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Experimental Hepatotoxicity.- A. Introductory Considerations.- B. Historical Aspects.- C. Relevance of Experimental Hepatotoxicity.- D. Vulnerability of the Liver to Toxic Injury.- I. Concentration of Agents in Liver.- II. Liver as Portal to Tissues.- III. Metabolism of Foreign Compounds.- IV. Enzyme Induction.- V. Factors That Modify Susceptibility.- 1. Species.- 2. Age.- 3. Sex and Other Endocrine Factors.- 4. Nutritional State.- E. Types of Experimental Models.- I. Whole Animals.- 1. Parameters of Injury.- 2. Histology.- 3. Chemical Changes in Hepatic Tissue.- 4. Physiological and Biochemical Measure of Hepatic Function and Injury.- II. In Vitro Models.- 1. Liver Perfusion.- 2. Tissue Homogenates and Slices.- 3. Hepatocyte Suspensions.- 4. Organelles.- 5. Nuclear Components.- F. Types of Toxic Hepatic Injury.- I. Changes Observed by Light Microscopy.- 1. Acute Hepatic Injury.- 2. Chronic Hepatic Injury.- 3. Carcinogenesis.- G. Classification of Hepatotoxins.- I. Intrinsic Hepatotoxins.- II. Hepatic Injury Owing to Host Idiosyncracy.- H. Direct Hepatotoxins.- I. Carbon Tetrachloride.- 1. Chemical Properties.- 2. Toxicity in Humans.- 3. Experimental Models.- 4. Factors in Susceptibility.- 5. Experimental Injury.- 6. Evolution of Hepatic Injury.- 7. Mechanism of Injury.- 8. Alcohol and Carbon Tetrachloride Toxicity.- 9. Chronic Toxicity of Carbon Tetrachloride.- a) Cirrhosis.- b) Carcinogenesis.- 10. Other Halogenated Hydrocarbons.- II. Phosphorous.- 1. Chemical Properties.- 2. Toxicity in Humans.- a) Histopathology.- b) Blood Changes.- 3. Experimental Animals and Susceptibility.- 4. Acute Toxicity.- 5. Chronic Toxicity.- 6. Mechanism of Injury.- I. Indirect Hepatotoxins.- I. Cytotoxic Indirect Hepatotoxins.- 1. Types of Injury.- 2. Mechanisms.- 3. Experimental Models.- 4. Ethionine.- a) Significance.- b) Chemical Properties.- c) Factors in Susceptibility.- d) Form of Hepatic Injury.- 5. Thioacetamide.- a) Significance.- b) Chemical Characteristics.- c) Factors in Susceptibility.- d) Experimental Toxicity.- e) Mechanism of Injury.- 6. Dialkylnitrosamines.- a) Significance.- b) Chemical Characteristics.- c) Factors in Susceptibility.- d) Toxic Effects.- e) Metabolism of DMN and Mechanism of Injury.- 7. Tannic Acid.- a) Significance.- b) Chemical Properties.- c) Injury in Humans.- d) Experimental Toxicity.- e) Factors in Susceptibility.- f) Acute Injury.- g) Chronic Toxicity.- h) Mechanism of Injury.- 8. Aflatoxins.- a) Significance.- b) Chemical Characteristics.- c) Sources.- d) Factors in Susceptibility.- e) Hepatic Injury.- f) Mechanism of Hepatic Injury.- 9. Pyrrolidizine Alkaloids.- a) Significance.- b) Chemical Characteristics.- c) Injury in Humans.- d) Factors in Susceptibility.- e) Experimental Toxicity.- f) Mechanism of Injury.- 10. Hepatotoxic Principles of Mushrooms.- a) Significance.- b) Chemical Characteristics of Toxic Principles.- c) Factors in Susceptibility.- d) Toxicity for Humans.- e) Experimental Studies.- f) Mechanism of Injury.- g) Prevention of Toxicity.- 11. Galactosamine.- a) Significance.- b) Chemical Characteristics.- c) Factors in Susceptibility.- d) Experimental Hepatotoxicity.- e) Mechanism of Injury.- 12. Orotic Acid.- a) Significance.- b) Chemical Characteristics.- c) Factors in Susceptibility.- d) Experimental Injury.- e) Mechanism of Injury.- II. Cholestatic Indirect Hepatotoxins.- 1. Icterogenin.- a) Chemical Properties.- b) Experimental Models.- c) Factors in Susceptibility.- d) Toxic Effects.- 2. Sporidesmin.- 3. ?-Naphthylisothiocyanate (ANIT).- a) Significance.- b) Chemical Characteristics.- c) Experimental Models.- d) Factors in Susceptibility.- e) Toxic Effects.- f) Mechanism of Injury.- K. Concluding Comments.- I. Toxins of Living Origin.- II. Toxins of Non-Living Origin.- Appendix. Meaning of Abbreviations.- References.- Liver Disease Due to Infection and Allergy.- A. Introduction.- B. Liver Disease Due to Infection.- I. Multicellular Parasites.- 1. Cestodes.