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Biomedical subjects

J F Nicolas

Publications and source records attributed to J F Nicolas.

At least 91 records · Page 5Linked to original sources

[Bias of index of T-lymphocytes and chronic inflammatory dermatoses].

The pathogenesis of chronic inflammatory and autoimmune diseases is still not understood. The hypothesis that a bias in the T cell receptor repertoire could explain the susceptibility of some individuals to a particular disease was recently proposed on the basis of results obtained in animal models of human diseases. In this review, we focus on the structure of the T cell receptor and on the new insights in the study of the T cell repertoire in human inflammatory diseases, with special emphasis to skin disorders.

Antibody Formation↗

Catecholaminergic neurons result from intracerebral implantation of embryonal carcinoma cells.

A replication-defective retrovirus was used to introduce the marker gene nlsLacZ into the murine embryonal carcinoma (EC) cell line PCC7-S-aza-R-1009. Undifferentiated EC cells were implanted into the central nervous system of adult rats. One month later, the grafted cells continued to express the nlsLacZ gene. Immunohistochemical analysis demonstrated the presence of EC-derived neurons. These neurons were capable of expressing tyrosine hydroxylase and extended neurites into the host parenchyma. EC-derived glial cells could not be detected. There was no evidence of tumorigenicity. These results demonstrate the utility of EC cells for introduction of exogenous gene products into the central nervous system in experimental models of gene therapy.

Animals↗

Contact sensitivity in mice: differential effect of vitamin D3 derivative (calcipotriol) and corticosteroids.

Vitamin D3 derivatives are new compounds used topically for the treatment of psoriasis. To get better insights into the mechanisms of action of these compounds, we studied the effect of local treatment with calcipotriol (vitamin D3 synthetic analogue) and compared it to that of betamethasone dipropionate in a murine contact sensitivity (CS) test, the Mouse Ear Swelling Test. Two haptens were used: oxazolone and paraphenylenediamine. Betamethasone and calcipotriol exerted a differential effect on the delayed-type hypersensitivity response. When drugs were applied to the abdomen (sensitization site) before sensitization, no effect was observed. When betamethasone was applied to the abdomen for 4 consecutive days after epicutaneous sensitization, a diminution of the CS response to the relevant hapten was observed, whereas calcipotriol given in the same conditions did not affect the reaction. Ointments were then administered to the ear (elicitation site) either for 4 consecutive days prior to the challenge, or for 4 days before and 2 days after the challenge. In both conditions, calcipotriol and betamethasone exerted a differential effect on elicitation, the latter inhibiting and the former increasing the CS response to oxazolone and paraphenylenediamine. From these results we conclude: (1) that vitamin D3 derivatives are devoided of immunosuppressive effects when applied topically, and (2) that clinical improvement of chronic inflammatory dermatoses observed with topical vitamin D3 derivatives and corticosteroids is due to different mechanisms.

Adrenal Cortex Hormones↗

In-situ preferential usage of V alpha 8 T-cell receptor gene segments in a patient with bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with the occurrence of autoantibodies directed to a limited series of antigens located at the basement membrane zone of the dermo-epidermal junction. Previous studies have demonstrated the presence of activated T cells in BP lesions although their actual contribution to the pathogenesis of the disease has remained unclear. One approach to better understanding the significance of these T-cell infiltrates is to study the diversity of the recognition receptors (TCRs) expressed at the lesion sites. We report here an extensive analysis, performed in one patient with typical BP, where 187 TCR in frame transcripts from a lesional area, from clinically normal skin or from peripheral blood lymphocytes have been sequenced and compared. The data show preferential usage of the V alpha 8 subfamily gene segments in the lesion. It is therefore suggested that T-cell infiltration in BP may not simply reflect a non-specific inflammatory process but include antigen-specific responses.

Amino Acid Sequence↗

Dissociation of allergenic and immunogenic functions in contact sensitivity to para-phenylenediamine.

