|Budget Amount *help
¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1993 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. We recently found that cultured smooth muscle cells (SMC) derived from arteries of patients with moyamoya disease responded poorly to serum mitogens, especially to platelet-derived growth factor (PDGF). In the present study, we investigated further the binding and processing of ^<125>I-PDGF, as well as down-regulation of the PDGF receptor in arterial SMC derived from patients with moyamoya disease. The specific binding sites of ^<125>I-PDGF were reduced significantly at both 4ﾟC and 22ﾟC on SMC from moyamoya disease compared with those from controls, though the apparent dissociation constant (Kd) were the same. Kinetics of ^<125>I-PDGF binding at 37ﾟC in cells from moyamoya disease showed fewer binding site and lower degradation per cell than in those from controls, though no difference was observed in either internalization or degradation of each receptor. When SMC were exposed to lower concentrations of nonlabeled PDGF at 37ﾟC, the percentage of remaining binding site on cells from moyamoya disease was significantly less than that from controls. This excess down-regulation of PDGF receptor in SMC from moyamoya disease may be interpreted as insufficient recycling or a decreased intracellular pool of the PDGF receptor. These results are closely correlated with the diminished proliferation responses to PDGF in SMC from moyamoya disease and provide evidence that functional alterrations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.
clomingを重ねることにより樹立が可能であり,今後例数を増やし,対照との比較を行なう。(3)in vitroでの血管病変の病態を明かにするために,モヤモヤ病患者頭皮血管の形態学的観察を行った。その結果,小児例の血管にも内膜肥厚が頻繁に認められ,しかも,頭蓋内狭塞部血管の病理組織像と酷似する所見が得られた。また電顕による観察から,モヤモヤ病においても中膜平滑筋細胞の遊走増殖が内膜肥厚をもたらすことが明かにされた。免疫組織学的検討を加え,この事実の証明も行った。(4).また,モヤモヤ病発症の遺伝的背景を明かにするために,孤発30例に対し,HLA typingを行ない,対★例との比較を行なうことにより,興味ある結果が得られた。