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| 1 | Comprehensive and innovative techniques for livertransplantation in rats: A surgical guide显示文摘AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries.RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model. | Tomohide Hori Justin H Nguyen Yasuhiro Ogura Toshiyuki Hata Shintaro Yagi Ann-Marie T Baine Norifumi Ohashi Christopher B Eckman Aimee R Herdt Hiroto Egawa Yasutsugu Takada Fumitaka Oike Seisuke Saka-moto Mureo Kasahara Kohei Ogawa Koichiro Hata Taku Iida Yukihide Yonekawa Lena Sibulesky Kagemasa Kuribayashi Takuma Kato Kanako Saito Mie Torii Naruhiko Sahara Naoko Kamo Tomoko Sahara Motohiko Yasutomi Shinji Uemoto | 2010 | World Journal of Gastroenterology2010,16,25: | 14 |
| 2 | Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats显示文摘AIM:To investigate oxidative stress(OS)-mediated damage and the behavior of extracellular matrices in various rat models because shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery. These injuries also cause fatal liver damage.METHODS: Rats were divided into four groups according to the surgery performed: control; hepatectomy with 40% liver remnant(60% hepatectomy); orthotopic liver transplantation(OLT) with whole liver graft(100% OLT); and split OLT(SOLT) with 40% graft(40% SOLT). Survival was evaluated. Blood and liver samples were collected at 6 h after surgery. Biochemical and histopathological examinations were performed. OSinduced damage, 4-hydroxynonenal, ataxia-telangiectasia mutated kinase, histone H2AX, phosphatidylinositol 3-kinase(PI3K) and Akt were evaluated by western blotting. Behavior of extracellular matrices, matrix metalloproteinase(MMP)-9, MMP-2, tissue inhibitor of metalloproteinase(TIMP)-1 and TIMP-2 were also evaluated by western blotting and zymography. RESULTS: Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival. Histopathological, immunohistological, biochemical and protein assays revealed that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60% hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant differences in 60% hepatectomy, 100% OLT and 40% SOLT. CONCLUSION: Under conditions with an insufficient liver remnant, prevention of OS-induced damage via the Akt/PI3K pathway may be key to improve the postoperative course. MMP-9 may be also a therapeutic target after surgery. | Tomohide Hori Shinji Uemoto Feng Chen Lindsay B Gardner Ann-Marie T Baine Toshiyuki Hata Takayuki Kogure Justin H Nguyen | 2014 | World Journal of Hepatology2014,6,2: | 7 |
| 3 | Simple and reproducible hepatectomy in the mouse using the clip technique显示文摘AIM: To investigate the reliability of massive hepatectomy models by using clip techniques. METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques. CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data. | Tomohide Hori Norifumi Ohashi Feng Chen Ann-Marie T Baine Lindsay B Gardner Toshiyuki Hata Shinji Uemoto Justin H Nguyen | 2012 | World Journal of Gastroenterology2012,18,22: | 4 |
| 4 | Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice显示文摘AIM:To investigate the effect of matrix metalloproteinase-9(MMP-9) on the remnant liver after massive hepatectomy in the mouse.METHODS:Age-matched,C57BL/6 wild-type(WT),MMP-9(-/-),and tissue inhibitors of metalloproteinases(TIMP)-1(-/-) mice were used.The mice received 80%-partial hepatectomy(PH).Samples were obtained at 6 h after 80%-PH,and we used histology,immunohistochemical staining,western blotting analysis and zymography to investigate the effect of PH on MMP-9.The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor.RESULTS:We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis.There were significantly fewer and smaller hemorrhagic and necrotic lesions in MMP-9(-/-) remnant livers compared with WT and TIMP-1(-/-) livers(P < 0.01),with no difference between WT and TIMP-1(-/-) mice.Serum alanine aminotransaminase levels were significantly lower in MMP-9(-/-) mice compared with those in TIMP-1(-/-) mice(WT:476 ± 83 IU/L,MMP-9(-/-):392 ± 30 IU/L,TIMP-1(-/-):673 ± 73 IU/L,P < 0.01).Western blotting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9(-/-) mice,which was in contrast to WT and TIMP-1(-/-) mice.No change in MMP-2 expression was observed in any of the study groups.Similar to MMP-9(-/-) mice,when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001,hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice(P < 0.05).These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver.CONCLUSION:Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and might be a potential therapy to ameliorate liver injury after massive hepatectomy. | Norifumi Ohashi Tomohide Hori Florence Chen Sura Jermanus Christopher B Eckman Akimasa Nakao Shinji Uemoto Justin H Nguyen | 2012 | World Journal of Gastroenterology2012,18,19: | 3 |
| 5 | Noradrenalin-secreting retroperitoneal schwannoma resected by hand-assisted laparoscopic surgery:report of a case显示文摘 | Tomohide H Kentaro Y Shintaro Y | 2006 | Surg Today2006,36,: | 1 |
