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排序方式: 共有218条查询结果,搜索用时 562 毫秒
91.
R Riblet L Claflin D M Gibson B J Mathieson M Weigert 《Journal of immunology (Baltimore, Md. : 1950)》1980,124(2):787-789
A set of recombinant inbred mouse strains has been constructed from the cross of NZB by C58. These strains provide new tools for the analysis of antibody heavy and light chain genes and NZB autoimmunity. Typing of heavy chain genes confirmed the allotype linkage of the dextran response locus Igh-Dex. One strain has fixed a recombinant chromosome carrying NZB allotype genes and the Dex+ variable region gene from C58. Two kappa-light chain variable region genes, Igk-Pc and Igk-Ef1, co-segregated with the Lyt-2 lymphocyte alloantigen locus. This confirms the tight linkage of these loci and decreases the maximum estimate of the recombination frequency between them to 1.7%. 相似文献
92.
Mohammad Husain Leonard G. Meggs Himanshu Vashistha Sonia Simoes Kevin O. Griffiths Dileep Kumar Joanna Mikulak Peter W. Mathieson Moin A. Saleem Luis Del Valle Sergio Pina-Oviedo Jin Ying Wang Surya V. Seshan Ashwani Malhotra Krzysztof Reiss Pravin C. Singhal 《The Journal of biological chemistry》2009,284(24):16648-16658
93.
Khurana S Chakraborty S Lam M Liu Y Su YT Zhao X Saleem MA Mathieson PW Bruggeman LA Kao HY 《The Journal of biological chemistry》2012,287(15):12027-12035
94.
Joyce JBC van Beers Annemiek Willemze Jeroen J Jansen Gerard HM Engbers Martin Salden Jos Raats Jan W Drijfhout Annette HM van der Helm-van Mil Rene EM Toes Ger JM Pruijn 《Arthritis research & therapy》2013,15(5):R140
Introduction
Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients.Methods
Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip.Results
Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations.Conclusions
Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores. 相似文献95.
Bevan HS Slater SC Clarke H Cahill PA Mathieson PW Welsh GI Satchell SC 《American journal of physiology. Renal physiology》2011,301(4):F733-F742
Laminar shear stress is a key determinant of systemic vascular behavior, including through activation of endothelial nitric oxide synthase (eNOS), but little is known of its role in the glomerulus. We confirmed eNOS expression by glomerular endothelial cells (GEnC) in tissue sections and examined effects of acute exposure (up to 24 h) to physiologically relevant levels of laminar shear stress (10-20 dyn/cm(2)) in conditionally immortalized human GEnC. Laminar shear stress caused an orientation of GEnC and stress fibers parallel to the direction of flow and induced Akt and eNOS phosphorylation along with NO production. Inhibition of the phophatidylinositol (PI)3-kinase/Akt pathway attenuated laminar shear stress-induced eNOS phosphorylation and NO production. Laminar shear stress of 10 dyn/cm(2) had a dramatic effect on GEnC permeability, reversibly decreasing the electrical resistance across GEnC monolayers. Finally, the laminar shear stress-induced reduction in electrical resistance was attenuated by the NOS inhibitors l-N(G)-monomethyl arginine (l-NMMA) and l-N(G)-nitroarginine methyl ester (l-NAME) and also by inhibition of the PI3-kinase/Akt pathway. Hence we have shown for GEnC in vitro that acute permeability responses to laminar shear stress are dependent on NO, produced via activation of the PI3-kinase/Akt pathway and increased eNOS phosphorylation. These results suggest the importance of laminar shear stress and NO in regulating the contribution of GEnC to the permeability properties of the glomerular capillary wall. 相似文献
96.
97.
