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info:eu-repo/semantics/published

info:eu-repo/semantics/published

Background and Aims: Chronic hepatitis C (CHC) has been associated with an increased prevalence of diabetes and insulin resistance (IR). Recently, a genotype-specific association between HCV genotype 1 and IR has been proposed. It remains unclear, however, whether this is a causal relationship. The present study investigated the association of sustained virologic response (SVR) with IR in patients enrolled in the ACHIEVE 1 and 2/3 trials. Method(s): 2255 treatment-naive patients with genotype 1 or 2/3 CHC were enrolled in 2 separate phase 3, active-controlled studies of albinterferon alfa-2b vs peginterferon alfa-2a plus ribavirin for 48 or 24 weeks, respectively. IR was measured at wk 0, 12, 24, or 48, and post-treatment wk12 using the homeostasis model for assessment of IR (HOMA-IR). Clinical evaluation by a single pathologist included age, gender, race, BMI, HCV viral load, alanine aminotransferase, gamma-glutamyl transpeptidase, total cholesterol, triglycerides, and baseline liver biopsy for steatosis, METAVIR inflammatory grade, and fibrosis stage. IR was considered categorically, setting a threshold of HOMA-IR >3. Change in HOMA-IR post-therapy was considered as a continuous variable; HOMA-IR data were log-transformed for analysis as a continuous variable. The ACHIEVE 1 and 2/3 cohorts were analyzed separately. Result(s): Matched pre- and 12wk post HOMA-IR measurements were available from 1038 nondiabetic patients (genotype 1 = 497, genotype 2/3 = 541). Respective SVR rates were 60% and 84% in genotype 1 and 2/3 patients. Baseline mean HOMA-IR scores were higher in patients with genotype 1 than with 2/3 (3.4 vs 2.9; P=.006). SVR was associated with a reduction in prevalence of IR (P <0.001) and in mean HOMA-IR (P =0.004) in genotype 1 patients, but not in genotype 2/3. This was independent of changes in BMI, alanine aminotransferase, gamma-glutamyl transpeptidase, and lipid levels. HOMA-IR did not change in nonresponders. No association between SVR and IR was

Background and Aims: Chronic hepatitis C (CHC) has been associated with an increased prevalence of diabetes and insulin resistance (IR). Recently, a genotype-specific association between HCV genotype 1 and IR has been proposed. It remains unclear, however, whether this is a causal relationship. The present study investigated the association of sustained virologic response (SVR) with IR in patients enrolled in the ACHIEVE 1 and 2/3 trials. Method(s): 2255 treatment-naive patients with genotype 1 or 2/3 CHC were enrolled in 2 separate phase 3, active-controlled studies of albinterferon alfa-2b vs peginterferon alfa-2a plus ribavirin for 48 or 24 weeks, respectively. IR was measured at wk 0, 12, 24, or 48, and post-treatment wk12 using the homeostasis model for assessment of IR (HOMA-IR). Clinical evaluation by a single pathologist included age, gender, race, BMI, HCV viral load, alanine aminotransferase, gamma-glutamyl transpeptidase, total cholesterol, triglycerides, and baseline liver biopsy for steatosis, METAVIR inflammatory grade, and fibrosis stage. IR was considered categorically, setting a threshold of HOMA-IR >3. Change in HOMA-IR post-therapy was considered as a continuous variable; HOMA-IR data were log-transformed for analysis as a continuous variable. The ACHIEVE 1 and 2/3 cohorts were analyzed separately. Result(s): Matched pre- and 12wk post HOMA-IR measurements were available from 1038 nondiabetic patients (genotype 1 = 497, genotype 2/3 = 541). Respective SVR rates were 60% and 84% in genotype 1 and 2/3 patients. Baseline mean HOMA-IR scores were higher in patients with genotype 1 than with 2/3 (3.4 vs 2.9; P=.006). SVR was associated with a reduction in prevalence of IR (P <0.001) and in mean HOMA-IR (P =0.004) in genotype 1 patients, but not in genotype 2/3. This was independent of changes in BMI, alanine aminotransferase, gamma-glutamyl transpeptidase, and lipid levels. HOMA-IR did not change in nonresponders. No association between SVR and IR was

