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.

TheobservationthatabloodclotspontaneouslydissolveswasfirstdescribedbyDenys in1889. Subsequently,thebloodclottingsystemwasshowntobeinvolvedintumor growth. Forexample,asearlyas1925,Fisherreportedthataviantissueexplantstrans- formedtomalignancybyvirusesgeneratedhighlevelsoffibrinolyticactivityundercon- ditionsinwhichculturesofnormalcellsdidnot. In1958,theconceptthatan equilibriumexistedbetweenthetendencyofbloodtoclotandtoremainfluidwaspro- posedbyAstrup. Atthattime,itwasbelievedthatthishemostaticbalancewasexplained bytheabilityofpolymerizingfibrintoorchestrateitsownclearancebystimulatingfib- rinolyticactivity. Sincethesepioneeringstudies,considerableinformationhasaccumu- latedthathasdefinedthecomponentsofthecoagulationandfibrinolyticsystemsand howtheyareinvolvedinphysiologicalandpathophysiologicalprocesses. Plasminogen: Structure, activation, and regulationfocusesonthebasicprinciplesandrecentdevelop- mentsintheplasminogen/plasminresearchfieldandhowtheseresultsprovideacon- ceptualframeworkforanunderstandingofthephysiologicalroleofplasminogenin healthanddisease. Theenzymaticcascadetriggeredbyactivationofplasminogenhasbeenimplicated inavarietyofnormalandpathologicaleventssuchasfibrinolysis,woundhealing,tis- sueremodeling,embryogenesis,angiogenesis,andtheinvasionandmetastasisoftumor cells. Thisimpressivelistofphysiologicalfunctionsforplasminogenreinforcesthewide diversityofrolesthatplasminogenplaysinvariousphysiologicalprocesses. Productive plasmingenerationrequirestheassemblyofbothplasminogenactivatorsandplasmino- genonasolidsupportsuchasthefibrinpolymerorthecellsurface. Theregulationof plasminproductioninvolvesacomplexinterplaybetweentheseplasminogenactivators, plasminogenactivatorinhibitors,andplasmininhibitors. Clearly,theexplosivegrowth inthisresearchfieldandthemanyexcitingdiscoveriessuggeststhattheresearchefforts inthenextdecadewillrevealthemechanismsbywhichthecomponentsoftheplas- minogensysteminteractandregulatebothplasminactivationandfunctionatacellular level. Plasminogen: Structure, activation, and regulationisdividedintotwosections. Thefirstsectiondealswiththestructureandregulationofplasminogen. Thechapters inthissectionrangefromdiscussionsofthestructureofplasminogenandtheregulation oftheplasminogengenetodiscussionsofthestructureandregulationofplasminogen activatorsandplasminogenactivatorinhibitors. Alsoexaminedistherelativelynewdata concerningthegenerationofanti-angiogenicmoleculesfromplasminogen. Thesecond sectiondealswiththephysiologicalandpathophysiologicalrolesofplasminogenaswell astheconsequencesofplasminogengeneknockout. Discussionsinthissectioninclude examinationoftheroleofplasminogeninhematopoieticmalignancies,tumorcell progression,angiogenesis,mammaryglandinvolution,woundhealing,andbone readsorption. xi xii Preface Inclosing,Iwouldliketothankmyadministrativeassistant,Ms. ViSommerfeld,for herinvaluableassistanceandtimelesseffortswiththeorganizationandeditingofthebook. Lastly,Iwouldliketoacknowledgetheeffortsoftheauthorsoftheindividualchapters, whoareauthorities inthisfield,foragreeingtotaketimefrombusyschedulestoprovide thesechaptersinatimelyfashion. DavidMortonWaisman Contents Part I. Plasminogen: Structure and Regulation 1. Human Plasminogen: Structure, Activation, and Function FrancisJ. Castellino and Victoria A. Ploplis 1. Introduction 3 2. StructureofHumanPlasminogen...3 2. 1. PrimaryProteinStructure...3 2. 2. GeneOrganization 5 3. ActivationofHumanPlasminogen...6 3. 1. ActivationbyPhysiologicalActivators 7 3. 1. 1. Urokinase-typePlasminogenActivator...7 3. 1. 2. Tissue-typePlasminogenActivator...8 3. 2. ActivationbyBacterial-derivedPlasminogenActivators...9 3. 2. 1. Streptokinase 9 3. 2. 2. Staphylokinase...9 4. TargetsforPlasminActivity...9 5. DysplasminogenemiasandPhenotypicManifestations 10 6. Conclusions 11 References...11 2. Plasminogen Activators: Structure and Function Vincent Ellis 1. Introduction ...19 2. SerineProteases...20 3. UrokinasePlasminogenActivator,uPA...21 3. 1. SerineProteaseDomain 22 3. 2. N-terminalDomains...24 3. 2. 1. KRModule 24 3. 2. 2. EGModule 24 4. MechanismsRegulatinguPAFunction...25 4. 1. ZymogenActivation...25 4. 2. ZymogenActivity...26 4. 3. ReciprocalZymogenActivation 27 4. 4. uPARStimulationofPlasminogenActivation...27 4. 4. 1. uPAandtheTemplateMechanism 28 4. 4. 2. PlasminogenandtheTemplateMechanism 29 4. 5. AvianuPA,aSpecialCase? 30 xiii xiv Contents 5. TissuePlasminogenActivator,tPA...30 5. 1. SerineProteaseDomain 31 5. 2. N-terminalDomains ,...33 5. 2. 1. KRModules ,. . ,. . ,...33 5. 2. 2. F1-EGSupermodule 33 6.

