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This book integrates topics in basic research and clinical medicine as well as molecular and cell biology.It presents innovative advances in the field of immunodeficiency syndromes and viral/bacterial respiratory infections, including a novel hyperbaric oxygen treatment for COVID-19. A comprehensive insight is offered into the unresolved molecular pathways in chemosensing that plays a vital role in detecting insufficient tissue oxygenation, as well as in sporting accomplishments. Other articles address cardiorespiratory and humoral responses to hypoxia, the function of cementum in the repair and regeneration of teeth, and periprosthetic fractures following hip arthroplasty in the elderly. The issue of the overwhelming burdens on caregivers to spinal injury patients, damaging both health and psychosocial status, is addressed.The book promotes translation of scientific advances to the general medical practice. It will be a valuable reference for clinical healthcare professionals and researchers interested in innovative practices to improve the prevention, diagnosis, and management of diseases.

Helminth infections are common, cause considerable pathology, and alter a host's immune profile. This can have important consequences not only on the host's ability to control a helminth infection, but also on their ability to control unrelated infections. In endemic areas, understanding how helminth infection influences the outcome of common infectious diseases and changes the efficacy of childhood vaccination programs is an important public health question.This book reviews how host immunity to helminths alters our ability to respond to the major pathogens that exist in helminth endemic regions. Current understanding of how helminths alter important but relatively neglected contributors to the host's anti-helminth immune responses are addressed, namely host antibody responses and how maternal infection may alter a child's immune development. These are discussed in relation to the control of helminth infection and unrelated infections. Also covered are how helminth infections alter the host's ability to control TB, HIV and malarial infections along with neglected bacterial infections, such as cholera, and how endemic helminth infections are likely to alter our ability to respond to life-saving vaccination strategies.

This book provides a comprehensive update on the state of the art in cancer immunology, which has rapidly evolved from a field of clinical research into an established discipline of oncology. The key recent developments in immuno-oncology are all covered, from the ever-changing immunological and regulatory frameworks to the most promising therapeutic concepts. Themes include combination therapies and personalized medicine, as well as identification of biomarkers to guide the clinical development of new approaches and to pinpoint the optimal treatment for each patient. The book acknowledges the continuing dynamic nature of the field as reflected in the development of next-generation immunotherapies that are already in clinical testing.Cancer Immunotherapy Meets Oncology is dedicated to the lifetime achievements of Christoph Huber, founder and chair of the Association for Cancer Immunotherapy (CIMT). It is also a tribute to those researchers and clinicians who are striving to develop novel diagnostics and tailored immunotherapies for the benefit of cancer patients.

Cancer research has progressed enormously in recent years. This review volume will address recent findings in the area of T-cell therapy for cancer, including use of tumour infiltrating lymphocytes (TILs) as a therapy for melanoma, choice of target antigens, advances in engineered receptors, methods of gene transfer to T cells, review of cell processing methods and clinical trial design. Written by leadings scientists in the field, this up-to-date review on cancer research will be an important reference source to the researchers and healthcare professionals in the field.

The Ninth Annual Pezcoller Symposium entitled'The Biology of Tumors'was held in Rovereto, Italy, June 4-7, 1997. It focused on the genetic mechanisms underlying het­ erogeneity of tumor cell populations and tumor cell differentiation, on interactions be­ tween tumor cells and cells of host defenses, and the mechanisms of angiogenesis. With presentations at the cutting edge of progress and stimulating discussions, this symposium addressed issues related to phenomena concerned with cell regulation and cell interactions as determined by activated genes through the appropriate and timely media­ tion of gene products. Important methodologies that would allow scientists to measure dif­ ferentially genes and gene products and thus validate many of the mechanisms of control currently proposed were considered, as were the molecular basis of tumor recognition by the immune system, interactions between cells and molecular mechanisms of cell regula­ tion as they are affected by or implemented through these interactions. The molecular and cellular mechanisms of tumor vascularization were also discussed. It was recognized that angiogenesis provides a potential site of therapeutic intervention and this makes it even more important to understand the mechanisms underlying it. We wish to thank the participants in the symposium for their substantial contribu­ tions and their participation in the spirited discussions that followed. We would also like to thank Drs.

