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1.
The selectivity of different external binding sites for quaternary ammonium ions in cloned potassium channels 总被引:1,自引:0,他引:1
W. Jarolimek K. V. Soman M. Alam A. M. Brown 《Pflügers Archiv : European journal of physiology》1995,430(5):672-681
Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K+ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K+ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K+ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C8, C10 chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy. 相似文献
2.
《Expert review of anticancer therapy》2013,13(7):1117-1132
Polo-like kinase 1 (Plk1) inhibitors belong to a new class of drugs for the treatment of malignant diseases. They selectively act against a target (Plk1) which is involved in different stages of mitosis such as centrosome maturation, spindle formation, chromosome separation and cytokinesis. Because Plk1 is mainly expressed in proliferating tissues and overexpressed in cancers, its inhibition is potentially less prone to toxicities associated with current antimitotic agents, which also act on nondividing cells. Several Plk1 inhibitors are being evaluated as cancer treatment drugs. Based on the essential role of Plk1 during mitosis, Plk1 inhibitors target all rapidly dividing cells irrespective of their tumor suppressor or oncogene mutations. In this article, their mechanisms of action, efficacy and toxicity profile are discussed. 相似文献
3.
Yu Sato Akiomi Yoshihisa Yusuke Kimishima Takatoyo Kiko Shunsuke Watanabe Yuki Kanno Satoshi Abe Makiko Miyata Takamasa Sato Satoshi Suzuki Masayoshi Oikawa Atsushi Kobayashi Takayoshi Yamaki Hiroyuki Kunii Kazuhiko Nakazato Takafumi Ishida Yasuchika Takeishi 《The Canadian journal of cardiology》2018,34(1):80-87
Background
It is widely recognized that overt hyper- as well as hypothyroidism are potential causes of heart failure (HF). Additionally it has been recently reported that subclinical hypothyroidism (sub-hypo) is associated with atherosclerosis, development of HF, and cardiovascular death. We aimed to clarify the effect of sub-hypo on prognosis of HF, and underlying hemodynamics and exercise capacity.Methods
We measured the serum levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4) in 1100 consecutive HF patients. We divided these patients into 5 groups on the basis of plasma levels of TSH and FT4, and focused on euthyroidism (0.4 ≤ TSH ≤ 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 911; 82.8%) and sub-hypo groups (TSH > 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 132; 12.0%). We compared parameters of echocardiography, cardiopulmonary exercise testing, and cardiac catheterization, and followed up for cardiac event rate and all-cause mortality between the 2 groups.Results
Although left ventricular ejection fraction did not differ between the 2 groups, the sub-hypo group had lower peak breath-by-breath oxygen consumption and higher mean pulmonary arterial pressure than the euthyroidism group (peak breath-by-breath oxygen consumption, 14.0 vs 15.9 mL/min/kg; P = 0.012; mean pulmonary arterial pressure, 26.8 vs 23.5 mm Hg, P = 0.020). In Kaplan-Meier analysis (mean 1098 days), the cardiac event rate and all-cause mortality were significantly higher in the sub-hypo group than those in the euthyroidism group (log rank, P < 0.01, respectively). In Cox proportional hazard analysis, sub-hypo was a predictor of cardiac event rate and all-cause mortality in HF patients (P < 0.05, respectively).Conclusions
Sub-hypo might be associated with adverse prognosis, accompanied by impaired exercise capacity and higher pulmonary arterial pressure, in HF patients. 相似文献4.
Ke Yang Fei Wang Dingshan Duan Tianli Zhang Chuanguang Luo Yann Cressault Zhishui Yu Lijun Yang Huan Li 《Materials》2021,14(2)
Multi-wire welding has received much attention in the machinery industry due to its high efficiency. The aim of this study was to investigate a novel pulse gas metal arc welding (GMAW) that has circular triple-wire electrodes. The effect of the pulse phage angle on arc stability was particularly studied. Research showed that for typical phase angles the arc stability from low to high is 180°, 0°, and 120°, and the arcs are very stable at 120°. The triple-wire welding was used to weld a 9 mm thick Q960E steel, which is typically used for the arm of construction machinery. When the welding heat input was controlled at 1.26–1.56 kJ/mm, the weld zone was dominated by acicular ferrite, and the coarse-grained zone of the heat-affected zone was a mixed structure of lath martensite and lath bainite. The tensile strength of the welded joint reached 85% of the base metal and the impact toughness was above 62 J, which can meet the requirements of construction machinery. This indicates that the triple-wire welding has great potential to achieve efficient and high-quality welding for the construction machinery. 相似文献
5.
