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981.
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized at the molecular level by the expression of Bcr-abl, a 210-kDa fusion protein with deregulated tyrosine kinase activity. Encouraged by the clinical validation of Bcr-abl as the target for the treatment of CML by imatinib, we sought to identify pharmacological agents that could target this kinase by a distinct mechanism. We report the discovery of a new class of Bcr-abl inhibitors using an unbiased differential cytotoxicity screen of a combinatorial kinase-directed heterocycle library. Compounds in this class (exemplified by GNF-2) show exclusive antiproliferative activity toward Bcr-abl-transformed cells, with potencies similar to imatinib, while showing no inhibition of the kinase activity of full-length or catalytic domain of c-abl. We propose that this new class of compounds inhibits Bcr-abl kinase activity through an allosteric non-ATP competitive mechanism.  相似文献   
982.
A high-performance liquid chromatography-diode array detection-tandem mass spectrometry (HPLC-DAD-MS(n)) method has been firstly developed for chemical fingerprint analysis of rhizomes of Gymnadenia conopsea R. Br. and rapid identification of major compounds in the fingerprints. Comparing the UV and MS spectra with those of reference compounds, seven main peaks in the fingerprints were identified as adenosine (1), 4-hydroxybenzyl alcohol (2), 4-hydroxybenzyl aldehyde (3), dactylorhin B (4), loroglossin (5), dactylorhin A (6) and militarine (7). Compounds 4-7 were succinate derivative esters and firstly discovered from this species. The Computer Aided Similarity Evaluation System (CASES) for chromatographic fingerprint of traditional Chinese medicine was employed to evaluate the similarities of 10 samples of the rhizomes of G. conopsea collected from Sichuan, Qinghai and Hebei provinces, Tibet autonomous region of China, and Nepal. These samples from different sources had similar chemical fingerprints. This method is specific and may serve for quality identification and comprehensive evaluation of this traditional Tibetan remedy.  相似文献   
983.
A sensitive high performance liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry (HPLC-APCI-MS) assay for determination of cyclovirobuxine D (CVB-D) in human plasma using mirtazapine as internal standard (I.S.) was established. After adjustment to a basic pH with sodium hydroxide, plasma was extracted by ethyl acetate and separated by high performance liquid chromatography (HPLC) on a reversed-phase C(18) column with a mobile phase of 30 mM ammonium acetate buffer solution containing 1% formic acid-methanol (48:52, v/v). CVB-D was determined with atmospheric pressure chemical ionisation-mass spectrometry (APCI-MS). HPLC-APCI-MS was performed in the selected-ion monitoring (SIM) mode using target ions at [M+H](+)m/z 403.4 for CVB-D and [M+H](+)m/z 266.2 for I.S. Calibration curves were linear over the range 10.11-4044 pg/ml. The lower limit of quantification was 10.11 pg/ml. The intra- and inter-run variability values were less than 9.5 and 12.4%, respectively. The mean plasma extraction recovery of CVB-D was in the range of 85.3-92.8%. The method was successfully applied to determine the plasma concentrations of CVB-D in Chinese volunteers.  相似文献   
984.
Ding Q  Wu Z  Guo Y  Zhao C  Jia Y  Kong F  Chen B  Wang H  Xiong S  Que H  Jing S  Liu S 《Proteomics》2006,6(2):505-518
The inability of the CNS to regenerate in adult mammals propels us to reveal associated proteins involved in the injured CNS. In this paper, either thoracic laminectomy (as sham control) or thoracic spinal cord transection was performed on male adult rats. Five days after surgery, the whole spinal cord tissue was dissected and fractionated into water-soluble (dissolved in Tris buffer) and water-insoluble (dissolved in a solution containing chaotropes and surfactants) portions for 2-DE. Protein identification was performed by MS and further confirmed by Western blot. As a result, over 30 protein spots in the injured spinal cord were shown to be up-regulated no less than 1.5-fold. These identified proteins possibly play various roles during the injury and repair process and may be functionally categorized as several different groups, such as stress-responsive and metabolic changes, lipid and protein degeneration, neural survival and regeneration. In particular, over-expression of 11-zinc finger protein and glypican may be responsible for the inhibition of axonal growth and regeneration. Moreover, three unknown proteins with novel sequences were found to be up-regulated by spinal cord injury. Further characterization of these molecules may help us come closer to understanding the mechanisms that underlie the inability of the adult CNS to regenerate.  相似文献   
985.
