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| 1 | Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy显示文摘AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage. | Mitsushige Sugimoto Masafumi Nishino Chise Kodaira Mihoko Yamade Takahiro Uotani Mutsuhiro Ikuma Kazuo Umemura Takahisa Furuta | 2011 | World Journal of Gastroenterology2011，17，14： | 10 |
| 2 | Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma显示文摘AIM: To investigate the clinical significance of KL-6 as a tumor marker of HCC in two different ethnic groups with chronic liver disease consecutively encountered at outpatient clinics.METHODS: Serum KL-6 was measured by the sandwich enzyme immunoassay method using the KL-6 antibody (Ab) as both the capture and tracerAb according to the manufacturer's instructions (Eisai, Tokyo, Japan).Assessment of alpha fetoprotein (AFP) and protein induced vitamin K deficiency or absence (PIVKA-Ⅱ) was performed in both groups using commercially available kits.RESULTS: A significantly higher mean serum KL-6(556±467 U/L) was found in HCC in comparison with non-HCC groups either with (391±176 U/L; P<0.001)or without (361±161 U/L; P<0.001) liver cirrhosis (LC).Serum KL-6 level did not correlate with either AFP or PIVKA-Ⅱ serU/Levels. Using receiver operating curve analysis for KL-6 as a predictor for HCC showed that the area under the curve was 0.574 (95%CI = 0.50-0.64)and the KL-6 level that gave the best sensitivity (61%) was found to be 334 U/L but according to the manufacturer's instructions; a cut-off point of 500 U/Lwas used that showed the highest specificity (80%)in comparison with AFP and PIVKA-Ⅱ (78% vs 72%respectively). Combining the values of the three markers improved specificity of AFP for HCC diagnosis from 78%for AFP alone; 93% for AFP plus PIVKA-Ⅱ to 99% for both plus KL-6 value (P<0.001). Mean serum alkaline phosphatase level was significantly higher in KL-6positive (564±475) in comparison with KL-6 negative (505±469) HCC patients (P = 0.021), but such a difference was not found among non-HCC corresponding groups.CONCLUSION: KL-6 is suggested as a tumor for HCC.Its positivity may reflect HCC-associated cholestasis and/or local tumor invasion. | Amal Gad Eiji Tanaka Akihiro Matsumoto Moushira Abd-el Wahab Abd el-Hamid Serwah Fawzy Attia Khalil Ali Howayda Hassouba Abd el-Raoof el-Deeb Tetsuya Ichijyo Takeji Umemura Hidetomo Muto Kaname Yoshizawa Kendo Kiyosawa | 2005 | World Journal of Gastroenterology2005，11，42： | 8 |
| 3 | Gastrointestinal polyposis with esophageal polyposis is useful for early diagnosis of Cowden's disease显示文摘Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been reported to be complicated by malignant tumors. Based on the criteria of the International Cowden Consortium, this disease is mainly diagnosed as trichilemmoma of the face and oral mucosal papillomatosis. However, Cowden's disease patients themselves often do not recognize trichilemmoma of the face and oral mucosal papillomatosis. We report a case of Cowden's disease in a 33-year-old female patient who was diagnosed based on the characteristic findings at gastrointestinal endoscopy. Clinically, the patient was aware of having bloody stools. Multiple polyps found endoscopically in the esophagus, stomach, ileum, colon and rectum showed histopathologically hamartomatous changes and epithelial hyperplasia. Physical examination revealed oral papillomatosis and facial trichilemmomas. A germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was found in this case. It was a point mutation of C to T at codon 1003 (CGA→TGA, arginine→stop codon). The characteristic findings on gastrointestinal endoscopy led us to a diagnosis of Cowden's disease. It has been reported that gastrointestinal polyposis with esophageal polyposis is found in about 85.7% of Japanese patients with Cowden's disease. The characteristic findings on gastrointestinal endoscopy can be a useful diagnostic clue to Cowden's disease. | Ken Umemura Sho Takagi Yasushi Ishigaki Masahiro Iwabuchi Shigeru Kuroki Yoshitaka Kinouchi Tooru Shimosegawa | 2008 | World Journal of Gastroenterology2008，14，37： | 6 |
