ユウドウガタ イッサンカ チッソ ゴウセイ コウソ イデンシ ケッソン ワ ノウ ドウミャクリュウ ノ シンコウ オ ヨクセイスル

京都大学0048新制・課程博士博士(医学)甲第10731号医博第2715号新制||医||859(附属図書館)UT51-2004-G578京都大学大学院医学研究科脳統御医科学系専攻(主査)教授 金子 武嗣, 教授 福山 秀直, 教授 橋本 信夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Symptomatic low-grade carotid stenosis with intraplaque hemorrhage and expansive arterial remodeling is associated with a high relapse rate refractory to medical treatment.

[BACKGROUND]: Carotid plaque characteristics influence future risk of stroke considerably. However, the severity of stenosis does not accurately reflect plaque burden in patients with expansive arterial remodeling. [OBJECTIVE]: To determine the therapeutic outcome of symptomatic carotid low-grade stenosis with vulnerable plaque based on magnetic resonance imaging (MRI) characterization. [METHODS]: We studied 25 (male, n = 23; age, 74.2 ± 5.6 years) of 29 consecutive patients with symptomatic carotid low-grade stenosis (<50%) and both high-signal plaque and expansive remodeling on T1-weighted MRIs. The remaining 4 were excluded because of impending stroke. A single antithrombotic and statin were administered, and recurrent ischemic stroke was treated with dual antithrombotics. We considered carotid endarterectomy when recurrence was refractory to aggressive medical treatment. [RESULTS]: During a 31.3 ± 16.4-month follow-up, 11 of the 25 patients developed a total of 30 recurrent ischemic events (46.0% per patient-year). The patients' characteristics did not differ significantly between the groups with and without recurrence (n = 11 and n = 14, respectively). Seven of 11 patients in the recurrence group treated with carotid endarterectomy remained free of ischemic events during a postoperative follow-up of 19.1 ± 14.6 months. [CONCLUSION]: Symptomatic low-grade carotid stenosis with vulnerable plaque confirmed by MRI was associated with a high rate of stroke recurrence that was refractory to aggressive medical treatment. However, carotid endarterectomy was safe and effective for such patients. Plaque characterization by MRI has the potential for more accurate stroke risk stratification in the management of carotid low-grade stenosis

Gene Microarray Analysis of Human Brain Arteriovenous Malformations

OBJECTIVE: Human brain arteriovenous malformations (BAVMs) display abnormal expression of various angiogenesis-related genes and their products. We examined gene expression patterns in BAVMs by the gene microarray technique. METHODS: We analyzed BAVM and control brain samples obtained by temporal lobectomy for medically intractable seizure by Affymetrix Human Gene Set U95Av2 (Affymetrix, Inc., Santa Clara, CA). The gene microarray data were compared with new and previously published data that used conventional molecular biology techniques. RESULTS: We analyzed six BAVM and five control brain samples. From 12,625 gene probes assayed, 1781 gene probes showed differential expression between BAVMs and controls. BAVM samples had a gene expression pattern that was distinct from those of control brain samples. Increased messenger ribonucleic acid expression of vascular endothelial growth factor A was accompanied by increased expression of its protein product. A majority of the gene data was in agreement with previously published data. The gene microarray data generated a new testable hypothesis regarding integrin, and we found increased expression of integrin αvβ3 protein in BAVMs. CONCLUSION: The gene expression pattern of BAVMs was distinct from those of control brain samples. We verified the gene microarray data by demonstrating that increased gene expression levels for angiogenesis-related molecules were accompanied by increased levels of their protein product expression. The gene microarray technique may be a useful tool to study multiple pathways simultaneously in BAVM specimens