All physicians practicing medicine encounter patients suffering from cardiovascular disease. This book has been outlined in such a way that vascular surgeons, general internists, neurologists and cardiologists should be able to use it. The book covers the complete scope of cardiac diseases in addition to chapters on hypertension and atherosclerosis. In many patients there is a family history of cerebrovascular accidents, myocardial infarction or peripheral arterial disease. Also in patients reporting collaps, palpitations and arrhythmias the family is crucial and can provide clues to a genetic cause of the disease. This book is published to guide physicians in the process of determining whether a genetic component is likely to be present. Furthermore, information is provided what the possibilities and limitations of DNA diagnostic techniques are. Finally, the importance of newly identified categories of potential patients, i. e. gene carriers without symptoms or any inducible sign of disease, is highlighted. For some patients a genetic diagnosis is essential to determine appropriate therapy and for counseling? In some other diseases DNA diagnostic tools are available but the relevant for the patients may be less clear. In other families the search for a disease causing gene is ongoing and the possibilities to find genes and to unravel the pathophysiology of the disease is limited by the lack of patients. To give insight into the current state of genetic diagnostics, the authors have classified the cardiovascular diseases.

The International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis was held in Academia Sinica, Taipei, Taiwan, Republic of China, on August 30 - September 1, 1989. This Symposium has provided a forum for the free exchange of information in this important and rapidly advancing research field. This proceedings volume provides a published record of 46 papers presented at the Symposium. The sponsors have exerted no influence on the scientific opinions or positions of the participants in the Symposium. It is hoped that this Symposium will stimulate further worldwide cooperation and collaboration in these vital fields for the benefit of all human kind. This volume is composed of four parts. The first part consists of 8 papers on Fibrinogen and Fibrin: Biochemistry, Molecular Biology, and Physiology. The second part contains 16 papers on Coagulation and Fibrinolysis: Biochemistry, Molecular Biology, and Physiology. The third part has 10 papers on Cardiovascular Cell Biology: Biochemistry, Molecular Biology, and Physiology. The fourth part comprises 12 papers on Clinical Studies of the Cardiovascular System: Thrombotic and Bleeding Disorders and Thrombolytic Therapy. The Author Index with addresses of all contributors and the Subject Index of all 46 papers are arranged at the end of this volume.

th It is a great pleasure for me to open the jubilee 25 International Symposium on Blood Transfusion here in Groningen. This symposium is co-sponsored by the World Health Organization and is being held under the auspices of the ISBT and the Secretary General of the Council of Europe, Mr Walter Schwimmer. The patronage was granted with great pleasure for several reasons. First of all, Dutch experts are very active in our Committees and have largely contributed in developing the Council of Europe principles in the blood area. Secondly, the Council of Europe is active today in the area of blood transfusion due to a tragic event, which occurred in 1953 in the Netherlands; following a flooding many of the blood products given for assistance' could not be used due to incompatibilities and differences in labelling. Some words to present the Council of Europe since the organisation is sometimes confused with institutions ofthe European Union: The organisation has been founded in 1949 to establish the principles of democracy and rule of law all over Europe. Since 1989, the year of the fall of the Berlin wall and the opening up of the iron curtain, these principles could be extended to the countries of Central and Eastern Europe. Today this makes the Council of Europe the only pan-European organisation with 41 Member States thus representing more than 750 million people.

