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Biomedical subjects

Andreas Erhardt

Publications and source records attributed to Andreas Erhardt.

At least 19 recordsLinked to original sources
PubMed2006

New multi protein patterns differentiate liver fibrosis stages and hepatocellular carcinoma in chronic hepatitis C serum samples.

AIM: To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for detection and differentiation of liver fibrosis (F1-F2), liver cirrhosis (F4) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). METHODS: Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System (PBS-IIc; Ciphergen Biosystems) after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks. RESULTS: A 4 peptide/protein multimarker panel (7486, 12,843, 44,293 and 53,598 Da) correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples (AUROC 0.943). Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern (2873, 6646, 7775, 10,525 and 67,867 Da) with a specificity of 100% and a sensitivity of 85% in training samples (AUROC 0.976) and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APRI score and alfa-fetopotein (AFP) improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION: SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Most probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.

Adult↗
PubMed2006

[Update hepatitis D].

The relevance of chronic hepatitis delta results from its high morbidity. Prevalence of hepatitis D decreases in classic endemic areas of the Mediterranean Basin, but increases in Eastern European countries. Hepatitis D is mainly a disease of immigrants in Germany. Hepatitis D virus (HDV) is an incomplete virus, which needs the hepatitis B surface protein (HBsAg) but not hepatitis B virus (HBV) replication for its propagation. In case of HBsAg detection a screening for HDV antibodies should be performed. Simultaneous HDV/HBV infection leading to spontaneous virus clearance in the majority of cases has to be differentiated from HDV superinfection with a high rate of chronification. Chronic hepatitis D is difficult to treat. Treatment regimens for hepatitis D are interferon-based so far. Pegylated interferons, a prolongation of treatment beyond 12 months, combination therapies with ribavirin and prenylation inhibitors are possibly new therapeutic options in chronic hepatitis C.

Antiviral Agents↗
PubMed2006

HFE mutations in idiopathic dilated cardiomyopathy.

BACKGROUND AND PURPOSE: Dilated cardiomyopathy is a typical complication of hereditary hemochromatosis (HH). The present study investigated, whether mutations of the hemochromatosis (HFE) gene might be etiologic and disease-modifying factors in idiopathic dilated cardiomyopathy PATIENTS AND METHODS: Clinical and biochemical assessment and HFE gene analysis were perfomed in 46 patients with IDCM and 350 healthy controls. Cardiomyopathy was angiographically defined according to the criteria of the Collaborative Research Group of the European Human and Capital Mobility Project of Familial Dilated Cardiomyopathy. RESULTS: A higher prevalence of C282Y homozygosity was found among patients with IDCM compared to healthy subjects (4.3% vs. 0.6%; p < 0.02). A total of 6.5% of the patients with IDCM were either C282Y homozygotes or C282Y/H63D compound heterozygotes. The C282Y allele frequency was somewhat higher among patients with IDCM (8.7%) compared to healthy controls (5.4%; p < 0.2), whereas the H63D allele frequency was not increased. No significant differences of serum iron, ferritin or transferrin saturation, cardiac iron loading, NYHA classification, Lown's classification, the history of cardiopulmonary resuscitation, LVEDD (left ventricular end-diastolic diameter), EF (ejection fraction), LADD (left atrial end-diastolic diameter) and CI (cardiac index) were seen between HFE carriers and noncarriers. CONCLUSION: The present study indicates that it is worth screening patients with IDCM for iron parameters given the increased prevalence of disease-predisposing HFE constellations. It remains unclear, to what extent iron or immune-mediated processes contribute to the pathomechanism of IDCM.

Adult↗
PubMed2006

Pollination crisis in the butterfly-pollinated wild carnation Dianthus carthusianorum?

