In the last six years, a remarkable series of stUdies have demonstrated an intimate relationship between red cell metabolism and the function of the cell as an organ of gas transport. First came the demonstration of binding of organic phosphocompounds of the red cell to hemoglobin; this was followed by studies that demonstrated modification of hemoglobin oxygen affinity by such binding. At present we are in an exhilirating phase of accrual of data showing that the levels of these phosphorylated inter mediates can be rapidly altered in the red cell to modulate hemo globin function. At one time it was said that the red cell was an inert bag full of hemoglobin. Now we know not only that the cell has an active metabolism crucial to its viability, but that this metabolism is just as crucial to the whole organism in the proper adjustment of oxygen transport. On October first, second and third, 1969, red cell biochemists, general biochemists, geneticists, cardio-pulmonary physiologists, exercise physiologists, experts in blood storage, and represen tatives from many other disciplines met in the Towsley Center for Continuing Medical Education at the University of Michigan, Ann Arbor, to present recent findings and discuss developments in this new interdisciplinary field. The meeting was dedicated to Dr. Alfred Chanutin, Professor Emeritus of the University of Virginia, to honor his retirement in 1967 and in recognition of his great contributions to the studies outlined in the first paragraph of this preface."

Hemoglobin and the red cell have continued to set a dizzying pace as the objects of research in the two and one-half year interval since the First International Conference on Red Cell Metabolism and Function. Most exciting perhaps, is a beginning molecular attack on sickle cell disease. The story of the inter action of red cell metabolism and oxygen transport has continued to unfold, and we can now infer that patients with hypoxia usually utilize red cell metabolic adjustments to improve oxygenation. This puts the red cell squarely in the center of medical practice, since much of medicine-heart, pulmonary, and blood disease- deals with inadequate oxygenation. On April 27th through the 29th, 1972, crystallographers, chemists, biochemists, physiologists, geneticists, and physi cians from many medical disciplines met in the Towsley Center for Continuing Medical Education at the University of Michigan, Ann Arbor to present new data, to review recent developments, and to try to piece together additional features of the red cell puzzle. The meeting was dedicated to Dr. Francis John Worsley Roughton, Professor Emeritus of Colloid Science, University of Cambridge, England, in recognition of his numerous excellent contributions to the understanding of hemoglobin and red cell function. The program got off to a good start with a paper from M. F. Perutz, Nobel Laureate, on the structure of hemoglobin. Dr."

This book is not a "proceedings" volume. Rather the chapters are essays by experts in the field of blood substitutes, invited by the editors to con tribute to the 1996 "Current Issues in Blood Substitutes Research and Development" course given in San Diego, March 18-21. The contributors were selected because of their expertise in areas deemed by the editors to be critical to the advancement of the field. The course, as in past years, is heavily influenced by feedback from par ticipants, and by research in this and related fields. In addition to the didactic lectures (for which these chapters are the foundation), the course also offers the opportunity for presentation of research reports, progress reports from the various companies currently commercializing products, and round table discussions of selected subjects. Thus, we are grateful to past participants for their helpful comments. Production of a book, especially on a short timeline, is not an easy feat."

Sixty years ago, G. Fanconi published a paper entitled: "Familiiire infantile pemiziosaartige Aniimie (pemizioses Blutbild und Konstitu- tion)", in which he reported that this type of severe aplastic anemia represents a hereditary disease distinct from other pancytopenias of childhood (Fanconi 1927). Later this syndrome was named Fan- coni anemia (FA; van Leeuwen 1933). A more recent study of the genetics of FA confirmed that the syndrome is inherited in an au- tosomal recessive manner (Schroeder et al. 1976). Prenatal diagno- sis in FA families showed that about 25% of fetuses are affected (Auerbach et al. 1985, 1986). In 1964, Schroeder et al. discovered high frequencies of chro- mosomal aberrations in cultured peripheral blood lymphocytes from patients with FA. Schuler et al. (1969) reported that cells from FA patients are particularly sensitive to the chromosome-breaking activity or clastogenic effect of a polyfunctional alkylating agent. Since that time, studies of baseline and induced frequencies of chromosomal aberrations have been used for the identification of patients with FA. There is now a large body of data concerning the possible mechanism(s) underlying the hypersensitivity of FA cells to DNA cross-linking agents, the biochemical basis for which is still unknown. Complementation analysis, using cells from different FA pa- tients, has demonstrated genetic heterogeneity in the syndrome.

The 6th volume of the book series Acute Leukemias presents both therapeutic and prognostic updates of the most recent results of major multicenter clinical trials. Additional chapters report on new trends in leucemia cell biology, the monitoring of minimal residual disease and secondary leucemias as well as new antileucemic drugs, antimicrobial strategies and the use of cytocines. Acute Leukemias VI provides a new update on the rapid progress being made internationally concerning leucemic diseases.

