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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 | Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B显示文摘AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB. | Ryuichi Noguchi Kosuke Kaji Tadashi Namisaki Kei Moriya Mitsuteru Kitade Kosuke Takeda Hideto Kawaratani Yasushi Okura Yosuke Aihara Masanori Furukawa Akira Mitoro Hitoshi Yoshiji | 2017 | World Journal of Gastroenterology2017，23，36： | 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 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats显示文摘 | Hitoshi Yoshiji Shigeki Kuriyama Junichi Yoshii Yasuhide Ikenaka Ryuichi Noguchi Toshiya Nakatani Hirohisa Tsujinoue Hiroshi Fukui | 2001 | Hepatology2001，，4： | 2 |
| 8 | Tissue inhibitor of metalloproteinases-1 attenuates spontaneous liver fibrosis resolution in the transgenic mouse显示文摘 | Hitoshi Yoshiji Shigeki Kuriyama Junichi Yoshii Yasuhide Ikenaka Ryuichi Noguchi Toshiya Nakatani Hirohisa Tsujinoue Koji Yanase Tadashi Namisaki Hiroo Imazu Hiroshi Fukui | 2002 | Hepatology2002，，4： | 1 |
| 9 | Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Kosuke Kaji Yasuhide Ikenaka Yusaku Shirai Tadashi Namisaki Mitsuteru Kitade Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui | 2010 | Journal of Gastroenterology2010，，4： | 1 |
| 10 | Imatinib mesylate(STI-571) attenuates liver fibrosis development in rats显示文摘 | Ryuichi Noguchi shigeki Kuriyama | 2005 | Am J Gastrointest Liver Physiol2005，288，： | 1 |
| 11 | Synergistic effect of basic fibroblast growth factor and vascular endothelial growth factor in murine hepatocellular carcinoma显示文摘 | Hitoshi Yoshiji Shigeki Kuriyama Junichi Yoshii Yasuhide Ikenaka Ryuichi Noguchi Daniel J. Hicklin James Huber Toshiya Nakatani Hirohisa Tsujinoue Koji Yanase Hiroo Imazu Hiroshi Fukui | 2002 | Hepatology2002，，4： | 1 |
| 12 | 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 |
| 13 | Usefulness of magnetic resonance imaging for diagnosing deep anorectal abscesses显示文摘 | Ryo Maruyama Tsuyoshi Noguchi Masahiro Takano Koichi Takagi Norikazu Morita Ryuichi Kikuchi Yuzo Uchida | 2000 | Diseases of the Colon & Rectum2000，，： | 1 |
| 14 | Combination of sorafenib and angiotensin-II receptor blocker attenuates preneoplastic lesion development in a non-diabetic rat model of steatohepatitis显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Tadashi Namisaki Kei Moriya Mitsuteru Kitade Yosuke Aihara Akitoshi Douhara Hideto Kawaratani Norihisa Nishimura Hiroshi Fukui | 2014 | Journal of Gastroenterology2014，，： | 1 |
| 15 | Branched-chain amino acids suppress insulin-resistance-based hepatocarcinogenesis in obese diabetic rats显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Mitsuteru Kitade Kosuke Kaji Yasuhide Ikenaka Tadashi Namisaki Junichi Yoshii Koji Yanase Masaharu Yamazaki Tatsuhiro Tsujimoto Takemi Akahane Hideto Kawaratani Masahito Uemura Hiroshi Fukui | 2009 | Journal of Gastroenterology2009，，5： | 1 |
| 16 | Prognostic value of CyclinB1 in patients with esophageal squamous cell carcinoma显示文摘 | Shinsuke Takeno Tsuyoshi Noguchi Ryuichi Kikuchi | 2002 | Cancer2002，94，11： | 1 |
| 17 | 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 |
| 18 | Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Kosuke Kaji Yasuhide Ikenaka Yusaku Shirai Tadashi Namisaki Mitsuteru Kitade Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui | 2010 | Journal of Gastroenterology2010，，4： | 1 |
| 19 | DNA methylation of angiotensin Ⅱ receptor gene in nonalcoholic steatohepatitis-related liver fibrosis显示文摘AIM To clarify whether Agtr1 a methylation is involved in the development of nonalcoholic steatohepatitis(NASH)-related liver fibrosis in adult rats.METHODS A choline-deficient amino acid(CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis.Agtr1 a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid(CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR.Hepatic stellate cells(HSCs) were isolated by collagenase digestion of the liver,followed by centrifugation of the crude cell suspension through a density gradient.Agtr1 a methylation and its gene expression were also analyzed during the activation of HSCs.RESULTS The mean levels of Agtr1 a methylation in the livers of CDAA-fed rats(11.5% and 18.6% at 8 and 12 wk,respectively) tended to be higher(P = 0.06 and 0.09,respectively) than those in the livers of CSAA-fed rats(2.1% and 5.3% at 8 and 12 wk,respectively).Agtr1 a was not methylated at all in quiescent HSCs,but was clearly methylated in activated HSCs(13.8%,P < 0.01).Interestingly,although Agtr1 a was hypermethylated,the Agtr1 a m RNA level increased up to 2.2-fold(P < 0.05) in activated HSCs compared with that in quiescent HSCs,suggesting that Agtr1 a methylation did not silence its expression but instead had the potential to upregulate its expression.These findings indicate that Agtr1 a methylation and its upregulation of gene expression are associated with the development of NASH-related liver fibrosis.CONCLUSION This is the first study to show that DNA methylation is potential y involved in the regulation of a renin-angiotensin system-related gene expression during liver fibrosis. | Kiyoshi Asada Yosuke Aihara Hiroaki Takaya Ryuichi Noguchi Tadashi Namisaki Kei Moriya Masakazu Uejima Mitsuteru Kitade Tsuyoshi Mashitani Kosuke Takeda Hideto Kawaratani Yasushi Okura Kosuke Kaji Akitoshi Douhara Yasuhiko Sawada Norihisa Nishimura Kenichiro Seki Akira Mitoro Junichi Yamao Hitoshi Yoshiji | 2016 | World Journal of Hepatology2016，8，28： | 1 |
| 20 | 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 |
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