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31.
Pak Hei Chan Jo Jo Hai Esther W. Chan Wen Hua Li Hung Fat Tse Ian C. K. Wong Gregory Y. H. Lip Chung Wah Siu 《PloS one》2016,11(3)
Background
The efficacy and safety of warfarin therapy for stroke prevention in atrial fibrillation (AF) depends on the time in therapeutic range (TTR). We aimed to assess the predictive ability of SAMe-TT2R2 score in Chinese AF patients on warfarin, whose TTR is notoriously poor.Methods and Results
This is a single-centre retrospective study. Patients with non-valvular AF on warfarin diagnosed between 1997 and 2011 were stratified according to SAMe-TT2R2 score, and TTR was calculated using Rosendaal method. The predictive power of SAMe-TT2R2 scores for good TTR i.e. >70% was assessed. We included 1,428 Chinese patients (mean age 76.2±8.7 years, 47.5% male) with non-valvular AF on warfarin. The mean and median TTR were 38.2±24.4% and 38.8% (interquartile range: 17.9% and 56.2%) respectively. TTR decreased progressively with increasing SAMe-TT2R2 score (p = 0.016). When the cut-off value of SAMe-TT2R2 score was set to 2, the sensitivity and specificity to predict TTR<70% were 85.7% and 17.8%, respectively. The corresponding positive and negative predictive values were 10.1% and 92.0%. After a mean follow-up of 4.7±3.6 years, 338 patients developed an ischemic stroke (4.96%/year). Patients with TTR≥70% had a lower annual risk of ischemic stroke of 3.67%/year compared with than those with TTR<70% (5.13%/year)(p = 0.08). Patients with SAMe-TT2R2 score ≤2 had the lowest risk of annual risk of ischemic stroke (3.49%/year) compared with those with SAMe-TT2R2 score = 3 (4.56%/year), and those with SAMe-TT2R2 score ≥4 (6.41%/year)(p<0.001). There was also a non-significant trend towards more intracranial hemorrhage with increasing SAMe-TT2R2 score.Conclusions
The SAMe-TT2R2 score correlates well with TTR in Chinese AF patients, with a score >2 having high sensitivity and negative predictive values for poor TTR. Ischemic stroke risk increased progressively with increasing SAMe-TT2R2 score, consistent with poorer TTRs at high SAMe-TT2R2 scores. 相似文献32.
Cheuk-Yiu Law Chung-Wah Siu Katherine Fan Wing-Hon Lai Ka-Wing Au Yee-Man Lau Lai-Yung Wong Jenny C.Y. Ho Yee-ki Lee Hung-Fat Tse Kwong-Man Ng 《Biochemistry and Biophysics Reports》2016
Patients with Danon disease may suffer from severe cardiomyopathy, skeletal muscle dysfunction as well as varying degrees of mental retardation, in which the primary deficiency of lysosomal membrane-associated protein-2 (LAMP2) is considerably associated. Owing to the scarcity of human neurons, the pathological role of LAMP2 deficiency in neural injury of humans remains largely elusive. However, the application of induced pluripotent stem cells (iPSCs) may shed light on overcoming such scarcity.In this study, we obtained iPSCs derived from a patient carrying a mutated LAMP2 gene that is associated with Danon disease. By differentiating such LAMP2-deficient iPSCs into cerebral cortical neurons and with the aid of various biochemical assays, we demonstrated that the LAMP2-deficient neurons are more susceptible to mild oxidative stress-induced injury.The data from MTT assay and apoptotic analysis demonstrated that there was no notable difference in cellular viability between the normal and LAMP2-deficient neurons under non-stressed condition. When exposed to mild oxidative stress (10 μM H2O2), the LAMP2-deficient neurons exhibited a significant increase in apoptosis. Surprisingly, we did not observe any aberrant accumulation of autophagic materials in the LAMP2-deficient neurons under such stress condition.Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury. 相似文献
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Tse AK Wan CK Shen XL Zhu GY Cheung HY Yang M Fong WF 《Experimental cell research》2007,313(8):1722-1734
