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L Tesson

Publications and source records attributed to L Tesson.

27 records · Page 2Linked to original sources
PubMed1996

Analysis of human CD59 tissue expression directed by the CMV-IE-1 promoter in transgenic rats.

The investigation of human complement (C) inhibitors with a view to overcoming C-mediated tissue injury stands to benefit from the production of anatomically suitable transgenic animals. In this study, we used the CMV-IE1 enhancer/promoter to control the expression in vivo in transgenic rats of the human terminal C protein inhibitor CD59. Five transgenic rats were identified, of which four possessed at least one complete copy of the transgene. The presence of human CD59 transcripts and protein was demonstrated in two transgenic rat lines. A widespread tissue distribution of cells expressing human CD59, similar in the two lines, was observed-principally in pancreas, brain, heart, kidney, intestine and striated muscle. Whereas expression in pancreas and brain was uniform, mosaicism of CD59 expression was observed in some tissues such as heart and kidney, a proportion of cells within the tissue not expressing the transgene. Immunohistological analysis revealed surface expression of human CD59 in a variety of cells, including fibroblasts, epithelial cells and muscle cells, but not in endothelial cells. In conclusion, this paper analyses at the cellular level human CD59 expression directed by the CMV promoter in transgenic rats, amd discusses how they could be used to investigate in vivo the role of C in a variety of pathologies.

Animals↗
PubMed1995

Leukaemia Inhibitory Factor derived from rat colon carcinoma cells increases host susceptibility to tumour growth.

We have tested Leukaemia Inhibitory Factor (LIF) production by 12 rat colon tumour clones isolated from a single cell line that display various degrees of tumorigenicity. A highly significantly relationship was found between levels of soluble LIF produced by the clones and their in vivo tumorigenicity. Such results suggested a role for LIF as a tumour facilitating agent. To test this hypothesis, the highly tumorigenic and LIF producing PROb clone was transfected with the LIF cDNA in antisense orientation in order to decrease LIF production. Conversely, REGb, a low LIF producer that is rejected by syngeneic animals, as well as nude mice, was transfected with the LIF cDNA to increase its production. PROb cells transfected with antisense cDNA were shown to have decreased LIF production along with decreased tumorigenicity. LIF-transfected REGb cells expressing high LIF levels still regressed in syngeneic rats, but could form progressive tumours in nude mice. We did not detect LIF receptors on PROb or REGb cells and their in vitro proliferation was not modified by the addition of exogenous LIF. Therefore, LIF was not an autocrine growth regulator for PROb and REGb cells. Instead, LIF appears to facilitate in vivo tumour growth, without being an immunosuppressive factor sufficient on its own to allow growth of immunogenic cells in fully immunocompetent hosts.

Adenocarcinoma↗
PubMed1994

Protection of rat endothelial cells from primate complement-mediated lysis by expression of human CD59 and/or decay-accelerating factor.

The present study analyzed the ability of human decay-accelerating factor (DAF) and CD59 to protect rat endothelial cell (EC) clones from human and primate complement-mediated lysis. By flow cytometry and Scatchard analysis, we show that human DAF and/or CD59 cDNAs under the transcriptional control of elongation factor 1-alpha promoter were expressed at levels similar to or higher than that of a human EC line. Human DAF and CD59 were released from the surface of transfected rat cells by phosphatidylinositol phospholipase C, demonstrating that the two molecules were linked to the cell membrane by means of a glycolipid anchor. The functional activity of the two human C regulatory proteins expressed on rat EC lines was studied using an in vitro assay of C-dependent cytotoxic in which rat EC were incubated with human or nonhuman primate sera as sources of xenogeneic natural antibodies and C. We demonstrate that human and monkey xenogeneic natural antibodies bind to rat cells and induce lysis by a C-dependent mechanism involving mainly the C direct activation pathway. Our data indicate that human DAF and CD59, expressed either alone or in combination, abrogated all EC cytotoxicity, even in the presence of 50% human serum. This protective phenotype was correlated with decreased membrane attack complex (CD59 and/or DAF transfectants) and C3 deposition (DAF transfectants) on EC surface. Antibodies against the transfected molecules abolished the protection against C-mediated lysis.

Animals↗
PubMed1990

Frequency of the major CF mutation in French CF patients.

We have studied 124 patients of French origin, whose CF status had already been clearly established. These children belong to families previously tested with restriction fragment length polymorphism (RFLP) markers in our laboratory for genetic counselling. The most common mutation (delta F508) accounts for 67% in this population sample.

Chromosome Deletion↗
PubMed1989

Usefulness of linkage disequilibrium of KM-19 and XV-2c DNA probes for genetic counselling in a high-risk CF family.

A French couple with an individual risk of carrying the cystic fibrosis (CF) mutation of 1/2 sought genetic counselling. From the DNA haplotypes generated by XV-2c and KM-19 RFLPs, it could be deduced that only one subject was a carrier, lowering the risk of having a CF baby from 1/16 to 1/200. The strong linkage disequilibrium between these RFLPs and the CF allele observed in France reduced the risk to 1/1600.

Blotting, Southern↗
PubMedDate not supplied

[Vascular beta-adrenergic remodeling in rat transgenic model over-expressing endothelial beta3-adrenoceptors].

In rat thoracic aorta, the stimulation of endothelial beta3-adrenoceptors (beta-AR) produces a vasorelaxation through activation of a NO synthase pathway and an increase in cGMP levels. In hypertension, a global decrease of the beta-AR response has been described. In spontaneously hypertensive rats (SHR), we have shown that beta3-adrenoceptor-mediated relaxation was not modified in SHR aorta at the age of 12 weeks, in spite of an upregulation of beta3-adrenoceptors. In order to determine the consequences of an over-expression of the beta3-AR, we have developed a transgenic rat over-expressing specifically in endothelial cells the human beta3-AR (Tg beta3). By real-time quantitative PCR, we have determined the expression level of the different beta-AR subtypes. We confirmed an over-expression of the beta3-AR transcripts in Tg beta3 (ratio = 3.39 +/- 0.8; n=3 for Tg beta3 vs wild type [WT] animals). Surprisingly, we observed in Tg beta3 a decrease of beta1-AR transcripts (ratio = 0.76 +/- 0.03; n=3 for Tg beta3 vs WT animals) and no variation for beta2-AR transcripts (ratio = 1.95 +/- 0.60; n=3 for Tg beta3 vs WT animals). In aorta rings from WT and Tg beta3, the isoproterenol-induced relaxation was similar (WT: Emax = 82 +/- 6%, n=6; Tg beta3: Emax = 85 +/- 6, n=6). By contrast, in the presence of 10 microM nadolol, a beta1-, beta2-AR antagonist, the isoproterenol-induced response was significantly increased in Tg beta3 (WT: Emax = 68 +/- 6%, n=6: Tg beta3: Emax = 86 +/- 3; p < 0.01 vs WT). This effect was loss on denuded aortic rings. In conclusion, our study reported similar results to those obtained in hypertension in which a decrease of the beta-AR expression was associated to an elevation of the beta3-AR density. Moreover, this over-expression in our transgenic model is associated to a potential response induced by beta3-AR. Therefore, an activation of beta3-AR could supply the beta1- / beta2-AR decrease. Then, our transgenic model should be used to characterize the physiological consequences of this over-expression as well as to determine the putative involvement of this receptor in the pathogenesis of hypertension.

Animals↗