Biomedical subjects
Publications and source records attributed to M Dubay.
Cyclin dependent kinases (CDKs) along with the complementary cyclins form key regulatory checkpoint controls on the cell cycle. Flavopiridol is a synthetic flavone that shows potent and selective cyclin-dependent kinase inhibitory activity. In this paper, we report modifications of the 3-hydroxy-1-methylpiperidinyl (D ring) of flavopiridol and their effect on CDK inhibitory activity.
The biochemical interactions between the Cdk2/Cyclin E kinase and its inhibitor p27, were investigated using purified, recombinant p27 and CAK-phosphorylated Cdk2/Cyclin E. From kcat/Km determinations using either histone H1 or pRb as substrates, we found that Cdk2/Cyclin E has 60-fold higher specificity for pRb than for histone H1. The IC50 value of p27 increased with increasing Cdk2/Cyclin E concentrations while it remained constant at various ATP and histone H1 concentrations, suggesting that p27 acts as a tight binding inhibitor of Cdk2/Cyclin E. We also found that p27 could be phosphorylated by Cdk2/Cyclin E only at high enzyme concentrations, and that p27 forms a stable interaction with Cdk2/Cyclin E regardless of its phosphorylation state. Our results further indicate that the Cdk2/Cyclin E/p27 ternary complex is kinetically inactive as an enzyme; instead it serves as a substrate for Cdk2/Cyclin E. These results suggest that if phosphorylation of p27 by Cdk2/Cyclin E is involved in its ubiquitin-dependent degradation, as previously suggested, then the target for such event is the phosphorylated p27 bound to Cdk2/Cyclin E and not free p27.
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Closing volume can be ascertained with Argon by the aid of the Quadrupol-mass-spectrometer produced in Hungary. The method is simple, sensible and applicable in the routine laboratorium for pulmonary function testing. It will show the obstruction of the small airways and the disturbance of gas distribution in the lower pulmonary parts already at a point of time when the usual spirometric methods are still inconspicuous.
The CO2-production of circulating lymphocytes of patients with sarcoidosis and other diseases was investigated in presence of an sarcoidosis extract and without it. In 32 of 36 patients with sarcoidosis an elevated CO2-production of the lymphocytes was observed in presence of a sarcoid extract, whereas it happened only in 3 of 26 cases of a control group.
Laboratory results indicate that the endocervix may be a source of bacterial contamination when vaginal hysterectomy is performed. In a series of 160 consecutive vaginal hysterectomies in premenopausal women, hot conization of the cervix was performed prior to the scrub with an iodophore. No preoperative antibiotics were used in this series. The postoperative febrile morbidity rate was 4.3 per cent and the average stay was 4.5 days. These results are compared with those of three other groups: (1) patients who received a three-dose parenteral prophylactic antibiotic course with the first dose two hours prior to surgery had a febrile morbidity rate of 8.6 per cent. (2) In patients who had prophylactic antibiotics for five days with the first dose given intraoperatively, the febrile morbidity rate was 10.1 per cent. (3) The febrile morbidity rate in the group with no antibiotic prophylaxis or hot conization was 49.1 per cent. Laboratory and clinical data suggest that preoperative conization may be effective in the reduction of postoperative febrile morbidity.
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