As a comprehensive reference on all aspects of the histiocytic disorders, Histiocytic Disorders of Children and Adults stands out a seminal text on the genetics, pathophysiology and clinical management of this wide range of diseases. The chapters, written by acknowledged experts in the field, cover all aspects of hystiocytic disorders, from Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis, to the uncommon cutaneous and extracutaneous histiocytic disorders. Views on the function of normal histiocytes in the immune system, the pathogenesis, underlying genetic defects, clinical presentation, treatment, controversies in therapy, salvage therapies and the late consequences are discussed in detail. Originally published in 2005, this book will be a valuable resource to clinicians and researchers who wish to learn more about histiocytic disorders.

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

It was the year of 1969 when this monograph was originally published in Japanese by Professor TADASHI KAWAI, titled as "The Plasma Proteins, Their Fundamental and Clinical Aspects." After I read through the Japanese edition, I was impressed by its rather complete coverage of the subjects and their detailed descriptions. I have felt that this excellent monograph should be distributed not only among our Japanese scien tists but also among many other colleagues throughout the world. I am happy, the refore, to know that the English edition of his monograph, partly revised, is ready to be published at this time. Professor KAWAI received his postgraduate medical training in U.S.A. for seven years, and was certified by the American Board of Pathology in both Anatomical and Clinical Pathology in Fall, 1962. Thus, I believe, he is the most suitable fellow for publishing the English edition of this kind.

This volume contains those papers which were presented at the Second International Symposium on Oxygen Transport to Tissue, to- gether with the discussions which followed. These discussions were generously summarized by the chairmen of the various sessions. This symposium in Mainz was the third international meeting, after those held in Dortmund in 1971 and Charleston-Clemson in 1973, which dealt primarily with problems relating to oxygen transport to tissue under physiological and pathophysiological conditions. It was the second symposium conducted by the International Society on Oxygen Transport to Tissue which was founded in 1973. We dedicate this volume to the memory of the first president of the International Society on Oxygen Transport to Tissue, Dr. Mel- vin H. Knisely. July, 1975 JUrgen Grote Daniel D. Reneau Gerhard Thews Contents Welcome xxi G. Thews Session I - OXYGEN MEASUREMENTS IN BLOOD AND TISSUE A Method for Simultaneous Measurements of Bioelectric Activity and Local Tissue P02 in the CNS * * . * ...* * . * 3 A. Lehmenkuhler, H. Caspers, and E. -J. Speckmann Oxygen Fields Induced by Recessed and Needle Oxygen Microelectrodes in Ho- geneous Media * . * . * 9 G. Schneiderman and T. K. Goldstick The Application of Histological Analysis for the Localization of Tissue P02 and Local Blood Flow with the Example of the Glomus Caroticum of the Rabbit (Oryctolagus cuniculus) . . * * ...* * * . . * . * . . * . 17 H. Weigelt, E. Seidl, H. Acker, and D. W.

Since there are many different tissues and organs in the body, a study of oxygen transport to tissue necessarily involves a great diversity of bodily functions. Furthermore, these tissue functions can be approached from the viewpoint of several disciplines. Even tually, however, all of these approaches must be combined to arrive at a comprehensive picture. This multidisciplinary effort, though imperative, has been implemented slowly because traditional biologi cal science has been largely organ- or discipline oriented. Initia tives to realize an effective international multidisciplinary collab oration have assumed increasing momentum for the past 20 years. These include meetings held in Bad Oeynhausen in 1965 (book in 1968, edited by D. W. Lubbers, U. C. Luft, G. Thews and E. Witzleb), in Nijmegen in 1968 (book in 1969, edited by F. Kreuzer), in Vancouver in 1970 (J. Strauss), and in Dortmund in 1971; this last was in connection with the 25th International Physiological Congress in Munich (book in 1973, edited by M. Kessler, D. F. Bruley, L. C. Clark, Jr., D. W. Lubbers, I. A. Silver and J. Strauss). This increasing international cooperation called for a more formal organization of these individual initiatives. The credit for taking this decisive step goes to H. I. Bicher and D. F. Bruley from the U. S. A. and D. W. Lubbers and M. Kessler from Germany, who got together in 1972 to plan a large-scale inter national meeting and to organize an international society."

