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Springer The LEC Rat A New Model for Hepatitis and Liver Cancer 1st Editon 2011 Softbound by Michio Mori, Michihiro C. Yoshida, Noritoshi Takeichi, Naoyuki Taniguchi
The LEC strain of rats, which spontaneously develop acute hepatitis as sociated with jaundice, chronic hepatitis, and ultimately hepatocellular carcinomas, was established by scientists in Sapporo, Japan. Careful ob servation and breeding led to the initial discovery of this characteristic, inherited liver disease in rats. Subsequent collaboration between scientists in Sapporo and other centers has revealed an autosomal recessive nature of inheritance, along with a variety of histopathological and biochemical findings. The causative mechanism(s) underlying this abnormality remained a mystery for some time, providing a challenge for many scientists who were attracted to the quest for clues to this enigma. In particular, the mech anism of spontaneous development of hepatocellular carcinomas in rats overcoming the acute phase of hepatitis and surviving with chronic hepatitis proved extremely interesting, because the involvement of a causative virus had been excluded in the early stages of investigation. Professor Michio Mori of Sapporo Medical College played a key role in the study of LEC rats, especially in the elucidation of the pathogenesis of hepatitis and hepatocellular carcinoma. He is one of the editors of this monograph which is composed of original contributions by the many scientists who have carried out their own studies on LEC rats. Of the various histopathological and biochemical alterations which have been reported, some are clearly secondary or tertiary events sequential to the primary change caused by gene mutation. 1 Establishment and Natural History.- 1 Origin of the LEC Strain with a New Mutation Causing Hereditary Hepatitis.- 2 Reproductive Performance and Effects of Pregnancy on the Acute Phase of Hepatitis in LEC Rats.- 3 Differences in the Course of Hereditary Hepatitis Between Males and Females, and Between Virgins and Parous Female LEC Rats.- 4 Pathological and Laboratory Findings of “LEC/Otk” Rats Maintained Under SPF Conditions.- 5 Clinical and Pathological Characteristics of LEC Rats with Spontaneous Hepatitis.- 6 High Susceptibility to Spontaneous Development of Hepatocellular Carcinoma in LEC Rats.- 2 Hepatitis.- 1. Pathology.- 7 Investigation of Infectious Agents Causing Spontaneous Hepatitis in LEC Rats.- 8 Possible Involvement of Abnormal Cytokinesis and Karyokinesis in the Manifestation of Hepatitis in LEC Rats.- 9 Sensitivity of LEC Rats to the Hepatotoxic Effects of D-Galactosamine.- 10 Consecutive Follow-up Study of the Liver of LEC Rats Before the Onset of Spontaneous Hepatitis.- 11 Acute Tubular Necrosis in LEC Rats with Hereditary Hepatic Failure—A New Animal Model of Hepatorenal Syndrome.- 12 Inhibitory and Intensifying Effects of Long-Term Exposure to Chemicals on Spontaneous Hepatic Injury in LEC Rats.- 2. Biochemistry.- 13 Abnormal Copper Accumulation in the Liver of LEC Rats: A Rat Form of Wilson’s Disease.- 14 Hereditary Low Levels of Plasma Ceruloplasmin in LEC Rats.- 15 Differential Expression of Mn- and Cu, Zn-Superoxide Dismutases in Various Tissues of LEC Rats.- 16 Decreased Activities of S-Adenosylmethionine Synthetase Isozymes in Hereditary Hepatitis in LEC Rats.- 17 LEC Rats Mimic LEA Rats Fed a Choline-Deficient Diet.- 18 Hypomethylation-Associated Expression of Cytochrome P-450 and ?-Glutamyl Transpeptidase During Hereditary Hepatocarcinogenesis in LEC Rats.- 19 Abnormal Lipid Metabolism in LEC Rats.- 20 Identifications of Carbonic Anhydrase III and Triosephosphate Isomerase in the Liver Proteins in LEC Rats on Two-Dimensional Gel Electrophoresis.- 21 Two-Dimensional Electrophoretic Analysis of Cellular Polypeptides from Livers of LEC Rats.- 3. Immunology.- 22 Combined Immunodeficiency in LEC Rats with Spontaneous Hepatitis.- 23 Genetic Analysis of Immunodeficiency and Hereditary Hepatitis in LEC Rats.- 24 Remarkable Reduction of Serum IgG2a Subclass in LEC Rats.- 25 Genetic Analysis of IgG Deficiency and T-Helper Immunodeficiency in LEC Rats.- 26 Arrest of Maturation of Helper T Cells in LEC Rats.- 3 Liver Cancer.- 1. Cytogenetics and Oncogenes.- 27 Chromosomal Analysis of Spontaneous Hepatomas, a Derived Cell Line, and Chemically Induced Hepatomas in LEC Rats.- 28 Drug-Metabolizing Ability and Inducibility of Chromosomal Aberrations and Sister Chromatid Exchanges in LEC Rats Exposed to Cyclophosphamide.- 29 Altered Oncogene Expression in Hepatocellular Carcinomas Developing Spontaneously in LEC Rats.- 2. Pathology.- 30 Progress from Chronic Hepatitis to Liver Cancer in Long-Surviving LEC Rats.- 31 Neoplastic and Non-Neoplastic Lesions in Aging LEC/Otk Rats.- 32 The Multistep Nature of Spontaneous Liver Cancer Development in the LEC Rat: Analysis of Incidence and Phenotype of Preneoplastic and Neoplastic Liver Lesions.- 33 High Sensitivity of LEC Rats to Carcinogens Based Upon a Short-Term Carcinogenicity Assay.- 34 Replicative and Unscheduled DNA Synthesis of LEC Rat Hepatocytes: Relevance to Natural Development of Hepatocellular Carcinoma.- 3. Biochemistry.- 35 Hepatoma-Associated Alterations of Serum ?1-Antitrypsin in LEC Rats.- 36 High Expression of Hexokinase Isozyme B During Hepatocarcinogenesis in LEC Rats.- 37 Chromosomal Mapping of the Placental Glutathione S-Transferase Gene and Its Expression in Livers of LEC Rats.