The Second Conference of the International Society of Hemorheology took place under the auspices of the University of Heidelberg from July 27 - August 1,1969 in Heidel berg. At this conference the name of the Society was changed to THE INTERNA TIONAL SOCIETY OF BIORHEOLOGY, since the members decided to enlarge the scope of the Society to include all fields of biorheology. Meanwhile the Society has become an Affiliated Commission of the International Union of Pure and Applied Biophysics. The abstracts of the scientific papers, as they appeared in the program of the Confe rence, have been reprinted in BIORHEOLOGY (volume 6, No.4, April 1970). This international journal has become the official organ of our Society. We are greatly indebted to the Honorary Chairman, Professor G. QUADBECK, Dean of the University of Heidelberg Medical School, who gave substantial aid to one of us (H. H. H.), the Conference Chairman, in organizing this international meeting. We are grateful to the Mayor of the City of Heidelberg who welcomed the participants and their families in the Cellar of the Great Barrel of the Heidelberger SchloB. We thank the members of the Ladies' Committee, Mrs. IRMGARD QUADBECK, Mrs. ELISABETH HARTERT and Mrs. KARIN KREITER, who arranged a most successful social program in Heidelberg and the romantic Neckar valley."

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.

A great deal of new information has been obtained during the past four years, and this monograph provides a clear and well reviewed update on biochemical mechanisms and the results of important new clinical studies using the interferons. Reviews include what is presently known about the biosynthesis, physiological role and mechanisms of action of the interferons (alpha, beta, gamma). New biochemical information on interferon-receptor interactions and signalling pathways is provided. The pharmacokinetic considerations in treating leukemia, lymphoma, myeloma, neuroendocrine tumors and other solid tumors are reviewed with special emphasis on studies of adjuvant chemotherapy in malignancies of the immune system.

As the demographics of the population shift toward an increasingly aged society, the number of individuals with cancer increases and with it the need to give the most comprehensive possible health care delivery. Although much has been written about the specific therapy best suited for the various types of cancer and about the basic and clinical research which has dramatically improved treat ment, overall patient care requires attention to supportive care, which includes such items as pain management, the use of blood products, nutrition, and psychosocial needs. Yet infection remains the leading cause of death in cancer patients and is a major cause of morbidity and hospitaliza tion, making it a major aspect of the supportive care of cancer patients. It therefore deserves a full exposition. Bone marrow transplantation is increasingly being utilized as part of a therapeutic modality in the treatment of cancer patients. Transplantation patients are at such a particularly high risk of developing a wide variety of different types of infection, that they inevitably can serve as an excellent framework for discussion of all the types of infections that occur during the treatment of cancer. The patient undergoing allogeneic bone marrow transplantation is at particularly high risk of infection due to the major perturbations of host defenses, which include granulo cytopenia, cellular immune dysfunction, humoral immune dysfunction, blood product transfusions, and vascular access devices. Each of these perturbations results in a different set of infectious disease problems."

Endocrine glands may be involved in patients with thalassemia major. In the last 20 years, new therapies have significantly improved life expectancy, while several endocrine abnormalities have been described in children, adolescents, and young adults suffering from thalassemia major.
The practical objective of this book is to establish guidelines for the management of endocrine disorders underlying the various phases of thalassemic life. Internationally acknowledged experts give a state-of-the-art account of physiopathological and therapeutical approaches to endocrine disorders in thalassemia and focus on such topics as growth hormones, thyroid diseases, puberty, hypogonadism, diabetes, and bone metabolism.

Progress in Basic and Clinical Immunology is a result of the 14th European Immunology Meeting - EFIS 2000, held in Poznan, Poland, on 23-27 September 2000. EFIS 2000 gathered over 1400 immunologists from all over the world. It was an exceptionally memorable meeting for a number of reasons: 1) it was held in the last year of the century and the millennium, thus provoking conclusions of past achievements of immunology and projections for the future; 2) it was held in Poland, a country that is a symbol of struggle for freedom for a large number of scientists originating from the 'Eastern Bloc' countries; and 3) EFIS celebrated its 25th anniversary at this occasion. This comprehensive volume contains 62 chapters grouped into 11 sections: T-cells, Immune Receptors, Antigen Presentation/Dendritic Cells, Cytokines, Immunodeficiencies, Autoimmunity, Allergy/Inflammation, Immunotherapy, Vaccines, Tumor Immunology, and Cancer Immunotherapy.