The International Workshop - Conference on Atherosclerosis was held at the University of Western Ontario, London, Ontario, Canada, September 1 - 3, 1975. This book does not represent in a strict sense the entire proceedings of the above Workshop - Conference, but does reflect largely the format and the essential content of the scientific sessions. Thus, each of the three Sections of the book is comprised of the summarized presentations either at the Plenary Sessions (Section I), Proffered Papers (Section II) or Workshops (Section III). Section I comprises all the presentations of the Plenary Session on September 1 and the first three presentations at the Plenary Session on the last day of the Conference (September 3). The remaining two addresses of the latter Session (Resume of Workshop - Conference and Closing Remarks) follow the Section III at the end of the book. Sections II and III are subdivided into Chapters which correspond to the individual Sessions of Proffered Papers and Workshops, respectively. To facilitate the orientation, particularly for those who attended the Workshop - Conference, a Summary Table of all Sessions of Proffered Papers designated as Chapters in this book, precedes Section II, and a similar Summary Table of Workshops, also designated as Chapters, precedes Section III. The Tables include, in addition, the names of both Chairmen of each Session. The Chairmen whose names do not appear on either Summary Table are those who chaired the two Plenary Sessions, i. e.

Before the introduction of DDA VP, centrnl diabetes insipidus was treated by the administration of a more or less purified extract from bovine or porcine posterior pituitaries, and the prepamtions were mostly given in the form of nasal snuff. In 1956, the structure of vasopressin became known and two forms were found, namely arginine vasopressin (A VP) in humans and most other species, and lysine vasopressin (L VP) which was found in the pig. In 1967, Zaornl et al. were the frrst to synthesize l-desamino-8-D-arginine vasopressin, DDA VP. In comparison with the compounds which were previously available, DDA VP offered increased antidiuretic potency and an equally distinct shift of the antidiuretic to pressor potency rntio. As a result of the pioneering studies of Cash and Mannucci, numerous publications appeared in the medical literature of the 80's, widening the fields of clinical application of the drug. A very important aspect of this drug is that it can be used as an alternative treatment for mild factor VllI deficiencies, mild hemophilia A and von Willebrnnd's disease. These congenital deficiencies are far from mre and have, up to now, been treated with plasma-derived factor VIII concentrates; in the countries in which desmopressin has not been used a consistent proportion of these patients have seroconverted for HIV 1 and hepatitis.

The book combines general concepts and methods to investigate calcium signalling in cells ranging from molecular biology approaches to manipulation of calcium in living cells. The focus within these methods in on the broad range of fluorescence imaging technology, in particular on optical sectioning techniques and fast image acquisition. In addition to these general guidelines there are application examples in a context beyond calcium signalling in two major fields: investigations of isolated cardiac myocytes and red blood cell related research. While the cellular cardiology section provides snapshots of certain calcium signalling aspects, the red blood cell part presents an overview from the functional identification of calcium-channels to a concept of physiological and pathophysiological relevance.

150 years after the first description of the clinical picture of "white blood" and the introduction of the term "leukemia" by R. Virchow it appears, that the leukemias, and the acute leukemias in particular, serve as an impressive example for the major improvements that have been achieved in the treatment but also in the understand ing of the biology of malignant dis orders. The international symposia "Acute Leukemia" which are held at Munster since 1986 have developed into an interna tional forum to review the current progress and the future perspectives of leukemia research and therapy at a high scientific and clinicallevel. Since the possibility for active participation in these symposia is somewhat restricted we are glad to have the opportunity to extend the information that was presented at the symposium "Acute Leukemias V - Experimental Approaches and Management of Refractory Disease" which was held from February 27 to March 2, 1994 to a broader audience of basic scientists and clinicians. This meeting was especiaIly designed to discuss experimen tal approaches and the management of refractory disease which allows to evaluate new experimental therapies on the basis of preclinical studies."

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.

Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc.

Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more and more answers every day.

"Stem Cells and Tissue Engineering" is a concise review on the functional, phenotypic, regenerative, transplantational and curative aspects of a stem cell's entity. It is critical and encouraging at the same time, providing truthful and appropriate samples from the practice and research that can lead toward optimal use of this immense source of adjuvant and curative therapy in human pathology. Written by a clinician and a researcher, who are currently teaching what they are doing, it is recommended as a teaching tool along with an original textbook.

Leading transplant physicians critically review and interpret twenty-one key clinical challenges in bone marrow/hematopoietic cell transplantation, and offer their best personal recommendations for treatment. Topics range from transplant strategies to complications of bone marrow transplantation, including a discussion of the indications, benefits, and the risks for a variety of leukemias, lymphomas, and solid tumors. The authors debate such contentious issues as the appropriateness of transplants in older patients, how many stem cells are sufficient for engraftment, and the pros and cons of umbilical cord blood transplantation. Up-to-date and clinically focused, Current Controversies in Bone Marrow Transplantation offers clinical oncologists, hematology/oncology fellows in training, and residents in internal medicine today's best ready reference and management guide for all their critical oncologic problems arising from the use of bone marrow/stem cell transplantation.

