Through numerous discussions with colleagues it became apparent that the time was right to begin a series of workshop-like meetings on myeloid tumorigenesis. Myeloid tumors are the nonlymphocytic tumors of the hematopoietic system which include tumors of the neutrophilic, monocytic, erythrocytic, basophilic (mast cell) and megakaryocytic lineages. Pioneering studies in myeloid tumorigenesis were initially made in chickens with the discovery of retroviruses that induce various kinds of myeloid tumors acutely (myelocytomatosis, myeloblastosis, and erythroblastosis). These avian retroviruses were subsequently shown to contain the oncogenes v-myb, v-~, v-~, v-erbA, or v-erbB. There have been dramatic advances in studying the pathogenesis of hematopoietic tumors in genetically defined mammalian systems. Many of the well developed model systems in inbred mice, have focused on T- and B-1ymphoma development. Although myeloid tumors have been found in mice, they have not been studied as intensively as lymphoid tumors. Possibly this is because myeloid tumors are less common than lymphoid tumors. Recently, there has been renewed interest in murine myeloid tumor systems. This focus has resulted from 1) the discovery of inbred strains of mice (e. g. BXH-2, AKXD- 23, SJL/J) that are highly susceptible to spontaneous or induced myeloid tumorigenesis; 2) establishment of transplantable murine myeloid tumors (e.

Due to the topology and structure of the lymph nodes, their role in the pathogenesis and development of diseases is a very special one. Each organ and even each organ-related region of the body has its own group of lymph nodes, specific topological reactions, such as in circumscribed inflammation or in the metastatic spread of malignant tumors. On the other hand, all the lymph nodes of an organism join in a uniform function effected by highly differentiated structures. Volume 84 of Current Topics in Pathology presents our current knowledge about the structure and reaction patterns of this "sec ondary" lymphoid organ. Despite our original intention to publish all the contributions in one book, it became necessary to divide them: Part 1 focuses on the involved nodal compartments, cell types, and functions, while Part 2 describes their reactions in inflammatory, neo plastic, and immune-deficient diseases. Even with the cooperation of more than 30 authors, the coverage cannot be exhaustive. The scope of both parts is limited to those reactions that can be described by direct and indirect morphological methods, including modern tech niques such as immune electron microscopy."

I am honored to be invited to prepare a foreword for the proceedings of the Second International Lubeck Conference on Erythropoietin (Epo). I congratulate Wolfgang Jelkmann, Horst Pagel and Christoph Weiss for their organization of an excellent program for this conference which updated all of us on the advances made in erythropoietin research during the past few years since the first conference in June of 1988. I am sure that Professor Paul Carnot, had he been present at this conference, would be very pleased and proud of the advances made in the field of erythropoietin since his and Madame DeFlandre's seminal finding in 1906 (1) that rabbits produced a humoral substance following bleeding which controls red blood cell production. The reports by Hjort in 1936 (2) and by Erslev in 1953 (3) that large volumes of plasma or serum from rabbits following a bleeding stimulus, when injected into normal donor rabbits, produced a reticulocytosis, were very significant in confirming the existence of a humoral factor which controls erythropoiesis. Reissmann's parabiotic rat experiments in 1950 (4) reawakened interest in erythropoietin when he proved that hypoxia stimulated the production of a factor which regulates red cell produc tion. The studies of several investigators such as Jacobson et al. (5), Fisher and Birdwell (6), Kuratowska et al. (7) and Nathan et al."

