Bronchorelaxation of the human bronchi by CFTR activators

The airway functions are profoundly affected in many diseases including asthma, COPD and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR (Cystic Fibrosis transmembrane Conductance Regulator) gene, which normally encodes a multifunctional and integral membrane cAMP regulated and ATP gated Cl⁻ channel expressed in airway epithelial cells.Using human lung tissues obtained from patients undergoing surgery for lung cancer, we demonstrated that CFTR participates in bronchorelaxation. Using human bronchial smooth muscle cells (HBSMC), we applied iodide influx assay to analyze the CFTR-dependent ionic transport and immunofluorescence technique to localize CFTR proteins. Moreover, the relaxation was studied in isolated human bronchial segments after pre-contraction with carbachol to determine the implication of CFTR in bronchodilation.We found in HBSMC that the pharmacology and regulation of CFTR is similar to that of its epithelial counterpart both for activation (using forskolin/genistein or a benzo[c]quinolizinium derivative) and for inhibition (CFTR_inh-172 and GPinh5a). With human bronchial rings, we observed that whatever the compound used including salbutamol, the activation of muscular CFTR leads to a bronchodilation after constriction with carbachol.Altogether, these observations revealed that CFTR in the human airways is expressed in bronchial smooth muscle cells and can be pharmacologically manipulated leading to the hypothesis that this ionic channel could contribute to bronchodilation in human.     

上消化道平滑肌肿瘤的临床及病理特点

目的：分析研究上消化道平滑肌肿瘤的临床表现极其病理特征。方法对我院收治的68例上消化道平滑肌肿瘤患者的临床资料、病理资料等进行了回顾性分析研究，探讨上消化道平滑肌肿瘤的临床及病理特点。结果上消化道平滑肌肿瘤通过内镜检查的确诊率为80．88％，进行内镜检查时可见肿瘤主要为隆起结节状，27．94％患者的肿瘤表面存在溃疡，内镜检查的确诊率为80．88％。结论上消化道平滑肌肿瘤主要表现为良性，通过内镜检查确诊的准确率较高。     

Attentional constraints on target selection for smooth pursuit eye movements

Saccadic eye movements are strongly influenced by shifts of attention to non-target objects. In contrast, we have shown previously that the initiation of smooth pursuit eye movements is relatively unaffected when attention is shifted to objects that are either stationary or move in the same direction as the pursuit target (Souto & Kerzel, 2008). Here, we asked how attention interacts with target selection when a choice has to be made between objects moving in opposite directions. In a dual-task paradigm, observers had to pursue a designated object while making a perceptual judgment on an object moving in the opposite direction. The perceptual target was briefly presented after motion onset and disappeared before the eye started to move. The priority assigned to the perceptual and pursuit task was varied. When priority of the perceptual task was equal or greater than priority of the pursuit task, observers frequently pursued the wrong target and pursuit was delayed. We conclude that when an oculomotor choice is to be made between two equally salient motion signals, the successful initiation of pursuit eye movements depends on the presence of an attentional bias towards the target location.     

Phenotype-specific inhibition of the vascular smooth muscle cell cycle by high glucose treatment

Aims/hypothesis Diabetes accelerates the development of atherosclerosis, which critically involves the proliferation of vascular smooth muscle cells (SMCs). However, how high glucose treatment regulates SMC proliferation is controversial. Considering the established SMC heterogeneity, we hypothesised that glucose treatment may have distinct effects on proliferation of the various phenotypic SMCs. Materials and methods We tested this possibility using cloned spindle-shaped and epithelioid SMCs and laser scanning cytometry. Results Our results showed that glucose treatment significantly inhibited the serum-independent proliferation of epithelioid SMCs, but had no effect on the proliferation of spindle-shaped cells either with or without serum stimulation. Furthermore, glucose treatment inhibited DNA synthesis, as detected by bromodeoxyuridine (BrdU) incorporation, and increased the production of reactive oxygen species in epithelioid SMCs. The inhibition of BrdU incorporation by glucose treatment was mimicked by glucosamine and phorbol 2,13-dibutyrate, a protein kinase C (PKC) activator, and reversed by azaserine, an inhibitor of the hexosamine pathway. In addition, the inhibitory effects of glucose treatment were blocked by GF 109203X (a PKC inhibitor) and PD98058 (a MAPK/ERK kinase, MEK inhibitor), and by knockdown of MEK1 by small interfering RNA (siRNA). The addition of either GF 109203X or PD98058 also reduced the phosphorylation of MAP kinase induced by glucose treatment. Conclusions/interpretation Glucose treatment inhibits the proliferation of epithelioid, but not spindle-shaped, vascular SMCs through the activation of PKC and the MAP kinase pathway, suggesting that the effects of hyperglycaemia on vascular disease depend on the phenotype of SMCs involved.     

单核细胞趋化因子1和Fractalkine对平滑肌细胞增殖、趋化和组织因子表达的影响

目的观察趋化因子单核细胞趋化因子1和Fractalkine对血管平滑肌细胞组织因子表达及血管平滑肌细胞增殖和趋化的影响。方法在细胞水平,采用酶联免疫吸附法检测单核细胞趋化因子1、Fractalkine和单核细胞趋化因子1 Fractalkine对组织因子抗原表达的影响,噻唑蓝法比较单核细胞趋化因子1、Fractalkine和单核细胞趋化因子1 Fractalkine对血管平滑肌细胞增殖的作用,细胞趋化实验比较单核细胞趋化因子1、Fractalkine和单核细胞趋化因子1 Fractalkine对血管平滑肌细胞趋化的影响。结果单核细胞趋化因子1和Fractalkine可增加血管平滑肌细胞组织因子抗原的表达,单核细胞趋化因子1与Fractalkine共同作用后,组织因子抗原表达量较二者单独作用时明显降低。Fractalkine对血管平滑肌细胞有明显的促增殖作用,但单核细胞趋化因子1 Fractalkine和单核细胞趋化因子1均无明显促增殖作用。Fractalkine和单核细胞趋化因子1 Fractalkine对血管平滑肌细胞有明显的趋化作用,而单核细胞趋化因子1的趋化作用不够明显。结论单核细胞趋化因子1和Fractalkine在动脉粥样硬化过程中分别对血管平滑肌细胞组织因子的表达、增殖和趋化发挥了不同程度的作用。     

胰岛素样生长因子1受体抗体对大鼠血管平滑肌细胞增殖的影响

目的观察胰岛素样生长因子1受体抗体对大鼠血管平滑肌细胞增殖的影响。方法球囊导管损伤大鼠一侧颈总动脉,7天后体外培养受损血管的中膜平滑肌细胞,以损伤侧血管细胞为实验组,以对侧正常血管中膜平滑肌细胞为对照组;采用-αactin免疫细胞化学法进行细胞鉴定;在细胞的培养悬液中加入不同浓度的胰岛素样生长因子1受体抗体作用24 h,然后采用5-溴-2脱氧尿苷细胞增殖检测法检测细胞的增殖程度。结果大鼠颈总动脉球囊损伤后,体外培养的中膜平滑肌细胞表现出显著的增殖性(与对照组比较,P<0.01);胰岛素样生长因子1受体抗体可以显著抑制大鼠平滑肌细胞的增殖,呈现出浓度依赖性特征(组间比较,P<0.01)。结论胰岛素样生长因子1受体抗体具有抑制平滑肌细胞增殖的作用,有望用于治疗平滑肌细胞增殖性疾病。