Note: Cover -- HIV-1: Molecular biology and Pathogenesis: Viral Mechanisms -- Copyright -- Dedication -- Contents -- Contributors -- Preface -- HIV-1 RNA Packaging -- I. Chapter Overview -- II. Introduction -- III. Packaging Pathway -- IV. RNA/Protein Recognition for Encapsidation: Molecular and Structural Biology -- V. Conclusions -- References -- Structure and Function of the HIV Envelope Glycoprotein as Entry Mediator, Vaccine Immunogen, and Target for Inhibitors -- I. Chapter Overview -- II. Introduction -- III. Structure of the Env (gp120-gp41) -- IV. Env Interactions with CD4 and Coreceptor (CCR5 or CXCR4) Leading to Membrane Fusion -- V. Env Interactions with Antibodies -- VI. The Env as Vaccine Immunogen and Target for Inhibitors -- VII. Conclusions -- Acknowledgments -- References -- HIV-1 Reverse Transcription: Close Encounters Between the Viral Genome and a Cellular tRNA -- I. Chapter Overview -- II. Introduction -- III. Reverse Transcription -- IV. Specificity of tRNA Primer Usage -- V. Identification of the PAS Motif -- VI. Proposed Mechanism of Primer Activation -- VII. HIV-1 Replication with a Nonself tRNA Primer Confirms the Importance of the PAS Motif -- VIII. Conclusions -- Acknowledgments -- References -- Transcription of HIV: Tat and Cellular Chromatin -- I. Chapter Overview -- II. Introduction -- III. Integrated HIV-1 LTR and Cellular Chromatin -- IV. The HIV-1 Tat Protein and Its Modifications -- V. Tat-Mediated Transactivation -- VI. Conclusions -- Acknowledgments -- References -- Posttranscriptional Control of HIV-1 and Other Retroviruses and Its Practical Applications -- I. Chapter Overview -- II. Introduction -- III. HIV-1 Regulation of Gene Expression -- IV. Rev and Its Export Receptor CRM1 -- V. Posttranscriptional Regulation of Other Complex Retroviruses. , VI. HIV-1 mRNAs Use Multiple Mechanisms to Express Many Proteins from One Transcript -- VII. Rev-Dependence of HIV-1 mRNAs -- VIII. Use of RNA Optimization to Achieve High Level of HIV-1 gag/pol and env Expression Plasmids -- IX. Posttranscriptional Control of Simple Retroviruses -- X. NXF1 -- XI. Cellular CTEs -- XII. transcriptional Control of LTR-Retroelements -- XIII. Comparison of RNA Export Systems -- XIV. Replacement of Rev Regulation Leads to SIV Attenuation -- XV. Conclusions -- Acknowledgments -- References -- HIV Accessory Genes Vif and Vpu -- I. Chapter Overview -- II. Vif: A Potent Regulator of Viral Infectivity -- III. HIV-1-Specific Vpu Protein -- References -- Interactions of HIV-1 Viral Protein R with Host Cell Proteins -- I. Chapter Overview -- II. Introduction -- III. Effects of HIV-1 Vpr on Host Cellular Activities -- IV. Activation and Counteraction of Host Immune Responses by Vpr -- V. Development of Anti-Vpr Therapies -- Acknowledgment -- References -- HIV-1 Protease: Structure, Dynamics, and Inhibition -- I. Chapter Overview -- II. Introduction -- III. Mature Protease: Structure, Dynamics, and Relationship to Function -- IV. Active Site Inhibitors and Drug Resistance -- V. Dissociation of the Mature Protease Dimer and Characterization of the Monomeric Structure -- VI. Insights into the Structure of the Protease Precursor and Its Maturation -- Acknowledgments -- References -- Properties, Functions, and Drug Targeting of the Multifunctional Nucleocapsid Protein of the Human Immunodeficiency Virus -- I. Chapter Overview -- II. The NC Protein: The Story So Far -- III. The Structure of HIV-1 NC -- IV. The Network of NC Functions -- V. The Role of NC in HIV-1 Assembly -- VI. The Role of NC in HIV-1 Variability and Fitness -- VII. Anti-NC Drug Screening -- VIII. Conclusions and Future Prospects -- Acknowledgments -- References. , Human Immunodeficiency Virus Type 1 Assembly, Release, and Maturation -- I. Chapter Overview -- II. Overview of HIV-1 Assembly, Release, and Maturation -- III. Multimerization of Gag to Form the Structural Framework of the Immature Virus Particle -- IV. Encapsidation of the Viral RNA Genome -- V. Trafficking Virion Components to the Site of Assembly -- VI. Acquisition of a Lipid Bilayer and Associated Env Glycoproteins -- VII. Virus Particle Release -- VIII. Generating a Mature Infectious Virion -- IX. HIV Assembly and Maturation as Targets for New Antiretroviral Drugs -- Acknowledgments -- References -- Role of Nef in HIV-1 Replication and Pathogenesis -- I. Chapter Overview -- II. Introduction -- III. Nef and HIV-1 Infection of PBMCs -- IV. Nef Studies in Human Thymic Systems -- V. Mechanism of Nef Enhancement of Replication and Pathogenesis -- VI. Conclusions -- References -- Treatment Implications of the Latent Reservoir for HIV-1 -- I. Chapter Overview -- II. Introduction -- III. What is the Latent Reservoir? -- IV. Resistance: Mechanism of Storage in the Latent Reservoir and Its Clinical Implications -- V. Genotypic and Phenotypic Assays: Treatment Implications of the Latent Reservoir -- VI. Drug Development: Taking the Latent Reservoir into Account -- VII. Conclusions -- References -- RNA Interference and HIV-1 -- I. Chapter Overview -- II. Introduction -- III. siRNA as Ant-HIV Therapy -- IV. HIV-1 Remodels Cellular miRNA Expression in Infected Cells -- V. Does HIV-1 Encode miRNAs? -- VI. Future Perspectives -- Acknowledgment -- References -- Index -- Contents of Previous Volumes.

Note: Front Cover -- Biological Response Mediators and Modulators -- Copyright Page -- Table of Contents -- Contributors -- Preface -- Acknowledgments -- CHAPTER 1. RECEPTOR-MEDIATED ENDOCYTOSIS AS EXEMPLIFIED BY THE LOW DENSITY LIPOPROTEIN RECEPTOR -- General Characteristics of Receptor-Mediated Endocytosis -- Pathway of Receptor-Mediated Endocytosis: The LDL Receptor -- Mechanism by Which LDL Receptors Reach Coated Pits -- Recycling of the LDL Receptor -- Functional Domains of the LDL Receptor: Biosynthesis Studies -- References -- CHAPTER 2. THE RECEPTOR FOR EGF FUNCTIONS AS A TYROSINE-SPECIFIC PROTEIN KINASE -- References -- CHAPTER 3. REGULATION OF INSULIN RECEPTOR METABOLISM: MECHANISM OF INSULIN-INDUCED RECEPTOR DOWN-REGULATION -- Change in Insulin Receptor Level Induced by Insulin -- Synthetic and Degradative Rates of Insulin Receptor in Control and Down-regulated Cells -- Effect of Insulin-Induced Down-Regulation on Insulin-Stimulated [1-14C]12-Deoxyglucose Transport -- Characterization of Cell Surface Insulin Receptor Cross-linked Covalently to 1 2 5I-Insulin -- Rate of Appearance of Heavy Receptors at and Loss of Light Receptors from the Plasma Membrane Following the Shift of Cells to Heavy Amino Acids -- Effect of Insulin on the Rates of Appearance of Newly-Synthesized Receptor at and the Net Removal of Previously-Synthesized Receptors from the Cell Surface -- Discussion -- Acknowledgments -- References -- CHAPTER 4. METABOLISM OF ARACHIDONIC ACID BY THE CYCLOOXYGENASE PATHWAY IN MAST CELLS AND BY THE 15- LIPOXYGENASE PATHWAY IN HUMAN EOSINOPHILS -- Acknowledgments -- References -- CHAPTER 5. PHYSIOLOGIC AND PATHOBIOLOGIC EFFECTS OF LEUKOTRIENES C4, D4, AND E4 -- Arachidonic Acid Metabolism in the 5-lipoxygenase Pathway -- Biological Effects on the Leukotrienes -- Cell Sources of the Leukotrienes -- Acknowledgment -- References. , CHAPTER 6. BIOLOGICAL ACTVITIES OF LEUKOTRIENE B4 AND OTHER HYDROXYEICOSATETRAENOIC ACIDS (HETEs) -- Formation of Leukotriene B* and Other Hydroxyeicosatetraenoic Acids -- Biological Activities of Leukotriene B4 and Other Hydroxyeicosatetraenoic Acids -- Conclusions -- References -- CHAPTER 7. ACETYL GLYCERYL ETHER PHOSPHORYLCHOLINE (AGEPC) A MODEL ANAPHYLACTOMIMETIC MEDIATOR -- Anaphylactomimetic Mediators -- Vasoactive Activity of AGEPC -- Smooth Muscle Contracting Activities of AGEPC -- AGEPC-induced Systemic Anaphylactoid Reactions -- Concluding Remarks -- Acknowledgments -- References -- CHAPTER 8. THE ROLE OF LIPOXYGENASE PRODUCTS OF ARACHIDONIC ACID IN INFLAMMATORY EVENTS MEDIATED BY HUMAN BASOPHILS AND MAST CELLS -- Methods and Results -- The Effect of Lipoxygenase Products on Histamine Release from Human Basophils and Mast Cells -- The Modulation of Histamine Release from Human Basophils and Mast Cells -- Discussion -- Acknowledgments -- References -- CHAPTER 9. THE CHEMISTRY AND BIOLOGY OF C3a, C4a, AND C5a AND THEIR EFFECTS ON CELLS -- Correlations Between Anaphylatoxin