Front Cover 1
Molecular Pathology 4
Series Page 3
Copyright Page 5
Dedication Page 6
Contents 8
List of Contributors 12
Preface 16
Foreword 18
Acknowledgments 20
Part I: Essential Pathology - Mechanisms of Disease 22
Chapter 1: Molecular Mechanisms of Cell Death 24
Introduction 24
Modes of Cell Death 24
Structural Features of Necrosis and Apoptosis 24
Cellular and Molecular Mechanisms Underlying Necrotic Cell Death 26
Pathways to Apoptosis 33
Mitochondria 36
Nucleus 39
Endoplasmic Reticulum 39
Lysosomes 39
Concluding Remark 40
Acknowledgments 40
References 41
Chapter 2: Acute and Chronic Inflammation Induces Disease Pathogenesis 46
Introduction 46
Leukocyte Adhesion, Migration, and Activation 46
Acute Inflammation and Disease Pathogenesis 49
Pattern Recognition Receptors and Inflammatory Responses 50
Chronic Inflammation and Acquired Immune Responses 53
Tissue Remodeling During Acute and Chronic Inflammatory Disease 55
References 58
Chapter 3: Infection and Host Response 62
Microbes and Hosts-Balance of Power? 62
The Structure of the Immune Response 62
Regulation of Immunity 64
Pathogen Strategies 64
The African Trypanosome and Antibody Diversity: Dueling Genomes 64
Staphylococcus Aureus: the Extracellular Battleground 69
Mycobacterium Tuberculosis and the Macrophage 73
Herpes Simplex Virus: Taking Over 76
HIV: The Immune Guerilla 78
Perspectives 81
References 82
Chapter 4: Neoplasia 84
Introduction 84
Cancer Statistics and Epidemiology 84
Classification of Neoplastic Diseases 91
Characteristics of Benign and Malignant Neoplasms 99
Clinical Aspects of Neoplasia 103
References 104
Part II: Concepts in Molecular Biology and Genetics 108
Chapter 5: Basic Concepts in Human Molecular Genetics 110
Introduction 110
Molecular Structure of DNA, DNA Transcription, and Proten Translation 110
Molecular Pathology and DNA Repair Mechanisms 113
Modes of Inheritance 117
Central Dogma and Rationale for Genetic Testing 122
Allelic Heterogeneity and Choice of Analytical Methodology 125
Conclusion 128
References 128
Chapter 6: The Human Genome: Implications for the Understanding of Human Disease 130
Introduction 130
Structure and Organization of the Human Genome 130
Overview of the Human Genome Project 132
Impact of the Human Genome Project on the Identification of Disease-Related Genes 134
Sources of Variation in the Human Genome 136
Types of Genetic Diseases 137
Genetic Diseases and Cancer 138
Perspectives 140
References 140
Chapter 7: The Human Transcriptome: Implications for the Understanding of Human Disease 144
Introduction 144
Gene Expression Profiling: The Search for Candidate Genes Involved in Pathogenesis 144
Transcriptome Analysis Based on Microarrays: Technical Prerequisites 147
Microarrays: Bioinformatic Analysis 151
Microarrays: Applications in Basic Research and Translational Medicine 158
Perspectives 167
References 169
Chapter 8: The Human Epigenome: Implications for the Understanding of Human Disease 172
Introduction 172
Epigenetic Regulation of the Genome 172
Genomic Imprinting 173
Cancer Epigenetics 175
Human Disorders Associated with Epigenetics 178
Environment and the Epigenome 181
References 181
Chapter 9: Clinical Proteomics and Molecular Pathology 186
Understanding Cancer at the Molecular Level: An Evolving Frontier 186
Microdissection Technology Brings Molecular Analysis to the Tissue Level 186
Serum Proteomics: an Emerging Landscape for Early Stage Cancer Detection 195
References 202
Chapter 10: Integrative Systems Biology: Implications for the Understanding of Human Disease 206
Introduction 206
Data Generation 207
Data Integration 209
Modeling Systems 210
Implications for Understanding Disease 211
Discussion 213
References 214
Part III: Principles and Practice of Molecular Pathology 216
Chapter 11: Pathology: The Clinical Description of Human Disease 218
Introduction 218
Terms, Definitions, and Concepts 218
A Brief History of Approaches to Disease 219
Current Practice of Pathology 224
The Future of Diagnostic Pathology 227
Conclusion 228
References 228
Chapter 12: Understanding Molecular Pathogenesis: The Biological Basis of Human Disease and Implications for Improved Treatment of Human D 230
Introduction 230
Hepatitis C Virus Infection 230
Acute Myeloid Leukemia 233
Cystic Fibrosis 234
References 237
Chapter 13: Integration of Molecular and Cellular Pathogenesis: A Bioinformatics Approach 240
Introduction 240
Overview of Bioinformatics 241
Database Resources 242
Data Analysis 243
