| Project/Area Number |
16390304
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
KUSUHARA Koichi Kyushu University, Graduate School of Medical Sciences, Associate Prof., 大学院医学研究院, 助教授 (20243941)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KIRA Ryutaro Kyushu University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究院, 助手 (70304805)
TORISU Hiroyuki Kyushu University, University Hospital, Instructor Research Associate, 大学病院, 助手 (10398076)
HARA Toshiro Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 教授 (40150445)
HOSOYA Mitsuaki Fukushima Medical University, Professor, 医学部, 教授 (80192318)
ICHIYAMA Takashi Yamaguchi University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20263767)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥4,200,000 (Direct Cost: ¥4,200,000)
|
|---|
| Keywords | SSPE / susceptibility / genetic / cytokine / Asia / host / measles / treatment / 脳血液関門 / SSPE / マイクロアレイ |
|---|
| Research Abstract |
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
|
