Search

Protein kinases are directly implicated in many human diseases; therefore, kinase inhibitors show great promises as new therapeutic drugs. In an effort to facilitate the screening and the characterization of [...]

A study was conducted to characterize the mouse Xist gene promoter region by examining promoter activity by chloramphenicol acetyltransferase assays after transfection in murine cell lines. Two regions, from -81 to +1, and, from -41 to -15, were identified to regulate promoter activity. A region located at -30 to -25 was shown to have binding affinity with a nuclear factor, while a region at -82 to -41 is needed for correct expression of the Xist gene.

Abstract Background The objective was to solve two problems of an already validated scale measuring inpatient opinion on care: 1) a high non-response rate for some items due to the "not applicable" response option and 2) a skewed score distribution with high ceiling effect. Methods The EQS-H scale ("échelle de qualité des soins en hospitalisation") comprised 26 items and 2 sub-scales of 13 items each, 'quality of medical information' (MI) and 'relationships with staff and daily routine' (RS). Three studies were conducted: a first mono-centre study (n = 552, response rate = 83.4%, self-completion of the scale the day before discharge) to construct a shorter version of the scale without the items with high non-response rate and maintaining those useful to ensure good internal validity (construct, convergent and divergent) and reliability; a second mono-centre study (n = 1246, response rate = 77.9%, self-completion of the scale before discharge) to confirm psychometric properties of the new version; a third multi-centre national study (n = 886, response rate 41.7%, self-completion at home 15 days after discharge) to test a new response pattern in order to reduce ceiling effect. Results Six items having a non-response rate >20% were deleted, increasing rates of exhaustive response to all items from 15% to 48%. Factorial analysis supported the evidence for removing 4 more items to ensure good internal validity and reliability of the new version. These good results (initial variance explained: 43%; Cronbach's α: 0.80 (MI) and 0.81 (RS)) were confirmed by the second study. The new response format produced a normalisation of the 2 scores with a large decrease in ceiling effect (25% to 4% for MI subscale and 61% to 8% for RS). Psychometric properties of the final version were excellent: the 2 subscales (8 items each) explained 66% of the variance in principal component analysis, Cronbach's α were respectively 0.92 (MI) and 0.93 (RS). Conclusion The new version of the EQS-H has better psychometric properties than the previous one. Rates of missing values are lower, and score distribution is normalized. An English version of this scale focused on quality of medical information delivered and on relationship with staff already exists, and this could be useful to conduct cross-cultural studies of health care service quality.

Purpose: Retinoblastoma is a malignant tumor that usually develops in early childhood. During retinoblastoma spreading, RB1 gene inactivation is followed by additional genomic modifications which progressively lead to resistance of tumor cells to death. Drugs that act at downstream levels of death signaling pathways should therefore be interesting in killing retinoblastoma cells. ABT-737, a BH3 mimetic molecule effective at the mitochondrial level, has been shown to induce apoptosis in different human tumoral cell lines as well as in primary patient-derived cells, and in a mouse xenograph model. Methods: In this report, we analyzed the pro-death effect of ABT-737 on two human retinoblastoma cell lines, Y79 and WERI-Rb, as well as on the mouse photoreceptor cell line 661W. Results: We observed that ABT-737 was very effective as a single agent in inducing human WERI-Rb cells apoptosis without affecting the mouse 661W photoreceptor cells. However human Y79 cells were resistant to ABT-737, as a probable consequence of the absence of Bax. The high sensitivity of WERI-Rb to ABT-737 can be increased by downregulating Mcl-1 using the proteasome inhibitor MG-132. Preliminary analysis in primary mouse retinoblastoma tumoral cell lines predicts high sensitivity to ABT-737. Conclusion: Our data suggest that ABT-737 or related compounds could be a highly effective drug in the treatment of some retinoblastomas. [ABSTRACT FROM AUTHOR]

Depression in patients with mastocytosis is often reported but its prevalence and characteristics are not precisely described. In addition, the impact of therapies targeting mast cells proliferation, differentiation and degranulation on psychic symptoms of depression have never been investigated. Our objective was to determine the prevalence and to describe features of depression in a large cohort of mastocytosis patients (n = 288) and to investigate the therapeutic impact of the protein kinase inhibitor masitinib in depression symptoms. The description of depression was based on the analysis of a database with Hamilton scores using Principal Component Analysis (PCA). Efficacy of masitinib therapy was evaluated using non parametric Wilcoxon test for paired data within a three months period (n = 35). Our results show that patients with indolent mastocytosis present an elevated prevalence of depression (64%). Depression was moderate in 56% but severe in 8% of cases. Core symptoms (such as psychic anxiety, depressed mood, work and interests) characterized depression in mastocytosis patients. Masitinib therapy was associated with significant improvement (67% of the cases) of overall depression, with 75% of recovery cases. Global Quality of Life slightly improved after masitinib therapy and did not predicted depression improvement. In conclusion, depression is very frequent in mastocytosis patients and masitinib therapy is associated with the reduction its psychic experiences. We conclude that depression in mastocytosis may originate from processes related to mast cells activation. Masitinib could therefore be a useful treatment for mastocytosis patients with depression and anxiety symptoms. [ABSTRACT FROM AUTHOR]

Background: The objective was to solve two problems of an already validated scale measuring inpatient opinion on care: 1) a high non-response rate for some items due to the "not applicable" response option and 2) a skewed score distribution with high ceiling effect. Methods: The EQS-H scale ("échelle de qualité des soins en hospitalisation") comprised 26 items and 2 sub-scales of 13 items each, 'quality of medical information' (MI) and 'relationships with staff and daily routine' (RS). Three studies were conducted: a first mono-centre study (n = 552, response rate = 83.4%, self-completion of the scale the day before discharge) to construct a shorter version of the scale without the items with high non-response rate and maintaining those useful to ensure good internal validity (construct, convergent and divergent) and reliability; a second mono-centre study (n = 1246, response rate = 77.9%, self-completion of the scale before discharge) to confirm psychometric properties of the new version; a third multi-centre national study (n = 886, response rate 41.7%, self-completion at home 15 days after discharge) to test a new response pattern in order to reduce ceiling effect. Results: Six items having a non-response rate >20% were deleted, increasing rates of exhaustive response to all items from 15% to 48%. Factorial analysis supported the evidence for removing 4 more items to ensure good internal validity and reliability of the new version. These good results (initial variance explained: 43%; Cronbach's a: 0.80 (MI) and 0.81 (RS)) were confirmed by the second study. The new response format produced a normalisation of the 2 scores with a large decrease in ceiling effect (25% to 4% for MI subscale and 61% to 8% for RS). Psychometric properties of the final version were excellent: the 2 subscales (8 items each) explained 66% of the variance in principal component analysis, Cronbach's a were respectively 0.92 (MI) and 0.93 (RS). Conclusion: The new version of the EQS-H has better psychometric properties than the previous one. Rates of missing values are lower, and score distribution is normalized. An English version of this scale focused on quality of medical information delivered and on relationship with staff already exists, and this could be useful to conduct cross-cultural studies of health care service quality. [ABSTRACT FROM AUTHOR]