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Summary— Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca2+ and 3) endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca2+ , which was more effective than increasing [Ca2+ ]i through elevating extracellular Ca2+ or the addition of forskolin which increased [Ca2+ ]i but desensitized the myofilaments to Ca2+ . 相似文献
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Shared care: a review of the literature 总被引:7,自引:1,他引:6
This review examines broad issues of concern regarding the primary/secondarycare interface. The main purpose was to identify areas of goodpractice which could be adapted for more general use. One ofthe most fundamental aspects identified was communication, whichis discussed in some detail. Also covered are shared prescribingand disease management. The data suggest that the most effectivesystem(s) of shared care has yet to be established. Furtherqualitative and economic evaluations are required, taking intoaccount patient preferences. Although the literature does describecertain practice exemplars, it is clear that inter- and intra-professionalcommunication continues to be a problem. Whilst informationtechnology may provide some of the solutions, it is concludedthat a culture change, which compels health professionals tomake sharing of patient information a much higher priority,is reauired. Keywords. Shared care, seamless care, hospital, general practice, family practice. 相似文献
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Quantitative determination of specific IgE antibodies to Echinococcus granulosus and IgE levels in sera from patients with hydatid disease. 下载免费PDF全文
High serum IgE levels were found in eighty-nine patients with hydatid disease. Specific IgE antibodies to E. granulosus hydatid fluid or to a pure E. granulosus antigen were isolated using immunoabsorbents and quantified by a radioimmunoassay. The procedure made it possible to quantify, for the first time, the concentration of IgE antibodies in units per millilitre. Significant levels of IgE antibodies were demonstrated in twenty-three out of thirty-nine patients, by the use of standardized hydatid fluid antigens. The amount of IgE antibodies to E. granulosus was not related to serological findings. However, a highly significant correlation was obtained between levels of total serum IgE and IgE antibodies. A pure antigenic fraction prepared from hydatid fluid and known to be specific for E. granulosus was shown to be the most potent antigen reactive with IgE antibodies. The relationship of IgE antibodies to the viability of the hydatid cyst and to the serum IgE level is discussed. 相似文献
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Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli 总被引:1,自引:0,他引:1
We developed a bacterial expression system for the human alpha and beta
cDNAs of propionyl-CoA carboxylase (PCC). These cDNAs (less the putative
mitochondrial matrix targeting presequences) were co-expressed in
Escherichia coli on one plasmid vector with each cDNA having its own
IPTG-inducible promoter. Only negligible amounts of active PCC were
measured despite the presence of both alpha and beta subunits as indicated
by Western blot analysis and the almost complete biotinylation of the alpha
subunit. Co-expression of this plasmid with a second plasmid vector
over-expressing the E. coli chaperonin proteins, groES and groEL, resulted
in a several hundred-fold increase in PCC specific activity, to a level
comparable with that found in crude human liver extracts. PCC was partially
purified on monomeric avidin affinity resin and the presence of both alpha
and beta subunits was demonstrated, thereby confirming the assembly of both
subunits into an active enzyme. Deficiency of either alpha PCC or beta PCC
results in propionic acidemia, an autosomal recessive disorder. We used
this expression system to characterize one missense mutation previously
described in five Japanese alleles, namely C1283T (Thr428lle) in beta PCC.
This mutation, when expressed in E.coli under the same conditions as that
of wild-type PCC, had null activity, despite the presence of assembled
alpha PCC and beta PCC subunits. This bacterial expression system can be
useful for analysis of either alpha PCC or beta PCC mutations. Our findings
indicated that the groES and groEL chaperonin proteins were essential for
folding and assembly of the human PCC heteromeric subunits.
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Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein. 总被引:4,自引:0,他引:4 下载免费PDF全文
G Torpier J F Colombel C Mathieu-Chandelier M Capron J P Dessaint A Cortot J C Paris A Capron 《Clinical and experimental immunology》1988,74(3):404-408
Ultrastructural study of mucosal eosinophils in a case of eosinophilic gastroenteritis involving stomach, duodenum and ileum showed an altered structure in ulcerated duodenal areas. The electron core density of eosinophil granules was inverted or disappeared and tubulovesicular structures occurred. Using immunogold staining with specific antibodies, major basic protein was detected diffusely in the matrix of eosinophil granules and out of the granules in tight association with extragranular membrane formations. In contrast, eosinophil cationic protein and eosinophil peroxidase were normally distributed in the granule matrix. When compared with the eosinophils in macroscopically normal duodenal mucosa in the same patient, these changes support a role for major basic protein in tissue damage in eosinophilic gastroenteritis. The diffusion of one granule protein from the granules to the exterior of the cells favours the view of a selective release of eosinophil mediators. 相似文献