The effect of temperature on the formation of recombinant protein, apolipoprotein A-IMilano was investigated in the present study. The temperature of the initial growth phase was set at 30°C, while temperature variation in induction phase was arranged in three modes. High cell-density culture of Escherichia coli and high expression of recombinant human by twice temperature-shifted induction were carried out. Experimental results showed that ApoA-IMilano reached 4.8 g/L with the final cell density of OD600, 150. It was found that twice temperature-shifted induction could successfully avoid the effect of acetic acid on cell density and the expression of the product. The present study provides a basic procedure for the production of recombinant ApoA-IMilano.  相似文献   
986.
类风湿关节炎与白细胞介素-18 的研究进展   总被引:3,自引:3,他引:0       下载免费PDF全文
类风湿关节炎发病机制不明,许多细胞因子参与了RA的发病机制。近年发现,白细胞介素-18可作用于RA发病的多个参与因素,成为研究RA的新热点。  相似文献   
987.
988.
Stem cells and progenitor cells derived from the developing human brain have been shown to differentiate into neurons and astrocytes. However, few studies have examined the functional, physiological properties of these differentiated neurons and astrocytes. In this study we have used immunocytochemistry in combination with electrophysiology to examine protein machinery and functional properties of neurons and astrocytes differentiated from human brain progenitor cells (hBPCs).Our results show that serum induces mainly astrocytic phenotype cells that express GFAP and have physiological properties that are typical of astrocytes. hBPCs differentiated with BDNF and PDGF develop mainly into neurons expressing mature neuronal proteins MAP-2, synaptobrevin II and vesicular glutamate transporter I in the process, plus a small population of GFAP-positive radial cells. Based on electrophysiology of BDNF/PDGF-treated cells two classes of cell were identified. Class I cells have functional neuronal properties, including functional voltage-gated Na(+) and K(+) currents, functional AMPA receptors and the ability to generate action potentials. A smaller subpopulation of cells (Class II cells) expresses GFAP and exhibit functional properties of astrocytes, including linear current-voltage relationship and dye-coupling.  相似文献   
989.
Nano-structured colorful zinc oxide (ZnO) replicas were produced using the wings of the Ideopsis similis butterfly as templates. The ZnO replicas we obtained exhibit iridescence, which was clearly observed under an optical microscope (OM). Field emission scanning electron microscope analysis shows that all the microstructure details are maintained faithfully in the ZnO replica. A computer model was established to simulate the diffraction spectral results, which agreed well with the OM images.  相似文献   
990.
Li Z  Ding S  Li Z  Tan T 《Biotechnology journal》2006,1(12):1453-1458
Batch and fed-batch fermentation studies were performed to evaluate the potential of corn steep liquor (CSL)-supplemented acid-hydrolysate of soybean meal (AHSM) as an alternative to yeast extract (YE) for the production of L-lactic acid by Lactobacillus casei LA-04-1. The CSL-supplemented AHSM gave an outstanding result in supporting L-lactic acid production from glucose. In the exponential fed-batch fermentation, the concentration, yield and productivity of L-lactic acid were 162.5 g/L, 89.7% and 1.69 g/L per h, respectively, which were lower than those with 20 g/L YE (180 g/L, 90.3%, 2.14 g/L per h) after 96 h of fermentation. However, the raw material cost of the nitrogen resource was estimated as only 25% of that using the YE.  相似文献   
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