| Project/Area Number |
11470246
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Hiroshi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90252676)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAGATA Yasuyuki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50273678)
SHIMAZU Takeshi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50196474)
SUGIMOTO Hisashi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (90127241)
SHIOZAKI Tadahiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60278687)
OGURA Hiroshi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70301265)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | trauma sepsis / multiple organ failure / leukocyte / superoxide / G-CSF / G-CSF / レオロジー / 生体防御 / 白血球機能 / NF-κB / マイクロパーテイクル / zymosan / 肺血症 |
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| Research Abstract |
We demonstrated the leukocyte functions in patient with sepsis by multiple organ failure,
1. Severe trauma enhanced expression of heat shock proteins (HSPs) in leukocytes during the acute phase. This enhanced expression of HSPs may regulate leukocyte functions. Sepsis also causes the enhanced expression of HSPs in activated leukocytes. In leukocytes with enhanced expression of HSP, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating leukocyte function in patients with sepsis.
2. Activated platelets enhance microparticle formation and platelet-leukocyte interaction in severe trauma and sepsis. Enhanced platelet-leukocyte interaction is dependent on P-selectin expression and may be involved in the systemic inflammatory response after severe inflammatory insult. Activated leukocytes also enhance production of leukocyte microparticles with increased adhesion molecules in patients with sepsis. Activated leukocyte microparticles may play a role in the pathogenesis of endothelial activation and leukocyte-endothelium interaction in the presence of sepsis.
3. G-CSF administration was effective in septic patients with a low percentage of immature neutrophils and insufficient endogenous G-CSF. It had little effect on patients with a high percentage of immature neutrophis whose G-CSF production was up-regulated and whose bone marrow was severely depressed. G-CSF causes leukocyte stiffness but attenuates inflammatory response without inducing lung injury in septic patients.
4. In the animal experiment, G-CSF administration attenuates zymosan-induced shock without suppression of reactive oxygen species. In addition, we found the enhanced expression of insulin-like growth factor in the group with G-CSF treatment by DNA micro-array method.
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