The 11 th meeting in "Modern Trends in Human Leukemia" took place from June 19 to 21, 1994 in Wilsede in the middle of the Liineburger Heide, South of Hamburg. Interwoven with the Leukemia program was the Nato-sponsored Symposium of the ASI-Series "Gene Technology in Analysis of Malignant and Inherited Human Diseases Related to Development" . The Wilsede meeting was continued on a ship of the Neva leading through lake Ladoga and lake Onega. The topics of both meetings included discussion on recent progress isolation and development of hematopoietic stem cells, genes crucial for development and diseases, methods of gene transfer, application of gene transfer; oncogenes and anti-oncogenes as targets for gene therapy; receptors and their ligands in normal development and diseases, immunology and immunotherapy, radiation biology, clinical leukemias and bone marrow transplantation. The Nato workshop concentrated not only on analysis of cell systems useful for somatic gene therapy, but also on actual themes directly related to correction of human diseases. The latter aspects emphasized themes related to biotechnology, the first part was by nature more general. We also included a few contributions that discussed perspectives for the future of gene therapy and possible relationships to evolution.

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.

Hairy cell Leukaemia (HCL) has always attracted an interest out of all proportion to its frequency and continues to do so. There are two reasons for this. The first is that the disease is unusually responsive to therapy and second is that it has provided a number of important insights into B-cell biology. This monograph is a comprehensive account of hairy cell leukaemia and aims to provide a more detailed account than is available in the existing literature. The work is timely because a consensus has now emerged concerning accurate differential diagnosis a nd curative treatment. These aspects therefore form the focus of the book and are considered in detail. The basic advances in the laboratory that encourage the belief that elucidation of the underlying oncogenic event in the disease may be within reach. The background to this belief is extensively renewed. As a result the monograph will be of interest and practical value to both clinicians and researchers in this and related fields.

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."

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.

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.

It is an honour and a pleasure to welcome you all at this 20th annual International Symposium on Blood Transfusion in the Netherlands. This year you celebrate its 20th anniversary and I congratulate the Staff of the Blood Bank Noord Nederland and especially Dr. Smit Sibinga for this great achievement. As most of you know, the name of the person of Dr. Smit Sibinga is unbreakably con nected with the annual symposium in Groningen which he has organized each year from the very start, 20 years ago. The reputation of any symposium depends heavily on the quality of the lectures. I think it is not possible to organize 20 symposia in a row if the topics lack actual relevance and the speakers are not of excellent reputation. Dr. Smit Sibinga has proven to have a keen eye for selecting interesting themes and eminent speakers. Although a lot of different topics have been dealt with in the past 20 years, which each attracted the attention of a different group in the field of blood transfusion, it is not surprising that after a tradition of 20 years several speakers but also a lot of attendees are not for the first time in Groningen to participate in this event. It gives the symposium a unique atmosphere of intimacy. It is not hard to admit that most of the newer developments in transfusion medicine take place outside the Netherlands."

THE PHILOSOPHY OF QUALITY ASSURANCE IN THE BLOOD BANK H. F. Taswell One year before this symposium, Cees Smit Sibinga and I began to discuss an approach to quality assurance in the blood bank which we felt would be both important and practical and could serve as the basis for the choice of subjects to be presented in the symposium. As an introduction to this book, I would like to outline our approach, the subjects chosen and the rationale behind our choice. What is the fundamental purpose of a blood bank and trans fusion service? Simply stated, the purpose of a blood bank and transfusion service and of a quality assurance program in blood banking is, for the one to provide and, the other to assure safe and effective transfusion therapy. This objective is in contrast to that of other clinical laboratories. The objective in a clinical chemistry laboratory is to produce accurate test results which will be meaningful to the clinician taking care of his patient. In most clinical laboratories, therefore, the goals of a quality assurance program are largely quantitative, that is, to assure accurate numerical test results. In contrast, in the blood bank, the goals of quality assurance are primarily qualitative, that is, to assure safe and effective transfusion. As a result, two somewhat different approaches to quality assurance are necessary.

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.

