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NF-κB and ERK-signaling pathways contribute to the gene expression induced by cag PAI-positive-Helicobacter pylori infection

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World Journal of Gastroenterology 2005年第39期11卷 6134-6143页

作者： Wataru Shibata Yoshihiro Hirata Haruhiko Yoshida Motoyuki Otsuka Yujin Hoshida Keiji Ogura Shin Maeda Tomoya Ohmae Ayako Yanai Yuzo Mitsuno Naohiko Seki Takao Kawabe Masao omata Department of Gastroenterology Graduate School of Medicine University of TokyoJapan Department of Functional Genomics Graduate School of Medicine University of ChibaJapan

AIM： To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Helicobacter pylori （H pylon） as a model of Hpylori-infected gastric epithelium, and to further examine the contribution of cag-pathogenicity islands （cagPAI）-coding type IV secretion system and the two pathways, nuclear factor kappa B （NF-κB） and extracellular signal-regulated kinases （ERK） on wild-type Hpylori-induced gene expression. METHODS： Gene expression profiles induced by Hpylori were evaluated in AGS gastric epithelial cells using cDNA microarray, which were present in the 4600 independent clones picked up from the human gastric tissue. We also analyzed the contribution of NF-κB and ERK signaling on H pylori-induced gene expression by using inhibitors of specific signal pathways. The isogenic mutant with disrupted cagE （△cagE） was used to elucidate the role of cagPAI-encoding type IV secretion system in the gene expression profile. RESULTS： According to the expression profile, the genes were classified into four clusters. Among them, the clusters characterized by continuous upregulation were most conspicuous, and it contained many signal transducer activity-associated genes. The role of cagPAI on cultured cells was also investigated using isogenic mutant cagE, which carries non-functional cagPAI. Then the upregulation of more than 80% of the induced genes （476/566） was found to depend on cagPAI. Signal transducer pathway through NF-κB or ERK are the major pathways which are known to be activated by cagPAI-positive H pylori. The role of these pathways in the whole signal activation by cagPAI-positive H pyloriwas analyzed. The specific inhibitors against NF-κB or ERK pathway blocked the activation of gene expression in 65% （367/566） or 76% （429/566） of the genes whose activation appealed to depend on cagPAI. CONCLUSION： These results suggest that more than half of the genes induced by cayPAI-positive H pylori depend on NF-κB and ERK signaling activation, and thes

关键词： Helicobacter pylort, Cag-pathogenicity islands cDNA microarray, Cluster analysis Signal transduction

Caspase-8 promotes scramblase-mediated phosphatidylserine exposure and fusion of osteoclast precursors

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Bone Research 2024年第3期12卷 611-620页

作者： Brenda Krishnacoumar Martin Stenzel Hilal Garibagaoglu Yasunori omata Rachel L.Sworn Thea Hofmann Natacha Ipseiz Magdalena A.Czubala Ulrike Steffen Antonio Maccataio Cornelia Stoll Christina Böhm Martin Herrmann Stefan Uderhardt Robert H.Jenkins Philip R.Taylor Anika Grüneboom Mario M.Zaiss Georg Schett Gerhard Krönke Carina Scholtysek Department of Internal Medicine 3-Rheumatology and Immunology Friedrich-Alexander University Erlangen-Nürnberg(FAU)and Universitätsklinikum Erlangen91054 ErlangenGermany Deutsches Zentrum für Immuntherapie(DZI) Friedrich-Alexander University Erlangen-Nürnberg(FAU)and Universitätsklinikum Erlangen91054 ErlangenGermany Department of Biopsectroscopy Leibniz Institut für Analytische Wissenschaften-ISAS-e.V.Bunsen-Kirchhoff-Str.11Dortmund 44227Germany Medical Faculty University HospitalUniversity Duisburg-EssenEssen 45147Germany Systems Immunity Research Institute Heath ParkCardiff UniversityCardiff CF144XNUK Optical Imaging Competence Centre(FAU OICE) Exploratory Research UnitFriedrich-Alexander University Erlangen-Nürnberg(FAU)ErlangenGermany Division of Infection&Immunity Heath ParkCardiff UniversityCardiff CF144XNUK Deutsches Rheuma-Forschungszentrum Berlin BerlinGermany Department of Rheumatology and Clinical Immunology Charité-Universitätsmedizin BerlinBerlinGermany

Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing ***,the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely *** we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.

