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991.
Lemos PA de Feyter PJ Serruys PW Saia F Arampatzis CA Disco C Mercado N Mainar V Morís C van den Bos AA Berghoefer G 《International journal of cardiology》2005,98(3):479-486
BACKGROUND: To evaluate the impact of the extent of coronary disease (single- or multivessel) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study (LIPS). METHODS: A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were randomized to receive fluvastatin (40 mg bid) or placebo for at least 3 years following a first successful percutaneous coronary intervention. The incidence of cardiac atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary re-interventions not related to restenosis) was evaluated. RESULTS: Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents. The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo (RR 1.67 [95% CI: 1.24-2.25]; p<0.001). In patients treated with fluvastatin, however, no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease (RR 1.28 [95% CI: 0.90-1.81]; p=0.2). CONCLUSIONS: Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention. However, the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment. 相似文献
992.
LeVan TD Von Essen S Romberger DJ Lambert GP Martinez FD Vasquez MM Merchant JA 《American journal of respiratory and critical care medicine》2005,171(7):773-779
RATIONALE AND OBJECTIVES: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. MATERIALS AND METHODS: Based on our findings of increased circulating CD14 associated with the CD14/-159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/-159TT farmers (n = 19) had significantly lower lung function as measured by FEV1 (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF25-75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/-1619GG genotype (n =11) were associated with lower lung function (FEV1, p = 0.008; FEF25-75, p = 0.009) compared with farmers with the A allele (n = 86). RESULTS: No association between CD14/-550 and lung function was observed (FEV1, p = 0.32; FEF25-75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/-159T (p = 0.013) or CD14/-1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. CONCLUSION: We conclude that the CD14/-159 or CD14/-1619 loci may play a role in modulating lung function and wheeze among agricultural workers. 相似文献
993.
The prevalence and natural history of spontaneous bacterial peritonitis in asymptomatic patients with ascites secondary to cirrhosis is unknown. From a prospectively recorded database, we reviewed the clinical and laboratory features of all outpatients with cirrhotic ascites undergoing paracentesis between July 1994 and December 2000. The prevalence of spontaneous bacterial peritonitis in the population of 427 cirrhotic outpatients as defined by neutrocytic ascites (absolute neutrophil count >or=250 cells/mm(3)) was 3.5%. Of the 15 patients with neutrocytic ascites, 6 were culture positive (1.4%) and 9 culture negative (2.1%). Eight other patients (1.9%) had bacterascites. The organisms cultured from ascitic fluid in these asymptomatic patients with culture positive neutrocytic ascites and bacterascites were predominantly gram positive. No patient developed hepatorenal syndrome, and 1-year survival of 67% was better than historical data from hospitalized patients with spontaneous bacterial peritonitis. Moreover, patients who did not receive antibiotics for neutrocytic ascites fared no worse than patients who did receive antibiotics. In conclusion, spontaneous bacterial peritonitis in outpatients with cirrhotic ascites is less frequent, occurs in patients with less advanced liver disease, and may have a better outcome than its counterpart in hospitalized patients. In addition, the organisms cultured from ascitic fluid in outpatients are predominantly gram positive. A reassessment of diagnostic criteria for spontaneous bacterial peritonitis in outpatients may be required. 相似文献
994.
995.
Wadi Mawad Lasse Løvstakken Solveig Fadnes Thomas Grønli Patrick Segers Luc Mertens Siri Ann Nyrnes 《Ultrasound in medicine & biology》2021,47(6):1514-1527
Using blood speckle tracking (BST) based on high-frame-rate echocardiography (HFRE), we compared right ventricle (RV) flow dynamics in children with atrial septal defects (ASDs) and repaired tetralogy of Fallot (rTOF). Fifty-seven children with rTOF with severe pulmonary insufficiency (PI) (n = 21), large ASDs (n = 11) and healthy controls (CTL, n = 25) were included. Using a flow phantom, we studied the effects of imaging plane and smoothing parameters on 2-D energy loss (EL). RV diastolic EL was similar in ASD and rTOF, but both were greater than in CTL. Locations of high EL were similar in all groups in systole, occurring in the RV outflow tract and around the tricuspid valve leaflets in early diastole. An additional apical early diastolic area of EL was noted in rTOF, corresponding to colliding tricuspid inflow and PI. The flow phantom revealed that EL varied with imaging plane and smoothing settings but that the EL trend was preserved if kept consistent. 相似文献
996.
997.