- 2. Trematodes (Flukes).- 3. Nematodes.- II. Protozoa.- 1. Malaria.- 2. Amoebiasis.- 3. Toxoplasmosis.- III. Mycoses.- 1. Actinomycosis.- 2. Blastomycosis.- 3. Coccidioidomycosis.- 4. Cryptococcosis.- 5. Histoplasmosis.- 6. Candidiasis.- 7. Mucormycosis.- IV. Bacteria.- 1. Pneumococcus.- 2. Staphylococcus.- 3. Streptococcus.- 4. Gonococcus.- 5. E. coli.- 6. Salmonellae.- 7. Shigella.- 8. Brucella.- 9. Minor Gram-Negative Bacterial Pathogens.- 10. Clostridia.- 11. Tuberculosis.- 12. Leprosy.- 13. Tularaemia.- 14. Leptospirosis.- 15. Syphilis.- V. Rickettsia.- Q Fever.- VI. Viruses (Excluding Classical Hepatitis Viruses A and B).- 1. Infectious Mononucleosis.- 2. Cytomegalovirus (CMV).- 3. Herpes Simplex.- 4. Psittacosis.- 5. Reovirus.- 6. Rubella.- 7. Varicella.- 8. Adenovirus.- 9. Coxsackie Viruses.- 10. Yellow Fever.- 11. "Marburg Virus" Disease.- 12. "Candidate" Human Hepatitis Viruses.- VII. Granulomatous Liver Disease.- 1. Granulomatous Response in Liver to Specific Infections.- 2. Granulomatous Response in Liver in Drug Allergy.- 3. Sarcoidosis of the Liver.- 4. Granulomatous Hepatitis of Unknown Origin.- C. Classical Human Viral Hepatitis.- I. History.- 1. Infectious and Serum Hepatitis.- 2. The Willowbrook Studies-MS-1 and MS-2 Sera.- 3. Hepatitis B Antigen.- 4. Association of Hepatitis B Antigen with Serum Hepatitis.- 5. Hepatitis A Antigen.- II. Features of Viral Hepatitis, Types A and B.- 1. Clinical Features.- 2. Biochemical Features.- 3. Immunological Features.- 4. Histological Features.- III. Epidemiology of Viral Hepatitis.- 1. General Aspects.- 2. Modes of Spread.- 3. Transfusion-Associated Hepatitis (Non A-Non B).- IV. Sequelae of Hepatitis.- 1. Differences for Type A and Type B Hepatitis.- 2. Mortality and Morbidity.- 3. Chronic Persisting Hepatitis.- V. Characteristics and Disease Associations of Hepatitis B Antigen (HBAg).- 1. Serological Demonstration.- 2. Electron Microscopy.- 3. Chemical Components of HBAg.- 4. Immunochemical Analyses-Subspecificities.- 5. HBAg in the Liver.- 6. HBAg Outside the Liver-Immune Complexes.- 7. Non-Correlation between HBsAg in Serum and Presence and Type of Liver Disease.- 8. HBAg Associated Chronic Active Hepatitis.- 9. Immune Response to HBAg.- 10. HBAg-A Unique Particle.- 11. Immune Aberrations and Persistence of Hepatitis B.- VI. Infection of Animals with Hepatitis Viruses.- 1. Viral Hepatitis in Animals.- 2. Human Hepatitis A Infection of Marmosets.- 3. Hepatitis B in Non-Human-Primates.- D. Liver Disease Associated with Autoimmune Reactions.- I. History.- II. Autoimmune "Lupoid" Type of Chronic Hepatitis.- 1. Definition.- 2. Clinical Features.- 3. Biochemical and Haematological Features.- 4. Histopathological Features.- 5. Hypergammaglobulinaemia and Humoral Autoantibodies.- 6. Serum Complement in Chronic Hepatitis.- 7. Damage by Immune Complexes.- 8. Cell Mediated Immunity in Chronic Active Hepatitis.- 9. Disease Associations in Chronic Active Hepatitis.- 10. Genetic Aspects of Chronic Hepatitis.- 11. Anti-Immune Drugs in Treatment of Chronic Hepatitis.- III. Autoimmune Cholangitis and Primary Biliary Cirrhosis (PBC).- 1. Definition.- 2. Clinical Features.- 3. Biochemical Features.- 4. Histological Features.- 5. Hypergammaglobulinaemia and Humoral Autoantibodies.- 6. Serum Complement.- 7. Cell-Mediated Immunity.- 8. Disease Associations.- 9. Hepatitis B Antigen.- 10. Genetic Determinant of PBC and Mitochondrial Antibody.- E. Experimental Models of Chronic Hepatitis.- I. Immune Induction of Chronic Liver Disease.- 1. Immunization with Liver in Freund's Complete Adjuvant.- 2. Damage by Allogeneic Cells.- 3. Damage by Antigen-Antibody Complexes.- II. Viral Induction of Chronic Liver Disease.- 1. Aleutian Mink.- 2. Canine Hepatitis Virus.- 3. Lymphocytic Choriomeningitis (LCM) Virus.- 4. Lactic Dehydrogenase (LDH) Virus.- 5. Reovirus 3.- 6. Liver Disease in New Zealand Black (NZB) Mice.- F. Liver Diseases Associated with Drug Reactions.- I. Differentiation and Types of Drug Associated …