Structure and Function -- A Duality of Anaphylatoxin Action on Pulmonary Tissue -- Duality of the Action of Anaphylatoxinsin Immunoregulation -- Summary and Conclusion -- Acknowledgments -- References -- CHAPTER 10. ON THE SIZE HETEROGENEITY AND MOLECULAR COMPOSITION OF THE TRANS-MEMBRANE CHANNELS PRODUCED BY COMPLEMENT -- Initial Indication from Electrical Conductance Experiments that Complement Channels are Heterogeneous with Respect to Size -- Molecular Sieving Estimates of the Maximal Size of C5b-8 and C5b-9 Channels -- Studies of the Heterogeneity of C5b-9 Channels by Molecular Sieving with Paired Markers -- The Relation Between Channel Size and the Molecular Composition of the C5b-9 Complex. , Functional Analysis of the Number of C5b6, C7, C8, and C9 Molecules Required for a Single Channel -- Disappearance of Small Channels at High C9 Multiplicity -- Models of Channel Structure -- Summary -- Acknowledgments -- References -- CHAPTER 11. MEMBRANE DAMAGE BY COMPLEMENT COMPONENTS C5b-C9: BIOCHEMICAL AND ULTRASTRUCTURAL STUDIES -- Nomenclature -- Properties of Fluid-phase Terminal Complement Complexes -- Subunit Composition -- Amphiphilic Properties -- Molecular Weight -- Ultrastructure and Membrane Orientation -- Is the Unit Complement Lesion a C5b~9 Monomer or Dimer? -- Mechanism of Membrane Damage by C5b-9(m) -- Perspectives -- Acknowledgments -- References -- CHSPTER 12. CYTOKINE-CELL INTERACTIONS THAT MODULATE INFLAMMATORY REACTIONS -- Interleukin 1 (IL-1) -- Colony Stimulating Factors -- Interleukin 2 (IL-2) -- Interferon -- Sequential Cytokine-Cell Interactions -- Immunopharmacological Implications -- References -- CHAPTER 13. INTERLEUKIN-2 AND THE REGULATION OF CYTOTOXIC CELLS -- Results -- Discussion -- References -- CHAPTER 14. PHARMACOLOGICAL MODULATIONS OF IgE-BINDING FACTOR -- Formation of IgE-potentiating Factors and IgE-suppressive Factors by Lymph Node Cells of Rats Infected with Nippostrongylus brasiliensis -- Pharmacologie Modulation of IgE-binding Factors -- Participation of Lipomodulin in the Selective Formation of IgE-suppressive Factors by Complete Freund's Adjuvant Treatment -- Summary -- Acknowledgments -- References -- CHAPTER 15. MECHANISMS OF ANTIVIRAL ACTION OF INTERFERONS -- Antiviral Actions of Interferons -- Sensitivity of Various Cell Lines to Interferon -- DNA Viruses and Interferons -- Interferon-induced Enzymes and Cell Growth -- Summary -- References -- CHAPTER 16. PHARMACOLOGICAL MANIPULATION OF THE CHEMOTACTIC FACTOR RECEPTOR ON LEUKOCYTES -- Summary -- References. , CHAPTER 17. SECRETORY PRODUCTS IN CYTOTOXICITY -- T Cells -- NK Cells and K Cells -- Granulocytes -- Macrophages -- Conclusions -- Acknowledgments -- References -- CHAPTER 18. ANTIBODY-MEDIATED TUMOR SUPPRESSION: POSSIBLE ROLE OF LYSOPHOSPHATIDYLCHOLINE AND INTERLEUKIN -- Lysophosphatidylcholine -- Interleukin -- Concluding Remarks -- Acknowledgments -- References -- Index.

Note: Front Cover -- HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS -- Copyright Page -- Contents -- Contributors -- Preface -- Chapter 1. HIV Therapeutics: Past, Present, and Future -- I. Individual Drugs and Their Pharmacology -- II. Clinical Studies -- III. Current Recommendations for Treating HIV-1 Infection -- Chapter 2. HIV Drug Resistance and Viral Fitness -- I. Introduction -- II. Methods of Assessment of Viral Fitness -- III. Resistance to Nucleoside Analogs -- IV. Resistance to Other Reverse Transcriptase Inhibitors -- V. Resistance to Protease Inhibitors -- VI. In Vivo Consequences of Resistance-Associated Loss of HIV Fitness -- References -- Chapter 3. Inhibitors of HIV-1 Reverse Transcriptase -- I. Introduction -- II. The Target -- III. Nucleoside Reverse Transcriptase Inhibitors (NRTI) -- IV. Nonnucleoside HIV-1 RT Inhibitors (NNRTI) -- V. Conclusions and Future Directions -- References -- Chapter 4. HIV-1 Protease: Maturation, Enzyme Specificity, and Drug Resistance -- I. Introduction -- II. Organization of the Gag-Pol Precursor and Molecular Structure of the Mature PR -- III. Mechanism and Regulation of PR Maturation -- IV. Substrate/Inhibitor Interactions -- V. Enzyme Specificity -- VI. Drug Resistance -- References -- Chapter 5. HIV-1 Integrase Inhibitors: Past, Present, and Future -- I. Introduction -- II. Chemistry of Retroviral Integration -- III. Role of Divalent Metals: Stoichiometry and Catalysis -- IV. Inhibitor Development -- V. Perspectives -- References -- Chapter 6. Selection of HIV Replication Inhibitors: Chemistry and Biology -- I. Introduction -- II. RNA-Protein Interactions as a Target for Therapeutic Interventions -- III. TAR RNA Ligands as Tat Antagonists -- IV. Encoded One-Bead/One-Compound Combinatorial Library Approach in Discovery of HIV Replication Inhibitors. , V. Ligands for RRE RNA as Inhibitors of Rev-RRE Interactions -- VI. Summary and Perspectives -- References -- Chapter 7. Therapies Directed against the Rev Axis of HIV Autoregulation -- I. Introduction -- II. Transdominant Rev Mutants and Modified Rev Proteins -- III. Antisense Oligonucleotides -- IV. Antisense RNA -- V. Ribozymes -- VI. RRE Decoys -- VII. Intracellular Antibodies against Rev -- VIII. Small Molecules Directed against the Rev Axis -- IX. Therapies against Rev Cofactors -- X. Rev-Activated Suicide and Antiviral Therapies -- XI. Miscellaneous Anti-Rev Effects -- XII. Clinical Trials -- XIII. Conclusion -- References -- Chapter 8. HIV-1 Gene Therapy: Promise for the Future -- I. Introduction -- II. HIV-1 Infection and Conventional Pharmaceutical Agents -- III. Genetic Antivirals to Block HIV-1 Replication -- IV. Genetic "Guns" to Deliver Genetic Antivirals -- V. Animal Model Systems -- VI. Clinical Trials -- References -- Chapter 9. Assessment of HIV Vaccine Development: Past, Present, and Future -- I. Introduction -- II. Virus-Host Interaction -- III. Envelope Glycoprotein -- IV. Viral Vaccine Strategies -- V. Progress in AIDS Vaccine Development -- VI. Factors to Consider in Designing an Envelope-Based Vaccine -- VII. Concluding Remarks -- References -- Chapter 10. HIV-1-Associated Central Nervous System Dysfunction -- I. Introduction -- II. HIV-1-Associated CNS Disease -- III. Cellular Aspects of HIV-1 CNS Infection -- IV. Chemotherapeutic Treatment of HIVD -- V. Summary -- References -- Chapter 11. Molecular Mechanisms of Human Immunodeficiency Virus Type 1 Mother-Infant Transmission -- I. Introduction -- II. Timing of HIV-1 Mother-Infant Transmission -- III. Factors In.uencing HIV-1 Mother-Infant Transmission -- IV. Effect of Smoking on HIV-1 Mother-Infant Transmission. , V. Diagnosis of HIV-1 Infection in Perinatally Infected Infants -- VI. Immunologic Abnormalities in HIV-1-Infected Infants -- VII. Clinical Manifestations in HIV-1-Infected Infants -- VIII. Prevention of HIV-1 Mother-Infant Transmission by Antiretroviral Therapy -- IX. Pathogenesis of HIV-1 Infection and Disease Progression -- X. Molecular and Biological Characterization of HIV-1 Involved in Mother-to-Infant Transmission -- XI. Chemokine Receptors and HIV-1 Mother-Infant Transmission -- XII. Genetic Analysis of HIV-1 Regions Following Mother-to-Infant Transmission -- References -- Chapter 12. Molecular Epidemiology of HIV-1: An Example of Asia -- I. Introduction -- II. Countries in the Advanced Stage of the HIV-1 Epidemic -- III. Countries with a High Potential for Rapid Heterosexual Transmission -- IV. Countries with Low HIV Prevalence Rates -- References -- Chapter 13. Simian Immunodeficiency Virus Infection of Monkeys as a Model System for the Study of AIDS Pathogenesis, Treatment, and Prevention -- I. Introduction -- II. SIV as a Model for Human AIDS -- III. Viral Load Measurements as a Prognostic Indicator -- IV. Modulation of Viral Replication by Partially Protective Vaccines -- V. Antiviral Therapy -- VI. Summary -- References -- Chapter 14. Animal Models for AIDS Pathogenesis -- I. Introduction -- II. Primate Lentiviruses Cause AIDS -- III. SIV Infection of Rhesus Monkeys -- IV. HIV Infection of Macaques -- V. SHIV Infection of Macaques -- VI. HSIV -- VII. HIV Infection of Chimpanzees -- VIII. HIV Infection of SCID Mice -- IX. HIV Infection of Rabbits -- X. Mice Transgenic for Primate Lentivirus Genes -- References -- Index -- Contents of Previous Volumes.

