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| 1 | Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function显示文摘AIM: To test the hypothesis that hydrolysis of sphingomyelin to ceramide changes the composition of tight junctions (TJs) with increasing permeability of the intestinal epithelium. METHODS: Monolayers of Caco-2 cells were used as an in vitro model for the intestinal barrier. Permeability was determined by quantifi cation of transepithelialflux and transepithelial resistance. Sphingolipid-rich membrane microdomains were isolated by a discontinuous sucrose gradient and characterized by Western-blot. Lipid content of microdomains was analysed by tandem mass spectrometry. Ceramide was subcellularly localized by immunofluorescent staining.RESULTS: Exogenous sphingomyelinase increased transepithelial permeability and decreased transepithelial resistance at concentrations as low as 0.01 U/mL. Lipid analysis showed rapid accumulation of ceramide in the membrane fractions containing occludin and claudin-4, representing TJs. In these fractions we observed a concomitant decrease of sphingomyelin and cholesterol with increasing concentrations of ceramide. Immunofluorescent staining confirmed clustering of ceramide at the sites of cell-cell contacts. Neutralization of surface ceramide prevented the permeability-increase induced by platelet activating factor. CONCLUSION: Our findings indicate that changes in lipid composition of TJs impair epithelial barrier functions. Generation of ceramide by sphingomyelinases might contribute to disturbed barrier function seen in diseases such as inflammatory, infectious, toxic or radiogenic bowel disease. | Jürgen Bock Gerhard Liebisch Joachim Schweimer Gerd Schmitz Gerhard Rogler | 2007 | World Journal of Gastroenterology2007，13，39： | 11 |
| 2 | AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma显示文摘Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways. | KJ Schmitz H Lang J Wohlschlaeger GC Sotiropoulos H Reis KW Schmid HA Baba | 2007 | World Journal of Gastroenterology2007，13，48： | 8 |
| 3 | 厚壁奥氏体焊缝超声波检测之探究(英文)显示文摘由于奥氏体焊缝中材料性能的各向异性和微观组织结构的不同,奥氏体焊缝的超声波检测是非常困难的。超声波在奥氏体焊缝中会沿金属结晶方向发生偏转,并在焊缝边界上发生散射。过去十年来,人们开发了多种模拟各向异性材料中声波传播的仿真工具。本文则以常规超声波检测方法为基础,将声线跟踪法和弹性动力学有限积分技术(EFIT)相结合,应用于含晶间应力腐蚀裂纹的厚壁奥氏体焊缝中,其结果显示声线跟踪法和弹性动力学有限积分技术(EFIT)结合应用,有助于超声波检测参数的选取。 | Han T Y Khler B Schmitz V Zimmer A Langenberg K J | 2009 | 无损检测2009，31，11： | 3 |
| 4 | Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection显示文摘AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159)polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD)and chronic hepatitis C virus (HCV) infection.METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls.Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined.RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci,serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However,no association was found between CD14 genotypes and histological staging or grading.CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease. | C Meiler M Mühlbauer M Johann A Hartmann B Schnabl N Wodarz G Schmitz J Schlmerich C Hellerbrand | 2005 | World Journal of Gastroenterology2005，11，38： | 3 |
| 5 | Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer显示文摘AIM:To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer.METHODS:Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals.Allelic discrimination was performed by quantitative real-time polymerase chain reaction.Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression.RESULTS:Thirty-nine(32%) patients displayed a CC genotype,57(46.7%) a CT genotype and 26(21.3%) a TT genotype.The frequency of the C allele(fC) in the patient group was 0.55,which was not signif icantly different from that of healthy blood donors.The distribution was compatible with the Hardy-Weinberg equilibrium.Analysis of clinicopathological parameters did not show any signif icant correlation of the T393C genotype with gender(P=0.50),differentiation(P=0.29),pT-category(P=0.19),pN-category(P=0.30),pM-category(P=0.25),R-category(P=0.95),the classifications according to WHO(P=0.34),Laurén(P=0.16),Goseki(P=1.00) and Ming(P=0.74).Dichotomization between C+(CC+CT) and C-genotypes(TT),however,revealed signif icantly more advanced tumor stages(P=0.023) and lower survival rates(P=0.043) for C allele carriers.CONCLUSION:The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers. | Hakan Alakus Stefan P Mnig Ute Warnecke-Eberz Gül Alakus Günther Winde Uta Drebber Klaus J Schmitz Kurt W Schmid Kathrin Riemann Winfried Siffert Elfriede Bollschweiler Arnulf H Hlscher Ralf Metzger | 2009 | World Journal of Gastroenterology2009，15，48： | 3 |
| 6 | IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 7 | The interrelationship between surface froth characteristics and industrial flotation performance显示文摘 | MOOLMAN D W ALDRICH C SCHMITZ G P J | 1996 | Minerals Engineering1996，9，8： | 1 |
| 8 | How does insertion in global value chains affect upgrading in industrial clusters 显示文摘 | Humphrey J Schmitz H | 2002 | Regional Studies2002，36，9： | 1 |
| 9 | Activation of extracellular regulated kinases (ERK1/2) but not AKT predicts poor prognosis in colorectal carcinoma and is associated with k-ras mutations显示文摘 | Schmitz KJ Wohlschlaeger J Alakus H | 2007 | Virchows Arch2007，450，2： | 1 |
| 10 | 2001, Governance in Global Value Chains 显示文摘 | Humphrey J Schmitz H | 2001 | IDS Bulletin2001，32，3： | 1 |
| 11 | Augmened vasoconstrictor response to serotonin precede development of artherosclerosis in aorta of WHHL rabbit显示文摘 | WINES P A SCHMITZ J M PFISTER S L | 1989 | Atheriosclerosis1989，9，2： | 1 |
| 12 | p27 and cyclin D1 abnormalities in uterine papillary serous carcinoma 显示文摘 | Schmitz MJ Hendricks DT Farley J | 2000 | Gyneeol Oncol2000，77，5： | 1 |
| 13 | How does insertion in global value chains affect upgrading in industrial clusters?显示文摘 | Humphrey J Schmitz H | 2002 | Regional Studies2002，36，9： | 1 |
| 14 | Differential modulation of apopto- sis sensitivity in CD95 type I and type I显示文摘 | Seaffidi C Schmitz I Zha J | 1999 | J Biol Chem1999，274，22： | 1 |
| 15 | IL-33,an intedeukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 16 | Three-dimensional relativistic calculation of strong-field photoionization by the phase-space-averaging method显示文摘 | SCHMITZ H BOUCKE K KULL H J | 1998 | Physical Review A1998，57，1： | 1 |
| 17 | Design of robust adaptive frequency hopping for wireless medical telemetry systems显示文摘 | Park K J Park T R Schmitz C D | | 0，，02： | 1 |
| 18 | How does insertion in glob- al value chains affect upgrading in industrial clusters 显示文摘 | HUMPHREY J SCHMITZ H | 2002 | Regional Studies2002，，36： | 1 |
| 19 | IL-33, an interleukin-1-likecytokine that signals via the IL-1 receptor-related protein ST2 andinduces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 20 | Antimicrobial re- sistance among urinary tract infection (UTI) isolates in Eu- rope: Results from the SENTRY Antimicrobial Surveillance Program 1997 显示文摘 | FLUIT AC JONES ME SCHMITZ F J | 2000 | Antonie Van Leeuwenhoek2000，77，2： | 1 |
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