Bantscheff M Hopf C Savitski MM Dittmann A Grandi P Michon AM Schlegl J Abraham Y Becher I Bergamini G Boesche M Delling M Dümpelfeld B Eberhard D Huthmacher C Mathieson T Poeckel D Reader V Strunk K Sweetman G Kruse U Neubauer G Ramsden NG Drewes G 《Nature biotechnology》2011,29(3):255-265
The development of selective histone deacetylase (HDAC) inhibitors with anti-cancer and anti-inflammatory properties remains challenging in large part owing to the difficulty of probing the interaction of small molecules with megadalton protein complexes. A combination of affinity capture and quantitative mass spectrometry revealed the selectivity with which 16 HDAC inhibitors target multiple HDAC complexes scaffolded by ELM-SANT domain subunits, including a novel mitotic deacetylase complex (MiDAC). Inhibitors clustered according to their target profiles with stronger binding of aminobenzamides to the HDAC NCoR complex than to the HDAC Sin3 complex. We identified several non-HDAC targets for hydroxamate inhibitors. HDAC inhibitors with distinct profiles have correspondingly different effects on downstream targets. We also identified the anti-inflammatory drug bufexamac as a class IIb (HDAC6, HDAC10) HDAC inhibitor. Our approach enables the discovery of novel targets and inhibitors and suggests that the selectivity of HDAC inhibitors should be evaluated in the context of HDAC complexes and not purified catalytic subunits. 相似文献
98.
Background
Interferon-α in combination with ribavirin is the current gold standard for treatment of chronic hepatitis C. It is unknown if the development of autoimmune thyroid disease (TD) during treatment confers an improved chance of achieving sustained virologic response. The aim of this study is to assess the chance of achieving sustained virologic response (SVR) in patients who developed TD during treatment when compared with those who did not.Methods
We performed a tertiary hospital-based retrospective nested case-control analysis of 19 patients treated for hepatitis C who developed thyroid disease, and 76 controls (matched for age, weight, gender, cirrhosis and aminotransferase levels) who did not develop TD during treatment. Multivariate logistic-regression models were used to compare cases and controls.Results
The development of TD was associated with a high likelihood of achieving SVR (odds ratio, 6.0; 95% confidence interval, 1.5 to 24.6) for the pooled group containing all genotypes. The likelihood of achieving SVR was increased in individuals with genotype 1 HCV infection who developed TD (odds ratio, 5.2; 95% confidence interval, 1.2 to 22.3), and all genotype 3 patients who developed TD achieved SVR.Conclusions
Development of TD during treatment for hepatitis C infection is associated with a significantly increased chance of achieving SVR. The pathophysiogical mechanisms for this observation remain to be determined.Trial Registration
The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRB12610000830099 相似文献99.
Savitski MM Lemeer S Boesche M Lang M Mathieson T Bantscheff M Kuster B 《Molecular & cellular proteomics : MCP》2011,10(2):M110.003830
Large scale phosphorylation analysis is more and more getting into focus of proteomic research. Although it is now possible to identify thousands of phosphorylated peptides in a biological system, confident site localization remains challenging. Here we validate the Mascot Delta Score (MD-score) as a simple method that achieves similar sensitivity and specificity for phosphosite localization as the published Ascore, which is mainly used in conjunction with Sequest. The MD-score was evaluated using liquid chromatography-tandem MS data of 180 individually synthesized phosphopeptides with precisely known phosphorylation sites. We tested the MD-score for a wide range of commonly available fragmentation methods and found it to be applicable throughout with high statistical significance. However, the different fragmentation techniques differ strongly in their ability to localize phosphorylation sites. At 1% false localization rate, the highest number of correctly assigned phosphopeptides was achieved by higher energy collision induced dissociation in combination with an Orbitrap mass analyzer followed very closely by low resolution ion trap spectra obtained after electron transfer dissociation. Both these methods are significantly better than low resolution spectra acquired after collision induced dissociation and multi stage activation. Score thresholds determined from simple calibration functions for each fragmentation method were stable over replicate analyses of the phosphopeptide set. The MD-score outperforms the Ascore for tyrosine phosphorylated peptides and we further show that the ability to call sites correctly increases with increasing distance of two candidate sites within a peptide sequence. The MD-score does not require complex computational steps which makes it attractive in terms of practical utility. We provide all mass spectra and the synthetic peptides to the community so that the development of present and future localization software can be benchmarked and any laboratory can determine MD-scores and localization probabilities for their individual analytical set up. 相似文献
100.
WalterDuartedeAraujo Filho Fábio Kurt Schneider Rigoberto EM Morales 《Biomedical engineering online》2012,11(1):1-14