血液病分子生物学 英文原版2025|PDF|Epub|mobi|kindle电子书版本百度云盘下载

血液病分子生物学 英文原版PDF格式电子书版下载

注意：本站所有压缩包均有解压码： 点击下载压缩包解压工具

Part I Hematopoiesis1

Chapter 1 STEM CELL BIOLOGY[Thalia Papayannopoulou Ihor Lemischka]1

Organization of Hematopoiesis1

Emergence of Hematopoiesis and Relationship to Vascular Cells3

Primitive and Definitive Hematopoiesis5

Hematopietic Stem Cells8

Chapter 2 HEMATOPOIETIC GROWTH FACTORS AND RECEPTOR[Kenneth Kaushansky]25

Paradigms in the Hematopoietic Growth Factors and Receptiors25

The Physiology of Specific Hematopoietic Growth Factors and Their Receptors29

Hematopoietic Growth Factors in Pathological Conditions48

Hematopoietic Growth Facetor Receptors in Hematological Disease54

Chapter 3 TRANSCRIPTION FACTORS THAT REGULATE LINEAGE DECISIONS[Stuart H.Orkin]80

Early Hematopoietic Development and Lineage Commitment:A Distinction80

Identification of Relevant Genes and Thier Functional Analysis81

Factors Required for Formation or Maintenance of the Earliest Progenitors of the hematopoietic Stem Cell83

Factors Influencing Expansion of Immature Progenitors85

Transcription Factors Required in One or Multiple Myeloerythroid Lineages for Lineage Selection or Cellular Maturation86

Factors Required for the Development of Lymphoid Lineages92

Possible Mechanisms of Lineage Selection94

Chapter 4 SIGNAL TRANSDUCTION IN THE REGULATION OF HEMATOPOIESIS[James N.Ihle]103

Introduction103

Receptor Tyrosine Kinases103

Cytokine Receptors and Janus Protein Tyrosine Kinases105

Potential Regulators of Cytokine Receptor Siganling:JABs,SOCS,CIS109

Substrates of Tyrosine Kinases109

Regulatory Subunits of PI-3K110

Phospholipases111

TGF-βSignal Transduction116

Chemokine Receptor Signal Transduction117

Signal Transduction by the Frizzled Farmily of Receptors118

Signal Transduction by the Death Domain-Containing and Related Receptors118

NF-kB Activation119

Bcl Family Members and Cytokine Signaling121

Notch Receptor Signaling122

IL-1 Receptor Mediated Signal Transduction122

The MAP Kinase Cascade123

Summary and Conclusions125

Part II Red Cells135

Chapter 5 HEMOGLOBIN SWITCHING[Gerge Stamatoyannopoulos Frank Grosveld]135

Hemoglobin Production During Development136

Mutations Affecting Switching137

Regulation of the Globin Genes141

The Locus Control Region148

Molecular Control of Switching153

Cell Biology of Switching154

Fetal Hemoglobin in the Adult158

Pharmacological Manipulation of Hemoglobin FSynthesis162

Future Prospects165

Chapte 6 THE THALASSEMISAS[D.J.Weatherall]183

Historical Perspective183

Definition and Classification184

The Complexity of the Thalassemias:The Thalassemia Syndromes186

αThalassemia186

βThalassemia199

The δβThalassemias212

δThalassemia215

εγδβThalessemia216

Thalassemias for Which the Cause Has Not Been Determined216

The Contord and Treatment of Thalassemias216

Chapter 7 HUMAN HEMOGLOBINS:SICKLE HEMOGLOBIN AND OTHER MUTANTS[H.Fanklin Bunn]227

Normal Human Hemoglobin227

Humna Hemoglobin Mutants234

Sickle Hemoglobin and Sickle Cell Disease236

Hemoglobin Mutants With a Thalassemia Phenotype259

The Unstable Hemoglobin Mutants (Congenital Heinz Body Hemolytic Anemia)259

Hemoglobin Mutants With Abnormal oxygen Binding261

M Hemoglobins262

Introduction275

Chapter 8 THE ERYTHROCYTE MEMBRANE AND CYTOSKELETON:STRUCTURE,FUNCTION,AND DISORDERS[Patrick G.Gallagher Edward J.Benz,Jr.]275

Structure and Function of Cell Membranes276

The Erythrocyte Membrane and Its Cytoskeleton280

Biogenesis and Assembly of the Membrane During Red Cell Development292

Disorders of Red Cell Membrane Lipids293

Disorders of Red Cell Cytoskeletal Proteins294

Molecular Defects Underlying Red Cell Membrane Protein Disorders300

Summary and Conclusions305

Chapter 9 RED CELL MEMBRANE ANTIGENS [Jonh B. Lowe]314

The RH Blood Group System314

The LW Blood Group System319

Glycophorins A, B, and E and the MNSs Blood Group Locus320

Glycophorins C and D and the Gerbich Blood Group Locus320

The Kell Blood Group System325

The Kidd Blood Group System326

The Duffy(Fy)Blood Group System327

The Lutheran Blood Group System328

Complement System Proteins as Blood Group Determinants: The Chido/Rodgers Antigens and the Cromer-Related Antigens329

