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Biomedical subjects

V Dumur

Publications and source records attributed to V Dumur.

At least 37 records · Page 2Linked to original sources
PubMed1989

Confirmation of linkage disequilibrium between haplotype B (XV-2c, allele 1; KM-19, allele 2) and cystic fibrosis allele in the French population.

In 237 French families with cystic fibrosis (CF) restricted fragment length polymorphisms (RFLPs) were detected by two DNA probes, XV-2c and KM-19, which are tightly linked to the CF allele. As in other European populations linkage disequilibrium is found between the haplotype B (XV-2c, allele 1: KM-19, allele 2) and the CF allele. Linkage disequilibrium alters the probability that a person bearing a given haplotype is a carrier.

Cystic Fibrosis↗
PubMed1988

Inhibition of glucocorticoid receptor transformation, subunit dissociation, and temperature-dependent inactivation by various N-substituted maleimides.

A series of N-substituted maleimides were synthesized, and their effect on the activation to the DNA binding state of the rat liver glucocorticoid receptor was studied. Unactivated (preincubated at 0 degrees C) cytosolic [3H]triamcinolone acetonide-receptor complexes were pretreated with various N-alkylmaleimides at 0 degrees C and then heated at 25 degrees C and assayed for DNA-cellulose binding. No inhibition of the DNA binding activity was observed with either N-ethylmaleimide or N-substituted maleimides bearing an ionizable substituent, like N-(omega-carboxyalkyl)maleimides and N-[2-(trimethylammonio) ethyl]maleimide. On the contrary, treatment with long-chain alkylmaleimides like N-heptylmaleimide resulted in significant inhibition. The highest inhibition was obtained with N-benzylmaleimide and, to a lesser extent, N-(ethylphenyl)-maleimide, whereas N-benzylsuccinimide was ineffective. Treatment of cytosol containing unactivated glucocorticoid complexes at 3 degrees C with N-benzymaleimide also prevents the temperature-mediated conversion of 8S receptor to 4S. Moreover, N-benzylmaleimide was able to inhibit the inactivation of the receptor steroid-binding activity caused by heat. N-Benzylmaleimide shares with molybdate ions the ability to inhibit glucocorticoid receptor activation, dissociation, and inactivation. However, their respective mechanisms of action are probably distinct, since their effects on receptor inactivation appear additive. It is suggested from the comparison of the various maleimides tested that the sulfhydryl groups essential for receptor activation and dissociation lie in a rather nonpolar environment including aromatic amino acid(s).

Animals↗
PubMed1987

[Cutaneous manifestations of zinc deficiency in ethylic cirrhosis].

Thirty-three patients with alcoholic cirrhosis (AC), selected on widely recognized criteria (16, 57), were investigated prospectively for cutaneous manifestations of zinc deficiency. The patients were divided into 3 groups: group A (n = 12): AC without skin lesions; group B (n = 12): AC with skin lesions responsive to a zinc-free topical treatment or resistant to enteral zinc sulfate intake; group C (n = 9): AC with skin lesions cured by oral zinc replacement therapy alone. The lesions observed in group C were studied microscopically. Data concerning zinc metabolism (Zn concentrations in plasma, red cells, urine and hair; alkaline phosphatase values), biochemical criteria of AC (plasma serum-albumin concentration, IgA/transferrin ratio) and a malabsorption test (xylosemia 120 min after oral absorption of D-xylose 25 g) were compared by the variance analysis method. A control group (D, n = 12) was used as reference. Few cases of cutaneous manifestations of zinc deficiency in AC patients have been published. In more than one half of the 15 or so we found in the literature, an aggravating factor (total parenteral nutrition, digestive tract surgery) had to be taken into account. In this prospective study 9 new cases in which AC was the only cause of zinc deficiency are reported. A clinical picture similar to acrodermatitis enteropathica with peribuccal bullous lesions was observed in only one patient. In all other cases the patients presented with a cracked and reticulated eczema on the extensor aspect of the limbs and (often erosive) in the perianal and genital regions. The eczema was associated with cheilitis, glossitis, stomatitis, alopecia and, seldom, ungual Beau's lines. Disorders of behaviour, diarrhoea and bouts of lever regressing under zinc replacement therapy were frequent. Histology was not very specific, except for the presence of necrotic areas in the stratum germinativum, sometimes associated with small subcorneal pustules containing altered polymorphonuclears. In every case, it was the rapid regression of symptoms under zinc sulfate treatment that confirmed the diagnosis. Plasma zinc concentrations were most significantly decreased in all AC groups as compared to controls (61.2 +/- 19.4 vs 97.8 +/- 10.4 micrograms/100 ml) and also in AC patients with skin manifestations of zinc deficiency as compared to the other AC patients (44.4 +/- 9.2 vs 66.5 +/- 18.8 micrograms/100 ml) table V). Changes in serum-albumin levels and in hepatocellular function were parallel to changes in plasma zinc concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1985

Characterization of the purified molybdate-stabilized glucocorticoid receptor from rat liver. An in vitro transformable complex.

