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P Leroy

Publications and source records attributed to P Leroy.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Effects of lithium chloride and retinoic acid on the expression of genes from the Xenopus laevis Hox 2 complex.

We show that Xenopus laevis has a Hox 2 complex, and that this complex is strongly conserved with the mammalian one, both in structure and in the rules of spatial and temporal sequential expression of its genes during the early stages of development. Lithium chloride and retinoic acid, two reagents known to alter axial patterning of the body when applied to Xenopus embryos, produce, respectively, embryos with reduced posterior but exaggerated anterior structures and embryos with truncation of anterior structures. We report here on the effect of these reagents on the expression of Hox 2 genes in the Xenopus embryos. LiCl has a dramatic effect on Hox genes, suppressing the expression of these genes during gastrulation and early neurulation. However, later on expression of these genes reaches significant levels, suggesting the existence of two phases in the control of Hox gene expression. Retinoic acid increases the steady state level of transcripts from Hox genes with the greatest effect on Hox 2.7, the most anterior of the genes studied. This suggests that the results obtained in EC cells (Simeone et al., 1990, 1991) reflect what occurs in vivo. Neither LiCl nor RA change the sequential order of the onset of expression of the genes, showing that these reagents do not perturb the molecular mechanisms used to establish the sequential activation of the genes of the Hox complexes.

Amino Acid Sequence↗
PubMed1992

The pharmacokinetics of tiopronin and its principal metabolite (2-mercaptopropionic acid) after oral administration to healthy volunteers.

We have studied the pharmacokinetics of tiopronin and its principal metabolite, 2-mercaptopropionic acid (2-MPA) in healthy volunteers after the oral administration of 500 mg (2 Acadione tablets), followed by simultaneous assay of the two compounds in plasma over a period of 48 h using a new method (emission of fluorescence after HPLC and post-column derivatization by pyrene-maleimide). The absorption of tiopronin was slow (tmax between 4 and 6 h) and the plasma concentrations subsequently fell biexponentially. The principal metabolite 2-MPA appeared later in the plasma (tmax between 10 and 12 h after a lag-time of 3 h) then disappeared monoexponentially. About 15% of the tiopronin was metabolized to 2-MPA.

Administration, Oral↗
PubMed1992

Lipoprotein lipase: recent contributions from molecular biology.

Lipoprotein lipase (LPL) is a glycoprotein enzyme that is produced in several cells and tissues. LPL belongs to a large lipase gene family that includes, among others, hepatic lipase and pancreatic lipase. After secretion, LPL becomes anchored on the luminal surface of the capillary endothelial cells. There it hydrolyzes triglycerides in triglyceride-rich lipoproteins, generating free fatty acids that can serve either as a direct energy source or can be stored. Through this action LPL plays a pivotal role both in energy and in lipoprotein metabolism. LPL production is regulated in a tissue-specific fashion by developmental, hormonal, and nutritional factors. The recent availability of the regulatory sequences of the LPL gene will greatly facilitate these regulatory studies in the future. In man, several mutations resulting in familial LPL deficiency have been delineated at a molecular level. The study of these mutations is not only very beneficial from a clinical point of view but also contributes in a major way to our understanding of the structure-function relationship of LPL and other lipases. In this review major attention is given to molecular studies relating to the regulation of LPL production, to the defects underlying LPL deficiency, and to structure-function relationship of the lipases.

Amino Acid Sequence↗
PubMed1992

[Sclerectasia in a pig farm in Sotouboua, Togo].

Cases of sclerectasia were described in a pig farm, Sotouboua, Togo. The causative agent may be a pestivirus, on top of a predisposition revealed by consanguinity. Livestock owners should be kept aware.

Animals↗
PubMed1991

Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element.

We have characterized the promoter of the mouse retinoic acid receptor alpha 2 (mRAR-alpha 2) isoform. This promoter contains a retinoic acid response element (RARE) that closely resembles the RARE that is present in the RAR-beta 2 promoter. Moreover, RAR-alpha 2 and RAR-beta 2 proximal promoter sequences are similar to each other and generate transcripts whose respective start sites are located at similar positions. The RAR-alpha 2 RARE consists of two directly repeated 5'-GTTCA-3' motifs to which all three RARs (alpha, beta, and gamma) bind in vitro.

