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131.
An N-methyl-D-aspartate receptor channel blocker with neuroprotective activity 总被引:3,自引:0,他引:3
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Tai KK Blondelle SE Ostresh JM Houghten RA Montal M 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(6):3519-3524
Excitotoxicity, resulting from sustained activation of glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype, is considered to play a causative role in the etiology of ischemic stroke and several neurodegenerative diseases. The NMDA receptor is therefore a target for the development of neuroprotective agents. Here, we identify an N-benzylated triamine (denoted as NBTA) as a highly selective and potent NMDA-receptor channel blocker selected by screening a reduced dipeptidomimetic synthetic combinatorial library. NBTA blocks recombinant NMDA receptors expressed in Xenopus laevis oocytes with a mean IC(50) of 80 nM; in contrast, it does not block GluR1, a glutamate receptor of the non-NMDA subtype. The blocking activity of NBTA on NMDA receptors exhibits the characteristics of an open-channel blocker: (i) no competition with agonists, (ii) voltage dependence, and (iii) use dependence. Significantly, NBTA protects rodent hippocampal neurons from NMDA receptor, but not kainate receptor-mediated excitotoxic cell death, in agreement with its selective action on the corresponding recombinant receptors. Mutagenesis data indicate that the N site, a key asparagine on the M2 transmembrane segment of the NR1 subunit, is the main determinant of the blocker action. The results highlight the potential of this compound as a neuroprotectant. 相似文献
132.
Aims/hypothesis The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association.Methods A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric.Results No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69–0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51–0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78–1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24–32% was observed among the three subgroups, although statistical significance was reached only among Asians.Conclusions/interpretation The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians. 相似文献
133.
Epidemiological studies have shown several strong predictors for selecting Japanese persons at high risk for esophageal squamous
cell carcinoma (ESCC). (1) Alcohol consumption and tobacco smoking synergistically increase the risk, and a low intake of
green and yellow vegetables or fruit and a low body mass index also increase the risk of ESCC. (2) The presence of esophageal
distinct iodine-unstained lesions and melanosis are associated with an increased risk of ESCC. (3) The combination of alcohol
consumption and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) and less-active homozygous alcohol dehydrogenase-1B
(ADH1B) increases the risk of ESCC in a multiplicative fashion. (4) The results of a simple flushing questionnaire predict
the ALDH2 phenotype with a high accuracy. (5) High mean corpuscular volume (MCV), which is induced by heavy drinking, high
acetaldehyde exposure, heavy smoking, and poor nutrition, may be useful in identifying high-risk persons. Endoscopic screening
with esophageal iodine staining in Japanese high-risk populations yields very high rates of early ESCC. Treatment of early
ESCC by endoscopic mucosectomy has become a widespread practice in Japan and has succeeded in improving the outcome of this
high-mortality cancer. New evidence concerning ALDH2/ADH1B/alcohol flushing/MCV-related cancer susceptibility has renewed
interest in alcohol and acetaldehyde as important subjects for cancer research and has served as a powerful tool for cancer
prevention and cancer screening of Japanese subjects.
Review articles on this topic also appeared in the previous issue (Volume 4 Number 3). An editorial related to this article
is available at . 相似文献
134.
Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype 总被引:1,自引:0,他引:1
Graham JB; Rizza CR; Chediak J; Mannucci PM; Briet E; Ljung R; Kasper CK; Essien EM; Green PP 《Blood》1986,67(6):1554-1559
Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection. 相似文献
135.
Previous studies have identified inhibitory deficits in dyslexic children, but we have little understanding of their neural mechanisms, especially for Chinese children with developmental dyslexia.We used a double-blind controlled trial to study the electroencephalogram responses of dyslexic and non-dyslexic children when performing the Stroop color-word test.Behavioral data showed differences in response time and accuracy between the 2 groups. In the event-related potentials (ERP) results, dyslexic children displayed larger P2 and P3b on congruent trials, while non-dyslexic children displayed larger P2 and P3b on incongruent trials, the 2 groups showed opposite brain activation patterns on the Stroop test.Dyslexic children have poor inhibitory function, and this poor inhibition may be related to their abnormal brain activation patterns. 相似文献
136.
Functional characterization of the crista terminalis in patients with atrial flutter: implications for radiofrequency ablation 总被引:1,自引:0,他引:1
Liu TY Tai CT Huang BH Higa S Lin YJ Huang JL Yuniadi Y Lee PC Ding YA Chen SA 《Journal of the American College of Cardiology》2004,43(9):1639-1645
OBJECTIVES: The aim of the study was to investigate the conduction properties and anisotropy of the crista terminalis (CT) in patients with atrial flutter (AFL) using non-contact mapping. BACKGROUND: The CT is a posterior barrier during typical AFL. However, the CT has transverse conduction capabilities in patients with upper loop re-entry (ULR). METHODS: Twenty-two patients (16 males, 63 +/- 15 years) with typical AFL and ULR were included. Non-contact mapping of the right atrium during AFL and pacing from coronary sinus (CS) and low anterolateral right atrium (LARA) was performed to evaluate transverse conduction across the CT. During ULR, the longitudinal (CV(L)) and transverse (CV(T)) conduction velocity along and across the CT were measured. The width of the CT conduction gap was evaluated to guide radiofrequency ablation (RFA). RESULTS: No transverse CT gap conduction was found during typical AFL. Transverse CT gap conduction was found in three patients during CS pacing and in three patients during LARA pacing. During ULR, CV(L) was greater than CV(T) (1.28 +/- 0.43 vs. 0.73 +/- 0.30 m/s, p < 0.001). The CV(L)/CV(T) ratio was 1.95 +/- 0.77, which was inversely related to the CT gap width (15.7 +/- 6.8 mm) (p < 0.001). The RFA of the CT gap was successful in 18 patients. Four patients had recurrence of arrhythmias during the follow-up of 11 +/- 3 months. CONCLUSIONS: Most of the CT conduction gaps were functional and only appeared during ULR. The width of the CT gap was inversely related to the anisotropic ratio of the CT. The RFA of the CT gap was effective in eliminating ULR. 相似文献
137.
