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11.
RG Wilde JT Billheimer SJ Germain EA Hausner PC Meunier DA Munzer JK Stoltenborg PJ Gillies DL Burcham SM Huang JD Klaczkiewicz SS Ko RR Wexler 《Canadian Metallurgical Quarterly》1996,4(9):1493-1513
Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds. 相似文献
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From the rhizomes of Polygonatum alte-lobatum, two new homologous series of 1,4-benzoquinones, polygonaquinones A and B, a novel homoisoflavanone, a new gentrogenin glycoside and 13 known compounds were isolated and characterized. The structures of the new compounds were determined as two homologous series of three 2,5-dihydroxy-3-methyl-6-alkyl-1,4-benzoquinones and three 2-hydroxy-3-methyl-6-alkyl-1,4-benzoquinones, with chain lengths C21 to C23, and 4',5,7-trihydroxy-6,8-dimethylhomoisoflavanone and gentrogenin 3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)] -beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside. 相似文献
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Although adenosine receptors have been implicated in the induction of preconditioning in a variety of experimental models, there is controversy concerning the specific adenosine receptor subtypes mediating this effect. Concentration-protection relationships for adenosine and adenosine agonists in rabbit cardiomyocytes were used to characterize the role of adenosine receptor subtypes in preconditioning. Isolated cells were ischemically preconditioned or pre-incubated for 10 min with increasing concentrations of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), APNEA (N6-2-(4-aminophenyl)ethyladenosine), or BNECA (N6-benzyl-5'-N-ethyl-carboxamidoadenosine) in the presence or absence of 1 or 10 microM of the selective A1-adenosine antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine). Following a 30-min post-incubation period, cells were pelleted, layered with oil and ischemically incubated for 180 min. Injury was assessed by osmotic swelling and trypan blue exclusion of sequential samples, and determination of the areas beneath the mortality curves. Adenosine produced a broad concentration-protection curve which was displaced to the right by DPCPX. The curve for A1-selective agonist CCPA was biphasic, with an initial response below 1 nM and a second above 1 microM. DPCPX abolished the early response leaving a steep monophasic curve between 0.1 and 10 microM CCPA. The APNEA curve appeared moriophasic, the major slope occurring between 1-100 nM; DPCPX (1 microM) shifted the concentration-response curve approximately 30-fold and decreased the slope. Adenosine receptor agonist BNECA produced preconditioning characterized by a shallow monophasic concentration-protection curve with a maximal effect of 49% and an EC50 of approximately 5 nM; DPCPX shifted the BNECA concentration-protection relationship approximately 40-fold with only a modest increase in slope. Analysis of the data suggests that induction of preconditioning results from interaction of agonists with the A1 receptor and a second adenosine receptor having properties consistent with the A3 receptor. Adenosine, CCPA, APNEA, BNECA and DPCPX each appear to be selective for the A1 adenosine receptor subtype in isolated rabbit cardiomyocytes. 相似文献
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Time-dependent thrombolytic resistance is a critical problem in thrombolytic therapy for acute myocardial infarction. Platelets have been regarded as the main source of plasminogen activator inhibitor-1 (PAI-1) found in occlusive platelet-rich clots. However, endothelial cells are also known to influence the fibrinolytic capacity of blood vessels, but their ability to actively mediate time-dependent thrombolytic resistance has not been fully established. We will show that, in vitro, tumor necrosis factor-alpha-stimulated endothelial cells secrete large amounts of PAI-1 over a period of hours, which then binds to fibrin and protects the clot from tissue plasminogen activator-induced fibrinolysis. In vivo, endothelial cells covering atherosclerotic plaques are influenced by cytokines synthesized by plaque cells. Therefore, we propose that continuous activation of endothelial cells in atherosclerotic blood vessels, followed by elevated PAI-1 secretion and storage of active PAI-1 in the fibrin matrix, leads to clot stabilization. This scenario makes endothelial cells a major factor in time-dependent thrombolytic resistance. 相似文献
16.
R. W. Rice 《Journal of Materials Science》1996,31(6):1509-1528
An extensive survey of the porosity dependence of (room temperature) physical properties shows that mechanical properties and electrical and thermal conductivity, i.e. properties dependent on the local flux or fields in the material, follow minimum solid area models. This is shown extensively for elastic properties and tensile (flexure) strength, but consistency with other properties, e.g. compressive strength, hardness, electrical and thermal conductivity is also shown. Although data for ceramics is most extensive, data for rocks, metals, and carbon are included, since the consistency of these, especially of metals with ceramics, provides important support for the minimum solid area concept. While porosity characterization is generally minimal, expected model trends with pore character are corroborated by correlating processing and resultant expected pore character with porosity-property results. It is argued that properties dependent on mass should be better fit by a linear, i.e. rule of mixture, relationship between such properties and porosity. Support for this is shown in dielectric constant-porosity data. 相似文献
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The acute and subacute effects of intracerebroventricularly (ICV) administered nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) on locomotor activity were evaluated in awake adult rats. Immediately after ICV injection through an implanted cannula, locomotor activity was measured by a computerized system using infrared photocells, which allowed us to record locomotion, motility, and rearing simultaneously. A single dose of 5 microg mouse beta-NGF produced significant increases in horizontal ambulatory components of locomotor activity (locomotion and motility), but not vertical movement (rearing) 30-45 min after ICV administration. These increases lasted for at least 3-4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic receptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induced marked increases in all three measures of behavior in both NGF and cytochrome-c-treated animals, locomotion and motility remained significantly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomotor activity by inducing acetylcholine release, and that nicotinic receptors are involved in the hyperactivity induced by NGF. ICV administration of 5 microg recombinant human BDNF had no significant effect on locomotor activity during the 0- to 4-h period after ICV injection. However, it produced significant decreases in locomotion, motility, and rearing 24-26 h later. Hence ICV administration of BDNF has entirely different effects on animal behavior from those evoked by NGF. While NGF elicits increases in ambulatory behavior within hours, BDNF causes delayed decreases in ambulatory behavior. 相似文献
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Two forms of glutathione synthetase deficiency have been described. While one form is mild, causing hemolytic anemia, the other more severe form causes 5-oxo-prolinuria with secondary neurological involvement. Despite the existence of two deficiency phenotypes, Southern blots hybridized with a glutathione synthetase cDNA suggest that there is a single glutathione synthetase gene in the human genome. Analysis of somatic cell hybrids showed the human glutathione synthetase gene (GSS) to be located on chromosome 20, and this assignment has been refined to subband 20q11.2 using in situ hybridization. 相似文献