| 6 | Matrix metalloproteinase-9 in the initial injury after hepatectomy in mice显示文摘AIM:To investigate the role of matrix metalloproteinase(MMP)-9 in the pathogenesis of postoperative liver failure(PLF) after extended hepatectomy(EH).METHODS:An insufficient volume of the remnant liver(RL) results in higher morbidity and mortality,and a murine model with 80%-hepatectomy was used.All investigations were performed 6 h after EH.Mice were first divided into two groups based on the postoperative course(i.e.,the PLF caused or did not),and MMP-9 expression was measured by Western blotting.The source of MMP-9 was then determined by immunohistological stainings.Tissue inhibitor of metalloproteinase(TIMP)-1 is the endogenous inhibitor of MMP-9,and MMP-9 behavior was assessed by the experiments in wild-type,MMP-9(-/-) and TIMP-1(-/-) mice by Western blotting and gelatin zymography.The behavior of neutrophils was also assessed by immunohistological stainings.An anti-MMP-9 monoclonal antibody and a broadspectrum MMP inhibitor were used to examine the role of MMP-9.RESULTS:Symptomatic mice showed more severe PLF(histopathological assessments:2.97 ± 0.92 vs 0.11 ± 0.08,P < 0.05) and a higher expression of MMP-9(71085 ± 18274 vs 192856 ± 22263,P < 0.01).Nonnative leukocytes appeared to be the main source of MMP-9,because MMP-9 expression corresponding with CD11b positive-cell was observed in the findings of immunohistological stainings.In the histopathological findings,the PLF was improved in MMP-9(-/-) mice(1.65% ± 0.23% vs 0.65% ± 0.19%,P < 0.01) and it was worse in TIMP-1(-/-) mice(1.65% ± 0.23% vs 1.78% ± 0.31%,P < 0.01).Moreover,neutrophil migration was disturbed in MMP-9(-/-) mice in the immunohistological stainings.Two methods of MMP-9 inhibition revealed reduced PLF,and neutrophil migration was strongly disturbed in MMP-9-blocked mice in the histopathological assessments(9.6 ± 1.9 vs 4.2 ± 1.2,P < 0.05,and 9.9 ± 1.5 vs 5.7 ± 1.1,P < 0.05).CONCLUSION:MMP-9 is important for the process of PLF.The initial injury is associated with MMP-9 derived from neutrophils,and MMP-9 blockade reduces PLF.MMP-9 may be a potential target to prevent PLF after EH and to overcome an insufficient RL. | Norifumi Ohashi Tomohide Hori Florence Chen Sura Jermanus Akimasa Nakao Shinji Uemoto Justin H Nguyen | 2013 | World Journal of Gastroenterology2013,19,20: | 1 |
| 7 | Fulminant liver failure models with subsequent encephalopathy in the mouse显示文摘BACKGROUND:A reliable model of fulminant liver failure (FLF) is urgently required in this research field.This study aimed to develop a murine FLF model.METHODS:We used three groups of male C57BL/6 mice:control,with azoxymethane treatment (AOM group),and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-α group).The effects of body temperature (BT) control on survival in all three groups were investigated Using BT control,we compared the survival,histopathological findings and biochemical/coagulation profiles between the two experimental groups.The effects of hydration on international normalized ratios of prothrombin time (PT INRs) were also checked.Dose-dependent survival curves were constructed for both experimental groups.Neurological behavior was assessed using a coma scale.RESULTS:No unexpected BT effects were seen in the control group.The AOM group,but not the Gal+TNF-α group showed a significant difference in survival curves between those with and without BT care.Histopathological assessment showed consistent FLF findings in both experimental groups with BT care.There were significant differences between the experimental groups in aspartate aminotransferase levels and PTINRs,and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups.There were significant differences between FLF models in the duration of each coma stage,with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4).The two FLF models with BT care showed different survival curves in the dose-dependent survival study.CONCLUSIONS:AOM provides a good FLF model,but requires a specialized environment and careful BT control.Other FLF models may also be useful,depending on the research purpose.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models. | Ann-Marie T Baine Tomohide Hori Lindsay B Gardner Shinji Uemoto Justin H Nguyen | 2011 | Hepatobiliary & Pancreatic Diseases International2011,10,6: | 1 |
| 8 | Hypothermia predicts hepatic failure after extensive hepatectomy in mice显示文摘AIM:To investigate the effect of hypothermia on the function of the liver remnant(LR)after extended hepatectomy.METHODS:We performed a 75% partial hepatectomy(PH)in male C57BL/6J mice.Body temperature was measured with a rectal probe.The study mice were prospectively grouped as hypothermic(HT)or normothermic(NT)if their body temperature was < 34 ℃ vs≥ 34 ℃,respectively.Blood and liver samples were obtained at 24 and 48 h after 75% PH.Various factors during and after 75% PH were compared at each time point and the most important factor for a good outcome after 75% PH was determined.RESULTS:At 24 and 48 h after 75% PH,LR weight was decreased in HT mice compared with that in NT mice and the assay results in the HT mice were consistent with liver failure.NT mice had normal liver regeneration.Each intra-and post-operative factor which showed statistical significance in univariate analysis was evaluated by multivariate analysis.The most important factor for a good outcome after 75% PH was body temperature at both 24 and 48 h after surgery.CONCLUSION:Hypothermia after an extensive hepatectomy predicts impending liver failure and may be a useful clinical marker for early detection of liver failure after extended hepatectomy. | Norifumi Ohashi Tomohide Hori Shinji Uemoto Sura Jermanus Feng Chen Akimasa Nakao Justin H Nguyen | 2013 | World Journal of Hepatology2013,5,4: | 1 |
| 9 | Alterations in mi- croRNA expression profile in HCV-infected hepatoma cells: Involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway 显示文摘 | Hisashi I Tomohide T Atsushi H | 2011 | BBRC2011,412,: | 1 |