Chen YJ Tai CT Chiou CW Wen ZC Chan P Lee SH Chen SA 《Journal of cardiovascular electrophysiology》1999,10(12):1578-1585
INTRODUCTION: Patients receiving VVI pacemakers have a higher incidence of paroxysmal atrial fibrillation (AF) than those receiving DDD pacemakers. However, the mechanism behind the difference is not clear. The purpose of this study was to investigate whether atrial electrophysiology and the autonomic nervous system play a role in the occurrence of AF during AV pacing. METHODS AND RESULTS: The study population consisted of 28 patients who had (group I, n = 15) or did not have (group II, n = 13) AF induced by a single extrastimulus during pacing with different AV intervals. Atrial pressure, atrial size, atrial effective refractory periods, and atrial dispersion were evaluated during pacing with different AV intervals. Twenty-four-hour heart rate variability and baroreflex sensitivity also were examined. Atrial pressure, atrial size, effective refractory periods in the right posterolateral atrium and distal coronary sinus, and atrial dispersion increased as the AV interval shortened from 160 to 0 msec. During AV pacing, group I patients had greater minimal (52+/-17 vs 25+/-7 msec; P < 0.005) and maximal (76+/-16 vs 36+/-9 msec; P < 0.005) atrial dispersion than group II patients. The differences in atrial size and atrial dispersion among different AV intervals were greater in patients with AF than in those without AF. Baroreflex sensitivity (6.6+/-1.7 vs 3.9+/-1.0; P < 0.00005), but not heart rate variability, was higher in patients with AF than in those without AF. CONCLUSION: Abnormal atrial electrophysiology and higher vagal reflex activity can play important roles in the genesis of AF in patients receiving pacemakers. 相似文献
138.
Insulin receptors on leukemia and lymphoma cells 总被引:1,自引:0,他引:1
Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia. 相似文献
139.
Truong Thi Vu Nu Nhu Hoa Thi Tran Eunjoo Nam Tan Tai Nguyen Won Jung Yoon Sungbo Cho Jungsuk Kim Keun-A. Chang Heongkyu Ju 《RSC advances》2018,8(14):7855
We present the immunoassay of tau proteins (total tau and phosphorylated tau) in human sera using surface plasmon resonance (SPR) fiber sensors. This assay aimed at harvesting the advantages of using both SPR fiber sensors and a blood-based assay to demonstrate label-free point-of-care-testing (POCT) patient-friendly assay in a compact format for the early diagnosis of Alzheimer''s disease (AD). For conducting the assay, we used human sera of 40 subjects divided into halves, which were grouped into AD patients and control groups according to a number of neuropsychological tests. We found that on an average, the concentrations of both total tau and phosphorylated tau proteins (all known to be higher in cerebrospinal fluid (CSF) and the brain) turned out to be higher in human sera of AD patients than in controls. The limits of detection of total tau and phosphorylated tau proteins were 2.4 pg mL−1 and 1.6 pg mL−1, respectively. In particular, it was found that the AD group exhibited average concentration of total tau proteins 6-fold higher than the control group, while concentration of phosphorylated tau proteins was 3-fold higher than that of the control. We can attribute this inhomogeneity between both types of tau proteins (in terms of increase of control-to-AD in average concentration) to un-phosphorylated tau proteins being more likely to be produced in blood than phosphorylated tau proteins, which possibly is one of the potential key elements playing an important role in AD progress.Blood-based early diagnosis of Alzheimer''s disease using a plasmonic fiber sensor that detects immunoreaction of tau proteins. 相似文献
140.
Dawei Ji Changfa Xiao Shulin An Hailiang Liu Kaikai Chen Junqiang Hao Tai Zhang 《RSC advances》2018,8(18):10097
Polysulfone (PSF)/fluorinated ethylene propylene (FEP) mixed matrix membranes (MMMs) with super hydrophobic surface were successfully fabricated via non-solvent induced phase separation (NIPS) method. The effects of FEP content on the morphology, roughness, wettability, pore size, and mechanical property of PSF/FEP MMMs were characterized by scanning electron microscope, confocal microscopy, contact angle goniometer, mercury porosimetry, and tensile testing instrument, respectively. When the FEP content was 9 wt%, the average roughness of M-4 reached 0.712 μm. Meanwhile, the water contact angle (CA) and the water sliding angle (SA) was 153.3° and 6.1°, respectively. M-4 showed super hydrophobicity with a micro- and nanoscale structure surface. Then, M-4 was used for separating of water-in-oil emulsion, showing high separation efficiency for water-in-kerosene and water-in-diesel emulsions of 99.79% and 99.47%, respectively. The flux and separation efficiency changed slightly after 10 cycles. Therefore, this study indicated that the obtained PSF/FEP MMM with super hydrophobic surface could be used for efficient water-in-oil emulsion separation.The PSF/FEP membrane with super hydrophobic and super oleophilic surface had an outstanding separation performance for water-in-oil emulsion. 相似文献