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| 1 | Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis显示文摘AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH. | Mitsuteru Kitade Hitoshi Yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yusaku Shirai Masaharu Yamazaki Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Masayoshi Sawai Motoyuki Yoshida Chie Morioka Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui | 2009 | World Journal of Gastroenterology2009，15，41： | 9 |
| 2 | Endoscopic papillary large balloon dilation for removal of bile duct stones显示文摘AIM:To investigate the efficacy and outcomes of endoscopic papillary large balloon dilation(EPLBD)for bile duct stones in a multicenter prospective study.METHODS:Lithotomy by EPLBD was conducted in 124patients with bile duct stones≥13 mm in size or with three or more bile duct stones≥10 mm.After endoscopic sphincterotomy,the papilla was dilated using balloons 12-20 mm in diameter fitting the bile duct diameter.RESULTS:The success rate of first-time lithotomy was 86.3%(107/124)and the final lithotomy success rate was 100%(124/124).Lithotripsy was needed in10 of the 124(13.6%)patients.Adverse events due to the treatment procedure occurred in 6(4.8%)patients,all of which were mild.Performing large balloon dilation after endoscopic sphincterotomy in patients with large stones or multiple stones in the bile duct is considered to ensure the safety of treatment and to reduce the need for lithotripsy.CONCLUSION:It is suggested that treatment by EPLBD for large bile duct stones may be safe and useful. | Yuji Sakai Toshio Tsuyuguchi Yoshiaki Kawaguchi Nobuto Hirata So Nakaji Katsuya Kitamura Shigeru Mikami Tatsuya Fujimoto Masashi Ijima Eishin Kurihara Shuhei Oana Takayoshi Nishino Ryo Tamura Dai Sakamoto Masato Nakamura Takao Nishikawa Harutoshi Sugiyama Hitoshi Yoshida Tetsuya Mine Osamu Yokosuka | 2014 | World Journal of Gastroenterology2014，20，45： | 6 |
| 3 | Combined treatment of vitamin K_2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis显示文摘Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC. | Hitoshi Yoshiji Ryuichi Noguchi Masaharu Yamazaki Yasuhide Ikenaka Masayoshi Sawai Masatoshi Ishikawa Hideto Kawaratani Tsuyoshi Mashitani Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui | 2007 | World Journal of Gastroenterology2007，13，23： | 5 |
| 4 | Dual therapy with zinc acetate and rifaximin prevents from ethanolinduced liver fibrosis by maintaining intestinal barrier integrity显示文摘BACKGROUND Hepatic overload of gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease(ALD)by inducing oxidative stress and activating Kupffer cells and hepatic stellate cells through toll-like receptor 4 signaling.Therefore,targeting the maintenance of intestinal barrier integrity has attracted attention for the treatment of ALD.Zinc acetate and rifaximin,which is a nonabsorbable antibiotic,had been clinically used for patients with cirrhosis,particularly those with hepatic encephalopathy,and had been known to improve intestinal barrier dysfunction.However,only few studies focused on their efficacies in preventing the ALD-related fibrosis development.AIM To investigate the effects of a combined zinc acetate with rifaximin on liver fibrosis in a mouse ALD model.METHODS To induce ALD-related liver fibrosis,female C57BL/6J mice were fed a 2.5%(v/v)ethanol-containing Lieber-DeCarli liquid diet and received intraperitoneal carbon tetrachloride(CCl4)injection twice weekly(1 mL/kg)for 8 wk.Zinc acetate(100 mg/L)and/or rifaximin(100 mg/L)were orally administered during experimental period.Hepatic steatosis,inflammation and fibrosis as well as intestinal barrier function were evaluated by histological and molecular analyses.Moreover,the direct effects of both agents on Caco-2 barrier function were assessed by in vitro assays.RESULTSIn the ethanol plus CCl4-treated mice,combination of zinc acetate and rifaximin attenuated oxidative lipid peroxidation with downregulation of Nox2 and Nox4.This combination significantly inhibited the Kupffer cells expansion and the proinflammatory response with blunted hepatic exposure of lipopolysaccharide and the toll-like receptor 4/nuclear factor kB pathway.Consequently,liver fibrosis and hepatic stellate cells activation were efficiently suppressed with downregulation of Mmp-2,-9,-13,and Timp1.Both agents improved the atrophic changes and permeability in the ileum,with restoration of tight junction proteins(TJPs)by decreasing the expressions of tumor necrosis factorαand myosin light chain kinase.In the in vitro assay,both agents directly reinforced ethanol or lipopolysaccharide-stimulated paracellular permeability and upregulated TJPs in Caco-2 cells.CONCLUSION Dual therapy with zinc acetate and rifaximin may serve as a strategy to prevent ALD-related fibrosis by maintaining intestinal barrier integrity. | Yuki Fujimoto Kosuke Kaji Norihisa Nishimura Masahide Enomoto Koji Murata Soichi Takeda Hiroaki Takaya Hideto Kawaratani Kei Moriya Tadashi Namisaki Takemi Akahane Hitoshi Yoshiji | 2021 | World Journal of Gastroenterology2021，27，48： | 4 |
