Biochemical pharmacology of blood and bloodforming organs
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書誌事項
Biochemical pharmacology of blood and bloodforming organs
（Handbook of experimental pharmacology, v. 101）
Springer-Verlag, c1992
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Includes bibliographical references and index
内容説明・目次
内容説明
How is haematopoiesis fundamentally controlled by haematopoietin and other haematopoietic growth factors? This volume gives an overview of our present knowledge and focuses in particular on recent advances. These include, for example, the purification of erythropoietin and colony stimulating factor and the availability and function of interleukins. Another aspect is the effect of toxic environmental agents on blood and blood-forming organs - how they suppress erythropoiesis, myelopoiesis and megokaryocytopoiesis as well as major haematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 1-alpha and 1-beta, 2, 3, 4, 5, 6 and 7. The contents are completed by chapters dealing with the application of growth factors in the treatment of anemia of end stage renal disease. An up-to-date overview of the chemotherapy of leukemia is also given.
目次
1 Introduction.- 2 Fundamental Control of Hematopoiesis.- A. Introduction.- B. Hierarchical Organization of Hematopoietic Cells.- C. Assay and Characterization of In Vitro Clonogenic Cells.- D. Use of In Vitro Clonogenic Cell Assays.- E. Newer Assays for More Primitive Cells.- F. Regulatory Mechanisms.- G. Future Outlook.- References.- 3 Kidney Regulation of Erythropoietin Production.- A. Introduction.- B. Model for the Control of Erythropoietin Production.- C. Hypoxia and Erythropoietin Production.- D. Adenosine and Erythropoietin Production.- References.- 4 The Mechanism of Action of Erythropoietin: Erythroid Cell Response.- A. Introduction.- I. The Erythropoietin Gene.- II. The Erythropoietin Molecule.- III. Erythropoietin-Responsive Cells.- IV. The Erythroid Burst-Forming Unit.- V. The Colony-Forming Unit Erythroid.- B. Model Systems for Studying the Interaction of Erythropoietin with Erythroid Progenitor Cells.- I. The Erythropoietin Receptor.- C. Interaction of Other Growth and Development Factors with Erythroid Progenitor Cells.- D. The Erythroid Differentiation Program.- I. Gene Expression During Erythroid Cell Differentiation.- E. Signal Transduction in Erythroid Progenitor Cells.- F. Erythropoietin as a Competence or Progression Factor.- G. Conclusion.- References.- 5 The Arachidonic Acid Cascade and Erythropoiesis.- A. Introduction.- I. Background.- II. Classification of Eicosanoids and Their Chemistry.- 1. Prostaglandins.- 2. Thromboxanes.- 3. Hydroperoxy/Hydroxy Fatty Acids.- 4. Leukotrienes.- 5. Diglyceride, Phosphatidic Acid, and Lysophosphatidic Acid.- III. Erythropoiesis and Eicosanoids.- B. Evidence for the Roles of Arachidonic Acid Metabolism in Erythropoiesis.- I. Criteria for Implicating Eicosanoids.- II. Target Cell Responses.- III. Cell-Cell Interactions.- IV. Specific Involvement of the Lipoxygenase Pathway.- C. Future Directions for Research.- References.- 6 Iron Deficiency and Megaloblastic Anemias.- A. Iron-Deficiency Anemia.- I. Introduction.- II. Iron Metabolism.- 1. Iron Absorption.- a) Nonheme Iron Absorption.