Rat liver glucocorticoid receptor was purified in the presence of molybdate by a three-step procedure comprising protamine sulfate precipitation, affinity chromatography on a dexamethasone matrix and high-performance size-exclusion chromatography (HPSEC) on a TSK G 3000 SW column. The [3H]triamcinolone-acetonide-receptor complex was obtained in 20% yield with an overall 11 800-fold purification. The dissociation rate constant of this complex was 1.6 X 10(-4) min-1. The purified receptor sedimented at 8.3 S in high-salt and 9.4 S in low-salt sucrose gradients containing molybdate. A 7.0-nm Stokes radius was determined by HPSEC on a TSK G 4000 column in high-salt buffer. The calculated Mr was 278000. Dodecyl sulfate/polyacrylamide gel electrophoresis revealed an almost homogeneous 90 000-Mr band. Three minor bands with Mr of 78 000, 72 000 and 48 000 were also inconstantly seen. An apparent pI = 5.1 was observed for the [3H]steroid complex by isoelectric focusing in agarose gel. Furthermore high-performance ion-exchange chromatography of the purified complex on a DEAE 545 LKB column (DEAE HPLC) yielded a sharp peak eluted at a 315 mM potassium ion concentration. This peak was shown to contain almost all the 90 000-Mr protein. Moreover the purified receptor complex appeared to be transformable to a DNA-binding state after molybdate removal followed by warming 30 min at 25 degrees C in presence of 0.2% bovine serum albumin: 50-78% transformation yield could be demonstrated by DNA-cellulose chromatography. Partial transformation could also be obtained at 0 degrees C in the absence of any added protein and was followed by DEAE HPLC. The transformed complex was eluted by 180 mM potassium.

Animals↗
PubMed1985

Covalent chromatography by thiol-disulfide interchange of the highly-purified non-transformed rat liver glucocorticoid-receptor.

Highly-purified non-transformed rat liver [3H]triamcinolone acetonide-receptor complex was shown to be covalently adsorbed on activated thiol sepharose 4B, a reactive sulfhydryl matrice. Elution by mercaptoethanol in excess and inhibition of binding by previous treatment of the complex with N-ethylmaleimide clearly demonstrated the specificity of the binding by thiol disulfide interchange. The transformed [3H]triamcinolone acetonide-receptor complex, partially purified by DNA-cellulose chromatography, was also retained on activated thiol sepharose 4B. The physicochemical characteristics of both the transformed and non-transformed glucocorticoid receptor complexes eluted from the covalent chromatography column were studied by HP size exclusion chromatography on a TSK G 3000 SW column and were found to be identical to those of the starting complexes. These results provide direct evidence for accessible sulfhydryl groups on the glucocorticoid receptor complex surface, probably distinct from the steroid binding essential sulfhydryl group.

Animals↗
PubMed1984

Inactivation of unbound rat liver glucocorticoid receptor by N-alkylmaleimides at sub-zero temperatures.

A series of N-alkylmaleimides was shown to inactivate effectively the rat liver glucocorticoid receptor at neutral pH. A partial purification of the unbound cytosolic receptor by protamine sulfate precipitation and a careful stabilization of the essential thiol by dithiothreitol and sodium molybdate before the alkylation step appeared essential to obtain pseudo-first-order kinetics. Moreover, performing the experiment at -12 degrees C in buffer containing 40% glycerol as antifreeze agent resulted in increased receptor stabilization and a slowing-down of the inactivation process, which could then be more accurately studied. This process was demonstrated to be dose- and pH-dependent in the case of N-ethyl- and N-nonylmaleimides. Furthermore, comparison of the various N-alkylmaleimides revealed a striking increase of receptor inactivation with increasing chain length of the maleimide derivative. Full protection against inactivation was afforded by previous [3H]dexamethasone binding on the receptor. Long-chain N-alkylmaleimides inactivated by beta-mercaptoethanol were still able to inhibit the [3H]-dexamethasone binding noncovalently. Likewise N-nonylsuccinimide was shown to compete with [3H]dexamethasone for receptor binding. It is suggested that the chain length effect observed in the inactivation process is related to nonpolar interactions in the binding of maleimides to the receptor prior to the irreversible alkylation of sulfhydryl groups. These groups lie in a hydrophobic environment, probably in the steroid binding site itself.

Animals↗
PubMed1984

Physico-chemical properties and evidence for electrophoretic variants of rat transcortin.

Isolation of rat plasma transcortin was carried out by affinity chromatography, as previously described for human. The protein was shown to be pure by PAGE and one single N-terminal amino acid was identified (Ser), which suggested that the protein molecule has a single polypeptide chain. This assumption is supported by SDS-PAGE. The amino acid composition was reported and compared with the one of human transcortin. The purified protein always migrated in PAGE (with or without SDS) as a double band; the faster component being more intense than the slower one. Whether transcortin was free or bound to corticosterone, the same aspect was observed. Molecular weight of these two variants were determined by SDS-PAGE as 65,900 and 75,800. Polymers only appeared after irreversible denaturation of the protein, as previously described for human transcortin. Various other physical parameters were determined: a sedimentation coefficient of 3.71 S +/- 0.18 was calculated by ultracentrifugation in sucrose gradient, association constants at 4 degrees C for corticosterone and cortisol (2.7 X 10(9) M-1 and 4.2 X 10(8) M-1, respectively).

Amino Acids↗
PubMed1976

The covalent structure of dog myoglobin.

The primary structure of the myoglobin of the domestic dog (German shepherd) was studied. Tryptic and thermolytic peptides were compared with the sequence of other known myoglobins; the stepwise automatic Edman's degradation of the whole globin and also the chymotryptic digestion of the median fragment obtained by CNBr cleavage completed this sequence. Comparison of the established dog myoglobin structure with those from other carnivora shows 16 differences versus badger, 20 versus harbour seal and 15 versus California sea lion.

Amino Acid Sequence↗
PubMed1976

[Specificity of thermolysin action on dog myoglobin].

The proteolytic specificity of thermolysin has been studied by quantitative analysis of an enzymic digest of dog myoglobin. Results confirm main specificities of thermolysin towards Phenylalanine, Isoleucine, Leucine or Tyrosine bonds; the influence of neighbourhood was also determined and the conclusions are in a good agreement with the known structure of the active site of thermolysin.

Amino Acid Sequence↗