The 2002 Nobel Prize in Physiology or Medicine was awarded to Sydney Brenner, H. Robert Horvitz, and John E. Sulston for their seminal discoveries concerning'genetic regulation of organ development and programmed cell death.'This clearly marked the prime importance of understanding the molecular mechanisms controlling cell death. The 1 st International Symposium on Programmed Cell Death was held in the Shanghai Science Center of the Chinese Academy of Sciences on September 8-12, 1996. A number of key issues in apoptosis were discussed at the meeting, and progress in major areas of apopto­ sis research was summarized by expert participants at the meeting and published by Plenum Publishing Corporation as a book entitled Programmed Cell Death. In the last six years, we have witnessed a real explosion in our knowledge on how cells undergo apoptosis, thereby participating in various developmental and pathophysiological processes. At this ever­ exciting time, we organized the 2nd International Symposium on Programmed Cell Death.

Provided here is a comprehensive examination of the basic and clinical condition of three innovative and promising approaches to cancer therapy, which may support or even substitute chemotherapy: differentiation, immunomodulation, and inhibition of angiogenesis. Differentiation shouldnormalize neoplastic cells and make them compatible with the host. Its feasibility with retinoids, interferons, chemotherapeutic and other agents is discussed. Modulation by biological agents, cytotoxic effector cells and drugs is considered in attempts to boost endogenous antitumour defenses and/or to render neoplastic cells more susceptible to the immune attack of the host. Finally, the important aspect of interfering with tumour blood vessel development and function is taken into account. Consideringthe importance that chemotherapy has in cancer treatment and in view of a more and more integrated strategy, the relationship between the aforementioned approaches and chemotherapeutic agents and chemoresistance is treated in detail.

Proceedings of a NATO ASI held in Cape Sounion, Greece, June 24-July 5, 1996

Gene therapy was conceived during the early and mid part of the 20th century. At first, it was considered a revolutionary biomedical procedure, which could potentially cure any disease for which the molecular bases were understood. Since then, gene therapy has gone through many stages and has evolved from a nearly unrealistic perspective to a real life application. Clinical efficacy in humans was demonstrated at the beginning of this century after its successful application in small-scale clinical trials to cure severe immunodeficiency in children. However, their successes were overshadowed some time later by the occurrence of vector-related leukaemia in a number of treated children. It is in this context that lentiviral vectors have appeared, with improved efficiency and, possibly, increased biosafety. Very recently, the first clinical trials with lentivectors have been carried out with some success. This Brief firstly defines gene therapy, and places lentivectors within this fascinating therapeutic strategy. Then follows a comprehensive description of the development of retroviral and lentiviral vectors and how to specifically target distinct cell types and tissues. The authors also discuss the application of lentivector gene therapy for the treatment of cancer and autoimmune diseases, ending with the application of lentivectors in human gene therapy clinical trials.

This is the sixth symposium in a series of symposia on immunology organized by IMMUNO covering this time tumor immunology. This volume deals with T cell recognition and CD95-associating signaling, clinical investigations: cells, costimulatory signals and therapeutic approaches: cytokines and vaccines.

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.

In metastasis, tumor cells disseminate from the primary lesion and home to secondary organs where they may remain dormant for a long time. Metastasis formation is still the most feared manifestation for tumor patients and clinicians. Although improvements have been made concerning earlier detection and specific therapy, most of the cancer patients still die of distant metastases. The purpose of these three volumes is to review the recent progress in molecular metas­ tasis research and to attempt to further understand the biol­ ogy of this multifocal process. With respect to present day molecular biology, the pioneers of metastasis research established the basic concepts of metasta­ sis formation in the 1970s and 1980s, namely, clonal selection of metastatic cells, heterogeneity of metastatic subpopulations, organ specificity of metastasis and the importance of angio­ genesis (Fidler, Kripke, Nicolson, Folkman and others). In the 1980s and 1990s, several of the molecules involved were identified and their network interactions elucidated. These three volumes of Current Topics in Microbiology and Immuno­ logy compile the most recent developments on these meta­ stasis-related molecules; their interactions, regulation, and ways to interfere with their action. It became evident that metastasis-related molecules are confined to distinct cellular compartments, such as the extracellular space, the cell membrane, the cytoplasmic signalling network, and the nuclear regulatory system. For the complex metastatic cascade, proteolysis and alterations in adhesive functions are the most obvious and thus one of the most thoroughly investigated processes.

