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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 | Deep-learning classifier with ultrawide-field fundus ophthalmoscopy for detecting branch retinal vein occlusion显示文摘AIM: To investigate and compare the efficacy of two machine-learning technologies with deep-learning(DL) and support vector machine(SVM) for the detection of branch retinal vein occlusion(BRVO) using ultrawide-field fundus images. METHODS: This study included 237 images from 236 patients with BRVO with a mean±standard deviation of age 66.3±10.6 y and 229 images from 176 non-BRVO healthy subjects with a mean age of 64.9±9.4 y. Training was conducted using a deep convolutional neural network using ultrawide-field fundus images to construct the DL model. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and area under the curve(AUC) were calculated to compare the diagnostic abilities of the DL and SVM models. RESULTS: For the DL model, the sensitivity, specificity, PPV, NPV and AUC for diagnosing BRVO was 94.0%(95%CI: 93.8%-98.8%), 97.0%(95%CI: 89.7%-96.4%), 96.5%(95%CI: 94.3%-98.7%), 93.2%(95%CI: 90.5%-96.0%) and 0.976(95%CI: 0.960-0.993), respectively. In contrast, for the SVM model, these values were 80.5%(95%CI: 77.8%-87.9%), 84.3%(95%CI: 75.8%-86.1%), 83.5%(95%CI: 78.4%-88.6%), 75.2%(95%CI: 72.1%-78.3%) and 0.857(95%CI: 0.811-0.903), respectively. The DL model outperformed the SVM model in all the aforementioned parameters(P<0.001). CONCLUSION: These results indicate that the combination of the DL model and ultrawide-field fundus ophthalmoscopy may distinguish between healthy and BRVO eyes with a high level of accuracy. The proposed combination may be used for automatically diagnosing BRVO in patients residing in remote areas lacking access to an ophthalmic medical center. | Daisuke Nagasato Hitoshi Tabuchi Hideharu Ohsugi Hiroki Masumoto Hiroki Enno Naofumi Ishitobi Tomoaki Sonobe Masahiro Kameoka Masanori Niki Yoshinori Mitamura | 2019 | International Journal of Ophthalmology(English edition)2019，12，1： | 16 |
| 3 | Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma显示文摘Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC. | Naofumi Mukaida Yasunari Nakamoto | 2018 | World Journal of Gastroenterology2018，24，17： | 13 |
| 4 | Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression显示文摘Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus(Pim)family proteins that exhibit serine/threonine kinase activity.Similar to the other Pim kinases(Pim-1 and Pim-2),Pim-3 is involved in many cellular processes,including cell proliferation,survival,and protein synthesis.Although Pim-3is expressed in normal vital organs,it is overexpressed particularly in tumor tissues of endoderm-derived organs,including the liver,pancreas,and colon.Silencing of Pim-3 expression can retard in vitro cell proliferation of hepatocellular,pancreatic,and colon carcinoma cell lines by promoting cell apoptosis.Pim-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack,and therefore,Pim-3 can exhibit its kinase activity once it is expressed.Pim-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors(e.g.,Ets-1)and post-translational modifiers(e.g.,translationally-controlled tumor protein),respectively.Pim-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse model.Furthermore,a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice,without inducing any major adverse effects.Thus,Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer. | Ying-Yi Li Naofumi Mukaida | 2014 | World Journal of Gastroenterology2014，20，28： | 6 |
| 5 | New 14-mm diameter Niti-S biliary uncovered metal stent for unresectable distal biliary malignant obstruction显示文摘AIM To investigate whether an uncovered self-expandable metal stent(UCSEMS) with a large diameter could prevent recurrent biliary obstruction(RBO).METHODS Thirty-eight patients with malignant biliary obstruction underwent treatment with an UCSEMS with a 14-mm diameter(Niti-S 14). Retrospectively, we evaluated technical and functional success rate, RBO rate, time to RBO, survival time, and adverse events in these patients.RESULTS Stent placement success and functional success were achieved in all patients. Two patients(5.3%) had RBO due to tumor ingrowth or overgrowth. The median time to RBO was 190(range, 164-215) d. The median survival time was 120(range, 18-502) d. The 6-mo non-RBO rate was 91%. Other adverse events other than RBO occurred as follows: Acute cholecystitis, post-ERCP pancreatitis, hemobilia, and fever without exacerbation of liver injury, and liver abscess in 4(10.3%), 3(7.9%), 2(5.3%), 1(2.6%), and 1(2.6%), respectively. Migration of the stents was not observed.CONCLUSION Niti-S 14 is considered to be a preferable metal stent because of a low rate of RBO with no migration. | Masataka Kikuyama Naofumi Shirane Shinya Kawaguchi Shuzou Terada Tsuyoshi Mukai Ken Sugimoto | 2018 | World Journal of Gastrointestinal Endoscopy2018，10，1： | 5 |
