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| 1 | Diagnosis of biliary strictures after liver transplantation:Which is the best tool?显示文摘AIM: To evaluate the diagnostic value of different indirect methods like biochemical parameters, ultrasound (US) analysis, CT-scan and MRI/MRCP in comparison with endoscopic retrograde cholangiography (ERC), for diagnosis of biliary complications after liver transplantation. METHODS: In 75 patients after liver transplantation, who received ERC due to suspected biliary complications, the result of the cholangiography was compared to the results of indirect imaging methods performed prior to ERC. The cholangiography showed no biliary stenosis (NoST) in 25 patients, AST in 27 and ITBL in 23 patients. RESULTS: Biliary congestion as a result of AST was detected with a sensitivity of 68.4% in US analysis (specificity 91%), of 71% in MRI (specificity 25%) and of 40% in CT (specificity 57.1%). In ITBL, biliary congestion was detected with a sensitivity of 58.8% in the US, 88.9%in MRI and of 83.3% in CT. However, as anastomotic or ischemic stenoses were the underlying cause of biliary congestion, the sensitivity of detection was very low. InMRI detected the dominant stenosis at a correct localization in 22% and CT in 10%, while US failed completely. The biochemical parameters, showed no significant difference in bilirubin (median 5.7; 4,1; 2.5 mg/dL), alkaline phosphatase (median 360; 339; 527 U/L) or gamma glutamyl transferase (median 277; 220; 239 U/L) levels between NoST, AST and ITBL.CONCLUSION: Our data confirm that indirect imaging methods to date cannot replace direct cholangiography for diagnosis of post transplant biliary stenoses. However MRI may have the potential to complement or precede imaging by cholangiography. Optimized MRCP-processing might further improve the diagnostic impact of this method. | Thomas Zoepf Evelyn J. Maldonado-Lopez Philip Hilgard Alexander Dech■ne Massimo Malago Christoph E. Broelsch Joerg Schlaak Guido Gerken | 2005 | World Journal of Gastroenterology2005，11，19： | 32 |
| 2 | Interferon-α response in chronic hepatitis B-transfected HepG2.2.15 cells is partially restored by lamivudine treatment显示文摘AIM: To characterize the IFN-response and its modul- ation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS: HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-a2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes (ISGs). In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS: Two genes (MxA, Cig5) with completely abolished and 4 genes (IFITM1, -2, -3, and 6-16) with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes (IFITM1, 6-16), the response to IFN-a could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Stat1 activation and ISGF3 formation after stimulation with IFN-a in HepG2.2.15 compared to HepG2 cells. CONCLUSION: These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expression by reducing HBV gene expression and replication. | Shi-He Guan Mengji Lu Petra Grünewald Michael Roggendorf Guido Gerken Joerg F Schlaak | 2007 | World Journal of Gastroenterology2007，13，2： | 22 |
