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Biomedical subjects

G Siest

Publications and source records attributed to G Siest.

At least 361 records · Page 20Linked to original sources
PubMed1981

Induction of group-1 and group-2 UDP-glucuronosyltransferase in microsomes from the livers of C57 Bl/6 mice.

In a study of multiple forms of liver microsomal UDPglucuronosyltransferase (EC 2.4.1.17) with different substrate specificities, enzyme induction was examined in inducible C57 Bl/6 mice pretreated with phenobarbital, 3-methylcholanthrene, Aroclor 1254, safrole, beta-naphthoflavone, and pregnenolone-16-alpha-carbonitrile. Phenobarbital and 3-methylcholanthrene were much more potent inducers than the other four compounds. 3-methylcholanthrene stimulated the glucuronidation of 4-nitrophenol, 4-bromophenol, and 4-chlorophenol ("group-1' substrates) more than phenobarbital, whereas phenobarbital stimulated the glucuronidation of 4-hydroxyphenobarbital, menthol, eugenol, 4-hydroxybiphenyl, morphine, 1-borneol, 4-hydroxyphenytoin, and 1,2,3,4-tetrahydro-1-naphthol ("group-2' substrates). This pattern is analogous to that previously observed in rat-liver microsomes.

Animals↗
PubMed1981

Effect of aflatoxin B1 on hepatic drug-metabolizing enzymes in female rats. Interaction with a contraceptive agent.

1. The effect of a contraceptive on aflatoxin B1 toxicity has been studied in female rats treated for 15 consecutive days with repeated doses of aflatoxin (0.40 mg/kg/day), norethindrone (0.60 mg/kg/day) and ethynylestradiol (0.012 mg/kg/day). 2. Increases occurred in hepatic microsomal cytochrome P-450 content (31%), and in the activities of epoxide hydrase (77%), UDP-glucuronyltransferase (67%) and gamma-glutamyltransferase (78%). 3. Aflatoxin alone caused a 22% increase in GSH S-epoxide transferase activity, whereas the contraceptive given alone or combined with aflatoxin increased the hepatic reduced glutathione. 4. The effect of aflatoxin plus contraceptive was not additive. 5. The effects caused by aflatoxin and the contraceptive were similar, and the contraceptive (depending on its progestogen/estrogen ratio), may modify aflatoxin toxicity by increasing the drug-metabolizing enzyme activities and the concentration of hepatic glutathione.

Aflatoxin B1↗
PubMed1981

[Study of factors of biological variations acting on the concentration of the alpha-1-serous antitrypsin in a "common population" (author's transl)].

We established by nephelometry the serous concentration in an antitrypsin alpha-1 from an example of common population of th preventive Medicine Center of VAndoeuvre-lès-Nancy (675 adults men and women). First of all, the technical qualities of the equipment (replication : 0.06) to 1.1 per cent) and the dosage method (replication : 1,6 to 2,9 per cent, reproduction 3,4 to 4,3 per cent) were estimated. We showed that the technique was well connected with the electroimmunodiffusion (r : 0.90), but that was an important dissociation between the concentrations established by the two methods. The analytical variation being known, we approached the study of biological variations. The distribution of antitrypsin alpha-1 values is quite log-normal (median : 1,71 g/l, medium : 1,76 G/l). The main factors of biological variation observed are the sex (increase in 6 to 11 per cent in women), the age (decrease in 10 per cent between 20-30 years old and 40-50 years old women), the tobacco (increase in 9,5 per cent in the men smoking more than 20 cigarettes a day), the drinking of alcohol (decrease in 10 per cent for two sexes), the taking of oral contraceptives (increase in 29 per cent). These factors of biological variation should be taken in account at the time of producing the reference values, in addition of the analytical, pathological and genetic factors.

Adult↗
PubMed1980

Automated quantification of bone and liver alkaline phosphatase isoenzymes of human serum.

