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Biomedical subjects

M Mathieu

Publications and source records attributed to M Mathieu.

At least 19 recordsLinked to original sources
PubMed1992

Specific binding sites for the activator protein, ALCR, in the alcA promoter of the ethanol regulon of Aspergillus nidulans.

ALCR is the specific activator of the Aspergillus nidulans ethanol-utilization pathway, mediating the induction of its own transcription and that of the structural genes alcA and aldA, encoding respectively, alcohol dehydrogenase I and aldehyde dehydrogenase. ALCR is a DNA binding protein in which 6 cysteines are coordinated in a zinc binuclear cluster. This domain was fused to glutathione-S-transferase (GST) and isolated as a GST-ALCR(7-58*) fusion protein from Escherichia coli. Mobility shift assays showed that the ALCR fusion protein binds at sites upstream of the alcA promoter. DNaseI protection footprinting experiments revealed three specific binding sites, two that are direct repeats and one that is an inverted repeat with the same half-site 5'-CCGCA-3'. The half-sites are separated by a variable number of nucleotides in both types of target. The interaction of the ALCR fusion protein with direct and inverted repeats were examined by using interference and protection footprinting assays. In both binding sites, modification of the guanines in the half-sites interfered with the formation of the DNA complex, but the adjacent ones did not. Our results suggest that the ALCR protein makes contact in the major groove of the DNA helix of the half-sites. The functionality of two out of three binding sites of the GST-ALCR protein was demonstrated after their deletion. Therefore, the region encompassing these binding sites is a cis-acting element involved in the full induction of the alcA gene.

Alcohol Dehydrogenase↗
PubMed1992

Purification of electron transfer flavoprotein from pig liver mitochondria and its application to the diagnosis of deficiencies of acyl-CoA dehydrogenases in human fibroblasts.

Medium chain acyl-CoA dehydrogenase (MCAD) and long chain acyl-CoA dehydrogenase (LCAD) deficiency are defects of mitochondrial beta-oxidation. The method of choice to measure specifically acyl-CoA dehydrogenase activity in human tissues uses purified electron transfer flavoprotein (ETF). We describe a simple and optimized method of purification allowing isolation of ETF with a degree of purity never reported so far. An assay for acyl-CoA dehydrogenase activity in cultured skin fibroblasts was developed using microquantities of electron transfer flavoprotein and substrate. MCAD deficiency was demonstrated in fibroblasts from nine patients and LCAD deficiency in fibroblasts from two patients.

Acyl-CoA Dehydrogenase↗
PubMed1992

Kinetics of action of salbutamol inhaled from a metered dose inhaler (MDI) and a "Diskhaler".

In a double-blind cross-over study, 12 patients with reversible airways obstruction were treated with 200 micrograms salbutamol base in aerosol or 400 micrograms of powder following methacholine-induced bronchoconstriction. Salbutamol was inhaled either from a conventional metered dose inhaler (MDI) or from an inhaler (Diskhaler) utilizing the powdered form of the drug. The efficacy of both forms was identical whether assessed in terms of FEV1 or vital capacity. The ratio of the increase in FEV1 or vital capacity after bronchodilatation to the decrease during the prior bronchoconstriction was 1.4, indicating that both FEV1 and vital capacity improved over baseline following bronchodilatation. In six subjects, the onset of action of the powder form was more rapid, and in four the MDI acted more rapidly. In the group as a whole, the mean time constant for the action of salbutamol was identical (3.8 min) for the two forms. It is concluded that salbutamol powder has a similar efficacy and time course of action as the aerosol, probably because both formulations produce similar sized particles of the drug.

Administration, Inhalation↗
PubMed1992

The occurrence and in vitro effects of molecules potentially active in the control of growth in the marine mussel Mytilus edulis L.

