The Molecular Basis of Human Disease
E-Book, Englisch, 664 Seiten
ISBN: 978-0-08-092219-5
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)
The book describes the integration of molecular and cellular pathogenesis using a bioinformatics approach and a systems biology approach to disease pathogenesis. It also discusses current and future strategies in molecular diagnosis of human disease, and the impact of molecular diagnosis on treatment decisions and the practice of personalized medicine.
This book is a valuable resource for students, biomedical researchers, practicing physician-scientists who undertake disease-related basic science and translational research, and pathology residents and other postdoctoral fellows.
* Exam Master® web site will host 'Self-assessment' questions that students can use to study for the molecular section of the board exam
* Companion Web Site - will host a complete set of PowerPoint slides: to include images from the book and additional images for teaching; course materials; lecture materials
* Teaches from the perspective of 'integrative systems biology,” which encompasses the intersection of all molecular aspects of biology, as applied to understanding human disease
* Outlines the principles and practice of molecular pathology
* Explains the practice of 'molecular medicine” and the translational aspects of molecular pathology
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Molecular Pathology;4
3;Series Page;3
4;Copyright Page;5
5;Dedication Page;6
6;Contents;8
7;List of Contributors;12
8;Preface;16
9;Foreword;18
10;Acknowledgments;20
11;Part I: Essential Pathology - Mechanisms of Disease;22
11.1;Chapter 1: Molecular Mechanisms of Cell Death;24
11.1.1;Introduction;24
11.1.2;Modes of Cell Death;24
11.1.3;Structural Features of Necrosis and Apoptosis;24
11.1.4;Cellular and Molecular Mechanisms Underlying Necrotic Cell Death;26
11.1.5;Pathways to Apoptosis;33
11.1.6;Mitochondria;36
11.1.7;Nucleus;39
11.1.8;Endoplasmic Reticulum;39
11.1.9;Lysosomes;39
11.1.10;Concluding Remark;40
11.1.11;Acknowledgments;40
11.1.12;References;41
11.2;Chapter 2: Acute and Chronic Inflammation Induces Disease Pathogenesis;46
11.2.1;Introduction;46
11.2.2;Leukocyte Adhesion, Migration, and Activation;46
11.2.3;Acute Inflammation and Disease Pathogenesis;49
11.2.4;Pattern Recognition Receptors and Inflammatory Responses;50
11.2.5;Chronic Inflammation and Acquired Immune Responses;53
11.2.6;Tissue Remodeling During Acute and Chronic Inflammatory Disease;55
11.2.7;References;58
11.3;Chapter 3: Infection and Host Response;62
11.3.1;Microbes and Hosts-Balance of Power?;62
11.3.2;The Structure of the Immune Response;62
11.3.3;Regulation of Immunity;64
11.3.4;Pathogen Strategies;64
11.3.5;The African Trypanosome and Antibody Diversity: Dueling Genomes;64
11.3.6;Staphylococcus Aureus: the Extracellular Battleground;69
11.3.7;Mycobacterium Tuberculosis and the Macrophage;73
11.3.8;Herpes Simplex Virus: Taking Over;76
11.3.9;HIV: The Immune Guerilla;78
11.3.10;Perspectives;81
11.3.11;References;82
11.4;Chapter 4: Neoplasia;84
11.4.1;Introduction;84
11.4.2;Cancer Statistics and Epidemiology;84
11.4.3;Classification of Neoplastic Diseases;91
11.4.4;Characteristics of Benign and Malignant Neoplasms;99
11.4.5;Clinical Aspects of Neoplasia;103
11.4.6;References;104
12;Part II: Concepts in Molecular Biology and Genetics;108
12.1;Chapter 5: Basic Concepts in Human Molecular Genetics;110
12.1.1;Introduction;110
12.1.2;Molecular Structure of DNA, DNA Transcription, and Proten Translation;110