Siegmund J. Baum It has become a tradition to commence advocated by Leonard Cole) (3). important meetings of this society with At about the same time, Alpen and reminiscence and nostalgia. Bone marrow Baum (4), using a larger mammal, the dog, transplantation, which has a history of only demonstrated that injecting autologous marrow 30 to 40 years, permits this process, since post irradiation would protect lethally some of the early investigators are still with irradiated animals (see Table). Certainly, us. For example, over the past 15 years, we protection was obtained from the cellular have had three symposia in honor of Egon constituents of the bone marrow. Lorenz. As we all know, the team of Lorenz, We undertook to test on dogs the Uphoff and Congdon was involved in the first hypothesis of Gengozian and Makinodum (5) that successful transplantation of syngeneic and increasing the radiation dose will increase allogeneic bone marrow into irradiated immunologic tolerance for allogeneic implants.

vitro methodology for the cultivation of erythroid The purpose of In Vitro Aspects of Erythropoiesis is to broaden our understanding of the regulation of stem cells. The second series of papers treats cellular normal and neoplastic hematopoietic cells by means and soluble factors which affect erythroid stem cell of a synthesis of different techniques, divergent no- differentiation. Hormonal modulation of in vitro menclature as well as a closer standardization of re- erythropoiesis is the theme of the third session fol- agents and methods which had heretofore produced lowed by a series of papers in the fourth which fo- vagaries of results among different laboratories. cuses on erythropoiesis after transformation by ei- Hence the papers, discussions and appendices pre- ther Friend or Rauscher viruses. The fifth session deals with serum inhibitors to erythropoiesis and the sented in this volume will be of value and interest to investigators and clinicians as well as to students and role of the macrophage in red blood cell production. teachers of hematology. Finally, the sixth session concentrates on the biogen- In Vitro Aspects of Erythropoiesis is comprised of esis of erythropoietin in vivo and in vitro. thirty papers delivered by twenty invited contribu- Each of the six sections is followed by a discus- tors at a three day conference which was held in sion which was transcribed and initially edited at the Capri, Italy in October of 1977. The contributors meeting.

51 worldwide leading experts in the field of erythrocyte research contributed to this first book on transport processes in red blood cells. It explains the latest findings on the basis of well-established principles, in an accessibly structured and carefully organized compilation.

This book describes all human leukemia-lymphoma cell lines that have been established and that grow continuously under standardised in vitro conditions. These lines are derived from cells belonging to all the major hematopoietic cell lineages, i.e. B- and T-lymphocytes, natural killer cells, granulocytic cells and megakaryocytic cells. The clinical data, the culture conditions and the major phenotypic features of the cell lines are described with citations. This book is the first book describing human leukemia-lymphoma cell lines and will be of interest to scientists involved in the areas of hematology, oncology, immunology, molecular biology and cytogenetics. Cancer Cell Lines, Volumes 1-3: These 3 volumes provide a comprehensive text on the culture of established cell lines from every type of human cancer. The volumes provide a basic manual and reference resource for every cancer research scientist using human cancer cells.

With this symposium the Red Cross Blood Bank Groningen-Drenthe affirms its well known reputation as an organizer of symposia of high standard and quality. Several important aspects of bloodbanking have been discussed in the past. The Blood Bank here is a specialist in its own field. Administrative processes in respect of the donor, information processes, the preparation of the blood and the laboratory process are automatized. New developments in these fields are undeway that you will certainly identify and investigate. I do hope that you will come to conclusions from which we can learn and get better results. As general manager of the Development and Investments Company for the Northern Netherlands - NOM - for several reasons I am very much interested in the outcome of this symposium. In the first place I am proud that the Red Cross Blood Bank Groningen Drenthe is doing its utmost to be excellent in regard of research, education and bloodprocessing. In being so, the Blood Bank can produce spinn-offs for healthservices and the related industry."

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

It is with great pleasure that I write this Foreword to the Proceedings of the International Conference on Behcet's Disease which was held in Berlin in June 2002. This was the first International Conference held under the auspices of the International Society for Behcet's Disease which was founded in 2000 in Seoul. First, I congratulate our colleagues in Berlin, led by Professor Christos Zouboulis of the Department of Dermatology at the Free University of Berlin, for having organised a most successful conference and for having compiled these proceedings so rapidly. It will be realised immediately on scanning the contents of this book that the conference was truly international with 210 participants from 26 countries, as Professor Zouboulis has noted in his preface. These included basic scientists, epidemiologists, pathologists, clinicians and, importantly, representatives from patient organisations. The latter held their own conference alongside the scientific-medical conference to mutual benefit. The combined session of patients and doctors (abstracts on pp 601 - 626) gave the opportunity for an exchange of information and fruitful discussion. The wide ranging scope of the communications is evident from the index and it was most encouraging to see their origin - from all parts of the world, from senior and junior colleagues and, from many different disciplines. Many communications may be regarded as preliminary reports of research in progress and we look forward to seeing the definitive publications in appropriate journals in due course."