Note: Front Cover -- Advances in Pharmacology: DNA Topoisomerases: Biochemistry and Molecular Biology -- Copyright Page -- Contents -- Contributors -- Preface -- Chapter 1. DNA Topoisomerases as Targets of Therapeutics: An Overview -- I. History and Classification of DNA Topoisomerases -- II. Catalysis of DNA Breakage and Rejoining by DNA Topoisomerases -- III. Catalysis of DNA-Dependent ATP Hydrolysis by Type II DNA Topoisomerases and Ligand-Dependent Allosteric Changes of the Enzymes -- IV. Biochemical Basis of DNA Topoisomerase-Targeting Therapeutics -- V. Biological Basis of DNA Topoisomerase-Targeting Drugs -- VI. Newly Identified DNA Topoisomerases -- VII. Similarities and Differences among DNA Topoisomerases -- VIII. Concluding Remarks -- References -- Chapter 2. Biochemistry of Bacterial Type I DNA Topoisomerases Yuk-Ching Tse-Dinh -- I. Introduction -- II. Escherichia coli DNA Topoisomerase I -- III. Escherichia coli DNA Topoisomerase III -- IV. Thermophilic Archaebacterial Type I Topoisomerases -- V. Site-Specific Type I Topoisomerase Activities -- References -- Chapter 3. The Biochemistry and Biology of DNA Gyrase -- I. Reactions of DNA Gyrase -- II. Structure of DNA Gyrase and Its Complex with DNA -- III. Inhibitors of DNA Gyrase -- IV. Mechanism of the DNA Supercoiling Reaction -- V. Biological Functions of DNA Gyrase -- VI. DNA Supercoiling and Transcription -- References -- Chapter 4. Mechanism of Catalysis by Eukaryotic DNA Topoisomerase I -- I. Introduction -- II. Summary of Reactions Catalyzed by Eukaryotic Type I Topoisomerase -- III. Methods for Uncoupling Closure from Nicking -- IV. Mode of Action of Camptothecin -- V. Specificity -- VI. Structure of Nicked Intermediate and Mechanism of the Reaction -- VII. Summary -- References -- Chapter 5. The DNA Binding, Cleavage, and Religation Reactions of Eukaryotic Topoisomerases I and II. , I. Eukaryotic DNA Topoisomerase I -- II. Eukaryotic Topoisomerase I -- References -- Chater 6. Roles of DNA Topoisomerases in Chromosomal Replication and Segregation -- I. Introduction: Topological Problems of Replication and Chromosome Segregation -- II. Overview of the Functions of Multiple Topoisomerases in Chromosomal Mechanics in Prokaryotic Cells -- III. Functions of Topoisomerases in DNA Replication in Prokaryotes -- IV. Eukaryotic Replication: Initiation and Elongation -- V. Chromosome Segregation in Bacteria -- VI. Chromosome Segregation at Mitosis and Meiosis -- VII. Problems and Paradigms -- References -- Chapter 7. Roles of DNA Topoisomerases in Transcription -- I. Introduction -- II. Effect of Transcription Elongation on DNA Conformation and Structure -- III. Transcription Elongation Affects DNA Functions -- IV. DNA Topoisomerases as Regulators of Transcription-Induced DNA Supercoiling -- V. Conclusion -- References -- Chapter 8. DNA Topoisomerase-Mediated lllegitimate Recombination -- I. Introduction -- II. Illegitimate Recombination Mediated by Type I Topoisomerases -- III. DNA Gyrase-Mediated Illegitimate Recombination -- IV. Illegitimate Recombination Mediated by Type II DNA Topoisomerases of Phage T4 -- V. Illegitimate Recombination Mediated by Mammalian DNA Topoisomerase -- VI. Concluding Remarks -- References -- Chapter 9. Cellular Regulation of Mammalian DNA Topoisomerases -- I. Introduction -- II. Topoisomerase Modifications -- III. Regulation of Topoisomerases during Different Physiological States -- IV. Promoter Activity Analyses -- V. Perspectives -- References -- Chapter 10. Structure of Eukaryotic Type I DNA Topoisomerase -- I. Sizes of Proteins, Transcripts, and Genes -- II. Regulation of the Expression of Topoisomerase I Genes -- III. Sequence Homologies among DNA Topoisomerase I. , IV. Resistance to the Anticancer Drug Camptothecin -- References -- Chapter 11.Type II DNA Topoisomerase Genes -- I. Introduction -- II. Bacterial DNA Gyrases -- III. Bacterial Topoisomerase IV Genes -- IV. T-Even Bacteriophage Topoisomerase Genes -- V. Eukaryotic Type II Topoisomerase Genes -- VI. Multiple Topoisomerase II Genes in Eukaryotes -- VII. Animal Virus-Encoded Topoisomerase II Gene -- VIII. Concluding Remarks -- References -- Chapter 12.Major Advances in Antibacterial Quinolone Therapy -- I. Introduction -- II. Chemistry -- III. Mechanism of Action -- IV. Antimicrobial Activity in Vitro -- V. Factors Affecting the Activity of Fluoroquinolones -- VI. Combination of Fluoroquinolones with Other Antimicrobial Agents -- VII. Resistance of Bacteria to Fluoroquinolones -- VIII. Pharmacology -- IX. Clinical Use -- X. Use of Quinolones in Pediatrics -- XI. Use of Fluoroquinolones in Immunocompromised Patients -- XII. Prophylactic Use of Quinolones -- XIII. Adverse Effects -- XIV. Conclusions -- References -- Chapter 13.4-Quinolones and the Physiology of DNA Gyrase -- I. Introduction -- II. Gyrase and the Control of DNA Supercoiling -- III. Effects of Quinolones on DNA Supercoiling -- IV. Quinolone-Induced DNA Lesions -- V. Quinolones and the Inhibition of DNA Synthesis -- VI. Effects of Quinolones on Gene Expression -- VII. Bactericidal Action of Quinolones -- VIII. Bacterial Resistance to Quinolones -- IX. Concluding Remarks -- References -- Chapter 14. Molecular Mechanisms of DNA Gyrase Inhibition by Quinolone Antibacterials -- I. Introduction -- II. Binding of Quinolones to DNA and to the Gyrase-DNA Complex -- III. The Inhibition Model and Its Implications -- IV. Concluding Remarks -- References -- Index -- Contents of Previous Volumes.

