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| 1 | NAT2*6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis显示文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, 'NAT2*4', was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity. | Norihide Higuchi Naoko Tahara Katsunori Yanagihara Kiyoyasu Fukushima Naofumi Suyama Yuichi Inoue Yoshitsugu Miyazaki Tsutomu Kobayashi Koh-ichiro Yoshiura Norio Niikawa, Chun-Yang Wen, Hajime Isomoto,Saburou Shikuwa, Katsuhisa Omagari, Yohei Mizuta, Shigeru Kohno, Kazuhiro Tsukamoto Norio Niikawa Chun-Yang Wen Hajime Isomoto Saburou Shikuwa Katsuhisa Omagari Yohei Mizuta Shigeru Kohno Kazuhiro Tsukamoto | 2007 | World Journal of Gastroenterology2007，13，45： | 21 |
| 2 | Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese显示文摘AIM: To examine an association between the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.METHODS: We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs)in CTLA4, such as C-318T in the promoter region, A+49G in exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT)n repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using χ2 and Fisher exact tests.RESULTS: The frequency of 'A/A' genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P= 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of'G/G' genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%)(P = 0.0388, OR=2.67).CONCLUSION: The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese. | Haruhisa Machida Kazuhiro Tsukamoto Chun-Yang Wen Yukiko Narumi Saburou Shikuwa Hajime Isomoto Fuminao Takeshima Yohei Mizuta Norio Niikawa Ikuo Murata Shigeru Kohno | 2005 | World Journal of Gastroenterology2005，11，27： | 4 |
| 3 | Enlarged accessory spleen presenting stomach submucosal tumor显示文摘A 62-year-old man presented with upper abdominal discomfort underwent upper gastrointestinal endoscopy. Gastroscopy and endoscopic ultrasonography revealed a submucosal tumor (SMT) with homogenous echogenicity originated from extragastric organs. An abdominal contrast-enhanced computed tomography (CT) showed that the well-marginated ovoid mass, approximately 6 cm in diameter, enhanced homogenously to a similar degree as splenic parenchyma. 99mTechnetium sulfur colloid scintigraphy revealed the splenic nature of the mass. A diagnosis of accessory spleen mimicking gastric SMT was made. Subsequent follow-up was uneventful without performing splenectomy. | Shunzen Chin Hajime Isomoto Yohei Mizuta Chun-Yang Wen Saburo Shikuwa Shigeru Kohno | 2007 | World Journal of Gastroenterology2007，13，11： | 4 |
| 4 | Crohn's disease in Japanese is associated with a SNP-haplotype of N-acetyltransferase 2 gene显示文摘AIM: To investigate the frequency and distribution of N-acetyltransferase 2 (NAT2) and uridine 5′-diphosphate (UDP)-glucuronosyltransferase 1A7 (UGT1A7) genes in patients with ulcerative colitis (UC) and Crohn's disease (CD).METHODS: Frequencies and distributions of NAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism (RFLP),PCR-denaturing high-performance liquid chromatography (DHPLC), and direct DNA sequencing.RESULTS: Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2*7B, significantly increased in CD patients, compared to that in controls (P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316). However,there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease (IBD).CONCLUSION: It is likely that the NAT2 gene is one of the determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, whereNAT2is located. | Haruhisa Machida Kazuhiro Tsukamoto Chun-Yang Wen Saburou Shikuwa Hajime Isomoto Yohei Mizuta Fuminao Takeshima Kunihiko Murase Naomichi Matsumoto Ikuo Murata Shigeru Kohno Chen-Yang Wen | 2005 | World Journal of Gastroenterology2005，11，31： | 3 |
| 5 | Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency显示文摘有风湿性关节炎(RA ) 的 29 年的历史的一个 56 岁的女人进入医院,抱怨高发烧,腹的疼痛和严重流血腹泻。结肠镜检查与从直肠延长到远侧的横向的冒号的自发的流血、弥漫的侵蚀和溃疡揭示了脆、水肿的粘膜。直肠的活体检视的组织病理学说的调查结果与 ulcerative (UC ) 兼容。作为有严重活跃左边的 UC 被诊断,她成功地被对待,静脉内的甲基氢化尼松由氢化尼松和 leukocytapheresis 列在后面。实验室测试揭示了低浆液和口水 IgA 层次,它可能在 UC 的发展起一个作用。到我们的知识,这是发生在 RA 的功课期间的 UC 的第一个盒子,由选择 IgA 缺乏伴随了。 | Yuki Asada Hajime Isomoto Saburo Shikuwa Chun Yang Wen Eiichiro Fukuda Masaru Miyazato, Kenta Okamoto Takashi Nakamura Hitoshi Nishiyama Yohei Mizuta Kiyoshi Migita Masahiro Ito Shigeru Kohno | 2006 | World Journal of Gastroenterology2006，12，32： | 2 |