Mononuclear phagocytes, which include macrophages, monocytes and their precursor cells, are the most important cells in the host defence against micro-organisms and tumor cells. During the last twenty-five years research on the biology of mononuclear phagocytes has increased tremendously. This motivated Professor R. van Furth to organize five international conferences on this subject in Leiden, the Netherlands. The edited proceedings of these meethings were published: in 1970 Mononuclear Phagocytes; in 1975 Mononuclear Phagocytes in Immunity, Infections and Pathology; in 1980 Mononuclear Phagocytes -- Functional Aspects; and in 1985 Mononuclear Phagocytes -- Characteristics, Physiology and Function. Reviews of these volumes, published in international journals, praised them as the most up-to-date state of the art publications. The publication of 1991 includes 88 chapters written by more than 200 authors.

Proceedings of the Twenty-Eighth International Symposium on Blood Transfusion, Groningen, NL, Organized by the Sanquin Division Blood Bank North-East, Groningen.

It is in many ways fitting that the last of these international symposia on blood transfusion should end with neonatal blood transfusion. The most fragile, least well studied and most at risk population requires special care and concern. We need to expand our knowledge of their unique physiology, biochemical pathways and in planning treatment and interventions, always "do no harm."

This proceedings of the last Groningen symposium presents a wealth of information on developmental immunology, the molecular basis of haematopoeisis, physiological basis of bleeding and thrombosis, transfusion risks and benefits and lastly, future therapies. Infants provide us with much to learn but in turn they will be the providers of (through cord blood) and the recipients of (through cellular engineering) the best that science can offer. Translational research, which has been the thrust of these presentations for 28 years, will benefit them in a way that no scientist could have ever predicted.

A comprehensive collection of classic and innovative methodologies used in many laboratories for the investigation of multiple myeloma. These readily reproducible techniques range from the standard Plasma Cell Labeling Index methodology to a final chapter on making sense of microarrays, and include the full spectrum of cytogenetic and molecular diagnostic methods. The protocols follow the successful Methods in Molecular Medicine (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. These proven techniques are ideal for studying the pathogenesis of multiple myeloma and identifying new therapeutic targets.

12 The average human body has in the order of 10 circulating platelets. They are crucial for hemostasis, and yet excessive platelet activation is a major cause of m- bidity and mortality in western societies. It is therefore not surprising that platelets have become one of the most extensively investigated biological cell types. We are, however, far from understanding precisely how platelets become activated under physiological and pathophysiological conditions. In addition, there are large gaps in our knowledge of platelet production from their giant precursor cell, the megakar- cyte. Understanding megakaryocyte biology will be crucial for the development of platelet gene targeting. The aim of Platelets and Megakaryocytes is therefore to bring together established and recently developed techniques to provide a comprehensive guide to the study of both the platelet and the megakaryocyte. It consists of five s- tions split between two volumes. The more functional assays appear in Volume 1, whereas Volume 2 includes signaling techniques, postgenomic methods, and a n- ber of key perspectives chapters. Part I of Volume 1, Platelets and Megakaryocytes: Functional Assays, describes many well established approaches to the study of platelet function, including aggregometry, secretion, arachidonic acid metabolism, procoagulant responses, pla- let adhesion under static or flow conditions, flow cytometry, and production of microparticles. Although one would ideally wish to perform experiments with human platelets, studies within the circulation using intravital microscopy require the use of animal models, which are described in Chapter 16, vol. 1.

