria, cosmetic allergy, drug allergy, latex allergy, atopic dermatitis, vasculitis, and a range of other commonly seen disorders of the skin. Each chapter comprises at least two cases that are followed by a differential diagnosis, discussion, and five multiple choice questions for thoughtful stimulation and excellent value as a teaching tool. Comprehensive, concise, and well-designed in presentation, Challenging Cases in Allergic and Immunologic Diseases of the Skin is a one-of-a-kind resource that will become a standard resource for all clinicians who care for patients with allergic and immunologic diseases of the skin.

This work is concerned with Cystic Fibrosis (CF), the most common fatal genetic disease in the Caucasian population. The decade of the 1980s was one of spectacular progress in understanding the genetic and molecu lar basis of CF. The research breakthroughs of the decade began with the first fundamental insights, published in 1981-1983, into the basic cellular pathophysiology of CF with demonstrations of altered ion transport in spe cialized exocrine epithelial tissues (1-3). Research progress shifted into a triumph of "reverse genetics," using restriction-fragment-Iength polymor phism DNA technology (4), with the localization of the CF gene to a region of chromosome 7 (5-7). Understanding, accelerated by an explOSion of in vitro methodologies for epithelial cell culture and transformation, allowed and physiological studies (8-11); these focused, controlled biochemical with increasing precision, on the molecular pathology of distal steps in the regulatory pathways for epithelial ion transport (12-19). Finally, the "end of the beginning" occurred in late 1989 with one of the great achievements of molecular genetics, the isolation and cloning of the CF gene (20). As a result, we now have a CF gene product, the cystic fibrosis transmembrane regulator (CFfR), possessing predicted amino acid sequence, suggested tertiary structure, and possible transmembrane transport function (21). These amazing developments have set the stage for the next round of advances, which surely will include: 1.

Our understanding of the humoral (B-cell) immune system has increased dramatically in recent years. IVIG Therapy Today highlights new third generation IgG products for intravenous use. Commercial gammaglobulin preparations first appeared in the early 1980s, and, since that time, therapeutic applications of intravenous immune serum globulin, or IVIG, have been developed at a rapid pace. Uses include replacement therapy in patients with antibody deficiencies and immunoregulatory/immunomodulatory agents in treatment of the autoimmune diseases. In two major parts, IVIG Therapy Today first presents reviews of primary and acquired humoral/B-cell immune deficiencies, featuring IVIG as replacement therapy, then explores the immunomodulatory effects of IVIG in autoimmune disorders.Chapters cover a wealth of timely background information and clinical applications, including: IVIG replacement therapy in primary immune deficiency syndrome * IVIG in prevention and treatment of neonatal bacterial infections * potential use of monoclonal antibodies in neonatal infections * immune deficiencies in chronic lymphocytic leukemia and multiple myeloma * IVIG in treatment of children with idiopathic thrombocytopenic purpura and autoimmune cytopenias * IVIG therapy in neonatal isoimmune thrombocytopenic purpura and alloimmunization thrombocytopenias * IVIG in Kawasaki disease and other autoimmune diseases * use of intravenous serum globulin in patients with antiphospholipid antibodies and recurrent pregnancy losses * IVIG in neurologic diseases * IVIG in asthma management. Dr. Ballow has assembled an outstanding collection of state-of-the-art information, making IVIG Therapy Today an essential guide for specialists in clinical and experimental immunotherapy.

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 usually 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.

Here is an up-to-date review of important new methods and results in anti-idiotypes, receptors, and molecular mimicry. It begins with a discussion of the theoretical background of the anti-idiotypic network, it's role in the regulation of immune response, and the physical characteristics of anti-idiotypic antibodies. It then goes on to explore many exciting applications in such areas as insulin action, thyroid cell function, the neurosciences, cardiology, virology, pharmacology, and reproduction.