The Future of Bioinformatics 244
References 245
Part IV: Molecular Pathology of Human Disease 246
Chapter 14: Molecular Basis of Cardiovascular Disease 248
Introduction 248
General Molecular Principles of Cardiovascular Diseases 248
The Cells of Cardiovascular Organs 248
Atherosclerosis 253
Ischemic Heart Disease 256
Aneurysms 256
Vasculitis 257
Valvular Heart Disease 257
Cardiomyopathies 259
References 264
Chapter 15: Molecular Basis of Hemostatic and Thrombotic Diseases 268
Introduction and Overview of Coagulation 268
Disorders of Soluble Clotting Factors 270
Disorders of Fibrinolysis 277
Disorders of Platelet Number or Function 277
Thrombophilia 281
References 283
Chapter 16: Molecular Basis of Lymphoid and Myeloid Diseases 286
Development of the Blood and Lymphoid Organs 286
Myeloid Disorders 292
Lymphocyte Disorders 300
References 308
Chapter 17: Molecular Basis of Diseases of Immunity 312
Introduction 312
Normal Immune System 312
Major Syndromes 317
References 325
Chapter 18: Molecular Basis of Pulmonary Disease 326
Introduction 326
Neoplastic Lung and Pleural Diseases 326
Non-neoplastic Lung Disease 344
Obstructive Lung Diseases 344
Interstitial Lung Diseases 352
Pulmonary Vascular Diseases 359
Pulmonary Infections 363
Pulmonary Histiocytic Diseases 373
Pulmonary Occupational Diseases 375
Developmental Abnormalities 377
References 379
Chapter 19: Molecular Basis of Diseases of the Gastrointestinal Tract 386
Introduction 386
Gastric Cancer 386
Colorectal Cancer 393
References 407
Chapter 20: Molecular Basis of Liver Disease 416
Introduction 416
Molecular Basis of Liver Development 416
Molecular Basis of Liver Regeneration 418
Adult Liver Stem Cells in Liver Health and Disease 420
Molecular Basis of Hepatocyte Death 421
Molecular Basis of Nonalcoholic Fatty Liver Disease 423
Molecular Basis of Alcoholic Liver Disease 427
Molecular Basis of Hepatic Fibrosis and Cirrhosis 428
Molecular Basis of Hepatic Tumors 429
References 433
Chapter 21: Molecular Basis of Diseases of the Exocrine Pancreas 442
Acute Pancreatitis 442
Chronic and Hereditary Pancreatitis 447
Summary 451
References 451
Chapter 22: Molecular Basis of Diseases of the Endocrine System 456
Introduction 456
The Pituitary Gland 456
The Thyroid Gland 460
The Parathyroid Gland 467
The Adrenal Gland 471
Puberty 475
References 480
Chapter 23: Molecular Basis of Gynecologic Diseases 486
Introduction 486
Benign and Malignant Tumors of the Female Reproductive Tract 486
Disorders Related to Pregnancy 498
References 502
Chapter 24: Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations 510
Introduction 510
Hereditary Component of Prostate Cancer Risk 511
Somatic Alterations in Gene Expression 511
Epigenetics 514
Advances in Mouse Models of Prostate Cancer 515
Conclusion 517
Acknowledgments 517
References 517
Chapter 25: Molecular Biology of Breast Cancer 522
Introduction 522
Traditional Breast Cancer Classification 522
Biomarkers 524
Gene Expression Profiling 530
Conclusion 534
References 534
Chapter 26: Molecular Basis of Skin Disease 540
Skin Diseases and Their Impact 540
Molecular Basis of Healthy Skin 540
Skin Development and Maintenance Provide New Insight into the Molecular Mechanisms of Disease 543
Molecular Pathology of Mendelian Genetic Skin Disorders 546
Molecular Pathology of Common Inflammatory Skin Diseases 552
Skin Proteins as Targets for Inherited and Acquired Disorders 556
Molecular Pathology of Skin Cancer 560
Molecular Diagnosis of Skin Disease 565
New Molecular Mechanisms and Novel Therapies 566
References 570
Chapter 27: Molecular Pathology: Neuropathology 572
Introduction 572
Anatomy of the Central Nervous System 572
Neurodevelopmental Disorders 575
Neurological Injury: Stroke, Neurodegeneration, and Toxicants 585
Neoplasia 598
Disorders of Myelin 604
References 608
Part V: Practice of Molecular Medicine 610
Chapter 28: Molecular Diagnosis of Human Disease 612
Introduction 612
History of Molecular Diagnostics 612
Molecular Laboratory Subspecialties 614
Future Applications 623
References 624
Chapter 29: Molecular Assessment of Human Disease in the Clinical Laboratory 626
Introduction 626
The Current Molecular Infectious Disease Paradigm 627
A. New Paradigm for Molecular Diagnostic Applications 628
BCR-ABL: A Model for the New Paradigm 631
Conclusion 633
References 633
Chapter 30: Pharmacogenomics and Personalized Medicine in the Treatment of Human Diseases 634
Introduction 634
Conclusion 641
References 641
Index 644