| 4 | Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in patients with non-alcoholic fatty liver disease显示文摘AIM To examine the relationship between serum autotaxin(ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD) patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman's test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P < 0.001) and correlated significantly with ballooning score and fibrosis stage(r = 0.36,P < 0.001 and r = 0.45,P < 0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(≥ F1),significant fibrosis(≥ F2),severe fibrosis(≥ F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD. | Naoyuki Fujimori Takeji Umemura Takefumi Kimura Naoki Tanaka Ayumi Sugiura Tomoo Yamazaki Satoru Joshita Michiharu Komatsu Yoko Usami Kenji Sano Koji Igarashi Akihiro Matsumoto Eiji Tanaka | 2018 | World Journal of Gastroenterology2018，24，11： | 6 |
| 5 | Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis显示文摘AIM The impact of mild drinking habit(less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease(NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD. METHODS A total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with nonalcoholic steatohepatitis, 26% with advanced fibrosis(F3-4)] were divided into the mild drinking group withe thanol consumption of less than 20 g/d(mild drinking group, n = 93) and the non-drinking group(n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma(HCC) occurrence were compared between the groups.RESULTS We observed significant differences in male prevalence(P = 0.01), platelet count(P = 0.04), and gammaglutamyl transpeptidase(P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group(6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox's regression model revealed that hepatic advanced fibrosis(F3-4)(P < 0.01, risk ratio: 11.60), diabetes mellitus(P < 0.01, risk ratio: 89.50), and serum triglyceride(P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal(P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis(F3-4), however, a drinking habit(P = 0.04, risk ratio: 4.83), alpha-fetoprotein(P = 0.01, risk ratio: 1.23), and diabetes mellitus(P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence. CONCLUSION A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis. | Takefumi Kimura Naoki Tanaka Naoyuki Fujimori Ayumi Sugiura Tomoo Yamazaki Satoru Joshita Michiharu Komatsu Takeji Umemura Akihiro Matsumoto Eiji Tanaka | 2018 | World Journal of Gastroenterology2018，24，13： | 6 |
| 6 | Association between endotoxemia and histological features of nonalcoholic fatty liver disease显示文摘AIM To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features ofnonalcoholic fatty liver disease(NAFLD).METHODS One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide(LPS)-binding protein(LBP) and anti-endotoxin core immunoglobulin G(Endo Cab Ig G) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores. RESULTS Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis(NASH) patients as compared with nonalcoholic fatty liver(NAFL) subjects and was correlated with steatosis(r = 0.38, P < 0.0001) and ballooning scores(r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum Endo Cab Ig G concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between Endo Cab Ig G and histological findings. CONCLUSION LBP/Endo Cab Ig G were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH. | Hiroyuki Kitabatake Naoki Tanaka Naoyuki Fujimori Michiharu Komatsu Ayaka Okubo Kyogo Kakegawa Takefumi Kimura Ayumi Sugiura Tomoo Yamazaki Soichiro Shibata Yuki Ichikawa Satoru Joshita Takeji Umemura Akihiro Matsumoto Masayoshi Koinuma Kenji Sano Toshifumi Aoyama Eiji Tanaka | 2017 | World Journal of Gastroenterology2017，23，4： | 5 |