Knowledge of pollination services provided by flower visitors is a prerequisite for understanding (co)evolutionary processes between plants and their pollinators, for evaluating the degree of specialization in the pollination system, and for assessing threats from a potential pollination crisis. This study examined pollination efficiency and visitation frequency of pollinators--key traits of pollinator-mediated fecundity--in a natural population of the wild carnation Dianthus carthusianorum. The five lepidopteran pollinator species observed differed in pollination efficiency and visitation frequency. Pollinator importance, the product of pollination efficiency and visitation frequency, was determined by the pollinator's visitation frequency. Pollination of D. carthusianorum depended essentially on only two of the five recorded pollinator species. Seed set was pollen-limited and followed a saturating dose-response function with a threshold of c. 50 deposited pollen grains for fruit development. Our results confirm that D. carthusianorum is specialized to lepidopteran pollinators, but is not particularly adapted to the two main pollinator species identified. The local persistence of D. carthusianorum is likely to be at risk as its reproduction depends essentially on only two of the locally abundant, but generally vulnerable, butterfly species.

Adaptation, Physiological↗
PubMed2006

Treatment of chronic hepatitis delta with pegylated interferon-alpha2b.

BACKGROUND/AIMS: Chronic hepatitis D is difficult to treat. The present pilot study investigated the efficacy and tolerability of pegylated (PEG)-interferon (IFN)-alpha2b in chronic hepatitis D. PATIENTS AND METHODS: Twelve patients with chronic hepatitis D were prospectively treated with 1.5 microg/kg PEG-IFN-alpha2b for 48 weeks and followed for 24 weeks. Sustained response (SR) was defined as undetectable hepatitis delta virus (HDV) RNA by reverse transcriptase-polymerase chain reaction and normalization of alanine aminotransferase (ALT) at 6 months after treatment. Investigations included HDV RNA kinetics, determination of hepatitis B virus (HBV) and HDV genotypes and histological evaluation. RESULTS: An SR was achieved in two out of 12 of patients (17%). The negative predictive value of a less than 3 log HDV RNA decrease at month 6 was 100%. The positive predictive value of a more than 3 log HDV RNA decrease at month 6 was 67%. A marked ALT reduction at the end of treatment was observed in responders and nonresponders. Ishak histological score was comparable at baseline and significantly improved in responders compared with nonresponders at the end of follow-up (13.5 vs. 8.0; P<0.02). CONCLUSION: The present study indicates that PEG-IFN-alpha2b is a promising treatment option in chronic hepatitis D. Nonresponders could be identified by a less than 3 log decrease of HDV RNA at 6 months of treatment.

Adult↗
PubMed2005

Elevated carbon dioxide increases nectar production in Epilobium angustifolium L.

Effects of elevated CO2 and nutrient availability on nectar production and onset of flowering in five different seed families (genotypes) of Epilobium angustifolium were investigated in a greenhouse experiment. Elevated CO2 significantly increased nectar production per day (+51%, p < 0.01), total sugar per flower (+41%, p < 0.05), amino acid concentration (+65%, p < 0.05) and total amino acids per flower (+192%, p < 0.001). All other parameters tested, i.e., nectar sugar concentration, proportion of glucose/fructose and proportion of sucrose/(glucose + fructose), were not significantly affected by elevated CO2 and/or fertilization. However, elevated CO2 caused a marginally significant trend for earlier flowering in highly fertilized plants. No significant family x CO2 interaction was found in any of the tested parameters, but the response in nectar production varied considerably among seed families (+10 to +104%) and was significantly positive in two of the five seed families investigated. Our results are not consistent with earlier studies on effects of elevated CO2 on nectar production and flowering phenology in other plant species. It seems, on the other hand, that CO2 effects on nectar production are specific to species and genotype. Hence, no general conclusions about effects of elevated CO2 on these floral traits can be drawn at present, but it must be cautioned that elevated CO2 might not only increase floral rewards as in E. angustifolium, but might also lead to shifts or even disruptions in fine-tuned plant-pollinator interactions.

Animals↗
PubMed2005

SEN virus has an adverse effect on the survival of HIV-positive patients.