The Complement Receptor I Protein and the Knops Blood Group Antigens330

Polymorphism in Red Cell Acetylcholinesterase: The Cartwright Blood Group System330

Polymorphism in Red Cell CD44: The Indian Blood Group System330

Polymorphism in the Red Cell Water Channel Aquaporin-1: The Colton Blood Group System330

Peptide Sequence Polymorphisms on Band 3, the Red Cell Anion Exchange Protein, and the Diego Blood Group System331

Antigens on Uncharacterized Proteins331

The ABO Blood Group Locus331

The H and Se Blood Group Loci339

The Lewis Blood Group Locus342

The Ii Blood Group System346

The P Blood Group System347

Chapter 10 MOLECULAR BASIS OF IRON METABOLISM[Tracey A. Rouault Richard D. Klausner]363

Iron Acquisition by Microorganisms363

Overview of Human Iron Economy364

Transferrin365

The Transferrin Receptor367

Ferritin371

Cellular Iron Homeostasis372

mammalian Iron Physiology375

Mitochondrial Iron Homeostasis380

Hereditary Hyperferritinemia and Bilateral Cataract Syndrome381

Mechanisms of Tissue Damage by Iron381

Perspectives and Future directions381

Part III Lymphopoiesis389

Chapter 11 GENE REARRANGEMENTS IN LYMPHOID CELLS [Ilan R. Kirsch W. Michael Kuehl]389

Introduction389

The Question of Immune Diversity390

The Basis of Immune Diversity--A Generic Overview390

The Mechanism of V(D)J Recombination396

Regulation of Transcription398

T-Cell Antigen Receptors400

Immunoglobulins405

Immune Receptor Gene Rearrangements as Markers of Clonal Proliferation412

Immune Receptors as Participants in the Generation of Chromosomal Aberrations416

The Use of Polymerase Chain Reaction to Follow Chromosomal Aberrations424

Immune Receptor Gene Deletions/Alterations and Disease424

Summary424

Chapter 12 LYMPHOCYTE DEVELOPMENT[Gerald Siu]431

Principles of Lymphocyte Development431

Architecture of the Immune System432

Defining Lymphocytes by Cell Surface Molecule Expression434

Thymopoiesis434

Peripheral Development of Mature T-Cell Subsets442

B-Cell Development444

Immunological Memory449

Conclusions451

Chapter 13 ANTIGEN PROCESSING AND T-CELL EFFECTOR MECHANISMS [Roger M. Pertmutter]459

Antigen Processing and Presentation460

Molecular Biology of the Human Leukocyte Antigen Complex460

Antigen Processing:Presentation of Endogenously Synthesized Proteins464

Allelic Variation in Major Histocompatibility Complex Genes467

Architecture of the T-Cell Receptor470

Recognition of Antigen by T Lymphocytes470

The Biochemistry of T-Cell Signaling472

T-Cell Effector Mechanisms477

Summary477

Part IV Myelopoiesis/White Blood Cell485

Chapter 14 INTEGRINS IN HEMATOLOGY [Roy Zent David M. Rose Mark H. Ginsberg]485

Integrins of Blood Cells485

Integrin Structure486

Integrin Signaling487

Integrin Ligands in Hematology491

Integrins in Hematopoiesis493

Integrins in Leukocyte Trafficking494

Integrins in Platelet Function496

Integrins and Hematological Diseases497

Chapter 15 CHEMOKINES AND THEIR RECEPTORS [David I. Jarmin Craig Gerard]510

Overview of the Chemokine superfamily510

CXC Chemokines512

CC Chemokines513

The C Subfamily515

The CX3C Subfamily515

Interspecies Homology and Function515

Chemokine Receptors515

Role of Chemokines in Normal Leukocyte Trafficking520

Regulatory Control of the Expression of Chemokines and Their Receptors521

Inflammatory Disease522

Infectious Diseases524

Chemokines as Regulators of Hematopoiesis526

Angiogenesis, Cancer, and Chemokines527

Animal Studies528

Conclusions and Future Directions528

Chapter 16 GENETIC DISORDERS OF PHAGOCYTE KILLING [John T. Curnutte Mary C. Dinduer]539

Microbicidal Pathways in Phagocytes539

The Respiratory Burst Oxidase542

Chronic Granulomatous Disease547

Hemolysis of Erythrocytes564

Chapter 17 PAROXYSMAL NOCTURNAL HEMOGLOBINURIA [Monica Bessler John P. Atkinson]564

Diagnosis564

The Glycosylphosphatidylinositol Anchor570

The PIGA Gene570

Future Directions574

Part V Hemostasis579

Chapter 18 VITAMIN K-DEPENDENT PROTEINS IN BLOOD COAGULATION [Johan Stenflo Bj?rn Dahlb?ck]579

