This book details the anatomy and physiology of the lymphovascular system as well as describes the mechanisms of metastasis. It provides readers with an understanding of immune responses of draining lymph nodes against cancer. Coverage also explains the rationale of adopting molecular therapeutics against growth factor receptors, apoptotic factors, signaling pathways and angiogenesis.

This book provides a state-of-the-art approach to the molecular basis of hematologic diseases and its translation into improved diagnostics and novel therapeutic strategies. Several representative hemato-oncologic malignancies are analyzed in detail: acute lymphoblastic leukemia, acute myeloid leukemia, B-cell Non-Hodgkin lymphomas, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. Experts in the field describe the molecular methods applied for modern diagnostics and therapies, such as hematopoietic stem cell transplantation, donor recipient matching, banking of biological material, analyses of post-transplant chimerism, and minimal residual disease monitoring. The volume concludes with an extensive section comprising thorough step-by-step protocols of molecular techniques in hematology, all of them validated in the authors' own laboratories.

JAK tyrosine kinases and STAT transcription factors constitute a signaling pathway, which is activated by cytokines. By activating gene transcription it regulates essential biological responses to environmental cues. The Jak-Stat pathway is involved in the regulation of cell development, differentiation, proliferation and apoptosis. Improper function may contribute to hematopoietic malignancies and cancer. This book provides comprehensive insights into the latest basic and clinical developments in the field. The first part reviews recent findings and new technologies pertaining to basics of Jak-Stat function. The second part describes the evolution of Jak-Stat signaling and the role of the pathway in invertebrate organisms. The third part focuses on Jak-Stat signaling in hematopoietic cells under both physiological and pathophysiological conditions. Finally, chapters in the fourth section describe the relationship of Jak-Stat signaling to various states of disease, particularly infection, leukemias and solid cancers. The book is intended for all scientists in molecular biology, biochemistry and cell biology dealing with biomedical issues.

Heparins remain amongst the most commonly used drugs in clinical practice. Almost 100 years have passed since the initial discovery of this complex substance and, during this time, understanding of the nature and uses of heparin and related molecules has grown dramatically. The aim of this volume is to summarise the developments that have led to the current status of both heparins as drugs and the field of heparin research, with a focus on the particularly rapid progress that has been made over the past three decades. Individual sections are dedicated to the nature of heparin as a biological molecule, the current approaches and techniques that are used to ensure the safety and reliability of heparin as a medicine, the clinical pharmacology of heparin as an anticoagulant drug, effects and potential applications of heparin aside of those involving haemostasis and, finally, the nature and potential uses of heparin-like materials from both natural and synthetic sources.

This is an essential guide to the data, basic science, outcome studies and decision-making processes involved in blood and marrow stem cell transplantation. Organized according to disease types and procedures, it contains more than 100 tables, figures and algorithms that reflect up-to-date research and give guidance on the choices between different types of chemotherapy, autologous vs. allogeneic transplantation, peripheral blood vs. bone marrow stem cells, and standard vs. experimental treatments. This new edition summarizes the research of the last four years and gives mature data for all established indications, such as acute myeloid leukemia, myelodysplastic syndrome and Hodgkin and non-Hodgkin lymphomas. New chapters discuss global trends in stem cell transplantation, cellular therapies including donor lymphocytes, and pediatric neurologic and metabolic disorders. With an expanded complications section, links to electronic databases and discussion of new drugs and alternative stem cell sources, this text belongs in every transplant unit.

Phase I trials are a critical first step in the study of novel cancer therapeutic approaches. Their primary goals are to identify the recommended dose, schedule and pharmacologic behavior of new agents or new combinations of agents and to describe the adverse effects of treatment. In cancer therapeutics, such studies have particular challenges. Due to the nature of the effects of treatment, most such studies are conducted in patients with advanced malignancy, rather than in healthy volunteers. Further, the endpoints of these trials are usually measures adverse effects rather than molecular target or anti-tumor effects. These factors render the design, conduct, analysis and ethical aspects of phase I cancer trials unique. As the only comprehensive book on this topic, Phase I Cancer Clinical Trials is a useful resource for oncology trainees or specialists interested in understanding cancer drug development. New to this edition are chapters on Phase 0 Trials and Immunotherapeutics, and updated information on the process, pitfalls, and logistics of Phase I Trials

From the world renowned Fred Hutchinson Cancer Research Center, this book is written for all physicians who treat patients with acute or chronic leukemias or myelodysplasia. It is designed to answer questions about treatment approaches that commonly arise in day-to-day practice. In keeping with the Center's groundbreaking research in bone marrow transplantation, the book provides exceptional coverage of the role of allogeneic transplant in treatment. It also addresses the important issues of supportive care and long-term complications of successful treatment. *Edited and written by experts at the Fred Hutchinson Cancer Research Center *Clinically focused and comprehensive coverage of treatment approaches *Allogeneic transplant addressed in detail *Separate chapters on supportive care and long-term complications