Scientists and engineers have been involved in medical radiology from the very beginning. At times advances in this field occur at a tremen dously fast pace. Developments in radiological diagnostics have - technologically and medically speaking - focused on morphology. At present, computer-aided tomography (CAT) is at a high point in deve1opment, medical application, and validation. The preconditions for this success were rapid advances in electronics and computer technology - in hardware and in software - and an unexpected cost reduction in these fields; the co operation of various scientific disci plines was also essential. Functional radiological diagnosis has been neglected in part, owing to the emphasis on morphology, but alone the synthesis of morphology and function prornises further advances. Apart from the limited capabilities ofuItrasonic techniques there is no way other than using X-rays to carry out functional studies of organs and their systems through an intact body surface. It is frequently necessary to do further processing and evaluation of image series which have been recorded from the morphological viewpoint. This further picture processing may be of selected points (pixels) in the image, of certain regions of interest (ROI), or of the overall picture. For the measure ment of rapid phenomena, such as the blood flow in the main arteries, high image-frame rates are required, and at the moment these can only be achieved with cinemascopic techniques. For slower processes, other techniques such as videography have some advan tages.

Stress, high blood pressure, smoking, pollution, fast foods, overweight, excessive travelling, surgery, less movement are common features in our modern life. These features are risky for blood clotting disorders. According to WHO, over 29% of the total mortalities worldwide are due to thrombosis. By the year, 2020 cardiovascular diseases (CVDs) may cause an estimated 25 million deaths per year, thus antithrombotic therapy is of great interest.

The available thrombolytic agents such as urokinase are highly expensive, antigenic, quite unspecific, pyretogenic and hemorrhagenic. Therefore, the production of fibrinolysing enzymes, which rapidly dissolute thrombi within the vascular tree, without the detriments by microorganisms, as described in this book, is the desirable aim of today s research. "

Leading international experts contribute to this selection of reviews covering the merging fields of growth factors, differentiation factors, and cytokines. These appear to play fundamental roles in a wide variety of physiological and pathophysiological processes that include the regulation of growth in normal and malignant cells, embryogenesis, the immune response, wound healing, inflammation, and atherogenesis. The major aspects of recent research and development are discussed, providing an important update in this pioneering field.

Hematopoietic stem cell and immune cell transplantation has cont- ued as a promising therapeutic alternative and a fascinating area of cell biology as well as a field of persistent procedural problems. This - plains why substantial parts of basic research on cell growth and d- ferentiation, immune tolerance and antitumor effects, gene transfer, minimal residual disease and supportive care have settled around cli- cal transplantation in hematology and oncology. This second volume again updates the current role of allogeneic and autologous transpl- tation in leukemias, lymphomas and solid cancers, including cont- versial strategies and novel experimental approaches. In particular, cellular immune therapy, new conditioning strategies, mismatched donor transplantation, updated clinical transplantation, antiangiogenesis and strategies against fungal infections are focused upon. Outstanding representatives of leading groups guarantee fir- hand information and indicate how we can work and cooperate more effectively to the benefit of our patients. The editors are indebted to the Gesellschaft zur Bekampfung der Krebskrankheiten Nordrhein-Westfalen for a substantial support of the publication. They also acknowledge the major contribution of Beate Kosel as coordinator of the editorial work."

th This book contains most of the papers presented at the Iy Inter- national Symposium on Bone Circulation which was held in Tou- louse, France, in September of1987. The symposium was attended by over 200 specialists from 17 different countries. Some of them were in Toulouse for the fourth time to discuss their favourite topic of study and research: bone circulation, its exploration, its pathol- ogy. Many, including a group of Japanese orthopaedic surgeons, were present for the first time, delighted to meet the authors of papers they had read. There were more than 100 oral presentations and posters, but many meaningful informal discussions took place both in and outside of the auditorium, in the hall and during meals. The organizers wished to maintain a balance between funda- mental themes and subjects of clinical and practical interest. This balance was accomplished: recent developments including scintig- raphy, magnetic resonance imaging and bone grafts played just as important a part as more sophisticated topics such as the evalua- tion of the blood flow rate in animal bone tissue. Thus, as did the previous symposia, this book aims to present a progress report on developments during the last 5 years in the study of bone circulation. We wish to thank all those who helped and encouraged us throughout the organization of the congress, especially C. Ar- noldi, M. Brookes, R. Burkhardt, L. Coutelier, S.P.F. Hughes, P. Kehr, J.P. Jones, A. Trias, K.Ono, T. Yizkelety and G.J.

