Molecular Pathology,

List of Contributors

Preface

Foreword

Acknowledgments

Part I Essential Pathology – Mechanisms of Disease

    Chapter 1 Molecular Mechanisms of Cell Death

         Introduction

         Modes of Cell Death

         Structural Features of Necrosis and Apoptosis

         Cellular and Molecular Mechanisms Underlying Necrotic Cell Death

         Pathways to Apoptosis

         Mitochondria

         Nucleus

         Endoplasmic Reticulum

         Lysosomes

         Concluding Remark

    Chapter 2 Acute and Chronic Inflammation Induces Disease Pathogenesis

         Introduction

         Leukocyte Adhesion, Migration, and Activation

         Acute Inflammation and Disease Pathogenesis

         Pattern Recognition Receptors and Inflammatory Responses

         Chronic Inflammation and Acquired Immune Responses

         Tissue Remodeling During Acute and Chronic Inflammatory Disease

    Chapter 3 Infection and Host Response

         Microbes and Hosts—Balance of Power?

         The Structure of the Immune Response

         Regulation of Immunity

         Pathogen Strategies

         The African Trypanosome and Antibody Diversity: Dueling Genomes

         Staphylococcus Aureus: the Extracellular Battleground

         Mycobacterium Tuberculosis and the Macrophage

         Herpes Simplex Virus: Taking Over

         HIV: The Immune Guerilla

         Perspectives

    Chapter 4 Neoplasia

         Introduction

         Cancer Statistics and Epidemiology

         Classification of Neoplastic Diseases

         Characteristics of Benign and Malignant Neoplasms

         Clinical Aspects of Neoplasia

Part II Concepts in Molecular Biology and Genetics

    Chapter 5 Basic Concepts in Human Molecular Genetics

         Introduction

         Molecular Structure of DNA, DNA Transcription, and Protein Translation

         Molecular Pathology and DNA Repair Mechanisms

         Modes of Inheritance

         Central Dogma and Rationale for Genetic Testing

         Allelic Heterogeneity and Choice of Analytical Methodology

         Conclusion

    Chapter 6 The Human Genome: Implications for the Understanding of Human Disease

         Introduction

         Structure and Organization of the Human Genome

         Overview of the Human Genome Project

         Impact of the Human Genome Project on the Identification of Disease-Related Genes

         Sources of Variation in the Human Genome

         Types of Genetic Diseases

         Genetic Diseases and Cancer

         Perspectives

    Chapter 7 The Human Transcriptome: Implications for the Understanding of Human Disease

         Introduction

         Gene Expression Profiling: The Search for Candidate

         Genes Involved in Pathogenesis

         Transcriptome Analysis Based on Microarrays: Technical Prerequisites

         Microarrays: Bioinformatic Analysis

         Microarrays: Applications in Basic Research and Translational Medicine Perspectives

    Chapter 8 The Human Epigenome: Implications for the Understanding of Human Disease

         Introduction

         Epigenetic Regulation of the Genome

         Genomic Imprinting

         Cancer Epigenetics

         Human Disorders Associated with Epigenetics

         Environment and the Epigenome

    Chapter 9 Clinical Proteomics and Molecular Pathology

         Understanding Cancer at the Molecular Level: An Evolving Frontier

         Microdissection Technology Brings Molecular Analysis to the Tissue Level

         Serum Proteomics: An Emerging Landscape for Early Stage Cancer Detection

    Chapter 10 Integrative Systems Biology: Implications for the Understanding of Human Disease

         Introduction

         Data Generation

         Data Integration

         Modeling Systems

         Implications for Understanding Disease

         Discussion

Part III Principles and Practice of Molecular Pathology

    Chapter 11 Pathology: The Clinical Description of Human Disease

         Introduction

         Terms, Definitions, and Concepts

         A Brief History of Approaches to Disease

         Current Practice of Pathology

         The Future of Diagnostic Pathology

         Conclusion

    Chapter 12 Understanding Molecular Pathogenesis: The Biological Basis of Human Disease and Implications for Improved Treatment of Human Disease

