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Wither J Cai YC Lim S McKenzie T Roslin N Claudio JO Cooper GS Hudson TJ Paterson AD Greenwood CM Gladman D Pope J Pineau CA Smith CD Hanly JG Peschken C Boire G;CaNIOS Investigators Fortin PR 《Arthritis research & therapy》2008,10(5):R108-13
Introduction
Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives.Methods
Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry.Results
We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait.Conclusions
The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity. 相似文献33.
A report on the First International Symposium of the Austrian Proteomics Platform, Seefeld, Austria, 26-29 January 2004. 相似文献
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Background
In many areas of medical research, a bivariate analysis is desirable because it simultaneously tests two response variables that are of equal interest and importance in two populations. Several parametric and nonparametric bivariate procedures are available for the location problem but each of them requires a series of stringent assumptions such as specific distribution, affine-invariance or elliptical symmetry. 相似文献36.
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López-Huertas MR Mateos E Díaz-Gil G Gómez-Esquer F Sánchez del Cojo M Alcamí J Coiras M 《The Journal of biological chemistry》2011,286(31):27363-27377
Integration of HIV-1 genome in CD4(+) T cells produces latent reservoirs with long half-life that impedes the eradication of the infection. Control of viral replication is essential to reduce the size of latent reservoirs, mainly during primary infection when HIV-1 infects CD4(+) T cells massively. The addition of immunosuppressive agents to highly active antiretroviral therapy during primary infection would suppress HIV-1 replication by limiting T cell activation, but these agents show potential risk for causing lymphoproliferative disorders. Selective inhibition of PKC, crucial for T cell function, would limit T cell activation and HIV-1 replication without causing general immunosuppression due to PKC being mostly expressed in T cells. Accordingly, the effect of rottlerin, a dose-dependent PKC inhibitor, on HIV-1 replication was analyzed in T cells. Rottlerin was able to reduce HIV-1 replication more than 20-fold in MT-2 (IC(50) = 5.2 μM) and Jurkat (IC(50) = 2.2 μM) cells and more than 4-fold in peripheral blood lymphocytes (IC(50) = 4.4 μM). Selective inhibition of PKC, but not PKCδ or -ζ, was observed at <6.0 μM, decreasing the phosphorylation at residue Thr(538) on the kinase catalytic domain activation loop and avoiding PKC translocation to the lipid rafts. Consequently, the main effector at the end of PKC pathway, NF-κB, was repressed. Rottlerin also caused a significant inhibition of HIV-1 integration. Recently, several specific PKC inhibitors have been designed for the treatment of autoimmune diseases. Using these inhibitors in combination with highly active antiretroviral therapy during primary infection could be helpful to avoid massive viral infection and replication from infected CD4(+) T cells, reducing the reservoir size at early stages of the infection. 相似文献
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FOXOs support the metabolic requirements of normal and tumor cells by promoting IDH1 expression 下载免费PDF全文
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The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC. 相似文献
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Ali Ebrahim Eivind Almaas Eugen Bauer Aarash Bordbar Anthony P Burgard Roger L Chang Andreas Dräger Iman Famili Adam M Feist Ronan MT Fleming Stephen S Fong Vassily Hatzimanikatis Markus J Herrgård Allen Holder Michael Hucka Daniel Hyduke Neema Jamshidi Sang Yup Lee Nicolas Le Novère Joshua A Lerman Nathan E Lewis Ding Ma Radhakrishnan Mahadevan Costas Maranas Harish Nagarajan Ali Navid Jens Nielsen Lars K Nielsen Juan Nogales Alberto Noronha Csaba Pal Bernhard O Palsson Jason A Papin Kiran R Patil Nathan D Price Jennifer L Reed Michael Saunders Ryan S Senger Nikolaus Sonnenschein Yuekai Sun Ines Thiele 《Molecular systems biology》2015,11(10)