Molecular Pathology: The Molecular Basis of Human Disease

Cover Page
......Page 1
Title Page
......Page 4
Copyright Page
......Page 5
Dedication......Page 6
List of Contributors......Page 12
Preface......Page 16
Foreword......Page 18
Acknowledgments......Page 20
Contents......Page 8
PART I:  Essential Pathology–Mechanisms of Disease......Page 22
Structural Features of Necrosis and Apoptosis......Page 24
Cellular and Molecular Mechanisms Underlying Necrotic Cell Death
......Page 26
Pathways to Apoptosis......Page 33
Mitochondria......Page 36
Lysosomes......Page 39
Concluding Remark......Page 40
Leukocyte Adhesion, Migration, and Activation......Page 46
Acute Inflammation and Disease Pathogenesis......Page 49
Pattern Recognition Receptors and Inflammatory Responses
......Page 50
Chronic Inflammation and Acquired Immune Responses
......Page 53
Tissue Remodeling During Acute and Chronic Inflammatory Disease
......Page 55
The Structure of the Immune Response......Page 62
The African Trypanosome and Antibody Diversity: Dueling Genomes
......Page 64
Staphylococcus Aureus: the Extracellular Battleground
......Page 69
Mycobacterium Tuberculosis and the Macrophage
......Page 73
Herpes Simplex Virus: Taking Over......Page 76
HIV: The Immune Guerilla......Page 78
Perspectives......Page 81
Cancer Statistics and Epidemiology......Page 84
Classification of Neoplastic Diseases......Page 91
Characteristics of Benign and Malignant Neoplasms
......Page 99
Clinical Aspects of Neoplasia......Page 103
PART II:  Concepts in Molecular Biology and Genetics......Page 108
Molecular Structure of DNA, DNA Transcription, and Protein Translation
......Page 110
Molecular Pathology and DNA Repair Mechanisms
......Page 113
Modes of Inheritance......Page 117
Central Dogma and Rationale for Genetic Testing
......Page 122
Allelic Heterogeneity and Choice of Analytical Methodology
......Page 125
Conclusion......Page 128
Structure and Organization of the Human Genome
......Page 130
Overview of the Human Genome Project......Page 132
Impact of the Human Genome Project on the Identification of Disease-Related Genes
......Page 134
Sources of Variation in the Human Genome......Page 136
Types of Genetic Diseases......Page 137
Genetic Diseases and Cancer......Page 138
Perspectives......Page 140
Gene Expression Profiling: The Search for Candidate Genes Involved in Pathogenesis
......Page 144
Transcriptome Analysis Based on Microarrays: Technical Prerequisites
......Page 147
Microarrays: Bioinformatic Analysis......Page 151
Microarrays: Applications in Basic Research and Translational Medicine
......Page 158
Perspectives......Page 167
Epigenetic Regulation of the Genome......Page 172
Genomic Imprinting......Page 173
Cancer Epigenetics......Page 175
Human Disorders Associated with Epigenetics......Page 178
Environment and the Epigenome......Page 181
Microdissection Technology Brings Molecular Analysis to the Tissue Level
......Page 186
Serum Proteomics: An Emerging Landscape for Early Stage Cancer Detection
......Page 195
Introduction......Page 206
Data Generation......Page 207
Data Integration......Page 209
Modeling Systems......Page 210
Implications for Understanding Disease......Page 211
Discussion......Page 213
PART III: Principles and Practice of Molecular Pathology......Page 216
Terms, Definitions, and Concepts......Page 218
A Brief History of Approaches to Disease......Page 219
Current Practice of Pathology......Page 224
The Future of Diagnostic Pathology......Page 227
Conclusion......Page 228
Hepatitis C Virus Infection......Page 230
Acute Myeloid Leukemia......Page 233
Cystic Fibrosis......Page 234
Introduction......Page 240
Overview of Bioinformatics......Page 241
Database Resources......Page 242
Data Analysis......Page 243
The Future of Bioinformatics......Page 244
PART IV: Molecular Pathology of Human Disease......Page 246
The Cells of Cardiovascular Organs......Page 248
Atherosclerosis......Page 253
Aneurysms......Page 256
Valvular Heart Disease......Page 257
Cardiomyopathies......Page 259
Introduction and Overview of Coagulation......Page 268
Disorders of Soluble Clotting Factors......Page 270
Disorders of Platelet Number or Function......Page 277
Thrombophilia......Page 281
Development of the Blood and Lymphoid Organs......Page 286
Myeloid Disorders......Page 292
Lymphocyte Disorders......Page 300
Normal Immune System......Page 312
Major Syndromes......Page 317
Neoplastic Lung and Pleural Diseases......Page 326
Obstructive Lung Diseases......Page 344
Interstitial Lung Diseases......Page 352
Pulmonary Vascular Diseases......Page 359
Pulmonary Infections......Page 363
Pulmonary Histiocytic Diseases......Page 373
Pulmonary Occupational Diseases......Page 375
Developmental Abnormalities......Page 377
Gastric Cancer......Page 386
Colorectal Cancer......Page 393
Molecular Basis of Liver Development......Page 416
Molecular Basis of Liver Regeneration......Page 418
Adult Liver Stem Cells in Liver Health and Disease......Page 420
Molecular Basis of Hepatocyte Death......Page 421
Molecular Basis of Nonalcoholic Fatty Liver Disease......Page 423
Molecular Basis of Alcoholic Liver Disease......Page 427
Molecular Basis of Hepatic Fibrosis and Cirrhosis......Page 428
Molecular Basis of Hepatic Tumors......Page 429
Acute Pancreatitis......Page 442
Chronic and Hereditary Pancreatitis......Page 447
Summary......Page 451
The Pituitary Gland......Page 456
The Thyroid Gland......Page 460
The Parathyroid Gland......Page 467
The Adrenal Gland......Page 471
Puberty......Page 475
Benign and Malignant Tumors of the Female Reproductive Tract......Page 486
Disorders Related to Pregnancy......Page 498
Introduction......Page 510
Somatic Alterations in Gene Expression......Page 511
Epigenetics......Page 514
Advances in Mouse Models of Prostate Cancer......Page 515
Acknowledgments......Page 517
Traditional Breast Cancer Classification......Page 522
Biomarkers......Page 524
Gene Expression Profiling......Page 530
Conclusion......Page 534
Molecular Basis of Healthy Skin......Page 540
Skin Development and Maintenance Provide NewInsight into the Molecular Mechanisms of Disease......Page 544
Molecular Pathology of Mendelian Genetic Skin Disorders......Page 545
Molecular Pathology of Common Inflammatory Skin Diseases......Page 552
Skin Proteins as Targets for Inherited and Acquired Disorders......Page 556
Molecular Pathology of Skin Cancer......Page 560
Molecular Diagnosis of Skin Disease......Page 565
New Molecular Mechanisms and Novel Therapies......Page 566
Anatomy of the Central Nervous System......Page 572
Neurodevelopmental Disorders......Page 575
Neurological Injury: Stroke, Neurodegeneration, and Toxicants......Page 585
Neoplasia......Page 598
Disorders of Myelin......Page 604
PART V: Practice of Molecular Medicine......Page 610
History of Molecular Diagnostics......Page 612
Molecular Laboratory Subspecialties......Page 614
Future Applications......Page 623
Introduction......Page 626
The Current Molecular Infectious Disease Paradigm......Page 627
A New Paradigm for Molecular Diagnostic Applications......Page 628
BCR-ABL: A Model for the New Paradigm......Page 631
Conclusion......Page 633
Introduction......Page 634
Conclusion......Page 641
Index......Page 644