Patrick J. Cimino Yue Yang Xianwu Li Jake F. Hemingway Makenzie K. Cherne Shawn B. Khademi Yoshinori Fukui Kathleen S. Montine Thomas J. Montine C. Dirk Keene 《Experimental and molecular pathology》2013
Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity. EP2 ablation in experimental AD results in reduced oxidative damage and amyloid beta (Aβ) burden. This discovery led us to hypothesize that genetic ablation of DOCK2 would replicate the anti-Aβ effects of loss of EP2 in experimental AD. To test this hypothesis, we crossed mice that lacked DOCK2 (DOCK2 −/−), were hemizygous for DOCK2 (DOCK2 +/−), or that expressed two DOCK2 genes (DOCK2 +/+) with APPswe-PS1Δe9 mice (a model of AD). While we found no DOCK2-dependent differences in cortex or in hippocampal microglia density or morphology in APPswe-PS1Δe9 mice, cerebral cortical and hippocampal Aβ plaque area and size were significantly reduced in 10-month-old APPswe-PS1Δe9/DOCK2 −/− mice compared with APPswe-PS1Δe9/DOCK2 +/+ controls. DOCK2 hemizygous APPswe-PS1Δe9 mice had intermediate Aβ plaque levels. Interestingly, soluble Aβ42 was not significantly different among the three genotypes, suggesting the effects were mediated specifically in fibrillar Aβ. In combination with earlier cell culture results, our in vivo results presented here suggest DOCK2 contributes to Aβ plaque burden via regulation of microglial innate immune function and may represent a novel therapeutic target for AD. 相似文献
998.
Elio Schouppe Camille Mommer Kiavash Movahedi Damya Laoui Yannick Morias Conny Gysemans Ariane Luyckx Patrick De Baetselier Jo A. Van Ginderachter 《European journal of immunology》2013,43(11):2930-2942
Tumor growth coincides with an accumulation of myeloid‐derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b+CD115+Ly6G?Ly6Chigh MDSCs and granulocytic CD11b+CD115?Ly6G+Ly6Cint polymorphonuclear (PMN)‐MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8+ T‐cell activation — including cytokine production, surface marker expression, survival, and cytotoxicity — is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen‐driven CD8+ T‐cell proliferation, but differ in their dependency on IFN‐γ, STAT‐1, IRF‐1, and NO to do so. Moreover, MO‐MDSC and PMN‐MDSCs diminish IL‐2 levels, but only MO‐MDSCs affect IL‐2Rα (CD25) expression and STAT‐5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN‐γ production by CD8+ T cells on a per cell basis, illustrating that some T‐cell activation characteristics are actually stimulated by MDSCs. Conversely, MO‐MDSCs counteract the activation‐induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8+ T‐cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL‐mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8+ T‐cell activation events in vitro, whereby some parameters are suppressed while others are stimulated. 相似文献
999.
Petra Ehling Manuela Cerina Patrick Meuth Tatyana Kanyshkova Pawan Bista Philippe Coulon Sven G. Meuth Hans-Christian Pape Thomas Budde 《Pflügers Archiv : European journal of physiology》2013,465(4):469-480
Mutations in genes coding for Ca2+ channels were found in patients with childhood absence epilepsy (CAE) indicating a contribution of Ca2+-dependent mechanisms to the generation of spike-wave discharges (SWD) in humans. Since the involvement of Ca2+ signals remains unclear, the aim of the present study was to elucidate the function of a Ca2+-dependent K+ channel (BKCa) under physiological conditions and in the pathophysiological state of CAE. The activation of BKCa channels is dependent on both voltage and intracellular Ca2+ concentrations. Moreover, these channels exhibit an outstandingly high level of regulatory heterogeneity that builds the basis for the influence of BKCa channels on different aspects of neuronal activity. Here, we analyse the contribution of BKCa channels to firing of thalamocortical relay neurons, and we test the hypothesis that BKCa channel activity affects the phenotype of a genetic rat model of CAE. We found that the activation of the β2-adrenergic receptor/protein kinase A pathway resulted in BKCa channel inhibition. Furthermore, BKCa channels affect the number of action potentials fired in a burst and produced spike frequency adaptation during tonic activity. The latter result was confirmed by a computer modelling approach. We demonstrate that the β2-adrenergic inhibition of BKCa channels prevents spike frequency adaptation and, thus, might significantly support the tonic firing mode of thalamocortical relay neurons. In addition, we show that BKCa channel functioning differs in epileptic WAG/Rij and thereby likely contributes to highly synchronised, epileptic network activity. 相似文献
1000.
The collection of cell-derived extracellular matrix (ECM) to form implantable biomaterials has therapeutic potential. However, a significant challenge to the creation of these biomaterials is the ability to produce an adequate quantity of ECM from cells in culture. Mechanical stimulation has long been viewed as a practical means to enhance cellular matrix production. In this study we explored the influence of vocally inspired mechanical stimulation, a unique combination of high frequency vibration and low frequency strain, on the production of ECM. Using a custom fabricated vocal bioreactor, tracheal fibroblast seeded sacrificial foams were treated for 3 weeks using either isolated cyclic strain, combined cyclic strain and vibration (dual mode), or static conditioning. When compared to static controls, ECM production was significantly increased for samples conditioned with either cyclic strain or dual mode stimulation. The quantity of ECM harvested from sacrificial foams increased from 25 ± 1 mg for statically conditioned control foams, to 34 ± 3 and 52 ± 10 mg for cyclic strain and dual mode conditioned samples respectively. Furthermore, mechanical conditioning significantly increased the elastic modulus of ECM biomaterials collected from sacrificial foams. Static control modulus increased from 40 ± 2 to 63 ± 7 kPa and 92 ± 7 kPa following isolated cyclic strain and dual mode conditioning, respectively. These results indicate that cyclic strain conditioning can be used to accelerate the production of ECM by human tracheal cells during growth in culture, and that the addition of high frequency vibration to the conditioning program further enhances ECM production. 相似文献