Animals↗
PubMed1991

Determination of 2-mercaptopropionylglycine and its metabolite, 2-mercaptopropionic acid, in plasma by ion-pair reversed-phase high-performance liquid chromatography with post-column derivatization.

A simple and fast high-performance liquid chromatographic method was developed for the simultaneous measurement of 2-mercaptopropionylglycine (Tiopronine) and its metabolite (2-mercaptopropionic acid) in human plasma after the administration of a pharmaceutical dosage form (Acadione). The sample treatment before high-performance liquid chromatographic analysis consisted of the reduction of the corresponding disulphides by tri-n-butylphosphine and protein precipitation with ethanol. Separation was achieved by ion-pair high-performance liquid chromatography on a reversed-phase column (LiChrospher RP 18e) with cetrimonium bromide as counter ion and detection by fluorimetry after post-column derivatization with a selective thiol reagent, i.e. pyrenemaleimide. The high frequency of the analyzed samples and validation results make the method suitable for pharmacokinetic studies, and this was demonstrated by the first results obtained after the administration of an oral dose of 500 mg of Tiopronine to two healthy subjects.

Chemical Precipitation↗
PubMed1991

A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter.

Genomic and cDNA sequences for the mouse cellular retinol binding protein I (mCRBPI) are presented. A specific cis-acting element responsible for retinoic acid (RA) inducibility of the mCRBPI promoter was identified and characterized. Deletion mapping of a CRBPI promoter--chloramphenicol acetyltransferase reporter gene construct localized this element to a 259 bp restriction fragment located approximately 1 kb upstream from the transcription start-site. A sequence closely resembling the previously characterized RA response element (RARE) of the RA receptor beta 2 (RAR-beta 2) promoter, and consisting of a direct repeat of the motif 5'-GGTCA-3' separated by three nucleotides, was found within this restriction fragment. Mutation of these 5'-GGTCA-3' motifs to GGAGC and GGGGC abolished RA-inducible transcription whereas a mutation to a direct repeat of the GTTCA motif found in the RARE of the RAR-beta 2 promoter resulted in enhanced inducibility. Oligonucleotides containing the direct repeat of the GGTCA motif were able to confer RA-dependent transcriptional enhancement to the herpes simplex thymidine kinase promoter, as well as to bind directly all three retinoic acid receptors (RARs) alpha, beta and gamma, as determined by gel retardation/shift assays. The control of CRBPI gene transcription by RA-RAR complexes interacting with the RARE characterized here may correspond to a feedback mechanism important in regulating retinoid metabolism and action.

Amino Acid Sequence↗
PubMed1991

Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid.

Together with the previously described mouse retinoic acid receptor alpha-1 (mRAR-alpha 1, formerly mRAR-alpha 0), we have isolated and characterized here a total of seven mRAR-alpha cDNA isoforms (mRAR-alpha 1 to alpha 7). These isoforms are generated from mRAR-alpha primary transcript(s) of a single gene by alternative splicing of at least eight different exons with the exon which encodes the amino acid sequence of their common B region. All of these isoforms differ in their 5'-untranslated regions (5'-UTRs) and, in the case of mRAR-alpha 1 and alpha 2, also in the sequences encoding the N-terminal A region which is known to be important for differential trans-activation by other members of the nuclear receptor superfamily. In addition, the sequences encoding the open reading frames (ORFs) of mRAR-alpha 3 and alpha 4 cDNA isoforms remain open to their very 5' ends, which suggests that these two isoforms may also encode RAR-alpha s with unique A region amino acid sequences. The two predominant isoforms, mRAR-alpha 1 and alpha 2, were found to be differentially expressed in mouse adult and fetal tissues, as well as in P19 and F9 embryonal carcinoma (EC) cell lines. Interestingly, the expression of mRAR-alpha 2, in contrast to that of the mRAR-alpha 1 isoform, was induced by retinoic acid (RA) in EC cells, thus suggesting the presence of two promoters in the 5' region of the mRAR-alpha gene, which differ in their response to RA. The conservation between mouse and human RAR-alpha 1 and alpha 2 cDNA isoform sequences, as seen by cross-hybridization in Southern blots or by DNA sequence analysis, together with their differential patterns of expression, strongly suggests that they perform specific functions during embryogenesis and in the adult.

