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| 1 | Immunological Effects of Silica and Asbestos显示文摘Silicosis patients(SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular,SIL sometimes complicates autoimmune diseases such as systemic scleroderma,rheumatoid arthritis(known as Caplan syndrome) ,and systemic lupus erythematoses. In addition,malignant complications such as lung cancer and malignant mesothelioma often occurr in patients exposed to asbestos,and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica,more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors,respectively. In addition,immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies,various cytokines,and molecule-targeting therapies. In particular,as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan,efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety. | Takemi Otsuki Megumi Maeda Shuko Murakami Hiroaki Hayashi Yoshie Miura Masayasu Kusaka Takashi Nakano Kazuya Fukuoka Takumi Kishimoto Fuminori Hyodoh Ayako Ueki Yasumitsu Nishimura | 2007 | Cellular & Molecular Immunology2007，4，4： | 9 |
| 2 | Dual therapy with zinc acetate and rifaximin prevents from ethanolinduced liver fibrosis by maintaining intestinal barrier integrity显示文摘BACKGROUND Hepatic overload of gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease(ALD)by inducing oxidative stress and activating Kupffer cells and hepatic stellate cells through toll-like receptor 4 signaling.Therefore,targeting the maintenance of intestinal barrier integrity has attracted attention for the treatment of ALD.Zinc acetate and rifaximin,which is a nonabsorbable antibiotic,had been clinically used for patients with cirrhosis,particularly those with hepatic encephalopathy,and had been known to improve intestinal barrier dysfunction.However,only few studies focused on their efficacies in preventing the ALD-related fibrosis development.AIM To investigate the effects of a combined zinc acetate with rifaximin on liver fibrosis in a mouse ALD model.METHODS To induce ALD-related liver fibrosis,female C57BL/6J mice were fed a 2.5%(v/v)ethanol-containing Lieber-DeCarli liquid diet and received intraperitoneal carbon tetrachloride(CCl4)injection twice weekly(1 mL/kg)for 8 wk.Zinc acetate(100 mg/L)and/or rifaximin(100 mg/L)were orally administered during experimental period.Hepatic steatosis,inflammation and fibrosis as well as intestinal barrier function were evaluated by histological and molecular analyses.Moreover,the direct effects of both agents on Caco-2 barrier function were assessed by in vitro assays.RESULTSIn the ethanol plus CCl4-treated mice,combination of zinc acetate and rifaximin attenuated oxidative lipid peroxidation with downregulation of Nox2 and Nox4.This combination significantly inhibited the Kupffer cells expansion and the proinflammatory response with blunted hepatic exposure of lipopolysaccharide and the toll-like receptor 4/nuclear factor kB pathway.Consequently,liver fibrosis and hepatic stellate cells activation were efficiently suppressed with downregulation of Mmp-2,-9,-13,and Timp1.Both agents improved the atrophic changes and permeability in the ileum,with restoration of tight junction proteins(TJPs)by decreasing the expressions of tumor necrosis factorαand myosin light chain kinase.In the in vitro assay,both agents directly reinforced ethanol or lipopolysaccharide-stimulated paracellular permeability and upregulated TJPs in Caco-2 cells.CONCLUSION Dual therapy with zinc acetate and rifaximin may serve as a strategy to prevent ALD-related fibrosis by maintaining intestinal barrier integrity. | Yuki Fujimoto Kosuke Kaji Norihisa Nishimura Masahide Enomoto Koji Murata Soichi Takeda Hiroaki Takaya Hideto Kawaratani Kei Moriya Tadashi Namisaki Takemi Akahane Hitoshi Yoshiji | 2021 | World Journal of Gastroenterology2021，27，48： | 4 |
