Additional Information
Book Details
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Contents | xi | ||
| Epigraph | vii | ||
| Preface | ix | ||
| Acknowledgements | xv | ||
| Part I Social Dimensions of Health | 1 | ||
| 1. Looking Back | 3 | ||
| The Witwatersrand and Mining | 4 | ||
| Political Tensions | 5 | ||
| 2. Socio-economic Factors and Health: Medical School and Beyond | 7 | ||
| 3. Trauma and Experiences in the Surgical Unit at Baragwanath | 9 | ||
| Esophageal Cancer | 14 | ||
| 4. South Africa in the Past and in the Present Millennium | 17 | ||
| WHO Millennium Development Goals (MDG) | 19 | ||
| References | 19 | ||
| Part II Mothers and Children | 21 | ||
| 5. Pregnancy and Hazards | 23 | ||
| Pre-eclampsia and Eclampsia | 24 | ||
| Uterine Rupture | 25 | ||
| Maternal Morbidity and Mortality during Labor and Delivery and in the Post-partum Period | 26 | ||
| Measures to Reduce Maternal Mortality and Morbidity | 27 | ||
| 6. Newborn Infants: Prematurity and Other Problems | 29 | ||
| Prematurity and Causes | 31 | ||
| Preterm Birth in Developed Countries | 32 | ||
| Spontaneous Preterm Birth | 32 | ||
| Preterm Births in the USA | 33 | ||
| Survival Rates of Preterm Infants | 33 | ||
| 7. Neural Tube Defects | 35 | ||
| World-wide Studies on Neural Tube Defects | 38 | ||
| Pathogenesis of Neural Tube Defects | 38 | ||
| Measurable Markers of Neural Tube Defectsduring Pregnancy | 39 | ||
| 8. Thyroid Hormone Deficiency in Infants and Children | 41 | ||
| Historical Discoveries Related to Hypothyroidism | 42 | ||
| Hypothalamic–pituitary Axis and Thyroid Function | 44 | ||
| Iodine Deficiency in Recent Decades | 45 | ||
| References | 46 | ||
| Part III Infection Related Diseases | 51 | ||
| 9. Fading, Emerging and Re-emerging Infectious Diseases | 53 | ||
| Rheumatic Fever | 55 | ||
| Damage to Heart Valves and Further Complications | 57 | ||
| Bacterial Endocarditis in the 21st Century | 57 | ||
| Post-streptococcal Glomerulonephritis | 58 | ||
| Prevention of Rheumatic Heart Disease and Acute Glomerulonephritis in the Antibiotic Era | 58 | ||
| Invasive Infections: New Diseases or Newly Recognized Diseases? | 59 | ||
| 10. Tuberculosis | 61 | ||
| A History of Tuberculosis | 63 | ||
| Tuberculosis and Societal Conditions | 64 | ||
| Tuberculosis Returns | 65 | ||
| Tuberculosis and the Possibilities for Effective Vaccines | 65 | ||
| Biomarkers of Active Tuberculosis | 67 | ||
| 11. Tetanus | 69 | ||
| 12. Viral Infections that May Lead to Cancer | 73 | ||
| (a) Hepatitis Viruses and Hepatoma | 73 | ||
| Discovery of Hepatitis B Virus | 74 | ||
| Hepatitis B Virus and Hepatoma | 75 | ||
| Development of an HBV Vaccine | 75 | ||
| Successes Achieved with HBV Vaccine | 76 | ||
| Hepatitis B Worldwide | 76 | ||
| Hepatitis B and Hepatitis C in Hepatocellular Carcinoma | 77 | ||
| Hepatocellular Carcinoma and Hepatitis B and C Viruses Worldwide | 77 | ||
| Attempts to Control Hepatitis C Virus Infections | 77 | ||
| Mycotoxins | 78 | ||
| (b) Human Papilloma Virus, Cervical and other Cancers | 78 | ||
| Development of a Vaccine that Induces Immunity to Human Papilloma Viruses | 79 | ||
| (b) Herpes 8 Virus and Kaposi Sarcoma | 79 | ||
| 13. HIV/AIDS | 81 | ||
| References | 81 | ||
| Part IV Infections, Therapy and Prevention | 87 | ||
| 14. The Golden Age of Antibiotics, and Has it Passed? | 89 | ||