| 5 | Immunotherapy for nonalcoholic steatohepatitis using the multiple cytokine production modulator Y-40138显示文摘AIM:To investigate the possible use of the multiple cytokine production modulator,Y-40138,as a novel immunotherapy in the rat nonalcoholic steatohepatitis (NASH) model. METHODS:We allocated 6-wk-old male F344 rats to choline-supplemented,L-amino acid-defined (CSAA) diet (control group),CSAA diet + Y-40138 (control + Y-40138 group),choline-def icient,L-amino acid-def ined (CDAA) diet (NASH group),or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group,we measured the plasma alanine aminotransferase (ALT) levels,and the plasma and liver levels of tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),and interleukin-10 (IL-10). Tissue specimens of phosphate buffered saline-perfused liver were subjected to hematoxylin and eosin staining,Azan staining,Sirius red staining,and immunohistochemical staining (for Kupffer cells and TNF-α). We then extracted Kupffer cells from the collagenase-perfused livers using the Percoll gradient centrifugation method,and measured the TNF-α levels in the supernatant (in vitro TNF-α production by Kupffer cells) using an enzyme-linked immunosorbent assay kit.RESULTS:In comparison to the NASH group,serumALT elevation was mild,production of serum and liver TNF-α and IFN-γ was inhibited,and IL-10 production was increased in the NASH + Y-40138 group. Amelioration of liver histology was also noted in the NASH + Y-40138 group. Kupffer cell immunohistochemical staining revealed no differences between groups,whereas TNF-α immunohistochemical staining showed fewer stained cells in the NASH + Y-40138 group than in the NASH group. The TNF-α levels in the in-vitro Kupffer cell culture supernatant were lower in the NASH + Y-40138 group than in the NASH group.CONCLUSION:Administration of Y-40138 to NASH model rats reduced hepatic inflammation and suppressed fibrosis. These results indicate that the multiple cytokine production modulator,Y-40138,is promising as a novel treatment for NASH. | Tatsuhiro Tsujimoto Hideto Kawaratani Toshiyuki Kitazawa Hitoshi Yoshiji Masao Fujimoto Masahito Uemura Hiroshi Fukui | 2009 | World Journal of Gastroenterology2009，15，44： | 4 |
| 6 | Eosinophilic cholecystitis along with pericarditis caused by Ascaris lumbricoides: A case report显示文摘Although the etiology of eosinophilic cholecystitis is still obscure, the postulated causes include allergies, parasites, hypereosinophilic syndrome, and eosinophilic gastroenteritis. It is sometimes accompanied by several complications, but a simultaneous onset with pericarditis is very rares. A 28-year-old woman complained of acute right hypocondrial pain and dyspnea associated with systemic eruption. Several imaging modalities revealed acute cholecystitis and pericarditis with massive pericardial effusion. A marked peripheral blood eosinophilia was observed, and the eruption was diagnosed as urticaria. Her serum had a high titer of antibody against Ascaris lumbricoides . Treatment with albendazole drastically improved all clinical manifestations along with normalization of the imaging features and eosinophilia. We report herein a rare case of simultaneous onset of acute cholecystitis and pericarditis associated with a marked eosinophilia caused by parasitic infection. | Kosuke Kaji Hitoshi Yoshiji Masahide Yoshikawa Masaharu Yamazaki Yasuhide Ikenaka Ryuichi Noguchi Masayoshi Sawai Masatoshi Ishikawa Tsuyoshi Mashitani Mitsuteru Kitade Hideto Kawaratani Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui | 2007 | World Journal of Gastroenterology2007，13，27： | 3 |
| 7 | Combination of vitamin K 2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Masahisa Toyohara Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masaharu Yamazaki Junichi Yamao Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Masao Fujimoto Tatsuhiro Tsujimoto Hideto Kawaratani Masahito Uemura Hiroshi Fuku | 2009 | Journal of Hepatology2009，，2： | 2 |
| 8 | Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C显示文摘AIM: To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-Ⅰ) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC). METHODS: Perindopril (an ACE-Ⅰ; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS: ACE-Ⅰdecreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-b was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION: The combination therapy of an ACE- Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect. | Hitoshi Yoshiji Ryuichi Noguchi Hideyuki Kojima Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Masaharu Yamazaki Masahisa Toyohara Akira Mitoro Hiroshi Fukui | 2006 | World Journal of Gastroenterology2006，12，42： | 2 |
