Search PubMedSearch

Biomedical subjects

B Durand

Publications and source records attributed to B Durand.

At least 19 recordsLinked to original sources

All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs.

Two cooperating retinoic acid response elements (RAREs) in the cellular retinoic acid-binding protein II (CRABPII) gene mediate differential transcriptional transactivation by retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in P19 embryonal carcinoma cells. RARE1 and RARE2 are direct repeats (DR) of two motifs separated by 2 bp (DR2) and 1 bp (DR1), respectively, and bind RAR-RXR heterodimers more efficiently than homodimers. Using all-trans and 9-cis RA, which differentially activate RARs and RXRs, and RAR and RXR dominant-negative mutants, RAR-RXR heterodimers bound to RARE1 and RARE2 are shown to be responsible for CRABPII promoter transactivation, arguing against a unique DR spacing specifying recognition by RARs. Within heterodimers, RAR and RXR independently and differentially transactivate, depending on the specific RARE. Consistent with these results, 9-cis RA increases CRABPII mRNA levels more efficiently than all-trans RA. In contrast, all-trans and 9-cis RA have identical effects on induction of RAR beta 2 transcripts.

Base Sequence

Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors.

Using several naturally occurring and synthetic retinoic acid (RA)-responsive reporter genes, we show that the patterns of transcriptional activation by various retinoic acid receptor (RAR) and retinoid X receptor (RXR) forms vary according to the nature of the RA response element and the context of the stimulated promoter. We demonstrate the presence of autonomous, ligand-inducible, and promoter context-dependent transactivation functions (AF-2s) located in the C-terminal region of all RARs and RXRs. In addition, promoter context-specific modulating transactivation functions are associated with the N-terminal A and B regions of RARs and RXRs. We also show that these transactivation and modulating functions exhibit response-element specificity. The modulating functions display a marked specificity in their cooperation with the AF-2 transactivation functions, cooperation that depends on the receptor origin of the modulating and transactivation functions and the promoter context of the RA-responsive gene, thus accounting for the specific transactivation properties of RAR and RXR types.

Animals

Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins.

Acute promyelocytic leukemia (APL) is due to a chromosomal t(15;17) translocation which involves a novel human gene, Myl, (also named PML) and the retinoic acid (RA) receptor alpha (RAR-alpha) gene. We report here the characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients. Myl displays similarities with a new family of proteins of which some members are fused to protooncogenes in the transforming proteins RFP-ret and T18. The speckled nuclear localization of Myl, as well as its sequence homology with the 52 kDa component of the RO/SSA ribonucleoprotein particle, suggest that Myl may be present in a ribonucleoprotein complex. In contrast to both Myl and RAR-alpha whose localization is essentially nuclear in the presence or absence of RA, MylRAR which is largely cytoplasmic in the absence of RA appears to be translocated to the nucleus in the presence of RA. Myl and MylRAR can associate in vitro and this association is mediated by a coiled coil in the Myl sequence. In vivo this association results in a colocalization of Myl and MylRAR which is identical to that of MylRAR alone. Studies of activation of transcription from the promoters of several RA target genes indicate that MylRARs have altered transcription activation properties when compared with RAR-alpha. Most notably, MylRAR represses markedly the activity of some RA target promoters in the absence of RA. Western blot analyses of patient samples show that MylRAR is expressed to a much higher level than wild type RAR-alpha originating from the normal allele. Taken together, these results suggest that MylRAR may interfere in a dominant manner with both Myl and RAR functions.

Alleles

P25 gene regulation in Bombyx mori silk gland: two promoter-binding factors have distinct tissue and developmental specificities.

The gene encoding the silk protein P25 is expressed in the posterior silk gland of Bombyx mori with strict territorial and developmental specificities. The cis-acting regulatory elements previously located within the 441-bp 5' proximal sequence of the gene were examined for protein-binding capacities. We identified two factors, BMFA and SGFB, that lead to prominent band shifts and the target sites for which are included in a region homologous to the fibroin gene enhancer sequence. Analysis of the tissue-specific incidence of both factors showed that BMFA is ubiquitous, whereas SGFB is restricted to the silk gland cells. However, SGFB was found in both posterior and middle silk gland cells and therefore likely directs organ-specific, but not territory-specific, expression. Developmental studies throughout the fourth larval molt, at which the P25 gene status changes from derepressed to repressed, revealed that BMFA is reversibly modified at the transition from intermolt to molt. Indeed, the preexisting BMFA is replaced by a structurally related factor, BMFA', during the 2 h following head capsule apolysis. The exact temporal coincidence of this conversion with the onset of gene repression suggests that BMFA' is involved in transcription inactivation and likely results from a transduction process initiated by the hormonal change at molting.