12.1.3;Molecular Pathology and DNA Repair Mechanisms;113
12.1.4;Modes of Inheritance;117
12.1.5;Central Dogma and Rationale for Genetic Testing;122
12.1.6;Allelic Heterogeneity and Choice of Analytical Methodology;125
12.1.7;Conclusion;128
12.1.8;References;128
12.2;Chapter 6: The Human Genome: Implications for the Understanding of Human Disease;130
12.2.1;Introduction;130
12.2.2;Structure and Organization of the Human Genome;130
12.2.3;Overview of the Human Genome Project;132
12.2.4;Impact of the Human Genome Project on the Identification of Disease-Related Genes;134
12.2.5;Sources of Variation in the Human Genome;136
12.2.6;Types of Genetic Diseases;137
12.2.7;Genetic Diseases and Cancer;138
12.2.8;Perspectives;140
12.2.9;References;140
12.3;Chapter 7: The Human Transcriptome: Implications for the Understanding of Human Disease;144
12.3.1;Introduction;144
12.3.2;Gene Expression Profiling: The Search for Candidate Genes Involved in Pathogenesis;144
12.3.3;Transcriptome Analysis Based on Microarrays: Technical Prerequisites;147
12.3.4;Microarrays: Bioinformatic Analysis;151
12.3.5;Microarrays: Applications in Basic Research and Translational Medicine;158
12.3.6;Perspectives;167
12.3.7;References;169
12.4;Chapter 8: The Human Epigenome: Implications for the Understanding of Human Disease;172
12.4.1;Introduction;172
12.4.2;Epigenetic Regulation of the Genome;172
12.4.3;Genomic Imprinting;173
12.4.4;Cancer Epigenetics;175
12.4.5;Human Disorders Associated with Epigenetics;178
12.4.6;Environment and the Epigenome;181
12.4.7;References;181
12.5;Chapter 9: Clinical Proteomics and Molecular Pathology;186
12.5.1;Understanding Cancer at the Molecular Level: An Evolving Frontier;186
12.5.2;Microdissection Technology Brings Molecular Analysis to the Tissue Level;186
12.5.3;Serum Proteomics: an Emerging Landscape for Early Stage Cancer Detection;195
12.5.4;References;202
12.6;Chapter 10: Integrative Systems Biology: Implications for the Understanding of Human Disease;206
12.6.1;Introduction;206
12.6.2;Data Generation;207
12.6.3;Data Integration;209
12.6.4;Modeling Systems;210
12.6.5;Implications for Understanding Disease;211
12.6.6;Discussion;213
12.6.7;References;214
13;Part III: Principles and Practice of Molecular Pathology;216
13.1;Chapter 11: Pathology: The Clinical Description of Human Disease;218
13.1.1;Introduction;218
13.1.2;Terms, Definitions, and Concepts;218
13.1.3;A Brief History of Approaches to Disease;219
13.1.4;Current Practice of Pathology;224
13.1.5;The Future of Diagnostic Pathology;227
13.1.6;Conclusion;228
13.1.7;References;228
13.2;Chapter 12: Understanding Molecular Pathogenesis: The Biological Basis of Human Disease and Implications for Improved Treatment of Human D;230
13.2.1;Introduction;230
13.2.2;Hepatitis C Virus Infection;230
13.2.3;Acute Myeloid Leukemia;233
13.2.4;Cystic Fibrosis;234
13.2.5;References;237
13.3;Chapter 13: Integration of Molecular and Cellular Pathogenesis: A Bioinformatics Approach;240
13.3.1;Introduction;240
13.3.2;Overview of Bioinformatics;241
13.3.3;Database Resources;242
13.3.4;Data Analysis;243
13.3.5;The Future of Bioinformatics;244
13.3.6;References;245
14;Part IV: Molecular Pathology of Human Disease;246
14.1;Chapter 14: Molecular Basis of Cardiovascular Disease;248
14.1.1;Introduction;248
14.1.2;General Molecular Principles of Cardiovascular Diseases;248
14.1.3;The Cells of Cardiovascular Organs;248
14.1.4;Atherosclerosis;253
14.1.5;Ischemic Heart Disease;256
14.1.6;Aneurysms;256
