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Biomedical subjects

A Bailly

Publications and source records attributed to A Bailly.

At least 37 records · Page 2Linked to original sources

[Results of weight-loss treatment at a hospital. Significance of the administration of triiodothyronine in small doses during a protein diet].

We report the short-term effects of very-low-calorie liquid formula diet (n = 51) and of 600 Kcalories diet (n = 13) in patients who were hospitalized during 3 weeks. Weight loss averaged 278 +/- 14 g/day (m +/- SEM). It was slightly higher with the very-low-calorie liquid formula diet (293 +/- 21 g vs 242 +/- 25 g, N.S.). Individual weight-loss was unpredictable and highly variable; it ranged from 62 to 636 g/day. During the very-low-calorie formula diet, the expected low T3 syndrome was observed and 12 patients were given T3 (25 micrograms during the second week and 50 micrograms during the third week). These rather small doses corrected T3 values, but lowered total and free T4 levels. T3 administration did not modify the magnitude of weight loss in our patients.

Adult↗

Receptors bound to antiprogestin from abortive complexes with hormone responsive elements.

The mechanism of action of antisteroids is not understood and explanations of their antagonistic activity have been sought at all levels of hormone action. It has been proposed that antisteroids, after binding to receptor, trap it into a non-activated (non DNA-binding) form possibly through interaction with a heat-shock protein of relative molecular mass (Mr) 90,000 (90 K), or that the antisteroids provoke binding of receptor to nonspecific DNA sites but not to hormone responsive elements (HREs), or that the antisteroid-receptor complexes can bind to HREs but form abortive complexes that fail to regulate transcription. We have constructed a deleted cDNA encoding a mutant form of rabbit progesterone receptor which exhibits constitutive activity, that is, binds to HREs in the absence of hormone and thus bypasses the first two steps discussed above. Co-transfection experiments allowed the expression of both constitutive and wild-type receptors in the same recipient cells. Antiprogestin RU486-wild-type receptor complexes completely suppressed the activity of the constitutive receptor on a reporter gene, showing that the inhibition is at the level of their common responsive elements.

Animals↗

Fatty acid composition and kinetic behaviour of liver retinyl esters in vitamin A sufficient and deficient rats.

Weanling rats were fed vitamin A deficient diets (-A) or diets supplemented with vitamin A (+A) (4.4 mg retinol equivalents/kg diet) for a period of 7 or 6 wk, respectively. In liver tissues of these two groups of animals both the subcellular localization as well as the fatty acid composition of the retinyl esters was studied. During vitamin A supplementation or deprivation, the kinetics of the different ester forms were investigated. Results indicate that the subcellular localization of all retinyl esters is similar and dependent on age. Two pools exist, ie one consisting of the nuclear/cell debris and mitochondrial-lysosomal fractions and the other containing the microsomal and cytosol fractions. HPLC analysis showed retinyl palmitate as the predominating (80%) form of the various retinyl esters. By supplementation clearly two kinetic behaviours can be demonstrated: one being a relatively stable storage of the palmitate and stearate, increasing with time and the second one being a more labile pattern for the ester forms with other saturated and unsaturated fatty acids. By vitamin A depletion all retinyl esters are affected indicating that the ester forms other than palmitate and stearate are also storage forms of vitamin A.

Animals↗

Estrogen and progesterone receptor-binding sites on the chicken vitellogenin II gene: synergism of steroid hormone action.

The chicken vitellogenin II gene is transcriptionally activated by estrogens. In transient transfection experiments in human T47D cells that contain receptors for various steroids, we showed estradiol, progestin, and androgen responses of a chimeric chicken vitellogenin II construct. This construct consists of DNA sequences from -626 to -590 upstream of the start of transcription of the chicken vitellogenin gene linked to the herpes simplex virus thymidine kinase promoter driving the transcription of the bacterial chloramphenicol acetyltransferase gene. Treatment of the transfected T47D cells with a combination of estradiol and the progestin R5020 led to a superinduction of chloramphenicol acetyltransferase activity, showing a synergistic action of these two steroids. This synergism was not observed upon treatment of the transfected cells with estradiol and the androgen dihydrotestosterone. Using point mutations in the vitellogenin gene fragment, we showed in functional and in in vitro DNase I footprinting assays with a purified progesterone receptor that, for the synergistic action of estradiol and R5020 to occur, the progesterone receptor must be bound to the vitellogenin gene fragment. The progesterone receptor-binding site was localized at -610 to -590, close to the consensus sequence (-626 to -613) for estrogen receptor binding and function. We therefore demonstrate here that two different steroid hormones can be functionally synergistic through the interaction of their corresponding receptors with two different binding sites adjacent to one another.