Current problems in research and treatment of leukemias as discussed at the symposium of the International Society of Haematology on leukemias in Dresden (Germany) are dealt with in detail in this volume. The characterization of leukemic cells and the evaluation of their function are themes, with the first hints emerging of the possibility of relating them to the intensity of treatment required. The cytokines, responsible for cooperation between cells, are also of great importance, and the beginnings of therapeutic applications can be discerned here. Not only are the cytokines themselves very interesting, but also the application of cells producing cytokines according to the range of macrophages found. The emphasis on cell-to-cell relationship is thus a main topic of the book. Of course, other treatment such as bone marrow transplantation and interferon therapy play an important part, too, and the latest results of chemotherapy are reported. A further essential area covered is the diagnosis and therapy of chronic leukemic diseases, the inclusion of which suitably rounds off the book. I am very grateful to the out standing specialists from both the West and the East who contributed to the symposium and this book: an important sign of collaboration and integration for the future."

This volume contains all relevant information discussed in a Workshop on thromboplastin calibration held in Leiden, The Netherlands on July 1, 1983. The Workshop was an initiative of the Dutch foundation for a Reference Laboratory for Anticoagulant Control (RELAC) and it was organized by the Boerhaave Committee for postgraduate teaching of the Faculty of Medicine of the University of Leiden. The Workshop was held under the auspices of five organizations i. e. the European Community Bureau of Refer ence (BCR), the European Committee for Clinical Laboratory Standards (ECCLS), the International Association of Biological Standardization (lABS), the International Committee for Standar dization in Haematology (ICSH), .and the International Committee on Thrombosis and Haemostasis (ICTH). The aim of the Workshop was to discuss and develop a method for calibration of reagents, i. e. thromboplastins and/or plasmas used for the prothrombin time. During the Workshop three recent thromboplastin calibration studies were discussed, the results of which are presented in chapters 4, 7 and 9. These studies were carried out on the basis of a new calibration model developed by experts working with BCR and WHO. The usefulness of this model and the standardization system based on it is the leading thread running through this volume. Statisticians and clinicians discuss the results from a scientific point of view. Thromboplastin manufacturers, for whom especially the use of the model and the system is intended, discuss the matter also from an economic and legal point of view."

Estimates reveal that there are some 200 million heterozygous carriers of abnormal hemoglobins genes worldwide, and tens of thousands of severely affected patients. Effective application of imaging techniques is essential to combat the continuing development of the disease and to ensure risk-free follow-up of the chronically ill. This is the first book to offer complete coverage of such radiologic applications with both conventional and the most modern imaging modalities. Interventional radiology, marrow transplantation, prenatal diagnosis by ultrasonography, and radiotherapy for bone marrow heterotopia are also featured.

A large number of chemical agents are known which affect blood and blood-forming organs. The purpose of this volume is to review the sig- nificant advances made over the past several years regarding such chemical agents. The purification, biological action, and therapeutic implications of several widely used hematopoietic growth factors such as interleukin 3 (IL-3 or multi-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), colony stimu- lating factor (CSF-I or M-CSF), thrombopoietin, and erythropoietin are included in this volume. These factors are important in regulating several hematopoietic cell lines such as neutrophils, monocytes, eosinophils, macrophages, megakaryocytes, platelets, and erythrocytes. People are exposed daily to numerous toxic chemical substances present in our environment which produce a suppression of erythropoiesis, myelo- poiesis, lymphocytopoiesis, and megakaryocytopoiesis. Attempts have been made in this volume to assess the therapeutic role of some of the hematopoietic factors such as erythropoietin in the anemia of end stage renal disease, as well as colony stimulating factors in other hematopoietic abnormalities. In addition, some of the chemical factors in our environment which suppress major hematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin I-alpha, interleukin I-beta, and interleukins 2, 3, 4, 5, 6, 7, and 9 are also included. An updating of the mechanism of action of each of these factors on the major hematopoietic lineages is covered.

This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

This second volume reports on the reaction patterns of lymph nodes in neoplastic and immunodeficient diseases. Based on the contents of volume 1, it presents a detailed survey of lymph node structures and their cellular components under these conditions. The patterns of nodal reactions to the development and spread of cancer have recently been investigated and discussed by several authors. Here, the immediate interactions between tumor tissue and the regional nodes have been assessed in experimental models and in human material. Using modern morphological methods such as im munohistochemistry on the light and electron microscopic level, new insights have been gained into the stepwise process of lymphogenous metastasis. Macrophages/reticulum cells were found to playa signifi cant role in this process, which is duly emphasized. Based on appro priate animal models, one chapter focuses on various subtypes of these cellular elements and their role in the two separate phases of tumor spread and the development of true metastases. The induction of fibronectin in lymph nodes is effected by tumor cells forming a special part of the extracellular matrix. The multifunctional fibronec tin molecule serves as a mediator between tumor cells and fibroblasts, furthering the formation of tumor stroma. This volume also contains a comprehensive survey of primary im munodeficiency syndromes and their nodal manifestations, reference being made to the most recent immunological knowledge."

