I am prepared to predict that this monograph by Dr. Ernest Beutler will long serve as a model for monographs dealing with topics in medical science. I make this bold statement because we encounter in this work a degree of accuracy and authoritativeness well beyond that found in much of the medical literature. Too often, a monograph is simply a review of past reviews. The preparation of an exhaustive and completely accurate study such as the present one is a very laborious task; consequently, many authors make extensive use of the reviews of earlier writers assum ing that the latter have checked and evaluated each previously published report. Unfortunately, however, this assumption of validity has not al ways been correct. Dr. Beutler, who is a world authority on the subject about which he writes, was determined to make this book as correct and complete as possible, and, to this end, has checked all the original sources. Nowhere else will such an exhaustive bibliography be found. Moreover, he has also undertaken to reevaluate in the light of current knowledge material pub lished in earlier days. This he is eminently able to do, and in some in stances his investigations have resulted in new interpretations. The result is a volume that will be recognized as truly the last word on this important subject.

Kurz nach Erscheinen unseres Handbuchs iiber die Non-Hodgkin-Lymphome wurden Stimmen laut, die nach einem klein en handlichen AbriB der Lymphom- diagnostik riefen. Auch die Mitglieder des Europiiischen Lymphom-Clubs (1. DIEBOLD, Paris, R. GERARD-MARCHANT, Villejuif, Y. KAPANCI, Genf, G. KE- LENYI, Pecs, H. NOEL, Briissel, F. RILKE, Mailand, A.G. STANSFELD, London, und J.A.M. VAN UNNIK, Utrecht) bestiirkten mich darin, einen solchen Ratgeber fUr den diagnostischen Alltag zu schreiben. Ja sie identifizierten sich mit diesem Plan und stell ten sich fUr die Obersetzung in mehrere Sprachen zur VerfUgung. So habe ich J. DIEBOLD, R. GERARD-MARCHANT, F. RILKE und A.G. STANSFELD fUr die prompte Obertragung ins Franzosische, Italienische und Englische zu danken. F. RILKE iibernahm die Initiative, einen Beitrag zur "Working Formula- tion for Clinical Usage" zu verfassen. Obersetzungen in weitere Fremdsprachen wurden von ehemaligen Mitarbeitern und befreundeten Kollegen bereitwillig durchgefUhrt, so von A. LLOMBART BOSCH ins Spanische, von IRENE LORAND und J.M. MACHADO ins Portugiesische und von N. MOHRI ins Japanische. Das Erscheinen in verschiedenen Sprachen einschlief3lich meiner Muttersprache sollte den Gebrauch des Abrisses im Alltag we iter erleichtern.

The development of new techniques such as immuno phenotyping, cytogenetic investigations and, more recently, molecular studies has considerably increased our diagnostic repertoire and broadened our ideas about the biology of acute leukemias. While immunophenotyping with mono clonal antibodies has yielded increased diagnostic precision and made it possible to develop a highly reproducible classification of acute leukemias based on cell-biological features, further insights have been gained into the patho genetic mechanisms involved in leukemogenesis by means of cytogenetic detection of acquired structural chromosomal abnormalities. Analysis of the leukemia-associated chromo somal breakpoints using molecular techniques can now pinpoint many genomic sites essential for normal develop ment and maturation of hematopoietic cells but functionally disrupted in leukemic cells. The main goal of the international workshop that we held in Berlin with a select group of scientists and clinicians involved in leukemia research was to describe the state of the art and new developments in the immunologic, cytogenetic, and molecular characterization of acute leukemias and to discuss the clinical importance of cell biological features. After introductory survey lectures dealing with the immunological and molecular-biological characteristics of normal vs. malignant lymphatic and myeloid progenitor cells, the workshop centered on con tributions characterizing the immunophenotype and both numerical and structural chromosomal abnormalities in acute leukemias."

Each of the four authors of this book has a particular interest in disorders of porphyrin metabolism and special experience in their management. Their individual involvement in the field varies from 12 to 52 years and, combined, represents more than a century of personal experience. Since it has been written by both basic scientists and practicing physicians, the book is intended to be of value to all those involved in porphyrin metab olism and the porphyrias. It is hoped that the fascination of porphyrin metabolism and the clinical challenge of the porphyrias experienced by each of the authors will be conveyed to the readers. Michael R. Moore Kenneth E. L. McColl Claude Rimington Abraham Goldberg vii CONTENTS Color Plates ............................................ xvii 1. The History, Classification, and Incidence of the Porphyrias 1 1.1. History ........................................ 1 1.1.1. Early Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1.2. Early Descriptions of Porphyria .............. 4 1.1.3. Biochemical Developments .................. 4 1.1.4. Acute Porphyria . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1.1.5. A Complete Pathway ...................... 8 1.2. Classification of the Porphyrias . . . . . . . . . . . . . . . . . . . . . 9 1.2.1. The Current Classification. . . . . . . . . . . . . . . 12 . . . .

