Project/Area Number |
11557129
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Pediatric surgery
|
Research Institution | Tohoku University |
Principal Investigator |
OHI Ryoji Tohoku University, school of Medicine, Professor, 大学院・医学系研究科, 教授 (50004734)
|
Co-Investigator(Kenkyū-buntansha) |
NIO Masaki Tohoku University, school of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70228138)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥9,600,000 (Direct Cost: ¥9,600,000)
|
Keywords | biliary atresia / apoptosis / bcl-2 / knock-out mouse / inv / cytokine |
Research Abstract |
As the expression of the bcl-2 gene is analyzed by using the liver biopsy sample at the time of the operation for biliary atresia it has become clear that lower expression of the bcl-2 gene in the liver specimen from patients with biliary atresia than those from controls. Thereupon, we tried to study the liver disease of biliary atresia using the bcl-2 knock-out mouse. Bcl-2 knock-out mice did not survive long enough to be appropriately evaluated. We paid attention to the inv variant mouse that happens to be complicated by cholestasis as well as situs inversus. Furthermore we are studying inv status in biliary atresia patients associated with situs inversus using their blood samples. These studies should elucidate the role of apoptosis inhibitory genes and inv genes in the pathogenesis of biliary atresia. Abnormally progressed apoptosis resulting in diffuse cholangitis would lead to inflammatory catastrophe all over the liver. We already disclosed the significant roles of the various kinds of fibrinogenic cytokines, mast cell, c-kit, and CD14 in the inflammatory process in biliary atresia. While hepatocytes and intrahepatic bile ducts can regenerate enough during and immediately after the embryonal period even when they are severely damaged, extrahepatic biliary atresia is irreversible. We hypothesized that biliary atresia is ultimately established in these process above
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