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排序方式: 共有1960条查询结果,搜索用时 15 毫秒
1.
RB Penn JL Parent AN Pronin RA Panettieri JL Benovic 《Canadian Metallurgical Quarterly》1999,288(2):428-437
The use of pharmacological inhibitors of protein kinases represents a potentially powerful tool in dissecting the regulatory features of intracellular signaling pathways. However, although the in vitro potency, selectivity, and efficacy of numerous kinase inhibitors have been characterized, little is known regarding the usefulness of these compounds as inhibitors in intact cells. In attempting to characterize the role of protein kinase A (PKA) in regulating the beta-2 adrenergic receptor (AR) in human airway cells, we observed a seemingly profound capacity of the isoquinoline H-89, a potent and widely used PKA inhibitor, to attenuate agonist-mediated desensitization of the beta-2 AR. Although additional experiments identified H-89 as an effective inhibitor of intracellular PKA, extended analysis of the compound determined the principal effect of H-89 was via its action as a beta-2 AR antagonist. Pretreatment with or the acute addition of H-89 significantly attenuated isoproterenol-stimulated cAMP accumulation. In cells pretreated with H-89 and then washed extensively, the subsequent dose-dependent response to isoproterenol suggested beta-2 AR antagonism by retained H-89. Competition binding of [125I]iodopindolol established Ki values of approximately 180 nM and 350 nM for H-89 antagonism of beta-2 AR and beta-1 AR, respectively. Additional receptor binding studies suggest selectivity of H-89 for the beta-2 AR and beta-1 AR, although a weak antagonism (Ki values of approximately 10 microM or greater) of other G protein-coupled receptors was observed. Results from additional pharmacological and biochemical analyses of various protein kinase inhibitors further established the need for careful characterization of pharmacological inhibitors when used in intact cell models. 相似文献
2.
R Lewis S Kapur C Jones J DaSilva GM Brown AA Wilson S Houle RB Zipursky 《Canadian Metallurgical Quarterly》1999,156(1):72-78
BACKGROUND: In the FRISC trial, dalteparin 120 IU/kg body weight twice daily for unstable coronary artery disease was safe and reduced the risk of new coronary events. This risk reduction was maintained during the following extended treatment with a fixed dose of 7500 IU dalteparin once daily. METHODS AND RESULTS: Minor bleeding was more frequent in women compared with men: relative risk (CI) 2.88 (1.78 to 4.67) during the weight-adjusted and 2.36 (1.37 to 2.63) during the fixed dose treatment. The anti-Xa activity determined in samples (n = 175) obtained during the acute phase treatment was higher in women compared with men (P <.001) and in nonsmokers compared with smokers (<.001) in multiple regression analysis. Also, during the fixed-dose treatment (n = 131) an independent relation between anti-Xa activity and sex (P <.001), but not smoking habits, persisted. CONCLUSION: To improve future low-molecular-weight heparin dose regimens for the treatment of acute coronary syndromes, it might be important to consider the influence of sex and smoking habits. 相似文献
3.
The inhibition of arylamine N-acetyltransferase (NAT) activity by ibuprofen was determined in a human colon tumour (adenocarcinoma) cell line. Two assay systems were employed, one with cellular cytosols (9000 g supernatant) and the other with intact colon tumour cell suspensions. The NAT activity in a human colon tumour cell line was inhibited by ibuprofen in a dose-dependent manner in both systems, i.e. the greater the concentration of ibuprofen in the reaction, the greater the inhibition of NAT activities in both systems. The data also indicated that ibuprofen decreases the apparent Km and Vmax of NAT enzyme from human colon tumour cells in both systems examined. This report is the first demonstration to show that ibuprofen affects human colon tumour cell NAT activity. 相似文献
4.
RB Everett 《Canadian Metallurgical Quarterly》1999,6(1):65-69
Radiologic assessment of fracture reduction in displaced supracondylar fractures of the elbow in children is notoriously difficult. The Baumann angle is often used as a guide to the adequacy of reduction. This is based on the assumption that the Baumann angle has a constant relationship to the carrying angle in a displaced fracture. The effect of rotation on the relationship between these angles has not been studied in detail. Computed tomography (CT) studies have shown that < or = 40 degrees of rotation may still be present after closed manipulation of a supracondylar fracture. A computer programme analysing vectors was designed to study the relationship between the Baumann angle and the carrying angle with predetermined displacements of the distal fragment. The relationship between the Baumann angle and the carrying angle was thus defined and, in contrast to the literature, found to be more complex than previously appreciated. The Baumann angle was found to be an inaccurate indicator of the carrying angle when treating displaced supracondylar fractures. 相似文献
5.
Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse. 相似文献
6.
