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| 1 | Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia显示文摘A 'leaky gut' may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. | Hiroshi Fukui | 2015 | World Journal of Hepatology2015，7，3： | 32 |
| 2 | Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment:A case report and review of the literature显示文摘A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients. | Tatsuhiro Tsujimoto Erika Shioyama Kei Moriya Hideto Kawaratani Yasuyo Shirai Masahisa Toyohara Akira Mitoro Jun-ichi Yamao Hisao Fujii Hiroshi Fukui | 2008 | World Journal of Gastroenterology2008，14，39： | 16 |
| 3 | Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome显示文摘AIM:To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease(NAFLD).METHODS:Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography.This study involved 11 714 apparently healthy Japanese men and women,18 to 83 years of age.NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d,known liver disease,or current use of medication.The revised criteria of the National Cholesterol Education Program Adult Treatment PanelⅢ were used to characterize the metabolic syndrome.RESULTS:NAFLD was detected in 32.2%(95%CI:31.0%-33.5%)of men(n=1874 of 5811)and in 8.7%(95%CI:8.0%-9.5%)of women(n=514 of 5903).Among obese people,the prevalence of NAFLD was as high as 67.3%(95%CI:64.8%-69.7%)in men and 45.8%(95%CI:41.7%-50.0%)in women.Although NAFLD was thought of as being the liver phenotype of metabolic syndrome,the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women.66.8%of men and 70.4%of women with NAFLD were not diagnosed with the metabolic syndrome.48.2%of men with NAFLD and 49.8%of women with NAFLD weren't overweight[body mass index(BMI)≥25 kg/m2].In the same way,68.6%of men with NAFLD and 37.9%of women with NAFLD weren't satisfied with abdominal classification(≥90 cm for men and≥80 cm for women).Next,authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome.The sensitivity of the definition'at least 1 criterion'was as good as 84.8%in men and 86.6%in women.Separating subjects by BMI,the sensitivity was higher in obese men and women than in non-obese men and women(92.3%vs 76.8%in men,96.1%vs 77.0%in women,respectively).CONCLUSION:Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome. | Masahide Hamaguchi Noriyuki Takeda Takao Kojima Akihiro Ohbora Takahiro Kato Hiroshi Sarui Michiaki Fukui Chisato Nagata Jun Takeda | 2012 | World Journal of Gastroenterology2012，18，13： | 13 |
| 4 | Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model显示文摘AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet,followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups,using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet,CEUS examination revealed a decrease in the signal intensity,20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group,compared with the controls,with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase,although the Kupffer cell numbers were unchanged,indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality,which can detect NASH in fatty liver patients. | Tatsuhiro Tsujimoto Hideto Kawaratani Toshiyuki Kitazawa Toshiko Hirai Hajime Ohishi Mitsuteru Kitade Hitoshi Yoshiji Masahito Uemura Hiroshi Fukui | 2008 | World Journal of Gastroenterology2008，14，39： | 12 |
| 5 | Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells显示文摘AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLC- assisted differentiation, spontaneous differentiation, and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4, hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone. RESULTS: The mRNA expression of α-fetoprotein, albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes, was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Immunocytochemical analysis revealed an increased ratio of ALB-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storageand urea synthesis were also demonstrated. CONCLUSION: MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells. | Ko Saito Masahide Yoshikawa Yukiteru Ouji Kei Moriya Mariko Nishiofuku Shigehiko Ueda Noriko Hayashi Shigeaki Ishizaka Hiroshi Fukui | 2006 | World Journal of Gastroenterology2006，12，42： | 11 |