         Introduction

         Hepatitis C Virus Infection

         Acute Myeloid Leukemia

         Cystic Fibrosis

    Chapter 13 Integration of Molecular and Cellular Pathogenesis: A Bioinformatics

Approach

         Introduction

         Overview of Bioinformatics

         Database Resources

         Data Analysis

         The Future of Bioinformatics

    Chapter 14 Molecular Basis of Cardiovascular Disease

         Introduction

         General Molecular Principles of Cardiovascular

         Diseases

         The Cells of Cardiovascular Organs

         Atherosclerosis

         Ischemic Heart Disease

         Aneurysms

         Vasculitis

         Valvular Heart Disease

         Cardiomyopathies

    Chapter 15 Molecular Basis of Hemostatic and Thrombotic Diseases

         Introduction and Overview of Coagulation

         Disorders of Soluble Clotting Factors

         Disorders of Fibrinolysis

         Disorders of Platelet Number or Function

         Thrombophilia

    Chapter 16 Molecular Basis of Lymphoid and Myeloid Diseases

         Development of the Blood and Lymphoid Organs

         Myeloid Disorders

         Lymphocyte Disorders

    Chapter 17 Molecular Basis of Diseases of Immunity

         Introduction

         Normal Immune System

         Major Syndromes

    Chapter 18 Molecular Basis of Pulmonary Disease

         Introduction

         Neoplastic Lung and Pleural Diseases

         Non-neoplastic Lung Disease

         Obstructive Lung Diseases

         Interstitial Lung Diseases

         Pulmonary Vascular Diseases

         Pulmonary Infections

         Pulmonary Histiocytic Diseases

         Pulmonary Occupational Diseases

         Developmental Abnormalities

    Chapter 19 Molecular Basis of Diseases of the Gastrointestinal Tract

         Introduction

         Gastric Cancer

         Colorectal Cancer

    Chapter 20 Molecular Basis of Liver Disease

         Introduction

         Molecular Basis of Liver Development

         Molecular Basis of Liver Regeneration

         Adult Liver Stem Cells in Liver Health and Disease

         Molecular Basis of Hepatocyte Death

         Molecular Basis of Nonalcoholic Fatty Liver Disease

         Molecular Basis of Alcoholic Liver Disease

         Molecular Basis of Hepatic Fibrosis and Cirrhosis

         Molecular Basis of Hepatic Tumors

    Chapter 21 Molecular Basis of Diseases of the Exocrine Pancreas

         Acute Pancreatitis

         Chronic and Hereditary Pancreatitis

         Summary

    Chapter 22 Molecular Basis of Diseases of the Endocrine System

         Introduction

         The Pituitary Gland

         The Thyroid Gland

         The Parathyroid Gland

         The Adrenal Gland

         Puberty

    Chapter 23 Molecular Basis of Gynecologic Diseases

         Introduction

         Benign and Malignant Tumors of the Female

         Reproductive Tract

         Disorders Related to Pregnancy

    Chapter 24 Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations

         Introduction

         Hereditary Component of Prostate Cancer Risk

         Somatic Alterations in Gene Expression

         Epigenetics

         Advances in Mouse Models of Prostate Cancer

         Conclusion

         Acknowledgments

    Chapter 25 Molecular Biology of Breast Cancer

         Introduction

         Traditional Breast Cancer Classification

         Biomarkers

         Gene Expression Profiling

         Conclusion

    Chapter 26 Molecular Basis of Skin Disease

         Introduction

         Skin Diseases and Their Impact

         Molecular Basis of Healthy Skin

         Skin Development and Maintenance Provide New Insight into the Molecular Mechanisms of Disease

         Molecular Pathology of Mendelian Genetic Skin Disorders

         Molecular Pathology of Common Inflammatory Skin Diseases

         Skin Proteins as Targets for Inherited and Acquired Disorders

         Molecular Pathology of Skin Cancer

         Molecular Diagnosis of Skin Disease

         New Molecular Mechanisms and Novel Therapies

    Chapter 27 Molecular Pathology: Neuropathology

         Anatomy of the Central Nervous System

         Neurodevelopmental Disorders

         Neurological Injury: Stroke, Neurodegeneration, and Toxicants

         Neoplasia

         Disorders of Myelin

Part V Practice of Molecular Medicine

    Chapter 28 Molecular Diagnosis of Human Disease

         Introduction

         History of Molecular Diagnostics

         Molecular Laboratory Subspecialties

         Future Applications

    Chapter 29 Molecular Assessment of Human Disease in the Clinical Laboratory

         Introduction

         The Current Molecular Infectious Disease Paradigm

         A New Paradigm for Molecular Diagnostic Applications

         BCR-ABL: A Model for the New Paradigm

         Conclusion

    Chapter 30 Pharmacogenomics and Personalized Medicine in the Treatment of Human

Diseases

         Introduction

         Conclusion

Index