Point-light display: a new tool to improve verb recovery in patients with aphasia? A pilot study.

Some studies have demonstrated that Action Observation (AO) could help patients with aphasia to recover use of verbs. However, the role of kinematics in this effect has remained unknown. The main aim was to assess the effectiveness of a complementary intervention based on the observation of action kinematics in patients with aphasia. Seven aphasic patients (3 males, 4 females) aged between 55 and 88 years participated in the studies. All patients received a classical intervention and an additional, specific intervention based on action observation. This consisted in visualizing a static image or a point-light sequence representing a human action and in trying to name the verb representing the action. In each session, 57 actions were visualized: 19 represented by a static drawing, 19 by a non-focalized point-light sequence, i.e., a point-light display with all dots in white, and 19 by a focalized point-light sequence, i.e., a point-light display (PLD) with the dots corresponding to the main limbs in yellow. Before (pre-test) and after (post-test) the intervention, each patient performed the same denomination task, in which all actions were presented in photographs. The results showed a significant improvement in performance between pre and post-test, but only when the actions were presented in focalized and non-focalized point-light sequences during the intervention. The presentation of action kinematics seems crucial in the recovery of verbs in patients with aphasia. This should be considered by speech therapists in their interventions.

High titers of autoantibodies in patients with sickle-cell disease.

OBJECTIVE: Frequency and titers of autoantibodies in patients with sickle-cell disease (SCD) have been reported as relatively high. In a prospective study of 88 patients, we examined this "hyper-autoreactivity" and its clinical consequences. METHODS: For 1 year, patients with SCD were screened for the presence in their serum of antinuclear, anti-double-stranded DNA, antiextractible nuclear antigens, anticardiolipin antibodies, and rheumatoid factors. A population of 85 sex-matched individuals of similar ethnic origin served as controls. RESULTS: Whereas prevalence of autoantibodies did not differ between the 2 groups, the type and rate of antinuclear antibodies were different. Autoantibodies from the SCD patients showed various immunofluorescence patterns, whereas only speckled patterns at low titers were present in controls. No antibody specificity was found in either group. SCD patients and controls displayed similar rates of anticardiolipin antibodies, but the SCD patients tended to be more frequently positive for rheumatoid factors. Six-year followup of the SCD patients did not provide any clinical evidence for onset of an autoimmune disease, except for 1 patient who developed rheumatoid arthritis, with increasing antinuclear antibodies followed by emergence of specific markers 5 years later. CONCLUSION: Patients with SCD displayed high titers of autoantibodies. This observation may be due only to immune activation and/or dysfunction in SCD, as neither pathogenic specificity of autoantibodies nor autoimmune clinical signs appeared in the majority of cases in our study.

PPAR activators and COX inhibitors selectively block cytokine-induced COX-2 expression and activity in human aortic smooth muscle cells.

Atherosclerotic complications are related to the unstable character of the plaque rather than its volume. Vulnerable plaques often contain a large lipid core, a reduced content of smooth muscle cells (SMCs), and an accumulation of inflammatory cells. Regulation of this inflammatory response is an essential element in chronic inflammatory diseases such as atherosclerosis. Nuclear receptors and particularly peroxisome proliferator-activated receptors (PPARs) have emerged as therapeutic targets with a widespread impact on the treatment of metabolic disorders because they can modulate gene expression involved in lipid and glucose homeostasis and can exert anti-inflammatory properties. However, little is known about nuclear receptor effects on SMC inflammation, which produces large amounts of IL-6 and prostanoids. The aim of this study was to evaluate anti-inflammatory properties of nuclear receptor activators in a human physiological SMC model. We show that PPAR activators, as well as liver X receptor alpha, farnesoid X receptor and retinoid X receptor alpha activators, inhibit IL-1beta-induced SMC 6-keto PGF1alpha synthesis, an index of cyclooxygenase (COX)-2 activity, with IC(50) between 1 and 69 microM. In contrast, PPARgamma activators, as exemplified by rosiglitazone and pioglitazone, were unable to inhibit cytokine-induced 6-keto PGF1alpha synthesis. We also demonstrate for the first time that the COX-2 inhibitor rofecoxib can reduce 6-keto PGF1alpha production by both enzymatic inhibition and transcriptional repression. These results show that some nuclear receptor activators have SMC anti-inflammatory properties due to COX-2 inhibition which could participate in their anti-atherosclerotic properties beyond lipid impacts.