| The Golden Age | 89 | ||
| A History of Penicillin Discovery | 91 | ||
| Antibiotic Discovery Processes | 92 | ||
| 15. Antibiotic Resistance Mechanisms | 95 | ||
| Genomes, Mobilomes, Information Transfer — Another Mechanism of Antibiotic Resistance Acquisition | 96 | ||
| Salmonella enterica Variants and Plasmids | 97 | ||
| Drug Resistant Mycobacterium tuberculosis | 98 | ||
| 16. Genomics and Natural Product Discovery | 101 | ||
| Additional Methods for Discovery of New Antibiotics | 102 | ||
| New Methods to Identify “Unculturable” Soil Microbes | 102 | ||
| 17. The Human Microbiome | 105 | ||
| The Gut Microbiome Kwashiorkor Connection | 105 | ||
| Antibiotics Impact Gut Microbiome and Clostridium difficile Infections | 106 | ||
| 18. Bacterial Microfilms | 109 | ||
| Treatment Strategies | 110 | ||
| 19. Strategies to Overcome the Problem of Bacterial Antibiotic Resistance | 113 | ||
| Novel Antibacterial Agents | 114 | ||
| Investigations Into Use of Bacteriophage to Fight Bacterial Infections | 114 | ||
| 20. Point of Care Diagnostics | 117 | ||
| 21. Defining Biomarkers to Help Distinguish Viral Diseases from Bacterial Diseases | 119 | ||
| 22. Vaccines in the 21st Century | 121 | ||
| Examples of Active Vaccine Research and Development of Candidate Vaccines in 2016 | 122 | ||
| Dengue fever | 122 | ||
| Polio | 122 | ||
| Emerging Problems with use of Attenuated Virus Vaccines | 123 | ||
| Possibilities for Development of Effective HIV Vaccines | 124 | ||
| Vaccine Development | 124 | ||
| Economic Factors in Vaccine Development | 125 | ||
| Vaccines against Ebola | 126 | ||
| 23. New Economic Approaches to Financing New Medications | 127 | ||
| References | 128 | ||
| Part V Nuclei, Chromosomes, Genomes and Gene Products | 133 | ||
| 24. Entering Genetics through Studies on Nuclei, Chromatin and Chromosomes | 135 | ||
| Training in Tissue Culture and Cytogenetics | 136 | ||
| Progress in Understanding Disorders of Sexual Development | 137 | ||
| Key Genes in Male Sexual Differentiation | 139 | ||
| Key Genes in Female Sexual Development | 139 | ||
| 25. Excursions into Enzymes, Polymorphisms and Biochemistry | 141 | ||
| Adventures in Biochemical Genetics | 141 | ||
| Testing Hypotheses on the Subunit Structure of the ADH1, ADH2 and ADH3 Gene Products | 142 | ||
| Molecular Genetic Studies on Alcohol Dehydrogenase | 143 | ||
| Additional ADH Gene Loci | 143 | ||
| Molecular Analyses of Individual Variation of ADH Genes | 143 | ||
| Use of Polymerase Chain Reactions (PCR) to Reveal ADH Polymorphisms | 144 | ||
| Class I ADH Genes and Population Studies | 145 | ||
| Clinical Relevance of ADH Studies | 145 | ||
| Fetal Alcohol Exposure | 146 | ||
| 26. Gene Mapping and Somatic Cell Genetics | 149 | ||
| Human Gene Mapping | 149 | ||
| Somatic Cell Hybrids | 150 | ||
| 27. Catching up on Developments in Molecular Genetics through the 1960s and 1970s | 153 | ||
| Intense Efforts on Molecular Biology followed Discovery of the DNA Structure | 154 | ||
| Enzymes and the Molecular Revolution | 155 | ||
| Polymerases | 155 | ||
| Reverse Transcriptase | 155 | ||
| Restriction Endonucleases | 155 | ||
| Ligases | 156 | ||
| Southern Blots | 156 | ||
| DNA Sequencing | 156 | ||
| The Impact of the Molecular Cloning Manual of Sambrook, Fritsch and Maniatis | 157 | ||
| Interrupted Genes | 157 | ||