We are celebrating this year the hundred years anniversary of allergen-specific immunotherapy. In 1911 Leonard Noon published his seminal work "Prophylactic inoculation against hay fever" describing his attempts to achieve active immunity against "grass pollen toxin" by administering increasing doses of grass pollen extract before the grass pollen season to allergic patients. Although it was unknown at that time that allergy represents an immunological hypersensitivity disease, the treatment was effective and many observations made by Noon remained valid until today. Today allergen-specific immunotherapy is well established as the only allergen-specific and disease-modifying treatment for IgE-mediated allergies and has long-lasting effects. In fact, more than 25% of the population suffer from IgE-mediated allergies which therefore represent a major health burden of our society, particularly because untreated allergy often progresses to severe disabling forms of disease, such as asthma and sometimes kills sensitized people through anaphylaxis.

ince the early 1980s, the HIV epidemic has been raging within the S 1 United States and around the world. Drug therapy for HIV infection has not been curative, prompting the search for alternative strategies to control HIV infection within infected persons. One potential alterna tive to drug therapy is a developing medical technology termed gene therapy. 2 Gene therapy involves introducing genetic elements into popu lations of cells in order to correct or prevent a pathologic process. A large number of gene therapy strategies have been developed in an at tempt to inhibit HIV expression and spread. These strategies fall into two general categories, genetic modification of cells in order to elicit an immune response against HIV and genetic modification of the target cells of HIV infection in order to block HIV expression and reproduction. In the first strategy, termed genetic immunotherapy by some, genetic material encoding HIV proteins is introduced into patient's cells in order to stimulate a cellular immune response above and beyond 3 5 that stimulated by the viral infection itself. - Two general genetic im munotherapy strategies have been developed. Genes encoding HIV pro teins have been directly injected into the dermis or muscle tissue of patients. These genes have been encoded in plasmids or viral DNA and have been injected either in the form of naked DNA or complexed with lipids."

Leading clinical experts survey the latest information available on the key rheumatic and allergic issues that physicians face in treating the HIV-infected patient. The physicians focus on the rheumatologic and dermatologic manifestations of HIV-1 infection, which include arthritis, myopathies, vasculitis, sicca syndrome, other autoimmune phenomena, and psoriasis. They also examine the question of allergic reactions in HIV patients, including drug hypersensitivity, with special attention given to adverse reactions to trimethoprim-sulfamethoxazole, the most frequently prescribed anti-infective. Practical advice for the diagnosis and treatment of these problems is given in full.

In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non invasive indicator. Significant progress has been made towards the characterization of the leukotriene receptor subtypes, exemplified by the cloning of the LTB4 receptor earlier this year. Coupled with this there has been a continued elucidation of signal transduction mechanisms underlying receptor activation. Consequent upon these advances has been the development of potent antagonists of the CysLT receptor, J and both these and inhibitors of leukotriene biosynthesis have entered clinical practice in the therapy of asthma. In this clinical setting antagonists of the CysLTJ receptor have been shown to be an effective therapy in chronic asthmatics, against antigen- and exercise-induced bronchoconstriction, and in aspirin-intolerant asthmatics. The advent of this new class of agents promises to change the way in which asthmatic patients are currently treated."

In recent years, epigenetic approaches to existing scientific problems have offered many new and exciting perspectives. This book focuses on epigenetic approaches to study asthma and allergy research. The authors briefly review cellular factors, immune signaling, and inflammatory pathways in allergy and asthma, as well as genetic influences in the pathogenesis of atopic disorders. Diseases that have been clearly linked to an epigenetic dysregulation will be discussed, as well as the role of epigenetics in the origin of complex diseases. The authors will examine the impact of environment factors in the predisposition to atopic disorders, and they will also describe the major unanswered questions and future perspectives of an exciting new field that studies allergic diseases from the epigenetic point of view.

Progress in Basic and Clinical Immunology is a result of the 14th European Immunology Meeting - EFIS 2000, held in Poznan, Poland, on 23-27 September 2000. EFIS 2000 gathered over 1400 immunologists from all over the world. It was an exceptionally memorable meeting for a number of reasons: 1) it was held in the last year of the century and the millennium, thus provoking conclusions of past achievements of immunology and projections for the future; 2) it was held in Poland, a country that is a symbol of struggle for freedom for a large number of scientists originating from the 'Eastern Bloc' countries; and 3) EFIS celebrated its 25th anniversary at this occasion. This comprehensive volume contains 62 chapters grouped into 11 sections: T-cells, Immune Receptors, Antigen Presentation/Dendritic Cells, Cytokines, Immunodeficiencies, Autoimmunity, Allergy/Inflammation, Immunotherapy, Vaccines, Tumor Immunology, and Cancer Immunotherapy.