Human adipocyte fatty acid-binding protein (aP2) gene promoter-driven reporter assay discriminates nonlipogenic peroxisome proliferator-activated receptor gamma ligands.

Peroxisome proliferator-activated receptors (PPARs) regulate storage and catabolism of fats and carbohydrates. PPARgamma activity increases insulin sensitivity and adipocyte differentiation at the expense of adipogenesis and weight gain. The goal of this study was to 1) clone the promoter of the human adipocyte fatty acid binding protein (aP2) gene, namely fatty acid-binding protein-4, 2) characterize its pharmacological regulation, and 3) determine its putative predictability for adipogenesis. Among the selected PPAR agonists, rosiglitazone and pioglitazone displayed the highest maximal efficacy (E(max)) on reporter-gene assays in COS-7 cells cotransfected by either a galactosidase 4-response element-based or a human aP2 promoter-based Luc reporter vector, along with either chimeric or full-length human PPAR expression plasmids. The non-subtype-selective 2-(4-[2-(3-[2,4-difluorophenyl]-1-heptylureido)ethyl]phenoxy)-2-methyl-butyric acid (GW-2331) and the compounds [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propoxyl]phenoxy]-acetic acid (L-165041), (4-((2S,5S)-5-(2-(bis(phenylmethyl)amino)-2-oxoethyl)-2-heptyl-4-oxo-3-thiazolidinyl)butyl)-benzoic acid (GW-0072), and indomethacin behaved as partial agonists relative to pioglitazone in full-length human aP2-PPARgamma2. Beyond their partial PPARgamma agonist properties, these compounds elicited a lower maximal up-regulation of mouse aP2 mRNA in 3T3-L1 adipocytes as compared with pioglitazone; these properties paralleled a time-dependent increase in neutral lipids. By contrast, the selective PPARalpha agonist 2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid (BM-17.0744) neither stimulated the human aP2-PPARalpha promoter reporter-gene assay, thus demonstrating a specific interaction between PPARgamma and the aP2 promoter, nor affected lipogenesis in 3T3-L1 cells. Altogether, these data characterized a functional promoter of the human aP2 gene; its in vitro pharmacological regulation in PPARgamma-mediated reporter-gene assay may represent an interesting complement or an alternative to time-consuming procedures aiming at discriminating PPAR ligands with low lipogenic properties.

Evaluation of the new multiplexed immunoassay, FIDIS, for simultaneous quantitative determination of antinuclear antibodies and comparison with conventional methods.

Our study was done to evaluate the FIDIS Connective kit (Biomedical Diagnostics, Marne la Vallée, France) for simultaneous quantitative determination in the same sample of 9 antinuclear antibody specificities directed against double-stranded DNA, SSA, SSB, Sm, Sm/RNP, Scl-70, Jo-1, ribosome, and centromere B and to compare it with standardized commercial methods, enzyme immunoassay and immunofluorescence. FIDIS technology constitutes a new multiplexed method using the Luminex 100 system (Luminex, Austin, TX) based on the use of distinct color-coded particles and flow cytometric detection. Serum samples from people with diagnosed rheumatic diseases with well-identified markers of autoimmunity were tested by a retrospective study. Specificity was assessed by testing blood donors and potential biologic interfering samples. This first evaluation demonstrated the analytic performance of FIDIS technology. Concordances with routine methods were between 99.1% and 100.0% on 222 samples. FIDIS was reliable (coefficients of variation < 10%) and accurate (correlation coefficients with enzyme-linked immunosorbent assay between 0.90 and 0.97) in a large measure range.