| 3 | Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor for elderly patients with previously untreated acute myeloid leukemia显示文摘 | Hitoshi Suzushima Naoko Wada Hiroshi Yamasaki Kenichiro Eto Taizo Shimomura Michiko H. Kugimiya Kentaro Horikawa Shintaro Nishimura Hiroyuki Tsuda Hiroaki Mitsuya Norio Asou | 2009 | Leukemia Research2009，，5： | 1 |
| 4 | Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: A possible linkage to homocysteine显示文摘 | Tomohiro Osanai Naoto Fujiwara Satoko Sasaki Norifumi Metoki Genta Saitoh Hirofumi Tomita Takashi Nishimura Shuji Shibutani Hiroaki Yokoyama Yoshiyuki Konta Koji Magota Ken Okumura | 2010 | Annals of Medicine2010，，1： | 1 |
| 5 | Recurrence in jejunal pouch after proximal gastrectomy for early upper gastric cancer显示文摘 | Masaki Nishimura Ichiro Honda Satoshi Watanabe Matsuo Nagata Hiroaki Souda Masaru Miyazaki | 2003 | Gastric Cancer2003，，3： | 1 |
| 6 | Effects of Edaravone on Muscle Atrophy and Locomotor Function in Patients with Ischemic Stroke显示文摘 | Hiroaki Naritomi Hiroshi Moriwaki Norifumi Metoki Hiroyuki Nishimura Yasuto Higashi Yasumasa Yamamoto Hiroyuki Yuasa Hiroshi Oe Kortaro Tanaka Kozue Saito Yasuo Terayama Tadafumi Oda Norio Tanahashi Hisao Kondo | 2010 | Drugs in R & D2010，，3： | 1 |
| 7 | 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 |
| 8 | Reprogramming of Mouse and Human Cells to Pluripotency Using Mature MicroRNAs显示文摘 | Norikatsu Miyoshi Hideshi Ishii Hiroaki Nagano Naotsugu Haraguchi Dyah Laksmi Dewi Yoshihiro Kano Shinpei Nishikawa Masahiro Tanemura Koshi Mimori Fumiaki Tanaka Toshiyuki Saito Junichi Nishimura Ichiro Takemasa Tsunekazu Mizushima Masataka Ikeda Hirofumi | 2011 | Cell Stem Cell2011，，6： | 1 |
| 9 | Perfluoroalkyl - philic character of poly(2 - hydroxyethyl vinyl ether) - block - poly micelles in water: selective solubilization of perfluorinated compounds 显示文摘 | KOZO MATSUMOTO HIROAKI MAZAKI RYUJI NISHIMURA | 2000 | Macromolecules2000，33，22： | 1 |
| 10 | Dietary cadmium intake and breast cancer risk in Japanese women: A case–control study显示文摘 | Hiroaki Itoh Motoki Iwasaki Norie Sawada Ribeka Takachi Yoshio Kasuga Shiro Yokoyama Hiroshi Onuma Hideki Nishimura Ritsu Kusama Kazuhito Yokoyama Shoichiro Tsugane | 2013 | International Journal of Hygiene and Environmental Health2013，，： | 1 |
| 11 | Reprogramming of Mouse and Human Cells to Pluripotency Using Mature MicroRNAs显示文摘 | Norikatsu Miyoshi Hideshi Ishii Hiroaki Nagano Naotsugu Haraguchi Dyah Laksmi Dewi Yoshihiro Kano Shinpei Nishikawa Masahiro Tanemura Koshi Mimori Fumiaki Tanaka Toshiyuki Saito Junichi Nishimura Ichiro Takemasa Tsunekazu Mizushima Masataka Ikeda Hirofumi | 2011 | Cell Stem Cell2011，，6： | 1 |
| 12 | Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells显示文摘 | Yoshie Miura Yasumitsu Nishimura Hironobu Katsuyama Megumi Maeda Hiroaki Hayashi Maolong Dong Fuminori Hyodoh Masafumi Tomita Yoshinobu Matsuo Ayuko Uesaka Kozo Kuribayashi Takashi Nakano Takumi Kishimoto Takemi Otsuki | 2006 | Apoptosis2006，，10： | 1 |
| 13 | Recurrence in jejunal pouch after proximal gastrectomy for early upper gastric cancer显示文摘 | Masaki Nishimura Ichiro Honda Satoshi Watanabe Matsuo Nagata Hiroaki Souda Masaru Miyazaki | 2003 | Gastric Cancer2003，，3： | 1 |