During the last decade, rapid progress has been made in the area of microbial immu- nity. New conceptual frameworks have emerged with regard to the processing and presen- tation of peptides and nonpeptide antigens from microbes, especially bacteria, to T cells in the context of classical MHC class I and nonconventional MHC I molecules. Experimen- tal models have been instrumental in defining some of these pathways for generating pro- tective immune responses against microbes, which form the basis for the design of new vaccines. New evidence has stressed the importance of innate immunity in microbial in- fections. The concept of dichotomy within T helper cells has revealed the role of these cell types in resistance and susceptibility to microbial-mediated pathology. These latest devel- opments in microbial immunity are discussed in this volume. Natural killer cell development is known to be regulated by the presence of MHC class I antigens. Receptors for MHC class I molecules on NK cells have been discovered. Interaction of these receptors with their specific ligands leads to inhibition of cytotoxicity. Vinay Kumar and colleagues review NK cell differentiation and ontogeny, and functions of NK cells in experimental animals. Lewis Lanier discusses the role of a newly discov- ered molecule, DAP 12, in KIR and other receptor-mediated signal transduction in NK cells. Eric Long describes the regulation of immune response by inhibitory receptors.

Progress in basic and clinical immunology within the last two decades has provided profound insight into the immune system and its role in preventing endogenous and exogenous damage. In contrast, disbalances within this system can result in autoimmune disorders which may affect diverse organs and result in distinct clinical pictures. In many of these, however, the individual etiopathogenetic mechanisms are poorly understood and even more their clinical symptoms are hard to treat. The book offers insight into basic mechanisms of autoimmune disorders. It includes neurological, gastrointestinal, ophthalmological and skin diseases as well as current and future therapeutic options including immunomodulatory drugs and different vaccination strategies. By addressing diverse organ systems, both singular and shared features are elaborated. Thus an exchange of ideas is intended across research on single organ systems within a truly interdisciplinary setting.

Focusing on the rapidly increasing interaction between biotechnology and advanced fiberoptics/electronics, Biosensors with Fiberoptics emphasizes the three major phases of the developmental process from concept to marketplace: research, development, and applications. With contributions by leading experts directly involved in key areas of this exciting, fast-paced field, the book describes novel biosensor technologies and such current and potential applications as: chemical sensing * fluorescent labels * evanescent-wave biosensors and immunosensors * clinical applications * immunoassay kinetics * luminescence * monitoring of environmental toxins. Researchers and clinicians in a broad spectrum of disciplines will find Wise and Wingard's Biosensors with FIBEROPTICS an extremely practical, up-to-date reference text.

It has been said that the development of vaccines against a variety of infectious diseases is among the greatest triumphs of immunology. Indeed, several pathogens have lost their horror through the availability of effective vaccination measures. Unfortunately, this does not hold true for the pathogens dealt within this volume. Malaria, schistosomiasis, leishmaniasis, leprosy, and tuberculosis together are prevalent in more than 100 countries, and over 400 million persons suffer from these diseases. It is becoming increasingly clear that the failure to control these infections in a satisfactory way is directly related to the complexity oftheir interactions with the immune system. These agents have lived with their hosts for long enough to give both-host and parasite-ample opportunity to develop a highly sophisticated interrelationship. The central role of T lymphocytes both in acquired resistance to and pathogenesis of these microbes is well appreciated. In the beginning it may have been thought that acq uired resistance against infectious agents is nothing but another aspect of the immune response, studied with soluble and particulate antigens. This simple concept has gradually changed, and it has become clear that the viability not only of the immune cells but also of the 'antigens' adds another dimension to the game. Several achievements in cellular immunology and molecular biology have now made it possible to better understand at least some mechanisms in this intricate interplay.