14.1.7;Vasculitis;257
14.1.8;Valvular Heart Disease;257
14.1.9;Cardiomyopathies;259
14.1.10;References;264
14.2;Chapter 15: Molecular Basis of Hemostatic and Thrombotic Diseases;268
14.2.1;Introduction and Overview of Coagulation;268
14.2.2;Disorders of Soluble Clotting Factors;270
14.2.3;Disorders of Fibrinolysis;277
14.2.4;Disorders of Platelet Number or Function;277
14.2.5;Thrombophilia;281
14.2.6;References;283
14.3;Chapter 16: Molecular Basis of Lymphoid and Myeloid Diseases;286
14.3.1;Development of the Blood and Lymphoid Organs;286
14.3.2;Myeloid Disorders;292
14.3.3;Lymphocyte Disorders;300
14.3.4;References;308
14.4;Chapter 17: Molecular Basis of Diseases of Immunity;312
14.4.1;Introduction;312
14.4.2;Normal Immune System;312
14.4.3;Major Syndromes;317
14.4.4;References;325
14.5;Chapter 18: Molecular Basis of Pulmonary Disease;326
14.5.1;Introduction;326
14.5.2;Neoplastic Lung and Pleural Diseases;326
14.5.3;Non-neoplastic Lung Disease;344
14.5.4;Obstructive Lung Diseases;344
14.5.5;Interstitial Lung Diseases;352
14.5.6;Pulmonary Vascular Diseases;359
14.5.7;Pulmonary Infections;363
14.5.8;Pulmonary Histiocytic Diseases;373
14.5.9;Pulmonary Occupational Diseases;375
14.5.10;Developmental Abnormalities;377
14.5.11;References;379
14.6;Chapter 19: Molecular Basis of Diseases of the Gastrointestinal Tract;386
14.6.1;Introduction;386
14.6.2;Gastric Cancer;386
14.6.3;Colorectal Cancer;393
14.6.4;References;407
14.7;Chapter 20: Molecular Basis of Liver Disease;416
14.7.1;Introduction;416
14.7.2;Molecular Basis of Liver Development;416
14.7.3;Molecular Basis of Liver Regeneration;418
14.7.4;Adult Liver Stem Cells in Liver Health and Disease;420
14.7.5;Molecular Basis of Hepatocyte Death;421
14.7.6;Molecular Basis of Nonalcoholic Fatty Liver Disease;423
14.7.7;Molecular Basis of Alcoholic Liver Disease;427
14.7.8;Molecular Basis of Hepatic Fibrosis and Cirrhosis;428
14.7.9;Molecular Basis of Hepatic Tumors;429
14.7.10;References;433
14.8;Chapter 21: Molecular Basis of Diseases of the Exocrine Pancreas;442
14.8.1;Acute Pancreatitis;442
14.8.2;Chronic and Hereditary Pancreatitis;447
14.8.3;Summary;451
14.8.4;References;451
14.9;Chapter 22: Molecular Basis of Diseases of the Endocrine System;456
14.9.1;Introduction;456
14.9.2;The Pituitary Gland;456
14.9.3;The Thyroid Gland;460
14.9.4;The Parathyroid Gland;467
14.9.5;The Adrenal Gland;471
14.9.6;Puberty;475
14.9.7;References;480
14.10;Chapter 23: Molecular Basis of Gynecologic Diseases;486
14.10.1;Introduction;486
14.10.2;Benign and Malignant Tumors of the Female Reproductive Tract;486
14.10.3;Disorders Related to Pregnancy;498
14.10.4;References;502
14.11;Chapter 24: Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations;510
14.11.1;Introduction;510
14.11.2;Hereditary Component of Prostate Cancer Risk;511
14.11.3;Somatic Alterations in Gene Expression;511
14.11.4;Epigenetics;514
14.11.5;Advances in Mouse Models of Prostate Cancer;515
14.11.6;Conclusion;517
14.11.7;Acknowledgments;517
14.11.8;References;517
14.12;Chapter 25: Molecular Biology of Breast Cancer;522
14.12.1;Introduction;522
14.12.2;Traditional Breast Cancer Classification;522
14.12.3;Biomarkers;524
14.12.4;Gene Expression Profiling;530
14.12.5;Conclusion;534
14.12.6;References;534
14.13;Chapter 26: Molecular Basis of Skin Disease;540
14.13.1;Skin Diseases and Their Impact;540
14.13.2;Molecular Basis of Healthy Skin;540
14.13.3;Skin Development and Maintenance Provide New Insight into the Molecular Mechanisms of Disease;543
