T-cell repertoire analysis in chronic plaque psoriasis suggests an antigen-specific immune response.

Psoriasis is a chronic inflammatory cutaneous disease of unknown etiology. Activation of T cells is thought to play a major role in the pathophysiology of psoriasis. In order to gain insight into the nature of the antigen (superantigen or nominal protein antigen) involved in psoriatic lesions, we have used a RT-PCR method to analyze the frequency of the 24 T cell receptor V beta chain (TCRBV) subfamilies and the size of the antigen-binding region (CDR3), using the immunoscope assay, in skin lesions of patients with chronic plaque-type psoriasis. Semi-quantitative analysis showed that no significant difference in V beta subfamily usage could be detected in T lymphocytes infiltrating lesional skin as compared to blood lymphocytes. Alternatively, determination of the size distribution of the CDR3 of all the V beta subfamilies revealed only in psoriatic skin a marked TCR oligoclonality defined by the presence in 3 to 5 V beta subfamilies of a single predominant CDR3 size which was associated with a unique V beta-J beta combination. Identical patterns of CDR3 length and V beta-J beta combination profiles were found in symetrical lesional sites from two psoriatic patients. This type of skewed CDR3 size profile is reminiscent of a local stimulation of T lymphocytes by nominal protein antigens. These data suggest that T lymphocytes infiltrating plaque-type psoriatic skin comprise expansions of oligoclonal T cells in response to stimulation by an antigen present in the skin.

Light-microscopic localization of somatostatin binding sites in the locus coeruleus of the rat.

Somatostatin (SS14) binding sites within locus coeruleus (LC) were localized at the light microscope level by [125I][Tyr0,D-Trp8]SS14 radioautography combined with an immunohistochemical/neurotoxic lesioning approach. In intact rats, the dense accumulation of SS14 binding sites of LC conspicuously overlapped with the cluster of tyrosine hydroxylase (TH) immunoreactive neurons; SS14 specific binding was directly proportional to the number of TH immunostained (TH+) cell bodies per mg of tissue throughout LC. Complete lesion of catecholaminergic nerve cell bodies of LC by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA) resulted in the total abolition of SS14 specific binding in the structure. In addition, specifically bound [125I][Tyr0, D-Trp8]SS14 and TH+ cell density were quantified serially in a set of rats bearing various partial neurotoxic lesions; a highly significant correlation was found between the two parameters at each of the 16 coronal levels of LC examined. The coefficient of proportionality was identical at all levels. These results strongly suggest that somatostatin binding sites are uniformly localized on all noradrenergic neurons of LC.

Suppression of active sleep by chronic treatment with chlorimipramine during early postnatal development: effects upon adult sleep and behavior in the rat.

In an attempt to study the possible role of active sleep in brain development, male rats were injected twice daily with chlorimipramine, a potent monoamine reuptake blocker, from 1 week to 3 weeks of postnatal age. AS was reduced to less than 10% of total sleep time, the level found in mature rats. Most of the AS reduction was compensated for by quiet sleep but a slight increase in wakefulness also occurred, owing to brief interruptions of sleep at times when AS was expected. In adulthood, the AS-deprived rats showed a higher percentage of AS than did the controls, due to an increase in frequency and duration of AS epochs. Moreover, many of the epochs contained abnormally frequent and strong jerky body movements and rapid-eye-movements, reminiscent of neonatal AS patterns. In addition, the amplitude of hippocampal theta waves during AS was greater than in control rats. The chlorimipramine-treated rats also showed behavioral abnormalities in later life. On the open field test exploratory behavior was much reduced, while increased rearing and defecation occurred. Masculine sexual performance was severely deficient, primarily due to the low level of intromissions and ejaculations. Experimental animals performed less efficiently than controls on a temporal learning task (differential reinforcement of low response rate) and responded more rapidly on a spatial task (left-right alternation learning). These results demonstrate that early interference with the functioning of monoaminergic systems can have long-lasting physiological and behavioral consequences. Furthermore, they are consistent with the hypothesis that AS is an important factor in normal brain development.

Evaluation of iodide deficiency in Togo using an optimized potentiometric method for iodide estimation in urine.

A pilot study was carried out in two Togolese localities (Gobe, Moretan) situated in an endemic goiter area. The aim of this work was to collect laboratory and nutritional data to assess and follow up campaigns against iodide deficiency. Ninety-seven urine samples were analysed. We studied the urinary excretion and the iodine concentration of important diet substances (water and salt) using an optimized potentiometric method. Mean values of urinary iodide/creatinine ratios (microgram/g) observed in the two Togolese localities were respectively 34.1 +/- 6.3 in Gobe and 39.2 +/- 6.4 in Moretan. These low values differ significantly (P < 10(-9)) from the physiological values determined in Amiens, France (147.5 +/- 56.3). The drinking water of the two localities showed a low iodide concentration (2 micrograms/l). The iodide concentration of cooking salts was also low (< 0.2 mg/kg) compared with iodized salt used in France (11.2 +/- 0.2 mg/kg) These results show an iodide deficiency in both localities, probably due to the lack of iodide in the local diet. Iodide determination is specific, easy and inexpensive. It can be proposed for use in campaigns against goiters of nutritional origin.

[Study of epitopic sites of the major bullous pemphigoid antigen (BPAg1)]. / Etude des sites épitopiques de l'antigène majeur de la pemphigoïde bulleuse (BPAg1).

Bullous pemphigoid is an acquired blistering skin disease associated with the production of IgG autoantibodies to 230 kDa BP Ag (BPAg1) and to 180 kDa BP Ag (BPAg2). The aim of our work was to better characterize the epitopes of BPAg1. For this, we firstly generated a bullous pemphigoid recombinant protein of 55 kDa Mr (rBP55) from a cDNA sequence encoding for the carboxyterminal region of the 230 kDa BP antigen. Ninety-two percent of sera from patients with autoantibodies to the 230 kDa polypeptide recognized the rBP 55 protein. These results confirm that this 555 aminoacid segment corresponding to rBP 55 contains major epitopes. In order to study the epitopes of the amino-terminal portion of the BPAg1 antigen, we generated immortalized B cell lines secreting human monoclonal antibodies to BPAg1 from two patients whose sera reacted with native BPAg1 but not with the recombinant rBP55 carboxy-terminal peptide. Blocking immunofluorescence experiments and phylogenetic studies showed that these human monoclonal antibodies recognize different epitopes of BPAg1. According to these studies, we can conclude on the wide variety of epitopes recognized by BPAg1 autoantibodies.