| 9 | Theoretical analysis of flow characteristics of muhiphase mixtures in a vertical pipe 显示文摘 | Hatta Natsuo Fujimoto Hitoshi Isobe Makoto | 1998 | International Journal of Multiphase Flow1998，24，4： | 1 |
| 10 | Three-dimensional numerical analysis of the deformation behavior of droplets impinging onto a solid suhstrate显示文摘 | Hitoshi Fujimoto Yu Shiotani Albert Y | 2007 | Int J Multiphase Flow2007，33，： | 1 |
| 11 | Combination of branched-chain amino acid and angiotensin?convertingenzyme inhibitor improves liver fibrosis progression in patients with cirrhosis显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yosuke Aihara Akitoshi Douhara Junichi Yamao Masahisa Toyohara Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Chie Morioka Masao Fujimoto Masahito Uemura Hiroshi Fukui | 2012 | Molecular Medicine Reports2012，，： | 1 |
| 12 | Effect of local pipe bends on pump performance of a small air-lift system in transporting solid particles 显示文摘 | Hitoshi Fujimoto | 2004 | International Journal of Heat and Fluid Flow2004，25，： | 1 |
| 13 | Combination of branched-chain amino acids and angiotensin-convertingenzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma:A randomized control trial显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yosuke Aihara Masaharu Yamazaki Junichi Yamao Masahisa Toyohara Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Chie Morioka Masao Fujimoto Masahito Uemura Hiroshi Fukui | 2011 | Oncology Reports2011，，6： | 1 |
| 14 | Branched-chain amino acids suppress the cumulative recurrence of hepatocellularcarcinoma under conditions of insulin-resistance显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Tadashi Namisaki Kei Moriya Mitsuteru Kitade Yosuke Aihara Akitoshi Douhara Junichi Yamao Masao Fujimoto Masahisa Toyohara Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Chie Morioka Masakazu Uejima Masahito Uemura Hiroshi F | 2013 | Oncology Reports2013，，2： | 1 |
| 15 | Extended survival observed in adoptive activated T lymphocyte immunotherapy for advanced lung cancer: results of a multicenter historical cohort study显示文摘 | Kazuro Iwai Kenzo Soejima Shoji Kudoh Yoshimasa Umezato Toru Kaneko Kouji Yoshimori Hitoshi Tokuda Tetsuo Yamaguchi Akira Mizoo Yasuhiro Setoguchi Takashi Kamigaki Katsunada Fujimoto Shigenori Goto | 2012 | Cancer Immunology Immunotherapy2012，，10： | 1 |
| 16 | Three-dimensional numerical a- nalysis of the deformation behavior of droplets impinging onto a solid substrate 显示文摘 | HITOSHI FUJIMOTO | 2007 | International Journal of Multi phase Flow2007，，： | 1 |
| 17 | Theoretical Analysis of Flow Characteristics of Multiphase In A Vertical pipe显示文摘 | Natsuo Hatta Hitoshi Fujimoto Makoto Isobe | 1998 | Internation- al Journal of Multiphase Flow1998，24，4： | 1 |
| 18 | A case of severe acalculous cholecystitis associated with sorafenib treatment for advanced hepatocellular carcinoma显示文摘Sorafenib,a multikinase inhibitor,is the first and only drug,which improves significantly the overall survival in patients with advanced hepatocellular carcinoma(HCC).However,many patients experience diverse side effects,some of them severe and unexpected.To date,acute acalculous cholecystitis has not been documented in association with a HCC patient treated with sorafenib.Here,we report the case of a 43-yearold woman with hepatitis C virus-related advanced HCC.She received sorafenib,and later complained ofa sudden onset of severe right hypocondrial pain with rebound tenderness and muscle defense.Laboratory examination showed mild elevation of transaminases,biliary enzymes,bilirubin,inflammation markers,and a marked peripheral eosinophilia.Abdominal computed tomography(CT) revealed a swollen gallbladder with exudate associated with severe inflammation without stones or debris.Consequently,sorafenib treatment was stopped immediately,and steroid-pulse therapy was performed.Steroid therapy drastically improved all clinical manifestations along with normalization of CT findings,eosinophilia,and liver functions.In summary,we herein report a rare case of acute severe acalculous cholecystitis associated with sorafenib in the patient with advanced HCC. | Yosuke Aihara Hitoshi Yoshiji Masaharu Yamazaki Yasuhide Ikenaka Ryuichi Noguchi Chie Morioka Kosuke Kaji Haruki Tastumi Keisuke Nakanishi Maiko Nakamura Junichi Yamao Masahisa Toyohara Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Masao Fujimoto Masahito Uemura Hiroshi Fukui | 2012 | World Journal of Gastrointestinal Oncology2012，4，5： | 1 |
| 19 | Threedimensional numerical analysis of the deformation behavior of droplets impinging onto a solid substrate显示文摘 | Hitoshi Fujimoto Yu Shiotani Albert Y | | 0，，3： | 1 |
| 20 | Effect of local pipe bends on pump performance of a small air-lift system in transporting solid particles 显示文摘 | Hitoshi Fujimoto | 2004 | International Journal of Heat and Fluid Flow2004，25，： | 1 |
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