Scintigraphic imaging with radiolabeled blood elements has continued to be a useful diagnostic modality. The major trust of recent investigation has been in simplifying labeling techniques and developing new agents that will label blood elements selectively in vitro. The VI Symposium of the International Society of Radiolabeled Blood Elements was held in Barcelona (Spain) during November 23 to 27, 1992.The conference was sponsored by the NATO Scientific Affairs Division, the USA Department of Energy and the Spanish National Health Service. This monograph comprises articles that represent most of the 85 papers (70 oral and 15 posters) presented during the symposium. The meeting was attended by 110 investigators hailed from 21 countries. Although lllIn-oxine and 99mTc-HMPAO remain the choice agents for labeling blood components for routine applications, there was heavy emphasis on developing new labeling agents that will either simplify the in vitro labeling procedure, or, even better, will label blood components selectively in vivo, by injecting the radioactive agents directly into patients. The degree of success in imaging target lesions in humans by using these agents has been excellent.

These Proceedings contain the contributions of the partIcIpants of the Third International Symposium on Dendritic Cells that was held in Annecy, France, from June 19 to June 24, 1994. This symposium represented a follow-up of the first and second international symposia that were held in Japan in 1990 and in the Netherlands in 1992. Dendritic cells are antigen-presenting cells, and are found in all tissues and organs of the body. They can be classified into: (1) interstitial dendritic cells of the heart, kidney, gut, and lung;(2) Langerhans cells in the skin and mucous membranes; (3) interdigitating dendritic cells in the thymic medulla and secondary lymphoid tissue; and (4) blood dendritic cells and lymph dendritic cells (veiled cells). Although dendritic cells in each of these compartments are all CD45+ leukocytes that arise from the bone marrow, they may exhibit differences that relate to maturation state and microenvironment. Dendritic cells are specialized antigen-presenting cells for T lymphocytes: they process and present antigens efficiently in situ, and stimulate responses from naive and memory T cells in the paracortical area of secondary lymphoid organs. Recent evidence also demonstrates their role in induction of tolerance. By contrast, the primary and secondary B-cell follicles contain follicular dendritic cells that trap and retain intact antigen as immune complexes for long periods of time. The origin of follicular dendritic cells is not clear, but most investigators believe that these cells are not leukocytes.

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

The title "Stem Cells from Cord Blood, In Utero Stem Cell Develop ment, and Transplantation-Inclusive Gene Therapy" suggests that more than one topic is combined in one workshop. Indeed, at first glance the recovery of stem cells from cord blood has to be seen as separate from the attempts to achieve effective in utero therapy by stem cell trans plantation, because the first issue deals with an innovative stem cell source as an alternative to bone marrow, which is already spreading rapidly in medical practice, whereas the second topic is still strictly ex perimental and only investigated in medical centers with the appropri ate background. It is, however, not only justified, but helpful to com bine the two topics in one workshop and consequently to cover them in the same volume of the Ernst Schering Research Foundation Work shop series, because they are intimately related and both based on the new insights into the biology of stem cells. Professor Werner Arber, the Nobel Laureate from the University of Basel, pointed out in his In- Professor Dr. W. Holzgreve VI Preface The participants of the workshop troductory Lecture that our understanding of hematopoietic stem cells as descendents of totipotent cells and our current approaches to using them in post-and prenatal therapy have been furthered significantly by genetic engineering technologies which are "artificial contributions to the process of biologic evolution.""

