| Project/Area Number |
63480241
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Nihon University |
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Principal Investigator |
KITAGAWA Teruo Nihon Univ. School of Medicine Professor of Pediatrics, 医学部・小児科, 教授 (50058765)
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| Co-Investigator(Kenkyū-buntansha) |
SAKIYAMA Takeshi Nihon Univ. School of Medicine Assistant Professor of Pediatrics, 医学部・小児科, 講師 (20130510)
OWADA Misao Nihon Univ. School of Medicine Associate Professor of Pediatrics, 医学部・小児科, 助教授 (40059506)
赤塚 章 日本大学, 医学部小児科, 助手 (60183133)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Inborn Errors of Metabolism / Lysosomal Storage Disease / Sphingomyelin / Niemann Pick Disease / Lysosome / Sphingomyelinase / Bone Marrow Transplant / Animal Model / 先天代謝異常症 / 骨髄移植 / ニ-マンビック病 / 疾患動物モデル / 酵素療法 / ニーマンピック症 / ライソゾーム |
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| Research Abstract |
Recently, bone marrow grafts have been considered as one form of treatment for certain inborn errors of metabolism. From our experiment with Niemann-Pick mice, the bone marrow graft did not improve the neurological manifestation. However, the accumulation of sphingomyelin and cholesterol in the spleen was decreased remarkably. Since no neurological improvement was noticed, this could be ascribed to some possible causes, such as the existance of blood-brain-barriers which prohibit the leucocytes from entering the necessary areas of the brain. In order to investigate therapeutic mechanism of bone marrow transplantation (BMT) in certain inherited metabolic diseases, subcellular fractionation of the liver and brain in Niemann-Pick mice before and after BMT was carried out by percholl gradient centrifugation. The marked decrease of acid sphingomyelinase activities and increase of sphingomyelin and cholesterol at the lysosomal fraction of the liver and brain in Niemann-Pick mice before BMT was noticed. On the other hand, after BMT, a significant increase of acid sphingomyelinase activity and a decrease of cholesterol and sphingomyelin accumulation in lysosome were demonstrated. Biochemical procedures, however, failed to demonstrate any change of acid sphingomyelinase activity and lipid contents in lysosome from the brain after BMT in Niemann-Pick mice. In the next study we examined the biochemical and pathological effects of transplanting haematopoietic cells from Niemann-Pick mice into inbred normal mice, and isolation of the lysosome from the liver and brain was carried out. A slight decrease of acid sphingomyelinase activity and a increase of lipid contents in the lysosome from the liver were noticed. This study is the first report of positive alterations in enzyme activity and lipid contents in the lysosome from the liver of the Niemann-Pick mice after BMT.
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