Note: Front Cover -- Apoptosis: Pharmacological Implications and Therapeutic Opportunities -- Copyright Page -- Contents -- Contributors -- Foreword -- Part 1: Biology of Cell Death -- Chapter 1. Apoptosis: An Overview of the Process and Its Relevance in Disease -- I. Introduction -- ll. Morphology of Apoptosis -- lll. Genetics and Biochemistry of Apoptosis -- IV. Apoptosis as a Therapeutic Target -- V. Conclusion -- References -- Chapter 2. Genetics of Apoptosis -- I. Introduction -- II. Programmed Cell Death Pathway in C. elegans -- III. Apoptosis in Drosophila melanogaster -- VI. Apoptosis in Mammals -- V. Viral Genes Involved in Host Cell Apoptosis -- VI. Programmed Cell Death in Unicellular Organisms -- VII. Conclusion -- References -- Chapter 3. Methods Utilized in the Study of Apoptosis -- I. Introduction -- ll. Detection of PCD Based on Morphology -- lll. Detection of DNA Fragmentation -- IV. Terminal Deoxyribonucleotidyl Transferase-Mediated dUTP Nick end Labeling (TUNEL) -- V. Flow Cytometry -- VI. Annexin V Staining -- VII. Alterations in Plasma Membrane Permeability -- VIII. Enzyme Assays -- IX. Use of Inhibitors to Study Apoptotic Processes -- Chapter 4. In Vitro Systems for the Study of Apoptosis -- I. Introduction of Cell-Free Systems for Apoptosis Studies -- ll. Examples of Cell-Free Systems -- lll. Criteria for Relevant Systems -- IV. Biochemical Dissection of in Vitro Systems -- V. Future Directions -- References -- Chapter 5. The Fas Pathway in Apoptosis -- I. Introduction -- ll. Fas -- lll. Fas Ligand -- IV. Regulatory Roles of Fas and FasL -- V. Signaling from the Fas Receptor -- VI. Fas/FasL-Associated Disease States -- VII. Modulating Fas and/or FasL for Therapeutic Purposes -- VIII. Conclusion -- References -- Chapter 6. Ceramide: A Novel Lipid Mediator of Apoptosis -- I. Introduction -- ll. The Sphingomyelin Cycle. , lll. Apoptosis -- IV. Conclusions and Prospects for the Future -- References -- Chapter 7. Control of Apoptosis by Proteases -- I. Introduction -- ll. The ICE/CED-3 Family of Proteases -- lll. Other Proteases Implicated in Apoptosis -- IV. Proteases as Therapeutic Targets in Apoptosis -- References -- Part 2: Apoptosis under Physiologic Conditions -- Chapter 8. Death and Dying in the Immune System -- I. Death -- ll. Dying -- lll. Summary -- References -- Chapter 9. Control of Apoptosis by Cytokines -- I. Introduction -- ll. Cytokines and Survival -- lll. Hematopoietic Growth Factors/Cytokines and Antiapoptotic Signals -- IV. Unresolved Issues Concerning Apoptotic Signals -- V. Novel Therapeutic Strategies Targeting Apoptosis: Tipping the Balance -- References -- Chapter 10. Glucocorticoid-Induced Apoptosis -- I. Introduction -- ll. The Decision to Die: Role of the Glucocorticoid Receptor and Glucocorticoid-Regulated Gens -- Ill. The Decision to Die: Cell Cycle Arrest and Mtabolic Changs -- IV. The Decision to Die: Regulation by Cytokines and T Cell Receptor -- V. Execution Phase: Role of Proteases -- VI. Execution and Degradation: Role of Calcium -- VII. Execution and Degradation: Role of Oxygen Radicals -- VIII. Execution Phase: Bcl-2 and p53 -- IX. Engulfment -- X. Degradation: Morphological Changes -- XI. Degradation: Endonuclease Activation and DNA Fragmentation -- XII. Defects in the Cell Death Pathway Associated with Glucocorticoid Resitance -- XIII. New Research Questions and Therapeutic Possibilities -- References -- Part 3: Apoptosis in Pathologic States -- Chapter 11. Apoptosis in AIDS -- I. Introduction -- ll. Animal Models and Human Studies of HIV-Induced CD4 T Cell Apoptosis -- Ill. Mechanisms of CD4 T Cell Apoptosis Following HIV Infection -- IV. Putting It All Together -- References -- Chapter 12. Virus-Induced Apoptosis. , I. Introduction -- ll. Inhibition of Virus-Induced Apoptosis -- lll. Induction of Programmed Cell Death by Viruses -- IV. Role of Apoptosis in Viral Pathogenesis -- References -- Chapter 13. Apoptosis in Neurodegenerative Diseases -- I. Introduction -- ll. Pathological Features of Neurodegenerative Diseases and Desorders -- lll. Mechanisms for Cytotoxicity in Alzheimer's Disease -- IV. Closing Remarks -- References -- Chapter 14. Apoptosis in the Mammalian Kidney: Incidence, Effectors, and Molecular Control in Normal Development and Disease States -- I. Introduction -- ll. Apoptosis in Normal and Abnormal Renal Development -- lll. Apoptosis and the Adult Kidney: Detection and Occurrence -- IV. Apoptosis in Tubulointerstitial and Glomerular Diseases of the Kidney -- V. Apoptosis in the Genesis and Resolution of Renal Neoplasms -- VI. Molecular and Genetic Factors Involved in the Regulation of Renal Cell Apoptosis -- VII. Summary -- References -- Chapter 15. Apoptosis in the Heart -- I. Introduction -- ll. Two Types of Cell Death-Necrosis and Apoptosis -- lll. Cardiomyocyte Death in Development -- IV. Cardiomyocyte Death in Ischemia and Reperfusion -- V. Modification of Cardiomyocyte Death -- VI. Perspective -- References -- Chapter 16. Apoptosis and the Gastrointestinal System -- l. Introduction -- ll. Liver -- lll. Pancreas -- IV. Small and Large Intestine -- V. Esophagus, Stomach, and Duodenum -- VI. A Vision for Apoptosis as a Therapeutic Target in GI Diseases -- Part 4: Apoptosis in the pathogenesis and Treatment of Cancer -- Chapter 17. Role of p53 in Apoptosis -- I. Introduction -- ll. The p53 Tumor Suppressor Gene -- lll. p53-Mediated GI Arrest -- IV. p53 and Cell Survival -- V. Implications for Tumor Progression and Therapy -- VI. Conclusion -- References -- Chapter 18. Chemotherapy-Induced Apoptosis -- I. Introduction. , ll. Induction of Apoptosis by Chemotherapeutic Agents -- lll. Mechanisms of Induction of Apoptosis by Chemotherapeutic Drugs -- IV. Issues for the Future -- References -- Chapter 19. Bcl-2 Family Proteins: Strategies for Overcoming Chemoresistance in Cancer -- I. Introduction -- ll. Bcl-2 Family Proteins as Determinants of Chemosensitivity -- lll. Dysregulation of Bcl-2 Family Protein Production in Human Cance: Prognostic Implications -- IV. Interactions among Bcl-2 Family Proteins -- V. Potential Functions of Bcl-2 Family Proteins -- VI. Bcl-2 Family Proteins as Pore Formers and Adaptor Proteins -- VII. Posttranslational Modifications of Bcl-2 -- VIII. Are Tumor Cells More Dependent on Bcl-2 Than Normal Cells? -- IX. Strategies for Inhibiting Bcl-2 Function in Cancers -- References -- Chapter 20. Role of Bcr-Abl Kinase in Resistance to Apoptosis -- I. Introduction -- ll. Chronic Myelogenous Leukemia -- lll. Apoptosis: Role of Cellular and Viral Genes -- IV. Abl Family of Tyrosine Kinases -- V. Activated Forms of Abl and Suppression of Apoptosis -- VI. Signaling Mechanism by which Bcr-Abl/v-Abl -- VII. Novel Therapeutic Strategies Based on Interfering with the Exprsion or Activity of Bcr-Abl -- VIII. Mechanism of Resistance to Apoptosis -- References -- Chapter 21. Apoptosis in Hormone-Responsive Malignancies -- I. Introduction -- ll. Breast Cancer -- lll. Prostate Cancer -- IV. Conclusions -- References -- Index -- Contents of Previous Volumes.