Atlas of Hematopathology: Morphology, Immunophenotype, Cytogenetics, and Molecular Approaches, Second Edition, will appeal to both a wide range of people undergoing training in a variety of medical fields and practicing non-hematopathologists. For clinicians, fellows and residents, correct diagnosis (and therefore correct treatment) of diseases depends on a strong understanding of the molecular basis for the disease, making this book a crucial resource. This atlas contains hundreds of high-quality color images that mirror the findings that fellows and clinicians encounter in practice. In addition, it provides information in a quick, simple and user-friendly manner, attracting both those in training and non- experts. Residents, fellows, practicing clinicians, and researchers in pathology, hematology and hematology/oncology will find this a useful resource.

Pocket Reference to Renal Anemia, Second edition, provides a comprehensive overview of anemia in patients with renal disease, including the definition and causes of renal anemia, current management approaches, and the latest clinical practice guidelines. Key learning points are highlighted throughout the book and also listed at the end of the book for a quick reference. The book is useful for general physicians, fellows, and other healthcare professionals wishing to learn more about renal anemia.

We are pleased to present our readers the proceedings of the International symposium on "New Aspects of Human Polymorpho- nuclear Leukocytes" which was held in Freiburg im Breisgau, FRG, from October 26-28th, 1989. The meeting provided an unique framework for close interaction between scientists from various disciplines, including bioche- mistry, biology, physiology, pathology, clinical chemistry, hematology, gynecology, surgery, intensive care medicine, nephrology, rheumatology, and infectious diseases. We would like to express our gratitude and appreciation for all those who have stimulated, encouraged, and supported us to hold the symposium in Freiburg. This endeavor could not have been possible without the generous financial support of Asid- Bonz (Boblingen), Bayer AG (Leverkusen), Bayropharm GmbH (Koln), Baxter (Munchen), Ciba-Geigy (Wehr/Baden), Cilag GmbH (Sulzbach), Fresenius AG (Oberursel), Gambro (Martinsried), Gry-Pharma GmbH (Kirchzarten), Hoechst AG (Frankfurt), Hospal (Nurnberg), Knoll AG (Ludwigshafen), Lederle-Cyanamid (Wolfratshausen) , E. Merck (Darmstadt), MSD Sharp and Dohme GmbH (Munchen), Pfizer GmbH (Karlsruhe), and Kabi/Pfrimmer (Erlangen). We are indebted to Mrs. I. Szkibik for her invaluable ass i- stance both with the organization of the meeting and the pre- paration of the manuscripts.

The extravasation of cytotoxic agents can result in severe local tissue damage and medical emergencies during tumour therapy. This revised compendium is intended to help clinicians assess any situation speedily and with certainty. The general section of the book includes topics such as predisposition, prevention, type of harm, general measures in handling extravasated drugs, specific antidotes, and documentation. In the 2nd edition, the scientific information contained in the general section and relating to the actual substances has been updated. The substance specific part of the book includes detailed instructions on handling more than 50 cytotoxic drugs, to initiate targeted measures. Templates for an extravasation set, overview tables, documentation sheets, and patient information, as we as a CD-ROM are included to support clinical practice. The book is the outcome of a consensus of an interdisciplinary working group that has collected and systematically reviewed all published literature on the topic.

Principles and Practice of Cancer Infectious Diseases is a comprehensive and insightful work dedicated to elucidating the problem of infections in cancer patients. This essential volume reviews common and less often encountered infections, while establishing the difficulties behind preventing, diagnosing, and treating infectious diseases in cancer patients. Key sections are devoted to the presentation of clinical symptoms and the identification of major etiologic agents. A cadre of leading clinicians provide a detailed assessment of the risk factors for various infections, critical strategies in preventing and managing infections, and study of the interactions between the pathogen and host's immune function and inflammatory response. With its in-depth knowledge and concise treatment of the distinct facets of infections in cancer patients, this volume is an indispensible tool for all infectious disease specialists and clinical oncologists.

Myelodysplastic syndromes (MDS) are the most common hematological malignancies involving mostly the elderly population. The major morbidity relates to patients' symptomatic cytopenias.MDS was previously named as "preleukemia " or " smoldering leukemia" as the lack of terminal cells in MDS and because about 25% of all cases progresses into acute myeloid leukemia. According to various reports the annual incidence of MDS ranges widely from 2-12 per 100.000, increasing to 30-50 cases per 100.000 among persons aged 70 or older. It is believed that the true incidence of MDS have been underestimated however it seems to be comparable to that for multiple myeloma and chronic lymphocytic leukemia. In the past decade much progress had been made; we know more on the disease pathology, there is more emphasis on the care and more targeted therapy had been invested. Athors provide updated knowledge in this book on all clinically important aspects of the disease. Hot topics of our days are discussed in chapters by outstanding and well known scientists from all over the world. We would offer this product both for medical students and postgraduates as well as for all who are interested in this very exciting and fast progressing field of hematology. With this work authors should call attention on the disease for decision makers in healt care systems as well.