Animals

Cellular retinoic acid-binding protein type 2 mRNA is overexpressed in human psoriatic skin as shown by in situ hybridization.

In situ hybridization with full length mouse cellular retinoic acid-binding protein type 1 and cellular retinoic acid-binding protein type 2 cDNA derived RNA probes showed overexpression of cellular retinoic acid-binding protein type 2 mRNA in lesional hyperplastic psoriatic skin whereas cellular retinoic acid-binding protein type 1 mRNA was undetectable. This suggests that the previously reported increase of cellular retinoic acid-binding protein in psoriatic epidermis corresponds to increased translation of cellular retinoic acid-binding protein type 2 gene. Cellular retinoic acid-binding protein types 1 and 2 mRNAs were not detectable in normal epidermis; however, type 2 message was detected in non-hyperplastic, non-lesional skin of psoriatic patients thus before altered epidermal differentiation and hyperplasia are morphologically detectable.

Antisense Elements (Genetics)

The Epstein-Barr virus (EBV) early protein EB2 is a posttranscriptional activator expressed under the control of EBV transcription factors EB1 and R.

From the cloning and characterization of cDNAs, we found that the Epstein-Barr virus (EBV) open reading frame (ORF) BMLF1-BSLF2 coding for the early protein EB2 is present in several mRNAs generated by alternative splicing and expressed in the leftward direction from two promoters PM and PM1. The PM promoter controls the expression of two abundant mRNA species of 1.9 and 2 kilobases (kb), whereas the PM1 promoter controls the expression of at least three mRNAs 3.6, 4.0, and 4.4 kb long. The PM promoter probably overlaps with the PS promoter which controls the transcription of a 3.6-kb mRNA expressed in the rightward direction and containing the ORF BSRF1. Although it increases the amount of chloramphenicol acetyltransferase enzyme expressed from the chimeric pMCAT gene, EB2 is not a promiscuous trans-activator of gene expression and does not positively regulate its own expression from promoter PM. The EB2 activation is not promoter dependent but could possibly act by stabilizing mRNAs and increasing their translation. The PM promoter is, however, activated by the two EBV transcription trans-acting factors, EB1 and R, encoded by the EBV ORFs BZLF1 and BRLF1, respectively. EB1 activates the PM promoter from a consensus AP-1 binding site, and R activates the PM promoter from an enhancer.

Base Sequence

Compartmentalization of MHC class II gene expression in transgenic mice.

A set of transgenic mouse lines carrying Ek alpha genes with promoter region deletions was created in an attempt to compartmentalize MHC class II gene expression. Fine immunohistological analyses established that one transgenic line is essentially devoid of E complex in the thymic cortex, another displays almost no E in the thymic medulla or on peripheral macrophages, and two lines display no E on greater than 98% of B cells. We have assayed these mice for immune function: E-dependent tolerance, antigen presentation, T cell priming, and antibody response. Certain of the findings are difficult to reconcile with currently popular hypotheses, e.g., tolerance induction to E molecules in the virtual absence of E complex in the thymic medulla and efficient antibody responses to E-restricted antigens when almost all B cells are E-.

Animals

Conserved major histocompatibility complex class II boxes--X and Y--are transcriptional control elements and specifically bind nuclear proteins.

A conserved sequence motif exists at the 5' end of all major histocompatibility complex class II genes. This motif consists of the 14-base X and Y boxes separated by a short stretch of variable sequence. In this report, we provide evidence that the X and Y boxes play an important role in controlling transcription of the murine class II gene E kappa alpha. We have developed transgenic mouse lines that carry E alpha genes cleanly deleted for either the X or Y box and have compared the expression of these mutant transgenes with that of a nondeleted control. Both the X and Y segments appear critical for accurate and efficient transcription of E kappa alpha. The most drastic effect is seen with gamma-interferon-treated macrophages, where deletion of the Y box completely abrogates transcription initiated by the normal promoter. In addition, we identify proteins from nuclear extracts that bind specifically to the X or Y box.

