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A Bernet

Publications and source records attributed to A Bernet.

8 recordsLinked to original sources

[Netrin-1 and its dependence receptors: role in colorectal cancers].

Currently, an increasing number of receptors appear to belong to the dependence receptors family. These proteins have the capacity to induce a program of apoptosis in settings of absence of their ligand. A cell that expresses one of these receptors is thus dependent on the presence of the ligand to survive. The observation that these receptors are lost in many cancers is then suggesting that this loss is a selective advantage for tumor development because it leads tumor cells not to be dependent for survival on the presence of the ligand. We propose to focus this review on the role of some of these receptors that have been intensively studied: the dependence receptors that bind the netrin-1. After having pointed out their role in the development of the nervous system and in cell death induction, we will discuss their putative role in the pathological context of tumorigenesis and more particularly in the control of colorectal cancers.

Animals↗

Non-erythroid genes inserted on either side of human HS-40 impair the activation of its natural alpha -globin gene targets without being themselves preferentially activated.

The human alpha-globin gene complex includes three functional globin genes (5'-zeta2-alpha2-alpha1-3') regulated by a common positive regulatory element named HS-40 displaying strong erythroid-specific enhancer activity. How this enhancer activity can be shared between different promoters present at different positions in the same complex is poorly understood. To address this question, we used homologous recombination to target the insertion of marker genes driven by cytomegalovirus or long terminal repeat promoters in both possible orientations either upstream or downstream from the HS-40 region into the single human alpha-globin gene locus present in hybrid mouse erythroleukemia cells. We also used CRE recombinase-mediated cassette exchange to target the insertion of a tagged alpha-globin gene at the same position downstream from HS-40. All these insertions led to a similar decrease in the HS-40-dependent transcription of downstream human alpha-globin genes in differentiated cells. Interestingly, this decrease is associated with the strong activation of the proximal newly inserted alpha-globin gene, whereas in marked contrast, the transcription of the non-erythroid marker genes remains insensitive to HS-40. Taken together, these results indicate that the enhancer activity of HS-40 can be trapped by non-erythroid promoters in both upstream and downstream directions without necessarily leading to their own activation.

Animals↗

Targeted inactivation of the major positive regulatory element (HS-40) of the human alpha-globin gene locus.

We have examined the role of the major positive upstream regulatory element of the human alpha-globin gene locus (HS-40) in its natural chromosomal context. Using homologous recombination, HS-40 was replaced by a neo marker gene in a mouse erythroleukemia hybrid cell line containing a single copy of human chromosome 16. In clones from which HS-40 had been deleted, human alpha-globin gene expression was severely reduced, although basal levels of alpha 1 and alpha 2-globin mRNA expression representing less than 3% of the level in control cell lines were detected. Deletion of the neo marker gene, by using FLP recombinase/FLP recombinase target system, proved that the phenotype observed was not caused by the regulatory elements of this marker gene. In the targeted clones, deletion of HS-40 apparently does not affect long-range or local chromatin structure at the alpha promoters. Therefore, these results indicate that, in the experimental system used, HS-40 behaves as a strong inducible enhancer of human alpha-globin gene expression.

Cell Line↗

[Pluri-dimensional study of psychological factors in coronary disease].

To palliate certain criticisms levelled at workers studying psychological factors in coronary artery disease, the authors have applied a pluri-dimensional approach associating a semi-direct psychological interview, a self-evaluation test (Bortner scale), an Eysenck personality test and Sandler and Hazari's test of obsessional behaviour. This protocol was applied to 222 patients hospitalised for coronary artery disease and 522 random controls. The psychological interview and Bortner test showed a significantly higher proportion of A pattern and especially extreme A pattern behaviour in patients with coronary artery disease (32.6 % in coronary patients 9.7 % in controls). The personality questionnaire showed a greater tendency to neurotic behaviour in the coronary patients. These results were independant of age and sex. In the present study, psychological factors are given equal importance to other major risk factors (tobacco, hypertension, hypercholesterolaemia). They are independant of these other factors. A prospective study using the same protocol is being prepared.

Adult↗