The provocative title stems from the recent International Blood Transfusion Symposium in Groningen, The Netherlands held under the auspicies of the World Health Organization (WHO), International Society of Blood Transfusion (ISBT) and Council of Europe (CoE). Transfusion medicine is a new discipline which has a wide remit. As defined recently, transfusion medicine deals with that part of the healthcare system which undertakes appropriate provision and use of human blood resources; transfusion practice is therefore a collective activity linking the blood donor with the patient. Transfusion medicine occupies areas in which it is deemed to be important or even essential that medical practitioners contribute to this bridging process. The broad issues and complex practices are presented in the masterly Introduction by the WHO's Assistant Director General with emphasis on education and multidisciplinary facets involving transfusion medicine. The challenging subjects are dealt in great details with a wealth of personal experience by 24 experts from the U.K., France, The Netherlands, U.S.A., Australia, Germany, Sweden, WHO and the Council of Europe.This is a comprehensive yet concise state of the art presentation involving donor and delivery system, ethics and legal elements, effects of modern techniques, importance of management and the future directions in this new economic environment. The book has been divided into four sections which discuss both the facts and the fiction.

Recent progress in molecular biology has led to a rapid expansion of our understanding of the proteins that are essential for hemostasis and thrombosis. The goal of the XXI Annual Scientific Symposium of the American Red Cross was to provide a forum to explore and document the impact of recombinant DNA technology in this field. The speakers described the essential features of the genes responsible for key plasma proteins important in hemostasis, including procoagulant Factors VIII and IX and anticoagulant proteins, Antithrombin III and Protein C. They emphasized the advances in recombinant DNA technology that have led to the cloning of these genes. Careful examination of the gene sequence has then provided a clearer understanding of the structure of the encoded proteins, and has given additional insight into their functional domains and their interactions in hemostasis. At the same time, these advances have made it possible to better characterize hemostatic disorders. A large number of published studies have shown that the mutations affecting biological activity are clustered in areas that define functional domains. They have led to fundamental advances in our understanding of specific diseases and they have made it possible to develop more accurate and sensitive diagnostic tests for the detection of the disease states.

A number of exciting new developments have occurred during the last few years concerning the platelet-vessel wall interaction. Although they may be obvious and clear to the specialist in the field, for the clinician the area has become rather confusing. Time has come to review current knowledge on the pathophysiology of the platelet-vessel wall interaction and show how this knowledge can constitute the rationale for pharmacotherapeutic interventions. A symposium was organized in Antwerp during which a number of outstanding speakers gave an overview of what is new on a particular topic and how this information can be translated to possible clinical applications. The proceedings of the symposium are not only of interest to the practising physician, but contain enough new fundamental data to be of use for all those who are interested in the role of platelets in the etiopathogenes ofcardiovascular diseases. Arnold G. Herman Antwerp, July 1-991 vii ListofContributors A.G. Herman DepartmentofPharmaceutical Sciences M.R. Buchanan University Hospital DepartmentofPathology Universiteitsplein I McMaster Clinic B-261O ANTWERP (Wilrijk) Hamilton General Hospital Belgium 237 Barton Street East HAMILTON, Ontario G. Homstra Canada L8L 2X2 DepartmentofHuman Biology UniversityofLimburg Co-author: SJ. Brister P.O. Box 616 6200MD MAASTRICHT J.-P. Cazenave The Netherlands Regional Centre ofBlood Transfusion 10, Rue Spielmann J.F. Martin F-67085 STRASBOURG Cedex Department ofMedicine France King's College School ofMedicine and Dentistry Co-authors: C. Gachet and F. Lanza LONDON SE5 9PE U.K.

The aim of the issue is to describe and explain the importance of the chemokine system in hematology. The chemokine system is probably important for many aspects of normal as well as malignant hematopoiesis. A major focus is the development and treatment of hematologic malignancies, including the immunobiology of stem cell transplantation. The present reviews illustrate that chemokines can be involved in leukemogenesis. The chemokine system is also important both for the crosstalk between malignant cells and their neighbouring nonmalignant stromal cells (including endothelial cells) as well as for immunoregulation in patients treated with allogeneic stem cell transplantation. Thus, chemokines are important both for the pathogenesis and treatment of hematological diseases.

In September 1998 experts from 19 countries came together for an interdisciplinary discussion of the function of animal peroxidases, a family of enzymes embracing myeloperoxidase, eosinophil peroxidase, thyroid peroxidase and lactoperoxidase. Their papers have been updated for publication, yielding a wide-ranging overview of the state of the art. The chapters cover a wide range of topics, including three-dimensional structure of representative family members, their biosynthesis and intracellular transport, mechanism of action as well as applications to clinical medicine. They are of clinical relevance in, for example, arteriosclerosis, multiple sclerosis, infections, tumorigenesis, rheumatic diseases and hypothyroidism. This book forms an excellent introduction for anyone interested in the peroxidase family of enzymes.