A molecular with a molecular weight, estimated by gel filtration, of approximately 22 kDa and immunoreactive to anti-human hypophysial growth hormone (hGH) has been identified by radioimmunoassay in the digestive gland and hemolymph of the mussel Mytilus edulis L. The dilution curve of this molecule was parallel to that of hGH, suggesting that the antigenic site of the Mytilus molecule is similar to that of hGH. Immunoreactive fractions resulting from gel filtration failed to stimulate protein synthesis in dispersed mantle-edge cells in vitro. No hGH-immunoreactive material was detected in the cerebral ganglia. It is thus clear that a small protein-synthesis-stimulating factor (PSSF), identified in the cerebral ganglia and hemolymph by its action in vitro on dispersed mantle-edge cells, is not analogous to the Mytilus hGH-immunoreactive molecule. Likewise, a somatostatin-immunoreactive molecule present in the hemolymph of Mytilus did not coelute with PSSF. Evidence is presented that PSSF is a hydrophilic peptide that stimulates DNA, RNA, and protein synthesis and that is not tissue specific. These characteristics suggest that PSSF is a growth hormone.

Animals↗
PubMed1992

Identification of the promoter region involved in the autoregulation of the transcriptional activator ALCR in Aspergillus nidulans.

The ALCR protein is the transcriptional activator of the ethanol utilization pathway in the filamentous fungus Aspergillus nidulans. This activator belongs to a family of fungal proteins having a conserved DNA-binding domain containing six cysteines (C6 class) with some striking features. At variance with other motifs of this class, the binding domain of ALCR is strongly asymmetrical in relation to the central cysteines and moreover was predicted to adopt a helix-turn-helix structure. This domain of ALCR was synthesized in Escherichia coli and purified as a glutathione-S-transferase fusion protein. Our results show that the transcriptional activator ALCR is a DNA-binding protein. The DNA-binding motif contains zinc that is necessary for the specific DNA binding. The ALCR peptide binds upstream of the coding region of alcR to two specific targets with different affinities that are characterized by a conserved 5-nucleotide core, 5'-CCGCA-3' (or its reverse). One site, the lower-affinity binding site, is a direct repeat, and the other, the higher-affinity binding site, is a palindromic sequence with dyad symmetry. Therefore, the ALCR binding protein is able to recognize one DNA sequence in two different configurations. An alcR mutant obtained by deletion of the two specific targets in the cis-acting region of the alcR gene is unable to grow on ethanol and does not express any alcohol dehydrogenase activity. These results demonstrate that the binding sites are in vivo functional targets (UASalc) for the ALCR protein in A. nidulans. They corroborate prior evidence that alcR is autoregulated.

Aspergillus nidulans↗
PubMed1992

Confirmation and refinement of the genetic localization of the Coffin-Lowry syndrome locus in Xp22.1-p22.2.

The Coffin-Lowry syndrome (CLS) is an X-linked inherited disease of unknown pathogenesis characterized by severe mental retardation, typical facial and digital anomalies, and progressive skeletal deformations. Our previous linkage analysis, based on four pedigrees with the disease, suggested a localization for the CLS locus in Xp22.1-p22.2, with the most likely position between the marker loci DXS41 and DXS43. We have now extended the study to 16 families by using seven RFLP marker loci spanning the Xp22.1-p22.2 region. Linkage has been established with five markers from this part of the X chromosome: DXS274 (lod score [Z] (theta) = 3.53 at theta = .08), DXS43 (Z(theta) = 3.16 at theta = .08), DXS197 (Z(theta) = 3.03 at theta = .05), DXS41 (Z(theta) = 2.89 at theta = .08), and DXS207 (Z(theta) = 2.73 at theta = .13). A multipoint linkage analysis further placed, with a maximum multipoint Z of 7.30, the mutation-causing CLS within a 7-cM interval defined by the cluster of tightly linked markers (DXS207-DXS43-DXS197) on the distal side and by DXS274 on the proximal side. Thus, these further linkage data confirm and refine the map location for the gene responsible for CLS in Xp22.1-p22.2. As no linkage heterogeneity was detected, this validates the use of the Xp22.1-p22.2 markers for carrier detection and prenatal diagnosis in CLS families.

Abnormalities, Multiple↗
PubMed1991

Biochemical diagnosis of hepatic glycogen storage diseases: 20 years French experience.

