Experimental Production of Diseases

Inhaltsverzeichnis

• 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.
• 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.
• 4. Ethionine.
• a) Significance.
• b) Chemical Properties.
• c) Factors in Susceptibility.
• d) Form of Hepatic Injury.
• 5. Thioacetamide.
• b) Chemical Characteristics.
• d) Experimental Toxicity.
• e) Mechanism of Injury.
• 6. Dialkylnitrosamines.
• d) Toxic Effects.
• e) Metabolism of DMN and Mechanism of Injury.
• 7. Tannic Acid.
• c) Injury in Humans.
• e) Factors in Susceptibility.
• f) Acute Injury.
• g) Chronic Toxicity.
• h) Mechanism of Injury.
• 8. Aflatoxins.
• c) Sources.
• d) Factors in Susceptibility.
• e) Hepatic Injury.
• f) Mechanism of Hepatic Injury.
• 9. Pyrrolidizine Alkaloids.
• e) Experimental Toxicity.
• f) Mechanism of Injury.
• 10. Hepatotoxic Principles of Mushrooms.
• b) Chemical Characteristics of Toxic Principles.
• d) Toxicity for Humans.
• e) Experimental Studies.
• g) Prevention of Toxicity.
• 11. Galactosamine.
• d) Experimental Hepatotoxicity.
• 12. Orotic Acid.
• d) Experimental Injury.
• II. Cholestatic Indirect Hepatotoxins.
• 1. Icterogenin.
• a) Chemical Properties.
• b) Experimental Models.
• 2. Sporidesmin.
• 3. ?-Naphthylisothiocyanate (ANIT).
• c) Experimental Models.
• e) Toxic Effects.
• 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.
• 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).
• 3. Biochemical Features.
• 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 Liver Injury.
• II. Allergic Cholangitis.
• 1. Acute Allergic Cholangitis.
• 2. Chronic Allergic Cholangitis.
• III. Allergic Hepatitis.
• 1. Acute Hepatitic Reactions.
• 2. Chronic Hepatitic Reactions.
• IV. Granulomatous Hepatic Reactions.
• V. Specific Drugs.
• 1. Iproniazid (Marsalid).
• 2. Isoniazid.
• 3. Phenazopyridine Hydrochloride (Pyridium).
• 4. Diphenyl Hydantoin.
• 5. Sulphonamides.
• 6. Penicillin and Oxacillin.
• 7. Erythromycin Ester.
• 8. Halothane.
• 9. Oxphenisatin.
• 10. Alpha Methyl Dopa (“Aldomet”).
• 11. Aspirin.
• 12. Para-Aminosalicylic Acid (PAS).
• VI. Immunological Basis of Allergic Liver Injury.
• 1. Acute Reactions.
• 2. Drug-Induced Hepatitis with Autoimmune Markers.
• 3. Experimental Models of Allergic Hepatitis.
• G. Conclusion: Immunology and the Liver.
• I. Immune Deficiency.
• 1. Phagocytic function.
• 2. Immunocyte function.
• II. “Hypersensitivity” Responses.
• III. Persistent Tolerated Infection: Hepatitis B Virus.
• IV. Autoimmunity.
• V. The Chronic Hepatitis-Cirrhosis Problem.
• 1. Extent of Problem.
• 2. Subtypes of Chronic Hepatitis?.
• 3. Morphological Correlates of Transition of Hepatitis to Cirrhosis?.
• 4. Immunopathogenesis of Chronic Hepatitis—Neoantigen or Auto-antigen.
• 5. Effector Mechanisms in Immune-Mediated Liver Disease.
• Abbreviations.
• Radiation-Induced Injury of the Liver.
• B. Preliminary Remarks.
• I. Preliminary Remarks on Physical Facts.
• 1. Radiation Spectrum.
• 2. Radiation Units.
• 3. Radiation Sources.
• II. Radiosensitivity.
• 2. General Remarks on Radiosensitivity.
• 3. Remarks on the Radiosensitivity of the Liver.
• III. Process of Radiation Damage.
• 1. General.
• 2. Liver.
• a) Morphological Characteristics.
• b) Process of Radiation Damage.
• c) Interrelations with Neighboring Organs.
• C. Radiation-Induced Changes of the Human Liver.
• I. Irradiation by External Radiation Sources.
• 1. Acute Radiation Changes.
• 2. Effects of Chronic Irradiation.
• 3. Detection of Lesions by Radioactive Hepatography.
• II. Irradiation by Internal Radiation Sources.
• 1. Morphological Findings in the Liver.
• a) Radiocirrhosis of the Liver.
• b) Radiocancers of the Liver.
• 2. Effects of Other Radioactive Elements.
• D. Experimental Investigations of the Radiation Effect.
• I. Preliminary Remarks.
• II. Early and Late Morphological Radiation Changes.
• 1. Early Radiation Changes of the Liver.
• a) Findings by Light Microscopy.
• b) Electronmicroscopic Features.
• 2. Late Radiation Changes.
• 3. Radiation Effect on Fetal Liver Tissue.
• III. Radiation Effect on Liver Regeneration with Special Regard to the Influence of Nucleic Acid Synthesis.
• 1. DNA Synthesis and Liver Proliferation after Partial Hepatectomy.
• a) Irradiation of the Liver after Partial Hepatectomy: Metabolic Processes.
• b) Irradiation before Partial Hepatectomy.
• c) Irradiation of Non-Hepatectomized Animals.
• IV. Effects on Metabolic Activities Other than DNA Synthesis.
• 1. Fat and Carbohydrate Metabolism.
• a) Changes in Lipid Metabolism.
• b) Changes in Glycogen Synthesis.
• c) Relations Between Lipid and Glycogen Metabolism.
• 2. Oxidative Metabolism.
• 3. Lipid Peroxides and Lysosomal Damage.
• 4. Amino Acid and Protein Metabolism.
• a) Effects on Amino Acid Metabolism.
• b) Changes in Detoxication Activity.
• c) Changes in Enzyme Activities.
• d) Changes in Protein Synthesis.
• e) Influence of Irradiation on the Inducibility of Enzymes.
• V. Effects on Liver Function by a Combination of Radiation and Drugs.
• 1. Changes of Liver Radiosensitivity.
• 2. Effect of Radiation on Experimental Chemical Carcinogenesis of the Liver and Non-Carcinogenic Alteration.
• Experimental Production of Gallstones.
• A. A Fat- and Cholesterol-Free Diet in Hamsters.
• B. A Lithogenic Diet Supplemented with Chenodeoxycholic Acid.
• C. A High Cholesterol Diet in Prairie Dogs.
• D. A Diet Supplemented with D-Thyroxine in Hamsters.
• E. A Fat-and Cholesterol-Rich Diet in Squirrel Monkeys.
• Author Index.