| 6 | Differentiation of embryonic stem cells into insulin-producing cells promoted by Nkx2.2 gene transfer显示文摘AIM: To investigate the ability of a genetically altered embryonic stem (ES) cell line to generate insulin-producing cells in vitro following transfer of the Nkx2.2 gene.METHODS: Hamster Nkx2.2 genes were transferred into mouse ES cells. Parental and Nkx2.2-transfected ES cells were initiated toward differentiation in embryoid body (EB)culture for 5 d and the resulting EBs were transferred to an attached culture system. Dithizone (DTZ), a zincchelating agent known to selectively stain pancreatic beta cells, was used to detect insulin-producing cells.The outgrowths were incubated in DTZ solution (final concentration, 100 μg/mL) for 15 min before being examined microscopically. Gene expression of the endocrine pancreatic markers was also analyzed by RT-PCR. In addition, insulin production was determined immunohistochemically and its secretion was examined using an ELISA.RESULTS: DTZ-stained cellular clusters appeared after approximately 14 d in the culture of Nkx2.2-transfected ES cells (Nkx-ES cells), which was as much as 2 wk earlier, than those in the culture of parental ES cells (wt-ES). The frequency of DTZ-positive cells among total cultured cells on day 28 accounted for approximately 1.0% and 0.1% of the Nkx-ES- and wt-ES-derived EB outgrowths, respectively. The DTZ-positive cellular clusters were found to be immunoreactive to insulin, while the gene expressions of pancreatic-duodenal homeobox 1(PDX1), proinsulin 1 and proinsulin 2 were observed in the cultures that contained DTZ-positive cellular clusters.Insulin secretion was also confirmed by ELISA, whereas glucose-dependent secretion was not demonstrated.CONCLUSION: Nkx2.2-transfected ES cells showed an ability to differentiate into insulin-producing cells. | Akira Shiroi Shigehiko Ueda Yukiteru Ouji Ko Saito Kei Moriya Yuko Sugie Hiroshi Fukui Shigeaki Ishizaka Masahide Yoshikawa | 2005 | World Journal of Gastroenterology2005，11，27： | 9 |
| 7 | 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 |
| 8 | Do vasopressin V2 receptor antagonists benefit cirrhotics with refractory ascites?显示文摘Hyponatremia is a frequent complication of advanced cirrhosis with ascites associated with increased morbidity and mortality. It is caused by an impairment in the renal capacity to eliminate solute-free water and is considered to be related to persistent secretionof vasopressin despite low serum osmolality. This nonosmotic release of vasopressin is mediated by the autonomic nervous system, which senses the underfilling of arterial vascular component. This reduction of effective arterial blood volume is closely related to the development of ascites. Although the short-time effects of vasopressin V2 receptor antagonists(vaptans) on hyponatremia and ascites have been repeatedly reported, their effects on the long-term management of cirrhotic ascites have not been established yet. Considering that their effects on water diuresis and their safety are limited by severe underfilling state of patients, cautious approaches with adequate monitoring are needed to advanced cirrhosis. Proper indication, adequate doses and new possibility of combination therapy should be explored in the future controlled study. As hyponatremia is frequent obstacle to ascites management, judicious combination with low-dose diuretics may decrease the incidence of refractory ascites. Although vaptans show much promise in the treatment of advanced cirrhosis, the problem of high cost should be solved for the future. | Hiroshi Fukui | 2015 | World Journal of Gastroenterology2015，21，41： | 7 |
| 9 | Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet显示文摘瞄准:调查肿瘤坏死 factor-alpha (TNF-alpha ) 的天生的有免疫力的反应,像使用费的受体 4 (TLR4 ) ,并且在非酒精的 steatohepatitis (NASH ) 的肝的 CD14 为老鼠建模。方法:男 F344 老鼠被喂一本胆碱缺乏的 L-amino-acid-defined (CDAA ) 食谱。老鼠在食谱的 4 或 8 wk 以后被打死,并且他们的肝为免疫被移开组织化学的调查和 RNA 抽取。肝标本是为 TNF-alpha, TLR4,和 CD14 染色的免疫。TNF-alpha, TLR4,和 CD14 的基因表情被 reverse-transcriptase 聚合酶链反应(RT-PCR ) 决定。Kupffer 房间被 Percoll 坡度远心沉淀从肝孤立,并且当时是有教养的测量 TNF-alpha 生产。结果:在老鼠作为与控制相比显著地增加了的 CDAA-fed 的 TNF-alpha 的浆液和肝层次组织,,与 steatohepatitis 的前进做了免疫组织化学的值和 TNF-alpha, TLR4,和 CD14 的基因表达式。从 CDAA-fed 老鼠的孤立的 Kupffer 房间的 TNF-alpha 生产被脂肪的多糖刺激提高。结论:TNF-alpha, TLR4,和 CD14 的表情在 NASH 模型增加了,建议 TLR4 和调停 CD14 的内毒素肝损坏可以也发生在 NASH。 | Hideto Kawaratani Tatsuhiro Tsujimoto Toshiyuki Kitazawa Mitsuteru Kitade Hitoshi Yoshiji Masahito Uemura Hiroshi Fukui | 2008 | World Journal of Gastroenterology2008，14，43： | 6 |
