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| 1 | HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?显示文摘AIM To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC)and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication,METHODS HCV-RNA was monitored in serumand PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-α therapy using a nested RT/ PCRtechnique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma.RESULTS In the IFN-α responding patients,HCV-RNA disappeared first from total RNApreparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNAreappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNAconcentration in serum was performed before and after transition from detectable to nondetectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMCpreparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMCfrom healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration-dependent PCR-positivity for HCV-RNA in reisolated PBMC.CONCLUSION The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMCpreparations of chronically infected patients. | Volker Meier Sabine Mihm Perdita Wietzke-Braun Guliano Ramadori | 2001 | World Journal of Gastroenterology2001，7，2： | 29 |
| 2 | Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver显示文摘AIM:To explore lipocalin-2(LCN-2)expression and its possible role and mechanism(s)of production in rat models of diet-inducible fatty liver.METHODS:Fatty liver was triggered in male SpragueDawley rats fed either with liquid Lieber-DeCarli(LDC)or LDC+70%cal fructose(L-HFr)diet for 4 or 8 wk.Chow-nourished animals served as controls.Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting.Serum LCN-2,fasting leptin,and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay,Radioimmunoassay,and colorimetric assays,respectively.The localization of LCN-2 in the liver was detected by using immunofluorescence staining.Furthermore,HE stain was used to evaluate hepatic fatdegeneration and inflammation.RESULTS:Both LDC-fed and L-HFr-fed rat histologically featured fatty liver.In the liver,mRNA transcriptions of Mcp-1,a2-m,Il-8 and Glut5 were increased in the L-HFr group at both time points(P<0.001),while the transcription of Tlr4,Inos,and Tnf-a was significantly up-regulated at week 4.Interestingly,hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control(P<0.001).In contrast to HDL-cholesterol,systemic levels of LCN-2,fasting leptin and triglycerides were elevated in the L-HFr regimen(P<0.001).Moreover,protein expression of hepatic LCN-2,CD14,phosphoMAPK,caspase-9,cytochrome c and 4-hydroxynonenal was increased in the L-HFr group.Conversely,the hepatic expression of PGC-1a(a mitochondrial-biogenic protein)was reduced in the L-HFr category at week 8.The localization of LCN-2 in the liver was predominantly restricted to MPO+granulocytes.CONCLUSION:Fructose diet up-regulates hepatic LCN-2 expression,which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction.The LCN-2 may be involved in liver protection. | Salamah Mohammad Alwahsh Min Xu Hatice Ali Seyhan Shakil Ahmad Sabine Mihm Giuliano Ramadori Frank Christian Schultze | 2014 | World Journal of Gastroenterology2014，20，7： | 7 |
| 3 | Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection显示文摘AIM:To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C.METHODS: Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specif ic probes.RESULTS: Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6±12.5 vs 45.7±11.5, P=0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P=0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P=0.003) and with bile duct damage (P<0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism.CONCLUSION: The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C. | Eva Askar Giuliano Ramadori Sabine Mihm | 2009 | World Journal of Gastroenterology2009，15，31： | 2 |
| 4 | Spontaneous elimination of hepatitis C virus infection: A retrospective study on demographic, clinical, and serological correlates显示文摘AIM: To fi nd correlates to spontaneous clearance of hepatitis C virus (HCV) infection, this study compared individuals with self-limited and chronic infection with regard to clinical, demographic, and serological pa-rameters. METHODS: Sixty-seven anti-HCV positive and repeatedly HCV RNA negative individuals were considered to have resolved HCV infection spontaneously. To determine the viral genotype these patients had been infected with HCV serotyping was performed. For comparison reasons, 62 consecutive patients with chronic hepatitis C were enrolled. Cases and controls were compared stratifi ed for age and sex. RESULTS: Retrospective analysis showed (1) a lower humoral reactivity to HCV in patients with self-limited compared to chronic HCV-infection and (2) that younger age, history of iv drug use, and acute/post-acute hepatitis A or B co-infections, but not viral genotypes, are independent correlates for spontaneous HCV clearance. CONCLUSION: The stronger humoral reactivity to HCV in patients with persistent infections and in those with a history of iv drug use is supposed to be due to continuous or repeated contact(s) to the antigen. Metachronous hepatitis A or hepatitis B infections might favor HCV clearance. | Perdita Wietzke-Braun Larissa Bettina Mnhardt Albert Rosenberger Angela Uy Giuliano Ramadori Sabine Mihm | 2007 | World Journal of Gastroenterology2007，13，31： | 2 |
| 5 | Preferential virological response to interferon-α 2a in patients with chronic hepatitis C infected by virus genotype 3a and exhibiting a lowγ-GT/ALT ratio显示文摘 | Sabine Mihm PhD Heinz Hartmann MD Afshin Fayyazi MD Prof. Dr. Giuliano Ramadori MD | 1996 | Digestive Diseases and Sciences1996，，6： | 1 |
| 6 | Fructose-enriched diet induced overexpression of lipocalin-2 in rat fatty liver显示文摘 | Salamah Mohammad Alwahsh Mix Xu Giuliano Ramadori Sabine Mihm Frank Christian Schultze | 2013 | Journal of Clinical and Experimental Hepatology2013，，1： | 1 |
| 7 | Ferritin L is the Sole Serum Ferritin Constituent and a Positive Hepatic Acute-Phase Protein显示文摘 | Naila Naz Federico Moriconi Shakil Ahmad Ahmad Amanzada Sajjad Khan Sabine Mihm Guiliano Ramadori Ihtzaz Ahmed Malik | 2013 | Shock2013，，6： | 1 |
| 8 | Preferential virological response to interferon-α 2a in patients with chronic hepatitis C infected by virus genotype 3a and exhibiting a lowγ-GT/ALT ratio显示文摘 | Sabine Mihm PhD Heinz Hartmann MD Afshin Fayyazi MD Prof. Dr. Giuliano Ramadori MD | 1996 | Digestive Diseases and Sciences1996，，6： | 1 |
| 9 | Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients显示文摘AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus(HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time,higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C.METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT).Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed(33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response(SVR) rate of only 11.8% (n = 4) could be achieved.CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN. | Perdita Wietzke-Braun Volker Meier Katrin Neubauer-Saile Sabine Mihm Giuliano Ramadori | 2005 | World Journal of Gastroenterology2005，11，39： | 0 |
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