This volume is a compendium of cutting-edge molecular methods for the successful transplantation of hematopoietic stem cells. The contributors are world-renown leaders in the field. They describe promising tools for stem cell transplant research models, such as in vivo bioluminescence imaging. They discuss HLA typing, PCR-SSP typing, and HLA antigens. This volume is an invaluable source for biochemists, molecular biologists, and clinicians.

12 The average human body has on the order of 10 circulating platelets. They are crucial for hemostasis, and yet excessive platelet activation is a major cause of m- bidity and mortality in Western societies. It is therefore not surprising that platelets have become one of the most extensively investigated biological cell types. We are, however, far from understanding precisely how platelets become activated under physiological and pathophysiological conditions. In addition, there are large gaps in our knowledge of platelet production from their giant precursor cell, the megakar- cyte. Understanding megakaryocyte biology will be crucial for the development of platelet gene targeting. The aim of Platelets and Megakaryocytes is therefore to bring together established and recently developed techniques to provide a comprehensive guide to the study of both the platelet and the megakaryocyte. It consists of five s- tions split between two volumes. The more functional assays appear in Volume 1, whereas Volume 2 includes signaling techniques, postgenomic methods, and a n- ber of key perspectives chapters. Part I of Volume 1, Platelets and Megakaryocytes: Functional Assays, describes many well-established approaches to the study of platelet function, including aggregometry, secretion, arachidonic acid metabolism, procoagulant responses, pla- let adhesion under static or flow conditions, flow cytometry, and production of microparticles. Although one would ideally wish to perform experiments with human platelets, studies within the circulation using intravital microscopy require the use of animal models, which are described in Chapter 16, vol. 1.

During the past few decades, technical and conceptual breakthroughs have led to a virtual revolution in developmental biology. In part through cross-species compa- sons and multidisciplinary approaches (combining, for example, classical embry- ogy, genetics, molecular biology, and systems biology), major questions have often been redefined and examined from new angles and with innovative tools. Analyses using such model systems as Drosophila, Xenopus, zebrafish, chick, human, and mouse have underscored the remarkable extent to which molecular and genetic pa- ways are conserved across species and throughout embryonic, fetal, and adult dev- opment. What we learn from the embryo, then, is not only of fundamental interest, but may well have future practical applications in the clinic. A number of excellent volumes, including several in this series (e. g. , Hema- poietic Stem Cell Protocols, Klug and Jordan, eds. , 2002), have surveyed methods used in the study of hematopoiesis-the processes by which the multiple lineages of the blood form from stem and progenitor cells during ontogeny and throughout the entire life of the animal. These collections of protocols have focused largely on the postnatal cells of mouse and human. Our understanding of hematopoietic devel- ment, however, has benefitted enormously from investigations in a variety of org- isms at different stages of ontogeny.

Building on the considerable expertise of the dysproteinemia unit at Mayo Clinic, this book spans the gamut from multiple myeloma, the most frequent and most serious of the monoclonal gammopathies, to the rarest related disorders. Laboratory evaluation, associations with nonhematologic disorders, monoclonal gammopathies of undetermined significance, the more obscure plasma cell dyscrasias, amyloidosis, other immunoglobulin deposition disorders, Waldenstrom macroglobulinemia, and Fanconi anemia are among the topics covered. Naturally, particular attention is paid to multiple myeloma: history, pathogenesis, clinical and laboratory diagnosis, modern therapy, and prognosis. Subsets of multiple myeloma such as solitary plasmacytoma, extramedullary plasmacytoma, and plasma cell leukemia are reviewed. This volume is designed to serve as a long-lasting reference for clinicians and scientists involved in the management of multiple myeloma and associated disorders."