The Fondazione Lorenzini has been sponsoring Postgraduate Courses for physicians and specialists, in Italy, since 1970. Its aim, as an institution, has been that of promoting post graduate medical education. In these years, recent advances in a wide range of medical fields have been discussed by distinguished experts from many countries throughout the world. Courses dealing with methodo logies and technical problems have been designed to include practical demonstrations of the various methods and techniques in the relevant fields. The Postgraduate Course on "Platelets and Thrombosis: Methods of Study" was held in Milan, at the Fondazione Lorenzini, from February 24th to 26th, 1972. This volume contains the edited and somewhat extended papers presented at the Course, which was sponsored and organized by the Italian Society for the Study of Atherosclerosis. The special contribution of the present volume is that of gathering a large amount of up-to-date information on the formidable problem of the methods used for testing platelet function in thrombosis.

WEGENER'S GRANULOMATOSIS & ANCA-ASSOCIATED DISEASES: THE STORY CONTINUES The disease now designated as Wegener's granulomatosis (WG) was first described in 1931 by Heinz Klinger, who considered it to be a special form of polyarteritis nodosa. Klinger's friend, Friedrich Wegener, expanded on the first observations and interpreted the pathological and clinical fmdings to represent a distinct disease entity (Wegener, 1939). He described this entity as a "peculiar rhinogenous granulomatosis with a unique participation of the arterial system and the kidneys". Later, Godman and Churg (1954) established the classical diagnostic criteria (the "WG triad"): granuloma, vasculitis, and glomerulonephritis. In 1958 Walton pointed out the poor prognosis of WG based on a small number of published cases (mean survival time: 5 months). In 1966 Carrington and Liebow reported "limited forms" of WG with a defmitely more favorable prognosis. Since then positive results have been reported with cyclophosphamide therapy. In addition, a retrospective study of combined low-dose cyclophosphamide and prednisolone in 85 WG patients over a period of 21 years found a similarly encouraging outcome. The*latter experience led to the current "standard" treatment protocol (FAUCI et al. , 1973 and 1983). More recently, strong evidence has emerged that some of the morbidity and mortality ofWG - and other types of systemic vasculitis - may be a consequence of this treatment (Hoffman et al. , 1992).

The term "lymphoma" was originally used by Billroth in 1871 [55], and by Virehow [763] some years before that, for the designation of swelling of lymph nodes that was not due to "eareinoma, sareoma, ehondroma, myxoma, ete. " In his paper, Billroth reeounted sueeessful treatment with arsenie (" Fowler's solution") of multiple "lymphomas" that had developed in a 40-year-old woman during a 10-month period. From this report it is not entirely clear if the multiple" lymphomas" deseribed were infeetious or if they were eonsis- te nt with what we now mean by "malignant lymphoma. " Today, the term "malignant lymphoma" is generally used eolleetively for malignant lymphoproliferative neoplasms that tend to arise in lymph nodes and also eneompasses Hodgkin's disease and non-Hodgkin's lymphomas. The adjeetive "malignant" seems somewhat superfluous sinee, in addition to Bill- roth's original eonnotation, the sense of malignaney is nowadays read into the word "lymphoma. " To be sure, true, i. e. , malignant, lymphomas have to be differentiated from "pseudolymphomas," or to put it more exaetly, "pseudomalignant lymphomas. " In this book, "lymphoma" and "malignant lymphoma" are used interehan- geably for malignant neoplastie lymphoproliferative disorders, and "pseudo- lymphoma" is used for benign lymphomatous proeesses. Our editorial eonsultant, Dr. M. Leider, disagrees with all of this. In his Dictionary of Dermatological Words, Terms, and Phrases [421] and other works, he maintains that there is no etymologieal basis for words bearing the eontrived suffix" -oma" or the true Greek suffix" -ma" to denote malignaney.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte. The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy."

This series of books, devoted to aspects of blood cell biochemistry, development, immu nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen tal studies and within their manuscripts. This has led to the production of a very interest ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature."