Immunization with a particulate fraction of blood-stage antigens was shown previously to protect mice against Plasmodium yoelii malaria. To identify antigens inducing the protective response, sera from immunized mice were used to screen a P. yoelii cDNA expression library. Sequence analysis of one 2.6-kb cDNA clone indicated that the identified gene, pypag-1, encoded a novel plasmodial antigen. Two nonoverlapping regions of pypag-1 were expressed in Escherichia coli. The first recombinant antigen, pAg-1N, contained the N-terminal 337 residues, which included a putative transmembrane domain and a region relatively rich in tryptophan residues. The second recombinant antigen, pAg-1C, contained the remaining C-terminal 211 residues, which included 31 copies of a 5-amino-acid degenerative repeat. Immunoblot studies using rabbit antiserum raised against recombinant pAg-1N showed that the native pypAg-1 protein migrated at approximately 98 kDa, considerably slower than its predicted molecular mass of 66 kDa. Immunofluorescence studies localized the expression of the native pypAg-1 protein both to the cytoplasm and at the surface of P. yoelii-infected erythrocytes. Immunization with either pAg-1N or pAg-1C induced a four- to sevenfold reduction in P. yoelii blood-stage parasitemia. As such, pypAg-1 appears to contain at least two distinct protective epitopes. To our knowledge, this is the first characterization of a protective antigen of P. yoelii that is associated with the erythrocyte membrane. 相似文献
7.
C. Boztug J. R. Sánchez‐Pérez F. F. Sudradjat RB Jacobson D. M. Paskiewicz M. G. Lagally R. Paiella 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(4):622-630
The use of tensilely strained Ge nanomembranes as mid‐infrared optical gain media is investigated. Biaxial tensile strain in Ge has the effect of lowering the direct energy bandgap relative to the fundamental indirect one, thereby increasing the internal quantum efficiency for light emission and allowing for the formation of population inversion, until at a strain of about 1.9% Ge is even converted into a direct‐bandgap material. Gain calculations are presented showing that, already at strain levels of about 1.4% and above, Ge films can provide optical gain in the technologically important 2.1–2.5 μm spectral region, with transparency carrier densities that can be readily achieved under realistic pumping conditions. Mechanically stressed Ge nanomembranes capable of accommodating the required strain levels are developed and used to demonstrate strong strain‐enhanced photoluminescence. A detailed analysis of the high‐strain emission spectra also demonstrates that the nanomembranes can be pumped above transparency, and confirms the prediction that biaxial‐strain levels in excess of only 1.4% are required to obtain significant population inversion. 相似文献
8.
The relationship of education to blood pressure: findings on 40,000 employed Chicagoans 总被引:3,自引:0,他引:3
The relationship of education to both actual blood pressure and the prevalence of high blood pressure, based on a systolic pressure of 160 mm Hg or greater or a diastolic pressure of 95 mm Hg or greater, was analyzed among 27,033 men and women, white and black, age 25-44 and 45-64, from the Chicago Heart Association Detection Project in Industry. The educational status of each individual was categorized as not a high school graduate, high school graduate, some college, or college graduate. A statistically significant inverse association between education and high blood pressure was present in all groups of whites. This association could not be "accounted for" by differences in age, relative weight, and heart rate among the educational strata. Controlling for these variables did, however, lessen the association. Among black males a significant inverse association between education level and blood pressure was found for the younger group. For the older black males there was a clear inverse association although with the small numbers it did not achieve statistical significance. For black females there was no clear association. 相似文献
9.
The influence of polymer surface-protein binding affinity on protein ion signals in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is examined. The surfaces of poly(vinylidene fluoride) and poly(ethylene terephthalate) polymer substrates are modified by pulsed rf plasma deposition of allylamine. By varying the on/off duty cycle of the pulsed rf plasma, the polymer substrate surfaces are coated with thin films having varying densities of surface amine groups. The varying surface amine density is shown to lead to systematic changes in the surface binding affinity for the 125I-radiolabeled peptides angiotensin I and porcine insulin. Unlabeled angiotensin I and porcine insulin are then deposited on the pulsed rf plasma-modified substrates and analyzed by MALDI mass spectrometry. The experimental approach involves applying the peptide to the modified polymer surface in an aqueous phosphate-buffered saline solution and allowing the peptide solution to dry completely under ambient conditions. Subsequently, the MALDI matrix alpha-cyano-4-hydroxycinnamic acid in methanol and 10% trifluoroacetic acid in water are added to the peptide-coated modified polymer surfaces. The results of these studies demonstrate that, for the sample preparation method employed, increases in the surface peptide binding affinity lead to decreases in the peptide MALDI ion signal. 相似文献