| 6 | Novel serine/threonine kinase 11 gene mutations in PeutzJeghers syndrome patients and endoscopic management显示文摘AIM:To explore mutations in serine/threonine kinase 11(STK11) gene in Peutz-Jeghers syndrome(PJS) with gastrointestinal(GI) hamartomatous polyps.METHODS:Six Japanese PJS patients in 3 families were enrolled in this study.Each of the cases had hamartomatous polyposis in the gastrointestinal tract,including the small intestine,along with mucocutaneous hyperpigmentation.Narrow-band imaging(NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions.NBI magnification findings could be classified into three groups(type A,type B,or type C).Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy.Genomic DNA was extracted from a whole blood sample from each subject.All of the coding exons of STK11 gene,its boundary regions,and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction,and direct sequencing was performed to assess the germline mutations.RESULTS:NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps.Overall,we found 5 cases of type A and one case without the examination for the gastric polyps,while there were 4 cases of type B and 2 case of type A for the colorectal polyps.Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications.The only delayed complication included the occurrence of bleeding in a case,and this was successfully managed with hemoclips.Resected polyps contained no malignant components.Based on mutation analysis,all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5,which resulted in the production of a truncated protein(Q220X).In Family II,a case had-252C>A and-193C>A in the promoter region.In Family III,a case was found to have the +1062C>G(F342L) mutation in exon 8.CONCLUSION:We found two novel mutations of STK11 in association with PJS.Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk. | Hiroyuki Yajima Hajime Isomoto Hiroaki Nishioka Naoyuki Yamaguchi Ken Ohnita Tatsuki Ichikawa Fuminao Takeshima Saburo Shikuwa Masahiro Ito Kazuhiko Nakao Kazuhiro Tsukamoto Shigeru Kohno | 2013 | World Journal of Gastrointestinal Endoscopy2013，5，3： | 2 |
| 7 | A new thin endoscopic method of transanal drainage tube insertion for acute colonic ob-struction due to colorectal cancer 显示文摘 | Ohnita K Shikuwa S Isomoto H | 2009 | Dig Endosc2009，21，4： | 1 |
| 8 | Relationship between ECG findings and pulmonary artery pressure in patients with acute massive pulmonary thromboembolism显示文摘 | Yoshinaga T Ikeda S Shikuwa M | 2003 | Circ J2003，67，： | 1 |
| 9 | Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study 显示文摘 | Isomoto H Shikuwa S Yamaguchi N | 2009 | Gut2009，58，3： | 1 |
| 10 | A Case of Cronkhite-Canada syndrome: Remission after treatment with anti-helicobacter pylori regimen 显示文摘 | OKAMOTO K ISOMOTO H SHIKUWA S | 2008 | Digestion2008，78，2： | 1 |
| 11 | A case of Cronkhite-Canada syndrome: remission after treatment with anti-Helicobacter pylori regimen显示文摘 | Okamoto K Isomoto H Shikuwa S | 2008 | Digestion2008，78，23： | 1 |
| 12 | Endoscopic submucosal dissection for laterally spreading tumours of the colorectum in 200 consecutive cases显示文摘 | Hitoshi Nishiyama Hajime Isomoto Naoyuki Yamaguchi Hiroyuki Ishii Eiichiro Fukuda Haruhisa Machida Takashi Nakamura Ken Ohnita Saburo Shikuwa Shigeru Kohno Kazuhiko Nakao | 2010 | Surgical Endoscopy2010，，： | 1 |
| 13 | Endoscopicsubmucosal dissection for early gastric cancer: a large-scale feasibility study 显示文摘 | Isomoto H Shikuwa S Yamaguchi N | 2009 | Gut2009，58，3： | 1 |
| 14 | Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study 显示文摘 | Isomoto H Shikuwa S Yamaguchi N | 2009 | Gut2009，58，： | 1 |
| 15 | Effect of oral pred- nisolone on esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: a case report显示文摘 | Yamaguchi N lsomoto H Shikuwa S | 2011 | Digestion2011，83，4： | 1 |
| 16 | Endoscopic submucosal dissection for rectal carcinoid tumors显示文摘 | Naoyuki Yamaguchi Hajime Isomoto Hitoshi Nishiyama Eiichiro Fukuda Hiroyuki Ishii Takashi Nakamura Ken Ohnita Tomayoshi Hayashi Shigeru Kohno Kazuhiko Nakao Saburo Shikuwa | 2010 | Surgical Endoscopy2010，，3： | 1 |
| 17 | Clinical outcomes of endoscopic submucosal dissection in elderly patients with early gastric cancer显示文摘 | Hajime Isomoto Ken Ohnita Naoyuki Yamaguchi Eiichiro Fukuda Kohki Ikeda Hitoshi Nishiyama Motohisa Akiyama Eisuke Ozawa Kazuhiko Nakao Shigeru Kohno Saburo Shikuwa | 2010 | European Journal of Gastroenterology & Hepatology2010，，3： | 1 |
| 18 | Usefulness of oral prednisolone in the treatment of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma显示文摘 | Naoyuki Yamaguchi Hajime Isomoto Toshiyuki Nakayama Tomayoshi Hayashi Hitoshi Nishiyama Ken Ohnita Fuminao Takeshima Saburo Shikuwa Shigeru Kohno Kazuhiko Nakao | 2011 | Gastrointestinal Endoscopy2011，，6： | 1 |
| 19 | Endoscopic submucosal dissection for early gastric cancer: A large-scale fea- sibility study显示文摘 | ISOMOTO H SHIKUWA S YAMAGUCHI N | 2009 | Gut2009，58，3： | 1 |
| 20 | Relationship between ECG findings and pulmonary artery pressure in patient s with acute massive pulmonary thromboembolism 显示文摘 | YOSHINAGA T IKEDA S SHIKUWA M | 2003 | Circ J2003，67，3： | 1 |
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