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21.
Postembolic colonic infarction 总被引:12,自引:0,他引:12
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The properties of the human alpha(1)beta(1) gamma-aminobutyric acid (GABA)(A) receptors were investigated after mutation of a highly conserved leucine residue at the 9' position in the second membrane-spanning region (TM2). The role of this residue in alpha(1) and beta(1) subunits was examined by mutating the 9' leucine to phenylalanine, tyrosine, or alanine. The mutations were in either the alpha(1) subunit (alpha*beta), the beta(1) subunit (alphabeta*), or in both subunits (alpha*beta*), and the receptors were expressed in Sf9 cells. Our results show that the rate of desensitization is increased as the size and hydrophobicity of the 9' residue in the alpha(1) subunit is increased: Y, F > L > A, T. Mutation of L9' in only the beta(1) subunit (alphabeta*) to either phenylalanine or tyrosine increased the EC(50) value for GABA at least 100 times, but the EC(50) was unchanged in alphabeta* alanine mutants. In the 9' alpha(1) mutants (alpha*beta, alpha*beta*) the GABA EC(50) was minimally affected. In alpha*beta and alpha*beta*, but not alphabeta*, the peak currents evoked by millimolar concentrations of GABA were greatly reduced. The reduction in currents could only be partially accounted for by decreased expression of the receptors These findings suggest different roles for the two types of subunits in GABA activation and later desensitization of alpha(1)beta(1) receptors. In addition, an increase in the resting membrane conductance was recorded in alanine but not in phenylalanine and tyrosine mutants, indicating that the side chain size at the 9' position is a major determinant of current flow in the closed conformation. 相似文献
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A case of achalasia complicated by Mycobacterium fortuitum pulmonary infection and empyema is reported. This association has been documented in the medical literature. Possible mechanisms explaining this association are discussed. 相似文献
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J E Dalziel B Birnir A B Everitt M L Tierney G B Cox P W Gage 《European journal of pharmacology》1999,370(3):345-348
Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation. 相似文献
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The effects of systemically administered oxytetracycline and erythromycin in a guinea pig model of acne-type inflammation were assessed histologically and by tissue measurement techniques. It was found that oxytetracycline significantly reduced the volume and maximum area of inflammation compared with both control and erythromycin treated groups. Oxytetracycline also altered the morphology of the inflammatory infiltrate significantly reducing the proportion of polymorphonuclear leucocytes present. In this model, erythromycin did not alter the inflammatory response but did seem to reduce the amount of transepidermal elimination of inflammatory debris. 相似文献
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Intraregional variation in treatment of end stage renal failure 总被引:4,自引:0,他引:4