| 6 | CCR5 gene expression in fulminant hepatitis and DTH in mice显示文摘CCR5geneexpressioninfulminanthepatitisandDTHinmiceGUOBaoYu1,ZHANGSuYing2,NaofumiMukaida3,AkihisaHarada3,KoujiKuno3,WANGJian... | GUO Bao-Yu ZHANG Su-Ying Naofumi Mukaida Akihisa Harada Kouji Kuno WANG Jian-Bin SUN Shu-Han Kouji Matsushima | 1998 | World Journal of Gastroenterology1998，4，1： | 5 |
| 7 | Fibroblasts, an inconspicuous but essential player in colon cancer development and progression显示文摘Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs. | Naofumi Mukaida Soichiro Sasaki | 2016 | World Journal of Gastroenterology2016，22，23： | 4 |
| 8 | Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study显示文摘 | Yuichiro Eguchi Hideyuki Hyogo Masafumi Ono Toshihiko Mizuta Naofumi Ono Kazuma Fujimoto Kazuaki Chayama Toshiji Saibara | 2012 | Journal of Gastroenterology2012，，5： | 3 |
| 9 | Blocking TNF-[alpha] in mice reduces colorectal carcinogenesis associated with chronic colitis显示文摘 | Popivanova Boryana K Kitamura Kazuya Wu Yu Kondo Toshikazu Kagaya Takashi Kaneko Shiuchi Oshima Masanobu Fujii Chifumi Mukaida Naofumi | 2008 | Journal of Clinical Investigation2008，，2： | 2 |
| 10 | Optimum Treatment Strategy for Superficial Esophageal Cancer: Endoscopic Mucosal Resection versus Radical Esophagectomy显示文摘 | Hiromasa Fujita Susumu Sueyoshi Hideaki Yamana Koji Shinozaki Uhi Toh Yuichi Tanaka Takashi Mine Masahiro Kubota Kazuo Shirouzu Atsushi Toyonaga Hiroshi Harada Sigeki Ban Masahide Watanabe Yukihiko Toda Emi Tabuchi Naofumi Hayabuchi Hiroki Inutsuka | 2001 | World Journal of Surgery2001，，4： | 2 |
| 11 | Chemokines in tumor development and progression显示文摘 | Naofumi Mukaida Tomohisa Baba | 2011 | Experimental Cell Research2011，，2： | 2 |
| 12 | Endurance training regimen based upon arterial blood lactate: Effects on anaerobic threshold显示文摘 | Takayoshi Yoshida Yoshihiro Suda Naofumi Takeuchi | 1982 | European Journal of Applied Physiology and Occupational Physiology1982，，2： | 2 |
| 13 | The Frequency of Type 2 CD8+ T Cells Is Increased in Peripheral Blood from Patients with Psoriasis Vulgaris显示文摘 | Makoto Inaoki Shinichi Sato Fumiaki Shirasaki Naofumi Mukaida Kazuhiko Takehara | 2003 | Journal of Clinical Immunology2003，，4： | 1 |
| 14 | Combined immunotherapy by tumor-derived gp96 and dendritic cells against murine lung cancer显示文摘 | Shinagawa Naofumi Yamazaki Koichi TamuraYasuaki | 2006 | AACR Meeting Abstracts2006，2006，： | 1 |
| 15 | Effects of substrate feed rates on heterologous protein expression by Pichia pastoris in DO-stat fed-batch fermentation显示文摘 | Chun Yeon Lee Atsushi Nakano Naofumi Shiomi Eun Kyu Lee Shigeo Katoh | 2003 | Enzyme and Microbial Technology2003，，4： | 1 |
| 16 | Mutation screening of the human Clock gene in circadian rhythm sleep disorders显示文摘 | Toshio Iwase Naofumi Kajimura Makoto Uchiyama Takashi Ebisawa Kimio Yoshimura Yuichi Kamei Kayo Shibui Keiko Kim Yoshinao Kudo Masaaki Katoh Tsuyoshi Watanabe Toru Nakajima Yuji Ozeki Mariko Sugishita Toru Hori Masaaki Ikeda Ryoichi Toyoshima Yuichi Inoue | 2002 | Psychiatry Research2002，，2： | 1 |
| 17 | Comparison Between Endoscopic Macroscopic Classification and F-18 FDG PET Findings in Gastric Mucosa–Associated Lymphoid Tissue Lymphoma Patients显示文摘 | Yasumitsu Hirose Hayato Kaida Masatoshi Ishibashi Jun Uozumi Shunji Arikawa Seiji Kurata Naofumi Hayabuchi Keita Nakahara Koichi Ohshima | 2012 | Clinical Nuclear Medicine2012，，2： | 1 |
| 18 | Superelective clay for radium uptake 显示文摘 | Naofumi Kozai William J Paulus | 2001 | Nature2001，410，： | 1 |
| 19 | Respiratory variation of the extrahepatic bile duct: evaluation with deep inspiratory and expiratory MRCP显示文摘 | Katsuyoshi Ito Ayame Shimizu Masahiro Tanabe Naofumi Matsunaga | 2012 | Magnetic Resonance Imaging2012，，： | 1 |
| 20 | Stimulation of interleukin-8 production by acidic polysaccharides from the root of Panax ginseng显示文摘 | Yoshiko S Tadashi K Naofumi M | 1998 | Immunophamacology1998，38，3： | 1 |
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