1,25-dihydroxyvitamin D(3) (VD(3)) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-kappaB) activity. Here we report a time-dependent biphasic regulation of NF-kappaB in VD(3)-treated HL-60 leukemia cells. After VD(3) treatment there was an early approximately 4 h suppression and a late 8-72 h prolonged reactivation of NF-kappaB. The reactivation of NF-kappaB was concomitant with increased IKK activities, IKK-mediated IkappaBalpha phosphorylation, p65 phosphorylation at residues S276 and S536, p65 nuclear translocation and p65 recruitment to the NF-kappaB/vitamin D responsive element promoters. In parallel with NF-kappaB stimulation, there was an up-regulation of NF-kappaB controlled inflammatory and anti-apoptotic genes such as TNFalpha, IL-1beta and Bcl-xL. VD(3)-triggered reactivation of NF-kappaB was associated with PI3K/Akt phosphorylation. PI3K/Akt antagonists suppressed VD(3)-stimulated IkappaBalpha phosphorylation as well as NF-kappaB-controlled gene expression. The early approximately 4 h VD(3)-mediated NF-kappaB suppression coincided with a prolonged increase of IkappaBalpha protein which require de novo protein synthesis, lasted for as least 72 h and was insensitive to MAPK, IKK or PI3K/Akt inhibitors. Our data suggest a novel biphasic regulation of NF-kappaB in VD(3)-treated leukemia cells and our results may have provided the first molecular explanation for the contradictory observations reported on VD(3)-mediated immune-regulation. 相似文献
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BACKGROUND: Basal cell adenocarcinoma of the parotid is rare and prone to recur. CASE: A 54-year-old woman had a history of afacial mass 12 years earlier that had been excised and was diagnosed as low grade adenocarcinoma of the parotid. Over the years, the patient had multiple local and lymph node recurrences. Histology of the excised local recurrent tumor showed basal cell adenocarcinoma, and FNAC of a separate recurrent nodule was performed. The aspirate showed moderate cellularity of basaloid cells with mildly pleomorphic nuclei, small nucleoli and occasional mitotic figures. The cells were mostly single, but some formed clusters with a rosettelike pattern of tumor cells surrounding central eosinophilic globules. A second, less prominent population of smaller cells with dark-staining nuclei was also noted. The differential diagnosis included adenoid cystic carcinoma, polymorphous low grade adenocarcinoma, and basal cell and pleomorphic adenoma. CONCLUSION: The cytologic features of basal cell adenocarcinoma are not distinctive, but the presence of two cell populations with moderate pleomorphism and a rosettelike pattern with central, eosinophilic globules may assist with its differentiation from other salivary gland neoplasms. 相似文献
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The fungal metabolite, brefeldin A (BFA), is known to inhibit guanine nucleotide exchange on the ADP-ribosylating factors that are involved in vesicle membrane trafficking. Here, we investigated the action of BFA on Ca2+-regulated exocytosis in single rat adrenal chromaffin cells. Incubation of chromaffin cells with BFA (1 or 10 microM) for 2 h effectively disrupted the Golgi membranes but did not affect the pattern of catecholamine release triggered by high extracellular K+, which was monitored with carbon fiber amperometry along with cytosolic Ca2+ measurement. The BFA treatment, however, increased the mean quantal size of catecholamine-containing vesicles and the occurrence of amperometric events with a "foot" or "stand alone" signal (which reflects sluggish or incomplete dilation of the fusion pore). To examine whether BFA altered the Ca2+-dependence of exocytosis, we employed the whole-cell recording technique in conjunction with the capacitance measurement to measure exocytosis evoked from the entire cell during voltage-gated Ca2+ entry. Our results suggested that BFA treatment did not alter either the initial rate of capacitance increase or the total amount of capacitance increase. Therefore, in chromaffin cells, BFA treatment affects Ca2+-regulated exocytosis predominantly by increasing the quantal size and by slowing the fusion kinetics of some vesicles. 相似文献
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