| 3 | Toll样受体介导小鼠原代肝细胞产生的天然免疫应答及其对乙型肝炎病毒复制的抑制作用显示文摘目的探讨肝细胞的Toll样受体(TLR)信号途径及其诱导的抗病毒免疫应答。方法分离野生型C57BL/6小鼠的原代肝细胞,定量逆转录一聚合酶链反应法检测TLR的表达。分别用TLR1~9配体刺激肝细胞并收集细胞上清液。酶联免疫吸附法检测细胞上清液内的细胞因子。病毒保护实验检测细胞上清液的抗脑膜炎心肌炎病毒因子,并将细胞上清液与HBV-Met细胞共孵育,用Southernblot法检测其对HBV复制的抑制效应。结果原代肝细胞能表达TLR1~9。与其TLR表达谱相应的,肝细胞在TLR1~9配体的刺激下均可以产生炎性细胞因子(肿瘤坏死因子α和白细胞介素6),而仅在TLRl、TLR3、TLR7和TLR9配体刺激下可产生I型干扰素(干扰素α和干扰素β)。在病毒保护实验中,TLR3和TLR7的配体可以刺激肝细胞产生大量的抗脑膜炎心肌炎病毒效应分子;而TLRl、TLR3和TLR4配体直接刺激的肝细胞上清液,以及TLR3、TLR7和TLR9配体转染刺激的肝细胞上清液,都能有效抑制HBV的复制。结论小鼠原代肝细胞有独特的TLR信号途径,并能通过TLR配体的激活产生抑制HBV复制的效应。这一发现对于制定基于TLR的抗肝脏靶向性病毒的治疗措施有指导意义。 | 吴珺 陈明发 夏幼辰 郭艳 林永 孙潺 张春燕 陈妍 刘慎沛 郝友华 陆蒙吉 Jorg F. Schlaak 杨东亮 | 2011 | 中华肝脏病杂志2011，19，11： | 9 |
| 4 | The Role of the Innate Immune System of the Liver in the Control of HBV and HCV显示文摘Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are among the most frequent causes of chronic liver disease worldwide. As recent studies suggested that Toll like receptor (TLR)-based therapies may represent a promising approach in the treatment of HBV infection, we have studied the role of the local innate immune system of the liver as possible mediator of this effect. Murine non-parenchymal liver cells (NPC; Kupffer cells, KC; sinusoidal endothelial cells, LSEC) were isolated from C57/BL6 and stimulated by TLR 1-9 agonists. Supernatants were harvested and assayed for their antiviral activity against HBV in HBV-Met cells and HCV in the murine HCV replicon cell line MH1. Only supernatants from TLR 3 and -4 stimulated KC and TLR 3 stimulated LSEC were able to potently suppress HBV and HCV replication. By using neutralizing antibodies we could demonstrate that the TLR 3-but not the TLR 4 mediated effect is exclusively mediated through IFN-β. Our data indicate that TLR 3 and -4 mediated stimulation of NPC leads to production of IFN-β which can potently suppress HBV and HCV replication. This is of relevance for the local control of viral hepatitis infection by the innate immune system of the liver, the development of novel TLR-based therapeutic approaches and sheds new light on the viral crosstalk between HCV (TLR 3 stimulator) and HBV. | Ruth Brring Jrg F. Schlaak | 2008 | Virologica Sinica2008，23，2： | 4 |
| 5 | Preclinical development of TLR ligands as drugs for the treatment of chronic viral infections显示文摘 | Xiaoyong Zhang Anke Kraft Ruth Broering Joerg F Schlaak Ulf Dittmer Mengji Lu | 2012 | Expert Opinion on Drug Discovery2012，，7： | 3 |
| 6 | Role of Toll-like receptor 2 in the immune response against hepadnaviral infection显示文摘 | Xiaoyong Zhang Zhiyong Ma Hongyan Liu Jia Liu Zhongji Meng Ruth Broering Dongliang Yang Joerg F. Schlaak Michael Roggendorf Mengji Lu | 2012 | Journal of Hepatology2012，，3： | 2 |
| 7 | Hepatic volume changes after lobar selective internal radiation therapy (SIRT) of hepatocellular carcinoma显示文摘 | J.M. Theysohn J. Ertle S. Müller J.F. Schlaak F. Nensa S. Sipilae A. Bockisch T.C. Lauenstein | 2013 | Clinical Radiology2013，，： | 2 |
| 8 | Toll‐like receptor‐mediated immune responses are attenuated in the presence of high levels of hepatitis B virus surface antigen显示文摘 | M. Jiang R. Broering M. Trippler L. Poggenpohl M. Fiedler G. Gerken M. Lu J. F. Schlaak | 2014 | J Viral Hepat2014，，12： | 1 |
| 9 | Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines显示文摘 | Entzian P Lnnemann K Schlaak M | 1996 | Am J Respir Crit Med1996，153，： | 1 |
| 10 | IFN-c subtypes : Distinct biological activities in anti-viral therapy显示文摘 | Gibbert K Schlaak JF Yang D | 2013 | Br J Pharmaeol2013，168，5： | 1 |
