在Visual Studio 2005 Betal发布两个月之后，微软公司再次发布了一个更新版本：Visual Studio 2005 Betal Refresh With Team System。在这个更新版本中，集成了微软最新的Team System。软件开发团队可以使用这个全新版本来建立一个包...在Visual Studio 2005 Betal发布两个月之后，微软公司再次发布了一个更新版本：Visual Studio 2005 Betal Refresh With Team System。在这个更新版本中，集成了微软最新的Team System。软件开发团队可以使用这个全新版本来建立一个包含了项目协作，源码管理、进度跟踪．Bug管理、集成测试、自动编译的完整开发环境。展开更多
Background Transforming growth factor beta （TGF-beta） plays an essential role in the regulation of normal physiologic processes of cells. TGF-beta has been shown to regulate several mitogen-activated protein kinases...Background Transforming growth factor beta （TGF-beta） plays an essential role in the regulation of normal physiologic processes of cells. TGF-beta has been shown to regulate several mitogen-activated protein kinases （MAPK） pathways in several epithelial cells. However, the effects of TGF-beta on soft tissue sarcoma are seldom reported. Our previous studies suggested that there should be some other signal transduction pathways besides Smads, which are important to regulate the growth of human embryonal rhabdomyosarcoma （RMS） cells. In the present study, we examined the expression and functional relations of extracellular signal-regulated kinase 2 （ERK2） and Smad4 in human RMS tissue and a RMS cell line, RD. Methods RD cells and normal human primary skeletal myoblasts （Mb） were treated with TGF-betal to establish the expression profile of ERK2 at the mRNA and protein levels detected by RT-PCR and immunofluorescence. Immunohistochemistry was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of human RMS and 23 specimens of normal skeletal muscles. Follow-up of specimens was performed 6 months to 70 months later. Results RD cells and human RMS tissues showed the higher expression of ERK2 and Smad4 than the normal control, either the protein level or the mRNA level. And, exogenous TGF-betal stimulation can lead to higher expression of ERK2 and its nuclear translocation, so TGF-betal can also activatedMAPK （ERK2） pathway, resulting in a sustained activation of ERK2 for at least 2 hours. Immunohistochemistry analysis, however, showed that there was no correlation between ERK2 and Smad4 protein. The overexpression of ERK2 and Smad4 had no indicative effects on histological subtypes, histological grading, gender, age, and prognosis. Conclusions In RMS, signaling of TGF-betal from cell surface to nucleus can also be directed through the MAPK （ERK2） pathway besides the TGF-betal/Smads pathway. The activation of ERK2 by TGF-betal may be Smad4 independent. Moreover, there may be some other tanglesome relationships between the TGF-betal/Smads pathway and the MAPK pathway which takes part in the development, invasion and metastasis of tumor cells.展开更多
Background Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia （IVOT）. We aimed to investigate whether the major genetic variants in β1-a...Background Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia （IVOT）. We aimed to investigate whether the major genetic variants in β1-and β2-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia （ILVT）.Methods Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the β1-adrenoceptor, Arg16Gly and Gln27Glu in the β2-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.Results A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of β2-adrenoceptor was associated with a higher risk of IVOT （OR：1.40, 95% CI： 1.12-1.75,P=0.003 in the addictive model and OR：. 1.62, 95% CI： 1.14-2.31, P=0.007 in the dominant model）. Patients with Gly16Gln27 haplotype also had a higher risk of IVOT （OR： 1.38, 95% CI： 1.11-1.73, P=0.012）. Other four variants,including Ser49Gly and Arg389Gly in β1-adrenoceptor, GIn27Glu in β2-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls.Conclusions Arg16Gly in β2-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in β1- and β2-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.展开更多
文摘在Visual Studio 2005 Betal发布两个月之后，微软公司再次发布了一个更新版本：Visual Studio 2005 Betal Refresh With Team System。在这个更新版本中，集成了微软最新的Team System。软件开发团队可以使用这个全新版本来建立一个包含了项目协作，源码管理、进度跟踪．Bug管理、集成测试、自动编译的完整开发环境。
基金This work was supported by a grant from China Medical Board of New York(No.CMB 00-722)
文摘Background Transforming growth factor beta （TGF-beta） plays an essential role in the regulation of normal physiologic processes of cells. TGF-beta has been shown to regulate several mitogen-activated protein kinases （MAPK） pathways in several epithelial cells. However, the effects of TGF-beta on soft tissue sarcoma are seldom reported. Our previous studies suggested that there should be some other signal transduction pathways besides Smads, which are important to regulate the growth of human embryonal rhabdomyosarcoma （RMS） cells. In the present study, we examined the expression and functional relations of extracellular signal-regulated kinase 2 （ERK2） and Smad4 in human RMS tissue and a RMS cell line, RD. Methods RD cells and normal human primary skeletal myoblasts （Mb） were treated with TGF-betal to establish the expression profile of ERK2 at the mRNA and protein levels detected by RT-PCR and immunofluorescence. Immunohistochemistry was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of human RMS and 23 specimens of normal skeletal muscles. Follow-up of specimens was performed 6 months to 70 months later. Results RD cells and human RMS tissues showed the higher expression of ERK2 and Smad4 than the normal control, either the protein level or the mRNA level. And, exogenous TGF-betal stimulation can lead to higher expression of ERK2 and its nuclear translocation, so TGF-betal can also activatedMAPK （ERK2） pathway, resulting in a sustained activation of ERK2 for at least 2 hours. Immunohistochemistry analysis, however, showed that there was no correlation between ERK2 and Smad4 protein. The overexpression of ERK2 and Smad4 had no indicative effects on histological subtypes, histological grading, gender, age, and prognosis. Conclusions In RMS, signaling of TGF-betal from cell surface to nucleus can also be directed through the MAPK （ERK2） pathway besides the TGF-betal/Smads pathway. The activation of ERK2 by TGF-betal may be Smad4 independent. Moreover, there may be some other tanglesome relationships between the TGF-betal/Smads pathway and the MAPK pathway which takes part in the development, invasion and metastasis of tumor cells.
文摘Background Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia （IVOT）. We aimed to investigate whether the major genetic variants in β1-and β2-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia （ILVT）.Methods Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the β1-adrenoceptor, Arg16Gly and Gln27Glu in the β2-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.Results A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of β2-adrenoceptor was associated with a higher risk of IVOT （OR：1.40, 95% CI： 1.12-1.75,P=0.003 in the addictive model and OR：. 1.62, 95% CI： 1.14-2.31, P=0.007 in the dominant model）. Patients with Gly16Gln27 haplotype also had a higher risk of IVOT （OR： 1.38, 95% CI： 1.11-1.73, P=0.012）. Other four variants,including Ser49Gly and Arg389Gly in β1-adrenoceptor, GIn27Glu in β2-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls.Conclusions Arg16Gly in β2-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in β1- and β2-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.