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."

On March 27, 1990, the National Cancer Institute sponsored a workshop on the epidemiology of multiple myeloma, held at the National Institutes of Health. This book comprises articles prepared by participants in this work shop. Discussed in these papers are: the descriptive and analytic epidemi ology, differences in risk factors between blacks and whites, monoclonal gammopathies and their progression, and hypotheses regarding the etiology and pathogenesis of multiple myeloma. Several epidemiologic research areas received particular attention during this workshop, and are reviewed in detail in this volume. There have been striking increases in the incidence of multiple myeloma over the past thirty years, especially among older individuals and blacks, which may not be entirely explained by changes in diagnostic capabilities. Occupational and environmental exposures have been associated with an increased risk of multiple myeloma, including farming exposures, occupational exposure to petroleum and rubber processing, exposure to ionizing radiation, and asso ciations with persistent virus infections. The most striking epidemiological finding is reflected in the differences in incidence rates of multiple myeloma which are twice as high in blacks as compared with whites. Further, since 1950 the mortality rates for multiple myeloma have quadrupled in blacks while doubling for whites. Among hematopoietic malignancies, multiple myeloma is the only one with increased incidence and mortality rates among blacks. 1\vo major possibilities for explaining ethnic/racial differences in suscepti bility to multiple myeloma are genetic and environmental factors.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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.

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.

Jaundice ofnewbom infants was described by several authors in the 17th century. The condition, however, was usually thought of as being similar to adult jaundice and due ro occlusion of the bile ducts by 'glutinous humours'. On the other hand, some writers reported on the fact that more than one consecutive baby was often affected, and there is a classic example of the disease in twins written by Louyse Bourgeois, the midwife of Marie de Medici, in 1609. It was not until early in the 20th century that it was realised that the common link between these familial cases was anaemia, and later still that this was of the haemolytic type. The breakthrough, in terms of an idea, came in 1938, when Darrow postulated that the baby's red cells were destroyed by an immune reaction on the part of the mother, the result of immunisation by paternal factors in the fetus. Shortly afterwards Wiener discovered an entirely new blood group system, 'Rh', and it was found that it was in compatibility within this system that was responsible for the vast majority of cases of haemolytic disease of the newborn."

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. "

Scientific and Ethical Discipline in Clinical Trials on Acute Leukemia G. MATHE Institut de Cancerologie ct d'Immunogenetique "', Hi'ipital Paul-Brousse "."", Villejuif/France Clinical research is still in an evolutionary stage. Although scientific technology was readily accepted and applied, scientific methodology has been accepted much more slowly and is very rarely properly applied. There are three reasons why this is so. First, medical ethics frequently limits the applicability of clinical research, for doctors have to be more than scientists. They must also remain moral philosophers, as they were before medicine became a science. Second, the heterogeneity of the material on which clinical researchers work in studying human diseases makes the application of scientific methodology difficult. Third, researchers must publish. This means that they must obtain publishable results, and too often this means results in accordance with established concepts, easily accepted by the editors of established journals, which are read by the establishment. It is the privilege of too many people to be able to accept "truth" and recipes from other people and confirm their truth and results. It is the mission of a very few others to accept nothing as "truth" and to consider no recipe ideal, either in concept or detail.

After many years of relative neglect, the importance of study of factors governing blood flow has at last achieved recognition; in this volume are documented many of the techniques, and the basic scientific and clinical observations, which have helped to open up understanding of this highly important aspect of human physiology and pathology in recent years. The text is logically divided into five sections beginning with blood cell deformability, then moving on to theoretical consideration of blood rheology, followed by accounts of the interrelationships between rheology, blood flow and vascular occlusion. The final two sections deal with blood rheology in clinical practice and therapeutic aspects of the study of blood flow. As regards blood cell deformability (Section A), the basic problem is set out by Kiesewetter and colleagues in the first paragraph of chapter 1 (p. 3), in which they point out that whereas human erythrocytes at rest have a diameter of approxi mately 7. 5 /-tm, nutritive capillaries have diameters ranging from 3-5 /-tm, and chapters in section A give an account of the ways in which the red cell can undergo deformation to permit capillary perfusion and the maintenance of the microcirculation."