Note: Front Cover -- HIV-1: Molecular Biology and Pathogenesis: Viral Mechanisms -- Copyright Page -- Contents -- Contributors -- Preface -- Chapter 1. HIV RNA Packaging and Lentivirus-Based Vectors -- I. Introduction -- II. HIV RNA Packaging -- III. Summary -- References -- Chapter 2. Multiple Biological Roles Associated with the Repeat (R) Region of the HIV-1 RNA Genome -- I. Introduction -- II. Transcription -- III. Polyadenylation -- IV. mRNA Translation -- V. RNA Dimerization/Packaging -- VI. Reverse Transcription -- VII. Perspective and Future Directions -- References -- Chapter 3. HIV Accessory Proteins: Multifunctional Components of a Complex System -- I. Introduction -- II. Vif: A Potent Regulator of Viral Infectivity -- III. Functional Domains in Vif -- IV. Vif Associates with the Cytoskeleton -- V. Vif as a Possible Regulator of Gag/Pol Polyprotein Processing -- VI. Virion-Associated Vif May Have a Crucial Role in Regulating Viral Infectivity -- VII. Vpr and Vpx -- VIII. Vpr as a Transcriptional Activator -- IX. Vpr as a Coactivator of the Glucocorticoid Receptor -- X. Vpr-Induced Cell-Cycle Arrest -- XI. Nuclear Import -- XII. The Multifunctional Nef Protein -- XIII. Downregulation of Cell-Surface CD4 -- XIV. Downregulation of MHC Class I -- XV. Enhancement of Viral Infectivity -- XVI. Acceleration of Disease Progression -- XVII. HIV-1-Specific Vpu Protein -- XVIII. Vpu-Mediated CD4 Degradation -- XIX. Enhancement of Viral Particle Release -- References -- Chapter 4. Role of Chromatin in HIV-1 Transcriptional Regulation -- I. Introduction -- II. HIV-1 Transcriptional Regulatory Elements -- III. Chromatin Is an Integral Component of the Transcriptional Regulatory Apparatus -- IV. HIV-1 Retroviral Integration and Chromatin -- V. DNase I-Hypersensitive Sites in the HIV-1 Genome -- VI. Nucleosomes Are Precisely Positioned in the 5 LTR. , VII. Disruption of a Single Nucleosome at the Transcription Start Site during HIV-1 Transcriptional Activation -- VIII. Two Novel Regulatory Regions Are Associated with DNase I-Hypersensitive Sites in the HIV-1 Provirus -- IX. Role of Histone Acetylation/Deacetylation in HIV-1 Transcriptional Regulation -- X. Role of Tat in HIV-1 Promoter Chromatin Remodeling and Transcriptional Activation -- XI. Study of HIV-1 Transcription using in vitro Chromatin- Reconstituted Templates -- XII. Conclusions -- References -- Chapter 5. NF-κB and HIV: Linking Viral and Immune Activation -- I. Introduction -- II. Historical Perspectives -- III. The NF-κB/Rel Transcription Factors -- IV. NF-κB and the Regulation of HIV Transcription -- V. Other Roles for NF-κB in HIV Infection -- VI. NF-κB and HIV Replication -- VII. NF-κB and HIV Pathogenesis -- VIII. Therapeutic Modulation of NF-κB: A Role in HIV Therapy? -- IX. Conclusions -- References -- Chapter 6. Tat as a Transcriptional Activator and a Potential Therapeutic Target for HIV-1 -- I. Mechanisms of Tat-Mediated Trans-Activation -- II. Cellular Cofactors for Trans-Activation -- III. Therapeutic Anti-Tat Strategies -- References -- Chapter 7. From the Outside In: Extracellular Activities of HIV Tat -- I. Introduction -- II. Tat and Angiogenesis-The Kaposi Connection -- III. Tat and Immunosuppression -- IV. Tat as a Cytokine -- References -- Chapter 8. Rev Protein and Its Cellular Partners -- I. Introduction -- II. Characteristics of the Rev Protein -- III. Rev and Nuclear Export Factors -- IV. Rev and Nuclear Import Factors -- V. Rev and RNA Splicing Factors -- VI. Rev Targeted Therapy -- VIII. Concluding Remarks -- References -- Chapter 9. HIV-1 Nef: A Critical Factor in Viral-Induced Pathogenesis -- I. Introduction -- II. Historical Background of Nef Involvement in Pathogenesis -- III. Nef Structure. , IV. Nef Function(s) -- V. Conclusions and Discussion -- References -- Chapter 10. Nucleocapsid Protein of Human Immunodeficiency Virus as a Model Protein with Chaperoning Functions and as a Target for Antiviral Drugs -- I. The Nucleocore -- II. Nucleic Acid Chaperoning Activities of Nucleocapsid Protein -- III. Nucleocapsid Protein and Virion Core Assembly -- IV. Phylogenic Relationships between HIV-1 NCp7 and Nucleocapsid Protein of Other Retroviruses -- V. NCp7 as a Target for Anti-HIV Inhibitors -- VI. Future Prospects -- References -- Chapter 11. Bioactive CD4 Ligands as Pre- and/or Postbinding Inhibitors of HIV-1 -- I. Introducing the CD4 Molecule -- II. Ligands of CD4 -- III. Dissection of CD4 Structure-Function Relationship by Mean of Antibodies and Synthetic Peptides -- IV. Which Conclusions Can Be Drawn about the Function of CDR3-Loop Ligands? -- V. Trials of Anti-CD4 mAbs for Treatment of HIV-Infected Patients -- VI. Trials of CD4-Interacting Peptides in Human Therapy -- VII. Future Developments of CDR3-Loop Ligands -- References -- Chapter 12. Coreceptors for Human Immunodeficiency Virus and Simian Immunode.ciency Virus -- I. Introduction -- II. Cellular Tropism of HIV and SIV -- III. A History of HIV Receptors -- IV. Assays for Coreceptor Activity -- V. Comparison of the Different Assays for Coreceptor Activity -- VI. Discovery of Additional Coreceptors (1996 to 1999) -- VII. Coreceptor Use for HIV-1, HIV-2, and SIV -- VIII. Summary of Coreceptor Use for HIV-1, HIV-2, and SIV -- IX. Expression and Activity of Coreceptors in Cells and Tissues -- X. Can Coreceptor Use Always Explain Tropism? -- XI. Envelope Interactions with CD4 and Coreceptor -- XII. Coreceptors and Pathogenesis -- XIII. Possible Roles for Alternative Coreceptors -- XIV. Some Remaining Questions Regarding Coreceptor Use -- XV. Concluding Remarks -- References -- Index. , Contents of Previous Volumes.