BACKGROUND: Patients infected with HIV are often coinfected with other viruses. OBJECTIVE: To investigate the effect of SEN virus (SENV) strains D and H on mortality in HIV-positive patients. METHODS: A total of 217 HIV-positive patients were analysed retrospectively after first presentation and blood sampling (January 1997 to July 1997) and the effect of coinfection with SENV-D and SENV-H on survival was examined. Analysis periods were the time from blood sampling to the end of follow-up, and the time from diagnosis of HIV infection to the end of study follow-up. SENV-H DNA was measured quantitatively. Prevalences of SENV-D and SENV-H were compared with those in 112 healthy blood donors. RESULTS: SENV prevalence was significantly higher in HIV-positive patients than in controls (56/217 and 12/112, respectively; P < 0.001). SENV positivity had no influence on survival, but a significant negative influence of SENV-H on survival was observed when SENV-H DNA was > 530 copies/ml, which was the mean SENV-H DNA level found in HIV-negative controls. This adverse effect was found for both studied time periods in a Kaplan-Meier analyses. A multivariate Cox regression analysis, including CD4 cell count, Centers for Disease Control and Prevention stage, age, sex, HIV RNA, highly active antiretroviral therapy and hepatitis C virus status, revealed that a high SENV DNA level was an independent risk factor or indicator for adverse disease outcome. CONCLUSION: SENV infection is common in HIV-positive patients. High SENV-H DNA levels were predictive for poor survival in HIV-positive patients.

Adult↗
PubMed2005

Amino acids in nectar enhance butterfly fecundity: a long-awaited link.

Thirty years ago, researchers discovered that flowers pollinated by butterflies are consistently rich in nectar amino acids, and more recent findings have shown that butterflies prefer nectar with high amino acid content. These observations led to speculation that amino acids in nectar enhance butterfly fitness and that butterflies have acted as agents of natural selection on nectar composition. Despite a number of experimental efforts over the years, convincing proof that nectar amino acids affect butterfly fitness has been lacking. Here, we provide the first evidence that amino acids in nectar have a positive effect on fecundity of one butterfly species, supporting the existence of a relationship between nectar preferences and fitness benefits. Map butterflies (Araschnia levana L.) raised under natural larval food conditions laid more eggs when they were fed nectar containing amino acids, whereas nectar amino acids had no effect on the number of eggs laid by butterflies raised on larval food rich in nitrogen. Uptake and utilization of nectar amino acids by map butterflies appear to be compensatory mechanisms enabling them to override impacts of poor larval food. These results provide strong support for the long-standing postulate that nectar amino acids benefit butterflies.

Amino Acids↗
PubMed2004

SEN virus seroprevalence in HIV positive patients: association with immunosuppression and HIV-replication.

BACKGROUND: Patients infected with HIV are often co-infected with other viruses. SEN virus (SENV) was isolated from a HIV positive patient with intravenous drug use and post-transfusion hepatitis. SENV strains D and H seem to be relevant for the development of post-transfusion hepatitis. We compared the prevalence of SENV strains D and H and the viral load of SENV H in HIV-infected patients with healthy blood donors. The results were correlated with clinical markers such as HIV stage, CD4 cell count, HIV-RNA positivity, HAART or the transmission mode in HIV infected individuals. OBJECTIVES: Blood samples of 143 HIV-positive patients were analysed and compared with a control group of 122 healthy blood donors. SENV D and -H was detected by PCR. RESULTS: SENV was detectable in 15.4% (22/143) of HIV-positive patients compared to 10.4% (12/122) in the control group (P=0.18). SENV H DNA-levels were significantly higher in HIV-positive patients (P=0.01). The prevalence in patients with CD4 cells less than 200/mm(3) was 31% (13/42), compared to 12.3% (8/65) in cases with CD4 cells between 200 and 500/mm(3), and 2.8% in cases with CD4 cells above 500/mm(3) (P=0.002 for CD4 cells <200 versus CD4 cells >200, P=0.031 for CD4 cells <500 versus CD4 cells >500). Prevalence of these strains was not significantly influenced by CDC stages. SENV was detected significantly more frequent in patients with detectable HIV-RNA (P=0.005). Patients undergoing HAART were significantly less frequent positive for SENV D or -H (P=0.029) than patients without HAART. In a multivariate analysis using a logistic regression model HIV-RNA positivity and CD4 cell count were identified as independent factors for SENV prevalence. CONCLUSION: SENV (D and H) prevalence is not significantly higher in HIV-positive patients in comparison to healthy blood donors. SENV prevalence depends on CD4 cell count and HIV-RNA.