| 14 | Association between ADAMTS13 activity-VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma显示文摘BACKGROUND Prediction of HAIC treatment response is important for improving the prognosis in patients with hepatocellular carcinoma(HCC).The progression of HCC is related to hypercoagulability and angiogenesis.It is known that ADAMTS13 and von Willebrand factor(VWF)are related to hypercoagulability.In addition,previous study reported that the association between ADAMTS13 and VWF,and angiogenesis via vascular endothelial growth factor(VEGF).Recently,ADAMTS13 and VWF have been associated with the prognosis in patients with various kinds of cancer undergoing chemotherapy.AIM To investigate whether ADAMTS13 and VWF become useful biomarkers of treatment response in HCC patients before the initiation of HAIC treatment.METHODS Seventy-two patients were enrolled in this study.ADAMTS13 activity(ADAMTS13:AC),VWF antigen(VWF:Ag)and VEGF levels were determined via enzyme-linked immunosorbent assay.Univariable and multivariable analyses were performed to determine the predictive factors of treatment response in patients with HCC undergoing HAIC treatment.RESULTS ADAMTS13:AC levels in HCC patients with stable disease(SD)+partial response(PR)of HAIC treatment were significantly higher than those with progressive disease(PD)(P<0.05).In contrast,VWF:Ag/ADAMTS13:AC ratio and VEGF levels in HCC patients with SD+PR were significantly lower than those with PD(both P<0.05).Patients with high VWF:Ag/ADAMTS13:AC ratio(>2.7)had higher VEGF levels than those with low ratio(≤2.7).Multivariable analysis revealed that VWF:Ag/ADAMTS13:AC ratio was a predictive factor of HAIC treatment response.CONCLUSION VWF:Ag/ADAMTS13:AC ratio may become a useful biomarker of treatment response in HCC patients before the initiation of HAIC treatment. | Hiroaki Takaya Tadashi Namisaki Kei Moriya Naotaka Shimozato Kosuke Kaji Hiroyuki Ogawa Koji Ishida Yuki Tsuji Daisuke Kaya Hirotestu Takagi Yukihisa Fujinaga Norihisa Nishimura Yasuhiko Sawada Hideto Kawaratani Takemi Akahane Masanori Matsumoto Hitoshi Yoshiji | 2020 | World Journal of Gastroenterology2020，26，45： | 0 |
| 15 | Plasma copeptin concentration is a predictor of tolvaptan efficacy in patients with hepatic ascites显示文摘Aims:No solid evidence-based opinion was raised regarding predictors of the degree of ascites reduction with tolvaptan.This retrospective cohort study aimed to examine whether serum copeptin concentration is a useful predictor of this.Methods:The study population consisted of 80 patients with liver cirrhosis treated with tolvaptan for hepatic ascites effusions at Nara Medical University Hospital from May 2014 to December 2018.Forty-three patients who lost>1.5 kg of body weight in the first week after starting tolvaptan were classified as good responders and the remaining 37 as poor responders.Various laboratory parameters were measured immediately before the start of tolvaptan therapy to examine factors associated with predicting its efficacy.Results:In the univariate analysis,no significant differences with respect to age(67.6 vs.69.8 years,p>0.05),sex,body mass index(24.8 vs.23.7 kg/m^(2),p>0.05),Child-Pugh score(9.4 vs.9.7,p>0.05),and Model for End-stage Liver Disease score(11 vs.12,p>0.05)were found between the two groups.Conversely,aspartate transferase and alanine transaminase(ALT)levels were significantly lower in the good response group(52.9±56.3 vs.68.8±50.7 U/L,p<0.05;26.2±30.6 vs.40.5±33.5 U/L,p<0.01),whereas serum copeptin and serum sodium concentrations were significantly higher(57.1±15.0 vs.45.8±16.0 pg/mL,p<0.01;136.3±3.4 vs.133.8±5.8 mEq/L,p<0.05).In the multivariate