The clinical and experimental effects of cytokines have been realized for a long time. The clinical effects of tumor necrosis factor were noted almost 100 years ago. The basic biological effects of interferons and the hemopoietic growth factors have been known for more than 20 years. Given the basis of modern molecular biotechniques, information concern­ ing the mediators of cellular interactions is expanding almost exponentially. New principles in the regulation of cell growth, microenvironment, immune response, and malignancy are being discoverd right now. New therapeutic options are becoming available and have, in some areas, already crossed the threshold of clinical application. However, the way forward might be more complicated than we are in a position to recognize today. Some of the first optimistic expectations have not yet been fulfilled. Nevertheless, we are experiencing a revolution in medicine. To contribute to this process and to stimulate scientific communi­ in this field, we have initiated the international symposia on cytokines cation in hemopoiesis, oncology and aids. Major contributions from the first sym­ posium are published in this book. We thank all the authors for their contri­ butions, particularly those from the Hannover Medical School, who have worked hard to realize the congress and prepare these proceedings. We also thank the pharmaceutical companies whose support made this book possible. Finally we thank Professors Deicher, Poliwoda, and Riehm, heads of the Departments of Hematology and Oncology, Immunology, and Pediatric Hematology and Oncology, respectively, who encouraged us and gave us their firm support.

Recombinant human interleukin-2 became available for clinical use in the mid 1980s. Recent years have seen an enormous amount of clinical research with this cytokine and interleukin-2 has now been registered for use in a number of European countries for the treatment of metastatic renal cell carcinoma. This book is designed to provide the clinical oncologist wishing to use interleukin-2 with a basic background concerning the biology of the agent, a discussion concerning practical aspects, of its clinical use including management of toxicity and an overview of the clinical results together with a description of how this internesting cytokine might be developed in the future.

In the 1960s, it was reported that interferons have antitumour activity in different experimental models. Since that time, numerous studies have been performed to elucidate the various mechanisms of action that have been proposed. However, there is much controversy in the literature and promising preclinical findings failed to translate into substantial clinical progress. The present book gives a critical overview of current knowledge of how interferons act in solid tumours. For this purpose, after two chapters of general aspects of interferon action and interaction, selected solid tumours which are commonly considered difficult to treat in advanced stages are discussed with respect to both preclinical data and clinical experience.

Recent experimental and clinical progress in the evaluation of cytokines in treatment concepts for cancer patients is the central theme of this book in the ESO Monographs series. The discussion revolves on the experimental basis as well as current clinical experience with the use of human recombinant cytokines. It gives the state of the art and, as such, puts into perspective potential areas of growth and future research.

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc­ tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process.

The development of new techniques such as immuno­ phenotyping, cytogenetic investigations and, more recently, molecular studies has considerably increased our diagnostic repertoire and broadened our ideas about the biology of acute leukemias. While immunophenotyping with mono­ clonal antibodies has yielded increased diagnostic precision and made it possible to develop a highly reproducible classification of acute leukemias based on cell-biological features, further insights have been gained into the patho­ genetic mechanisms involved in leukemogenesis by means of cytogenetic detection of acquired structural chromosomal abnormalities. Analysis of the leukemia-associated chromo­ somal breakpoints using molecular techniques can now pinpoint many genomic sites essential for normal develop­ ment and maturation of hematopoietic cells but functionally disrupted in leukemic cells. The main goal of the international workshop that we held in Berlin with a select group of scientists and clinicians involved in leukemia research was to describe the state of the art and new developments in the immunologic, cytogenetic, and molecular characterization of acute leukemias and to discuss the clinical importance of cell­ biological features. After introductory survey lectures dealing with the immunological and molecular-biological characteristics of normal vs. malignant lymphatic and myeloid progenitor cells, the workshop centered on con­ tributions characterizing the immunophenotype and both numerical and structural chromosomal abnormalities in acute leukemias.

