モヤモヤ病における血管壁細胞の機能異常の解析とgene mapping

1997 Fiscal Year Annual Research Report

• Project/Area Number: 09671412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 松島 善治 東京医科歯科大学, 医学部, 助教授 (20134679)
• Co-Investigator(Kenkyū-buntansha): 玉置 正史 東京医科歯科大学, 医学部, 助手 ; 山本 清高 東京都老人総合研究所, 細胞生物部門, 主任研究員 (90073022) ; 青柳 傑 東京医科歯科大学, 医学部, 講師 (40134704)
• Keywords: モヤモヤ病 / elastin / 炎症性のcytokine / linkage analysis

Research Abstract

(1)モヤモヤ病患者の浅側頭動脈血管では、有意に若年性に内膜肥厚が発症していた。また、多層のelastin fiber の形成がみとめられ、elastin産生の亢進の可能性が示唆された。この事実は、in situ hybridisation及び、培養平滑筋細胞のelastin合成、elastin mRNAの発現を比べることにより明かとなった(Stroke,1997)。また、モヤモヤ病に血管は炎症性反応に対し、遺伝的に抑制された特異的な反応性と示すとの仮説のもとに研究を行なった。本症血管平滑筋細胞は、炎症性のcytokineに対し、対照細胞とは全く異なる反応性を示すことが明かとなった(Stroke,in press)。炎症性sytokineは多機能性であり、虚血、内膜肥厚に重要な役割を果たしている。NO,Prostaglandin合成系、MAPkinase,NF-kB等、顆粒の種々の伝達系を更に検索中である。(2)モヤモヤ病家族発症例について、詳細な家計図を作成し、MR angiographyを可能なかぎり施行し、疾患の有無を明かにした。現在までに4家計について検討を行った。最も頻度の高い家計は6人の右疾患患者が明らかになった家計である。これら家族例より、非発症例を含めgenomic DNAを抽出し、microsatellite analysisによるlinkage analysisを施行中である。これまでの検索から、HLA locus,NF-1,PDGF,PDGF receptor,FGF,elastin,Down syndrome,tuberous sclerosisとのlinkageは否定された。

Research Products

• [Publications] Matsushima Y, Oian L, Aoyagi M: "Comparison of Moyamoya disease in Japan and Moyamoya disease(or syndrome)in People's Republic of China." Clinical Neurology and Neurosurgery. 99,Suppl.2. S19-S22 (1997)
• [Publications] Matsushima Y, Aoyagi M, Nariai T, Takada Y, and Hirakawa K: "Long-term intelligence outcome of post-EDAS childhood Moyamoya patients." Clinical Neurology and Neurosurgery. 99,Suppl.2. S147-S150 (1997)
• [Publications] Aoyagi M, Fukai N, Yamamoto M, Mastushima Y, Yamamoto K: "Development of Intimal thickening in STA in patients with Moyamoya disease" Clinical Neurology and Neurosurgery. 99,Suppl.2. S213-217 (1997)
• [Publications] Aoyagi M, Yamamoto M, Azuma H, Niimi Y, Tajim S, Yamamoto K: "Smooth musble cell proliferation, elastin formation,and tropoelastin transcripts during the development of intimal thickening in rabbit carotid arteries after endothelial denudation" Histochem Cell Biol. 107. 11-18 (1997)
• [Publications] Ymanoto M, Aoyagi M, Azuma H, Yamamoto K: "Changes in ostcopontin mRNA expression during phenotypic transition of rabbit arterial smooth muscle" Histochem Cell Biol. 107. 279-287 (1997)
• [Publications] Aoyagi M, Yamamoto M, Azuma H, Nagashima G, Niimi Y, Yamamoto K: "Expression of p53 protein and p53 gene transcript in rabbit carotid arteries after baloon denudation" Histochem Cell Biol. 107. 365-370 (1997)
• [Publications] Wakomoto H, Yoshida Y, Aoyagi M Hirakawa K, Hamada H: "Efficient retrovirus-medlated cytokine-gene transduction of primary-cultured human giioma cells for tumor vaccination therapy" Jpn J Cancer Res. 88. 296-305 (1997)
• [Publications] Funato H, Inoshita N, Okada F, Yamamoto S, Aoyagi M: "Cystic ganglloneurocytoma outside ventricular region" Acta Neuropathol. 94. 95-98 (1997)
• [Publications] Tamaki M, Ohno K, Niimi Y, Aoyagi M, Nagashima G, Ichimura K, Hirakawa K: "Parenchymal damage in the territory of the anterior choroidal artery following supraophthalmic intracarotid administration of CDDP for treatment of malignant glioma" J Neuro-Oncol. 35. 65-72 (1997)
• [Publications] Yamamoto S, Wakimoto H, Aoyagi M, Hirakawa K, Hamada H: "Modulation of motility and proliferation of glioma cells by hepatocyte growth factor" Jpn J Cancer Res. 88. 564-577 (1997)
• [Publications] Aoyagi M, Yamamoto M, Azuma H, Nagashima G, Tamaki M, NIimi Y, Hirakawa K, Yamamoto K: "Immmnolocalization of matrix metalloproteinases in rabit carotid after baloon denudation" Histochem and Cell Biol. 109. 97-102 (1998)
• [Publications] Hara M, Aoyagi M, Nagashima G, Wakimoto H, Mikami T, Yamamoto S, Tamaki M, Hirakawa K: "Recurrence in meningeal hemangioglastomas" Surg Neurol. (in press). (1998)
• [Publications] Yamamoto K, Yamamoto M, Akzawa K, Tajima S, Wakimoto K, Aoyagi M: "Decrease in elastin gene expression and protein synthesis in fibroblasts derived from cardinal ligaments of patients with prolapse uteri" Cell Biology International. (in press). (1997)
• [Publications] Yamamoto M, Aoyagi M, Akazawa K, Tajima S, Yamamkto K: "Decrease in p53 Protein in cultured cardinal llgament fibroblasts from patients with uterine prolapse" Cell Biology International. (in press). (1997)
• [Publications] Matsushima Y: "Chapter of Moyamaya disease in Principles and Practice of Pediatric Neurosurgery(ed.Albright AL et al.)" Thieme (in press), (1998)
• [Publications] Matsushima Y: "Chapter of Moyamoya disease in Atlas of Pediatric Neurosurgery(ed.Albright AL et al.)" Thieme (in press), (1998)