Contact sensitivity to para-phenylenediamine (PPD) is a frequent delayed-type hypersensitivity resulting in contact dermatitis. The aim of the present study, conducted in 16 patients allergic to PPD (as assessed by a positive patch test), was to get better insight into the mechanism of T-cell activation in PPD contact sensitivity. PPD was unable to induce significant proliferation of T cells from a first set of 9 patients. In 7 further patients, lymphocyte proliferation was assessed using PPD and 2 PPD metabolites, namely Brandrowski's base (BB) and benzoquinone (BQ). BB specifically stimulated T-cell proliferation in a dose-dependent fashion in all 7 patients whereas BQ, like PPD, was ineffective. The peripheral blood mononuclear cells (PBMC) of 8 PPD nonallergic individuals did not respond to either PPD, BB or BQ. We concluded from this study that: (1) the immunogenic hapten in PPD hypersensitivity is not PPD itself, and (2) BB might be the oxidative derivative of PPD endowed with T-cell-activating properties. Further support to this statement was provided by the observation that a T cell line derived from PBMC of a PPD-allergic patient in the presence of PPD responded to BB but not to PPD. Our in vitro results suggest that PPD is a prohapten which when applied on the skin is metabolized and converted into products (such as BB) which are the immunogenic haptens able to activate specific T cells.

Benzoquinones↗

Alpha interferon treatment in atopic dermatitis.

Eight patients suffering from atopic dermatitis were treated with interferon alpha 2b. They received low or intermediate doses (9-15 x 10(6) U/week) for a short period of time (4-8 weeks), with a moderate improvement of skin lesions in 4 of them and no change or an exacerbation of the disease in the other 4. Among the 4 patients who slightly improved at 4 weeks, 3 did not show any beneficial effect of interferon after 8 weeks. Serum IgE levels, which were increased in all patients before treatment, were not reduced under interferon therapy. This study shows that intermediate doses of interferon alpha 2b are not effective in the short-term treatment of atopic dermatitis.

Adult↗

Clonal analysis in the intact mouse embryo by intragenic homologous recombination.

A method of cell labelling based on homologous recombination has been developed to analyze the lineage of cells in intact embryos. In this method a LacZ gene bearing an inactivating duplication in its coding frame (termed LaacZ gene) is inserted into the genome of mice. Subsequently, in transgenic embryos, homologous recombination within the duplication recreates an open reading frame for beta-galactosidase. The descendants of the modified cell are identified histochemically. This recombination occurs at random and with low frequency. It can occur in cells in which the gene is not transcribed. It can also be intragenic (in adjacent sequences) as single transgene copies are found to recombine. To analyze the lineage of cells in the myotome the expression of the LaacZ gene is driven by a promoter which confers expression specifically to cells of this compartment. The analysis in 40-somite embryos (E11.5) is reported. We show that individual beta-gal+ myotomal clones may contribute to somites from both sides of the animal, in which case the right and the left somites are labelled consecutively and at the same antero-posterior level. It reflects predictable clonal origin of myotomal cells at the primitive streak stage or before and demonstrates three morphogenetic movements in the mesoderm: bilateral, antero-posterior and mediolateral. The results also show that the left-right assignation of myotomal cells in mouse is late, probably occurring during cell migrations at gastrulation. It applies also to presumptive myotomal cells of limb musculature. These results contrast with early left-right assignation of most tissues in Xenopus and Zebrafish. Some clones contribute to distant somites, suggesting persistence of presumptive myotomal cells in the presumptive paraxial mesoderm and clonal organisation of the myotome.

Animals↗

[Interleukin-2 immunotherapy and cutaneous manifestations].

The cutaneous manifestations which follow the administration of recombinant interleukin-2 (rIL-2) are well known, but their nature and severity have not yet been fully studied. The authors report the dermatological changes observed in 12 patients treated with rIL-2 for renal cancer. The predominant lesion was generalized erythema followed by desquamation.

Adult↗

Lineage control of an integration site-dependent transgene combined with the beta-globin locus control region.

In mice, the expression of integration site-dependent transgenes is controlled by host DNA elements. These may involve locus control regions (LCR), enhancers and silencers. We analysed the interaction between the LCR of the beta-globin locus (beta-LCR) and an integration site-dependent LacZ transgene (HPRTnlsLacZ). We obtained LacZ expression in erythroid cells of all transgenic mice, independent of temporal control, correlated to transgene copy-number. These results demonstrate that an integration site-dependent transgene can be region-controlled by the beta-LCR and establish that the beta-LacZ transgenic lines constitute a valuable source of genetically marked cells for the three erythroid series. This also extends to in vivo regulation in all three erythroid series the notion that the beta-LCR contains the information for region-control of non-erythroid genes. In non-erythroid lineages of all mice, we observed integration site-dependent LacZ expression. It suggests that a single LCR is not sufficient to insulate the LacZ gene from endogenous cis-acting control elements.

Animals↗