Our motivation for putting together this book was the need for a single source reference that could be used as an introduction to cell-mediated cytotoxicity for newcomers to this field, such as students and fellows beginning work in our laboratories. At present no such book is available, and we felt that it would be useful as a teaching tool and as a way of conveying our enthusiasm about recent progress in the cytotoxicity field to our colleagues in allied areas. It was with some hesitation that we approached our colleagues with the proposal for this book, and we were pleased to find them very supportive of the idea and willing to participate. We thought it important to broaden the scope of the book to include historical, molecular, cell biological, and clinical aspects of cell-mediated cytotoxicity. To our knowledge this is the first book on cell-mediated cytotoxicity with such a broad scope. Historically, studies on cellular cytotoxicity were part of cellular immunology from its origin. One development of tremendous import was the advent of the 51 Cr assay, which allowed this arm of the immune response to be measured easily and quantitatively. Thus, a readout of this effector pathway is available within a few hours; other immune effector functions can take days or even longer to assay, and the assays are often less quantitative.

The interplay between tumors and their immunologic microenvironment is complex, difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. The present review discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment.

This updated volume provides a “user-friendly” reference for dermatologists, dermatology residents and students, as well as for health care workers in related fields to better understand immune-mediated skin diseases and their therapies.The focus is on what is needed by the physician/resident or student for betting understanding the pathophysiology of the disease as well as the mechanisms of action of the therapies. The reader can easily read about groups of related diseases as well as groups of related therapies.The level of complexity of the book is such that it has practical applications on a daily basis but can also be used by the resident as a teaching tool and as a handy source of review for the boards. In addition, it can be used the practicing dermatologist to study for recertification.The scope of the book is immunology, immunogenetics, immunopathology and immunopharmacology as they relate to clinical dermatology.

Advances in Immunology presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for future research.

One of the first comprehensive references dealing specifically with this new field of interdisciplinary research in medicine, Immunoendocrinology in Health and Disease offers a full scientific picture of where the immune and neuroendocrine systems intersect-placing current understanding of system components, mechanisms, and functions side by side w

As a phylogenetically old system complement is now regarded as a part of innate immunity. But it is much more than that. It bridges innate and adapted immunity, participates not only in host defense but also in many essential physiological processes, old and new diseases and adverse conditions. Indeed, complement became a term that almost defies categorization. What was for a long time a subject for a limited number of specialists has now moved into the mainstream of experimental and clinical immunology. In 1973 I visited the Basel Institute of Immunology and met its director, the eminent scientist and Nobel laureate Nils Jerne. When I entered his office he greeted me with the following words: “Complement, does that really exist?” I was never certain whether he wanted only to tease me or whether he sincerely believed that the complement system was an unimportant biological curiosity, a misstep of evolution. But, of course, missteps do not survive the evolutionary process. Little did I foresee the dramatic developments of recent years when Hans J. Müller-Eberhard and I started to unravel the specifics of the action of the cobra venom factor on the complement system in 1968 and defined a new pathway to its activation. An elucidation of the role of the system in diseases and its control for therapeutic reasons is now getting closer to actual realization in the clinic although many problems, in particular those of highly specificinhibition free of side effects, have still to be resolved.

The history of science has shown the majority of hypotheses to be wrong. Sharp scientific criticism and strictly controlled experimental studies reject most of the hypotheses, leaving behind only a small number of assumptions and ideas. Nevertheless, each logical assumption should have its rightful place on the scientific “battlefield” supposed to assess its validity and determine its final fate. Even when a hypothesis is wrong, it still finds its place in the entire efforts of the humankind towards attaining the scientific truth. Namely, the wrong hypotheses serve largely to illuminate the way towards the correct ones or, at least, to show which way not to follow. Correct or not, ideas and hypotheses are necessary for the progress of science. They epitomize the efforts of human thought to elucidate nature without experimental verification and in the circumstances of scant data availability. Finally, hypotheses and ideas represent a symbiotic creation of our knowledge and imagination, the two most impressive appearances in the evolution of humans.

