Essential Concepts in Molecular Pathology (eBook)

Front Cover 1
Essential Concepts in Molecular Pathology 4
Copyright Page 5
Dedication 6
Contents 8
List of Contributors 14
Preface 18
Foreword 20
Acknowledgements 22
Part I: Essential Pathology - Mechanisms of Disease 24
Chapter 1: Molecular Mechanisms of Cell Death 26
Introduction 26
Modes of Cell Death 26
Structural Features of Necrosis and Apoptosis 26
Cellular and Molecular Mechanisms Underlying Necrotic Cell Death 28
Pathways to Apoptosis 31
Mitochondria 33
Nucleus 35
Endoplasmic Reticulum 35
Lysosomes 36
Concluding Remark 36
Acknowledgments 36
Key Concepts 36
Suggested Readings 37
Chapter 2: Acute and Chronic Inflammation Induces Disease Pathogenesis 38
Introduction 38
Leukocyte Adhesion, Migration, and Activation 38
Acute Inflammation and Disease Pathogenesis 40
Pattern Recognition Receptors and Inflammatory Responses 41
Chronic Inflammation and Acquired Immune Responses 43
Tissue Remodeling During Acute and Chronic Inflammatory Disease 45
Key Concepts 47
Suggested Readings 47
Chapter 3: Infection and Host Response 48
Microbes and Hosts-Balance of Power? 48
The Structure of the Immune Response 48
Regulation of Immunity 49
Pathogen Strategies 49
The African Trypanosome and Antibody Diversity: Dueling Genomes 50
Staphylococcus Aureus: the Extracellular Battleground 52
Mycobacterium Tuberculosis and the Macrophage 57
Herpes Simplex Virus: Taking Over 59
HIV: The Immune Guerilla 61
Perspectives 65
Key concepts 65
Suggested Readings 65
Chapter 4: Neoplasia 68
Introduction 68
Cancer Statistics and Epidemiology 68
Classification of Neoplastic Diseases 73
Characteristics of Benign and Malignant Neoplasms 79
Clinical Aspects of Neoplasia 82
Key Concepts 83
Suggested Readings 84
Part II: Concepts in Molecular Biology and Genetics 86
Chapter 5: Basic Concepts in Human Molecular Genetics 88
Introduction 88
Molecular Structure of DNA 88
Modes of Inheritance 89
Central Dogma and Rationale for Genetic Testing 94
Allelic Heterogeneity and Choice of Analytical Methodology 97
Conclusion 98
Key Concepts 99
Suggested Readings 99
Chapter 6: The Human Genome: Implications for the Understanding of Human Disease 100
Introduction 100
Structure and Organization of the Human Genome 100
Overview of the Human Genome Project 102
Impact of the Human Genome Project on the Identification Of Disease-Related Genes 104
Sources of Variation in the Human Genome 106
Types of Genetic Diseases 106
Genetic Diseases and Cancer 107
Perspectives 109
Key Concepts 109
Suggested Readings 110
Chapter 7: The Human Transcriptome: Implications for the Understanding of Human Disease 112
Introduction 112
Gene Expression Profiling: The Search for Candidate Genes Involved in Pathogenesis 112
Transcriptome Analysis Based on Microarrays: Technical Prerequisites 114
Microarrays: Applications in Basic Research and Translational Medicine 115
Perspectives 124
Key concepts 124
Suggested readings 126
Chapter 8: The Human Epigenome: Implications for the Understanding of Human Disease 128
Introduction 128
Epigenetic Regulation of the Genome 128
Genomic Imprinting 129
Cancer Epigenetics 131
Human Disorders Associated with Epigenetics 133
Key Concepts 135
Suggested Readings 135
Chapter 9: Clinical Proteomics and Molecular Pathology 136
Understanding Cancer at the Molecular Level: An Evolving Frontier 136
Microdissection Technology Brings Molecular Analysis to the Tissue Level 136
Serum Proteomics: an Emerging Landscape for Early Stage Cancer Detection 141
Key concepts 145
Suggested Readings 145
Chapter 10: Integrative Systems Biology: Implications for the Understanding of Human Disease 148
Introduction 148
Data Generation 149
Data Integration 151
Modeling Systems 152
Implications for Understanding Disease 153
Discussion 155
Key Concepts 156
Suggested Readings 156
Part III: Principles and Practice of Molecular Pathology 158
Chapter 11: Pathology: The Clinical Description of Human Disease 160
Current Practice of Pathology 160
The Future of Diagnostic Pathology 163
Conclusion 164
Key Concepts 164
Suggested Readings 164
Chapter 12: Understanding Molecular Pathogenesis: The Biological Basis of Human Disease and Implications for Improved Treatment of Human Disease 166
Introduction 166
Hepatitis C Virus Infection 166
Acute Myeloid Leukemia 169
Cystic Fibrosis 171
Key Concepts 174
Suggested Readings 174
Chapter 13: Integration of Molecular and Cellular Pathogenesis: A Bioinformatics Approach 176
Introduction 176
Overview of Bioinformatics 177
Database Resources 178
Data Analysis 179
The Future 180
Key Concepts 181
Suggested Readings 181
Part IV: Molecular Pathology of Human Disease 182
Chapter 14: Molecular Basis of Cardiovascular Disease 184
