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991.
Perrin G Ferreira G Meurisse M Verdin S Mouly AM Lévy F 《Behavioral neuroscience》2007,121(1):148-155
Recent evidence indicates that reactivation of consolidated memories returns them to a protein-synthesis-dependent state called reconsolidation. The hypothesis that memories reconsolidate has never been assessed in social memory. The authors tested whether sheep (Ovis aries) mothers' memory of their lambs undergoes reconsolidation upon reactivation. After 7 days of mother-young contact, ewes were separated from their lambs for 8 hr, after which the lambs were reintroduced to their mothers for a 10-min reactivation session. Before reactivation, mothers received a subcutaneous injection of either the protein-synthesis inhibitor cycloheximide (CY, 1 mg/kg) or vehicle. Mothers' lamb memory was tested 1 hr (short-term memory [STM]) or 16 hr (long-term memory [LTM]) after reactivation. Mothers treated with CY exhibited intact STM but deficient LTM. CY injection without reactivation or before presentation of an alien lamb induced no deficit in LTM. CY-induced LTM deficit was alleviated by (a) introducing a reminder just before the LTM test, (b) extending mother-young contact, and (c) preventing suckling by the familiar lamb during reactivation. Thus, reconsolidation can be shown to exist in social memory, and some of its boundary conditions are discussed. 相似文献
992.
Chevigné A Yilmaz N Gaspard G Giannotta F François JM Frère JM Galleni M Filée P 《Journal of immunological methods》2007,320(1-2):81-93
Mapping of epitopes is a crucial step for the study of immune pathways, the engineering of vaccines and the development of immunoassays. In this work, the Bacillus licheniformis beta-lactamase BlaP has been engineered to display heterologous polypeptides in a permissive and solvent-exposed loop. When combined with phage display, this modified enzyme can be used for epitope mapping by cloning random gene fragments. The procedure presented in this paper allows the selection of large infectious phage libraries with high diversity and efficient beta-lactamase activities. A useful aspect of the proposed technique results from the possibility of using the beta-lactamase activity carried by phages to evaluate the proportion of immobilised phages during the successive enrichment steps of the library or competition experiments with the selected phages. Another advantage of the technique derives from the fact that the epitope is selected as a bifunctional hybrid protein, which can be overproduced and purified. The resulting recombinant protein associates an epitope with a specific and efficient enzymatic activity. This constitutes an original tool for immunoassay development. A virus influenza hemagglutinin (HA1)-gene fragment library has been generated with this system and used to identify a linear epitope. 相似文献
993.
Bourdeaut F Fréneaux P Thuille B Lellouch-Tubiana A Nicolas A Couturier J Pierron G Sainte-Rose C Bergeron C Bouvier R Rialland X Laurence V Michon J Sastre-Garau X Delattre O 《The Journal of pathology》2007,211(3):323-330
Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected. 相似文献
994.
995.
Lyles KW Colón-Emeric CS Magaziner JS Adachi JD Pieper CF Mautalen C Hyldstrup L Recknor C Nordsletten L Moore KA Lavecchia C Zhang J Mesenbrink P Hodgson PK Abrams K Orloff JJ Horowitz Z Eriksen EF Boonen S;HORIZON Recurrent Fracture Trial 《The New England journal of medicine》2007,357(18):1799-1809
996.
Sorafenib in advanced clear-cell renal-cell carcinoma 总被引:1,自引:0,他引:1
997.
John E. Cobb Jean Leblond Frédéric S. Dumont Luc Noreau 《Disability and health journal》2018,11(4):583-590
Background
Various types of limitations on community participation are experienced by people with spinal cord injury (SCI).Objectives
To determine: 1) the perceived influence of six intrinsic/extrinsic factors (i.e. physical impairment, emotional condition, thinking skills, environment, lack of assistance, discrimination) on participation in 26 life activities, 2) if this influence varied based on extent of participation, and 3) if personal or environmental characteristics influenced perceptions.Methods
Secondary analysis of a cohort (SCI Community Survey, n?=?1508) using the SCI Person-Perceived Participation in Daily Activities Questionnaire. Frequency tables, Fisher’s exact tests and correspondence analyses.Results
Respectively, 79.6% and 38.5% of respondents perceived that their physical impairment and the natural and/or built environment were the main factors that limited participation across all activities. Considering participation between three groups (no participation; less than wanted; as much as wanted), significant differences (p?<?0.001) of perceptions were observed in 65% of the combinations (26 activities x 6 factors). The hypothesis that respondents who did not participate would perceive the highest proportion of limitations was confirmed in 41% of the combinations. Perceived influence of the intrinsic/extrinsic factors on participation was not significantly influenced by other personal or environmental characteristics.Conclusion
A majority of people with SCI perceived that their participation is limited by one or more of intrinsic/extrinsic factors. Perceptions regarding which factors influence participation differ between activities and these perceptions appear related to the extent of participation suggesting that those who actively participate could be the most sensitive to limitations in certain activities. 相似文献998.