High pressure in the lungs, or pulmonary hypertension, is most commonly due to smoking-related lung disease and conditions affecting the left heart, for example, high blood pressure in the arteries, faulty heart valves, and a weakened heart muscle. Pulmonary arterial hypertension (PAH), is a rare and complex disease, associated with many different medical conditions, which is caused by a growth of cells lining the inside of the lung arteries, resulting in high pressure in areas of the body. Both conditions lead to strain and potential failure of the right heart, and therefore awareness and early diagnosis of the condition is needed to lead to better outcomes: however this depends on education of all specialists and primary care clinicians about PAH. This practical handbook covers both PH and PAH, providing information required by the wide range of clinicians who will encounter these conditions, including cardiologists, respiratory physicians, rheumatologists, specialists in liver and AIDS medicine, and haematologists. It covers what it is, who it is likely to affect, how it is diagnosed, including the pitfalls of the various diagnostic tests, the different and evolving forms of treatment, long term management of this often devastating chronic disease, and the crucial role of multidisciplinary management in optimizing clinical care of these patients who usually have multi-system diseases. It also covers the up new classification for both PH and PAH, and new drugs that have recently become available.

This book contains the proceedings of a symposium on the use of synthetic substrates in clinical blood coagulation assays, which was held at the University of Leuven, Belgium, on March 1st, 1980. This meeting was organized in order to exchange and discuss recent develop ments and applications in this field. Advantages and disadvantages of synthetic substrates are discussed, while expert workers report on their practical experience with the use of chromogenic substrates in routine assays for blood coagulation and fibrinolysis. The indications when to perform antithrombin III, a2-antiplasmin, factor X and factor II determinations are discussed. For each of the determinations a critical evaluation of the chromogenic assay as compared to the classical assay is presented. The clinical relevance of these assays for anticoagulated and cirrhotic patients, detection of vitamin K deficiency, monitoring heparin therapy and the fibrinolytic system are discussed. Recent developments in the use of fluorogenic substrates for the assay of low concentrations of fibrin olytic activators are presented. Taking into account all practical, medical and economical con siderations an answer is prepared to the question "Are synthetic sub strates to be recommended for routine use?." To make this symposium useful, rapid publication of the proceedings has been undertaken. We are grateful to the participants in this meeting for their co operation and for their willingness to provide manuscripts of their presentations. The manuscripts provided by C. Kluft and H.H.D.M."

This book reviews the respiratory function of vertebrate red cells. I have defined the phrase "respiratory function" broadly to include, in addition to the actual oxygen and carbon dioxide transport, erythropoiesis, haemoglobin synthesis, red cell structure, the deformability of red cells in circulation, ion and substrate transport across the cell membrane, cellular metabolism, and control of cellular volume and pH. All of these aspects of the red cell function may affect gas transport between the respiratory epithelia and the tissues. Throughout the book, I have tried to relate our current knowledge about the nucleated red cell function to the wealth of information about the function of mammalian red cells. However, whenever possible, I have placed the emphasis on the nucleated red cell function for two reasons. First, the erythro cytes of 90% of vertebrate species are nucleated, and, second, nucleated red cell function has not been reviewed earlier in a single volume. This being the case, I have tried to make the reference list as complete as I could with regard to nucleated red cells. I hope that the approach adopted is useful for both com parative and human physiologists. Many people have contributed to the making of this book directly or in directly. Antti Soivio started me in this field. Prof. Henrik Wallgren has always encouraged fresh scientific ideas in his department. My present ideas of red cell function have been influenced by work carried out with Prof. Roy E."