Oncology has developed as a subspecialty of medicine with unique and often complex clinical problems. This handbook ofhematologic and oncologic emer gencies provides a compact, concise, yet comprehensive guide to the manage ment of a variety of difficult clinical situations. The authors of the various chapters are all clinicians with experience in the management of these difficult patients. Their efforts provide insight and a ready source of practical infor mation which lends itself to use in the clinic and in the inpatient ward. The authors sincerely hope that this handbook will be of service to house officers and fellows alike, as they develop skills in the management of the emergent problems of patients with hematologic and other neoplasms. Janice P. Dutcher Peter H. Wiernik Bronx, New York;; Contents 1. Syndrome of Inappropriate Antidiuretic Hormone Secretion and Hyponatremia . . . . . . . . . . . . . . . . . . . . . . . . 000 . . . . . . . . . . . Stuart L. Marcus, M.D., Ph.D., and Joachim Z. Fuks, M.D. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3. Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. Acute Tumor Lysis Syndrome: Prevention and Management . . 9 Stuart L. Marcus, M.D., Ph.D., and Avi I. Einz;ig, M.D. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2. Risk Factors for the Development of Azotemia in Acute Tumor Lysis Syndrome........................................... 10 3. Metabolic Abnormalities That Occur during Acute Tumor Lysis Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 . . . . . . . . . . . . . . 4. Prevention of Acute Tumor Lysis Syndrome: Management prior to Beginning Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . 5. Posttreatment Management: Indications for Dialysis . . . . . . . . . . 14 . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 . . . . . . . . . . . . . ."

The International Symposium on Heparin, held May 13-15, 1974, in St. Louis, Missouri, as a part of the dedication of the Shoenberg Pavilion of the Jewish Hospital of St. Louis, was conceived as a forum to bring together physicians and scientists with a basic in terest in the structure, function and clinical usefulness of heparin. Few naturally occurring substances have commanded the breadth of interest among members of the biomedical research community as this compound has. Aspects of its covalent and three-dimensional struc ture, its biosynthesis, its interaction with and effect on physio logically important moieties and its use as a therapeutic agent in a variety of disease states have been actively studied for the past several decades. Thus, the present state of these studies seemed to be a timely subject for discussion, not only to gather together in one place representative samples of the myriad of data on heparin but also to underscore the ever increasing necessity for communica tion between basic research and clinical practice."

A description of the latest methods of oncological and hematological diagnostics, such as immunological, molecular genetic and histological essays. All methods are described in principle in their different variations and compared with regard to their effectiveness and cost. Written for scientists, clinicians and personnel in research, specialised and routine diagnostic laboratories in hospitals, this book satisfies the increased demand for information on new methods in hematology and oncology.

380 years ago, in the year 1614, Ubbo Emmius transplanted the gene ofscience from Ostfriesland into the education genome ofthe city ofGroningen as devel- oped by Regnerus Praedinius. He thereby founded the University ofGroningen. It is with great pleasure that the Faculty of Medicine as one of the founding faculties ofour University, welcomes you to this 19th International Symposium ofBloodTransfusion, whichwill coverthe themeofHereditaryDiseasesandtheir relation to Transfusion Medicine, where cell expansion, gene transfer and gene therapy are the read thread. Since the earlydays there has beena specificand sincere interest in inborn errors ofmetabolism and hereditarydisorders. This interest has resulted in a structured research, diagnostic and counselling facilities, and therapeuticapproaches where various disciplines within our faculty work closely together with groups from related faculties of the University of Groningen, as well as other national and international scientific institutions. The field of inborn errors, genetic abnormalities and mutations, and hereditary diseases covers a broad gamma of extremely interesting and exciting scientific aspects,whichrangefrom clearphysicalaberrationstomolecularanalysisofgenes and genomes, coding areas and amino acid sequences. It is intriguing to realise that the balance of life seemingly depends on the position or presence of one single molecule as a part ofthe total complex ofgenetic information in the cell.

Since the first concepts of gene therapy were formulated, the hemopoietic system has been considered the most natural first target tissue for genetic manipulation. The reasons for this include the fact that a very large number of inherited disorders (including some of the most common disorders, such as the hemoglobinopathies) are disorders of the hemopoietic system, and the large amount of experience in hematopoietic transplantation biology. The consequence of this resulted in the first clinical trial of gene therapy in 1989, where two children suffering from severe combined immune deficiency (ADA-SCID) were transplanted with T-cells express ing adenosine deaminase (the defective enzyme in patients with this disorder). The partial success of this treatment was perhaps responsible for undue optimism among those proposing other gene therapy treatments within the hematopoietic system, and it has since become clear that there are a number of technical and biological difficulties to overcome before hematopoietic gene therapy becomes a mainstream therapeutic strategy. The chapters in this book evaluate the need for gene therapy in the hematopoietic system, discuss how efficient gene transfer and expression can be achieved in the target cells, highlight areas of difficulty to be addressed, and examine a number of potential applications of the gene therapy approach. The book begins with a chapter by Testa and colleagues, discussing the various sources of hematopoietic cells for both transplantation and gene therapy.