French experience of 242 cases of liver glycogenoses is reported. Screening tests based on serum biochemical data and glucagon tolerance tests are briefly reviewed. The diagnosis of types I glycogen storage disease (GSD) was ascertained in 73 patients' liver biopsies by measurement of glycogen content and by studying the glucose-6-phosphatase system. Liver biopsies were also required at the beginning for the diagnosis of other hepatic GSDs; later on, the possibilities of diagnosis using peripheral blood cells were investigated. Eighty-four cases of type III GSD were confirmed by measurement of debranching enzyme activity and glycogen content using either liver biopsies (78 cases) and/or erythrocytes (37 cases); enzyme determination was also performed in leukocytes and/or fibroblasts for 18 patients. Twenty-four cases of type VI GSD underwent liver biopsies, and the diagnosis could be confirmed using mononuclear or polymorphonuclear cells for 11 of these patients. Sixty-one patients were identified as type IX GSD; phosphorylase kinase deficiency was demonstrated in erythrocytes for all patients, and a liver biopsy was analyzed for 26 of these cases. From this experience, the possibilities of diagnosis of liver GSD using peripheral blood cells are emphasized.

Blood Chemical Analysis↗
PubMed1991

Estradiol down-regulates the mannose-6-phosphate/insulin-like growth factor-II receptor gene and induces cathepsin-D in breast cancer cells: a receptor saturation mechanism to increase the secretion of lysosomal proenzymes.

We have studied the regulation by estradiol of the mannose-6-phosphate (Man-6-P)/insulin-like growth factor-II (IGF-II) receptor concentration in different breast cancer cell lines. The mRNA level was assayed by Northern blot using the H5.1 cDNA probe. The protein level was assayed by Western ligand blot, by binding saturation with [125I]procathepsin-D on total membrane preparations, and by immunoprecipitation of 35S-labeled proteins. In three estrogen receptor-positive cell lines (MCF7, T47D, and ZR75-1), estradiol specifically decreased the steady state level of the Man-6-P/IGF-II receptor protein and mRNA. Moreover, in different cell lines and in primary culture of normal mammary cells, the secretion of procathepsin-D was inversely correlated with the level of Man-6-P/IGF-II receptor protein and mRNA. We conclude that estradiol down-regulates the Man-6-P/IGF-II receptor in breast cancer cells. Since two of its ligands, procathepsin-D and IGF-II, are induced by estrogen, we propose that the Man-6-P/IGF-II receptor becomes saturated after estrogen treatment. This model might explain the previously described estrogen-induced secretion of procathepsin-D and other lysosomal proenzymes routed by the same transport system.

Breast Neoplasms↗
PubMed1979

Effect of intravenous hydrocortisone administration on glucose homeostasis in small for gestational age infants.

The effects of I.V. hydrocortisone (H) (10 mg/kg) on glucose homeostasis were evaluated at 25 to 85 hours of age in 14 infants who were small for gestational age (SGA) in comparison to 17 control SGA infants. Three hours after H administration, higher levels of plasma glucose than in controls were detected (mean +/- S.E.M.): 4.78 +/- 0.2 vs. 2.88 +/- 0.2 mmol/l (p less than 0.01), while lower levels were found for blood pyruvate (38 +/- 7 vs. 89 +/- 12 mumol/l--p less than 0.01), plasma insulin (6.4 +/- 0.5 vs. 12 +/- 0.8 muIU/ml--p less than 0.05) and plasma glucagon (62.25 +/- 6.6 vs. 81.6 +/- 6.6 pmol/l--p less than 0.05). Three hours after H administration, I.V. injection of L-alanine (150 mg/kg) produced a significant rise over baseline of plasma glucose concentration from 4.78 +/- 0.2 to 5.94 +/- 0.2 mmol/l at 50 min (p less than 0.05), whereas no significant change was observed in controls. There was no significant change in plasma glucagon and insulin concentrations after L-alanine injection in either group. These results show that in SGA infants primed with H, the rise of plasma glucose concentration after L-alanine administration is observed with low plasma insulin levels and without stimulation of glucagon secretion. They suggest that H induced a reduced peripheral utilization of glucose by lowering the plasma levels of insulin and a production of glucose from alanine through gluconeogenesis.

Alanine↗
PubMed1979

The directive sex therapies in psychiatric outpatient settings.

The treatment techniques and associated outcome studies of the directive sex therapies (DST) are briefly reviewed and data on the treatment of 12 couples are presented. The directive sex therapies have achieved rather impressive results but only with highly selected populations. Studies, such as the present, with a range of patients more typical of psychiatric outpatient settings have consistently achieved lower success rates. The important effect of patient selection on outcome with DST has, to date, received little attention. The present authors discuss selection criteria for DST in the light of the literature and the outcome in their own cases.

Adult↗