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171.
Yufeng Tian Grzegorz Gawlak Alok S. Shah Katherine Higginbotham Xinyong Tian Yoshihiro Kawasaki Tetsu Akiyama David B. Sacks Anna A. Birukova 《The Journal of biological chemistry》2015,290(7):4097-4109
Hepatocyte growth factor (HGF) attenuates agonist-induced endothelial cell (EC) permeability and increases pulmonary endothelial barrier function via Rac-dependent enhancement of the peripheral actin cytoskeleton. However, the precise mechanisms of HGF effects on the peripheral cytoskeleton are not well understood. This study evaluated a role for Rac/Cdc42-specific guanine nucleotide exchange factor Asef and the multifunctional Rac effector, IQGAP1, in the mechanism of HGF-induced EC barrier enhancement. HGF induced Asef and IQGAP1 co-localization at the cell cortical area and stimulated formation of an Asef-IQGAP1 functional protein complex. siRNA-induced knockdown of Asef or IQGAP1 attenuated HGF-induced EC barrier enhancement. Asef knockdown attenuated HGF-induced Rac activation and Rac association with IQGAP1, and it abolished both IQGAP1 accumulation at the cell cortical layer and IQGAP1 interaction with actin cytoskeletal regulators cortactin and Arp3. Asef activation state was essential for Asef interaction with IQGAP1 and protein complex accumulation at the cell periphery. In addition to the previously reported role of the IQGAP1 RasGAP-related domain in the Rac-dependent IQGAP1 activation and interaction with its targets, we show that the IQGAP1 C-terminal domain is essential for HGF-induced IQGAP1/Asef interaction and Asef-Rac-dependent activation leading to IQGAP1 interaction with Arp3 and cortactin as a positive feedback mechanism of IQGAP1 activation. These results demonstrate a novel feedback mechanism of HGF-induced endothelial barrier enhancement via Asef/IQGAP1 interactions, which regulate the level of HGF-induced Rac activation and promote cortical cytoskeletal remodeling via IQGAP1-Arp3/cortactin interactions. 相似文献
172.
吴红样 《中国微生态学杂志》2015,27(5)
目的探讨孟鲁司特联合舒利迭对哮喘急性发作期患者疗效及免疫功能的影响。方法 2012年1月至2014年1月选取在本院收治的120例哮喘急性发作期患者为研究对象,根据随机数字表将患者分为观察组及对照组各60例,对照组给予舒利迭雾化吸入治疗,50 mg/250 mg,2次/d,观察组在对照组基础上口服孟鲁司特,10 mg/次,1次/d,疗程为2周。对比分析两组患者治疗效果及治疗前后肺功能及免疫功能的变化。结果观察组总有效率为96.67%,对照组总有效率为76.67%,差异有统计学意义(P0.05)。观察组患者治疗后第1秒呼吸气体的容积(FEV1)、用力呼吸的肺活量(FVC)及FVC占预计值百分比(FVC%)改善优于对照组(P0.05)。观察组治疗后白细胞介素4(IL-4)、免疫球蛋白(Ig E)水平、IL-4/INF-γ显著低于对照组,而干扰素(IFN-γ)与对照组相比差异无统计学意义。结论孟鲁司特联合舒利迭能有效改善哮喘急性发作期患者肺功能及免疫功能,提高哮喘患者治疗效果。 相似文献
173.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献174.
Robert Linder Eva R?nmark Jamshid Pourazar Annelie Behndig Anders Blomberg Anne Lindberg 《Respiratory research》2015,16(1)
Background
Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.Methods
Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.Results
Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).Conclusion
Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes. 相似文献175.
目的观察人工饲养条件下实验恒河猴肺脏病理改变,探讨实验猴呼吸系统疾病分布规律和病理改变特点,丰富实验猴自发病变基本研究资料。方法对1998~2008年云南地区饲养的自然死亡的155只恒河猴(年龄2~20岁)的肺脏进行病理检查,按年龄分为幼年组、成年组、老年组,并对观察结果进行统计学分析。结果实验猴肺脏主要病变有大叶性肺炎、支气管肺炎、间质性肺炎、肺气肿、支气管扩张症、胸膜炎、肺肉芽肿性炎等12种,出现率最高的为支气管肺炎(18.71%)和大叶性肺炎(16.74%)。恒河猴肺脏病变在不同年龄阶段均有发生,老年猴组肺脏病变发生率最高,疾病类型和发生率在不同年组中分布不相同,统计学分析显示:支气管炎病变成年组发病率明显高于幼年组;肺气肿病变老年组明显高于成年组和幼年组,(P〈0.05)。结论人工饲养条件下死亡实验猴肺脏病变检出率较高,实验猴肺脏病变在不同年龄阶段存在差异,实验猴肺脏病理改变结果丰富了实验猴的基本研究资料,对实验猴的质量控制和相关动物实验有重要价值。 相似文献
176.
