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61.
PR Jefferies TA Blumenkopf PJ Gengo LC Cole JE Casida 《Canadian Metallurgical Quarterly》1996,39(12):2331-2338
Ryanodine (1) and dehydroryanodine (2) have a polar face formed by cis-hydroxyls at C-2, C-4, C-6, and C-12. The importance of the hydroxyls to the action of 1 and 2 at the ryanodine receptor (ryr) of calcium release channels is examined at [3H]-1 binding sites in brain and skeletal muscle and in heart membranes relative to cardiac contractility, a pharmacologic response which appears to be mediated by the ryr. Five types of changes are considered: blocking the 4- and 6-hydroxyls as cyclic borates and boronates; blocking the 10- and 12-hydroxyls as cyclic phosphates, phosphonates, and phosphoramidates; methylation at nitrogen or hydroxyls at C-4 and C-10; dehydration of the C-2 hydroxyl; additional data for a 4,12-oxygen-bridged series. The first change has little effect on potency possibly due to the lability of the boron protective groups whereas the cyclic phosphorus compounds have reduced activity. Methylation reduces potency the least at nitrogen and the C-4 hydroxyl. Dehydration of 1 to 2-deoxy-2(13)-dehydro-1 allows the restoration of oxygen at C-2 by conversion to epoxides or a diol. One of the epoxides and 2-deoxy-2(13)-dehydro-2 retain 8-31% of ryanodine's potency in the ryr assays and 81% in the cardiac contractility system. In the 4,12-oxygen-bridged series, high potency at the receptor and cardiac muscle is retained in the 4-hydroxy ketal. 相似文献
62.
Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S) 总被引:1,自引:0,他引:1
TR Pedersen AG Olsson O Faergeman J Kjekshus H Wedel K Berg L Wilhelmsen T Haghfelt G Thorgeirsson K Py?r?l? T Miettinen B Christophersen JA Tobert TA Musliner TJ Cook 《Canadian Metallurgical Quarterly》1998,97(15):1453-1460
BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients. 相似文献
63.
Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene 总被引:3,自引:0,他引:3
The authors have designed and constructed a plant-optimize synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E. coli. Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to the bacterial LT-B gene. The plant-derived LT-B assembled into native pentameric structures as evidenced by its ability to bind ganglioside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the anti-LT-B serum IgG and faecal IgA to that produced in mice gavaged with bacterial LT-B. Mice were fed three weekly doses of 5 g tuber tissue containing either 20 or 50 micrograms LT-B, or gavaged weekly with 5 micrograms of LT-B from recombinant E. coli. One week after the third dose, mice immunized with potato LT-B had higher levels of serum and mucosal anti-LT-B than those gavaged with bacterial LT-B. Mice were challenged by oral administration of 25 micrograms LT, and protection assessed by comparing the gut/carcass mass ratios. Although none of the mice were completely protected, the higher dose potato vaccine compared favourably with the bacterial vaccine. These findings show that an edible vaccine against E. coli LT-B is feasible. 相似文献
64.
Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops. 相似文献
65.
Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line. 相似文献
66.
Being a foreign body, intrauterine coil causes decubitus and inflammation of the adjacent tissues. Long-term carriage of the coil may give rise to endometritis, myometritis, parametritis, salpingo-oophoritis, tubo-ovarian inflammatory infiltrates. These infiltrates invade retroperitoneal pelvic fat and may obstruct pelvic ureters. Ureteral obstruction may bring about ureterohydronephrosis, pyelonephritis and renal calculi. The coil may be also responsible for chronic pyelonephritis. The authors have treated 64 females aged 18-45 years with urological complications due to intrauterine coils which stayed from 6 months to 14 years. 34 of them presented with attack of acute pyelonephritis, 29 with renal colic and acute pyelonephritis, 26 with renal calculi. To arrest renal colic and attack of acute pyelonephritis ureteral catheterization and renal pelvis drain were performed in 31 patients. One patient has undergone ureterolithotomy. 8 patients rejected removal of the coil and had recurrent renal colics and acute pyelonephritis attacks. Removal of the coil arrested pyelonephritis and lithogenesis in the kidney. In one case of coil removal there was injury to the uterine cervix and urinary bladder eventuating in vesicovaginal fistula. 相似文献
67.
K Hashimoto C Azuma Y Tokugawa T Nobunaga TA Aki Y Matsui T Yanagida H Izumi F Saji Y Murata 《Canadian Metallurgical Quarterly》1997,28(7):862-865
An unusual clinical presentation of a patient with neuronal intestinal dysplasia is presented. A 46-year-old male noted a palpable mass in the right lower quadrant of his abdomen for two months. A computed axial tomographic scan showed a thickened wall of the cecum with a tumor-like appearance. The excised specimen consisted of a mass caused by the thickened, edematous wall of the dilated cecum and appendix. The wall of the cecum and appendix measured up to 2.5 and 0.8 cm, respectively, in thickness. Microscopic studies showed extensive hyperplasia and hypertrophy of the ganglia and nerve plexuses and hypertrophy of the muscularis propria, consistent with neuronal intestinal dysplasia. 相似文献
68.
选取植物油中典型的多不饱和脂肪酸亚油酸(LA)和α-亚麻酸(ALA)为原料,分为7个不同摩尔浓度配比实验组(组1,LA;组2,10∶1 LA/ALA;组3,5∶1 LA/ALA;组4,1∶1 LA/ALA;组5,1∶5 LA/ALA;组6,1∶10 LA/ALA;组7,ALA)体外评估不同比例n-6/n-3 PUFAs对HepG2细胞炎症因子的影响。结果表明:60μmol/L各实验组均可降低HepG2细胞产生的促炎因子TNF-α和IL-6水平,提高抗炎因子IL-10和抗炎介质LXA4水平,其中组4(1∶1 LA/ALA)作用最显著。 相似文献
69.
在准备金评估中,由于多数随机准备金模型基本假设的限制是不能直接处理含有零值和负值增量赔款三角形,本文利用一个变换和广义线性模型的混合模型去解决这种情况. 相似文献
70.
塔程程 《吉林化工学院学报》2021,38(8):76-79
信息检索课程的系统化讲授,对于大学生优化信息检索行为,提高信息检索使用效率具有不容忽视的教学辅助作用.立足问卷调查形成的一系列相关数据,探讨大学生信息检索行为存在问题,最终在课程教学中提出优化大学生信息检索的对策:明确信息检索目的,提升实施效果;有效提升检索行为实施频率,增强综合质量;使得信息获取多元发展,优化成效凸显... 相似文献