Amino Acid Sequence↗
PubMed1991

Differentially expressed isoforms of the mouse retinoic acid receptor beta generated by usage of two promoters and alternative splicing.

Using anchored PCR, three different cDNA isoforms of the mouse retinoic acid receptor beta [mRAR-beta 1, mRAR-beta 2 (formerly mRAR-beta 0) and mRAR-beta 3], generated from the same gene by differential promoter usage and alternative splicing, were isolated. These three isoforms encode RAR proteins with different N-terminal A regions and identical B - F regions. The sequence encoding the first 59 amino acids of the mRAR-beta 3 A region is identical with the entire A region of mRAR-beta 1. However, the sequence of mRAR-beta 3 region A differs from that of mRAR-beta 1 by an additional 27 C-terminal amino acids encoded in an 81 nucleotide-long putative exon which is spliced in between the exons encoding the A and B regions of mRAR-beta 1. Both mRAR-beta 1 and beta 3 cDNAs differ entirely from mRAR-beta 2 in their 5'-untranslated (5'-UTR) and A region coding sequences. This N-terminal variability, in a region which was shown to be important for cell-type specific differential target gene trans-activation by other nuclear receptors, suggests that the three mRAR-beta isoforms may be functionally distinct. The conservation of RAR-beta isoform sequences from mouse to human, as seen by cross-hybridization on Southern blots or DNA sequence analysis, as well as their differential patterns of expression in various mouse tissues, corroborates this view. Additionally, the mRNA analysis data suggest that mRAR-beta 2, whose expression predominates in RA-treated embryonal carcinoma (EC) and embryonic stem (ES) cells, may be important during early stages of development. mRAR-beta 1 and beta 3, on the other hand, which are predominantly expressed in fetal and adult brain, may play some specific role in the development of the central nervous system.

Amino Acid Sequence↗
PubMed1991

Urinary glucuronide excretion of fenofibric and clofibric acid glucuronides in man. Is it polymorphic?

The possible polymorphism of the glucuronidation reaction in man has been investigated using two hypolipidaemic compounds, fenofibrate and clofibrate, as the test probes. The formation of fenofibryl and clofibryl glucuronides was identified by their susceptibility to hydrolyses by beta-glucuronidase. The urinary excretion of the glucuronides was measured in 72 healthy volunteers after a single dose of fenofibrate, and in 104 subjects given a single dose of clofibric acid. Fenofibrate was excreted at a lower rate than clofibrate, since 13.94% and 26.55% of the doses of fenofibrate and clofibrate respectively, were recovered in urine in 8 h. Correlation analysis indicated that sex and body mass index significantly influenced the formation of fenofibryl glucuronide, whereas age and oral contraceptives affected the excretion of clofibryl acid glucuronide. The 8-hour urinary excretion patterns of clofibryl glucuronide and of clofibric acid presented a Gaussian distribution, whereas those of fenofibryl glucuronide and fenofibric acid showed 2 populations. When the metabolic ratio free fenofibric acid/glucuronide was considered, 84.7% of subjects presented the ratio 0.147, and 15.3% had the 3-fold higher ratio of 0.421. The study has shown, in the human population studied, that the glucuronidation of fenofibric acid but not that of clofibric acid may present a polymorphism.

Adult↗
PubMed1991

[Serological survey on the prevalence of bovine type-4 herpesvirus infection in cattle in the Accra plains of Ghana].

Sera from cattle of the Accra Plains in Ghana were screened for bovine type-4 herpesvirus (BHV-4) antibodies by an indirect immunofluorescence test. Among the 176 screened serums, 14% were found positive at a 1/100 dilution. Further studies are necessary for a better understanding of the relationships between BHV-4 or some other agents and necrotic vaginitis associated with poor fertility observed in cattle in this area.

Animals↗
PubMed1990

Murine isoforms of retinoic acid receptor gamma with specific patterns of expression.