Animals

[Antitetanus vaccination: preliminary results of a study in Africa].

Two commercialized anatoxins, titrating 30 Lf per dose and adsorbed on Ca phosphate and Al hydroxide respectively, were studied in comparison with an experimental anatoxin titrating 25 Lf per dose and adsorbed on Al phosphate, and with a placebo. 595 schoolchildren from Cameroun were randomly assigned to four groups and inoculated twice, with a year's interval between the two inoculations. Serological checks were carried out by double-blind trials using the passive hemagglutination (HA) method on days 7, 90, 365 and 395. HA titers rose substantially after three months and then fell during the 12th month. The HA method does not give a clear indication of the amount of protection obtained after only one inoculation, but this amount would seem to be small according to the results of neutralization tests carried out on samples. It is only after the second injection that protection is provided for most subjects. Results vary depending on the anatoxin and are not linked to the--benign--clinical reactions observed. This study confirms that if anatoxins with high antigenicity are to be used, two injections are necessary and sufficient to guarantee good immunity protection.

Adolescent

[The passive hemagglutination test in the evaluation of antitetanus immunity].

The conditioned, passive hemagglutination method, which is simple, quick, economical and very sensitive, is suited for large-scale studies in which it is not possible to carry out the in vivo seroneutralization. However, our experience has confirmed that it has certain drawbacks and restrictions: (1) the technique must be applied very carefully and good laboratory training is required. The results obtained by this method vary according to several factors, especially the degree to which the antigen has been purified and its blood carriers, therefore these results are not always consistent; (2) the antibodies found were not a good indication of the degree of protection except at high titers. A study of correlations between HA titers and neutralizing (mice) titers carried out on the basis of 509 double titrations has demonstrated that, whereas they are satisfactory in clearly immune subjects, they show only mediocre results in subjects who are receptive or who are displaying a primary response: a wide range of variation has been observed as well as an optimalization of HA titers, perhaps because of IgM's. Therefore, the HA method, despite its usefulness, cannot provide precise evaluations for: --the amount of protection provided by an anti-tetanus vaccine, --the proportion of protected subjects in a certain group of people, --an injured person's anti-tetanus immunity. We should work to develop in vitro tests which are both sensitive and reliable in terms of the anti-tetanus protection threshold.

Adolescent

[Reduction of the effects of indomethacin by aspirin. Value of measurement of the articular index and sigma ESR].

Two groups, A and B, were selected at random amongst a total of 31 patients suffering from chronic inflammatory rheumatic disorders. The patients in group A (n = 16) received succesively: Placebo (2d), Indomethacin (5d). Indomethacin + aspirin (5d). The order of the 5 day treatment periods was reversed for the patients in group b (n = 15). The daily dose of indomethacin was 150 mg. That of aspirin was 1500 mg. Four parameters were measured at the end of each period of treatment: total serum indomethacin, articular index (Ritchie), ESR (Westergren) and the sigma ESR - a new technique for the measurement of sedimentation rate. No conclusions could be drawn from the analysis of variations in ESR. Concordant and statistically significnat variations in articular index and the sigma ESR showed a reduction in the activity of indomethacin under the influence of aspirin. The inhibitory effect of aspirin. The inhibitory effect of aspirin continues after the drug stopped. This reduction in indomethacin activity is not related to a decrease in serum concentrations of the medication which are not significantly altered when aspirin is taken.

Adult

[Epidemiologic study of the focus of cutaneous leishmaniasis in Mokolo (North Cameroon)].

Fifty-eight patients with cutaneous leishmaniasis are studied in the North of Cameroon. All of them are living in an area located not further than 30 miles away from Mokolo. Both sexes are equally concerned. Young adults are representing the age group the most frequently infected. The greatest number of cases is observed in August and September during the rainy season. Uncovered parts of the body, the face and the limbs, are mostly concerned. They are only one, or more often many different lesions, which are separated one from the next, and which are evoluting naturally towards cicatrization, leaving usually a cicatricial mark. Diagnosis is achieved by discovering the Leishman-bodies in the smears or in the skin sections.

Adolescent