14.13.4;Molecular Pathology of Mendelian Genetic Skin Disorders;546
14.13.5;Molecular Pathology of Common Inflammatory Skin Diseases;552
14.13.6;Skin Proteins as Targets for Inherited and Acquired Disorders;556
14.13.7;Molecular Pathology of Skin Cancer;560
14.13.8;Molecular Diagnosis of Skin Disease;565
14.13.9;New Molecular Mechanisms and Novel Therapies;566
14.13.10;References;570
14.14;Chapter 27: Molecular Pathology: Neuropathology;572
14.14.1;Introduction;572
14.14.2;Anatomy of the Central Nervous System;572
14.14.3;Neurodevelopmental Disorders;575
14.14.4;Neurological Injury: Stroke, Neurodegeneration, and Toxicants;585
14.14.5;Neoplasia;598
14.14.6;Disorders of Myelin;604
14.14.7;References;608
15;Part V: Practice of Molecular Medicine;610
15.1;Chapter 28: Molecular Diagnosis of Human Disease;612
15.1.1;Introduction;612
15.1.2;History of Molecular Diagnostics;612
15.1.3;Molecular Laboratory Subspecialties;614
15.1.4;Future Applications;623
15.1.5;References;624
15.2;Chapter 29: Molecular Assessment of Human Disease in the Clinical Laboratory;626
15.2.1;Introduction;626
15.2.2;The Current Molecular Infectious Disease Paradigm;627
15.2.3;A. New Paradigm for Molecular Diagnostic Applications;628
15.2.4;BCR-ABL: A Model for the New Paradigm;631
15.2.5;Conclusion;633
15.2.6;References;633
15.3;Chapter 30: Pharmacogenomics and Personalized Medicine in the Treatment of Human Diseases;634
15.3.1;Introduction;634
15.3.2;Conclusion;641
15.3.3;References;641
16;Index;644
List of Contributors
Dara L. Aisner, M.D., Ph.D., Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA M. Michael Barmada, Ph.D., Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA, USA Philippe Bedard, M.D., Translational Research Unit, Jules Bordet Institute Université, Libre de Bruxelles, Brussels, Belgium David O. Beenhouwer, M.D., Department of Medicine, David Geffen School of Medicine at University of California, and Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA Jaideep Behari, M.D., Ph.D., Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Maria Berdasco, M.D., Cancer Epigenetics and Biology Program, Catalan Institute of Oncology, Barcelona, Catalonia, Spain Carlise R. Bethel, Ph.D., Sidney Kimmel Comprehensive Cancer Center, Department of Pathology, and the Brady Urological Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA Joseph R. Biggs, Ph.D., Departments of Pathology and Biological Sciences, University of California, San Diego, La Jolla, CA, USA Grant C. Bullock, M.D., Ph.D., Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA Sheldon M. Campbell, M.D., Ph.D., F.C.A.P., Department of Laboratory Medicine, Yale University School of Medicine Pathology and Laboratory Medicine, VA Connecticut Healthcare System, West Haven, CT, USA Wai-Yee Chan, Ph.D., Laboratory of Clinical Genomics, National Institute of Child Health and Human Development, NIH, Bethesda, MD, and Departments of Pediatrics, Biochemistry & Molecular Biology, Georgetown University School of Medicine, Washington, D.C., USA William B. Coleman, Ph.D., Professor and Director of Graduate Studies, Department of Pathology and Laboratory Medicine, Curriculum in Toxicology, Program in Translational Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA Angelo M. De Marzo, M.D., Ph.D., Sidney Kimmel Comprehensive Cancer Center, Department of Pathology, and the Brady Urological Research Institute,Johns Hopkins University School of Medicine, Baltimore, MD, USA Phuong Dinh, M.D., Translational Research Unit, Jules Bordet