General Molecular Principles of Cardiovascular Diseases 184
The Cells of Cardiovascular Organs 184
Atherosclerosis 187
Ischemic Heart Disease 190
Aneurysms 190
Valvular Heart Disease 191
Cardiomyopathies 192
Key Concepts 196
Suggested Readings 196
Chapter 15: Molecular Basis of Hemostatic and Thrombotic Diseases 198
Introduction and Overview of Coagulation 198
Disorders of Soluble Clotting Factors 200
Disorders of Platelet Number or Function 205
Thrombophilia 208
Key concepts 210
Suggested Readings 210
Chapter 16: Molecular Basis of Lymphoid and Myeloid Diseases 212
Development of the Blood and Lymphoid Organs 212
Myeloid Disorders 216
Lymphocyte Disorders 221
Key concepts 225
Suggested Readings 225
Chapter 17: Molecular Basis of Diseases of Immunity 228
Introduction 228
Normal Immune System 228
Major Syndromes 231
Key Concepts 238
Suggested Readings 238
Chapter 18: Molecular Basis of Pulmonary Disease 240
Introduction 240
Neoplastic lung and pleural diseases 240
Obstructive Lung Diseases 251
Interstitial Lung Diseases 258
Pulmonary Vascular Diseases 261
Developmental Abnormalities 263
Key Concepts 265
Suggested Readings 265
Chapter 19: Molecular Basis of Diseases of the Gastrointestinal Tract 266
Gastric Cancer 266
Colorectal Cancer 271
Key Concepts 283
Suggested Readings 284
Chapter 20: Molecular Basis of Liver Disease 286
Introduction 286
Molecular Basis of Liver Development 286
Molecular Basis of Liver Regeneration 288
Adult Liver Stem Cells in Liver Health and Disease 289
Molecular Basis of Hepatocyte Death 290
Molecular Basis of Nonalcoholic Fatty Liver Disease 291
Molecular Basis of Alcoholic Liver Disease 294
Molecular Basis of Hepatic Fibrosis and Cirrhosis 295
Molecular Basis of Hepatic Tumors 297
Key Concepts 300
Suggested Readings 300
Chapter 21: Molecular Basis of Diseases of the Exocrine Pancreas 302
Acute Pancreatitis 302
Chronic and Hereditary Pancreatitis 307
Key concepts 310
Suggested readings 311
Chapter 22: Molecular Basis of Diseases of the Endocrine System 312
Introduction 312
The Pituitary Gland 312
The Thyroid Gland 315
Familial Nonautoimmune Hyperthyroidism 318
The Parathyroid Gland 319
The Adrenal Gland 322
Puberty 325
Key Concepts 329
Suggested Readings 329
Chapter 23: Molecular Basis of Gynecologic Diseases 332
Introduction 332
Benign and Malignant Tumors of the Female Reproductive Tract 332
Disorders Related to Pregnancy 342
Key Concepts 344
Suggested Readings 345
Chapter 24: Molecular Pathogenesis of Diseases of the Kidney 346
Introduction 346
Normal Kidney Function 346
Focal Segmental Glomerulosclerosis 346
Fabry Disease 348
Polycystic Kidney Disease 350
Disorders of Renal Tubular Function 353
Key Concepts 355
Suggested Readings 355
Chapter 25: Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations 358
Introduction 358
Hereditary Component of Prostate Cancer Risk 359
Somatic Alterations in Gene Expression 359
Epigenetics 361
Conclusion 362
Acknowledgments 362
Key Concepts 363
Suggested Readings 363
Chapter 26: Molecular Biology of Breast Cancer 364
Introduction 364
Traditional Breast Cancer Classification 364
Biomarkers 366
Gene Expression Profiling 369
Conclusion 371
Key Concepts 371
Suggested Readings 371
Chapter 27: Molecular Basis of Skin Disease 374
Molecular basis of healthy skin 374
Skin development and maintenance provide new insight into molecular mechanisms of disease 375
Molecular pathology of Mendelian genetic skin disorders 377
Molecular pathology of common inflammatory skin diseases 382
Skin proteins as targets for inherited and acquired disorders 384
Molecular pathology of skin cancer 387
Molecular diagnosis of skin disease 391
New molecular mechanisms and novel therapies 393
Key concepts 395
Suggested Readings 395
Chapter 28: Molecular Pathology: Neuropathology 396
Anatomy of the Central Nervous System 396
Neurodevelopmental Disorders 399
Neurological Injury: Stroke, Neurodegeneration, and Toxicants 403
Neoplasia 413
Disorders of Myelin 417
Key Concepts 420
Suggested Readings 420
Part V: Practice of Molecular Medicine 422
Chapter 29: Molecular Diagnosis of Human Disease 424
Introduction 424
History of Molecular Diagnostics 424
Molecular Laboratory Subspecialties 426
Key Concepts 434
Suggested Readings 434
Chapter 30: Molecular Assessment of Human Disease in the Clinical Laboratory 436
Introduction 436
The Current Molecular Infectious Disease Paradigm 437
A New Paradigm for Molecular Diagnostic Applications 438
BCR-ABL: A Model for the New Paradigm 441
Conclusion 443
Key Concepts 443
Suggested Readings 443
Chapter 31: Pharmacogenomics and Personalized Medicine in the Treatment of Human Diseases 444
Introduction 444
Conclusion 451
Key Concepts 451
Suggested Readings 451
Index 452