Animals↗

[Gene expression of D-beta-hydroxybutyrate dehydrogenase. I. Metabolic control in diabetes].

The effect of various metabolic conditions inducing an overproduction of ketone bodies in the rat have been studied at the different level of the D-beta-hydroxybutyrate dehydrogenase (BDH) expression: the enzymatic activity and the protein content in isolated mitochondria, and at the translational activity of isolated polysomes. The strongest variations were obtained under a diabete where the BDH expression is largely decreased. Insulin is able to reverse this diabete dramatic effect. The results are in agreement with the absence of direct relationships between the ketone bodies production and the D-beta-hydroxybutyrate dehydrogenase expression but appears to be controlled by insulin at different levels at least at the transcriptional, post translational and catalytic activities.

Animals↗

[Gene expression of D-beta-hydroxybutyrate dehydrogenase. II. Incorporation of pre-BDH into mitochondria].

beta-hydroxybutyrate dehydrogenase (BDH), a major protein located in the inner mitochondrial membrane is encoded, as most of mitochondrial proteins, in the nuclear genome. It is synthetized on the free polysomes and post-translationally imported into the mitochondria. The neosynthesized protein is a higher molecular weight precursor. The presequence is cleaved by the matrix protease to give the mature protein. The translocation across the mitochondrial membranes needs energy. The results also indicate that cytosolic factors with low molecular weight are essential in the recognition of precursor by mitochondria and to sort out newly synthetized nuclear encoded mitochondrial proteins from others nuclear encoded proteins.

Animals↗

[Gene expression of D-beta-hydroxybutyrate dehydrogenase. III. Molecular cloning of a DNAc].

In order to continue the molecular studies of D-beta-hydroxybutyrate dehydrogenase (BDH) undertaken in our laboratory for several years, we have initiated a genetic approach which consists in the BDH cDNA cloning from a rat liver cDNA library. The immunoscreening method allowed to isolate a clone which exhibits a DNA insert shorter than the expected full length BDH cDNA.

Animals↗

The usefulness of fructosamine determination in diabetic patients and its relation to metabolic control.

In 116 diabetics and 101 control subjects, we measured both HbA1 and fructosamine values, neither could definitely separate the 2 populations. We observed an excellent correlation between both variables and between each of them and various other parameters of metabolic control. It appeared that the correlation with recent (4 weeks) diabetes control was better with fructosamine than with HbA1 levels. The opposite was true when a 8 week period was considered. The presence of diabetic complications did not modify the fructosamine levels. These results confirm the value of fructosamine measurement in the evaluation of recent diabetes control, but clearly, HbA1 determination remains the best parameter of long-term glycemic control.

Blood Glucose↗

Sequence-specific DNA binding of the progesterone receptor to the uteroglobin gene: effects of hormone, antihormone and receptor phosphorylation.

The effects of ligand binding and receptor phosphorylation on the interaction of progesterone receptor with specific DNA sequences in the uteroglobin gene were studied by nitro-cellulose filter binding and DNase I footprinting. High affinity sites were mapped upstream from the transcription start and in the first intron. They contained a common TGTTCACT sequence. These sites were occupied with similar affinity by the receptor, either in its free state, or complexed with the hormone or an antagonist (RU486); and also by receptor which had been phosphorylated in vivo in a hormone-dependent manner. In all cases identical footprints were observed. These experiments led to the following conclusions. The hormone-dependency of receptor binding to DNA or chromatin is observed in intact cells and in crude cellular extracts but not with purified receptor. Thus in situ, the unliganded receptor probably interacts with some nuclear component(s) which stabilizes it in a 'non-activated' form (non-chromatin and non-DNA binding form). When isolated, the receptor may undergo activation, even in the absence of the hormone. Binding by receptor of an antihormone (and possibly receptor phosphorylation) exerts an effect on gene transcription through a mechanism which is different from (and probably follows) receptor interaction with the gene.

Animals↗

Randomized study of minocycline + gentamicin compared with metronidazole + gentamicin for prophylaxis or treatment of mixed infections in abdominal surgery.

Seventy patients admitted for abdominal surgery requiring short-term perioperative prophylaxis were randomized to receive minocycline + gentamicin or metronidazole + gentamicin. Thirty patients were considered to be infected at the time of surgery and were treated with the same regimen. In the prophylactic cohort, one patient from each group developed postoperative fever. One patient receiving minocycline developed a wound infection. The overall infection rate was 2.6%. In the treatment cohort, it appeared that the patients receiving metronidazole had more severe underlying diseases than those receiving minocycline. Consequently, more postoperative non-infectious complications were observed in the former. Minocycline + gentamicin appeared at least as effective than metronidazole + gentamicin in preventing postoperative infectious complications associated with abdominal surgery or in treating intra-abdominal infections.