analysis,serum copeptin concentration and ALT were statistically significant factors(p<0.01,p<0.05).Regression analysis of the association between the tolvaptan efficacy for refractory ascites and pretreatment serum copeptin concentration showed that a copeptin concentration cutoff of 45.9 pg/mL could predict treatment efficacy with a sensitivity,specificity,and area under the curve of 76.7%,59.5%,and 0.71%,respectively.Conclusion:Serum copeptin concentration may be a predictor of tolvaptan efficacy for refractory ascites effusion in Japanese patients with liver cirrhosis. | Fumimasa Tomooka Kei Moriya Takahiro Kubo Akihiko Shibamoto Jyunya Suzuki Satoshi Iwai Soichi Takeda Yuki Fujimoto Masahide Enomoto Koji Murata Yuki Tsuji Yukihisa Fujinaga Koh Kitagawa Norihisa Nishimura Hiroaki Takaya Kosuke Kaji Hideto Kawaratani Tadashi Namisaki Takemi Akahane Akira Mitoro Hitoshi Yoshiji | 2023 | Portal Hypertension & Cirrhosis2023，2，3： | 0 |
| 16 | Feasibility study of laser-driven neutron sources for pharmaceutical applications显示文摘We predict the production yield of a medical radioisotope^(67)Cu using^(67)Zn(n,p)^(67)Cu and ^(68)Zn(n,pn)^(67)Cu reactions with fast neutrons provided from laser-driven neutron sources.The neutrons were generated by the p+9Be and d+9Be reactions with high-energy ions accelerated by laser–plasma interaction.We evaluated the yield to be(3.3±0.5)×10^(5) atoms for^(67)Cu,corresponding to a radioactivity of 1.0±0.2 Bq,for a Zn foil sample with a single laser shot.Using a simulation with this result,we estimated^(67)Cu production with a high-frequency laser.The result suggests that it is possible to generate^(67)Cu with a radioactivity of 270 MBq using a future laser system with a frequency of 10 Hz and 10,000-s radiation in a hospital. | Takato Mori Akifumi Yogo Yasunobu Arikawa Takehito Hayakawa Seyed R.Mirfayzi Zechen Lan Tianyun Wei Yuki Abe Mitsuo Nakai Kunioki Mima Hiroaki Nishimura Shinsuke Fujioka Ryosuke Kodama | 2023 | High Power Laser Science and Engineering2023，11，2： | 0 |
| 17 | Radiation Temperature Measurement of an Imploded X-Ray Source with a Filtered-Multi-Channel Pinhole Camera显示文摘压破球形的 CH 塑料壳驾驶的强烈 X 光来源的 Plankian 放射温度与一个 filtered-multi-channel 针孔照相机被测量。与使用的 GEKKO-XII 激光设备的所有 12 根激光横梁,当在核心的温度象 818eV 一样高时,平均放射温度被测量在 465eV 附近。这价值被使用的另外的仪器证实。[从作者抽象] | 王首钧 董全力 张翼 李玉同 张蕾 Shinsuke Fujioka Norimasa Yamamoto Hiroaki Nishimura 张杰 | 2010 | Chinese Physics Letters2010，27，12： | 0 |
| 18 | Preliminary study of photodynamic diagnosis using 5-aminolevulinic acid in gastric and colorectal tumors显示文摘AIM:To investigate the utility of photodynamic diagnosis(PDD) using 5-aminolevulinic acid(5-ALA) to detect gastric/colorectal tumors.METHODS:This prospective single-center study investigated inter-subject variability in patients with early-stage gastric/colorectal tumor indicated for endoscopic resection.Subjects were patients with gastric or colorectal tumors who had undergone endoscopic resection between November 2012 and November 2013.Selection criteria included age 20-80 years,either sex,and provision of informed consent.Patients were orally administered 20 mg/kg of 5-ALA enteric-coated capsules(SBI ALApromo Co.,Tokyo,Japan).Administration of5-ALA was followed by endoscopic resection of gastric or colorectal tumors,and the resected specimens were examined using a video autofluorescence processor and a fluorescence endoscope(SAFE-3000 and EB-1970 AK,respectively;Pentax,Tokyo,Japan).The primary endpoint was the presence of fluorescence in tumors.Endoscopic,macroscopic,and histopathologic findings of tumors were assessed.We