| 7 | Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion显示文摘AIM: To investigate the role of pre-core and basal core promoter(BCP) mutations before and after hepatitis Be antigen(HBe Ag) seroconversion.METHODS: The proportion of pre-core(G1896A) and basal core promoter(A1762T and G1764A) mutant viruses and serum levels of hepatitis B virus(HBV) DNA, hepatitis B surface antigen(HBs Ag), and HB core-related antigen were analyzed in chronic hepatitis B patients before and after HBe Ag seroconversion(n = 25), in those who were persistently HBe Ag positive(n = 18), and in those who were persistently anti-HBe positive(n = 43). All patients were infected with HBV genotype C and were followed for a median of 9 years.RESULTS: Although the pre-core mutant became predominant(24% to 65%, P = 0.022) in the HBe Ag seroconversion group during follow-up, the proportion of the basal core promoter mutation did not change. Median HBV viral markers were significantly higher in patients without the mutations in an HBe Ag positive status(HBV DNA: P = 0.003; HBs Ag: P < 0.001; HB core-related antigen: P = 0.001). In contrast, HBV DNA(P = 0.012) and HBs Ag(P = 0.041) levels were significantly higher in patients with the pre-core mutation in an anti-HBe positive status.CONCLUSION: There is an opposite association of the pre-core mutation with viral load before and after HBe Ag seroconversion in patients with HBV infection. | Nozomi Kamijo Akihiro Matsumoto Takeji Umemura Soichiro Shibata Yuki Ichikawa Takefumi Kimura Michiharu Komatsu Eiji Tanaka | 2015 | World Journal of Gastroenterology2015，21，2： | 4 |
| 8 | Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions显示文摘AIM To investigate daclatasvir(DCV) and asunaprevir(ASV) efficacy in hepatitis C(HCV) patients, with respect to resistance-associated substitutions(RASs).METHODS A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses(SVR) according to pretreatment factors(gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion(SVR12).RESULTS The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/m L was significantly lower than those with viral loads of < 6.0 log IU/m L(P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative(P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure.CONCLUSION Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure. | Hideki Fujii Atsushi Umemura Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Hideki Nakamura Kohichiroh Yasui Masahito Minami Saiyu Tanaka Hiroki Ishikawa Hiroyuki Kimura Shiro Takami Yasuyuki Nagao Toshihide Shima Yoshito Itoh | 2017 | World Journal of Hepatology2017，9，25： | 3 |
| 9 | Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in patients with EGFR mutation-positive lung adenocarcinoma显示文摘 | Tatsuya Yoshida Genichiro Ishii Koichi Goto Kiyotaka Yoh Seiji Niho Shigeki Umemura Shingo Matsumoto Hironobu Ohmatsu Kanji Nagai Yuichiro Ohe Atsushi Ochiai | 2013 | Journal of Cancer Research and Clinical Oncology2013，，10： | 3 |
| 10 | An oral fluoropyrimidine agent S-1 induced interstitial lung disease:A case report显示文摘A 66-year-old Japanese man with pancreatic cancer received eleven courses of gemcitabine monotherapy.The tumor responded to gemcitabine until metastatic liver tumors progressed.Subsequently,he was treated with S-1,an oral fluoropyrimidine anticancer agent,as salvage chemotherapy.Forty-two days after initiating S-1,he presented with dyspnea and fever.Chest computed tomography showed diffuse interstitial lesions with thickening of the alveolar septa and ground glass opacity.Serum KL-6 level was elevated to 1,230 U/mL and he did not use any other drugs except insulin.Thus,the development of interstitial lung disease(ILD)was considered to be due to S-1.Arterial blood oxygen pressure was 49.6 Torr in spite of oxygen administration(5 L/min).Steroid therapy improved his symptoms and the interstitial shadows on chest radiograph.Although S-1-induced ILD has mostly been reported to be mild,clinicians should be aware that S-1 has the potential to cause fatal ILD. | Hiromichi Yamane Masahide Kinugawa Shigeki Umemura Yasuhiro Shiote Kenichiro Kudo Toshimitsu Suwaki Haruhito Kamei Nagio Takigawa Katsuyuki Kiura | 2011 | World Journal of Clinical Oncology2011，2，7： | 3 |