Background: Human myelogenous leukemia characterized by either the non random t(8; 21)(q22; q22) or t(16; 21)(q24; q22) chromosome translocations differ for both their biological and clinical features. Some of these features could be consequent to differential epigenetic transcriptional deregulation at AML1 targets imposed by AML1-MTG8 and AML1-MTG16, the fusion proteins deriving from the two translocations. Preliminary findings showing that these fusion proteins lead to transcriptional downregulation of AML1 targets, marked by repressive chromatin changes, would support this hypothesis. Here we show that combining conventional global gene expression arrays with the power of bioinformatic genomic survey of AML1-consensus sequences is an effective strategy to identify AML1 targets whose transcription is epigenetically downregulated by the leukemia-associated AML1-MTG16 protein. Results: We interrogated mouse gene expression microarrays with probes generated either from 32D cells infected with a retroviral vector carrying AML1-MTG16 and unable of granulocyte differentiation and proliferation in response to the granulocyte colony stimulating factor (G-CSF), or from 32D cells infected with the cognate empty vector. From the analysis of differential gene expression alone (using as criteria a p value < 0.01 and an absolute fold change > 3), we were unable to conclude which of the 37 genes downregulated by AML1-MTG16 were, or not, direct AML1 targets. However, when we applied a bioinformatic approach to search for AML1-consensus sequences in the 10 Kb around the gene transcription start sites, we closed on 17 potential direct AML1 targets. By focusing on the most significantly downregulated genes, we found that both the AML1-consensus and the transcription start site chromatin regions were significantly marked by aberrant repressive histone tail changes. Further, the promoter of one of these genes, containing a CpG island, was aberrantly methylated. Conclusion: This study

Consensus Development Conference, Journal Article, info:eu-repo/semantics/published

Consensus Development Conference, Journal Article, info:eu-repo/semantics/published

The gold-bearing massive sulphides have generally been related to three volcanic episodes, though recent Ar-Ar dating suggests only two. The relationships between mineralisation and associated hydrothermal facies, and the stratigraphic position of the volcanic rocks as determined by palaeontology, suggest that volcanic activity and its associated mineralisation migrated with time from NNW to SSE of the district. The main Pannonian period of mineralisation is correlated with a major break in volcanic activity and evidence of phreatomagnetic explosion in most mines, where breccia veinlets, dykes and pipes all contain a very wide range of clast sizes and origins. The presence of several generations of breccia dykes, some containing mineralised and hydrothermally altered pebbles, show how their evolution was related to sinistral strike-slip faulting and how the mineralising phenomena generally followed a sequence from Pb-Zn-Cu through Sb to a gold-bearing association. Pb isotope signatures are usually closely spaced, not varying for a particular generation of ore within a single mine but only from one mine to another. Such signatures are typical of Neogene mineralisation deriving from a single crustal source., The gold-bearing massive sulphides have generally been related to three volcanic episodes, though recent Ar-Ar dating suggests only two. The relationships between mineralisation and associated hydrothermal facies, and the stratigraphic position of the volcanic rocks as determined by palaeontology, suggest that volcanic activity and its associated mineralisation migrated with time from NNW to SSE of the district. The main Pannonian period of mineralisation is correlated with a major break in volcanic activity and evidence of phreatomagnetic explosion in most mines, where breccia veinlets, dykes and pipes all contain a very wide range of clast sizes and origins. The presence of several generations of breccia dykes, some containing mineralised and hydrothermally altered pebbles, show how their evolution was related to sinistral strike-slip faulting and how the mineralising phenomena generally followed a sequence from Pb-Zn-Cu through Sb to a gold-bearing association. Pb isotope signatures are usually closely spaced, not varying for a particular generation of ore within a single mine but only from one mine to another. Such signatures are typical of Neogene mineralisation deriving from a single crustal source.