Frédéric Cosnier Hervé Nunge Élodie Bonfanti Stéphane Grossmann Anne-Marie Lambert-Xollin Samuel Muller 《Xenobiotica; the fate of foreign compounds in biological systems》2018,48(7):684-694
1.?Multiple exposures are ubiquitous in industrial environments. In this article, we highlight the risks faced by workers and complete the data available on the metabolic impact of a common mixture: toluene (TOL) and methylethylketone (MEK).2.?Rats were exposed by inhalation under controlled conditions either to each solvent individually, or to mixtures of the two. How the interaction between the two solvents affected their fate in the blood and brain, their main relevant urinary metabolites (o-cresol, benzylmercapturic acid for TOL and 2,3-butanediols for MEK) and their hepatic metabolism were investigated.3.?Although the cytochrome P450 concentration was unchanged, and the activities of CYP1A2 and CYP2E1 isoforms were not additively or synergistically induced by co-exposure, TOL metabolism was inhibited by the presence of MEK (and vice versa). Depending on the relative proportions of each compound in the mixture, this sometimes resulted in a large increase in blood and brain concentrations. Apart from extreme cases (unbalanced mixtures), the amount of o-cresol and benzylmercapturic acid (and to a lesser extent 2,3-butanediols) excreted were proportional to the blood solvent concentrations.4.?In a co-exposure context, ortho-cresol and benzylmercapturic acid can be used as urinary biomarkers in biomonitoring for employees to relatively accurately assess TOL exposure. 相似文献
999.
Frédéric Cosnier Stéphane Grossmann Hervé Nunge Céline Brochard Samuel Muller Anne-Marie Lambert-Xolin 《Drug and chemical toxicology》2018,41(1):42-50
Methylethylketone (MEK) is widely used in industry, often in combination with other compounds. Although nontoxic, it can make other chemicals harmful. This study investigates the fate of MEK in rat blood, brain and urine as well as its hepatic metabolism following inhalation over 1 month (at 20, 200 or 1400?ppm). MEK did not significantly accumulate in the organism: blood concentrations were similar after six-hour or 1-month inhalation periods, and brain concentrations only increased slightly after 1 month’s exposure. Urinary excretion, based on the major metabolites, 2,3-butanediols (± and meso forms), accounted for less than 2.4% of the amount inhaled. 2-Butanol, 3-hydroxy-2-butanone and MEK itself were only detectable in urine in the highest concentration conditions investigated, when metabolic saturation occurred. Although MEK exposure did not alter the total cytochrome P450 concentration, it induced activation of both CYP1A2 and CYP2E1 enzymes. In addition, the liver glutathione concentration (reduced and oxidized forms) decreased, as did glutathione S-transferase (GST) activity (at exposure levels over 200?ppm). These metabolic data could be useful for pharmacokinetic model development and/or verification and suggest the ability of MEK to influence the metabolism (and potentiate the toxicity) of other substances. 相似文献
1000.
Rohini Sharma Lars Wilkinson Hrvoje Vrazic Evan Popoff Sandra Lopes Steve Kanters 《Current medical research and opinion》2018,34(9):1595-1603
Objective: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin.Methods: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA1c, weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (±4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity.Results: Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0?mg and 0.5?mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA1c for once-weekly semaglutide 1.0?mg vs SGLT-2is ranged from ?0.66% for canagliflozin 300?mg (95% Credible Intervals [CrI]: ?0.82, ?0.50%) to ?1.11% for dapagliflozin 5?mg (95% CrI: ?1.37, ?0.85%). Once-weekly semaglutide 1.0?mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data.Conclusion: Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy. 相似文献