Mr. Chairman, ladies and gentlemen, with great pleasure I like to welcome you in the cityofGroningen and hope that you will have an enriching and enlighten ing discussion on the conference theme on risk management in blood trans fusion. The organisation of this symposium aims at scientific networking by discussing in an international forum the most important themes of current interest in relation to the state of the art in transfusion medicine. Dr. Cees Smit Sibinga took the initiative in 1976 to start organising the blood bank symposia as they were named in the beginning. Without doubt these symposia have contributed considerably to the development of transfusion medicine. To illustrate the fact that these symposia came to my attention I recollect that I have attended the symposium in 1978, chaired by Dr. Leo Vroman, in my capacity in those days of alderman deputy mayor of the city. So, it has been a long time since. After having been away from Groningen for 18 years I have been inaugurated last week as a mayor and it is a plcasure to be again in your midst. The scries of annual symposia on blood transfusion have contributed to mark the city of Groningen on the map of the international scientific world. A great number of prestigious institutes all over the world involved in the development of transfusion medicine have linked to Groningen and we are proud of that."

Welcome to the City of Groningen, the center of the North of the Netherlands. Groningen is proud of the long lasting tradition of scientific symposia organised by the Sanquin Blood Bank. These Sanquin International Symposia on Blood Transfusion have become a true traditional event in Groningen, marking the early academic year and have contributed to the specific reputation of Groningen and its University in the scientific field of Transfusion Medicine. The growing tradition has also contributed to initiatives of both University, Province and the City of Groningen to bring science and industry together - BioMedCity Groningen. Such repu- tion does not just happen, but is the result of creative and scientific leadership, of vision and an open mind, to explore in a team spirit horizons. Groningen is particularly proud of this reputation thanks to its leadership, the Sanquin Blood Bank North-East. This year in particular the theme chosen some two years ago is extremely timely as it illustrates the activities and scientific interest of an integrated team which includes our regional Sanquin Blood Bank North-East and fits in the City initiatives within the concept of BioMedCity, Groningen.

The first book to cover both basic science and clinical research, providing a comprehensive review of the current knowledge on cytokines and cancer. Written by leading figures in the field of cytokine biology and cytokine therapeutics.

Edited by two leading orthopedic surgeons who are specialists in the treatment of hemophilia, Orthopedic Surgery in Patients with Hemophilia shows all the surgical techniques needed for surgical treatment of musculoskeletal complications of hemophilia. A practical guide, designed for use on the ward or in the office, this book draws on the experience of numerous specialists worldwide, from developed and developing countries. As well as orthopedic surgery, it also covers research, hematology, and rehabilitation. Although of primary interest to the orthopedic surgeon, rheumatologist, and physiotherapist, this book will also be relevant to the hematologist responsible for the care of the hemophiliac patient.

Active specific immunotherapy is a promising but investigational modality in the management of cancer patients. Currently, several different cancer vaccine formulations such as peptides, proteins, antigen-pulsed dendritic cells, whole tumor cells, etc. in combination with various adjuvants and carriers are being evaluated in clinical trials (1-3). To determine the optimal cancer vaccine strategy, a surrogate immunological end-point that correlates with clinical outcome needs to be defined, since it would facilitate the rapid comparison of these various formulations. Traditional immunological assays such as ELISA, proliferation and cytotoxicity assays can detect immune responses in vaccinated patients but are not quantitative. In contrast, novel assays such as enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine assay and tetramer assay can quantitate the frequency of antigen-specific T cells. Of these, the ELISPOT assay has the 5 lowest detection limit with 1/10 peripheral blood mononuclear cells (PBMC) and has been determined to be one of the most useful assays to evaluate immune response to cancer vaccines (4). However, the IFN-? ELISPOT assay is not an exclusive measure of cytotoxic T-lymphocyte (CTL) activity as non-cytotoxic cells can also secrete IFN-?. Additionally, CTL with lytic activity do not always secrete IFN-? (5). A more relevant approach to assess functional activity of cytotoxic lymphocytes would be to measure the secretion of molecules that are associated with lytic activity. One of the major mechanisms of cell-mediated cytotoxicity involves exocytosis of cytoplasmic granules from the effector toward the target cell.

In general, several mathematical models can be designed in order to describe a biological or medical process and there is no unique criterion which model gives the best description. This book presents several of these models and shows applications of them to different biological and medical problems. The book shows that operations research expertise is necessary in respect to modeling, analysis and optimization of biosystems.