Inhibition of murine T-cell responses by anti-oxidants: the targets of lipo-oxygenase pathway inhibitors.

We have previously established that oxidative phenomena are involved in human T-cell activation (Sekkat, Dornand & Gerber, 1988). In the present work we have studied the effect of different anti-oxidants (scavengers of O2-, .OH and lipo-oxygenase inhibitors) on the stimulation of murine T cells. We report here that all the anti-oxidants used suppressed T-lymphocyte proliferation and IL-2 synthesis, the former effect resulting very likely from the latter. This inhibition was concomitant with the triggering of activation. We also demonstrate that the various anti-oxidants have different biochemical targets. Unlike the other compounds, the phenolic drugs nordihydroguaiaretic acid (NDGA) and butylated hydroxyanisole (BHA), which block lipid peroxidation, affect both signals triggered by the binding of lectin to its receptors: they suppress the rise of intracellular free calcium concentration and inhibit some of the events, depending on the sole protein kinase C activation, namely IL-2 receptor expression and phorbol myristate acetate (PMA)-induced pH change. Our results are discussed within the framework of a possible involvement of reactive oxygen species and of arachidonic acid derivative(s) in T-cell activation and IL-2 production.     

Scalp topography of the spontaneous K-complex and of delta-waves in human sleep

Objective: Together with spindles, K-complexes are well known hallmarks of stage 2 sleep (S2). However, little is known about their topographical distribution in comparison to delta-waves and to K-complexes superimposed by spindles. Patients and methods: In this study, the topographical distribution of spontaneous K-complexes and delta-waves in S2 and delta-waves in stage 4 sleep (S4) in 10 healthy young adults (aged 20 to 35 years, 7 female) was investigated. K-complexes with and without spindles in S2, delta-waves with and without spindles in S2, and delta-waves in S4 distributed all over the night were visually selected. EEG power maps and statistical parametric maps were calculated. Results: Absolute delta power of S2 K-complexes appeared to be significantly higher than of S2 delta-waves and delta power of S4 delta-waves was higher than of S2 delta-waves. In K-complexes and delta-waves, power was found to be highest over medio-frontal regions in the delta frequency band (0.5 - 4.0 Hz) with a second maximum occipitally in delta-waves, no matter whether superimposed by a spindle or not. Conclusion: K-complexes and delta-waves in S2 differ in topographical distribution. Even though in S2 delta-waves have less power, they have a similar topographical distribution in S2 and S4, supporting the hypothesis that delta-waves in S2 further develop towards delta-waves in slow wave sleep. The delta frequency components of K-complexes and delta-waves are unaffected by spindles.     

CCL22-induced responses are powerfully enhanced by synergy inducing chemokines via CCR4: evidence for the involvement of first beta-strand of chemokine

In an attempt to clarify how cells integrate the signals provided by multiple chemokines expressed during inflammation, we have uncovered a novel mechanism regulating leukocyte trafficking. Our data indicate that the concomitant exposure to CCR4 agonists and CXCL10/IP-10 strongly enhances the chemotactic response of human T lymphocytes. This enhancement is synergistic rather than additive and occurs via CCR4 since it persists after CXCR3 blockade. Besides chemotaxis, other cellular responses are enhanced upon stimulation of CCR4-transfected cells with CCL22/MDC plus CXCL10. Several other chemokines in addition to CXCL10 were able to increase CCL22-mediated chemotaxis. The first beta-strand of the chemokine structure is highly and specifically implicated in this phenomenon, as established using synergy-inducing and non-synergy-inducing chimeric chemokines. As shown in situ for skin from atopic and allergic contact dermatitis patients, this organ becomes the ideal environment in which skin-homing CCR4(+) T lymphocytes can accumulate under the stimulus offered by CCR4 agonists, together with the synergistic chemokines that are concomitantly expressed. Overall, our results indicate that chemokine-induced synergism strengthens leukocyte recruitment towards tissues co-expressing several chemokines.     

Spatial memory and learning deficits after experimental pneumococcal meningitis in mice

Survivors of bacterial meningitis frequently suffer from long-term sequelae, particularly from learning and memory deficits. For this reason, spatial memory and learning was studied in a mouse model of ceftriaxone-treated Streptococcus pneumoniae meningitis. Persistent deficits of spatial learning despite normal motor function were observed in mice infected with 10(4) colony-forming units (CFU) in 25 microl of saline into the right forebrain in comparison to mice treated with an equal amount of saline. Survivors of meningitis performed significantly worse in memorizing a hidden platform in a Morris water maze. After 2 weeks, the difference between post-meningitis and control mice diminished. Yet, when the platform was moved after 180 days, learning of the new location was still strongly impaired in mice surviving meningitis.     

Evidence for a fourth locus in Usher syndrome type I.

Usher syndrome type I (US1) is an autosomal recessive condition in which three different genes have been already localised (USH1A, USH1B, and USH1C on chromosomes 14q32, 11q13, and 11p15 respectively). The genetic heterogeneity of US1 has been confirmed in a previous study by linkage analysis of 20 French pedigrees. Here, we report the genetic exclusion of the three previously reported loci in two large multiplex families of Moroccan and Pakistani origin, suggesting the existence of at least a fourth locus in Usher syndrome type I.