The LEC Rat

1. Front Matter

   Pages I-XVI

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2. Establishment and Natural History

   1. Front Matter

      Pages 1-1

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   2. Origin of the LEC Strain with a New Mutation Causing Hereditary Hepatitis

      • Michihiro C. Yoshida, Motomichi Sasaki, Ryuichi Masuda

      Pages 3-10

   3. Reproductive Performance and Effects of Pregnancy on the Acute Phase of Hepatitis in LEC Rats

      • Noriyuki Kasai, Eikichi Kamimura, Ichiro Miyoshi, Michihiro C. Yoshida

      Pages 11-19

   4. Differences in the Course of Hereditary Hepatitis Between Males and Females, and Between Virgins and Parous Female LEC Rats

      • Kazuto Yamazaki, Masaaki Nakayama, Koji Tomobe, Hiroshi Ohyama, Yumi Sawada, Tsuneo Wakabayashi et al.

      Pages 20-29

   5. Pathological and Laboratory Findings of “LEC/Otk” Rats Maintained Under SPF Conditions

      • Kazuya Kawano, Tsukasa Hirashima, Shigehito Mori, Sumio Bando, Kenichi Yonemoto, Fumiko Abe et al.

      Pages 30-40

   6. Clinical and Pathological Characteristics of LEC Rats with Spontaneous Hepatitis

      • Tsutomu Namieno, Noritoshi Takeichi, Motomichi Sasaki, Kimimaro Dempo, Michio Mori, Jun-ichi Uchino et al.

      Pages 41-53

   7. High Susceptibility to Spontaneous Development of Hepatocellular Carcinoma in LEC Rats

      • Ryuichi Masuda, Michihiro C. Yoshida, Motomichi Sasaki, Kimimaro Dempo, Michio Mori

      Pages 54-66

3. Hepatitis

   1. Front Matter

      Pages 67-67

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   2. Pathology

      1. Investigation of Infectious Agents Causing Spontaneous Hepatitis in LEC Rats

         • Tsutomu Namieno, Noritoshi Takeichi, Motomichi Sasaki, Kimimaro Dempo, Michio Mori, Jun-ichi Uchino et al.

         Pages 70-80

      2. Possible Involvement of Abnormal Cytokinesis and Karyokinesis in the Manifestation of Hepatitis in LEC Rats

         • Yoshinori Fujimoto, Michio Mori, Minako Nagao

         Pages 81-86

      3. Sensitivity of LEC Rats to the Hepatotoxic Effects of D-Galactosamine

         • Hidetoshi Takahashi, Katsuhiko Enomoto, Hirofumi Sakamoto, Hirotoshi Tobioka, Kimimaro Dempo, Michio Mori

         Pages 87-94

      4. Consecutive Follow-up Study of the Liver of LEC Rats Before the Onset of Spontaneous Hepatitis

         • Hirofumi Sakamoto, Yasuhiro Kamimura, Takashi Minase, Shigeaki Yokoyama, Masaaki Satoh, Michio Mori

         Pages 95-102

      5. Acute Tubular Necrosis in LEC Rats with Hereditary Hepatic Failure — A New Animal Model of Hepatorenal Syndrome

         • Hiroyuki Tochimaru, Yasushi Akutsu, Yasushi Nagata, Yasuo Takekoshi, Shuzo Matsumoto, Noritoshi Takeichi

         Pages 103-113

      6. Inhibitory and Intensifying Effects of Long-Term Exposure to Chemicals on Spontaneous Hepatic Injury in LEC Rats

         • Keisuke Izumi, Hisanori Uehara, Hisashi Otsuka, Kozo Matsumoto

         Pages 114-119

   3. Biochemistry

      1. Abnormal Copper Accumulation in the Liver of LEC Rats: A Rat Form of Wilson’s Disease

         • Yu Li, Yuji Togashi, Noritoshi Takeichi

         Pages 122-132

      2. Hereditary Low Levels of Plasma Ceruloplasmin in LEC Rats

         • Takao Ono, Syuiti Abe, Michihiro C. Yoshida

         Pages 133-141

      3. Differential Expression of Mn- and Cu,Zn-Superoxide Dismutases in Various Tissues of LEC Rats

         • Keiichiro Suzuki, Toshiyuki Nakata, Han Geuk Seo, Nobuko Miyazawa, Toshihiro Sugiyama, Naoyuki Taniguchi

         Pages 142-148

      4. Decreased Activities of <i>S</i>-Adenosylmethionine Synthetase Isozymes in Hereditary Hepatitis in LEC Rats

         • Kinji Tsukada, Michio Mori

         Pages 149-154

      5. LEC Rats Mimic LEA Rats Fed a Choline-Deficient Diet

         • Toshihiro Sugiyama, Mikako Matsunaga, Yoshitaka Ikeda, Naoyuki Taniguchi

         Pages 155-161

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.

• Hepatitis B
• aging
• cancer
• carcinogenesis
• carcinoma
• cytogenetics
• cytokines
• genetics
• hepatitis
• hepatocellular carcinoma
• liver
• liver disease
• oncogene
• pathology
• pregnancy
• hepatology

• Department of Pathology, Sapporo Medical College, Minami 1, Nishi 17, Chuo-ku, Sapporo, 060, Japan

  Michio Mori

• Chromosome Research Unit, Faculty of Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku Sapporo, 060, Japan

  Michihiro C. Yoshida

• Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060, Japan

  Noritoshi Takeichi

• Department of Biochemistry, Osaka University Medical School, Suita, Osaka, 565, Japan

  Naoyuki Taniguchi

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