| Project/Area Number |
08281103
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOJIMA Somei The University of Tokyo, Institute of Medical Sciences, Professor, 医科学研究所, 教授 (00009622)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAYAMA Kenji Saitama Medical University, Professor, 医学部, 教授 (60189868)
MATSUMOTO Yoshitugu The University of Tokyo, Graduate School of Agiculture, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00173922)
AIKAWA Masamichi Tokai University, Research Institute of Medical Sciences, Professor, 総合科学技術研究所, 教授 (90271593)
CHINZEI Yasuo Mie University, Schcol of Medicine, Professor, 医学部, 教授 (60024709)
KOBAYASHI Fumie Kyorin University, School of Medicine, Assistant Professor, 医学部, 助手 (20118889)
太田 伸生 名古屋市立大学, 医学部, 教授 (10143611)
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| Project Period (FY) |
1996 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥181,700,000 (Direct Cost: ¥181,700,000)
Fiscal Year 1999: ¥40,000,000 (Direct Cost: ¥40,000,000)
Fiscal Year 1998: ¥44,000,000 (Direct Cost: ¥44,000,000)
Fiscal Year 1997: ¥44,700,000 (Direct Cost: ¥44,700,000)
Fiscal Year 1996: ¥53,000,000 (Direct Cost: ¥53,000,000)
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| Keywords | Malaria / Mechanism of cerebral malaria / Protection from infection / Cytokine / Knob protein / vector / molecular biology |
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| Research Abstract |
1) Molecular mechanism of cerebral malaria and its prevention
In the animal model of cerebral malaria using P. berghei ANKA strain, significant expression of chemokine mRNA was found in brain within 24 hrs and induction of chemokine in the astrocyte by parasite antigen was observed. This indicates participation of neural cells as well as immuno-systems in cerebral malaria. Increase of soluble Fas ligand was found when monkey model, P. coatneyi, showed coma suggesting apoptosis also is one of the important factor for cerebral malaria. In fact, administration of matrix methalloprotease inhibitor (MMPI) which inhibits release of soluble Fas ligand and TNF- to infected monkey resulted in the re-increase of peripheral T cells and suppression or delay of parasitemia. In addition, production of IL-12 and IL-18 from macrophages and Kupffer cells in the liver activated CD8 ^+NK1.1^+T cells caused liver injury and finally hepatitis in mice.
2) Host immunoresponse and mechanism of protection against malaria infection
Protective function of extrathymic T cells was shown by the expression of MHC class I antigen and CD1 in the borne-marrow red blood cells and infection of merozoites into the red blood cells.
3) Molecular interaction between malaria parasite and vector
CTRP (circumsporozoite protein and thrombospondin-related adhesive protein [TRAP]- related protein) was found to play a crucial role in malaria infection of the mosquito midgut lumen. In addition, the result suggested that similar molecular mechnisms are used by malaria parasites to invade in the insect vector and the mammalian host.
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