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1.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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Vasopressin (AVP) receptor binding within hypothalamic sites was compared between cycling and lactating female golden hamsters. The density of AVP receptor binding was analyzed by quantitative autoradiography within the ventrolateral hypothalamus and dorsomedial hypothalamic nucleus. Lactation was correlated with a disappearance of AVP receptor binding within the ventrolateral hypothalamus. In contrast, lactation was associated with a two- to three-fold increase in the density of AVP receptor binding within the dorsomedial hypothalamic nucleus. These results suggest that AVP receptor binding within the ventrolateral hypothalamus is responsive to gonadal hormones in female golden hamsters. However, the increase in binding observed within the dorsomedial hypothalamus may be related to other neurobiological changes associated with lactation. 相似文献
3.
Early glottic carcinoma, specifically stage I or II, can be treated with endoscopic excision, radiation therapy, or open partial laryngectomy. Over the past two decades, this topic has received intensive interest, and controversies have often focused on techniques and outcomes comparing the use of endoscopic excision versus radiation therapy. This article will discuss philosophy, techniques, and outcomes of resection using the endoscopic approach to early glottic carcinoma. Optimization through appropriate instrumentation, staging, and technical details are critical to postoperative oncologic and vocal outcomes. The reader must remember that over 90% of T1 lesions and approximately 75% of T2 lesions are curable, and therefore adherence to the principles described below is important to achieve these outcomes. 相似文献
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Respiratory symptoms and lung function in relation to passive smoking: a comparative study of American and French women 总被引:3,自引:0,他引:3
F Kauffmann D W Dockery F E Speizer B G Ferris 《International journal of epidemiology》1989,18(2):334-344
Results are reported from a parallel analysis of the association of passive smoking with respiratory symptoms and lung function (FEV1, FVC and FEV1/FVC) in 2220 US and 3855 French women from the general population examined over the same time period using similar methods. Age, city, educational level, occupational exposure and height (for lung function) were taken into account. In the US survey, being a never smoker married to a current or former smoker was significantly associated only with wheezing compared to being a true never smoker. A borderline significant association between passive smoking and dyspnoea was observed among women older than 40 in the French survey. No association was observed with cough or phlegm production. Passive smoking was significantly related to lower FVC and FEV1 values among French women 40 years or more, even among those without a history of wheeze or asthma. However, even among US women older than 40 years of age, there was no significant association between passive smoking and level of lung function. Better housing conditions, higher divorce rates, more frequent exposure to passive smoking in childhood, and different selection factors for active smoking in the US compared to France might explain the lack of association of current spousal smoking habits with lower lung function in American women. 相似文献
6.
SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a). 相似文献
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C A Wilson E Stefánsson L Klombers L D Hubbard S C Kaufman F L Ferris 《American journal of ophthalmology》1988,106(2):131-134
We measured retinal vessel diameter before and after panretinal photocoagulation in 59 eyes with diabetic retinopathy and moderate to severe optic disk neovascularization. Treatment significantly reduced mean arteriolar and venular diameter. The diameter of the retinal arterioles after treatment correlated significantly with the amount of regression in disk neovascularization. Eyes with large diameter vessels after treatment usually had little or no regression of proliferative retinopathy, whereas regression was more frequently seen in eyes with smaller diameter vessels after treatment. 相似文献
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Variations in Helicobacter pylori lipopolysaccharide to evade the innate immune component surfactant protein D 总被引:2,自引:0,他引:2 下载免费PDF全文
Khamri W Moran AP Worku ML Karim QN Walker MM Annuk H Ferris JA Appelmelk BJ Eggleton P Reid KB Thursz MR 《Infection and immunity》2005,73(11):7677-7686
Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen. 相似文献