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Jean-Luc Carrier Pasha Javadi Emilie Bourrier Céline Camus Evelyne Ségal-Bendirdjian A?da Karniguian 《PloS one》2012,7(11)
A determining role has been assigned to cAMP in the signaling pathways that relieve resistance to anti-leukemia differentiation therapy. However, the underlying mechanisms have not been elucidated yet. Here, we identify cFos as a critical cAMP effector, able to regulate the re-expression and splicing of epigenetically silenced genes associated with maturation (CD44) in retinoid-resistant NB4-LR1 leukemia cells. Furthermore, using RNA interference approach, we show that cFos mediates cAMP-induced ROS generation, a critical mediator of neutrophil maturation, and in fine differentiation. This study highlights some of the mechanisms by which cAMP acts to overcome resistance, and reveals a new alternative cFos-dependent pathway which, though nonexistent in retinoid-sensitive NB4 cells, is essential to rescue the maturation program of resistant cells. 相似文献
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Ching-Shuan Lau Kris A. Bunnell Edgar C. Clausen Gregory J. Thoma Jackson O. Lay Jennifer Gidden Danielle Julie Carrier 《Journal of industrial microbiology & biotechnology》2011,38(2):363-370
Xylose oligomers, which have a prebiotic effect, have been used as additives to human and animal food. These oligomers are
also the primary intermediate in hemicellulose degradation during the pretreatment of biomass. Centrifugal partition chromatography
(CPC) was used in this study to separate and purify xylan-derived oligomers from birchwood xylan. The xylan was partially
hydrolyzed to achieve varying degrees of polymerization at 130°C using 0.98% aqueous sulfuric acid for 20 min with a 2.5%
solid loading. The CPC solvent system consisting of dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and water in a 1:6:3
volumetric ratio was used because of its ability to dissolve xylose oligomers of different degrees of polymerization. The
CPC was operated in the ascending mode with the water- and DMSO-rich bottom phase acting as the stationary phase, while the
THF-rich top phase was the eluent. This paper delineates a method for the production and purification of xylose monomer and
xylose oligomers (up to xylopentaose) using CPC. The amount and purity of compounds collected from the CPC fractionation based
on 1 g of birchwood xylan were 25.26 mg of xylose at 91.86% purity, 10.71 mg of xylobiose at 85.07% purity, 4.15 mg of xylotriose
at 54.71% purity, 5.03 mg of xylotetraose at 38.33% purity and 3.31 mg of xylopentaose at 30.43% purity. 相似文献
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OBJECTIVES: To evaluate the demand for organs for transplantation and to recommend a reorganization of transplantation services in Quebec. DESIGN: Retrospective study. SETTING: Province of Quebec, 1988 to 1992. PATIENTS: All patients on waiting lists for organ transplantation and patients who received transplants registered in national data banks. MAIN OUTCOME MEASURES: The actual annual demand for organ transplantation and the rate of transplantations performed. RESULTS: The rates of heart transplantation were lower than the actual annual demand, which resulted in many patients dying while awaiting transplantation. The actual annual demand for heart transplantation decreased during the last 5 years from 10.9 per million people in 1987 to 6.7 in 1992. The rates of heart transplantation in Quebec were higher than the Canadian average. The actual demand for lung transplantation was only 2.9 per million people on average in 1992. Demand for liver transplantation increased annually, reaching 8.6 per million in 1992. The rate of transplantation increased likewise but remained insufficient. The demand for kidney transplantation reached 27.2 per million people in 1992, and the transplantation rate was 17.8. CONCLUSIONS: Taking into account the actual demand for and supply of organ transplantation, to insure high-quality service and to control costs associated with organ transplantation, we recommend that the present system in Quebec be reorganized so that transplantations are performed in 12 centres: 7 for kidney transplantation, 2 for hearts, 2 for livers and 1 for lungs. 相似文献
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Rebecca Lyn Carrier 《Biotechnology and bioengineering》2010,105(2):421-430
A model was developed for predicting the influence of cyclodextrins (CDs) delivered as a physical mixture with drug on oral absorption. CDs are cyclic oligosaccharides which form inclusion complexes with many drugs and are often used as solubilizing agents. The purpose of this work is to compare the simulation predictions with in vitro as well as in vivo experimental results to test the model's ability to capture the influence of CD on key processes in the gastrointestinal (GI) tract environment. Dissolution and absorption kinetics of low solubility drugs (Naproxen and Nifedipine) were tested in the presence and absence of CD in a simulated gastrointestinal environment. Model predictions were also compared with in vivo experimental results (Glibenclamide and Carbamazepine) from the literature to demonstrate the model's ability to predict oral bioavailability. Comparisons of simulation and experimental results indicate that a model incorporating the influence of CD (delivered as a physical mixture) on dissolution kinetics and binding of neutral drug can predict trends in the influence of CD on bioavailability. Overall, a minimal effect of CD dosed as a physical mixture was observed and predicted. Modeling may aid in enabling rational design of CD containing formulations. Biotechnol. Bioeng. 2010; 105: 421–430. © 2009 Wiley Periodicals, Inc. 相似文献