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51.
Lerch M Keller M Britschgi M Kanny G Tache V Schmid DA Beeler A Gerber BO Luethi M Bircher AJ Christiansen C Pichler WJ 《The Journal of allergy and clinical immunology》2007,119(6):1529-1536
BACKGROUND: Approximately 3% of patients exposed to iodinated contrast media develop delayed hypersensitivity reactions. OBJECTIVE: We wanted to better understand the molecular basis of contrast media cross-reactivity. METHODS: Cross-reactivity was assessed by skin testing and measurement of T-cell activation (CD69 upregulation) and proliferation ((3)H-thymidine uptake, 5,6-carboxyfluorescein diacetate succinimidyl ester staining) of PBMCs, T-cell lines, and T-cell clones of 2 patients with delayed hypersensitivity reactions to iohexol and iomeprol, respectively. Thirteen different contrast media and potassium iodide were compared. RESULTS: Skin testing and analyses of PBMCs, T-cell lines, and clones showed broad cross-reactivity in both patients. Broad as well as more restricted cross-reactivity patterns were found in iohexol-specific and iomeprol-specific CD4(+) T-cell clones, whereas 1 iomeprol-specific CD8(+) T-cell clone showed no cross-reactivity at all. The reactivity to equimolar concentrations of iohexol and its dimer iodixanol was very similar, suggesting that the dimer was not more stimulatory than its monomer. Consistently low reactivity to iobitridol was found in both patients, but never to iodide. A frequency analysis of contrast medium-specific peripheral T cells gave values between 0.6 % (iomeprol) and 0.05 % (iobitridol). CONCLUSION: Clinically observed cross-reactivity between different contrast media is a result of the presence of contrast media-specific T cells, some of which show a broad cross-reactivity pattern. Iodide ions, known to be present at low concentration in contrast media solutions, do not seem to be the causative moiety. CLINICAL IMPLICATIONS: Detailed in vitro analysis might help identify noncross-reactive contrast media. 相似文献
52.
HIV-1 integrates into resting CD4+ T cells even at low inoculums as demonstrated with an improved assay for HIV-1 integration 总被引:1,自引:1,他引:0
Human Immunodeficiency Virus Type 1 (HIV-1) establishes a latent reservoir early in infection that is resistant to the host immune response and treatment with highly active antiretroviral therapy (HAART). The best understood of these reservoirs forms in resting CD4(+) T cells. While it remains unclear how reservoirs form, a popular model holds that the virus can only integrate in activated CD4(+) T cells. Contrary to this model, our previous results suggest that HIV-1 can integrate directly into the genomes of resting CD4(+) T cells. However, a limitation of our previous studies was that they were conducted at high viral inoculum and these conditions may lead to cellular activation or saturation of restriction factors. In the present study, we tested if our previous findings were an artifact of high inoculum. To do this, we enhanced the sensitivity of our integration assay by incorporating a repetitive sampling technique that allowed us to capture rare integration events that occur near an Alu repeat. The new technique represents a significant advance as it enabled us to measure integration accurately down to 1 provirus/well in 15,000 genomes--a 40-fold enhancement over our prior assay. Using this assay, we demonstrate that HIV can integrate into resting CD4(+) T cells in vitro even at low viral inoculum. These findings suggest there is no threshold number of virions required for HIV to integrate into resting CD4(+) T cells. 相似文献
53.
A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates 总被引:3,自引:0,他引:3 下载免费PDF全文
Hislop AD Ressing ME van Leeuwen D Pudney VA Horst D Koppers-Lalic D Croft NP Neefjes JJ Rickinson AB Wiertz EJ 《The Journal of experimental medicine》2007,204(8):1863-1873
gamma 1-Herpesviruses such as Epstein-Barr virus (EBV) have a unique ability to amplify virus loads in vivo through latent growth-transforming infection. Whether they, like alpha- and beta-herpesviruses, have been driven to actively evade immune detection of replicative (lytic) infection remains a moot point. We were prompted to readdress this question by recent work (Pudney, V.A., A.M. Leese, A.B. Rickinson, and A.D. Hislop. 2005. J. Exp. Med. 201:349-360; Ressing, M.E., S.E. Keating, D. van Leeuwen, D. Koppers-Lalic, I.Y. Pappworth, E.J.H.J. Wiertz, and M. Rowe. 2005. J. Immunol. 174:6829-6838) showing that, as EBV-infected cells move through the lytic cycle, their susceptibility to EBV-specific CD8(+) T cell recognition falls dramatically, concomitant with a reductions in transporter associated with antigen processing (TAP) function and surface human histocompatibility leukocyte antigen (HLA) class I expression. Screening of genes that are unique to EBV and closely related gamma 1-herpesviruses of Old World primates identified an early EBV lytic cycle gene, BNLF2a, which efficiently blocks antigen-specific CD8(+) T cell recognition through HLA-A-, HLA-B-, and HLA-C-restricting alleles when expressed in target cells in vitro. The small (60-amino acid) BNLF2a protein mediated its effects through interacting with the TAP complex and inhibiting both its peptide- and ATP-binding functions. Furthermore, this targeting of the major histocompatibility complex class I pathway appears to be conserved among the BNLF2a homologues of Old World primate gamma 1-herpesviruses. Thus, even the acquisition of latent cycle genes endowing unique growth-transforming ability has not liberated these agents from evolutionary pressure to evade CD8(+) T cell control over virus replicative foci. 相似文献
54.
Papanastasiou Evangelos I. Theodorou Daphne J. Theodorou Stavroula J. Pakos Emilios E. Ploumis Avraam Korompilias Anastasios V. Gelalis Ioannis D. 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2020,30(3):441-446
European Journal of Orthopaedic Surgery & Traumatology - To evaluate the associations between magnetic resonance imaging (MRI) findings and pain, disability and quality of life before surgery... 相似文献
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56.
Philipp Y Maximov Russell E McDaniel Daphne J Fernandes Valeriy R Korostyshevskiy Puspanjali Bhatta Thomas E Mürdter David A Flockhart V Craig Jordan 《British journal of pharmacology》2014,171(24):5624-5635
Background and Purpose
Tamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of endoxifen for its effect, we determined the anti-oestrogenic efficacy of tamoxifen and its metabolites, including endoxifen, at concentrations corresponding to serum levels measured in breast cancer patients with various CYP2D6 genotypes (simulating tamoxifen treatment).Experimental Approach
The biological effects of tamoxifen and its metabolites on cell growth and oestrogen-responsive gene modulation were evaluated in a panel of oestrogen receptor-positive breast cancer cell lines. Actual clinical levels of tamoxifen metabolites in breast cancer patients were used in vitro along with actual levels of oestrogens observed in premenopausal patients taking tamoxifen.Key Results
Tamoxifen and its primary metabolites (4OHT and NDMTAM) only partially inhibited the stimulant effects of oestrogen on cells. The addition of endoxifen at concentrations corresponding to different CYP2D6 genotypes was found to enhance the anti-oestrogenic effect of tamoxifen and its metabolites with an efficacy that correlated with the concentration of endoxifen; at concentrations corresponding to the extensive metabolizer genotype it further inhibited the actions of oestrogen. In contrast, lower concentrations of endoxifen (intermediate and poor metabolizers) had little or no anti-oestrogenic effects.Conclusions and Implications
Endoxifen may be a clinically relevant metabolite in premenopausal patients as it provides additional anti-oestrogenic actions during tamoxifen treatment. 相似文献57.
Pranav Jani Krista Lowe Murray Hinder Claire Galea Daphne D'ruz Nadia Badawi Mark Tracy 《Transfusion》2019,59(10):3093-3101
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