| Incorporation of DNA Technology into Human Gene Mapping and Linkage Studies | 158 | ||
| DNA markers for human gene mapping and linkage studies | 158 | ||
| DNA Amplification through use of the Polymerase Chain Reaction (PCR) | 159 | ||
| Discovery of Polymorphic Markers through Application of PCR Technology | 160 | ||
| Physical Mapping of Markers to Chromosomes | 160 | ||
| In situ hybridization | 160 | ||
| Advances in Nucleic Acid Sequencing Techniques | 161 | ||
| 28. The Human Genome Project and Advances in Genetics and Genomics | 163 | ||
| Early Fruits of the HGP: A Map of Sequence Tagged Sites | 164 | ||
| Draft Sequence of the Human Genome | 164 | ||
| Next-Generation Sequencing Methods | 165 | ||
| Massively parallel sequencing | 165 | ||
| Third Generation Sequencing Methods | 166 | ||
| Nanopore Sequencing | 166 | ||
| Analysis of Functional Elements in the Genome | 166 | ||
| Chromatin Architecture and Transcription | 167 | ||
| Non-protein-coding RNA | 167 | ||
| Relevance of Information on the Human Genome Sequence and of Transcription Information for Clinical Medicine | 168 | ||
| Microarrays | 168 | ||
| Analysis of a Specific Gene or Analysis of a Gene Panel | 169 | ||
| Whole Exome or Whole Genome Sequencing | 169 | ||
| Mutation Types and Consequences | 170 | ||
| Genome-wide Association Studies | 171 | ||
| Impact of Gene Interactions | 171 | ||
| Genome-wide Association Studies and Information on Susceptibility to Medication Toxicity | 172 | ||
| DNA Analysis in Forensics | 172 | ||
| DNA Analysis in Cancer | 173 | ||
| Hereditary Cancer Syndromes | 174 | ||
| Analysis of Gene Expression in Tumors | 174 | ||
| Cancer Databases | 174 | ||
| Circulating Tumor DNA and Liquid Biopsy | 175 | ||
| Exosome Shedding by Tumors | 175 | ||
| Emerging Plasma Biomarkers in Cancer Diagnoses | 176 | ||
| 29. Gene Regulation and “Endless Forms Most Beautiful” | 177 | ||
| Interconnected: A Gene Shared Family — the Homeodomain Genes | 178 | ||
| Temporal and Spatial Differences in Gene Expression at Different Life Stages | 179 | ||
| Differences in Expression of Products of a Gene | 179 | ||
| Enhancers | 179 | ||
| Promoters | 180 | ||
| Insights into Transcription and its Control | 182 | ||
| One Gene, Different Transcripts, Different Proteins | 183 | ||
| Cell Type Specific Splicing | 183 | ||
| Regulation of Exon Usage | 184 | ||
| Impact of RBFOX1 Gene Expression Levels | 184 | ||
| Regulatory Functions of RNA | 185 | ||
| What Happens to mRNA Spliced out from Introns Contained in Primary RNA Transcripts? | 186 | ||
| Long Non-coding RNAs | 186 | ||
| Epigenetics | 186 | ||
| Nucleotide Modifications | 187 | ||
| Chromatin, Histones: Architecture and Modifications | 187 | ||
| Patterns of Histone Modifications and Gene Expression | 188 | ||
| Chromatin Architecture and Chromatin Remodeling | 188 | ||
| Transcription Factors | 189 | ||
| Nutrition and Epigenetics | 189 | ||
| Environmental Factors and Epigenetics | 189 | ||
| Deficiencies on our Understanding of Gene Regulation | 189 | ||
| References | 190 | ||
| Part VI Genetic Variation and Diseases | 199 | ||
| 30. Founder Mutations, Specific Genetic Disorders in Different Countries | 201 | ||
| 31. Hypercholesterolemia, Heart Disease and Atherosclerosis | 203 | ||
| Low-density Lipoprotein Receptor (LDLR) Mutations | 204 | ||
| Additional Causes of Raised LDL Cholesterol Levels | 205 | ||
