Search results for "2A"
showing 10 items of 282 documents
eIF2α confers cellular tolerance to S. aureus α-toxin
2015
We report on the role of conserved stress-response pathways for cellular tolerance to a pore forming toxin. First, we observed that small molecular weight inhibitors including of eIF2α-phosphatase, jun-N-terminal kinase (JNK), and PI3-kinase sensitized normal mouse embryonal fibroblasts (MEFs) to the small pore forming S. aureus α-toxin. Sensitization depended on expression of mADAM10, the murine ortholog of a proposed high-affinity receptor for α-toxin in human cells. Similarly, eIF2α (S51A/S51A) MEFs, which harbor an Ala knock-in mutation at the regulated Ser51 phosphorylation site of eukaryotic translation initiation factor 2α, were hyper-sensitive to α-toxin. Inhibition of translation w…
The Interaction Mechanism of Intrinsically Disordered PP2A Inhibitor Proteins ARPP-16 and ARPP-19 With PP2A
2021
Protein phosphatase 2A (PP2A) activity is critical for maintaining normal physiological cellular functions. PP2A is inhibited by endogenous inhibitor proteins in several pathological conditions including cancer. A PP2A inhibitor protein, ARPP-19, has recently been connected to several human cancer types. Accordingly, the knowledge about ARPP-19—PP2A inhibition mechanism is crucial for the understanding the disease development and the therapeutic targeting of ARPP-19—PP2A. Here, we show the first structural characterization of ARPP-19, and its splice variant ARPP-16 using NMR spectroscopy, and SAXS. The results reveal that both ARPP proteins are intrinsically disordered but contain transient…
Direct radiofluorination of [18F]MH.MZ for 5-HT2A receptor molecular imaging with PET
2012
Imaging the serotonin 2A neuroreceptor with positron emission tomography has been carried out with [11C]MDL 100907 and [18F]altanserin for years. Recently, the MDL 100907 analogue [18F]MH.MZ was developed by combining the increased selectivity profile of MDL 100907 and the favourable radiophysical properties of fluorine-18. Here, we want to report the synthesis of [18F]MH.MZ via direct radiofluorination. Unfortunately, the direct radiofluorination did not have any significant benefits over the indirect labelling method. This is mainly because the precursor for the direct labelling approach is not completely stable and slowly decomposes. However, only one HPLC separation is necessary for the…
Topical application of the adenosine A2Areceptor agonist CGS-21680 prevents phorbol-induced epidermal hyperplasia and inflammation in mice
2014
The nucleoside adenosine is a known regulator of immunity and inflammation that mediates, at least in part, the anti-inflammatory effect of methotrexate, an immunosuppressive agent widely used to treat autoimmune inflammatory diseases. Adenosine A2A receptors play a key role in the inhibition of the inflammatory process besides promoting wound healing. Therefore, we aimed to determine the topical effect of a selective agonist, CGS-21680, on a murine model of skin hyperplasia with a marked inflammatory component. Pretreatment with either CGS-21680 (5 μg per site) or the reference agent dexamethasone (200 μg/site) prevented the epidermal hyperplasia and inflammatory response induced by topica…
Cost Effectiveness of Peginterferon ??-2a Plus Ribavirin versus Interferon ??-2b Plus Ribavirin as Initial Therapy for Treatment-Naive Chronic Hepati…
2004
Introduction: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon α-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon α-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon α-2a plus ribavirin is worth the incremental cost. Methods: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon α-2a plus ribavirin or interferon α-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genot…
PIN31: THE COST-EFFECTIVENESS OF PEGINTERFERON ALFA-2A (40KD) (PEGASYS) PLUS RIBAVIRIN (COPEGUS) VS. INTERFERON ALFA-2B PLUS RIBAVIRIN FOR CHRONIC HE…
2003
Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin.
2005
Background/Aims: Prediction of sustained virological response (SVR) during treatment would allow clinicians to identify patients most likely to benefit from therapy. Methods: Retrospective analysis of data from 1121 adults with chronic hepatitis C treated for 48 weeks with peginterferon alfa-2a (40 KD) 180 mu g/week plus placebo or ribavirin (1000/1200 mg/day), or interferon alfa-2b 3 MIU three times/week plus ribavirin in a randomized, multinational, study. Results: 67% of patients treated with peginterferon alfa-2a (40 KD)/ribavirin with early virological responses (HCV RNA negative or >= 2 log(10) decrease) at week 12 had SVRs at week 72 (HCV RNA 80 % of the planned ribavirin dose. Concl…
Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa-2a/ribavirin
2012
Summary. It is unclear whether the current threshold for ‘high’ hepatitis C virus (HCV) RNA level (800 000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono-infected and 176 HIV–HCV co-infected patients treated with peginterferon alfa-2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono-infected patients, the difference in SVR rates between those with low and high baseline HC…
New approaches in the treatment of Adamantiades-Behçet's disease.
2005
Purpose of review To update clinicians on the recent advances in the treatment of Adamantiades-Behcet's disease. Recent findings Interferon-α-2a and infliximab have proved able to induce prompt remission in the vast majority of Adamantiades-Behcet's patients with DMARD-resistant uveoretinitis. Efficacy of interferon-α-2a has also been reported for mucocutaneous lesions, arthritis, and (more anecdotally) for neuro-Behcet, while results from small case series suggest that infliximab is beneficial for mucocutaneous lesions and (more anecdotally) for arthritis and gastro-intestinal manifestations. Two cases of neuro-Behcet treated with infliximab showed a complete resolution. Finally, in a rand…