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排序方式: 共有124条查询结果,搜索用时 515 毫秒
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A. T. Axon C. A. O'Moráin K. D. Bardhan J. P. Crowe A. D. Beattie R. P. Thompson P. M. Smith F. D. Hollanders J. H. Baron D. A. Lynch M. F. Dixon D. S. Tompkins H. Birrell K. R. Gillon 《BMJ (Clinical research ed.)》1997,314(7080):565-568
OBJECTIVE: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration. DESIGN: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued. SETTING: Teaching and district general hospitals between 1991 and 1994. SUBJECTS: 107 patients with benign gastric ulcer associated with H pylori. MAIN OUTCOME MEASURES: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test). RESULTS: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001). CONCLUSIONS: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use. 相似文献
64.
Karen K. Hedberg G. Bruce Birrell Philip L. Mobley O. Hayes Griffith 《Journal of cellular physiology》1994,158(2):337-346
Phorbol ester–induced reorganization of the actin cytoskeleton was investigated in C6 rat glioma cells. Observations by fluorescence microscopy and photoelectron microscopy indicated that pretreatment with the transition metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) for 1–2 h at 50 μM reduced the sensitivity of the actin cytoskeleton to disruption by the subsequent addition of 200 nM phorbol myristate acetate (PMA). The protective effect of TPEN was eliminated by adding back Zn2+ prior to PMA addition, implicating chelation of metal ions as the mechanism of action of TPEN. C6 cells exposed to PMA experience potent activation of protein kinase C (PKC) and substantial redistribution of the kinase from a soluble to a particulate cellular fraction (translocation). TPEN pretreatment did not block PKC translocation in PMA-exposed cells. By two-dimensional gel analysis, TPEN also did not reduce, but rather slightly increased, the PMA-stimulated phosphorylation of the acidic 80 kDa endogenous PKC substrate, as well as two other proteins at 18 kDa and 50 kDa. In contrast, TPEN significantly suppressed phosphorylation of a 20 kDa protein, both in cells treated with TPEN only and in TPEN-pretreated PMA-exposed cells. The results indicate that the ability of TPEN to protect against PKC-mediated actin cytoskeletal disruption is not due to either a block of PKC translocation or to general inhibition of PKC activity. Rather, the action of TPEN is more selective and probably involves chelation of Zn2+ at a critical Zn2+ -dependent phosphorylation step downstream from the initial tumor promoter–-induced effects on PKC. © 1994 Wiley-Liss, Inc. 相似文献
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66.
A novel approach to the ultrastructural localization of cell surface receptors: affinity-gold labeling of Na, K-ATPase 总被引:1,自引:0,他引:1
R J Mrsny G B Birrell J J Volwerk J H Widdicombe O H Griffith 《European journal of cell biology》1988,45(2):200-208
We describe here a novel method of affinity-gold labeling for the ultrastructural localization and biochemical characterization of functional cell surface receptors. This approach combines the widely used colloidal gold technique, a previously published method for coating the gold with a matrix of derivatized dextran, small receptor-specific ligands, and a photoactivatable cross-linker. The resulting gold-affinity probe directed to a selected receptor by the ligand, is subsequently attached to the receptor by light activation of the cross-linker. As a specific example, a gold affinity probe prepared with ouabain, a selective inhibitor of Na,K-ATPase, as the directing ligand was used to investigate the ultrastructural localization of this enzyme complex in cell membranes. The biological activity of ouabain covalently linked to derivatized dextran containing the photoactivatable cross-linker was examined by its action on ion transport across dog trachea epithelium and on the enzyme activity of Na,K-ATPase preparations obtained from the rectal gland of the elasmobranch, Mustelus californicus. By these tests the probe mimics the effects of free ouabain. Electron micrographs of labeled human erythrocytes and cultured human foreskin fibroblasts showed an apparent random distribution of Na,K-ATPase on the plasma membranes of these cells. Binding of the probe was blocked in the presence of excess ouabain, a result demonstrating that the affinity probe binds at the same sites as free ouabain. Covalent attachment of probe by light activation of the nitroarylazido groups greatly enhanced retention during washing and standard procedures of fixation and dehydration. The high density of the gold probe was utilized to isolate the covalently attached membrane components from labeled human foreskin fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
67.
Phosphate analyses are fundamental to a broad range of biochemical applications involving inorganic phosphate and organic phosphoesters such as phospholipids, phosphorylated proteins, and nucleic acids. A practical automated method utilizing robotics is described in this report. Five colorimetric methods of phosphate analyses based on formation of a phosphomolybdate complex and compatible with the automated assay were tested, and the fundamental chemistry is discussed. The relative sensitivities are malachite green > crystal violet > quinaldine red > ascorbate reduction > antimony-modified ascorbate reduction, although only a fourfold improvement was observed in going from the modified ascorbate procedure to malachite green. Malachite green was selected to optimize the assay because this dye provided the highest sensitivity. However, where color stability and low blanks are more important than sensitivity, the ascorbate reduction and quinaldine red methods were found to be better choices than malachite green. Automation using a robotic liquid-handling system substantially reduces the labor required to process large arrays of samples. The result is a sensitive, nonradioactive assay of inorganic phosphate with high throughput. A digestion step in an acid-resistant 96-well plate was developed to extend the assay to phosphate esters. The robotic-based assay was demonstrated with inorganic phosphate and a common phospholipid, phosphatidylcholine. 相似文献
68.
A V Rukavishnikov T O Zaikova G B Birrell J F Keana O H Griffith 《Bioorganic & medicinal chemistry letters》1999,9(8):1133-1136
The synthesis of a fluorogenic substrate for mammalian phosphoinositide-specific phospholipase C is described. The substrate, based on the widely used fluorescein molecule, is a water-soluble substrate analog of phosphatidylinositol-4-phosphate. The fluorogenic substrate 2 is shown to be a sensitive substrate for human PI-PLC-delta1 in a continuous assay. 相似文献
69.
D Haigh G Allen H C Birrell D R Buckle B C Cantello D S Eggleston R C Haltiwanger J C Holder C A Lister I L Pinto H K Rami J T Sime S A Smith J D Sweeney 《Bioorganic & medicinal chemistry》1999,7(5):821-830
Rhizopus delemar lipase catalysed ester hydrolysis of the alpha-methoxy-beta-phenylpropanoate 1 affords the (R)-(+) and (S)-(-) isomers in > 84% enantiomeric excess. Absolute stereochemistry was determined by a single crystal X-ray analysis of a related synthetic analogue. The activity of these two enantiomers on glucose transport in vitro and as anti-diabetic agents in vivo is reported and their unexpected equivalence attributed to an enzyme-mediated stereospecific isomerisation of the (R)-(+) isomer. Binding studies using recombinant human PPARgamma (peroxisomal proliferator activated receptor gamma), now established as a molecular target for this compound class, indicate a 20-fold higher binding affinity for the (S) antipode relative to the (R) antipode. 相似文献
70.
The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy 总被引:3,自引:0,他引:3
Mclay LM Halley F Souness JE McKenna J Benning V Birrell M Burton B Belvisi M Collis A Constan A Foster M Hele D Jayyosi Z Kelley M Maslen C Miller G Ouldelhkim MC Page K Phipps S Pollock K Porter B Ratcliffe AJ Redford EJ Webber S Slater B Thybaud V Wilsher N 《Bioorganic & medicinal chemistry》2001,9(2):537-554
RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies. 相似文献