This volume presents the proceedings of the Fourth Annual Symposium on the Molecular Biology of Hemopoiesis, held in Reno, Nevada, November 1 and 2, 1988. Its focus on erythropoiesis represents an attempt to cover a rapidly expanding field, which has gone from elegant studies of erythro poietin physiology, to molecular biology, to clinical applications and again to physiology. The rapid development has been made possible by cloning of erythropoietin gene and the availability of recombinant hormone. The regulation of heme and its derivatives has also been aided by techniques of molecular biology; there is now a concerted effort to better understand how these enzymes contribute to proliferation, differentiation and maturation of the erythron. Globin gene derrangements have been targets of recent research in an attempt to correct the defect by genetic engineering. In the chapters of this book, several groups "expressed" their views on this subject. Finally, we analyze various regulators of erythropoiesis, both in vivo and in vitro. Dr. Richard Levere was a pioneer in many studies of heme metabolism and of erythropoiesis. He has been a generous supporter of research in this field and of our past meetings. It is only. fitting that this volume should be dedicated to him."

Cytokines are cellular growth factors which also provide communication between cells and their milieu. This clearly is an exciting area in modern medicine that will have significant impact on various facets of transfusion. Erythropoietin therapy stimulates red cell production while thrombopoietin seems to positively affect megakaryopoiesis and can be an added armamentarium for the thrombocytopenic patient. Using haematnopoietic growth factors, stem cells could be mobilized early to the peripheral blood for collection and subsequent transplantation into haemato-oncology patients instead of bone marrow transplantation. Using a cocktail of cytokines in cell culture, stem cells could be expanded and selected for therapy. Cytokines and growth factors can even be modified, which may lead to successful gene therapy in malignancies, including solid tumour vaccines. However, the presence of cytokines in certain blood products could have biological effects following transfusion, although its clinical relevance needs to be ascertained. There is much potential for the use of cytokines in the treatment of infections. Early diagnostic methods are now available to monitor their levels and relevance. It is likely that cytokines will increasingly play a role in therapy and could develop our fundamental knowledge about the development of T-cells. An ethical dilemma remains, however, regarding the use of cytokines in healthy donors for harvesting suitable specific cells. Longer clinical observation will be necessary to gather the necessary information. Cytokines and growth factors in blood transfusion was the theme of the 21st International Symposium in Blood Transfusion, where twenty clinicians and scientists, experts in their own fields, were invited to update the above information. Their findings are presented in four sections in this volume: Fundamental aspects - cytokines in development of T-cells, growth factors in haematopoiesis, growth factor receptors and signal transduction, cytokine response in platelet and whole blood transfusions. Function, production and diagnosis &endash; laboratory diagnostics of cytokines and growth factors, cytokines in blood components, cytokines and growth factors in cell expansions, cytokines for genetic modification towards gene therapy, progenitor cells from healthy donors. Application in clinical medicine &endash; clinical relevance of cytokines in transfusion products, cytokines and growth factors in solid tumours, gene therapy in malignancies, vaccine strategies inducing T-cell immunity against tumours, cytokines in the treatment of infections, thrombopoietin and megakaryopoiesis. Future potential use in transfusion medicine &endash; erythropoietin, immunotherapy, ethical aspects of the use of cytokines and growth factors in donors, potential of cytokines and growth factors in transfusion medicine.

All medical specialists who must contend with the possibility of thrombosis will be interested in Anticoagulation. This book evaluates anticoagulation procedures from various points of view - from Current Trends in Anti-thrombotic Drugs, to Treatment of Ischemic Vascular Disorders; from Anticoagulants in Pregnancy, to Anticoagulation in the Elderly, from the Effects of Anticoagulant Therapy on the Heart, to Anticoagulation in various Surgical Procedures. Anticoagulation is a resource of approaches to the management of this common medical problem.

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.

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.

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.

Our understanding of the function of natural killer (NK) cells has dramatically changed in recent years. The discovery of NK receptors specific for MHC class I molecules, and the study of the role of co-stimulatory and adhesion molecules have led to an understanding of how NK cells recognize tumor and virally infected cells that have lost expression of MHC class I molecules or have altered distribution of normal cell surface molecules. Such recognition events lead to intracellular signals which can be either stimulatory or inhibitory. This book provides an insight into how NK cells develop, how they learn to distinguish altered cells from normal cells, and into their biological role in controlling infections and tumors.

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."

Recent developments in recombinant DNA technology have led to the large-scale production of human erythropoietin and to the demonstration that it is effective in the treatment of renal and possibly some other anaemias. This has lent a new impetus to studies of the pathophysiology and pharmacology of the hormone which is reflected in this report of the proceedings of a meeting held in Liibeck in June 1988. In 15 papers, all from European centres, the broad topics covered are erythropoietin's physiology and chemistry, the patho- physiology of erythropoiesis and the use of erythropoietin in the treatment of anaemia. Several of the papers include up-to-date reviews of the literature. The field is now expanding rapidly, and this volume, though not comprehensive, usefully points up many areas of recent understanding as well as others of continuing un- certainty. Overall, it contains material likely to be of interest to biochemists and experimental haematologists as well as to phar- macologists, clinical haematologists and nephrologists.