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81.
82.
Hsu LC Ali SR McGillivray S Tseng PH Mariathasan S Humke EW Eckmann L Powell JJ Nizet V Dixit VM Karin M 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(22):7803-7808
NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1beta. Yet, the molecular mechanism by which NOD2 can stimulate IL-1beta secretion, and its biological significance were heretofore unknown. We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1beta processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. Importantly, Bacillus anthracis infection induces IL-1beta secretion in a manner that depended on caspase-1 and NOD2. In vitro, Anthrax lethal toxin strongly potentiated IL-1beta secretion, and that response was NOD2 and caspase-1-dependent. Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion. 相似文献
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84.
Nonpharmacological therapy for malignant ventricular arrhythmias: Implantable defibrillator trials 总被引:2,自引:0,他引:2
Sanjeev Saksena Gunter Breithardt Paul Dorian H. Leon Greene Nandini Madan Michael Block 《Progress in cardiovascular diseases》1996,38(6):429-444
Implantable cardioverter-defibrillators (ICDs) are an important nonpharmacological option in the treatment of malignant ventricular arrhythmias. Technological advances in current devices permit nonthoracotomy implantation with transvenous lead systems using biphasic shocks. Decreasing device size has resulted in pectoral implantation. Battery longevity is still short in comparison with that of pacemakers. Lead failure rates as well as pacing thresholds are significantly higher than those for cardiac pacing lead systems. Other complications of ICD systems include infection, perforation, and thrombosis. The long-term performance of nonthoracotomy lead systems for ICD devices has now been extensively studied. Sudden death recurrence rates for these systems are less than 2% in 3 years and less than 5% at 5 years. Clinical trials with both monophasic and biphasic systems show a high degree of prevention of sudden death. Comparison of ICD outcome with that of drug therapy in three large retrospective studies and two small prospective randomized trials favors improved survival and sudden death prevention with device therapy. However, these studies need corroboration from large prospective trials. Two large prospective trials, CIDS and the AVID study, are now in progress to address this issue. 相似文献
85.
Sanjeev Saksena 《Journal of interventional cardiac electrophysiology》2004,10(3):189-189
Editorial Introduction
The Journal Evolves 相似文献86.
Atul Prakash Sanjeev Saksena Ryszard B. Krol Artur Filipecki George Philip 《Journal of interventional cardiac electrophysiology》2002,6(2):165-172
Atrial flutter or tachycardia may coexist with atrial fibrillation [AF] and can be treated with ablation techniques in attempt to reduce the total AF burden. The role of ablation of latent atrial tachyarrhythmias elicited at electrophysiologic study in conjunction with atrial pacing and antiarrhythmic drugs in patients with refractory AF has not been evaluated. We evaluated the efficacy of catheter ablation of electrically induced atrial flutter or atrial tachycardia in improving rhythm control in patients with refractory AF. Methods: Consecutive patients with refractory AF, and spontaneous atrial flutter (Group 1) or without spontaneous atrial flutter (Group 2) underwent programmed stimulation in a baseline drug-free state. All patients had electrically induced atrial flutter or tachycardia. Radiofrequency ablation of the arrhythmia substrate was performed in all patients. Primary endpoints evaluated for patient outcome in both groups included maintenance of rhythm control and freedom from recurrent atrial tachyarrhythmias. Results: Forty-three patients, with a mean age of 66±13 years were studied. Group 1 consisted of 22 patients while Group 2 had 21 patients. Ablation of the tricuspid valve-inferior venacaval isthmus was performed in 41 patients who had common atrial flutter induced at electrophysiologic study. Ablation of other atrial sites was performed in 8 patients with induced atypical flutter and 4 patients with induced atrial tachycardia. Ten of these patients had ablation of more than one arrhythmia. 17 patients (40%) had atrial pacing instituted and 28 patients remained on a class 1/3 antiarrhythmic drug. During a mean follow-up of 26±14 months, 33 patients (82.5%) remained in rhythm control. Actuarial analysis showed 96% of patients in rhythm control at 6 months, 94% at 12 months, and 90% at 24 months. Freedom from symptomatic AF recurrence was 64% at 6 months, 58% at 12 months, and 42% at 24 months. The outcome for both of these endpoints was similar for Group 1 and Group 2 (p = NS). The AF free interval increased significantly from 7±9 days to 172±121 days (p < 0.01) after ablation. This increase was again similar in both the groups. In the 14 patients were who did not receive atrial pacing and who remained on the same class 1/3 antiarrhythmic drug, the AF free interval increased from 18±17 days to 212±102 days (p < 0.01).
