Transfusion medicine provides an excellent bridge connecting the healthy community donors with the patient's needs at the bedside; the dominant philosophy has been on patient care and science, but it is now realised that blood banks manufacture increasing amounts of blood components to administer to patients -- a role analogous to manufacturing functions. The concept of Good Manufacturing Practice (GMP) is therefore relatively new. While quality has always been important, the impact of GMP, Total Quality Management (TQM) and Quality Assurance (QA) will be profound. As the regulatory agencies, like the FDA in the U.S.A. and the EEC Commission in Europe, increase their enforcement activities, doctors, technical experts and managers will have to face many issues of quality assurance including documentation, validation, audit system, regulatory laws, licensing, teaching and training of staff and their job descriptions, standards, processing facilities, procedure validations, automation, record keeping, internal and external quality control of products and their release.The expansion of this philosophy to include Good Clinical Practice (GCP) is an even greater challenge demanding consensus therapy protocols and quality management of transfusion through auditing by the hospital transfusion committees. Such comprehensive plans will profoundly affect the financial and organisational structure of blood transfusion in the future.

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."

The idea to compile recent results on the ectoenzymes aminopeptidase N/CD13 and dipeptidylpeptidase IV/CD26 arose from the great interest given by readers world-wide to the two proceedings volumes edited by us in 1997 and 2000 (Ansorge and Langner, 1997; Langner and Ansorge, 2000). These volumes contained the presentations at two symposia held in Magdeburg (Germany) in 1996 and 1999 under the title "Cellular peptidases in immune functions and diseases", which was also the name of the Sonderforschungsbereich in Magdeburg, sponsored by the Deutsche Forschungsgemeinschaft between 1995 and 2001. Our groups in Magdeburg and Halle during the last two decades have provided results on these two enzymes in cells of the hematopoietic system that justify a review in an edited monograph like the present one (see the reviews by Kahne et at. , 1999; Lendeckel et at. ,1999; Riemann et at. , 1999). There are, however, many other groups in Europe, US and Japan which made important contributions to this field and particularly in topics improving the understanding of physiological and pathophysiological roles ofAPN/CD13 and DPIV/CD26. Therefore we decided to invite some of them to contribute reviews of their results to this book. Having worked for about 40 years in the field of proteolysis, for both of us to see the development of activities and knowledge from protein chemistry and enzymology to physiology and pathophysiology and even to therapy is very stimulating and fascinating. Of course, this development also reflects the dramatic improvement and refinement of methods.

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."

The mammalian erythrocyte is a very suitable model for the study of aging at the cellular and molecular level. It is not only a matter of apparent simplicity in terms of biochemistry, biophysics and physiology but more likely this cell offers a great possibility for elucidating some basic problems in the process of aging. In fact, nowadays, it is possible to follow individual cells all along their life span in circulation, it is possible to obtain these cells when young, middle aged or old and it is possible to obtain cells from individuals of defined ages and transfuse them into compatible recipients to investigate the role of the environment where the cell lives, and finally it is possible to easily manipulate the red cell content in terms of enzymatic activities and/or metabolic properties to investigate the possible effect of these manipulations on cell survival. This book, Red Blood Cell Aging, is based on a symposium held in Urbino, Italy, at the end of 1990 and examines the impact of age on the membrane, metabolism, structural and enzymatic proteins of mammalian erythrocytes. The various contributions to this symposium not only described those processes of aging which affect the cell but also provided a nearly complete picture of the event{s} and mechanism{s} that every day permits to recognize among 25 trillion circulating red cells {in an average adult} that 1 percent that have reached the end of their 120 day life span in circulation.

The European Study Group for Cell Proliferation held its XVth Meet ing at Sundvolden, Norway, in September 1987. The program included a symposium on the cell kinetics of the in flammatory reaction, with invited speakers. This volume of Current Topics in Pathology contains the manuscripts submitted by the speak ers. Inflammation is a very broad area, and the cell kinetics of the inflammatory reaction comprises a large number of topics. A full cover age would fill more than one book. This volume therefore contains only a few of the important aspects of the cell kinetics of the inflammatory reaction. It is hoped that it will serve as inspiration for further research in this important area. Inflammatory diseases are even more important than cancer, and there is a great need for a more detailed information about inflammation. OLAV HILMAR IVERSEN Contents Chapter I The Cell Kinetics of the Inflammatory Reaction. Introduction and Overview."

Volume therapy or infusion therapy is used worldwide for the treatment of hypovolemia caused by surgical blood and plasma losses, trauma, burns, or infections. Interestingly, significant differences exist between countries regarding the use of plasma substitutes. In the United States, crystalloids and albumin are more popular, whereas in Europe artificial colloids such as hydroxyethyl starch are preferred. From an international perspective, it is notable that volume therapy using hydroxyethyl starch is an established therapy for the treatment of cerebral, retinal, otogenic, and peripheral circulation disorders in Germany. In other countries, crys talloids are mostly used to treat dehydration or hypovolemia, for example in brain stroke. In recent years, new data made it possible to overcome national differences and agree on an evidence-based, international con sensus. The efficacy of different plasma substitutes for a volume therapy last ing several days has not been sufficiently studied in the past. Long-term volume therapy of patients with cerebral perfusion disorders is an excel lent model for studying the effects of artificial colloids in detail, because of the high doses of colloids that are administered. Through a compari son of commonly used plasma substitutes, we were able to show that sig nificant differences exist between different colloids, for example in their effect on coagulation. After repeated infusion, hydroxyethyl starches that are difficult to degrade lead to an accumulation of large molecules that are difficult to eliminate. These large molecules impair factor VIII/von Willebrand factor."

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.

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.