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Dyspnea may be easily appreciated during exercise with dyspneic scales, but methodological standardisation still needs to be specified. Authors review the basic physiological mechanism relating dyspnea to indices obtained during a stress test. They propose to use the dyspnea/VE relationship. With the concept of dyspneic threshold (close to the ventilatory threshold) and the ramp that both could be modified (for instance by rehabilitation programmes including exercise training). Interpretation of dyspnea during an exercise test obviously needs to be integrated with other parameters studied during exercise. 相似文献
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Enzymic catalysts of thiol:disulfide oxidoreduction contain two cysteine residues in their active sites. Another common residue is an aspartate (or glutamate), the role of which has been unclear. Escherichia coli thioredoxin (Trx) is the best characterized thiol:disulfide oxidoreductase, and in Trx these three active-site residues are Cys32, Cys35, and Asp26. Structural analyses had indicated that the carboxylate of Asp26 is positioned properly for the deprotonation of the thiol of Cys35, which would facilitate its attack on Cys32 in enzyme-substrate mixed disulfides. Here, Asp26 of Trx was replaced with isologous asparagine and leucine residues. D26N Trx and D26L Trx are reduced and oxidized more slowly than is wild-type Trx during catalysis by E.coli thioredoxin reductase. Stopped-flow spectroscopy demonstrated that the cleavage of the mixed disulfide between Trx and a substrate is slower in the D26N and D26L enzymes. Buffers increase the rate of mixed disulfide cleavage in these variants but not in wild-type Trx. These results indicate that Asp26 serves as an acid/base in the oxidation/reduction reactions catalyzed by Trx. Specifically, Asp26 protonates (during substrate oxidation) or deprotonates (during substrate reduction) the thiol of Cys35. A similar role is likely filled by the analogous aspartate (or glutamate) residue in protein disulfide isomerase, DsbA, and other thiol:disulfide oxidoreductases. Moreover, these results provide the first evidence for general acid/base catalysis in a thiol:disulfide interchange reaction. 相似文献
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The p53 tumor suppressor gene encodes a phosphoprotein which when overexpressed can induce growth arrest at the G1 and G2/M phases of the cell cycle, promote differentiation and apoptosis. This paper demonstrates that p53 can associate with trk tyrosine kinase. Expression of a murine temperature-sensitive (ts) p53 mutant in PC12 cells overexpressing trk (a model system to analyse cellular differentiation and signal transduction induced by NGF) induces morphological changes in the absence of NGF stimulation at 32 degrees C but not at 37 degrees C. In cells differentiated by p53, trk, but not EGFr, was hyperphosphorylated on tyrosine. Furthermore trk was not phosphorylated when expressed in Saos-2 cells (human osteosarcoma cells that lack expression of both endogenous trk and p53) at either temperature. However, transfection of ts p53 into these cells induces trk phosphorylation at 32 degrees C in the absence of NGF stimulation. Association of trk and p53 can be detected in NIH3T3 and PC12 cells co-expressing trk and the ts p53 mutant, in NIH3T3 and PC12 cells transfected with trk alone, and in untransfected PC12 cells, showing that overexpressed and/or endogenous trk associates with endogenous, low levels of p53. These data suggest a novel function for p53 which involves the stimulation of signal transduction pathways (mediating morphological properties of cells), possibly through association with and hyperphosphorylation of trk. 相似文献
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The traditional approach to severe subglottic stenosis (SGS) in the pediatric age group is laryngotracheal reconstruction (LTR). This approach may be complex and multistaged, with variable and unpredictable success rates in the individual patient. Excellent results have been reported in adults who had severe SGS and underwent partial resection of the cricoid and primary thyrotracheal anastomosis. This procedure has not been widely reported in infants and children. We report our experience with this procedure in 16 pediatric patients with grade III or IV SGS. Eleven patients had multiple previous LTR operations. The preoperative evaluation, surgical techniques, postoperative care, complications, and final results are described and discussed. Fourteen patients were decannulated after the procedure, 1 patient needed a second open procedure prior to decannulation, and 1 patient with concomitant bronchopulmonary dysplasia remains cannulated, for an overall 94% decannulation rate. Fourteen patients have no limitation of respiration, and 1 patient has moderate exercise intolerance. The results of this series suggest that partial cricotracheal resection with primary anastomosis is a relatively safe and effective procedure for pediatric patients with severe SGS. 相似文献
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T Omland T Aarsland A Aakvaag RT Lie K Dickstein 《Canadian Metallurgical Quarterly》1993,72(3):255-259
Case reports from the United Kingdom (UK) in 1989 have suggested that the introduction of human insulin in 1985 was associated with an increased risk of sudden death in insulin-treated diabetic patients. If human insulin increases the risk of sudden death, the number of these should have increased during the period where human insulin was introduced. We therefore identified all cases of sudden death in Denmark in younger insulin-treated diabetic patients, age at death below 50 years. During this period the consumption of human insulin went from 0.2% to 70% of the total consumption in Denmark. The total number of cases fulfilling the inclusion criteria was 226, and the annual number of sudden deaths did not change during the study period (p = 0.14). The number of deaths due to hypoglycaemia and cases with unexplained cause of death also remained constant (test for trend: p = 0.44). Chronic alcohol abuse or acute alcohol intoxication was found in 50% of the 135 patients dying from hypoglycaemia, ketoacidosis or unknown cause of death (including found dead in bed), while this was the case in only 16% of the remaining 91 cases dying from other natural causes. We conclude that introduction of human insulin in Denmark was not followed by an increase in sudden deaths among younger insulin-treated diabetic patients. 相似文献
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