Introduction579

Modular Organization of Vitamin K-Dependent Plasma Proteins581

Gla-Containing Modules583

Epidermal Growth Factor-Like Modules592

Kringle Modules596

A Module in Protein S With Thrombin-Sensitive Bonds597

Serine Protease Modules597

A Module in Protein S Resembling Sex Hormone-Binding Globulin602

Introduction614

Protein C614

Chapter 19 THE PROTEIN C ANTICOAGULANT SYSTEM[Bj?rn Dahlb?ck Johan Stenflo]614

Thrombomodulin621

Cell Surface Receptors for Protein C and Activated Protein C630

Protein S631

C4b-Binding Protein633

The Protein C Anticoagulant System, an Important Regulator of Blood Coagulation in Vivo635

Molecular Genetics of Venous Thromboembolism636

Tissue Factor Pathway Inhibitor657

Chapter 20 REGULATION OF BLOOD COAGULATION BY PROTEASE INHIBITORS[George J. Broze, Jr. Douglas M. Tollefsen]657

Antithrombin662

Heparin Cofactor II669

Chapter 21 HEMOPHILIA A, HEMOPHILIA B, AND VON WILLEBRAND DISEASE [J. Evan Sadler Earl W. Davie]680

Factor VIII and Hemophilia A680

Factor IX and Hemophilia B691

von Willebrand Factor and von Willebrand Disease697

Chapter 22 THE MOLECULAR BASIS OF FIBRIN [Russell F. Doolittle]719

Fibrinogen: The Precursor of Fibrin719

Fibrin Formation723

Fibrinolysis726

Fibrinogen Biosynthesis728

Genetically Defective Fibrinogens729

Molecular Ecology of Fibrinogen and Fibrin732

Concluding Remark733

Chapter 23 FIBRINOLYSIS AND THE CONTROL OF HEMOSTASIS [H. R. Lijnen D. Collen]740

Introduction740

Components of the Fibrinolytic System741

Mechanisms of Fibrin-Specific Fibrinolysis748

Pathophysiology of Fibrinolysis750

Clinical Aspects of Thrombolysis753

Chapter 24 PLATELETS [Philip W. Majerus]764

Biology of Platelet Production764

Physiology of Platelet Plug Formation767

Platelet Membrane Receptors and Their Disorders772

Von Willebrand Factor Receptor774

Stimulus-Secretion Coupling in Platelet Activation778

Platelet--Vessel Wall Interactions in the Control of Hemostasis780

Part VI Molecular Oncology791

Chapter 25 MOLECULAR ASPECTS OF ONCOGENESIS [Douglas R. Lowy Linda Wolff]791

Introduction791

Background:Tumor Viruses, Familial Cancers, and Cell Cycle Control792

Cancer Is a Disease of Abnormal Growth792

Oncogenes adn Proto-Oncogenes799

Tumor Suppressor Genes819

Cancer: Collaboration Among Genes That Regulate Growth823

Future Directions824

Chapter 26 MECHANISMS OF LEVKEMOGENESIS [Charles L. Sawyers Owen N. Witte]832

Hematopoietic Growth Factors as Definitive Participants in Leukemogenesis832

Receptor Alterations in Leukemogenesis833

Intracellular Signaling Mechanisms836

Ras-Controlled Pathways Are Key Intracellular Mediators of Leukemogenesis840

Transcription Factor Translocations841

Translocations in Genes Essential for Hematopoietic Development843

Translocations in Genes That Affect Hematopoietic Differentiation845

Translocations That Target Genes Involved in Homeotic Function847

Translocations That Target Genes Affecting Apoptosis848

Abnormalities in Genes Involved in Cell Cycle Progression849

Summary851

Part VII Viruses861

Chapter 27 THE MOLECULAR AND BIOLOGICAL PROPERTIES OF THE HUMAN IMMUNODEFICIENCY VIRUS [Eric O. Freed Malcolm A. Martin]861

Introduction861

The Classification, Genomic Organization, and Proteins Encoded by Human Immunodeficiency Virus861

The Virus Life Cycle: Overview863

Molecular Biology of Human Immunodeficiency Virus Replication867

Human Immunodeficiency Virus Life Cycle: Clinical Perspectives888

Prospects for a Human Immunodeficiency Virus-I Vaccine893

Chapter 28 VIRAL PATHOGENESIS OF HEMATOLOGICAL DISORDERS916

B 19 PARVOVIRUSES[Neal Young]916

The Parvoviruses916

B19 Parvovirus918

Epidemiology923

Clinical Syndromes924

Immune Response927

Conclusion929

RETROVIRUSES(HTLVs)[Mitsuaki Yoshida]935

Introduction to Retroviruses935

Human Retroviruses936

HERPESVIRUSES[Eric Bruening Bill Sugden]951

Structural Properties of Herpesviruses952

Infection by Human Cytomegalovirus in Cell Culture953

Latent and Lytic Infections by Herpesviruses953

Infection by Epstein-Barr Virus in Cell Culture955

Infections in the Human Host956

Part VIII Gene Therapy969

Chapter 29 GENE THERAPY FOR HEMATOPOIETIC DISEASES[Brian P. Sorrentino Arthur W. Nienhuis]969

The Science of Gene Therapy for Hematopoietic Disorders969

Disease-Specific Applications and Clinical Trials983

SUMMARY992

INDEX1005