119 research outputs found
Evaluating tumour response to primary radiochemotherapy in breast cancer patients: what role for breast magnetic resonance imaging?
HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation
HIV's evasion of the cellular immune response
Despite a strong cytotoxic T-lymphocyte (CTL) response directed against viral antigens, untreated individuals infected with the human immunodeficiency virus (HIV-1) develop AIDS, We have found that primary T cells infected with HIV-1 downregulate surface MHC class I antigens and are resistant to lysis by HLA-A2-restricted CTL clones. In contrast, cells infected with an HIV-1 in which the nef gene is disrupted are sensitive to CTLs in an MHC and peptide-specific manner. In primary T cells HLA-A2 antigens are downmodulated more dramatically than total MHC class I antigens, suggesting that nef selectively downmodulates certain MHC class I antigens. In support of this, studies on ceils expressing individual MHC class I alietes have revealed that nef does not downmodulate HLA-C and HLA-E antigens, This selective downmodulation allows Infected cells to maintain resistance to certain natural killer cells that lyse infected cells expressing low levels of MHC class I antigens. Downmodulation of MHC class I HLA-A2 antigens occurs not only in primary T cells, but also in B and astrocytoma cell lines. No effect of other HIV-1 accessory proteins such as vpu and vpr was observed. Thus Nef is a protein that may promote escape of HIV-1 from immune surveillance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75570/1/j.1600-065X.1999.tb01283.x.pd
Structural and regulatory diversity shape HLA-C protein expression levels
Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression
Profiling Trait Anxiety: Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice
Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait âanxietyâ. We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior
Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers
BACKGROUND: Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers. METHODS: To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively. RESULTS: We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13(Z )(amplified at ZNF217 only) in 9.9%, and 20q13(Co )(co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13(Z )and 20q13(Co )(1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype. CONCLUSION: Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers
«La relation de limitation et dâexception dans le français dâaujourdâhui : exceptĂ©, sauf et hormis comme pivots dâune relation algĂ©brique »
Lâanalyse des emplois prĂ©positionnels et des emplois conjonctifs dâ âexceptĂ©â, de âsaufâ et dâ âhormisâ permet dâenvisager les trois prĂ©positions/conjonctions comme le pivot dâun binĂŽme, comme la plaque tournante dâune structure bipolaire. PlacĂ©es au milieu du binĂŽme, ces prĂ©positions sont forcĂ©es par leur sĂ©mantisme originaire dĂ»ment mĂ©taphorisĂ© de jouer le rĂŽle de marqueurs dâinconsĂ©quence systĂ©matique entre lâĂ©lĂ©ment se trouvant Ă leur gauche et celui qui se trouve Ă leur droite. Lâopposition qui surgit entre les deux Ă©lĂ©ments nâest donc pas une incompatibilitĂ© naturelle, intrinsĂšque, mais extrinsĂšque, induite. Dans la plupart des cas (emplois limitatifs), cette opposition prend la forme dâun rapport entre une « classe » et le « membre (soustrait) de la classe », ou bien entre un « tout » et une « partie » ; dans dâautres (emplois exceptifs), cette opposition se manifeste au contraire comme une attaque de front portĂ©e par un « tout » Ă un autre « tout ». De plus, lâinconsĂ©quence induite mise en place par la prĂ©position/conjonction paraĂźt, en principe, tout Ă fait insurmontable. Dans lâassertion « les Ă©cureuils vivent partout, sauf en Australie » (que lâon peut expliciter par « Les Ă©cureuils vivent partout, sauf [quâils ne vivent pas] en Australie »), la prĂ©position semble en effet capable dâimpliquer le prĂ©dicat principal avec signe inverti, et de bĂątir sur une telle implication une sorte de sous Ă©noncĂ© qui, Ă la rigueur, est totalement inconsĂ©quent avec celui qui le prĂ©cĂšde (si « les Ă©cureuils ne vivent pas en Australie », le fait quâils « vivent partout » est faux). NĂ©anmoins, lâanalyse montre quâalors que certaines de ces oppositions peuvent enfin ĂȘtre dĂ©passĂ©es, dâautres ne le peuvent pas. Câest, respectivement, le cas des relations limitatives et des relations exceptives. La relation limitative, impliquant le rapport « tout » - « partie », permet de rĂ©soudre le conflit dans les termes dâune somme algĂ©brique entre deux sous Ă©noncĂ©s pourvus de diffĂ©rent poids informatif et de signe contraire. Les valeurs numĂ©riques des termes de la somme Ă©tant dĂ©sĂ©quilibrĂ©es, le rĂ©sultat est toujours autre que zĂ©ro. La relation exceptive, au contraire, qui nâimplique pas le rapport « tout » - « partie », nâest pas capable de rĂ©soudre le conflit entre deux sous Ă©noncĂ©s pourvus du mĂȘme poids informatif et en mĂȘme temps de signe contraire : les valeurs numĂ©riques des termes de la somme Ă©tant symĂ©triques et Ă©gales, le rĂ©sultat sera toujours Ă©quivalent Ă zĂ©ro
Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients
Objective:
To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA).
Design:
Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0â4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country.
Results:
In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69â4.97] and 3.30 [2.17â5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32â2.06] and 1.38 [1.15â1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA.
Conclusion:
Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR
Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice
Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function
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