In June 1986 a symposium was held in Giessen on Modern Trends in Virology. It was initiated by the Deutsche Forschungsgemeinschaft, which had supported virus research for the past 18 years in the Sonderforschungsbereich 47 at the University of Giessen. The purpose of the meeting was to serve as a forum for the members of the Sonderforschungsbereich to discuss scientific topics of mutual interest with about 200 virologists that had come from various parts of Europe, the United States, and Japan. It was not by chance that the symposium took place shortly after the 60th birthday of Rudolf Rott, who had founded the Sonderforschungsbereich in 1968 and has been its speaker ever since. Without his vision and his never resting energy Giessen would not have gained the position in the field of virology that it has today. This Festschrift, which contains the contributions presented at the plenary sessions of the symposium, is therefore dedicated to Rudolf Rott. HEINZ BAuER HANS-DIETER KLENK CHRISTOPH SCHOLTISSEK Table of Contents A Genetic Approach to Determining Glycoprotein Topology: The Influenza B Virus NB Glycoprotein has an Extracellular NHz-Terminal Domain Containing two N-linked Carbohydrate Chains R. A. LAMB and M. A. WILLIAMS . . . . . . . . . . . . . . . . . . . . . . . . . 1 Paramyxovirus Metabolisms Associated with the Cytoskeletal Framework Y. NAGAI, T. ToYODA, and M. HAMAGUCHI . . . . . . . . . . . . . . . . . . . 15 Correlation of High Evolutionary Rate of Influenza A Viruses in Man with High Mutation Rate Measured in Tissue Culture: A Hypothesis P. PALESE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Few publications focus on the mysterious, genetically acquired disease paroxysmal nocturnal hemoglobinuria (PNH) and the related "intractable" disorders aplastic anemia and myelodysplastic syndromes. Now, however, the latest understanding of the clinical and molecular genetic aspects of PNH is summarized here in the proceedings of the International Symposium held in Tokyo in 2001. Major topics reviewed include the molecular mechanisms of the PIG-A gene mutation; complement activation and inhibitors; experimental animal models; pathogenesis; the history of PNH research; the natural history of the disease; the mechanism of PNH clone expansion; the emergence of PNH clones under bone marrow failure syndromes; and treatment of the disease by immunosuppressive agents and stem cell transplantation. This book provides an invaluable summary of current research on the fundamental aspects of PNH pathology, presented by renowned experts in the field.

"

Das ist das Schwerste von aHem, was Dir das Leichteste diinket: mit den Augen zu sehen, was vor den Augen Dir liegt. Goethe, Xenien, 1797 That is the most difficult which seems the easiest: to see with your eyes what lies there to be seen. All the diseases in question here are rare. The most common, mucopolysacchari- . dosis (MPSosis III), occurs at a rate of 1 in 160000. Consequently, anyone doctor will only encounter a few cases as a rule, and the literature offers mainly casuistic descriptions. Up till now, there has been no systematic and comprehen- sive review. We thus felt that it would be of interest and benefit to prepare a collective report on a large body of material gathered over a period of many years, the material being extensive enough to provide adequate possibilities for making comparisons. In so doing, we were also able to describe for the first time the specific, and, in some cases, the pathognomonic symptoms for each disease.

The translation of Blood Smears Reinterpreted was begun when the French original was still undergoing revisions. I was accorded the oppor tunity to question any statement or turn of phrase that was unclear to me or appeared liable to misinterpretation. It is my hope that as a result, ambiguities-particularly those inherent in differences between American and Eu ropean usage-have been removed and that I have at least ap proached the ultimate goal of any translation: to reflect the author's intention accurately while remaining as readable as the original. Beyond the role of translator, I was encouraged to assume the role of critic. As a result, some pages or even single sentences were hotly debated, sometimes for hours, as Marcel Bessis insisted that any inter pretations on which we could not agree should be so indicated. In fact our discussion invariably ended in agreement, though they led to changes of a sentence here or a word there and, on occasion, to the addition of a footnote or a brief paragraph.

Within the last few years, iron research has yielded exciting new insights into the under standing of normal iron homeostasis. However, normal iron physiology offers little protec tion from the toxic effects of pathological iron accumulation, because nature did not equip us with effective mechanisms of iron excretion. Excess iron may be effectively removed by phlebotomy in hereditary hemochromatosis, but this method cannot be applied to chronic anemias associated with iron overload. In these diseases, iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic iron toxicity. Iron chelating therapy has changed the quality of life and life expectancy of thalassemic patients. However, the high cost and rigorous requirements of deferoxamine therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Such development, and the evolution of improved strategies of iron chelating therapy require better understanding of the pathophysiology of iron toxicity and the mechanism of action of iron chelating drugs. The timeliness of the present volume is underlined by several significant develop ments in recent years. New insights have been gained into the molecular basis of aberrant iron handling in hereditary disorders and the pathophysiology of iron overload (Chapters 1-5)."