| 11 | Effect of dietary docosahexaenoic acid in the rat middle cerebral artery thrombosis model显示文摘 | K. Umemura Y. Toshima F. Asai M. Nakashima | 1995 | Thrombosis Research1995，，5： | 2 |
| 12 | Analysis software for upper atmospheric data developed by the IUGONET project and its application to polar science显示文摘To comprehensively understand the Arctic and Antarctic upper atmosphere,it is often crucial to analyze various data that are obtained from many regions.Infrastructure that promotes such interdisciplinary studies on the upper atmosphere has been developed by a Japanese inter-university project called the Inter-university Upper atmosphere Global Observation Network(IUGONET).The objective of this paper is to describe the infrastructure and tools developed by IUGONET.We focus on the data analysis software.It is written in Interactive Data Language(IDL)and is a plug-in for the THEMIS Data Analysis Software suite(TDAS),which is a set of IDL libraries used to visualize and analyze satellite-and ground-based data.We present plots of upper atmospheric data provided by IUGONET as examples of applications,and verify the usefulness of the software in the study of polar science.We discuss IUGONET’s new and unique developments,i.e.,an executable file of TDAS that can run on the IDL Virtual Machine,IDL routines to retrieve metadata from the IUGONET database,and an archive of 3-D simulation data that uses the Common Data Format so that it can easily be used with TDAS. | Yoshimasa Tanaka Atsuki Shinbori Tomoaki Hori Yukinobu Koyama Shuji Abe No-rio Umemura Yuka Sato Manabu Yagi Satoru UeNo Akiyo Yatagai Yasunobu Ogawa Yoshizumi Miyoshi | 2013 | Advances in Polar Science2013，24，4： | 2 |
| 13 | Ability of Rabeprazole to Prevent Gastric Mucosal Damage From Clopidogrel and Low Doses of Aspirin Depends on CYP2C19 Genotype显示文摘 | Takahiro Uotani Mitsushige Sugimoto Masafumi Nishino Chise Kodaira Mihoko Yamade Shu Sahara Takanori Yamada Satoshi Osawa Ken Sugimoto Tatsuo Tanaka Kazuo Umemura Hiroshi Watanabe Hiroaki Miyajima Takahisa Furuta | 2012 | Clinical Gastroenterology and Hepatology2012，，8： | 2 |
| 14 | Long‐term outcome of Japanese patients with type 1 autoimmune hepatitis显示文摘 | Kaname Yoshizawa Akihiro Matsumoto Tetsuya Ichijo Takeji Umemura Satoru Joshita Michiharu Komatsu Naoki Tanaka Eiji Tanaka Masao Ota Yoshihiko Katsuyama Kendo Kiyosawa Masanori Abe Morikazu Onji | 2012 | Hepatology2012，，： | 2 |
| 15 | Intracoronary Ultrasound Diagnosis of an Aortic Dissection Causing Anterior Acute Myocardial Infarction显示文摘 | Kiyoshi Hibi Kazuo Kimura Tomoyori Nakatogawa Jun Okuda Satoshi Umemura Paul G. Yock | 2003 | Circulation: Journal of the American Heart Association2003，，20： | 2 |
| 16 | Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction显示文摘 | Satoshi Kurisu Ichiro Inoue Takuji Kawagoe Masaharu Ishihara Yuji Shimatani Kenji Nishioka Takashi Umemura Suji Nakamura Masashi Yoshida Hikaru Sato | 2003 | Journal of the American College of Cardiology2003，，： | 2 |
| 17 | Soluble adhesion molecules and C-reactive protein in the progression of silent cerebral infarction in patients with type 2 diabetes mellitus显示文摘 | Kawamura T Umemura T Kanai A | 2006 | Metabolism2006，55，： | 1 |
| 18 | Proteomic analysis of mechanisms of hypoxia-induced apoptosis in trophoblastic cells 显示文摘 | Ishioka S Ezaka Y Umemura K | 2007 | Int J Med Sei2007，4，1： | 1 |
| 19 | Magnetic thin films of cobalt nanocrystals encapsulated in graphite-like carbon, 显示文摘 | Hirono S Tomita T Umemura S | 1996 | Nature 19961996，772，： | 1 |
| 20 | Preparation and application of methacrylate-based cation-exchange monolithic columns for capillary ion chromatography显示文摘 | UEKI Y UMEMURA T LI J X | 2004 | Anal Chem2004，76，： | 1 |
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