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101.
Scism JL Laska DA Horn JW Gimple JL Pratt SE Shepard RL Dantzig AH Wrighton SA 《In vitro cellular & developmental biology. Animal》1999,35(10):580-592
Summary Cocultures of human umbilical vein endothelial cells (ECV304) and rat glioma cells (C6) from two commercial sources, American
Type Culture Collection and European Collection of Animal Cell Cultures, were evaluated as an in vitro model for the blood-brain
barrier. Monolayers of endothelial cells grown in the presence or absence of glial cells were examined for transendothelial
electrical resistance, sucrose permeability, morphology, multidrug resistance-associated protein expression, and P-glycoprotein
expression and function. Coculture of glial cells with endothelial cells increased electrical resistance and decreased sucrose
permeability across European endothelial cell monolayers, but had no effect on American endothelial cells. Coculture of European
glial cells with endothelial cells caused cell flattening and decreased cell stacking with both European and American endothelial
cells. No P-glycoprotein or multidrug resistance-associated protein was immunodetected in endothelial cells grown in glial
cell-conditioned medium. Functional P-glycoprotein was demonstrated in American endothelial cells selected in vinblastine-containing
medium over eight passages, but these cells did not form a tight endothelium. In conclusion, while European glial cells confer
blood-brain barrier-like morphology and barrier integrity to European endothelial cells in coculture, the European endothelial-glial
cell coculture model does not express P-glycoprotein, normally found at the blood-brain barrier. Further, the response of
endothelial cells to glial factors was dependent on cell source, implying heterogeneity among cell populations. On the basis
of these observations, the umbilical vein endothelial cell-glial cell coculture model does not appear to be a viable model
for predicting blood-brain barrier penetration of drug molecules. 相似文献
102.
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105.
Cowart M Pratt JK Stewart AO Bennani YL Esbenshade TA Hancock AA 《Bioorganic & medicinal chemistry letters》2004,14(3):689-693
2-aminoethylbenzofurans constitute a new class of H(3) antagonists that are more rotationally constrained than most previously reported H(3) antagonists. They retain high potency at human and rat receptors, with efficient CNS penetration observed in 35. The SAR of the basic amine moiety was compared in three different series of analogues. The greatest potency was found in analogues bearing a 2-methylpyrrolidine, a 2,5-dimethylpyrrolidine, or a 2,6-dimethylpiperidine. 相似文献
106.
A common open representation of mass spectrometry data and its application to proteomics research 总被引:12,自引:0,他引:12
Pedrioli PG Eng JK Hubley R Vogelzang M Deutsch EW Raught B Pratt B Nilsson E Angeletti RH Apweiler R Cheung K Costello CE Hermjakob H Huang S Julian RK Kapp E McComb ME Oliver SG Omenn G Paton NW Simpson R Smith R Taylor CF Zhu W Aebersold R 《Nature biotechnology》2004,22(11):1459-1466
A broad range of mass spectrometers are used in mass spectrometry (MS)-based proteomics research. Each type of instrument possesses a unique design, data system and performance specifications, resulting in strengths and weaknesses for different types of experiments. Unfortunately, the native binary data formats produced by each type of mass spectrometer also differ and are usually proprietary. The diverse, nontransparent nature of the data structure complicates the integration of new instruments into preexisting infrastructure, impedes the analysis, exchange, comparison and publication of results from different experiments and laboratories, and prevents the bioinformatics community from accessing data sets required for software development. Here, we introduce the 'mzXML' format, an open, generic XML (extensible markup language) representation of MS data. We have also developed an accompanying suite of supporting programs. We expect that this format will facilitate data management, interpretation and dissemination in proteomics research. 相似文献
107.
A new role of apolipophorin III (apoLp-III) as an immune activator has emerged recently. To gain insight into this novel function, the interaction of apoLp-III with lipopoly-saccharide (LPS) was investigated. ApoLp-III from Galleria mellonella was incubated with LPS from Escherichia coli O55:B5, and analyzed by non-denaturing polyacrylamide gel electrophoresis (PAGE). Protein staining showed that apoLp-III mobility was significantly reduced. In addition, silver and LPS fluorescent staining demonstrated that LPS mobility was increased upon incubation with apoLp-III. This result suggests association of apoLp-III with LPS. Sodium dodecyl sulfate (SDS) PAGE analysis showed decreased apoLp-III mobility upon LPS addition, indicative of LPS apoLp-III interaction in the presence of SDS. The unique tyrosine residue that resides in apoLp-III was used to provide additional evidence for LPS binding interaction. In the absence of LPS, apoLp-III tyrosine fluorescence was relatively low. However, LPS addition resulted in a progressive increase in the fluorescence intensity, indicating tertiary rearrangement in the environment of tyrosine 142 upon LPS interaction. Other well-characterized apoLp-IIIs were also examined for LPS binding. Manduca sexta , Bombyx mori and Locusta migratoria apoLp-III were all able to interact with LPS. The ability of apoLp-III to form complexes with LPS supports the proposed role of apoLp-III in innate immunity. 相似文献
108.
The class C beta-lactamase of Enterobacter cloacae P99 is known to catalyze the hydrolysis of certain acyclic (thio)esters. Previous experiments have employed thioglycolate, m-hydroxybenzoate, and phenylphosphate leaving groups. The relative effectiveness of these leaving groups has now been quantitatively assessed by employment of a series of compounds with common acyl groups, and found to rank in the order phenylphosphate >m-hydroxybenzoate >thioglycolate. Structural models suggest that these leaving groups interact during acylation principally with Tyr 150, Lys 315, and Thr 316 of the beta-lactamase active site. The positions of the leaving group carboxylates in these models is compared with those in published crystal structures of complexes of class C beta-lactamases with beta-lactams. The particular effectiveness of the acyl phosphate indicates the positions of two oxyanions that strongly interact with the active site. This information should be useful in the design of inhibitors of class C beta-lactamases. 相似文献
109.
Aryl malonamates are demonstrated to be novel substrates of a broad range of beta-lactam-recognizing enzymes. These compounds are isomers of the aryl phenaceturates, which are well-known substrates of these enzymes, but the new compounds contain a retro-amide side chain. Several lines of evidence, including comparisons of steady-state kinetic parameters between enzymes and a detailed investigation of the methanolysis kinetics, solvent deuterium isotope effects, and pH-rate profile for turnover of a retro substrate by the Enterobacter cloacae P99 beta-lactamase, suggested that the new substrates are likely to be hydrolyzed by the same chemical mechanisms as "normal" substrates. Molecular modeling indicated that the retro-amide group fits snugly into the active site of the P99 beta-lactamase by hydrogen bonding to the conserved lysine-67 residue. The retro-amide side chain may represent a lead to novel mechanism-based and transition state analogue inhibitors. 相似文献
110.