Adult↗
PubMed2004

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration.

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-alpha) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV. METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA. RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV (50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=0.05). CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy. Response rate of SENV to the combination therapy depends on SENV DNA level.

Adult↗
PubMed2004

Genotype-specific response of a lycaenid herbivore to elevated carbon dioxide and phosphorus availability in calcareous grassland.

Effects of elevated CO2 and P availability on plant growth of the legume Lotus corniculatus and consequences for the butterfly larvae of Polyommatus icarus feeding on L. corniculatus were investigated in screen-aided CO2 control chambers under natural conditions on a calcareous grassland in the Swiss Jura mountains. Elevated CO2 conditions and P fertilisation increased the biomass production of L. corniculatus plants and affected the plant chemical composition. CO2 enrichment increased the C/N ratio and sugar concentration and decreased the N and P concentrations. C- and N-based allelochemicals (cyanoglycosides, total polyphenols and condensed tannins) were only marginally affected by CO2 enrichment. P fertilisation increased the specific leaf area and concentrations of water, N, sugar and P, while the C/N ratio and the concentration of total polyphenols decreased. Furthermore, P availability marginally enhanced the effect of elevated CO2 on the total dry mass and sugar concentration while the opposite occurred for the total polyphenol concentration. The changes in food-plant chemistry as a result of P fertilisation positively affected larval mass gain and accelerated the development time of P. icarus. Only a marginal negative effect on larval mass gain was found for CO2 enrichment. However, we found genotype-specific responses in the development time of P. icarus to elevated CO2 conditions. Larvae originating from different mothers developed better either under elevated CO2 or under ambient CO2 but some did not react to CO2 elevation. As far as we know this is the first finding of a genotype-specific response of an insect herbivore to elevated CO2 which suggests genetic shifts in insect life history traits in response to elevated CO2.

Analysis of Variance↗
PubMed2004

Mating frequency influences nectar amino acid preference of Pieris napi.

It is generally assumed that butterflies, as is the case with many holometabolous insects, rely primarily on nutrients gathered by larval feeding for somatic maintenance and fecundity. These reserves can be supplemented by adult feeding and in some cases by nuptial gifts passed from the males to the females during mating. Recent findings indicate that female butterflies detect and prefer nectar with high levels of amino acids, thus calling new attention to this nutritive source. Polyandrous species can further supplement their larval stores with additional nuptial gifts. This study examined how mating frequency of the polyandrous butterfly Pieris napi affects the female's preference for nectar amino acids. Females of this species generally detect and prefer nectar mimics containing amino acids. However, nectar amino acid preference is significantly lower in mated females. Furthermore, nectar amino acid preference increases when females are not allowed to remate, whereas the preference of twice-mated females remains constant at a lower level. These results indicate a versatile response of females to nectar amino acids, depending on their nutritional status; they may even switch their source of amino acids between adult feeding and nuptial gifts.

Amino Acids↗
PubMed2004

Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients.

BACKGROUND AND AIMS: Novel, potent, and well-tolerated hepatitis C virus (HCV) drugs are needed. BILN 2061 is a potent and specific inhibitor of HCV serine protease in vitro. Preclinical toxicology data and studies in healthy volunteers supported the administration of BILN 2061 to patients with HCV infection. METHODS: The antiviral efficacy, pharmacokinetics, and tolerability of 25, 200, and 500 mg BILN 2061 twice daily given as monotherapy for 2 days in 31 patients infected with chronic genotype 1 HCV infection and with minimal liver fibrosis (Ishak score of 0-2) were assessed in a placebo-controlled, double-blind pilot study. In 2 subsequent placebo-controlled studies of similar design, 200 mg BILN 2061 twice daily was administered for 2 days to 10 patients with advanced liver fibrosis (Ishak score of 3 or 4) and to 10 patients with compensated cirrhosis (Ishak score of 5 or 6). RESULTS: Viral RNA reductions of 2-3 log 10 copies/mL were achieved in most of the patients. There was a trend toward a higher number of patients receiving 500 mg BILN 2061 achieving a viral RNA reduction > or =3 log(10) copies/mL as compared with patients receiving 25 mg BILN 2061. Advanced fibrosis or compensated cirrhosis did not affect the antiviral efficacy of BILN 2061. BILN 2061 was well tolerated in all studies. CONCLUSIONS: BILN 2061 is a well-tolerated and very active compound that reduced serum viral RNA concentrations after 2 days of treatment in patients infected with genotype 1 HCV independent of the degree of fibrosis. Nevertheless, further clinical trials are on hold pending resolution of animal toxicity issues.