关键词： incomplete exact activation

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Long-term survival of a case with multiple liver metastases from duodenal gastrointestinal stromal tumor drastically reduced by the treatment with imatinib and hepatectomy

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World Journal of Gastroenterology 2006年第17期12卷 2793-2797页

作者： Chouhei Sakakura Akeo Hagiwara Koji Soga Koji Miyagawa Susumu Nakashima tetsuji Yoshikawa Shuichi Kin Yuenn Nakase Nobuki Yamaoka Yoshihiko Sagara Hisakazu Yamagishi Department of Digestive Surgery Kyoto Prefectural University of Medicine Kawaramachi-doriKamigyokuKyoto 602-0841Japan

Constitutive activation of KIT receptor tyrosine kinase is a critical factor in the pathogenesis of gastrointestinal stromal tumors （GISTs）. But there is little information on whether combination of imatinib mesylate （IM） and surgical treatment can prolong survival in the cases with unresectable multiple liver metastases. We report a case of postoperative recurrence of GIST treated by the tyrosine kinase inhibitor IN and surgical treatment. The initial complete response （CR） to treatment continued for 18 mo, but single liver metastasis showed regrowth in the left hepatic lobe during IN treatment. After partial resection of the recurrent tumor, postoperative course was uneventful and the patient has survived without recurrence for 24 too. Currently, imatinib is the first- line therapy for non-resectable GISTs, but a single agent therapy often leads to tumor resistance. Even if tolerance to imatinib occurs, a combination of imatinib and surgical treatment can prolong survival in some cases as reported here. However, further studies on a large number of cases of recurrent GIST are necessary to evaluate the effectiveness of IN treatment combined with surgery.

关键词： GIST Imatinib mesylate Liver metastases

Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C

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World Journal of Gastroenterology 2008年第14期14卷 2200-2207页

作者： Ying Yuan Ichiro Shimizu Mi Shen Eriko Aoyagi Hidetaka Takenaka Tatuzo Itagaki Mari Urata Katsutaka Sannomiya Nao Kohno Katsuyoshi Tamaki Masayuki Shono tetsuji Takayama Jiangsu Key Laboratory of Neuroregeneration Nantong University Nantong 226001 Jiangsu Province China Department of Digestive and Cardiovascular Medicine Institute of Health Biosciences Tokushima 7708503 Japan Support Center for Advanced Medical Sciences University of Tokushima Graduate School Tokushima 7708503 Japan

AIM:To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and macrophage chemotactic protein (MCP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls. METHODS:The PBMCs were separated from agematched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. Cytokines in the culture supernatant were measured by an enzyme-linked immunosorbent assay. RESULTS:The highest levels of the spontaneous production of TNF-α, IL-1β, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the premenopausal female healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone. CONCLUSION:These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.

关键词： Estradiol Progesterone Mononuclear cell Proinflammatory cytokine Chemokine

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography

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World Journal of Gastroenterology 2012年第12期18卷 1385-1390页

作者： Ryota Masuzaki Ryosuke Tateishi Haruhiko Yoshida Toru Arano Koji Uchino Kenichiro Enooku Eriko Goto Hayato Nakagawa Yoshinari Asaoka Yuji Kondo Tadashi Goto Hitoshi Ikeda Shuichiro Shiina Masao omata Kazuhiko Koike Department of Gastroenterology Graduate School of MedicineThe University of Tokyo Department of Clinical Laboratory The University of Tokyo Hospital Yamanashi Prefectural Hospital Organization

METHODS： Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled, Liver stiffness was obtained noninvasively by using Fibroscan （Echosens, Paris, France）, The date of blood transfusion was obtained by interview, Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement （LSM）. Patients were stratified into four groups based on the duration of infection （17-29 years; 30-39 years; 40-49 years; and 50-70 years）. The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS： A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis （225 with HCC and 291 without）. The patients were 244 men and 272 women, with a mean age of 67.8 ±9.5 years. The median liver stiffness was 14.3 kPa （25.8 in HCC group and 7.6 in non HCC group）. The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC （r = 0.132, P = 0.024） but not in patients with HCC （r = -0.103, P = 0.123）. Liver stiffness was significantly higher in patients with HCC than in those without in each duration group （P 〈 0.0001）. The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion （P 〈 0.0001）, duration of infection （P = 0.0015）, and heavy alcohol consumption （P = 0.043）CONCLUSION： Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardle

关键词： Transfusion-associated hepatitis C Transientelastography Hepatocellular carcinoma Liver stiffness Ultrasonography Liver fibrosis

Novel wide band gap alloyed semiconductors,x（LiGaO2）1/2-（1-x）ZnO,and fabrication of their thin films

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中国科学:技术科学 2010年第4期 444-444页

作者： T.omata K.TANAKA A.TAZUKE K.NOSE S.OTSUKA-YAO-MATSUO Division of Materials and Manufacturing Science Graduate School of EngineeringOsaka University

Oxide semiconductor alloys of x(LiGaO2) 1/2-(1-x) ZnO were fabricated by the solid state reaction betweenβ-LiGaO2 and ZnO and rf-magnetron *** the solid state reaction,the wurtzite-type single phases were obtained in the composition range of x≤*** formation range of the alloys was wider than that of the(Mg1-xZnx) O system,because the β-LiGaO 2possesses a wurtzite-derived structure and approximately the same lattice constants with *** electrical resistivity and energy band gap of the 0.38(LiGaO2) 1/2-0.62ZnO alloyed ceramic were 0.45-cm and 3.7 eV,respectively,at room *** the alloying by sputtering,the films consisting of the wurtzite-type single phase were obtained over the entire composition range of x(LiGaO2) 1/2-(1-x) *** energy band gap was controllable in the range from 3.3 to 5.6 *** the as-deposited film fabricated using the 0.4(LiGaO2) 1/2-0.6ZnO alloyed ceramic target,the energy band gap was 3.74 eV,and the electrical resistivity,carrier density and the Hall mobility at room temperature were 3.6-cm,3.4×1017 cm-3and 5.6 cm 2 V-1s-1,respectively.