also evaluated adverse events of the present procedure as a secondary endpoint and examined each patient for the presence of known adverse effects of 5-ALA,namely,hematocytopenia,liver dysfunction,hypotension,nausea,and photosensitivity.RESULTS:We enrolled 10 patients(7 men,3 women)(n = 13 lesions:10 gastric/3 colorectal tumors).Fluorescence was detected in 7/13(53.8%) lesions.No significant differences in sex(male:55.6%vs female:50.5%,P = 1.00),age(67.1 ± 1.9 years vs 65.0 ±2.0 years,P= 0.45),tumor color(reddish:60.0%vs discolored:33.3%,P = 0.56),tumor diameter(15.0± 2.1 mm vs 14.2 ± 2.3 mm,P= 0.80),macroscopic type(protruded:70.0%vs depressed 0%,P = 0.07),histologic type(differentiated type:58.3%vs 0%,P = 0.46),invasion depth(mucosal layer:55.6%vs submucosal layer:33.3%,P = 1.00),lymphatic invasion(present:33.3%vs absent:50.0%,P= 1.00),venous invasion(present:0%vs absent:54.5%,P= 1.00) or procedure time of endoscopic resection(36.3 ± 8.3 min vs 36.7 ± 9.0 min,P = 0.98) were observed between the patients with and without fluorescence.Fluorescence detection rate tended to be high for elevated lesions.Liver dysfunction developed in 4/10(40.0%) patients.The extent of the liver dysfunction was a slight increase in transaminases and total bilirubin levels,which spontaneously improved in the patients.None of the patients developed photosensitivity.CONCLUSION:Results of this preliminary study suggest the utility of PDD using 5-ALA for screening of gastric and colorectal cancers. | Munetaka Nakamura Jun Nishikawa Kouichi Hamabe Atsushi Goto Junichi Nishimura Hiroaki Shibata Misato Nagao Sho Sasaki Shinichi Hashimoto Takeshi Okamoto Isao Sakaida | 2015 | World Journal of Gastroenterology2015，21，21： | 0 |
| 19 | Spectroscopic Studies on Impurity Transport of Core and Edge Plasmas in LHD显示文摘Spectroscopic diagnostics have been extensively developed for studies of impurityand neutral particle transports at core and edge plasmas in LHD.Diagnostics of core plasmas aresimilar to a tokamak case,i.e.,Z_(eff)from visible bremsstrahlung,K-x-ray measurements from x-ray spectroscopy using Si(Li)detectors and a compact crystal spectrometer,and high-Z impuritydiagnostics from VUV spectroscopy using a flat-field EUV spectrometer.A combination of impu-rity pellet injection and visible bremsstrahlung is an active tool for determination of the diffusioncoefficient D and convective velocity V.Using this tool the spatial structures of D and V areobtained and discussed with a neoclassical effect.On the other hand,the spectroscopic methodfor edge diagnostics is considerably different from the tokamak case because of the existence of athick ergodic layer in addition to the x-points necessarily included into the diagnostic chord view.In order to break this negative situation,Zeeman and polarization spectroscopy are adopted toLHD edge plasmas.As a result,2-dimensional emission contours of HeI and H_α are successfullyobtained.Laser absorption spectroscopy is tried to measure hydrogen neutrals directly.Radialprofiles of edge impurities are also measured with a mirror-assembled 3 m VUV spectrometer.Recent results of and progress in LHD spectroscopy are briefly reviewed. | Shigeru MORITA Motoshi GOTO SadatsuguMUTO Ryuji KATAI Hisamichi YAMAZAKI Hideaki NOZATO AtsuslliI WAMAE Makoto ATAKE Takashi FUJIMOTO Atsushi SAKAUE Hiroaki NISHIMURA Ikuya SAKURAI Chiho MATSUMOTO Akihiro FURUZAWA Yuzuru TAWARA Mitsutoshi ARAMAKI Yuji OKUMURA Koichi SASAKI 龚先祖 李建刚 万宝年 崔正英 | 2006 | Plasma Science and Technology2006，8，1： | 0 |
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