| 32. Cardiomyopathy | 207 | ||
| Criteria to Determine that a Mutation is Pathogenic | 209 | ||
| 33. Porphyria | 211 | ||
| A Diligent Physician and an Amazing Story | 211 | ||
| Porphyria Variegata | 212 | ||
| Discovery of the Enzyme Defect in Variegate Porphyria and Characterization of Gene Defect | 213 | ||
| Porphyria New York | 213 | ||
| 34. Gaucher Disease | 217 | ||
| 35. Hemoglobins and Hemoglobinopathies | 219 | ||
| History of Hemoglobin and Hemoglobinopathies | 220 | ||
| Hemoglobin in Patients with Anemia | 220 | ||
| Application of Molecular Biology to the Study of Thalassemias | 222 | ||
| Thalassemias | 224 | ||
| Alpha Thalassemia | 225 | ||
| Alpha Thalassemia and Clinical Manifestations in World Populations | 226 | ||
| Other Hemoglobinopathies that Occur with High Frequencies in Specific Populations | 227 | ||
| Hemoglobin E (HbE) | 227 | ||
| Hemoglobin C (HbC) | 228 | ||
| My Interest in Hemoglobins Takes a Personal Turn | 228 | ||
| My Later Involvement with Hemoglobinopathies | 230 | ||
| Hemoglobinopathies in Europe | 231 | ||
| Current Comprehensive Programs for Treatment of Severe Hemoglobinopathies | 231 | ||
| Sickle cell disease | 231 | ||
| Thalassemias | 231 | ||
| New Approaches to the Treatment of Beta Globin Hemoglobinopathies | 232 | ||
| Investigations into Regulators of Gamma Globin Production | 232 | ||
| Pre-clinical Studies Investigating Gene Editingto Treat Hemoglobinopathies | 233 | ||
| 36. Hemophilia | 235 | ||
| Hemophilia: Breakthroughs and Setbacks | 236 | ||
| Treatment of Hemophilia | 237 | ||
| Isolation, Cloning and Characterization of FVIII and FIX Genes | 237 | ||
| Management of Treatment of Hemophilia in Recent Decades | 238 | ||
| Additional Setbacks: Development of Inhibitors to Infused FVIII or FIX | 238 | ||
| Gene Therapy in Hemophilia | 239 | ||
| The Future: Possibilities for Gene Editing in Hemophilia | 239 | ||
| 37. Cystic Fibrosis | 241 | ||
| A History of Cystic Fibrosis | 241 | ||
| Transformative Reports | 242 | ||
| Genetics of Cystic Fibrosis | 243 | ||
| The CFTR Gene and its Gene Product | 244 | ||
| CFTR Mutations and their Functional Effects | 244 | ||
| General Treatment in Cystic Fibrosis | 246 | ||
| Molecular Screening for Therapeutic Agents | 246 | ||
| Other Phenotypes that Occur in Patients with CFTR Mutations | 247 | ||
| 38. Inborn Errors of Metabolism | 249 | ||
| A First Case | 249 | ||
| Phenylketonuria, Newborn Screening and Inborn Errors of Metabolism Clinic | 250 | ||
| Advances in the Treatment of PKU | 251 | ||
| Advances in Analysis and Treatment of Inborn Errors of Metabolism | 251 | ||
| Clinical Presentations of Inborn Errors of Metabolism | 252 | ||
| Approaches to the Treatment of Inborn Errors of Metabolism | 252 | ||
| Lysosomal Storage Diseases | 253 | ||
| Progress in Enzyme Replacement Therapy | 254 | ||
| Chaperone Therapy | 255 | ||
| References | 255 | ||
| Part VII Complexities and Striving for Insights | 265 | ||
| 39. Evolution of Therapies, Complexities, Root Causes, and Moves Toward Personalized Medicine | 267 | ||
| Therapies in Modern Times | 267 | ||
| Addressing Root Causes | 267 | ||
| Complex Causation | 269 | ||
| Genome-wide Association Studies (GWAS) | 269 | ||
| Gene–Environment Interactions and Natural Selection | 270 | ||
| The Move Toward Personalized Precision Medicine | 271 | ||
