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The Year in Hematology 1977 the Year in Hematology 1977 The Year in Hematology 1977 The Year in Hematology 1977 Edited by AlbertS. Gordon, Ph.D., F.R.S.M. Graduate School of Arts and Science New York University New York, New York Robert Silber, M.D. New York University School of Medicine New York, New York and Joseph LoBue, Ph.D. Graduate School of Arts and Science New York University New York, New York SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging in Publication Data Main entry under title: The Year in hematology, 1977. Includes bibliographies and index. 1. Hematology. 2. Blood-Diseases. I. Gordon, Albert Saul, 1910- II. Silber, Robert, 1931- III. LoBue, Joseph. (DNLM: 1. Hematology-Period, W1 YE395) RC633.Y4 616.1'5 77-8412 ISBN 978-1-4899-6690-2 ISBN 978-1-4899-6688-9 (eBook) DOI 10.1007/978-1-4899-6688-9 © Springer Science+Business MediaNew York 1977 Originally published by Plenum Publishing Corporation in 1977 Softcover reprint of the hardcover 1st edition 1977 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors John W. Adamson, M.D., Associate Professor of Medicine, Division of Hematology, Department of Medicine, University of Washington School of Medicine; and Chief, Hematology Section, Veterans Administration Hospital, Seattle, Washington Israel F. Charo, M.S., M.D., Ph.D. Candidate, Department of Biochemis­ try, State University of New York Downstate Medical Center, Brook­ lyn, New York 11203 W. Cieplinski, M.D., Ph.D., Research Associate, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 Martin J. Cline, M.D., Bowyer Professor of Medical Oncology, and Chief of Hematology-Oncology, Department of Medicine, University of California School of Medicine, Los Angeles, California 90024 Harvey J. Cohen, M.D., Ph.D., Associate, Division of Hematology­ Oncology, Children's Hospital Medical Center; and Assistant Profes­ sor of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115 Neville Colman, M.B., B.Ch., Ph.D., Research Associate, Veterans Administration Hospital, Bronx, New York 10468; and Assistant v vi CONTRIBUTORS Professor of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York 11209 Maryrose Conklyn, B.S., Graduate Student, Department of Biology, New York University Graduate School of Arts and Sciences, New York, New York 10003 Maria da Costa, M.D., Associate Professor of Medicine, Division of Hematology/Oncology, Department of Medicine, New York Medical College, New York 10029 Thomas C. Detwiler, Ph.D., Professor of Biochemistry, Department of Biochemistry, State University of New York Downstate Medical Cen­ ter, Brooklyn, New York 11203 Alfred G. Ehlenberger, M.D., Ph.D., Resident, Department of Psychia­ try, Stanford University Medical Center, Palo Alto, California 94304 Michael L. Freedman, A.B., M.D., Professor of Medicine, Department of Medicine, New York University Medical Center, New York, New York 10016 Robert C. Gallo, M.D., D.Sc. (hon.), Chief, Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20014; and Adjunct Professor of Genetics, George Washington University, Washington, D.C. 20007 David H. Gillespie, Ph.D., Head, Nucleic Acid Hybridization Section, Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20014 David W. Golde, M.D., Associate Professor of Medicine, University of California School of Medicine, Los Angeles, California 90024 Ronald B. Herberman, M.D., Chief, Laboratory of Immunodiagnosis, National Cancer Institute, Bethesda, Maryland 20014 Victor Herbert, M.D., J.D., Director, Hematology and Nutrition Labora­ tory, Veterans Administration Hospital, Bronx, New York 10468; and Professor of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York 11209 Elizabeth Jacob, M.D., Assistant Professor of Medicine, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York 11209 Simon Karpatkin, M.D., Professor of Medicine, New York University Medical School, New York, New York 10016 Sanford B. Krantz, M.D., Professor of Medicine and Chief of Hematol­ ogy, Departments of Medicine, Vanderbilt University School of \1ed­ icine; and Veterans Administration Hospital, Nashville, Tennessee 37203 CONTRIBUTORS vii Mahin D. Maines, Ph.D., Associate Professor, The Rockefeller Univer­ sity, New York, New York 10021 Julia A. McMillan, M.D., Assistant Instructor, Department of Pediatrics, State University of New York, Upstate Medical Center, Syracuse, New York Victor Nussenzweig, M.D., Professor of Pathology, Department of Pathology, New York University School of Medicine, New York, New York 10016 Frank A. Oski, M.D., Professor and Chairman, Department of Pediatrics, State University of New York, Upstate Medical Center, Syracuse, New York Oscar D. Ratnoff, M.D., Professor of Medicine, Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals of Cleveland, Cleveland, Ohio 441 06; Career Investigator of the American Heart Association Sheldon P. Rothenberg, M.D., Professor and Vice Chairman, Depart­ ment of Medicine, and Chief, Division of Hematology/Oncology, New York Medical College, New York, New York 10029 M.D. Scharff, M.D., Professor and Chairman, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 Robert Silber, M.D., Director of Hematology and Professor of Medicine, New York University School of Medicine, New York, New York 10016 Thomas P. Stossel, M.D., Chief, Medical Oncology Unit, Massachusetts General Hospital; and Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts 02114 S. Donald Zaentz, M.D., Assistant Professor, Departments of Medicine, Division of Hematology, Vanderbilt University School of Medicine; and Veterans Administration Hospital, Nashville, Tennessee 37203 Preface Scientists, physicians, or students cannot be considered educated unless acquainted with the important developments in their chosen discipline. Over the last decade there has been an enormous production of valuable experimental and clinical observations in hematology. The published information must be assessed as to how the new differs from the old, what can be discarded as of little use, and what should be avidly pursued in the hope of yielding significant answers to important questions. This review series will endeavor to provide a critical appraisal of some recent observa­ tions of the normal and abnormal functions in the hematopoietic system, the overall objective being to provide current information in fields rich in new concepts which point the way to future work. The contributors to this first volume have attempted to present a summary of some high points of recent research against a background of historical perspective. Good reviews are not born from an instinctive ability for preparing compendia. Instead, they are the result of intelligent, patient, critical analysis which culminates in a scholarly labor of love. We thank our contributors for the generous gift of their time, and we trust ix X PREFACE that their efforts will be rewarded by the expert guidance provided to students of hematology. The readers' reaction is invited to guide us in the preparation of future volumes. Albert S. Gordon Robert Silber Joseph LoBue New York Contents Chapter 1 Heme Metabolism: Factors Affecting the in Vivo Oxidation of Heme Mahin D. Maines 1.1. Introduction . 1 1.2. Heme and Bile Pigments . 1 1.3. Mechanism of Heme Oxidation . 6 1.3.1. Nonenzymatic Heme Oxidation . 6 1.3.2. Enzymatic Heme Oxidation . 9 1.3.3. Substrate Specificity. 13 1.3.4. Heme Oxygenase: Postulated Mode of Action . 15 1.4. Factors Regulating Heme Degradation . 17 1.4.1. Heme (Hemoglobin, Hematin, Methemalbumin) . 17 1.4.2. Metals..................................... 19 1.4.3. Hormonal and Metabolic Factors............. 23 1.4.4. Effect of Endotoxins and Drugs on Heme Degradation . 27 1.5. Catabolism of Heme Compounds in Vivo . 29 1.5.1. Hemoglobin . 29 xi xii CONTENTS 1.5.2. Microsomal Cytochromes . 31 1.5.3. Myoglobin and Mitochondrial Cytochromes . 36 References . 38 Chapter 2 Hemoglobin Synthesis in Normal and Abnormal States Michael L. Freedman 2.1. Normal Hemoglobin Synthesis . 47 2.1.1. Ontogeny of Hemoglobin Synthesis . 47 2.1.2. Hemoglobin Synthesis during Erythropoiesis . 48 2.1.3. Transcription, Processing, and Translation of Globin Messenger RNA . 53 2.1.4. Assembly of Hemoglobin.. 60 2.1.5. Molecular Control Mechanisms in Normal Hemoglobin Synthesis . 62 2.2. Abnormal Globin Synthesis . 71 2.2.1. Synthesis of Globin in Thalassemia and Related States . 71 2.2.2. Synthesis of Structurally Abnormal Hemoglobins . 7 8 2.2.3. Synthesis of Hemoglobin in Heme-Deficient States . 82 References . 85 Chapter 3 Clinical Significance of 2,3-Diphosphoglycerate in Hematology Frank A. Oski and Julia A. McMillan 3.1. Oxygen Transport and Delivery . 104 3.2. Factors Modifying Hemoglobin's Affinity for Oxygen . 107 3.3. Clinical Conditions Associated with Alterations in Red Cell 2,3-DPG . 110 3.3 .I. Cardiac Disease . 111 3.3.2. Hypoxemia of Altitude or Pulmonary Disease . 115 3.3.3. Anemia . 117 3.3.4. Abnormalities of Serum Inorganic Phosphate . 118 3.3.5. liver Disease . 119 3.3.6. Endocrine Disorders . 120 3.3.7. Blood Storage and Transfusion . 120 3.3.8. The Newborn Infant . 121 CONTENTS xiii 3.4. Physiologic Significance of Shifts in the Oxygen- Hemoglobin Dissociation Curve . 124 References. 125 Chapter 4 The Interaction of Folate Ligands with Macromolecules Maria da Costa and Sheldon P. Rothenberg 4.1. Introduction . 131 4.2. Methods of Identification of Folate Binding Macromolecules . 132 4.3. Definition of Terminology . 133 4.4. Nonspecific Folate Binder Complexes in Serum . 135 4.5. Specific Folate Binder Complexes in Serum............ 136 4.6. Properties of the Specific Folate Binder in Serum . 138 4. 7. Significance of the Serum Folate Binder . 139 4.8. Serum Folate Binders and Radioassay for Folate . 140 4.9. Folate Binder in Erythrocytes . 141 4.10.
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