- b) Heme Iron Absorption.- c) Regulation of Iron Absorption.- 2. Iron Transport.- 3. Intracellular Iron Metabolism.- 4. Iron Storage.- III. Biochemical and Physiologic Roles of Iron in Mammalian Tissues.- IV. Iron-Deficiency Anemia.- 1. Clinical Aspects.- 2. Diagnosis of Iron Deficiency.- 3. Management of Iron Deficiency.- a) Oral Iron Therapy.- b) Parenteral Iron Therapy.- B. Megaloblastic Anemias.- I. Definition and Differential Diagnosis.- II. Clinical Manifestations.- III. Biochemistry of Folic Acid and Vitamin B12.- IV. Vitamin B12 Deficiency.- 1. General Considerations.- 2. Vitamin B12 Metabolism.- a) Vitamin B12 Binding Proteins.- b) Vitamin B12 Absorption.- c) Transport and Intracellular Metabolism of Vitamin B12.- 3. Causes of Vitamin B12 Deficiency.- 4. Diagnosis of Vitamin B12 Deficiency.- 5. Management of Vitamin B12 Deficiency.- V. Folate Deficiency.- 1. General Considerations.- 2. Folate Metabolism.- a) Folate Absorption.- b) Transport and Intracellular Metabolism of Folate.- 3. Causes of Folate Deficiency.- 4. Diagnosis of Folate Deficiency.- 5. Management of Folate Deficiency.- References.- 7 Erythropoietin in the Anemia of End-Stage Renal Disease.- A. Assay of Erythropoietin.- B. Pathogenesis of the Anemia of Chronic Renal Failure.- I. Inhibition of Erythropoietin Action.- II. Inhibition of Heme Synthesis.- III. Inhibition of Colony Formation.- C. Kidney Production of Erythropoietin.- D. Erythropoietin in Therapy of Renal Anemia.- E. Conclusions.- References.- 8 Humoral Control of Thrombocytopoiesis.- A. Introduction.- B. Model for Megakaryocytopoiesis.- C. Controlling Factors.- I. Megakaryocyte-Colony Stimulating Factor.- II. Autoregulation of Megakaryocytopoiesis.- III. Thrombopoietin.- 1. Background and Historical Aspects.- 2. Assays.- 3. Site of Production.- 4. Antibodies to Thrombopoietin.- 5. Purification.- a) Methods for Purification.- b) Characterization of the Molecule.- 6. Effects on Megakaryocytopoiesis.- a) In Vitro Effects.- b) In Vivo Effects.- 7. Effects on Thrombocytopoiesis.- a) Platelet Counts.- b) Platelet Sizes.- c) Isotope Incorporation.- D. Other Factors Affecting Thrombocytopoiesis.- I. Effects of Hypoxia.- II. Effects of Erythropoietin and Other Growth Factors.- E. Clinical Aspects of Thrombopoietin.- F. Future of Thrombopoietin.- References.- 9 Arachidonic Acid Metabolism Platelets and Thromboembolic Disease.- A. Arachidonic Acid Metabolism.- I. Introduction.- II. The Cyclooxygenase Pathway.- III. Shunting of Endoperoxides.- IV. The Lipoxygenase Pathway.- V. The Epoxygenase Pathway.- VI. Pharmacology of Antiplatelet Agents.- B. Thromboembolic Disease.- I. Introduction.- II. Unstable Angina.- III. Acute Myocardial Infarction.- 1. Secondary Prevention.- 2. Coronary Thrombolysis.- 3. Primary Prevention.- IV. Coronary Bypass Grafts.- V. Peripheral Arterial Grafts.- VI. Cerebrovascular Disease.- VII. Prosthetic Valves.- VIII. Coronary Angioplasty.- C. Concluding Comments.- References.- 10 Chemical Agents That Inhibit Platelet Aggregation.- A. Introduction.- B. Platelet Physiology.- C. Platelet Structure.- D. Platelet Involvement in Thrombosis.- E. Platelet Responses.- I. Shape Change.- II. Adhesion.- III. Aggregation.- F. Inhibition of Platelet Aggregation.- I. Cyclic AMP.