| 11 | Age-related decrease in accessory cell function of human alveolar macrophages显示文摘 | Zissel G Schlaak M Muller-Quernheim J | 1999 | J Invest Med1999，47，： | 1 |
| 12 | Endoscopic Therapy of Posttransplant Biliary Stenoses After Right-Sided Adult Living Donor Liver Transplantation显示文摘 | Thomas Zoepf Evelyn J. Maldonado–lopez Philip Hilgard Joerg Schlaak Massimo Malago Christoph E. Broelsch Ulrich Treichel Guido Gerken | 2005 | Clinical Gastroenterology and Hepatology2005，，11： | 1 |
| 13 | HBV-specific immune defect in chronic hepatitis B (CHB) is correlated with dysregulation of pro-and anti-inflammatory cytokines显示文摘 | SCHLAAK JF TULLY G LOHY HF | 1999 | Clin Exp Immunol1999，115，3： | 1 |
| 14 | Obstructive sleep apnea and circadian rhythms of homrones and cyokines显示文摘 | Entzian P Linnemann K schlaak M | 1996 | Am J Respir Crit Care Med1996，153，3： | 1 |
| 15 | Success-ful treatment of a folliculotropic mycosis fungoides with bexarotene and PUVA 显示文摘 | Kronke A Schlaak M Arin M | 2012 | Eur J Dermatol2012，22，2： | 1 |
| 16 | Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration显示文摘AIM:To investigate the molecular events involved in liver regeneration following subtotal hepatectomy (SH) as previous studies have largely focused on partial hepatectomy (PH). METHODS: Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis (TUNEL assay) and transcription factors (NF-κB,Stat3; ELISA) or cytokines (HGF, TNF-a,IL-6,TGF-a,TGF-b; quantitative RT-PCR) involved in liver regeneration. RESULTS:Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-κB activation was detected 12 h after surgery (313.21±17.22 ng/mL), while there was no activation after SH (125.22 ± 44.36 ng/mL) compared to controls (111.43±32.68 ng/mL) at this time point. In SH, however, NF-κB activation was delayed until 24 h (475.56±144.29 ng/mL). Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH (i.e. TNF-a 24 h postoperatively: 2375±1220 in 70% and 88±31 in 90%; IL-6 12h postoperatively:2547±441 in 70% and 173±82 in 90%). TUNEL staining revealed elevated apoptosis rates in SH (0.44% at 24 h;0.63% at 7d) compared to PH (0.27% at 24h; 0.15% at 7d). CONCLUSION: The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-κB and suppression of proregenerative cytokines. | Jan-Peter Sowa Jan Best Tamas Benko Maximillian Bockhorn Yanli Gu Eva-Maria Niehues Agnieska Bucchi Eva-Maria Benedetto-Castro Guido Gerken Ursula Rauen Jorg Friedrich Schlaak | 2008 | World Journal of Gastroenterology2008，14，46： | 1 |
| 17 | Proliferative response of CD4+ T cells and Hepatitis B virus clearance in chronic hepatitis with or without hepatitis B eminus Hepatitis B virus mutants 显示文摘 | Lohr HF Weber W Schlaak J | 1995 | Hepatology1995，22，1： | 1 |
| 18 | IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-gamma promoter in primary CD4+T lymphocytes显示文摘 | Barbulescu K Becker C Schlaak JF | 1998 | J Immunol1998，160，： | 1 |
| 19 | Measurement in vivo of the survival rate in autologous adipocyte transplantation显示文摘 | REICK B SCHLAAK S | 2011 | Plast Reconstr Stag2011，111，7： | 1 |
| 20 | Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines显示文摘 | Entzian P Linnemann K Schlaak M | 1996 | Am J Respir Crit Care Med1996，153，： | 1 |
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