The fourth edition of The Cytokine Handbook provides an encyclopedic coverage of the molecules that induce and regulate immune responses. Now expanded to two volumes, co-edited by Michael T Lotze, and written by over 120 international experts, the scope of the book has been broadened to include a major emphasis on the clinical applications of cytokines. The early chapters discuss individual cytokines, chemokines and receptors. Additional chapters discuss the clinical implications and applications of cytokines, including cytokine gene transfer, antisense therapy and assay systems. This book is essential for researchers and clinicians interested in cytokines, including anyone working in cancer biology, transplantation, infectious diseases, autoimmunity or bioinformatics.Key Features• Covers all main cytokines and chemokines • Written by experts• Up-to-date- includes detailed referencing accessing current, modern literature and reflects the newest findings from the human genome • The new edition has been thoroughly revised and extended (now 2 volumes) as compared to the last edition, including new co-editor (MTL), new authors, new hot topics and new chapters• Includes major emphasis on clinical applications• Extensively illustrated with tables and figures

Recent advances in immunology and molecular biology have resulted in new therapeutic approaches being generated and implemented in cancer clinics. The discovery of new antigens, mechanisms of antigen presentation, and interplay of cells involved in anti-tumor immunity have made the clinical control of some cancers more plausible than previously tho

Advances in Immunology presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for future research.

Volume 70 begins with two'Foundations in Cancer Research'articles, a staple of the Advances in Cancer Research series. The first article by Michael Stoker presents a review of some of the early advances made by cancer cell biology researchers. The second article by Emmanuel Farber describes the methods by which researchers delineate the phenotype of cells and ways to alter these phenotypes to prevent or delay carcinomas. Chidambaram and Dean illustrate the tumors and associated malformations of nevoid basal cell carcinoma. Koli and Keski-Oja review the effects of how transforming growth factor-b regulates cell proliferation, differentiation, and morphogenesis and its regulation by the steroid hormone superfamily. Jean-Marc Lemaitre and colleagues discuss the involvement of protooncogenes in the control of the cell cycle and embryonic development with specific attention paid to c-Myc expression and c-Myc function. A review of the various studies involving tumor-infiltrating lymphocytes and their possible role in cancer prevention is presented by Steven Rosenberg and co-workers. Finally, Bruce Ponder and Darrin Smith review the genetic and biological aspects of multiple endocrine neoplasia type-2 syndromes and the phenotypes associated with ret mutations.

From the Reviews of Previous Volumes'Provides unrivalled value in both academic and fiscal terms and should be purchased by hard pressed librarians as a major priority to be jealously defended.'-JOURNAL OF MEDICAL MICROBIOLOGY'Advances in Immunology must find itself among the most active volumes in the libraries of our universities and institutions.'-SCIENCE'A provocative and scholarly review of research.'-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION'Deserves a permanent place in biomedical libraries as an aid in research and in teaching.'-JOURNAL OF IMMUNOLOGIC METHODS

Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular bases of drug action, both applied and experimental. Volume 40, GeneTherapy, features important new research on gene transfers and therapy in the herpes simplex virus, anti-tumor immunity, steroid receptors, cystic fibroses, and more.Key Features• It provides an excellent overview on a series of topics on gene therapy for the serious investigator

Advances in Immunology presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for future research.

This book provides comprehensive coverage of the cytokines from a pharmacological approach. The chapters are presented in a consistent format allowing easy cross-reference, with sample diagrams and a summary table of essential facts for each chapter at the end of the book.Cytokines is unique in stressing cytokine biology and the application of research data to provide disease therapy. With 33 detailed and up-to-date chapters about individual cytokines, this comprehensive reference will provide both clinicians and researchers in immunology and pharmacology with invaluable information. - Genetic information and sequences - Protein structure - Cell sources and production - Biological activity - Cytokine receptor structure and signal transduction - Discussion of the role of cytokines in disease and the potential for therapy - Summary table of essential facts - Comprehensive bibliography