- II. Cyclic GMP.- III. Receptor Antagonism.- 1. Catecholamines.- 2. Serotonin.- 3. ADP.- 4. Prostaglandin Endoperoxides and Thromboxane A2.- 5. Vasopressin.- 6. Platelet Activating Factor.- 7. Thrombin.- 8. Collagen.- IV. Arachidonate Metabolism.- 1. Source of Arachidonate.- 2. Inhibitors of Phospholipase A2.- 3. Inhibitors of Cyclooxygenase.- 4. Thromboxane Synthase Inhibitors.- 5. Inhibitory Prostaglandins.- V. Experimental Drugs with Unknown Actions.- G. Conclusions.- References.- 11 Anticoagulants, Antithrombotic and Thrombolytic Agents.- A. Anticoagulants.- I. Heparin.- 1. Clinical Applications.- 2. Prophylactic (Low-Dose) Heparin.- 3. Complications.- II New Therapies.- 1. Heparin plus Dihydroergotamine.- 2. Low Molecular Weight Heparins.- III. Oral Anticoagulants.- 1. Complications.- B. Thrombolytic Therapy.- I. Streptokinase.- II Urokinase (and Single Chain Urokinase).- III. Tissue Plasminogen Activator.- IV. Acyl Plasminogen Streptokinase Activation Complex.- V. Novel Approaches.- 1. Defibrotide and Brinase.- VI. Side Effects and Complications.- VII. Clinical Considerations.- 1. Acute Myocardial Infarction (Coronary Thrombosis).- 2. Arterial Occlusion.- 3. Pulmonary Embolism.- 4. Deep Venous Thrombosis.- C. Antithrombotic Therapy.- I. Dextrans.- II. Physical Methods.- III. Refibrinogenating Agents.- References.- 12 Granulocyte-Macrophage Growth Factors.- A. Introduction.- B. Historical Background.- C. Growth Factors.- I. Colony Stimulating Factor-1.- II. Granulocyte-Macrophage-Colony Stimulating Factor.- III. Granulocyte-Colony Stimulating Factor.- IV. Interleukin-3.- D. Other Interleukins.- I. Interleukin-1.- II. Interleukin-2.- III. Interleukin-4.- IV. Interleukin-5.- V. Interleukin-6.- VI. Interleukin-7.- E. Inhibitors.- F. Cellular Production and Networking.- G. Microenvironment.- H. Conclusions.- References.- 13 Chemical Agents Which Suppress Myelopoiesis: Agranulocytosis and Leukemia.- A. Introduction.- B. Normal Marrow Cell Kinetics.- C. Pathophysiologic Mechanisms for Drug-Induced Neutropenia.- D. Neutropenia Associated with Cytotoxic Chemotherapeutic Agents.- E. Drug-Induced Myeloid Suppression.- I. Ethanol.- II. Phenothiazines.- III. Anticonvulsants.- IV. Antiinflammatory Agents.- V. Antiviral Agents.- VI. H2 Receptor Antagonists.- VII. Miscellaneous Agents.- F. Idiosyncratic Neutropenias.- I. Analgesics.- II. Antibiotics.- III. Cardiovascular Drugs and Diuretics.- IV. Thyrostatic Agents.- V. Sulfonamides.- G. Pseudoneutropenia.- I. Complement Activation.- II. Expression of Membrane Adhesion Molecules.- H. Secondary Leukemia.- J. Conclusions.- References.- 14 Drugs Useful in the Chemotherapy of the Acute Leukemias.- A. Introduction.- B. Antimetabolites.- I. Cytosioc Arabinoside (1-?-D-arabinofuranosylcytosine).- II. 6-Mercaptopurine and 6-Thioguanine.- III. Methotrexate.- C. Drugs that Intercalate in DNA.- I. Daunorubicin and Doxorubicin.- II Amsacrine.- D. Podophyllotoxin Derivatives.- I. Etoposide and Teniposide.- E. Vinca Alkaloids.- I. Vincristine.- F. Alkylating/DNA Binding Agents.- I. Cyclophosphamide.- II Carboplatin.- G. Adrenal Glucocorticoids.- I. Prednisone.- H. Enzymes.- I. Asparaginase.- J. Multidrug Resistance.- References.
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