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81.
The Women Health Initiative Clinical trial results suggest that post-menopausal women receiving estrogen + progesterone are at risk for heart disease compared with estrogen alone supplemented women. We examined the hypothesis that progesterone but not 17beta-estradiol (E) increases the secretion of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. U937 human monocytes were cultured with normal or high glucose in the presence and absence of estrogen or progesterone at 37 degrees C for 24 h. Results show that estrogen inhibits IL-6 but not TNF-alpha secretion (p < 0.05) in monocytes activated by lipopolysaccharide (LPS) or high glucose. In addition, progesterone increased the TNF-alpha secretion in activated monocytes. Thus, progesterone supplementation along with estrogen may increase blood levels of pro-inflammatory cytokine TNF-alpha and thus risk of heart disease in post-menopausal women. 相似文献
82.
Shen L Prouty C Conway BR Westover L Xu JZ Look RA Chen X Beavers MP Roberts J Murray WV Demarest KT Kuo GH 《Bioorganic & medicinal chemistry》2004,12(5):1239-1255
Palladium catalyzed cross-coupling reactions were used to synthesize two key intermediates 3 and 5 that resulted in the synthesis of novel series of macrocyclic bis-7-azaindolylmaleimides. Among the three series of macrocycles, the oxygen atom and thiophene containing linkers yielded molecules with higher inhibitory potency at GSK-3 beta (K(i)=0.011-0.079 microM) while the nitrogen atom containing linkers yielded molecules with lower potency (K(i)=0.150->1 microM). Compound 33 and 36 displayed 1-2 orders of magnitude selectivity at GSK-3 beta against CDK2, PKC beta II, Rsk3 and little or no inhibitions to the other 62 protein kinases. Compound 46 was at least 100-fold more selective towards GSK-3 beta than PKC beta II, and it had little or no activity against a panel of 65 protein kinases, almost behaved as a GSK-3 beta 'specific inhibitor'. All three compounds showed good potency in GS assay. Molecular docking studies were conducted in an attempt to rationalize the GSK-3 beta selectivity of azaindolylmaleimides. The high selectivity, inhibitory potency and cellular activities of these non-crown-ether typed molecules may provide them as a valuable pharmacological tools in elucidating the complex roles of GSK-3 beta in cell signaling pathways and the potential usage for the treatment of elevated level of GSK-3 beta involved diseases. 相似文献
83.
Background
Analysis of heart rate variation (HRV) has become a popular noninvasive tool for assessing the activities of the autonomic nervous system (ANS). HRV analysis is based on the concept that fast fluctuations may specifically reflect changes of sympathetic and vagal activity. It shows that the structure generating the signal is not simply linear, but also involves nonlinear contributions. These signals are essentially non-stationary; may contain indicators of current disease, or even warnings about impending diseases. The indicators may be present at all times or may occur at random in the time scale. However, to study and pinpoint abnormalities in voluminous data collected over several hours is strenuous and time consuming. 相似文献84.
85.
Chemical potential measurements of deoxyhemoglobin S polymerization. Determination of the phase diagram of an assembling protein 总被引:10,自引:0,他引:10
We have used the "osmotic stress" method to determine the phase diagram of deoxyhemoglobin S polymerization. This method involves equilibration, through a semipermeable membrane, of the protein with solutions of inert polymers of known osmotic pressure. With deoxyhemoglobin A and S solutions, in which we have demonstrated achievement of equilibrium, plots of osmotic pressure versus concentration initially agree closely with the results of other methods of measurement of colligative properties. However, once the known solubility value is exceeded for the deoxyhemoglobin S solutions at various temperatures, there is a rapid rise in hemoglobin concentration over a narrow osmotic pressure range and then a more gradual increase in concentration. We believe that these two regions correspond, respectively, to the onset of the polymerization process, and of subsequent continuing growth and compression or alignment of polymer. We derive the thermodynamic values for these processes and show that the behavior of the deoxyhemoglobin S system is analogous to the phase transition for a simple chemical system. These results are relevant to understanding the intracellular polymerization of deoxyhemoglobin S in sickle cell disease, and these concepts are applicable to other protein assembly systems. 相似文献
86.
Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli 总被引:3,自引:0,他引:3
Strains of Escherichia coli carrying Tn10, a transposon consisting of two
IS10 insertion sequences flanking a segment encoding for a
tetracycline-resistance determinant, gain a competitive advantage in
chemostat cultures. All Tn10-bearing strains that increase in frequency
during competition have a new IS10 insertion that is found in the same
location in the genome of those strains. We mapped, by a gradient of
transmission, the position of the new IS10 insertion. We examined 11
isolates whose IS10 insertion was deleted by recombinational crossing-
over, and in all cases the competitive fitness of the isolates was
decreased. These results show that the IS10-generated insertion increases
fitness in chemostat cultures. We named the insertion fit::IS10 and suggest
that transposable elements may speed the rate of evolution by promoting
nonhomologous recombination between preexisting variations within a genome
and thereby generating adaptive variation.
相似文献
87.
Members of the ZFY and ZNF6 gene families have been cloned from species
representing different taxa and different modes of sex determination.
Comparisons of these genes show the ZFY-like and ZNF6 sequences to be
strongly conserved across marsupials, birds, and lepidosaurians. Sequence
analyzed by neighbor-joining indicated that both gene families are
monophyletic with a high bootstrap value. Pairing of sequences from males
and females of nonmammalian species showed there to be no significant
difference between male and female sequences from a single species,
consistent with autosomal locations. The molecular distances between murine
Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have
undergone a period of rapid evolutionary change not seen in human ZFY.
相似文献
88.
W F Prouty 《Journal of virology》1975,16(4):1090-1093
Incorporation of an analoque into MS2 coded proteins prevents the maturation of phages. In addition, there is an alteration in the relative amount of coat protein to replicase protein synthesized, which supports the hypothesis that normal coat protein serves a physiological role as a translation repressor. Further, abnormal proteins, synthesized from the phage genome, are degraded, presumably by a host catabolic system, more rapidly than the normal gene products. 相似文献
89.
90.