Abdomen↗

Effects of retinoic acid on hepatic cytochrome P-450 dependent enzymes in rats under different vitamin A status.

The temporal effects of retinoic acid supplementation on hepatic cytochrome P-450-dependent enzymes were studied on the rat. Four groups of male weanling rats were fed semi synthetic diets: two groups containing 0 or 4.4 mg retinol equivalents per kg diet as retinyl palmitate (A- RA- and A+ RA- groups) and two similar groups supplemented with all trans retinoic acid (12 mg/kg diet) (A- RA+ and A+ RA+ groups). After five or ten weeks of feeding, the rats were killed, liver microsomes were prepared and assayed for aniline hydroxylase, aminopyrine N demethylase activities and cytochrome P-450 levels. Whereas no change was observed between the four groups after 5 weeks, the following modifications appeared after 10 weeks: Vitamin A deficiency decreased hepatic drug metabolism by phase I enzymes (hydroxylase and N demethylase) but only when liver storage pool was not detectable. Vitamin A concentration as low as 4 micrograms/g is sufficient to avoid any perturbation of these enzymes. Parallel to a sparing effect on liver reserves of vitamin A, retinoic acid maintained a normal activity of enzymes of xenobiotic metabolism. However, retinoic acid treatment produced an alteration of phase I enzymes in vitamin A supplemented group (A+ RA+). As this was accompanied by a doubling of vitamin A liver reserves, compared to A+ RA- group, it is suggested that this might result from a liver vitamin A overloading, leading to membrane damage perturbing microsomal enzymes. These results indicate the need for a more careful use of retinoids as a therapeutic agent.

Aminopyrine N-Demethylase↗

Evidence for two subcellular pools and different kinetic behaviour of retinyl palmitate in rat liver.

Rats were fed vitamin A deficient diets (-A) or supplemented with vitamin A (+A) (4.4 mg retinol equivalents/kg diet), either without (-RA) or with retinoic acid (+RA) (12 mg/kg diet) supplementation for up to six weeks. Plasma and liver levels as well as the subcellular localization of vitamin A were determined. In rats reared on the vitamin A rich diet the localization of retinyl palmitate (principal reserve form) is shown to be dependent on age. Two pools exist, i.e. one consisting of the nuclear and mitochondrial-lysosomal fractions and the other containing the microsomal and cytosol fractions. A rapid replenishment of mitochondrial-lysosomal fractions occurs in the first weeks after the weaning. During six weeks of deficient diet an identical mobilization was seen from the different subcellular fractions. Supplementation with RA caused an immediate and sustained reduction of serum vitamin A levels but did not disturb the subcellular localization of retinyl palmitate. A relationship between these phenomena and the subcellular distribution of the retinyl palmitate hydrolase (RPH) and the cellular vitamin A binding proteins (CRBP) is likely to exist.

Animals↗

The rabbit uteroglobin gene. Structure and interaction with the progesterone receptor.

The study of the regulation of uteroglobin gene in the rabbit endometrium constitutes a model for analyzing the mechanism of action of progesterone in mammals. The gene has been cloned into lambda phage and sequenced. Comparison of the sequence of the gene with the amino acid sequence of preuteroglobin and the three-dimensional structure of uteroglobin established by crystal x-ray diffraction showed that the 3 exons correspond to different functional domains of the protein and that at least one of the splice junctions does not map at the surface of the protein. S1 mapping allowed us to define the RNA polymerase initiation site. No difference was observed when analyzing premessengers from the endometrium, where the gene is controlled by progesterone and estradiol, and from lung where the gene is constitutively expressed and not controlled by these hormones. In addition, S1 mapping revealed the existence of several minor transcription initiation sites. In the 5' flanking region between positions -33 and -24 there is the sequence AATACAAAAA which may correspond to a Goldberg-Hogness box. Two other A- and T-rich sequences were found further upstream from the gene, one of these preceding by about 30 nucleotides a minor start of transcription. No obvious feature, possibly related to steroid regulation, was observed in the nucleotide sequence. A fragment of the gene containing the "promoter" region (from nucleotide +10 to nucleotide -394) was preferentially retained on nitrocellulose filters after incubation with purified rabbit uterine receptor. A competitive binding assay was used to compare the affinity for the receptor of various DNA fragments. Labeled "promoter" region DNA was incubated with receptor and various concentrations of nonlabeled competing DNA, and the nitrocellulose-bound radioactivity was measured. This method showed the existence of several high affinity binding sites in the 5' part of the gene and in adjacent regions. However, no high affinity binding sites were observed in the 3' part of the gene. Also, within the "promoter" region there were at least two high affinity binding sites for the receptor.

Amino Acid Sequence↗