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排序方式: 共有163条查询结果,搜索用时 406 毫秒
101.
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Shen W Gill RM Zhang JP Jones BD Corbly AK Steinberg MI 《American journal of physiology. Heart and circulatory physiology》2005,288(4):H1508-H1514
We compared the cardiac inotropic, lusitropic, and chronotropic responses to the Na(+) channel enhancer LY-368052 in conscious dogs before and after development of congestive heart failure (CHF). We also examined the effect of LY-368052 on baroreflex sensitivity and the efferent neural mechanisms of the bradycardic response in heart failure. Dogs were chronically instrumented, and heart failure was induced by right ventricular pacing at 240 beats/min for 3-4 wk. LY-368052 dose-dependently increased left ventricular contractile performance before and after the development of CHF to a similar extent. The inotropic effect of LY-368052 in heart failure was not altered by either ganglionic or beta-adrenergic receptor blockade. LY-368052 improved cardiac relaxation and induced bradycardia in dogs with heart failure but not in normal dogs. The negative chronotropic effect of LY-368052 was eliminated by ganglionic blockade but not beta-adrenergic blockade, suggesting that the bradycardia was mediated by the autonomic nervous system via enhanced parasympathetic tone. Baroreflex sensitivity was assessed as the pulse interval-mean arterial pressure slope in response to temporary pharmacological (nitroglycerin or phenylephrine) and mechanical (brief occlusion of inferior vena cava) alterations of arterial pressure in conscious dogs before and after development of heart failure. Baroreflex sensitivity was significantly depressed in heart failure and restored completely by acute treatment with LY-368052. Thus the Na(+) channel enhancer LY-368052 maintains its beta-receptor-independent inotropic effect in chronic CHF and specifically improves ventricular relaxation and depressed baroreflex function. 相似文献
103.
Durnaś B Góźdź S Piestrak E Zółcińska D Dzierzanowska D 《Medycyna do?wiadczalna i mikrobiologia》2003,55(3):285-295
The aim of the presented study was the analysis of microbiological data obtained from patients hospitalized in The Holly Cross Cancer Center in Kielce in 2001. The frequency of important nosocomial pathogens in selected specimens and their susceptibility to antibiotics were determined. The strains were identified by using commercial tests (bioMerieux) and their antibiotic susceptibility patterns were performed by disc diffusion technique. The most prevalent bacteria were Gram-negative rods of Enterobacteriaceae family (43%), mainly Escherichia coli. Only 2.7% strains of isolated Escherichia coli isolated from clinical specimens collected from hospitalized patients were beta-lactamase--positive (ESBL+). The second important group of microorganisms were Staphylococci, followed by Enterococcus spp., Pseudomonas aeruginosa and Candida spp. About twenty eight percent of Staphylococcus aureus isolates were resistant to methicillin. 相似文献
104.
The temporal firing of replication origins throughout S phase in yeast depends on unknown determinants within the adjacent chromosomal environment. We demonstrate here that the state of histone acetylation of surrounding chromatin is an important regulator of temporal firing. Deletion of RPD3 histone deacetylase causes earlier origin firing and concurrent binding of the replication factor Cdc45p to origins. In addition, increased acetylation of histones in the vicinity of the late origin ARS1412 by recruitment of the histone acetyltransferase Gcn5p causes ARS1412 alone to fire earlier. These data indicate that histone acetylation is a direct determinant of the timing of origin firing. 相似文献
105.
Nuclear proteins in Drosophila melanogaster cells after heat shock and their binding to homologous DNA 总被引:2,自引:0,他引:2
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After 5 minutes heat shock at 37 degrees C Drosophila melanogaster Kc-cell nuclear proteins were extracted wit 0.4M NaCl and compared by SDS gel electrophoresis with extracts from cells grown at 25 degrees C. Two proteins (39 000 and 46 000) were only found in heat shock nuclei. Reconstitution with total Drosophila DNA or a DNA fragment from the heat inducible locus 87A/C covalently coupled to sepharose was performed. In the presence of calf thymus competitor DNA these proteins and also others of lower molecular weight showed preferential binding to the homologous DNA. 相似文献
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107.
Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity. 总被引:5,自引:2,他引:3
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D P Bonita S Miyake M L Lupher Jr W Y Langdon H Band 《Molecular and cellular biology》1997,17(8):4597-4610
Recent studies have demonstrated that Cbl, the 120-kDa protein product of the c-cbl proto-oncogene, serves as a substrate of a number of receptor-coupled tyrosine kinases and forms complexes with SH3 and SH2 domain-containing proteins, pointing to its role in signal transduction. Based on genetic evidence that the Caenorhabditis elegans Cbl homolog, SLI-1, functions as a negative regulator of the LET-23 receptor tyrosine kinase and our demonstration that Cbl's evolutionarily conserved N-terminal transforming region (Cbl-N; residues 1 to 357) harbors a phosphotyrosine binding (PTB) domain that binds to activated ZAP-70 tyrosine kinase, we examined the possibility that oncogenic Cbl mutants may activate mitogenic signaling by deregulating cellular tyrosine kinase machinery. Here, we show that expression of Cbl-N and two other transforming Cbl mutants (CblY368 delta and Cbl366-382 delta or Cb170Z), but not wild-type Cbl, in NIH 3T3 fibroblasts leads to enhancement of endogenous tyrosine kinase signaling. We identified platelet-derived growth factor receptor alpha (PDGFR alpha) as one target of mutant Cbl-induced deregulation. In mutant Cbl transfectants, PDGFR alpha was hyperphosphorylated and constitutively complexed with a number of SH2 domain-containing proteins. PDGFR alpha hyperphosphorylation and enhanced proliferation of mutant Cbl-transfected NIH 3T3 cells were drastically reduced upon serum starvation, and PDGF-AA substituted for the maintenance of these traits. PDGF-AA stimulation of serum-starved Cbl transfectants induced the in vivo association of transfected Cbl proteins with PDGFR alpha. In vitro, Cbl-N directly bound to PDGFR alpha derived from PDGF-AA-stimulated cells but not to that from unstimulated cells, and this binding was abrogated by a point mutation (G306E) corresponding to a loss-of-function mutation in SLI-1. The Cbl-N/G306E mutant protein, which failed to induce enhanced growth and transformation of NIH 3T3 cells, also failed to induce hyperphosphorylation of PDGFR alpha. Altogether, these findings identify a novel mechanism of Cbl's physiological function and oncogenesis, involving its PTB domain-dependent direct interaction with cellular tyrosine kinases. 相似文献
108.
109.
A E Sumner B Falkner M R Diffenderfer P H Barrett J B Marsh 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1999,221(4):352-360
The purpose of this study was to determine the relationship between insulin resistance and apoB100 metabolism in African American males. Fifteen subjects, 33 +/- 7.6 years old, were divided into two groups, insulin-resistant (IR) or insulin-sensitive (IS), based on the sum of the plasma insulin concentrations during an oral glucose tolerance test. The IR group (n = 8) differed significantly from the IS group (n = 7) with respect to body mass index (BMI) (30.1 vs 23.1 kg/m2; P = 0.0003), fasting triglycerides, (118 vs 54 mg/dl, P = 0. 013), and total plasma apolipoprotein B100 (80 vs 59 mg/dl, P = 0.014). Significantly elevated apoB100 levels in the IR group were seen in very low density lipoprotein (VLDL) (5.1 vs 3.4 mg/dl, P = 0.045) and intermediate density lipoprotein (IDL) (18 vs 12 mg/dl, P = 0.017) but not in low density lipoprotein (LDL) (57 vs 46 mg/dl, P = 0.19). Total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A-I, and blood pressure were not significantly different between the two groups. There was a high correlation between the sum of insulins during the oral glucose tolerance test and the BMI (rho = 0.88, P = 0.0001). In five IR and five IS subjects, apoB100 kinetics were determined in the fasting state using a bolus dose of deuteroleucine and multicompartmental modeling. IR subjects had significantly lower fractional catabolic rates (FCR) in the larger VLDL1 (-70%), the smaller VLDL2 (-71%), and the IDL (-53%) fractions. No significant differences in production rates were observed for any lipoprotein class. There was a significant correlation between the sum of insulins and the FCR of the apoB100 of VLDL1 (rho = -0.65, P = 0.05) and of IDL (rho = -0.85, P = 0.004). The correlation coefficient of the sum of insulins and the FCR of VLDL2 was -0.61 with P = 0.067. We conclude that in this population of African American males, IR is correlated with a decreased FCR of apoB100 in VLDL and IDL and elevated plasma levels of apoB and triglycerides (TG). These changes might be explained by decreased clearance of the TG-rich lipoproteins. We postulate that this may reflect decreased lipoprotein and/or hepatic lipase activity related to insulin resistance and its association with obesity. 相似文献
110.