Note: Front Cover -- Catecholamines: Bridging Basic Science with Clinical Medicine -- Copyright Page -- Contents -- Contributors -- Preface -- PART A: CATECHOLAMINE SYNTHESIS AND RELEASE -- Overview -- Section I: Regulation and Expression of Tyrosine Hydroxylase -- Chapter 1. The Effect of Phosphorylation at Ser-40 on the Structure and Thermal Stability of Tyrosine Hydroxylase -- Chapter 2. Factors Affecting Adrenal Medullary Catecholamine Biosynthesis and Release -- Chapter 3. Regulation of Tyrosine Hydroxylase by Neuropeptides -- Chapter 4. Regulation of Tyrosine Hydroxylase Gene Expression by Transsynaptic Mechanisms and Cell-Cell Contact -- Chapter 5. A New Regulatory Protein of Catecholamine Synthesizing- Enzyme Expression -- Chapter 6. Unique and Cell-Type-Specific Tyrosine Hydroxylase Gene Expression -- Chapter 7. Triple Colocalization of Tyrosine Hydroxylase, Calretinin, and Calbindin D-28k in the Periventricular-Hypophyseal Dopaminergic Neuronal System -- Chapter 8. Genetic Disorders Involving Recycling and Formation of Tetrahydrobiopterin -- Chapter 9. Genetic Basis of Dominant Dystonia -- Chapter 10. Mutations in the Tyrosine Hydroxylase Gene Cause Various Forms of L-Dopa-Responsive Dystonia -- Chapter 11. Catecholamine Biosynthetic Enzyme Expression in Neurological and Psychiatric Disorders -- Section II: Other Catecholamine-Synthesizing Enzymes -- Chapter 12. Multiple Pathways in Regulation of Dopamine β-Hydroxylase -- Chapter 13. Examining Adrenergic Roles in Development, Physiology, and Behavior through Targeted Disruption of the Mouse Dopamine β-Hydroxylase Gene -- Chapter 14. Genetic Diseases of Hypotension -- Chapter 15. Dopamine β-Hydroxylase Deficiency Associated with Mutations in a Copper Transporter Gene -- Chapter 16. Glucocorticoid-Phenylethanolamine-N-methyltransferase Interactions in Humans. , Chapter 17. Determinants of Phenylethanolamine-N- methyltransferase Expression -- Chapter 18. Neural Control of Phenylethanolamine-N- methyltransferase via Cholinergic Activation of Egr- I -- Chapter 19. Synexin (Annexin VII) Hypothesis for Ca2+/GTP-Regulated Exocytosis -- Chapter 20. Monoamine Transmitter Release from Small Synaptic and Large Dense-Core Vesicles -- Chapter 21. Calcium Channels for Exocytosis in Chromaffin Cells -- Chapter 22. Characteristics of Transmitter Secretion from Individual Sympathetic Varicosities -- Chapter 23. Neurotransmitter Release at Individual Sympathetic Varicosities, Boutons -- Chapter 24. Appropriate Target Cells Are Required for Maturation of Neurotransmitter Release Function of Sympathetic Neurons in Culture -- Chapter 25. Effects of Neuropeptide Y at Sympathetic Neuroeffector Junctions -- Chapter 26. Strategies for Receptor Control of Neurotransmitter Release -- Chapter 27. Pattern of Adenosine Triphosphate and Norepinephrine Release and Clearance: Consequences for Neurotransmission -- Chapter 28. Corelease of Norepinephrine and Adenosine Triphosphate from Sympathetic Neurones -- Chapter 29. Neuropeptide Y: An Adrenergic Cotransmitter, Vasoconstrictor, and a Nerve-Derived Vascular Growth Factor -- Chapter 30. Neuropeptide Y: A Cardiac Sympathetic Cotransmitter? -- Chapter 31. Biochemistry of Somatodendritic Dopamine Release in Substantia Nigra: An in Vivo Comparison with Striatal Dopamine Release -- Chapter 32. The Use of Dual-Probe Microdialysis for the Study of Catecholamine Release in the Brain and Pineal Gland -- Chapter 33. Kinetics and Geometry of the Excitatory Dopaminergic Transmission in the Rat Striatum in Vivo -- Chapter 34. In Vivo and in Vitro Assessment of Dopamine Uptake and Release -- PART B: CATECHOLAMINE REUPTAKE AND STORAGE -- Overview -- Section I: The Plasma Membrane Transporters. , Chapter 1. Molecular Physiology and Regulation of Catecholamine Transporters -- Chapter 2. Localization of Dopamine Transporter Protein by Microscopic Histochemistry -- Chapter 3. Cellular and Subcellular Localization of the Dopamine Transporter in Rat Cortex -- Chapter 4. Cloned Catecholamine Transporters Expressed in Polarized Epithelial Cells: Sorting, Drug Sensitivity, and Ion-Coupling Stoichiometry -- Chapter 5. Inactivation of the Dopamine Transporter Reveals Essential Roles of Dopamine in the Control of Locomotion, Psychostimulant Response, and Pituitary Function -- Chapter 6. Role of Protein Kinase C and Second Messengers in Regulation of the Norepinephrine Transporter -- Chapter 7. Electrophysiological Analysis of Transporter Function -- Chapter 8. Voltammetric Approaches to Kinetics and Mechanism of the Norepinephrine Transporter -- Chapter 9. Voltage-Dependency of the Dopamine Transporter in Rat Brain -- Chapter 10. Modulation of Quantal Dopamine Release by Psychostimulants -- Chapter 11. Regulation of Dopamine Transporter mRNA Levels in the Central Nervous System -- Chapter 12. Structural Diversity in the Catecholamine Transporter Gene Family: Molecular Cloning and Characterization of an L-Epinephrine Transporter from Bullfrog Sympathetic Ganglia -- Chapter 13. Positron Emission Tomography Radiogands for Dopamine Transporters and Studies in Human and Nonhuman Primates -- Chapter 14. Single Photon Emission Computed Tomography Imaging of Dopaminergic Function: Presynaptic Transporter, Postsynaptic Receptor, and "Intrasynaptic" Transmitter -- Chapter 15. Dopamine Transporter Changes in Neuropsychiatric Disorders -- Section II: Vesicular Transporters and Catecholamine Storage -- Chapter 16. Molecular and Biochemical Studies of Rat Vesicular Monoamine Transporter. , Chapter 17. A Chimeric Vesicular Monoamine Transporter Dissociates Sensitivity t o Tetrabenazine and Unsubstituted Aromatic Amines -- Chapter 18. Ligand Recognition by the Vesicular Monoamine Transporters -- Chapter 19. Molecular Pharmacology of the Vesicular Monoamine Transporter -- Chapter 20. Ultrastructural Localization of the Vesicular Monoamine Transporter 2 in Mesolimbic and Nigrostriatal Dopaminergic Neurons -- Chapter 21. ICA 512, Receptor Tyrosine Phosphatase-Like Protein, is Concentrated in Neurosecretory Granule Membranes -- Chapter 22. Protein Targeting in Neurons and Endocrine Cells -- Chapter 23. The Vesicular Monoamine Transporter VMAT2 and Vesicular Acetylcholine Transporter VAChT Are Sorted to Separate Vesicle Populations in PC I 2 Cells -- Chapter 24. Recycling of Synaptic Vesicles -- Chapter 25. The Secretory Cocktail of Adrenergic Large Dense-Core Vesicles: The Functional Role of the Chromogranins -- Chapter 26. A Novel, Catecholamine Release-Inhibitory Peptide from Chromogranin A: Autocrine Control of Nicotinic Cholinergic-Stimulated Exocytosis -- Chapter 27. Transcription Regulation Coupled to Calcium and Protein Kinase Signaling Systems through TRE- and CRE-Like Sequences in Neuropeptide Genes -- Chapter 28. Imaging of Monoaminergic and Cholinergic Vesicular Transporters in the Brain -- PART C: CATECHOLAMINE METABOLISM: FROM MOLECULAR UNDERSTANDING TO CLINICAL DIAGNOSIS AND TREATMENT -- Overview -- Section I: Monoamine Oxidase -- Chapter 1. Monoamine Oxidase A and B: Structure, Function, and Behavior -- Chapter 2. Genetic Deficiencies of Monoamine Oxidase Isoenzymes: A Key to Understanding the Function of the Enzymes in Humans -- Chapter 3. Biological Markers, with Special Regard to Platelet Monoamine Oxidase (trbc-MAO), for Personality and Personality Disorders -- Chapter 4. Visualization of Monoamine Oxidase in Human Brain. , Chapter 5. Aliphatic N-Methylpropargylamines: Monoamine Oxidase-B Inhibitors and Antiapoptotic Drugs -- Chapter 6. Antiapoptotic Actions of Monoamine Oxidase B Inhibitors -- Chapter 7. Therapeutic Actions of L-Deprenyl in Dogs: A Model of Human Brain Aging -- Chapter 8. Apomorphine Is a Potent Radical Scavenger and Protects Cultured Pheochromocytoma Cells from 6-OHDA and H2O2-lnduced Cell Death -- Section II: O-Methylation and Conjugation -- Chapter 9. Catechol O-Methyltransferase: Characterization of the Protein, Its Gene, and the Preclinical Pharmacology of COMT Inhibitors -- Chapter 10. X-Ray Crystallography of Catechol O-Methyltransferase: Perspectives for Target-Based Drug Development -- Chapter 11. Catechol O-Methyltransferase Inhibition and the Treatment of Parkinson's Disease -- Chapter 12. The Structure and Function of the UDP- Glucuronosyltransferase Gene Family -- Chapter 13. Catecholamine Sulfation in Health and Disease -- Chapter 14. Metabolism of Endobiotics and Xenobiotics by UDP- Glucuronosyltransferase -- Section III: Catecholamine Metabolizing Systems -- Chapter 15. Molecular Structure of the Carrier Responsible for Hepatic Uptake of Catecholamines -- Chapter 16. Catecholamine Uptake and Metabolism in the Liver -- Chapter 17. Catecholamine Uptake and Metabolism in Rat Lungs -- Chapter 18. The Extraneuronal Monoamine Transporter Exists in Human Central Nervous System Glia -- Chapter 19. Removal of Circulating Catecholamines by Extraneuronal Amine Transport Systems -- Chapter 20. Catecholamine Metabolites in Internal Jugular Plasma: A Window into the Human Brain -- Chapter 21. Norepinephrine Metabolites in Plasma as Indicators of Pharmacological Inhibition of Monoamine Oxidase and Catechol O-Methyltransferase -- Chapter 22. The Adrenal Gland as a Source of Dihydroxyphenylalanine and Catecholamine Metabolites. , Chapter 23. Clues to the Diagnosis of Pheochromocytoma from the Differential Tissue Metabolism of Catecholamines.

