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| 1 | Overlap syndromes among autoimmune liver diseases显示文摘The three major immune disorders of the liver are autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC) and primary sclerosing cholangitis(PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis(AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice. | Christian Rust Ulrich Beuers | 2008 | World Journal of Gastroenterology2008，14，21： | 41 |
| 2 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 3 | Overlap Syndromes显示文摘 | Ulrich Beuers Christian Rust | 2005 | Semin Liver Dis2005，，03： | 2 |
| 4 | A comparison of the optical pulse characteristics of intracloud and cloud-to-ground lightning as observed above clouds显示文摘 | GOODMAN S J CHRISTIAN H J RUST W D | 1988 | J App Met1988，27，： | 1 |
| 5 | A comparison of the optical pulse characteristics of intracloud and cloud-to-ground lightning as observed above clouds显示文摘 | Goodman S J Christian H J Rust W D | 1988 | J Appl Meteorol1988，27，12： | 1 |
| 6 | 1,25-(OH) 2 -vitamin D 3 prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4 ?/? model显示文摘 | Florian P. Reiter Simon Hohenester Jutta M. Nagel Ralf Wimmer Renate Artmann Lena Wottke Marie-Christine Makeschin Doris Mayr Christian Rust Michael Trauner Gerald U. Denk | 2015 | Biochemical and Biophysical Research Communicatio2015，，2： | 1 |
| 7 | Soluble intracellular adhesion molecule, M 30 and M 65 as serum markers of disease activity and prognosis in cholestatic liver diseases显示文摘 | Gerald Denk Ahmed‐Jawid Omary Florian Paul Reiter Simon Hohenester Ralf Wimmer Stefan Holdenrieder Christian Rust | 2014 | Hepatol Res2014，，13： | 1 |
| 8 | Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health显示文摘 | Karin Dilger Simon Hohenester Ursula Winkler-Budenhofer Barbara A.J. Bastiaansen Frank G. Schaap Christian Rust Ulrich Beuers | 2012 | Journal of Hepatology2012，，1： | 1 |
| 9 | Phosphatidylinositol-3-kinase p110γ contributes to bile salt-induced apoptosis in primary rat hepatocytes and human hepatoma cells显示文摘 | Simon Hohenester Anna Gates Ralf Wimmer Ulrich Beuers M. Sawkat Anwer Christian Rust Cynthia R.L. Webster | 2010 | Journal of Hepatology2010，，5： | 1 |
| 10 | A comparison of the optical pulse characteristics of intracloud and cloud to-ground lightning as ob- served aboveclouds显示文摘 | Goodman S J Christian H J Rust W D | 1988 | JApplMeteorol1988，27，13： | 1 |
| 11 | A comparison of the optical pulse characteristics of intracloud and cloud to ground lightning as observed above clouds 显示文摘 | Goodman S J Christian H J Rust W D | 1988 | J Appl Meteorol1988，27，： | 1 |
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