Antiviral Agents↗
PubMed2003

[Iron as comorbid factor in chronic hepatitis C].

Hepatitis C virus infection is often associated with an elevation of iron parameters. Free liver iron causes liver damage and liver fibrosis preferentially through induction of reactive oxygen species. With an allele frequency of 5-10% for the C282Y mutation and 6-30% for the H63D mutation, there is a frequent coincidence of hemochromatosis (HFE) mutations and chronic hepatitis C. There is increasing evidence that HFE homozygosity and even HFE heterozygosity are associated with an increased liver iron concentration and liver fibrosis progression in chronic hepatitis C. In addition, present data suggest an impact of iron on the outcome of interferon therapy. Thus, HFE mutations and liver iron stores seem to be important comorbid factors in chronic hepatitis C. Screening for iron parameters and HFE mutations should be considered in patients with hepatitis C.

Antiviral Agents↗
PubMed2003

IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3.

Eighty percent of patients newly infected with the hepatitis C virus (HCV) develop chronic infection, suggesting that HCV can develop effective strategies to escape the unspecific and specific immune response of the host. Because SOCS molecules have been recognized to be powerful inhibitors of cytokine signaling via the Jak/STAT pathway, virus-induced expression of these molecules should be an efficient instrument to counteract the cellular response toward interferons (IFNs), an essential part of first line antiviral immune response. This study shows that overexpression of HCV core protein inhibits IFN-alpha-induced tyrosine phosphorylation and activation of STAT1 in hepatic cells. With the use of a STAT1-YFP fusion protein, further evidence is given that HCV core is capable to inhibit nuclear translocation of STAT1. Inhibition of STAT1-tyrosine phosphorylation was accompanied by the induction of SOCS3-mRNA expression, suggesting that the HCV core protein impairs IFN-alpha-induced signal transduction via induction of SOCS3 expression. HCV core protein was competent to partially rescue growth of a genetically engineered influenza A virus lacking its own IFN antagonist. These IFN-antagonistic properties of the HCV core protein may be part of the molecular basis of IFN-alpha unresponsiveness in about one-half of chronically infected HCV-patients.

Active Transport, Cell Nucleus↗
PubMed2003

HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis.

BACKGROUND/AIMS: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied. METHODS: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients. RESULTS: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated. CONCLUSIONS: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection.

Adult↗
PubMed2003

Combination treatment of IFNalpha2b and ribavirin in patients with chronic hepatitis C and persistently normal ALTs.

Combination therapy of interferon-alpha2b and ribavirin was prospectively evaluated in 20 patients with chronic replicative hepatitis and persistently normal ALTs. Patients with normal ALTs on three or more occasions within 6 months received interferon-alpha2b 3 MU three times a week with ribavirin 1000-1200 mg everyday for 12 months and had a follow-up of 6 months. HCV genotype 1 was found in 16, and HCV genotype 2 or 3 in 4 patients. No patient experienced an ALT elevation during therapy. Ten of 20 patients (50%) cleared virus at the end of treatment. In an intent-to-treat analysis, a sustained virological response (SR) was achieved in 8 of 20 patients (40%). Nonresponse occurred in 5 patients. Relapse and breakthrough were seen in 2 patients each. Treatment was discontinued in 3 patients due to side effects. Interferon (IFN) ribavirin combination therapy is effective in patients with normal ALTs and appears superior to IFN monotherapy.

Administration, Oral↗