This book reflects the personal prejudices I have developed in twenty years of reading the scientific literature. I like monographs; good ones assemble a great deal of information in a logical sequence and in enough detail to enable one to see why current beliefs are held. For this purpose, it is entirely useless to write "as Smith has shown21 ,81,117 **** " That only means that one must go to the library and turn up Smith's original papers, and one's object in reading a monograph is precisely to avoid that neces sity. One needs to know what Smith did and why he thought his observa tions proved whatever he claimed. Because life is short, it is impossible to deal with several thousand papers in this way, and the author must there fore select a relatively few papers that he regards as crucial. Often, several papers of equal merit might be quoted, and the selection is then arbitrary. I therefore apologize to authorities who do not find their work discussed. Omission does not mean that I thought their work was not valuable; it means only that I preferred to quote twenty references that people might read rather than two thousand that assuredly no one would read. Another strong prejUdice is that the full understanding of present knowledge requires one to know how present views have developed.

Pocket Reference to Renal Anemia, Second edition, provides a comprehensive overview of anemia in patients with renal disease, including the definition and causes of renal anemia, current management approaches, and the latest clinical practice guidelines. Key learning points are highlighted throughout the book and also listed at the end of the book for a quick reference. The book is useful for general physicians, fellows, and other healthcare professionals wishing to learn more about renal anemia.

Multiple myeloma is currently still an incurable disease, but during the past decade knowledge of its molecular pathogenesis has increased rapidly. This has led to remarkable progress in both diagnosis and therapy, including in particular the approval of novel and first-in-class drugs such as thalidomide, bortezomib, and lenalidomide. This book, written by internationally acknowledged experts, covers a wide range of topics relating to multiple myeloma, including history, epidemiology, pathophysiology, clinical features, staging, and prognostic systems. The principal focus, however, is on therapy, with detailed information on the various promising treatment options which give hope that this cancer will be transformed into a chronic disease or even become curable. Individualized therapy and the variety of supportive treatment options, as described in this volume, will help in achieving this goal, as well as in reducing adverse events and improving quality of life.

Under the broad heading of blood oxygenation there may be specific areas of study, such as the kinetics of the oxygen hemoglobin reaction, diffusion of gases through the red cell, blood preservation, blood chemistry, oxygen electrode design and the design and evaluation of artificial blood oxygenators. ~lood oxygenation is of interest to many disciplines including physicians, chemists, physicists, biologists, physiologists and engineers. The International Symposium on Blood Oxygenation was or ganized in order to bring together the people working in the various areas of blood oxygenation. This multidiscipline meet ing was held at the University of Cincinnati on December 1, 2 and 3 of 1969. It was jOintly sponsored by the U. S. Army Medi cal Research and Development Command and the University of Cin cinnati. Participants came from Australia, England, Israel, Italy, Japan and the United States. There were 122 persons registered for the Symposium. From the nature of the discussion during the meeting, it seemed apparent that the participants were benefiting from the contacts with colleagues in other disciplines. The result was a significant contribution to the present fund of knowledge of blood oxygenation and an enhancement of the future work.

This comprehensive treatise on the reticuloendothelial system is a project jointly shared by individual members of the Reticuloendothelial (RE) Society and bio medical scientists in general who are interested in the intricate system of cells and molecular moieties derived from those cells which constitute the RES. It may now be more fashionable in some quarters to consider these cells as part of what is called the mononuclear phagocytic system or the lymphoreticular sys tem. Nevertheless, because of historical developments and current interest in the subject by investigators from many diverse areas, it seems advantageous to present in one comprehensive treatise current information and knowledge con cerning basic aspects of the RES, such as morphology, biochemistry, phylogeny and ontogeny, physiology, and pharmacology as well as clinical areas including immunopathology, cancer, infectious diseases, allergy, and hypersensitivity. It is anticipated that, by presenting information concerning these apparently het erogeneous topics under the unifying umbrella of the RES, attention will be focused on the similarities as well as interactions among the cell types constitut ing the RES from the viewpoint of various disciplines. The treatise editors and their editorial board, consisting predominantly of the editors of individual vol and enormous task umes, are extremely grateful for the enthusiastic cooperation undertaken by members of the biomedical community in general and especially and Japanese Reticuloen by members of the American as well as European dothelial Societies.