[目的]探讨BACTEC MGIT 960仪在肺结核病诊断中的应用。[方法]应用BACTEC MGIT 960仪对肺结核病人的痰标本进行培养,并与BACTEC TB 460仪、改良罗氏培养法及涂片抗酸染色法进行对照。[结果]BACTEC MGIT 960仪阳性率为31.96%,与BACTEC TB 460仪的阳性率接近,比改良罗氏培养法及涂片抗酸染色法高。[结论]BACTEC MGIT 960仪能显著缩短(初代阳性平均分离时间为11.6d,比BACTEC TB 460仪快1.9d,比改良罗氏培养法快9.1d。)报告时间,且阳性检出率高。 相似文献
6.
液体培养基比色法快速检测结核分枝杆菌耐药性 总被引:4,自引:0,他引:4
目的探讨液体培养基比色法在结核分枝杆菌(MTB)耐药性快速测定中的应用价值。方法将MTB分别接种于含药和不含药的液体培养基中,37℃培养6d,然后加入NaNO3试剂,37℃培养1d,进行硝酸盐还原检测试验。根据液体培养基颜色变化情况,判断药敏结果。将检测结果与Bactec.960测定结果比较,分析硝酸盐还原酶比色法检测MTB耐药性的敏感性、特异性和准确性。结果以Bactee.960检测结果为判断标准,液体培养基比色法检测链霉素、异烟肼、利福平和乙胺丁醇耐药性结果与Bactec.960的符合率分别为100.0%、96.9%、98.1%和97.5%。结论液体培养基比色法检测MTB耐药性具有很高的敏感性和特异性,且需时较短、操作简便、结果准确、不需特殊仪器设备,可作为MTB耐药性的快速筛选方法。 相似文献
7.
When Schaudinn and Hoffmann made the initial discovery of T. pallidum in 1905, they did so with an ordinary light microscope. The difficulty of visualizing the pale treponeme under those circumstances will become apparent immediately to anyone who cares to try it, and the virtual transparency of the organism was, of course, the feature that led to Schaudinn's choice of “pallida” (and later “pallidum”) for the species name of his find. Shortly after the discovery, several German optical firms exhibited prototypes of the newly developed darkfield microscopes, and, in 1906, Landsteiner and Mucha1 were the first to recommend the use of these instruments to demonstrate T. pallidum. Within a year, darkfield microscopy had become almost routine in the investigation of early and congenital syphilis in the European clinics. The procedure was introduced into the United States in 1909 by Udo Wile,2 and a survey of the literature of the period shows that by 1914 a recognition of both the strengths and weaknesses of the technique and an understanding of the morphology of the organisms likely to be encountered were remarkably complete.The strongest indications for the use of the darkfield in the current management of venereal disease exist in two special situations: 1) the investigation of lesions in suspected cases of congenital syphilis and 2) the search for organisms in suspected cases of primary syphilis, especially during the initial period of seronegativity. The procedure has lost ground in the latter situation, owing in part to the increasing effectiveness of the newer treponemal and nontreponemal tests in detecting the presence of the disease in its earliest state; but it is premature to conclude, as in the recent statement by one experienced venereologist, that “in the foreseeable future the darkfield examination will be of historical interest, except for those in research.”3The purpose of this section is to summarize the technique and the findings to be expected in the darkfield and other methods employed in the examination of material taken directly from early syphilitic lesions. A step-by-step method for combining the results of these procedures and the results of physical examination and serologic testing to make the diagnosis of infectious syphilis is given in Chapter 11. 相似文献
8.
9.
BACTEC MGIT^TM960全自动分枝杆菌培养鉴定/药敏仪,能大大缩短分枝杆菌的检测时间,该仪器自动化程度高,无放射性污染,可进行药敏学动态研究。 相似文献
10.
Kenichi Otoshi Shinichi Kikuchi Kinshi Kato Ryohei Sato Takahiro Igari Takahiro Kaga Shinichi Konno 《Journal of orthopaedic science》2018,23(6):942-947