We have characterized seven murine retinoic acid receptor gamma cDNA isoforms (mRAR-gamma 1 to -gamma 7) generated by alternative splicing of at least seven exons. These isoforms differ from one another in their 5' untranslated region and in two cases (mRAR-gamma 1 and -gamma 2) differ in their N-terminal A region, which is known to be important for differential transactivation by other nuclear receptors. mRAR-gamma 1 and -gamma 2, the predominant isoforms, are differentially expressed in adult tissues and during embryogenesis. Most notably, skin contains almost exclusively mRAR-gamma 1 transcripts. The conservation of the RAR-gamma isoforms from mouse to human together with their patterns of expression suggests that they perform specific functions, which may account for the pleiotropic effect of retinoic acid in embryogenesis and development.

Animals↗
PubMed1990

A field study of post-exercise values of blood biochemical constituents in jumping horses: relationship with score, individual and event.

The variability of the post-exercise values (PEV) of blood lactate and of some other blood constituents were studied in 8 healthy and fit jumpers through 5 national competitions of equal difficulty. The effects of factors such as the individual, performance and competition on these PEV were analysed. Venous blood was sampled immediately after the 5 show-jumping contests and was analysed for packed cell volume (PCV), blood lactate, blood glucose (GLU), total plasma protein (TPP), bicarbonate (HCO3-), sodium (Na+), potassium (K+), chloride (Cl-), calcium (Ca2+), serum activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), glutamic-oxalacetic transminase (GOT) and gamma glutamyl transferase (gamma GT). PEV of these 13 blood parameters were analysed using a fixed linear model which included the effect of horse, score and competition and their respective interactions. The analysis of the influence of each of the 3 fixed variables showed that (1) there was no relationship between the PEV variations and the score; (2) there were significant (P less than 0.05) variations induced by the competition in Na+, Ca2+, TPP, LDH and GLU, and (3) there were significant interindividual variations as regards Ca2+, TPP, CPK, gamma GT and PCV with P less than 0.05, LDH with P less than 0.01 and blood lactate with P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis.

We report here the gene expression patterns, as revealed by in situ hybridisation, of the retinoic acid receptors alpha, beta and gamma (RAR-alpha, -beta and -gamma), and the cellular binding proteins for retinol and retinoic acid (CRBP, CRABP) in non-neural tissues of mouse embryos during the period of organogenesis. At all stages, RAR-alpha transcripts were almost ubiquitous, whereas the distribution of transcripts of the other four genes was distinctive in all systems. At early stages in the formation of an organ, the expression patterns were different in the epithelium, the adjacent mesenchyme, and in mesenchyme more distant from the epithelium, suggesting a role for RA and RA receptors in epithelial-mesenchymal tissue interactions. In the developing face, limb bud and genital tubercle, where large expanses of mesenchyme are present, differential patterns of expression were established before the onset of overt tissue differentiation, suggesting some significance for pattern formation in these regions. The distribution of RAR-beta transcripts in tracheobronchial, intestinal and genital tract epithelial is consistent with the possibility that RAR-beta plays a role in mediating retinoid effects on the differentiated stage of these epithelia. Possible developmental roles of RARs in relation to the expression patterns of other genes are discussed. CRBP expression domains showed a high degree of overlap with RAR-beta and RAR-gamma, and a mutual exclusivity with CRABP expression domains. Correlation of these expression patterns with the morphogenetic effects of vitamin A deficiency and retinoid excess lead us to propose that the function of CRBP is to store and release retinol where high levels of RA are required for specific morphogenetic processes, while CRABP serves to sequester RA in regions where normal developmental functions require RA levels to be low. Where both binding protein genes are expressed in a non-overlapping pattern within a large area of mesenchyme, a gradient of free RA may be created between them by release of retinol-derived RA from CRBP-expressing cells, with binding to CRABP enhancing the steepness of the decline in concentration distant to the source.

Animals↗
PubMed1990

[A note on the first case of dry gangrene of the limbs in cattle, caused by Salmonella typhimurium in Ghana].

Ischaemia and terminal tissue dry gangrene are among the sequels of Salmonella infection. Up to now, these lesions had been described in Europe and in Chile, on calf exclusively. This time, the syndrome was observed on adult cattle reared in the Accra Plains (Ghana) and infected by S. typhimurium. This case give evidence of the spreading of salmonellosis on the African continent and should foster the search of adequate control measures.

Animals↗