Conclusions: We conclude that electrophysiologic studies can elicit latent atrial flutter or tachycardia in patients with refractory AF without spontaneous monomorphic atrial tachyarrhythmias. Catheter ablation of electrically induced atrial flutter or tachycardia either alone, or with atrial pacing and with antiarrhythmic drug may improve rhythm control and reduce AF recurrences. This is similar in patients with and without spontaneous atrial flutter and refractory AF. 相似文献
87.
Integrin and extracellular matrix interactions regulate engraftment of transplanted hepatocytes in the rat liver 总被引:2,自引:0,他引:2
BACKGROUND & AIMS: Recognition and circumvention of the hepatic endothelial barrier is critical in the engraftment of transplanted cells. We examined whether interactions between integrin and extracellular matrix component receptors could be manipulated for improving transplanted cell engraftment and liver repopulation. METHODS: Fischer 344 rat hepatocytes were transplanted into syngeneic dipeptidyl peptidase IV-deficient rats. Coating of cells or of liver sinusoids with natural collagen, natural laminin, or an engineered fibronectin-like polymer was studied with analysis of cell engraftment and liver repopulation using histologic and molecular assays. Focal adhesion complexes were identified by vinculin immunostaining. The role of integrin receptors in cell engraftment was analyzed with RGD peptide inhibition assays. RESULTS: Coating of cells with extracellular matrix components before transplantation did not enhance cell engraftment. In contrast, intraportal infusion of collagen or fibronectin-like polymer in recipients prior to cell transplantation increased cell engraftment. Adherence of transplanted cells to the hepatic endothelium resulted in rapid activation of vinculin-containing focal adhesion complexes. Superior cell engraftment in animals treated with fibronectin-like polymer was RGD sensitive, verifying the integrin-dependent nature of this process. Moreover, studies in the retrorsine-partial hepatectomy rat model showed that intraportal infusion of the fibronectin-like polymer before cell transplantation significantly accelerated liver repopulation. CONCLUSIONS: Integrin-extracellular matrix component interactions can be manipulated for enhancing cell engraftment in the liver. Such mechanisms will be relevant for engraftment of other cell types and for strategies concerning liver-directed cell therapy. 相似文献
88.
Objective
We report prevalence and risk factors of metabolic syndrome (MS) in the obese workforce of organized sector in hill city of Himachal Pradesh (HP), India.Methods
The cross-sectional survey study of employees of organized sectors in Shimla city of HP, India, was conducted to collect data of demographics, health behavior, psychosocial factors, anthropometry, blood pressure, and blood chemistry to measure blood glucose and lipid profile in fasting state in 3004 employees using validated tools. Out of 3004 subjects screened, data of 418 subjects with body mass index of ≥30 are analyzed to estimate the prevalence of MS and its risk determinants. The association of demographics, health behavior, and psychosocial factors as the risk determinants were analyzed using multivariable logistic regression modeling.Results
MS was prevalent in 57.6% [95% confidence interval (CI): 52.8%–62.3%]. The central obesity (odds ratio: 10.6, 95% CI: 2.32–48.4) and consumption of frequent or daily alcohol (odds ratio: 1.94, 95% CI: 1.05–3.59),and extra salt (odds ratio: 3.34, 95% CI: 1.09–10.2) were independent risk factors for MS. The consumption of tobacco, vegetables, sugar-sweetened drinks, physical inactivity, and psychosocial factors had no significant association with MS in obese population.Conclusions
MS is highly prevalent among obese employees of organized sector. The consumption of alcohol and extra salt were major behavioral risk factors for MS and therefore have important implications in behavioral modifications for prevention of MS among obese employees in organized sectors. 相似文献89.
Ashwani Khurana Deok Jung-Beom Xiaoping He Sung-Hoon Kim Robert C. Busby Laura Lorenzon Massimo Villa Alfonso Baldi Julian Molina Matthew P. Goetz Viji Shridhar 《Clinical & experimental metastasis》2013,30(4):407-415
Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death. 相似文献
90.