Note: Front Cover -- HIV-1: Molecular Biology and Pathogenesis -- Copyright Page -- Contents -- Contributors -- Preface written by Robin A. Weiss -- Chapter 1: Global Molecular Epidemiology of HIV: Understanding the Genesis of AIDS Pandemic -- I. Chapter Overview -- II. Introduction -- III. Genotype Classification of HIVs -- A. HIV Types (HIV-1 and HIV-2) -- B. Genotype Classification of HIV-1s -- C. HIV-2: Genotype Classification and Geographic Distribution -- IV. Global Distribution of HIV Genotypes -- A. Global HIV-1 Variability -- B. HIV-1 Variants in Asia -- C. Other HIV-1 Variants of Geographical Relevance -- D. Emergence og HIV-1 Recombinants Worldwide -- V. Methods for Identifying HIV Genetic Forms -- A. Phylogenetic Sequeuce Analysis -- B. Alternative Methods (Heteroduplex Mobility Assay and Serotyping) -- VI. Origin of HIVs and Genesis of HIV-1 Pandemic -- A. HIV/AIDS as a "Zoonosis -- B. Dating the Origin of Pandemic HIV-1 Strains -- VII. Biological Significance of HIV-1 Variability and Recombination -- A. HIV-1 Subtypes and Disease Progression -- B. HIV-1 Dual Infection, Superinfection, and Recombination -- C. Biological Implications of Recombination -- VIII. Conclusions -- Acknowledgments -- References -- Chapter 2: Current Clinical Treatments of AIDS -- I. Chapter Overview -- II. HIV Medications -- A. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors -- B. Nonnucleoside Reverse Transcriptase Inhibitors -- C. Protease Inhibitors -- III. HIV Treatment -- A. Initiation of Therapy -- B. Initial Regimen -- C. Long-Term Management -- D. Resistance -- E. Drugs in Development -- IV. Conclusion -- References -- Chapter 3: HIV-1-Specific Immune Response -- I. Introduction -- II. Humoral HIV-1-Specific Response -- III. HIV-1-Specific T-Cell Responses -- A. Protective Role of HIV-1-Specific T-Cell Responses. , B. Kinetics of HIV-1-Specific T-Cell Responses in Primary Infection -- C. Phenotypic and Functional Profiles of HIV-1-Specific CD4 and CD8 T-Cell Responses -- D. Phenotype -- E. Function -- F. Specificity and Breadth of HIV-1-Specific T-Cell Responses -- References -- Chapter 4: Targeting HIV Attachment and Entry for Therapy -- I. Chapter Overview -- II. Background -- III. Inhibition of Viral Attachment -- A. gp120 Inhibitors -- B. Targeting CD4 -- IV. Chemokine Receptors in HIV Infection -- V. Targeting Coreceptor Binding -- A. CXCR4 Inhibition -- B. Targeting CCR5 for HIV Therapy -- VI. Fusion Inhibitors -- A. Targeting gp41 -- B. Inhibition of Membrane Fusion -- VII. Resistance to Inhibitors of Viral Entry -- VIII. Use Entry Inhibitors as Microbicides -- References -- Chapter 5: Inhibitors of HIV-1 Reverse Transcriptase -- I. Chapter Overview -- II. Introduction -- III. The Target -- A. Structure of HIV-1 RT -- B. Mechanism of HIV-1 RT DNA Polymerase Activity -- IV. Nucleoside RT Inhibitors -- A. Mechanisms of NRTI Inhibition -- B. NRTI Approved for Clinical Use -- C. Investigational NRTI -- D. HIV-1 Resistance to NRTIs -- V. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) -- A. Mechanisms of NNRTI Inhibition -- B. NNRTI Approved for Clinical Use -- C. Investigational NNRTI -- D. HIV-1 Resistance to NNRTIs -- E. Interactions Between NNRTI and NRTI Resistance Mutations -- F. Use of NNRTI as Microbicides -- VI. Other Inhibitors of HIV-1 RT -- A. Inhibitors of HIV-1 RT RNH -- B. Inhibitors of HIV-1 RT Dimerization -- C. Inhibitors of the Initiation of Reverse Transcription -- D. RT-Directed Mutagenic Inducers -- VII. Conclusion -- Acknowledgments -- References -- Chapter 6: Development of Protease Inhibitors and the Fight with Drug-Resistant HIV-1 Variants -- I. Chapter Overview -- II. Introduction -- III. Targeting Viral Protease. , A. Mechanism of Action of PIs -- B. Protease Structures and Substrate-Based Inhibitors -- C. Design of Symmetry-Based Inhibitors -- D. Structure-Based PIs -- IV. The Role of PIs and Challenges in HAART -- V. "Boosting": A Critical Modification of Clinical Efficacy of PIs -- VI. Viral Resistance to PIs -- A. Emergence of Drug Resistance to PIs -- B. Primary and Secondary Mutations -- C. Active site Mutants -- D. Nonactive Site Mutants -- E. Cleavage Site Mutants -- F. Noncleavage Site Mutants -- G. Insertions in Gag-Pol Polyproteins -- VII. PIs with Activity Against Drug-Resistant HIV-1 -- A. Mutations That Allow Discrimination of PIs from Natural Substrates -- B. Development of Pls with Activity Against Drug-Resistant HIV -- C. Design Rationale of Darunavir -- D. HIV-1 Resistance to Darunavir -- E. Tipranavir and Darunavir -- VIII. Conclusions -- Acknowledgments -- References -- Chapter 7: HIV-1 Integrase Inhibitors: Update and Perspectives -- I. Chapter Overview -- II. Foreword -- III. Integration: A Crucial Step in the HIV Life Cycle -- A. HIV-1 IN Structure -- B. Chemistry of Retroviral Integration -- C. Integration Occurs Within a Large Macromolecular Complex -- IV. Approaches to Inhibit HIV Integration -- A. Small Molecule Inhibitors of HIV IN Enzymatic Activities -- B. Targeting the PIC -- V. Inhibitors in Clinical Trials -- VI. Inhibitors in Preclinical Development -- VII. Perspectives -- References -- Chapter 8: Topical Microbicides: A Promising Approach for Controlling the AIDS Pandemic via Retroviral Zinc Finger Inhibitors -- I. Chapter Overview -- II. The AIDS Pandemic and the Rationale for a Microbicide -- III. Topical Microbicides in Preclinical Development -- IV. Characteristics of an Ideal Microbicide -- V. The Retroviral Zinc Fingers of HIV-1 NCp7 as a Potential Microbicide Target -- VI. Characteristics of the SAMT Chemotype. , VII. Application of Thioesters for Microbicides -- VIII. Target Specificity of the SAMT NCp7 Inhibitors -- IX. Conclusions -- X. Addendum -- References -- Chapter 9: Viral Drug Resistance and Fitness -- I. Chapter Overview -- II. Introduction -- A. Entry Inhibitors -- B. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors -- C. Non-Nucleoside Reverse Transcriptase Inhibitors -- D. Integrase Inhibitors -- E. Protease Inhibitors -- References -- Chapter 10: Gene Therapy to Induce Cellular Resistance to HIV-1 Infection: Lessons from Clinical Trials -- I. Chapter Overview -- II. Introduction: Do We Need HIV-1 Gene Therapy? -- III. Gene Therapy of HIV Infection: Lessons from Early Clinical Trials -- A. Clinical Trials Using Dominant Negative Forms of the HIV-1 Rev Protein -- B. Clinical Trials Using the RRE Decoy -- C. Clinical Trials Using Antisense RNAs -- D. Clinical Trials with Ribozymes -- IV. Gene Therapy of HIV Infection: Current Developments -- A. Gene Transfer to Hemapoietic Progenitors -- B. Gene Therapy Using Lentiviral Vectors -- C. RNA Interference as a Therapeutic Tool -- D. Targeting HIV-1 Internalization -- V. Gene Therapy for HIV Infection: Where Are We Heading? -- Acknowledgments -- References -- Chapter 11: Identification of Potential Drug Targets Using Genomics and Proteomics: A Systems Approach -- I. Chapter Overview -- II. Introduction -- III. Viral Targets -- A. Viral Genomics -- B. Current Therapies and Future Prospects -- IV. Cellular/Viral Protein-Protein Interactions -- A. Cellular Protein Interactions of Tat -- B. Cellular Protein Interactions of Nef -- C. Cellular Protein Interactions of Gag -- V. Viral-Induced Cellular Alterations -- A. Tat: Effects on Cellular Transcription -- B. Nef: Altering the Cell Surface -- C. Gag: Using Cellular Factors to Facilitate Budding -- VI. Other Approaches -- A. Virion Proteome. , B. Biomarkers -- C. RNA Interference -- VII. Conclusion -- Acknowledgments -- References -- Chapter 12: Rapid Disease Progression to AIDS due to Simian immunodeficiency virus Infection of Macaques: Host and Viral Factors -- I. Chapter Overview -- II. Introduction -- III. SIV Strain Diversity -- IV. Biology of SIV -- V. Pathogenesis of SIV in Macaques -- A. SIV-sm and SIV-mac Infection as Models for AIDS -- B. Variation in Disease Progression -- C. Acutely Lethal SIV-smPBj -- D. Clinical Correlates of Disease Progression -- VI. Unique Immunologic, Virological, and Pathological Features of Rapid Disease -- A. Immunologic Features -- B. Virological Features -- C. Pathological Features -- VII. Host Factors That Influence Disease Progression -- A. Macaque Species -- B. Host Immune Responses and Major Histocompatibility Complex -- VIII. Role of Virus Genotype/ Phenotype in Rapid Disease Progression -- A. Specific Genes Involved in Pathogenesis -- B. Evolution of SIV in RPs -- C. In Vivo Studies of the Role of Virus in Rapid Disease -- IX. Summary -- Acknowledgments -- References -- Chapter 13: Nonprimate Models of HIV-1 Infection and Pathogenesis -- I. Chapter Overview -- II. Introduction -- III. SCID-Hu Thy/Liv Mice -- IV. The hu-PBL-SCID Mouse -- V. NOD/LtSz-SCID Mice -- VI. Rag2-/- gammaC-/- and NOD-SCID gammaC-/- Mice -- VII. Humanized Immune Competent Mice and Rats -- VIII. HIV-1 Tg Mice -- IX. Rabbit Model of HIV Pathogenesis -- X. Conclusion -- References -- Chapter 14: Perspectives for a Protective HIV-1 Vaccine -- I. Chapter Overview -- II. Introduction -- A. Natural History of HIV-1 Infection -- B. Immune Response Elicited During HIV-1 Infection -- C. Requirements for an Effective HIV-1 Vaccine -- III. Current Strategies in Developing an HIV-1 Vaccine -- A. Live-Attenuated HIV -- B. Induction of Antibody-Mediated Immunity. , IV. Concluding Remarks.