目的通过观察糖皮质激素对机械通气大鼠肺组织诱导型一氧化氮合酶(iNOS)及一氧化氮(NO)表达的影响,探讨糖皮质激素对呼吸机所致肺损伤(ventilator induced lung injury,VILI)的干预作用。方法 24只雄性Wistar大鼠随机分为对照组、机械通气组、地塞米松(DXM)干预组。用逆转录-聚合酶链反应(RT-PCR)法检测肺组织iNOS mRNA表达,用免疫组织化学染色法检测肺组织iNOS蛋白表达,用硝酸还原酶法测定肺组织和血浆NO含量。结果机械通气组和DXM干预组大鼠肺组织iNOS mRNA及其蛋白表达水平,以及血浆和肺组织NO含量均明显高于对照组(P〈0.01);DXM干预组上述指标与机械通气组比较均明显降低(P〈0.01)。结论糖皮质激素可通过抑制肺组织iNOS的表达,减少NO的生成,对机械通气大鼠肺组织具有保护作用。 相似文献
177.
目的分析结核急性感染小鼠脾脏和肺脏的组织荷菌量以及病理的动态变化。方法以3×105CFU结核分枝杆菌标准株H37Rv尾静脉途径感染雌性C57BL/6J小鼠,测定感染后1 d、1周、2周、3周、4周、6周和8周肺脏及脾脏组织的荷菌量,脾脏和肺脏组织经HE染色分析病理变化。结果感染动物的脾脏荷菌量在前3周逐步提高,在4~8周脾脏荷菌量维持稳定,肺脏组织在2~8周组织荷菌量逐步升高。病理分析显示动物感染3周后肺脏和脾脏出现肉芽肿,在6~8周病理损伤加重。结论小鼠经尾静脉感染高剂量结核分枝杆菌在8周前表现为急性感染状态,适用于抗结核药物的体内药效学评价。 相似文献
178.
A BAC transgenic Hes1-EGFP reporter reveals novel expression domains in mouse embryos 总被引:1,自引:0,他引:1
Klinck R Füchtbauer EM Ahnfelt-Rønne J Serup P Jensen JN Jørgensen MC 《Gene expression patterns : GEP》2011,11(7):415-426
Expression of the basic helix-loop-helix factor Hairy and Enhancer of Split-1 (Hes1) is required for normal development of a number of tissues during embryonic development. Depending on context, Hes1 may act as a Notch signalling effector which promotes the undifferentiated and proliferative state of progenitor cells, but increasing evidence also points to Notch independent regulation of Hes1 expression. Here we use high resolution confocal scanning of EGFP in a novel BAC transgenic mouse reporter line, Tg(Hes1-EGFP)1Hri, to analyse Hes1 expression from embryonic day 7.0 (e7.0). Our data recapitulates some previous observations on Hes1 expression and suggests new, hitherto unrecognised expression domains including expression in the definitive endoderm at early somite stages before gut tube closure and thus preceding organogenesis. This mouse line will be a valuable tool for studies addressing the role of Hes1 in a number of different research areas including organ specification, development and regeneration. 相似文献
179.
Milena Niemiec Maciej G?ogowski Dobromira Tyc-Szczepaniak Marek Wierzchowski Lucyna K?pka 《Reports of Practical Oncology and Radiotherapy》2011,16(2):49-53
Background and aim
Long-term survival of lung cancer patients with brain metastases (BM) is very rare. Our aim is to report the characteristics of patients who survived for at least three years after a BM diagnosis.Materials and methods
Nineteen lung cancer patients who had survived ≥3 years after a BM diagnosis were identified in our database. Seven (37%) had undergone whole-brain radiotherapy (WBRT) only, five (26%) BM surgery + WBRT, three (16%) BM surgery + WBRT + BM radiosurgery, and four (21%) no WBRT (one, surgery; one, radiosurgery; two, BM surgery + radiosurgery). Their characteristics were compared with historical data for 322 lung cancer patients with BM (control group, CG), who had received WBRT between 1986 and 1997.Results
Median survival from BM in long survivors group was 73 months (in CG – 4 months). Characteristics comparison: median age 55 vs. 58 (CG), p = 0.16; female sex 68% vs. 28% (CG), p = 0.003; RTOG/RPA class 1 – 75% vs. 13% (CG), p = 0.00001; adenocarcinoma histology 84% vs. 24% (CG), p < 0.00001; control of primary tumor 95% vs. 27% (CG), p < 0.00001; extracranial metastases 0 vs. 26% (CG), p = 0.01; single BM 63% vs. 9% (CG), p = 0.00001; surgery of BM 53% vs. 14% (CG), p = 0.00001.Conclusions
Beside prognostic factors already recognized as favorable in patients with BM, the adenocarcinoma histology and female sex were prevalent in long-term survivors of BM from lung cancer. 相似文献180.
目的:探讨小青龙汤治疗慢性支气管哮喘的临床疗效。方法:选取2009年1月至2011年1月我院收治入院的哮喘患者84例,随机分为对照组和治疗纽,对照组采用西药对症治疗,治疗组在对照纽的基础上联合应用小青龙汤,治疗结束后对两组患者的临床疗效和肺功能进行分析。结果:临床疗效比较:治疗组总有效率显著高于对照组(95.42%VS80.95%,P〈0.05);治疗结束后,两组患者肺功能FEV1占预计值%和PEF占预计值%均显著升高,肺功能明显好转(P〈0.05),且治疗组肺功能改善更为明显(P〈0.05)。结论:小青龙汤作为中医经典方剂治疗慢性支气管哮喘,可显著改善肺功能,提高临床疗效。 相似文献