Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies.

Approximately 2% of the Caucasian population is affected by psoriasis (PS); a chronic inflammatory skin disease triggered by both genetic and environmental risk factors. In addition to a major contribution from the HLA class I region, PS susceptibility loci have been mapped to a number of regions including 1q21, 3q21, 4qter, 14q31-q32, 17q24-q25, 19p13.3 and 20p. Some of these overlap with loci implicated in other autoimmune/inflammatory diseases. Global gene expression studies are beginning to provide insights into the etiology of these and other complex diseases. We used Affymetrix oligonucleotide arrays comprising approximately 12 000 known genes to initiate a more comprehensive analysis of the transcriptional changes that occur in involved and uninvolved skin of 15 psoriatic patients versus six normal controls. Expression levels of the transcripts detected on the arrays were first used to determine the relationship of samples to each other using hierarchical clustering. This analysis clearly differentiated involved psoriatic skin from uninvolved and normal skin. Clusters of differentially expressed genes with similar expression patterns in the same samples were then identified. Six out of 32 clusters contained a total of 177 transcripts that were differentially expressed in involved psoriatic skin versus normal skin. These differences were independent of the gender, age, skin site and HLA class I status of the patient. Ten of the 177 genes were also differentially expressed in uninvolved skin, and several mapped to regions previously shown to harbor psoriasis susceptibility loci.

[Cerebral distress in the infant (author's transl)]. / La souffrance cérébrale du nourrisson. données E.E.G. évolutives. A propos de quelques observations.

The authors using a E.E.G. laboratory not specialised in infant recordings, analysed the serial E.E.G. data in 8 infants presenting variable degrees of cerebral distress. In 2 cases not ventilated artifically and who finally died, the tracings were characterized by periodic activity in the occipital region similar to that seen in the isolated cerebral cortex. Autopsy revealed significant hydrocephalus with porencephaly and preservation of a narrow band of histologically normal occipital cortex. The authors observations of variable evolution illustrate some well known facts and in particular the importance of serial high quality E.E.G. tracings during the neonatal period to assist accurate prognosis and to repeat the tracing over the ensuing months.

[An electrophysiological study of direct occipito-frontal connections in centrum semi-ovale of Papio papio]. / Etude electrophysiologique des connexions occipito-frontales directes au niveau du centre ovale chez Papio papio

1. Evoked responses to single visual stimuli (VEP) and driving by intermittent light stimulation (ILS) were recorded with macroelectrodes from the central white matter (centrum semiovale) of 12 Papio papio baboons. 2. Two types of VEP were identified: VEPs with constant morphology, localized in the long associative bundles connecting the occipital, temporal and frontal lobes; VEPs with variable morphology and without any preferential localization; these probably originate from other types of fibres also belonging to the centrum semi-ovale. 3. Concerning the long associative bundles which have been individualized, they might be the equivalent of the occipito-frontal and the superior and inferior longitudinal bundles well known in man. The fusion frequency observed in these bundles during ILS increases from the frontal to the occipital lobe, because of their involvement (particularly in the parieto-temporal region) with other fibres of the centrum semi-ovale also likely to be driven by ILS. The existence of driving by ILS in these bundles demonstrates an activation of the frontal lobe by visual impulses.

Neurophysiology of photically induced epilepsy in Papio papio.

This chapter critically reviews arguments supporting the role of the frontal cortex in light-sensitive epilepsy of the baboon Papio papio in the light of the most recent neurophysiological research. In particular, it is known that spontaneous or ILS-induced paroxysmal discharges, as well as generalized seizures, originate in the frontorolandic cortical region. In this region during ILS, neurons behave in the same manner as hyperexcitable neurons in focal epileptogenic lesions of animals and man. Aso, section of the corpus callosum causes deterioration or even destruction of the synchronization that exists naturally between the two frontorolandic areas. Lastly experimental focal irritative lesions enhance light sensitivity if they are located in the frontorolandic region and inhibit it if they are located in the occipital cortex. Opposing these arguments are those that support the important role the occipital cortex plays, since its ablation makes excessive light sensitivity in the baboon disappear. Studies of the primary and nonprimary visual messages and pathways have also contributed evidence. In particular, demonstration of the existence of large numbers of direct occipitofrontal connections may help reconcile the two opposing arguments. Other evidence favoring the role of the frontal cortex is furnished by the still fragmentary studies on activation of the motor pathways and by studies in neuropharmacology. The significance and value of this type of epilepsy as an animal model of the generalized reflex epilepsies of man are discussed.