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| 1 | Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis显示文摘AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy. | Sebastian Mueller Gunda Millonig Lucie Sarovska Stefanie Friedrich Frank M Reimann Maria Pritsch Silke Eisele Felix Stickel Thomas Longerich Peter Schirmacher Helmut Karl Seitz | 2010 | World Journal of Gastroenterology2010，16，8： | 10 |
| 2 | CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes显示文摘AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling. | Toni Urbanik Bruno Christian Koehler Laura Wolpert Christin Elbner Anna-Lena Scherr Thomas Longerich Nicole Kautz Stefan Welte Nadine Hovelmeyer Dirk Jager Ari Waisman Henning Schulze-Bergkamen | 2014 | World Journal of Gastroenterology2014，20，45： | 3 |
| 3 | Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines: The Role of Neutrophils and Neutrophil-Derived Elastase显示文摘 | Thomas Gro?e-Steffen Thomas Giese Nathalia Giese Thomas Longerich Peter Schirmacher G. Maria H?nsch Matthias M. Gaida G. Opdenakker | 2012 | Clinical and Developmental Immunology2012，，： | 2 |
| 4 | Frequency and diagnostic patterns of lymphomas in liver biopsies with respect to the WHO classification显示文摘 | Christoph Loddenkemper Thomas Longerich Michael Hummel Karen Ernestus Ioannis Anagnostopoulos Hans-Peter Dienes Peter Schirmacher Harald Stein | 2007 | Virchows Archiv2007，，5： | 2 |
| 5 | Application of inductively coupled argon plasma mass spectrometry(ICAP-MS)for the determination of uranium and thorium in tourmalines显示文摘 | Kantipuly C J longerich H P Strong D F | 1988 | Chemical Geology1988，69，2： | 1 |
| 6 | Factors of transforming growt h factor beta signalling are co-regulated in human hepatocellular carcinoma显示文摘 | Longerich T Breuhahn K Odenthal M | 2004 | Virchows Arch2004，445，6： | 1 |
| 7 | The application of laser-ablationmicroprobe; inductively coupled plasma-mass spectrometry (LAM-ICP-MS) to in situtrace-element determinations in minerals显示文摘 | JACKSON S E LONGERICH H P DUNNING G R | 1992 | The Canadian Mineralogist1992，304，： | 1 |
| 8 | The appli- cation of laser-ablation microprobe~ inductively coupled plas- ma-mass spectrometry (LAM ICP MS) to in situ trace-element determinations in minerals显示文摘 | Jackson S E Longerich H P Dunning G R | 1992 | Can Mineral1992，30，4： | 1 |
| 9 | Dysregu- lation of growth factor signaling in human hepatocellular carcino- ma显示文摘 | BREUHAHN K LONGERICH T SCHIRMACHER P | 2006 | Oncogene2006，25，27： | 1 |
| 10 | Application of a frequency quintupled Nd: YAG source (lambda = 213 nm) for laser ablation inductively coupled plasma massspectrometric analysis of minerals显示文摘 | JEFFRIES T E JACKSON S E LONGERICH H P | 1998 | Journal of Analytical Atomic Spectrometry1998，13，9： | 1 |
| 11 | Laser ablation inductively coupled plasmamass spectrometric transient signal data aquisition and analyte concentrationcalculation显示文摘 | LONGERICH H P JACKSON S E GNTHER D | 1996 | Journal of Analytical Atomic Spectrometry1996，11，： | 1 |
| 12 | Salt-induced hypertension in WKY rats: prevention by alpha-lipoic acid supplementation 显示文摘 | Vasdev S Gill V Longerich L | 2003 | Mol Cell Biochem2003，254，12： | 1 |
| 13 | Antimelanoma activity of CTL generated from peripheral blood mononuclear cells 'after stimulation with autologous dendritic cells pulsed with melanoma gp100 peptide G209-2M is correlated to TCR avidity 显示文摘 | Yang S Linette GP Longerich S | 2002 | J Immunol2002，169，1： | 1 |
| 14 | Dysregulation of growth factor signaling in human hepatocellular carcinoma显示文摘 | BREUHAN K LONGERICH T SCHIRMACHER P | 2006 | Oncogcne2006，25，： | 1 |
| 15 | Etiology-dependent molecular mechanisms in human hepatocarcinogenesis显示文摘 | Schlaeger C Longerich T Schiller C | | 0，，： | 1 |
| 16 | Effects of operating conditions on the determination of the rare earth elements by inductively coupled plasma- mass spectrometry ( ICP-MS ) 显示文摘 | Longerich H P Fryer B J Strong D F Kantipuly C J | 1987 | Spectrochimica Acta Part B: Atomic Spectroscopy1987，42，12： | 1 |
| 17 | Determination of Zr and Hf in a flux-free fusion of whole rock samples using laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) with isotope dilution calibration 显示文摘 | Reid J E Horn i Longerich H R Forsythe L Jenner G A | 1999 | Geostandard Newslett1999，23，2： | 1 |
| 18 | Effects of operating conditions on the determination of the rare earth elements by inductively coupled plasma- mass spectrometry ( ICP-MS ) 显示文摘 | Longerich H P Fryer B J Strong D F Kantipuly C J | 1987 | Spectrechimica Acta: Part B1987，42，： | 1 |
| 19 | Factors of transforming growth factor beta signalling are coregulated in human hepatocellular carcinoma显示文摘 | Longerich T B reuhahn K O denthal M | 2004 | Virchows Arch2004，445，： | 1 |
| 20 | The E3 ubiquitin ligase RAD18 regulates ubiquitylation and chromatin loading of FANCD2 and FANCI 显示文摘 | Williams SA Longerich S Sung P | 2011 | Blood2011，117，19： | 1 |
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