| Co-Investigator(Kenkyū-buntansha) |
OMATA Yoshitaka Assoc.Prof., Vet.Physiol., Obihiro Univ., 畜産学部, 助教授 (10132987)
SATO Motoyoshi Assoc.Prof., Vet.Radiol., Obihiro Univ., 畜産学部, 助教授 (50003140)
IGARASHI Ikuo Assoc.Prof., Res.Ctr.Prot., Obihiro Univ., 原虫免疫研究所, 教授 (80159582)
SAITO Atushi Prof., Vet.Physiol., Obihiro Univ., 畜産学部, 教授 (10002263)
HIROSE Tuneo Prof., Vet.Radiol., Obihiro Univ., 畜産学部, 教授 (60003076)
三浦 弘之 帯広畜大, 肉畜保臓学, 教授 (90003079)
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| Budget Amount *help |
¥28,200,000 (Direct Cost: ¥28,200,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1992: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1991: ¥11,600,000 (Direct Cost: ¥11,600,000)
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| Research Abstract |
An imunomodulator, such as TLA (Toxoplasma lysate antigens) was tested in the experiments. Growth of the tumor autoinduced by 20-methylcholanthrene (MC) in rats and mice was inhibited after intramuscular injection of TLA.The antitumor activity of TLA was most obvious in the early stage of tumor growth. When TLA was administered to rats before the appearance of tumor, tumor formation was delayd slightly. According to the immunohistological examination of tumor tisue with anti-Thy-1 antibody, the rats treated with TLA showed large Thy-1 positive or Lymphokine-Activated Killer (LAK) cells, whereas the untreated rats indicated only a few small Thy-1 positive or NK cells. In a series of these studies, TLA induces NK cells, cytotoxic T-lymphocytes and LAK cells in animals after injection, and the induction of these killer cells needs to exist in combination with macrophages and lymphocytes in in vivo. An activity unit in TLA was isolated now as TLA-H6E,and the inhibitory activation to the tu
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mor growth was significantly strong in comparison with others. Using the TLA-H6E monoclonal antibody, the structure of H6E is now making clear.
Newly synthesized peptides of the activity units which were isolated from cytokines (lymphokines) as an immunoregulator, Obiopeptide, were examined in the effect of Toxoplasma chronically infected animals. Mice chronically infected with Toxoplasma were treated with Chclophosphamide (Cyp), Obiopeptide-1 (Obio-1) and/or anti-CD4 monoclonal antibody to determine the effect of these immunosuppressive agents on the cysts in the brain. In the brain of non-treated, and infected Cyp-Obi-1 treated mice, with HE staining or anti-Toxoplasma ABC labelling staining, large typically rounded tissue cysts were mostly detected, and in some regions dividing microcysts were also founded. In contrast, brain tissue from Cyp only or anti-CD4 treated infected mice had multiple degenerated cysts of varied sizes in some brain regions, as well as clusters of microcysts, however, such change was more striking in the anti-CD4 treated mice. Infected mice treated with a combination of Cyp and Obi-1 showed a significantly higher survival of 80% compared to 20% survival in mice treated with Cyp only. Percent neutrophilic leucocytes, monocytes and lymphocytes in mice treated with a combination of Obi-1 and anti-CD4, or Obi-1 and Cyp were higher compared to those groups treated with anti-CD4 antibody, or Cyp only. The increase in neutrophilic leucocyte and lymphocyte counts after a combined Cyp and Obi-1 treatment may, like wise, contribute to the induction of resistance in mice aginst Toxoplasma gondii. These results indidcate that reactivation of rupture of tissue cysts in mice treated with Cyp, chronicaly infected with Toxoplasma, might be mainly mediated by CD4 positive cells rather than other CD8, CD5 cells. Furthermore, the increase of neutrophilic leukocytes might contribute to the induction of the resistnce to Toxoplamsa in mice, after treatment with Obi-1 and Cyp in combination. However, these results seem to suggest that the reactivation or rupture of tissue cysts in mice chronically infected with Toxoplasma is not principally correlated with the death of Cyp treated mice. Less
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