| 40. Psychiatry | 273 | ||
| New Insights through Comprehensive Genetic Studies | 273 | ||
| Demonstration of Polygenic Risk in Psychiatric Disorders | 274 | ||
| 41. Aging | 277 | ||
| Genomic Instability | 277 | ||
| Epigenetic Changes in Aging | 278 | ||
| Proteostasis | 279 | ||
| Mitochondrial Function Deterioration and Aging | 280 | ||
| Nutrient Sensing | 280 | ||
| Cellular Senescence | 280 | ||
| Stem Cell Exhaustion | 281 | ||
| Intercellular Communication | 281 | ||
| Brain Plasticity | 281 | ||
| Neurogenesis in the Adult Brain | 282 | ||
| Aging, Neurodegenerative Disease and Advances | 283 | ||
| 42. Neurodegenerative Diseases | 285 | ||
| Evidence for Origin of Aggregates in One Region and Spread to Other Regions | 286 | ||
| Clinical Features | 286 | ||
| Family Studies and Genetics | 286 | ||
| Alzheimer’s Disease | 287 | ||
| Parkinson’s Disease | 288 | ||
| Amyotrophic Lateral Sclerosis (ALS) | 288 | ||
| Tau Protein in Neurodegenerative Diseases | 289 | ||
| Therapeutic Approaches | 290 | ||
| References | 290 | ||
| Part VIII The Future | 295 | ||
| 43. Stem Cells and Pluripotent Stem Cells | 297 | ||
| Somatic Cell Nuclear Fusion | 297 | ||
| Studies on Teratomas and Teratocarcinomas | 298 | ||
| Embryonic Stem Cells Derived from the Blastocyst | 298 | ||
| Studies Leading up to the 2006 Discovery of Induced Pluripotency in Cells by Takahashi and Yamanaka | 298 | ||
| Vectors used to Transfer Pluripotency Factors | 299 | ||
| Protocols to Establish Induced Pluripotent Stem Cells (IPS cells) | 299 | ||
| Use of IPS Cells as Models to Study Disease-associated Cellular Defects | 300 | ||
| Pluripotent Stem Cells and Cardiomyopathies | 301 | ||
| IPS Cells and Studies of the Aging Process | 301 | ||
| Pluripotent Stem Cells and Regenerative Medicine | 302 | ||
| Cellular Therapies using Bone Marrow-derived Cells | 303 | ||
| Tissue and Organ Chips | 303 | ||
| 44. Gene Editing | 305 | ||
| Gene Editing Technologies | 305 | ||
| Clinical Trials of Gene Edited Cells | 308 | ||
| 45. Antisense Oligonucleotides | 309 | ||
| 46. Towards the Future of Cancer Diagnosis and Therapy | 311 | ||
| Targeted Therapies in Clinical Use for Cancer | 312 | ||
| Liquid Biopsies: Analysis of Circulating Tumor Nucleic Acids | 312 | ||
| Exosomes | 312 | ||
| Cancer Metastases | 313 | ||
| Exosomes | 313 | ||
| Changes in Metabolism in Tumors | 313 | ||
| Immunotherapy in Cancer | 314 | ||
| Immune Modulators | 314 | ||
| Adaptive Cell Transfer and Immunotherapy | 315 | ||
| Tumor Antigens | 316 | ||
| Engineered T Cell Receptors in Cancer Therapy | 316 | ||
| Cancer Vaccines | 316 | ||
| Lipid-complexed Nucleic Acids, Dendritic Cells and Cancer Immunotherapy | 317 | ||
| The Cancer Moonshot | 318 | ||
| Tumor Recurrences | 319 | ||
| Tumor Heterogeneity and Therapy Resistance | 320 | ||
| New Approaches to Early Detection of Tumors | 320 | ||
| New Approaches to Clinical Trials | 321 | ||
| 47. Improved Health, Prolonged Survival and Wellness | 323 | ||
| The Wellness Concept | 323 | ||
| 48. Health: Human and Planetary | 325 | ||
| Expanding Concepts of Health and of the Dimensions of Environmental Impact | 325 | ||
| Planetary Health | 327 | ||
| ARBO viruses | 329 | ||
| Diseases Caused by ARBO Viruses | 330 | ||
| Zika ARBO virus | 330 | ||
| Convergence | 331 | ||
| References | 331 | ||
| Index | 337 |