Carbohydrate as the primary product of photosynthesis has a vital role in the maintenance of life on this planet. Until relatively recently, interest in complex carbohydrates focussed on their structural role in the extracellular matrix/ cell wall of animal, plant, and microbial cells and on their role as energy sources (e.g., starch and glycogen) and struc tural components (e.g., cellulose) in natural products. There was, however, indirect evidence that carbohydrates could play an informational role; this evidence was from the find ing last century that plant lectins caused specific agglutina tion of certain animal cells and, more recently, that the agglutination was mediated by interactions between the plant lectin and cell surface carbohydrates. It is now clear that endogenous carbohydrate binding proteins are important in cell-cell recognition phenomena in animal systems. Recently, impressive evidence has been presented that complex oligosaccharides, derived from cell walls, are also important in plant recognition events, for example in signalling the defence mechanisms of a plant to respond to attack by insects and microbial pathogens."

Phagocytic cells and complement are probably the most important components of host defense against bacteria which, after overcoming the mucosal and epithelial barriers, multiply in the subepithelial tissue and may threaten to disseminate and invade the blood stream and different organs. Questions concerning the factors which regulate the interactions of the bacterial cell with host defenses are a challenge to research and lead to practical applications for the prevention, treatment and diagnosis of infectious diseases. The questions of expression and regulation of virulence related bacterial genes and gene products, the specific mechanisms of defence reactions by complement and phagocytic cells, their mutual interactions with bacteria and especially bacterial surfaces are focused. Considerations on how to translate this knowledge into the management of infectious diseases are also included.

I have been a student of Sjogren's syndrome for virtually all of my professional life. My education in this disease began in 1962 when I arrived at the National Institutes of Health to begin a Clinical Asso- ciateship with Dr. Joseph J. Bunim. Bunim introduced me to a pat- ient with Sjogren's syndrome of 8 years duration who had devel- oped malignant lymphoma 6 months previously. He told me that there were other such patients. I obtained serum samples from these patients and studied them by the then new technique of immuno- electrophoresis. We observed that an initial hypergammaglobulin- emia could progressively decline to hypogammaglobulinemia with loss of autoantibodies. One patient in this initial series had macrog- lobulinemia. We published this report and suggested that the auto- immunity predisposed to the malignant transformation. Thus began my love affair with this disease. In those days many rheumatologists considered Sjogren's syn- drome simply a variant of rheumatoid arthritis. It's curious that two decades ago there was little confusion between Sjogren's syndrome and systemic lupus erythematosus, whereas today there is great con- fusion. There is still a great need for internationally agreed upon di- agnostic criteria, which merely illustrates once again the difficulty of accurate diagnosis in our profession. The multidisciplinary aspects of Sjogren's syndrome require au- thorities in several areas of medicine. The various chapter contribu- tors are experts in their field and have often put aside other respon- sibilities to complete their contributions and not delay publication.

This volume of Current Topics in Microbiology and Immunology is concerned with a class of molecules that are the most potent polyclonal stimulators of T lymphocytes of several species. These molecules have been named "superantigens" because they use a mechanism of T cell stimulation closely mimicking MHC-restricted recognition of specific antigen: they act on variable parts of T cell antigen receptors and are presented by MHC class II molecules. Prototypes of these molecules are the pyrogenic exotoxins produced by S. aureus and S. pyogenes, of which the staphylococcal enterotoxins and the toxic shock syndrome toxin are the best known. Superantigens also occur endogen ously in mice, most notably the enigmatic Mis determinants, that have withstood characterization for nearly 20 years. Only very recently was it found that Mis is probably encoded by endogenous retroviruses. The list of candidates that are implicated as being superantigens is growing. In many cases, however, the proof that a given molecule indeed falls into this category is still missing.

It has long been known that every individual has a large number of antibodies of different specificities. Antibodies are gammaglobulins, and protein structure in cells is genetically determined. The extreme multiplicity of structure of the combining sites of antibodies relative to the degree of multiplicity generated by ordinary genetic mechanisms is a fascinating problem of bio-medical importance. The functional heterogeneity of reactions mediated by immunoglobulins-is remarkable, ranging from protection against life-threatening toxins and microbes to the production of laryngeal edema leading to suffocation and death from anaphylaxis. An approach to the understanding of immunoglobulin polymorphism based upon "a knowledge of genetic markers of immunoglobulin structure is not biased by the question of whether or not this polymorphism is related to combining site diversity. Though several recent reviews of the multifacetted problems related to immuno globulins are available, it was decided to publish this survey in the belief that know ledge of the genetic markers of immunoglobulins prqvides such information about immunoglobulin differentiation and its control as cannot be obtained from other sources. Several of the human genetic im unoglobulin markers are well understood at the molecular level. The Gm system may serv as a model for other immuno genetic systems. The published data on the human immunoglobulin factors are widely scattered in journals of different perspectives. There is a need for a systematic presentation of these data and for their critical evaluation."