关键词： zinc oxide transparent conductor ultraviolet light band gap engineering oxide electronics

Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes

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Journal of Clinical and Translational Hepatology 2015年第2期3卷 85-92页

作者： Yukiya Ono Masatoshi Ishigami Kazuhiko Hayashi Shinya Wakusawa Hisao Hayashi Kotaro Kumagai Natsuko Morotomi tetsuji Yamashita Miwa Kawanaka Minemori Watanabe Hiroaki Ozawa Mayumi Tai Hiroaki Miyajima Kentarou Yoshioka Yoshiki Hirooka Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of Medicine Nagoya Japan Department of Medical Laboratory Sciences Nagoya University Graduate School of Medicine Nagoya Japan Department of Medicine Aichi Gakuin University School of Pharmacy Nagoya Japan Digestive Disease and Lifestyle Related Disease Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan Department of Internal Medicine Moji Hospital Kitakyushu Japan Department of Medicine Yoshida Hospital Matsuyama Japan General Internal Medicine 2 Kawasaki Hospital Kawasaki Medical School Okayama Japan Department of Endocrinology and Diabetes Okazaki City Hospital Okazaki Japan Department of Pathology Okazaki City Hospital Okazaki Japan Department of Gastroenterology Fukushima Rohsai Hospital Fukushima Japan First Department of Medicine Hamamatsu University School of Medicine Hamamatsu Japan Department of Liver Biliary Tract and Pancreas Diseases Fujita Health University Toyoake Japan

In biology,redox reactions are essential and sometimes harmful,and therefore,iron metabolism is tightly regulated by *** the state of copper in iron overload syndromes remains unclear,we investigated whether copper metabolism is altered in these *** patients with iron overload syndromes participated in this *** clinical diagnoses were aceruloplasminemia (n=2),hemochromatosis (n=5),ferroportin disease (n=2),and receiving excess intravenous iron supplementation (n=2).Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray *** addition to a large amount of iron associated with oxygen and phosphorus,the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur,regardless of disease ***-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within *** stasis was unlikely in noncirrhotic *** enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in *** conclusion,we have demonstrated that copper accumulates in hemosiderins in iron overload conditions,perhaps due to alterations in copper metabolism.

关键词： Aceruloplasminemia Cuproprotein induction Ferroportin disease Hemochromatosis Hemosiderin Iron copper interaction Iron overload syndromes

2007年亚太肝病学会有关丙型肝炎诊断、处理和治疗的共识

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传染病信息 2007年第3期20卷 187-189页

作者： McCaughan GW omata M Amarapurkar 罗生强吉英杰

1HCV感染与实验室检测1．1抗HCV检测应由获准的第三代或第四代酶联免疫试验（EIA）进行（Ⅱ-2）。

关键词：亚太肝病学会肝炎诊断丙型治疗酶联免疫试验抗HCV检测实验室检测 HCV感染

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家鸭乙型肝炎病毒种肝脏疾病

吉林大学学报(医学版) 1984年第5期 487-490页

作者： Masao omata,叶维法,Anna PO'Connell,刘俊平日本千叶大学医学部内科生物化学动力研究所中国白求恩医科大学肝病研究室美国Fox Chase肿瘤中心肿瘤研究所

本文研究了61只家鸭血清中乙型肝炎病毒和肝病间的关系。61只家鸭中24只来源于中国启东县;20只来源于中国长春市;17只来源于日本千叶地区。通过电子显微镜检查、内源性DNA多聚酶活性测定和鸭乙型肝炎病毒DNA杂交试验,37只长春和千叶地... 详细信息

本文研究了61只家鸭血清中乙型肝炎病毒和肝病间的关系。61只家鸭中24只来源于中国启东县;20只来源于中国长春市;17只来源于日本千叶地区。通过电子显微镜检查、内源性DNA多聚酶活性测定和鸭乙型肝炎病毒DNA杂交试验,37只长春和千叶地区的家鸭乙型肝炎病毒全部阴性,亦未见肝脏病变,而启东24只家鸭中12只(50％)血清中存在病毒样颗粒,大多数启东鸭的肝脏可见到包括慢性肝炎和肝硬变的各种肝脏病理改变。其中鸭乙型肝

关键词： DHBV 内源性肝病家鸭 DNA 多聚酶聚合酶病毒颗粒