Note: Cover Page -- Contents -- Abbreviations -- Contributors -- Chapter 1: The Role of GABA in the Mediation and Perception of Pain -- I. Chapter Overview -- II. Introduction -- III. Molecular and Anatomical Considerations -- IV. Pharmacological Studies -- V. Summary and Conclusions -- Acknowledgments -- References -- Chapter 2: Distribution of GABA Receptors in the Thalamus and Their Involvement in Nociception -- I. Chapter Overview -- II. Introduction -- III. GABA Receptors in the Thalamus -- IV. Role of GABA Receptors in Nociception Within the Thalamus -- References -- Chapter 3: GABAA Agonists and Partial Agonists: THIP (Gaboxadol) as a Non-Opioid Analgesic and a Novel Type of Hypnotic -- I. Chapter Overview -- II. GABA Receptors: Multiplicity, Structure, and Function -- III. GABAA Agonists -- IV. Partial GABAA Agonists -- V. 4-PIOL Analogs as GABAA Antagonists -- VI. Behavioral and Clinical Effects of the Partial GABAA Agonist THIP (Gaboxadol) -- VII. Conclusions -- Acknowledgments -- References -- Chapter 4: Rat Modeling for GABA Defects inSchizophrenia -- I. Chapter Overview -- II. Introduction -- III. Rodent Model for Postmortem Findings in Schizophrenia -- IV. Commentary -- Acknowledgments -- References -- Chapter 5: Epigenetic Targets in GABAergic Neurons to Treat Schizophrenia -- I. Chapter Overview -- II. Introduction -- III. Regulation of Histone Acetylation -- IV. Chromatin Remodeling at Neuromuscular Junction -- V. Chromatin Remodeling During Memory Formation -- VI. Role of Reelin and Apolipoprotein E Receptors in Hippocampal Plasticity and Learning -- VII. Is Reelin Expressed Only in a Selective Subpopulation of GABAergic Neurons? -- VIII. RELN and GAD67 CpG Island Promoter Hypermethylation and Reelin and GAD67 Expression Downregulation in SZ Patients. , IX. Increased DNA-Methyltransferase-1 Expression in Cortical GABAergic Neurons of SZ Patients -- X. Relationship Between DNMT1 Overexpression and Reelin and GAD67 Downregulation in GABAergic Neurons of SZ Patients -- XI. Pharmacological Strategies to Reduce Reelin and GAD67 Promoter Hypermethylation in SZ Patients -- XII. The MET-Induced Epigenetic Mouse Model to Evaluate Prospective HDAC Inhibitors to be Used to Influence Epigenetic Mechanisms in Cortical GABAergic Neurons -- XIII. Conclusions -- References -- Chapter 6: GABAAergic Malfunction in the Limbic System Resulting from an Aboriginal Genetic Defect in Voltage-Gated Na+-Channel SCN5A is Proposed to Give Rise to Susceptibility to Schizophrenia -- I. Chapter Overview -- II. Introduction -- III. Levels of Concern -- IV. The Hypothalamo-Hypophyseal System -- V. The Cybernins -- VI. A Failed Therapeutic Adventure -- VII. Linkage of Propranolol Cognitive Effects with Correction of a Limbic System Defect that Results in Failure of Habituation in Schizophrenia (See Gruzelier, 1978) -- VIII. Susceptibility to Schizophrenia may Result from Mutation of the Na+ Channel-Coding SCN5A Gene, Which Occurs at Uniquely High Levels in Neural Components of the Limbic System -- IX. Recyberneticizing Substances and Mechanisms of Their Action -- X. Problems in Therapy with Racemic Propranolol -- XI. The GABA System and Schizophrenia -- Acknowledgments -- References -- Chapter 7: GABAA Receptpor Mutations Associated with Generalized Epilepsies -- I. Chapter Overview -- II. GABAA Receptors -- III. GABAA Receptor Epilepsy Genes -- IV. Conclusions -- References -- Chapter 8: From Gene to Behavior and Back Again: New Perspectives on GABAA Receptor Subunit Selectivity of Alcohol Actions -- I. Abstract -- II. Chapter Overview -- III. alpha-Subunit Knockout Mice -- IV. beta-Subunit Knockout Mice. , V. gamma-2-Subunit Knockout and Transgenic Mice -- VI. delta-Subunit Knockout Mice -- VII. GABAA Receptor Subunit Knock-in Mice -- VIII. Functional Compensation in Genetically Altered Mice: Gene-Behavior Associations Put into Context -- IX. GABAA Receptor Subunit-Associated Quantitative Trait Loci -- X. GABAA Receptor Subunit-Associated Gene Expression Patterns -- XI. Conclusions -- References -- Chapter 9: A Role for GABA in Alcohol Dependence -- I. Chapter Overview -- II. Alcohol and GABA -- III. Targets Within the Addiction Cycle Relevant for Actions of GABA -- IV. Extended Amygdala: A Basal Forebrain Macrostructure as a Focal Point for GABAergic Actions on Alcohol Reinforcement -- V. Role for GABA in Acute Alcohol Reinforcement -- VI. Effects of GABAergic Agents on Self-Administration of Alcohol in Nondependent Rats -- VII. Effects of GABAergic Agents on Self-Administration of Alcohol in Dependent Rats -- Acknowledgments -- References -- Chapter 10: Structure, Pharmacology, and Function of GABAA Receptor Subtypes -- I. Chapter Overview -- II. Introduction -- III. Heterogeneity of GABAA Receptors -- IV. Pharmacology of GABAA Receptors -- V. Function of GABAA Receptor Subtypes in the Brain -- VI. GABAA Receptor Structure -- Acknowledgments -- References -- Chapter 11: Structure-Activity Relationship and Pharmacology of alpha-Aminobutyric Acid (GABA) Transport Inhibitors -- I. Chapter Overview -- II. The GABAergic Synapses -- III. Transporter Heterogeneity, Nomenclature, and Function -- IV. Structure-Activity Relationship of GABA Uptake Inhibitors -- V. Kinetics of GABA Uptake Inhibitors -- VI. Reevaluation of Lipophilic Aromatic GABA Uptake Inhibitors -- VII. Conclusions -- Acknowledgments -- References -- Chapter 12: Modulation of Ionotropic GABA Receptors by Natural Products of Plant Origin -- I. Chapter Overview -- II. Introduction. , III. Ionotropic GABA Receptors -- IV. Flavonoids -- V. Terpenoids -- VI. Other Phenolic Compounds -- VII. Polyacetylenic Alcohols -- VIII. Alcoholic Beverages Containing GABA Receptor Modulators -- IX. GABA Receptor Modulators in Tea and Coffee -- X. Plant Sources of GABA Receptor Modulating Substances: Implications for Herbal Medicines -- Acknowledgments -- References -- Index -- Contents of Previous Volumes.