| 10 | Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl_4-treated mice显示文摘AIM: To transplant undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl4)-treated mice to determine their ability to differentiate into hepatocytes in the liver. METHODS: CCl4, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 (n = 12), 1 x 105 undifferentiated ES cells (0.1 mL of 1 x 106/mL solution), genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice (n = 12) were injected with 0.2 mL of saline twice a week, instead of CCl4, and the same amount of ES cells was transplanted into the spleens. Group 3 mice (n = 6) were treated with CCl4 and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d (PD) 10, 20, and 30. RESULTS: Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice (CCl4-treated) on PD 10, however, not in those untreated with CCl4 (group 2). The GFP-positive cells were also immunopositive for albumin (ALB), alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantationduring the experimental period. CONCLUSION: Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth. | Kei Moriya Masahide Yoshikawa Ko Saito Yukiteru Ouji Mariko Nishiofuku Noriko Hayashi Shigeaki Ishizaka Hiroshi Fukui | 2007 | World Journal of Gastroenterology2007，13，6： | 5 |
| 11 | 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 |
| 12 | 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 |
| 13 | 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 |
| 14 | Cryptogenic cirrhosis in the region where obesity is not prevalent显示文摘瞄准:最近的研究证明了肥胖是起因不明的肝硬化(CC ) 和非酒精的 steatohepatitis 的普通特征。然而,几乎在肥胖不是流行的区域的 CC 上没有很少信息。方法:CC 的临床的特征,和肝相关的病态和死亡在肥胖的流行是低的日本被分析。在 652 个肝脏硬化症的病人之中,我们与 CC 识别了 29 个病人(4.4%) 。这些,被跟随在上面因为超过 6 个月在盒子控制被比较的 24 个 CC 病人与年龄学习 -- ,性别 -- ,并且病毒的病原学的孩子呸匹配分数的控制有肝硬化。结果:肥胖(BMI>or=25 kg/m (2 )) ,糖尿病,和 hypertriglyceridemia 是更经常的,并且内脏的胖区域比在控制在 CC 病人是更大的。抗胰岛素性的索引更高,浆液 aminotransferase 层次比在控制在 CC 病人是更低的。逻辑回归分析作为 CC 的独立预言者识别了提高的血红素 A1c, BMI>or=25 kg/m (2 ) ,和正常 aminotransferase 层次。Kaplan-Meier 分析与在那些组之间的肝相关的病态的类似的累积概率相对照比在控制在 CC 表明了肝细胞癌和更高的幸存率的更低的出现。结论:CC 更经常甚至在肥胖不是流行的区域与控制相比与非酒精的 steatohepatitis 暗示的临床的特征介绍。肝细胞癌和更高的幸存率的更低的出现可以作为与病毒的肝硬化相比在 CC 显示一堂懒惰临床的功课。 | Hideyuki Kojima Shinya Sakurai Masahiko Matsumura Norie Umemoto Masahito Uemura Hiroyo Morimoto Yasuhiro Tamagawa Hiroshi Fukui | 2006 | World Journal of Gastroenterology2006，12，13： | 3 |
| 15 | Local regulator adrenomedullin contributes to the circulatory disturbance in cirrhotic rats显示文摘瞄准:调查是否 adrenomedullin,有势力血管扩张药肽,在肝硬化在循环骚乱起一个作用。方法:肝硬化被四氯化碳的每周的管饲法在老鼠导致。血液动力学的研究用孤立的大动脉的戒指是用放射性的微范围和在试管内的执行在活体内。adrenomedullin 集中被放射性免疫测定测量。结果:到控制老鼠的 adrenomedullin 的尖锐管理与氮的氧化物(NOx ) 的稳定的代谢物的浆液层次的增加一起减少了全身的动脉压,以一种剂量依赖者方式。adrenomedullin 的长期的注入减少了脉管的抵抗并且在全身、内脏的发行量增加了血流。而这抗体改善了, anti-adrenomedullin 抗体的静脉内的管理没在肝脏硬化症的老鼠影响任何血液动力学的参数对脱羟肾上腺素的弄钝的可收缩的反应, alpha 肾上腺素能的受体收缩筋,在肝脏硬化症的老鼠的大动脉的戒指。在主动脉的 adrenomedullin 集中比在控制在肝脏硬化症的老鼠是更高的,并且在肝脏硬化症的老鼠与吝啬的动脉压相关。而且, adrenomedullin 弄钝可收缩的反应到脱羟肾上腺素在控制主动脉和肝脏硬化症的主动脉,然而并非面对 NG-nitro-L-arginine 甲基酉旨,一没有 synthase 禁止者。结论:Adrenomedullin 在脉管的墙中生产过多可以作为脉管的音调而非传播荷尔蒙的一个本地管理者在肝硬化贡献循环骚乱。 | Shinya Sakurai Hideyuki Kojima Masahito Uemura Hiroyasu Satoh Hiroshi Fukui | 2006 | World Journal of Gastroenterology2006，12，13： | 2 |
| 16 | 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 |
| 17 | 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 |
| 18 | Changes in the expression and localization of hepatocellular transporters and radixin in primary biliary cirrhosis显示文摘 | Hideyuki Kojima Anne T Nies J?rg K?nig Wolfgang Hagmann Herbert Spring Masahito Uemura Hiroshi Fukui Dietrich Keppler | 2003 | Journal of Hepatology2003，，5： | 1 |
| 19 | Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance显示文摘 | Sizuo Kajiyama Goji Hasegawa Mai Asano Hiroko Hosoda Michiaki Fukui Naoto Nakamura Jo Kitawaki Saeko Imai Koji Nakano Mitsuhiro Ohta Tetsuo Adachi Hiroshi Obayashi Toshikazu Yoshikawa | 2008 | Nutrition Research2008，，3： | 1 |
| 20 | LINE-1 Hypomethylation in a Choline-Deficiency-Induced LiverCancer in Rats: Dependence on Feeding Period显示文摘 | Kiyoshi Asada Yashige Kotake Rumiko Asada Deborah Saunders Robert H. Broyles Rheal A. Towner Hiroshi Fukui Robert A. Floyd | 2006 | Journal of Biomedicine and Biotechnology2006，，： | 1 |
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