Two infonnal meetings of consultants expert in hemostatic phenomena and in atherogenesis were held in Bethesda, Maryland, in December 1975 and February 1976 by the National Heart, Lung, and Blood Institute. Their purpose was to discuss the current status of knowledge concerning the thrombotic process in the pathogenesis of atherosclerosis. It was readily agreed that thrombosis often played a major role in plaque building and in plaque complication. It was also commented, however, that the data were qualitative in nature and that quantitative infonnation was remarkably sparse. The term thromboatherogenesis was thought to be appropriate for those phenomena in which the full expression of the thrombotic process is manifest. At the same time, recent research was noted in which what appears to be an important pathway for the initiation of atherogenesis arises from the reaction of platelets with injured arterial endothelium and'Subendothelium without necessarily involving the complete classical thrombotic process. A name was not coined for this circumstance, but it was held that thromboatherogenesis was not a fully appropriate one.

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

This comprehensive book, lavishly illustrated with over 700 colour pictures, addresses the subject of bone in internal medicine. It is based on biopsies of bone and first describes the normal range of physiological findings in iliac crest biopsies in young, middle-aged and elderly individuals. The book then deals systematically with the osseous disorders most frequently encountered in internal medicine, and some that would be considered in the differential diagnosis. Numerous up-to-date references are included. The clinical applications of biopsies of bone are emphasized as well as their clinical interpretation; sections on histomorphometry and functional aspects of bone cells are also included. The book will be of particular interest to specialists in internal medicine, endocrinology, nephrology, haematology and oncology, as well as being a bench manual for the practising pathologist.

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)."

In 1868, Ernst Neumann recognized that blood cells re quire continuous replenishment during postnata1life. Before him, the assumption was that cells of the blood, like nerves once formed in the embryo, remain in the body throughout life. Neumann also recognized that this process occurred within the bone marrow, because this tissue provided a fa vorable environment for proliferation and differentiation of blood cell precursors. Vera Danchakoff, the Russian embryologist working in the US, in 1916 made an analogy to the soil and the seed. Bone marrow forms the soil, providing a favorable environment for the growth of seed, the hemopoietic stem cell, and other progenitor cells. Imagine in the remote past a heap of similar tree seeds. These seeds develop in our moderate climate into a tall and many branched tree. Suppose the wind bears a part of the seeds away and brings them to a land possessing different environmental conditions, we will say the arc tic lands. There the seeds may develop but they may pro duce trees no higher than our moss."

Cellular drug resistance is a major limitation to the success of chemotherapy of leu kemia and lymphoma. The importance of this has now been recognized by both clinicians and scientists. It is of utmost importance to bridge the gap between laboratory and clinic in this field of research. This is the main purpose of the series of International Symposia on Drug Resistance in Leukemia and Lymphoma. These are held every three years in Am sterdam, The Netherlands, since 1992. This book contains the proceedings of the third of these meetings, organised in 1998. The book covers all important aspects of drug resistance in leukemia and lymphoma, both in the form of extensive reviews as in manuscripts describing original data. General mechanisms of resistance are discussed, including the drug resistance related proteins p glycoprotein, MRP (multi-drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases. Moreover, more drug type-specific mechanisms of resistance are a topic, such as for glucocorticoids and antifolates. Much in formation is provided on apoptosis and its regulators, and on the results of cell culture drug resistance assays. Several papers focus on the modulation or circumvention of drug resistance.

There should be, and in the best of cases there is, a synergy between basic research and patient care. However, this synergy is hard to develop because the techniques required to be a successful researcher are so different from the skills required to be an outstanding physician. Harold R. Roberts, M.D., of the University of North Carolina at Chapel Hill, is an example of a physician-researcher who has benefited from having his feet in both the world of patient care and the world of the laboratory: he has let clinical problems direct his basic research effort and conversely has adopted research advances in his care of patients. Dr. Roberts's long and continuing career has included many research and clinical advances. He was part of the first group to determine the amino acid sequence of the important thrombin inhibitor hirudin and part of the group that prepared the first cryoprecipitates which were the first alternative to plasma as therapy in hemophilia A. Dr. Roberts has made significant advances in understanding the protein chemistry behind hemophilia B; he was among the first researchers to identify some patients as not being completely deficient but instead as having measurable levels of protein and subsequently demonstrated that this protein was dysfunctional. This important advance led him to a classification scheme for patients into Cross Reacting Material (CRM) positive, negative, and reduced. Dr.