There is no field of medicine in which advances in therapy have been so closely linked to a better understanding of molecular medicine than in the area of hematologic malignancies. For example, recent insights into the understanding of Epstein-Barr virus have led to new treatment options for patients with posttransplant lymphoproliferative disorders, as discussed in the chapter by Dr. Richard Ambinder et al. Similarly, Drs. Slack and Gallagher discuss the explosion of recent information regarding the molecular pathogenesis of acute promyelocytic leukemia. This particular morphologic subtype of acute my- eloid leukemia warrants separate discussion because of our increased under- standing of the pathogenesis of leukemia, as well as the dramatic advances in outcome that have occurred with differentiation therapy provided by the vitamin A derivative aW-trans retinoic acid, as discussed in the chapter by Drs. Frankel and Powell. New approaches in the therapy of diffuse aggressive lymphomas in relationship to prognostic factors are discussed by Drs. Koc and Schenkein. Novel approaches to cutaneous T-cell lymphomas are discussed by Drs. Foss and Kuzel. Drs. Fonseca and Greipp discuss prognostic factors in myeloma, which are potentially important since they may serve to identify patients who may benefit from aggressive therapy such as bone marrow trans- plantation, which is discussed in the chapter by Dr. David Vesole. State-of-the-art reviews are provided in the chapters on AIDS-related non- Hodgkin's lymphoma by Drs. Volm and Von Roenn, adult acute lympho- blastic leukemia by Drs.

Experimental Hematology Today - 1988 presents the latest results of research reflecting the diverse interests of basic and clinical hematologists. The major areas explored are hematopoietic regulation by cytokines; hematopoietic cellular growth regulation, with emphasis on the interaction of stromal with hematopoietic stem and progenitor cells; granulopoietic regulators; gene transfers into hematopoietic progenitor cells; leukemogenesis; and bone marrow transplantation. All chapters report on research or clinical findings of the past year.

Historically, the field of hematopoietic growth factor research began with the work of Carnot and Deflandre-in 1906 they suggested that the rate of erythropoiesis is regulated by a humoral factor found in the blood, namely, erythropoietin. From this comparatively early start, accelerating progress has been made in erythropoietin research, which demon strates the general trends in this field of study. Erythropoietin was purified to homogeneity by 1977 (from enormous quantities of urine from aplastic anemia patients). Subsequently, the gene for erythropoietin has been cloned (1985), and massive quantities of this growth factor have been produced for clinical trials (late 1980s onward). Erythropoietin has become established as a pharmaceutical product of great value in the treatment of a number of diseases, most notably chronic renal failure. Once the ligand had been cloned, interest turned to the erythropoietin receptor, which was cloned in 1989. Since then, structure/ function studies have been performed on receptor mutants, cellular signaling events down stream from the occupied receptor have been identified, and the specific producer cell types and molecular stimuli for erythropoietin production have been thoroughly investigated, as has the regulation of erythropoietin gene transcription. This schedule of events since the 1970s typifies that seen for a number of hematopoietic growth factors. Along the way, the hematopoietic growth factors have been recognized as members of the cytokine family of signaling molecules that are important in a number of different physiological and patholog ical situations (see below).

Proceedings, with Commentary, of the Symposium held at London, England October 3-4, 1981

To produce a comprehensive overview of macrophages and related cell types in a short review volume is an impossible task. When I selected the topics to be included, some equally important areas were omitted by necessity, and for this I apologize. My choices have been somewhat eclectic, touching subjects of personal interest (such as osteoclast biology and macrophage electrophysiology) or of current fashion (apopto sis, antigen processing, cell adhesion molecules). The book has also had to encompass areas of a more general flavor to provide balance for the general reader (such as reviews of macrophage development, heterogeneity, and function, and of the surface molecules expressed by macrophages). I thank all the authors for their prompt sub missions; all have been of high quality, and my editorial tasks, thankfully, have been minimal. Michael A. Horton London, United Kingdom ix Contents Chapter J An Overview of Receptors of MPS Cells lain Fraser and Siam on Gordon 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. The Mononuclear Phagocyte System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3. Diversity of Macrophage Plasma Membrane Receptors. . . . . . . . . . . . . . . . 6 3. 1 A Structural Approach to Classification . . . . . . . . . . . . . . . . . . . . . . . . . . 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3. 2 Multisubunit Receptors 3. 3 Soluble Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3. 4 Lectins and Lectin-Like Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. Functions and Selected Examples. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4. 1 Growth, Differentiation, and Modulation . . . . . . . . . . . . . . . . . . . . . . . . 14 4. 2 Cell-Cell and Cell-Matrix Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 3 Endocytosis and Scavenger Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 4 Secretory Responses and Biosynthesis of Effector Molecules . . . . . . 17 5. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 6. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 . . . . . . . . . . . . . . . . . . . .

Sjoegren's Syndrome is slowly being recognised as one of the most common auto-immune diseases, and considered pivotal in the spectrum of auto-immune disorders. Sjoegren's Syndrome in Clinical Practice is a unique, concise book which explores important insights into Sjoegren's links with other conditions and devotes itself to shedding new light on this disease. Aimed at young medics but also suitable for the informed lay reader, physicians and pharma, Sjoegren's Syndrome in Clinical Practice will help with the diagnosis and treatment of this increasingly recognised disorder.