Comprehensive search for genes associated with susceptibility to subacute sclerosing panencephalitis in Asia.

全面寻找与亚洲亚急性硬化性全脑炎易感性相关的基因。

• 批准号: 16390304
• 负责人: KUSUHARA Koichi
• 金额: $ 6.85万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390304/
• 关键词: SSPE; susceptibility; genetic; cytokine; Asia; host; measles; treatment; 脳血液関門; SSPE; マイクロアレイ

Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurological illness without established treatment. SSPE is prevalent in some Asian countries where coverage rate of measles vaccine is low. As the precise mechanism how measles virus causes SSPE is still unknown, full clarification of pathogenesis and pathophysiology is essential to establish effective strategy to treat the illness. In this project, we performed a comprehensive search for novel susceptibility genes of SSPE based on the known pathogenesis and data on DNA microarray analysis. High-density oligonucleotide microarray and subsequent quantitative reverse transcriptase polymerase chain reaction demonstrated that the mRNA levels of granulysin were decreased in SSPE patients and were increased in measles patients, suggesting that granulysin might play a role in the host defense against MV and possibly be involved in the pathogenesis or pathophysiology of SSPE. We demonstrated that functional polymorphisms of … More MxA, interleukin (IL)-4 and interferon regulatory factor-1 (IRF-1) genes are associated with the development of SSPE in Japanese. However, the same analysis on Filipino SSPE patients and controls failed to reveal the association between these genes and SSPE. As novel candidate genes for susceptibility to SSPE, a total of 27 polymorphisms of 12 genes encoding molecules involved in double-strand RNA recognition, costimulatory molecules and related molecules were analyzed. PD-1 was associated with the development of SSPE in both Japanese and Filipino, while TLR-3 showed same association only in Japanese.Analyses of patients treated with intraventricular administration of ribavirin which has been developed as a novel treatment for SSPE showed that it is crucial to maintain CSF ribavirin concentration at optimum level to eradicate SSPE virus from CNS and reduce the adverse events during the treatment.Immunological aspect of the pathophysiology of SSPE was analyzed in terms of serum and CSF cytokines. IL-6、 IL-4、 IL-2、 interferon-γ、 TNF-α、 IL-10、 sTNFR1 and two molecules associated with blood brain barrier, MMP-9 and TIMP-1 were associated with the pathological inflammatory process of SSPE.. Less

亚急性硬化性全脑炎（SSPE）是一种进行性和致命的神经系统疾病，没有既定的治疗。SSPE在一些麻疹疫苗覆盖率低的亚洲国家流行。由于麻疹病毒引起SSPE的确切机制尚不清楚，充分阐明其发病机制和病理生理学对于制定有效的治疗策略至关重要。本研究以已知的SSPE发病机制为基础，结合DNA微阵列分析数据，对SSPE的新易感基因进行了全面的研究。高密度寡核苷酸芯片和随后的定量逆转录聚合酶链反应显示，颗粒溶素的mRNA水平在SSPE患者中降低，而在麻疹患者中升高，提示颗粒溶素可能在宿主对MV的防御中起作用，并可能参与SSPE的发病或病理生理过程。我们证明， ...更多信息 MxA、白细胞介素（IL）-4和干扰素调节因子-1（IRF-1）基因与日本人SSPE的发生相关。然而，对菲律宾SSPE患者和对照的相同分析未能揭示这些基因与SSPE之间的关联。作为SSPE易感性的新候选基因，共分析了12个编码双链RNA识别分子、共刺激分子和相关分子的基因的27个多态性。在日本人和菲律宾人中，PD-1与SSPE的发生相关，而TLR-对脑室内注射利巴韦林（一种治疗SSPE的新方法）治疗的患者进行的分析表明，维持CSF中利巴韦林的最佳浓度对于从CNS中根除SSPE病毒和减少治疗期间的不良事件至关重要。免疫学方面从血清和CSF细胞因子方面分析SSPE的病理生理学。IL-6、IL-4、IL-2、IFN-γ、TNF-α、IL-10、sTNFR 1及血脑屏障相关分子MMP-9和TIMP-1参与了SSPE的病理炎症过程。少

项目成果

今日の治療指針2004年版.

今天的治疗指南2004年版。

• 发表时间: 2004
• 作者: 水澤英洋;細矢光亮;楠原浩一他;楠原浩一(分担執筆);楠原浩一(分担執筆)
• 通讯作者: 楠原浩一(分担執筆)

Analysis of serum an cerebrospinal fluid cytokine levels in subacute sclerosing panencephalitis in Papua New Guinea.

巴布亚新几内亚亚急性硬化性全脑炎血清脑脊液细胞因子水平分析。

• 发表时间: 2006
• 期刊: Cytokeine 33(1)
• 作者: Ishizu T;et al.;Ichiyama T. et al.
• 通讯作者: Ichiyama T. et al.

SSPEにおける宿主側遺伝子要因の解析

SSPE宿主遗传因素分析

• 发表时间: 2004
• 期刊: Neuroinfection 9(1)
• 作者: 楠原浩一;吉良龍太郎;原寿郎
• 通讯作者: 原寿郎

細菌性髄膜炎の診療ガイドライン

细菌性脑膜炎临床指南

• 发表时间: 2007
• 作者: 楠原浩一;細矢光亮;市山高志(分担執筆)
• 通讯作者: 市山高志(分担執筆)

Gene expression profiles in peripheral blood mononuclear cells from patients with subacute sclerosing panencephalitis using oligonucleotide microarrays.

使用寡核苷酸微阵列分析亚急性硬化性全脑炎患者外周血单核细胞的基因表达谱。

• 发表时间: 2006
• 期刊: Journal of Neurovirology 11(3)
• 作者: M. Sanefuji;T. Hoshina;JR. Pipo-Deveza;Y. Ishizaki;M. Sanefuji;Takashi Ichiyama;Masafumi Sanefuji;楠原浩一;鳥巣浩幸;T. Ichiyama;M. Sanefuji;Masafumi Sanefuji;楠原 浩一;鳥巣 浩幸;Takaaki Ishizu;Megumi Takemoto
• 通讯作者: Megumi Takemoto