Why another series on infectious disease? The question is a fair one in view of the proliferation of monographs, texts, and periodicals on the vast subject of infectious disease. The goal of this series is to provide an additional service to the clinician in the form of clinical information not usually assembled in one convenient volume. One type of monograph presented in this series will cover a specific infection, detailing microbiologic, research and clinical aspects. It is hoped that such a compilation will be helpful in both its thoroughness and breadth to the clinician interested in this particular problem. The other type of monograph that this series will provide will discuss a clinical presentation that comprises many possible specific etiologies. Volumes in the series will be multiauthored, giving us the opportunity to invite authorities in each specific area to contribute their expertise and experience. Regular revisions are planned so that each volume will remain as current as it is thorough. We hope that our goals are met and that the present series of mono graphs establishes its own identifiable and valuable niche in the growing compendium of resource material available to the clinician. Preface to the Second Edition Since the first edition of Infectious Mononucleosis was published, we have seen exciting advances in our understanding of this disease."

Readers will be aware that asthma is one of the commonest chronic diseases of industrialised societies, with an increase in morbidity and mortality, despite the availability of a range of different drugs. In an effort to improve the treatment of asthmatic patients, international guidelines have recently recognised asthma as an inflammatory disease, and there has been a change in emphasis from bronchodilator drugs towards earlier use of anti-inflammatory treatments. This volume brings together the latest developments in our understanding of the mechanisms of asthma, considers the safety ofbeta-adrenoceptor agonists, and explores latest developments in the use of phosphodiesterase (PDE) inhibitors in asthma therapy. The second international conference on "New Drugs in Allergy and Asthma" was held in Davos on 8-10 July 1992. There were six sessions with specialist chairmen: PDE isoenzymes (c. D. Nicholson), atopy and the environment (8. Villiger), adhesion molecules (R. H. Gundel), cytokines (M. Baggiolini), airway hyperreactivity (S. Makino) and neurotransmitters (J. G. Widdicombe). The success of the meeting was ensured by a high standard of presentation, with extensive reference to recent experimental data. The chairmen were instrumental in fostering stimulating discussion periods, that considerably enlivened the meeting. Particular thanks are due to the Swiss Institute for Asthma and Allergy Research (SIAF) and also to the e1inicians of Davos for their assistance and hospitality. In addition, a number of pharmaceutical companies were kind enough to support this meeting that was devoted to academic aspects of drug discovery. John Morley FRCPath.

The international symposium "New Trends in Allergy," held in Munich from July 13 to 15, 1990, brought together for the third time since 1980 some of the most experienced researchers working in the field of allergy. This volume comprises the papers presented at this meeting. All over the world, and not merely in the industrialized countries, allergy is becoming a cause of evermore serious diseases. In recent years, research in the field of allergy has provided numerous impor tant and fascinating results extending our knowledge considerably. Despite the new insights into basic mechanisms of allergic reactions, improved diagnostic methods, and new therapeutic approaches, how ever, many questions remain to be answered, including: Are allergies really increasing in frequency? If so, what are the reasons? Especially, does environmental pollution playa role? Which factors influence IgE synthesis? Can the IgE immune response be switched off? Does the nervous system interact with allergic reactions? If so, what are the mechanisms? Are new approaches in allergy prophylaxis and allergy therapy effi cient? What measures have proven useful and deserve to be employed in daily practice? In this volume, these questions and other current topics are dealt with. As each issue is covered by authors competent in the respective fields, the result is an extensive and critical review of the state of the art. Going through these papers, one comes to the conviction that allergy research is a multifacetted, explosively expanding, most stimulating field of work."