Institute Université, Libre de Bruxelles, Brussels, Belgium Vladislav Dolgachev, Ph.D., Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA Virginia Espina, M.S., M.T., George Mason University, Center for Applied Proteomics and Molecular Medicine Manassas, VA, USA Manel Esteller, Ph.D, Cancer Epigenetics and Biology Program, Catalan Institute of Oncology, Barcelona, Catalonia, Spain Carol Farver, M.D., Director, Pulmonary Pathology, Vice-Chair for Education, Pathology and Laboratory Medicine Institute, Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA Claudia Fredolini, Ph.D., George Mason University, Center for Applied Proteomics and Molecular Medicine Manassas, VA, USA William K. Funkhouser, M.D., Ph.D., Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA Matthias E. Futschik, Ph.D., Institute for Theoretical Biology, Charité, Humboldt-Universität, Berlin, Germany, Centre for Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal Avrum I. Gotlieb, M.D.C.M., Department of Pathology, Toronto General Research Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Robert Hevner, Ph.D., M.D., Professor, Neurological Surgery/Neuropathology, University of Washington School of Medicine, USA W. Edward Highsmith, Ph.D., Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA C. Dirk Keene, M.D., Ph.D., Associate Professor, Neurological Surgery/Neuropathology, University of Washington School of Medicine, USA Wolfgang Kemmner, Ph.D., Department of Surgery and Surgical Oncology, Robert-Rössle-Klinik Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany Nigel S. Key, M.D., Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA Hong Kee Lee, Ph.D., Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA Joel A. Lefferts, Ph.D., Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA John J. Lemasters, M.D., Ph.D., Center for Cell Death, Injury and Regeneration, Departments of Pharmaceutical & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC, USA Markus M. Lerch, M.D, Department of Internal Medicine A, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany Lance Liotta, Ph.D., George Mason University, Center for Applied Proteomics and Molecular Medicine, Manassas, VA, USA Amber Chang Liu, M.Sc., Department of Pathology, Toronto General Research Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Karen Lu, M.D., Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Nicholas W. Lukacs, Ph.D., Professor of Pathology, Director Molecular and Cellular Pathology Graduate Program University of Michigan Medical School, Ann Arbor, MI, USA Alice Ma, M.D., Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA Arlene Martin, M.D., Department of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA Malcolm M. Martin, M.D., Department of Pediatrics, Georgetown University School of Medicine, Washington, DC, USA Julia Mayerle, Department of Internal Medicine A, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany John A. McGrath, M.D. FRCP, Genetic Skin Disease Group, St John’s Institute of Dermatology, King’s College London, Guy’s Campus, London, UK Kara A. Mensink, M.S., Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Samuel Chi-ho Mok, Ph.D., Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA Satdarshan (Paul) Singh Monga, M.D., Director-Division of Experimental Pathology, Associate Professor of Pathology and Medicine, University of Pittsburgh, School of Medicine Pittsburgh, PA, USA Thomas J. Montine, M.D., Ph.D., Division of Neuropathology, Department of Pathology,...