The first International Meeting on Apheresis was held in Dyon in 1984. At the congress it became clear that both the technical and therapeutic sides developed very rapidly and it appeared fruitful to bring together the investigators of the different countries working in the areas. At that time immunology had come to pervade many clinical specialities, and hemapheresis, especially plasmapheresis was considered a therapeutic tool in many immunological diseases which hitherto had proved to be fatal. New methods to identify certain antibodies and circulating immune complexes in the serum and the possibilities to remove them from the blood by several techniques (filtration, centrifugation, immunoabsorp tion) led to an almost uncontrolled use of plasma exchange in a variety of diseases. Since then the technical possibilities of this technique were further recognized, as was the impact of immunology on many diseases, and the possibilities to collect specific components for therapeutic pur poses. But also we became aware of the limited contributions of anec dotal data on successes or failures of apheresis as adjuvant treatment. Therefore international prospective studies were initiated to make critical assessment possible of apheresis in various diseases.

In transfusion medicine the scientific fundamentals of immunology have had a considerable clinical impact. Transfusion may suppress the immunity but some patients could suffer disadvantages including GvHD, alloimmunisation and possible cancer, where white cells (WBC) play pivotal roles in this phenomenon, presenting antigens and producing cytokines. A clinical application of this practice is LAK-cells targeted against cancer. MHC on the WBC may provide additional immunological modulations through series of secondary messengers. Thus reduction of WBC in the blood and bone marrow may be advantageous for patients. On the other hand, sharing a part of MHC or making the transplanted white cells anergic by storage may be even more advantageous for patients. CMV infection could mimic part of this MHC. UV radiation is effective in the inactivation of the WBC although filters are easy means for such removal. However, their accurate quantification requires flow cytometry that has considerable potential application in blood transfusions. Idiotypic antibody could play an important role in platelet theory. However, the potential infection risks in transfusion like HIV and HCV remain, but application of molecular biological methods like PCR or RT/PCR has great potentials in detection of infectious diseases, transplantation and genetic disorders. Immuno affinity purified concentrates, like factor IX and protein C, could reduce patients' immune functions, where in the future protein C could be derived from transgenic animals. Advances are sure to emerge through adoptive immunotherapy and gene therapies are exciting prospects when genes transferred into lymphocytes could be used to correct cell mediated immune deficiency, as in ADA.

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."

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."

The hematopoietic system plays roles that are crucial for survival of the host: delivery of oxygen to tissues, arrest of accidental blood leaking from blood vessels, and fending off of invading microbes by humoral, cell-mediated, and phagocytic immunity. The activity of the hematopoietic system is staggering: daily, a normal adult produces approximately 2.5 billion erythrocytes, 2.5 billion platelets, and 1 billion granulocytes per kilogram of body weight. This production is adjusted in a timely fashion to changes in actual needs and can vary from nearly none to many times the normal rate depending on needs which vary from day to day, or even minute to minute. In response to a variety of stimuli, the cellular components of the blood are promptly increased or decreased in production to maintain appropriate numbers to optimally protect the host from hypoxia, infection, and hemorrhage. How does this all happen and happen without over or under responding? There has been extraordinary growth in our understanding ofhematopoiesis over the last two decades. Occupying center stage is the pluripotent stern cell and its progeny. Hematopoietic stern cells have been characterized by their capacity for self renewal and their ability to proliferate and differentiate along multiple lineages. Few in number, the stern cell gives rise to all circulating neutrophils, erythrocytes, lymphoid cells, and platelets. In hematopoietic transplantation, the stern cell is capable of restoring long-term hematopoiesis in a lethally irradiated host.

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.

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.

1 2 D. FITZGERALDI, I. PASTAN , and J. ROBERTUS Introduction . . . . . . . . . . . . . I 2 Toxin Structure-Function Properties 2 2. 1 Functions. . . . . . . . . . . . . . . . . . . . . . . . 2 2. 2 Binding. . . . . . . . . . . . . . . . . . . . . . . . . 3 3 Intracellular Processing - Cleavage and Reduction . . . . . . 4 3. 1 Cytosolic Activity . . . . . . . . . . . . . . . . 5 4 Immunotoxin Design and Testing. 6 5 Conclusion. . 8 References. . . . . 8 1 Introduction While various treatment approaches for cancer include reversal of the transformed phenotype, stimulation of immune responses, inhibition of metastatic spread and deprivation of key nutrients, the goal of immunotoxin treatment is the direct killing of malignant cells. Because they are enzymatic proteins that act catalytically to kill cells, bacterial and plant toxins are often employed as the cell-killing component of immunotoxins. Here we provide background information into the structure-func tion relationships of toxins and discuss how they can be combined with cell-binding antibodies or other ligands to generate immunotoxins. Bacterial and plant toxins (e. g. , diphtheria toxin, Pseudomonas exotoxin and ricin) are among the most toxic substances known. However, because they bind to cell surface receptors that are present on most normal cells, unmodified toxins are generally useless as anti-cancer agents. To convert toxins into more selective agents, their binding domains are either eliminated or disabled and replaceq with cell binding antibodies that are tumor-selective.

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."