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

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.

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.

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.

This comprehensive treatise on the reticuloendothelial system is a project jointly shared by individual members of the Reticuloendothelial (RE) Society and bio- medical scientists in general who are interested in the intricate system of cells and molecular moieties derived from those cells that constitute the RES. It may now be more fashionable in some quarters to consider these cells as part of what is called the mononuc1ear phagocytic system or the lymphoreticular system. Nevertheless, because of historical developments and current interest in the subject by investigators from many diverse areas, it seems advantageous to present in one comprehensive treatise current information and knowledge con- cerning basic aspects of the RES, such as morphology, biochemistry, phylogeny and ontogeny, physiology, and pharmacology, as well as c1inical areas inc1uding immunopathology, cancer, infectious diseases, allergy, and hypersensitivity. It is anticipated that, by presenting information concerning these apparently het- erogeneous topics under the unifying umbrella of the RES, attention will be focused on the similarities as well as interactions among the cell types constitut- ing the RES from the viewpoint of various disciplines. The treatise editors and their editorial board, consisting predominantly of the editors of individual vol- umes, are extremely grateful for the enthusiastic cooperation and enormous task undertaken by members of the biomedical community in general and especially by members of the American as well as European and Japanese Reticuloen- dothelial Societies.

Granulocyte colony-stimulating factor (G-CSF or GCSF) is a secreted glycoprotein that stimulates the proliferation and differentiation of granulocyte precursor cells, and induces mobilization of peripheral blood progenitor cells from the bone marrow. Development of recombinant human G-CSF has had a profound impact on the treatment of many diseases, including severe chronic neutropenia and cancer, and has enabled peripheral stem cell transplantation to supplant bone marrow transplantation in the autologous setting. This Milestones in Drug Therapy volume describes the experience of the last 20 years of treatment with recombinant human G-CSF, including the basic science, the use of recombinant human G-CSF in both the oncology and nononcology settings, and the safety and economics of its use. Many of the authors were the original investigators of recombinant human G-CSF and other authors are key researchers who provide their outlook for the next 20 years for use of and research with recombinant human G-CSF.

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.

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).

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 . . . . . . . . . . . . . . . . . . . .

Proceedings of a NATO ARW held in Cargese, France, October 9-13, 1989

This book reflects the personal prejudices I have developed in twenty years of reading the scientific literature. I like monographs; good ones assemble a great deal of information in a logical sequence and in enough detail to enable one to see why current beliefs are held. For this purpose, it is entirely useless to write "as Smith has shown21 ,81,117 **** " That only means that one must go to the library and turn up Smith's original papers, and one's object in reading a monograph is precisely to avoid that neces sity. One needs to know what Smith did and why he thought his observa tions proved whatever he claimed. Because life is short, it is impossible to deal with several thousand papers in this way, and the author must there fore select a relatively few papers that he regards as crucial. Often, several papers of equal merit might be quoted, and the selection is then arbitrary. I therefore apologize to authorities who do not find their work discussed. Omission does not mean that I thought their work was not valuable; it means only that I preferred to quote twenty references that people might read rather than two thousand that assuredly no one would read. Another strong prejUdice is that the full understanding of present knowledge requires one to know how present views have developed.

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well."

Blood has long been viewed as a conduit for therapy, stemming from the ancient days of phlebotomy to remove evil humors to the development of successful blood transfusions to replace missing blood components. The identification and characterization of hematopoietic stem cells by Drs. Till and McCulloch revolutionized the field and soon after, non-hematopoietic stem and progenitor cells were characterized from the blood and bone marrow. Some of these cell types and various blood-derived cell lineages are involved in the repair of various types of tissue damage that span the spectrum of medical disorders. The goal of this book is to provide an up-to-date review of the various types of blood-derived cells with regenerative capacity, identify opportunities for intervention by examining specific clinical applications, and recognize the regulatory environment that will encompass future therapies in regenerative medicine.

It can honestly be said that the scope and magnitude of this meeting surpassed initial expectations with respect to the number and quality of the papers presented. Our group has grown since we last met in Dortmund in 1971. This is a good indication that a spiraling of our interests has taken place with the effects of the initial good work felt, not just in one corner of the globe, but in all four. With such a start, it was only appropriate that an international society was formed at the meeting to further coordinate our mutual undertaking. Henceforth it shall be known as the International Society of Oxygen Transport to Tissue. A final note of acknowledgement should be made to those who were in the supporting cast, not only in making the meeting in Charleston and Clemson a success, but also in the compiling of this book. Gratitude is due to Dr. Daniel H. Hunt for his efforts, the end product of which you have in your hands. Considerable service was rendered by Mr. Robert J. Adams, Mr. Buddy Bell and Mr. Nathan Kaufman during the symposium itself. Much typing, organizing and record keeping was done by our lovely secretaries, Laura B. Grove, Muff Graham and Kaye Y. Zook.

Each year, it becomes more apparent that trace elements play an important role in human metabolism. The concept is no longer new. The literature on the subject is voluminous. Dr. Prasad, who has been interested in this field for many years, has undertaken the enormous task of bringing our knowledge together in a comprehensive fashion. This monograph should prove very informative and extremely useful to everyone who is concemed with human disease and with the maintenance of good health. His coverage of the subject is broad. Because ofthe importance of iron, in addition to "trace" elements, in human metabolism and nutrition, a chapter dealing with iron has been included. Maxwell M. Wintrobe, M.D. vii PREFACE It has been known for several decades that many elements are present in living tissues, but it was not possible to measure their precise concentra tions until recently. They were therefore referred to as occurring in "trace" amounts, and this practice led to the use of the term "trace elements." Although techniques now available are such that virtually alI trace elements can be determined with reasonable accuracy, the designation "trace ele ments" remains in popular usage."

This book covers a wide range of disorders such as atrial fibrillation, artificial heart valves, deep vein thrombosis, pulmonary embolism and stroke. Handbook of Oral Anticoagulation aims to provide an accessible overview of the exciting new developments in this field. Incorporating numerous quick-reference tables and figures and fully referenced throughout to key papers and the latest reviews, it will be a useful resource for all healthcare professionals involved in thromboprophylaxis.