Coupling two Technicon AAII samplers synchronised at 50 per hour with a 2 : 1 sample to wash ratio, sera are denatured and collected automatically. The incubation is done in continuous flow by passage through a U device made of large metallic needles soaked in a water bath at 60 +/- 0.1 degree C. This allows a very quick temperature equilibration and a very reproducible incubation time of 35 sec. Initial and residual activities of alkaline phosphatase (ALP: EC 3.1.3.1) are measured on a Rotochem II (Aminco) with the procedure recommended by the Société Française de Biologie Clinique (SFBC). For a mixture of bone and liver ALP, the initial rate constant of heat denaturation Kapp = (A X Kb) + (B X Kl), where A and B are the fractions of each isoenzyme in the mixture, and Kb and Kl the rate constants for bone (b) and liver (l) experimentally determined as 1.8 min-1 and 0.45 min-1 respectively. An equation was derived which converts the percent residual activity to a percentage of bone and liver isoenzyme: % bone ALP = 183--2.38 X % residual activity. This automated method was applied to 2700 people of both sexes from 4 to 100 years old.

Adolescent↗
PubMed1980

Kinetic properties of gamma-glutamyltransferase from human liver.

We studied the kinetic properties of purified "heavy" form of human liver gamma-glutamyltransferase (EC 2.3.2.2) in the presence and absence of the acceptor substrate glycylglycine under Vmax conditions and as a function of pH. gamma-Glutamyl carboxynitroanilide was used as the donor substrate. Our data suggest that hydrolysis of donor substrate is the major pathway in the absence of acceptor. Autotransfer, if it occurs, is not important. Hydrolysis and transfer reactions have different pH profiles both for Vmax and Km. The pH dependency of Vmax and Km for both the hydrolase and the transferase reactions most probably reflects a change in the rate-limiting step: deacylation of the enzyme at acidic pH and acylation at alkaline pH. Negative cooperativity, observed for both donor and acceptor substrates near neutral pH, is interpreted in terms of more than one active site per dimer for each substrate.

1-Carboxyglutamic Acid↗
PubMed1980

[Recent data on the metabolism of drugs by UDP-glucuronosyltransferases and sulfotransferases (author's transl)].

The authors review recent work on UDP-glucuronosyltransferases and sulfotransferases. UDP-glucuronosyltransferases are membrane enzymes which are strongly dependent on the lipid environment ; this is why they have only recently been isolated and purified. It seems at present, that at least two enzyme forms exist. The sulfotransferases are cytosol enzymes, more easily isolated. Their importance in the metabolism of drugs appears owing to an equilibrium with UDP-glucuronosyltransferases.

Animals↗
PubMed1980

Personal and familial factors in cholesterolemia: criteria for selection of a reference population.

We studied factors affecting cholesterolemia in a presumably healthy population of 23 300 subjects, ages 20 to 59 years. Multiple-contingency tables were established, to quantify the information obtained by means of a factorial correspondence analysis. The relations between values for cholesterol and those for triglycerides, uric acid, and overweight were constant for all ages and both sexes. Cholesterolemia paralleled alcohol and tobacco consumption and arterial blood pressure. Use of oral contraceptives did not influence cholesterol values. We classified variation factors according to the statistical method of segmentation, by sex and age. This classification permitted us to establish criteria for excluding subjects from a population sampled with the aim of producing reference values for plasma cholesterol. The values of cholesterol for the 50th percentile were 5.40 mmol/L for men 20 to 39 years old and 5.79 mmol/L for those older than 40. For women, the 50th percentile values increased from 5.34 mmol/L between ages 20 to 39 to 5.92 mmol/L for ages 40 to 49 and to 6.51 mmol/L after 50.

Adult↗
PubMed1979

Effects of membrane perturbants on UDP-glucuronosyltransferase activity in rat-liver microsomes. Circular dichroism studies.

Rat-liver microsomes were treated with two non-ionic detergents, Triton X-100 and Lubrol WX, with phospholipase A2, or with aqueous acetone solution. The activity of the membrane-bound UDP-glucoronosyltransferase (UDPGT, EC 2.4.1.17) was measured after the treatment with these perturbants. At the same time, modifications of the secondary structure of the microsomal proteins were followed and studied by circular dichroism (CD) spectroscopy. The detergents greatly activated UDPGT, maximally at a 1 mM concentration of either detergent. The maximally activating Triton X-100 treatment did not greatly change the ellipticity of the microsomes at 222 nm ((theta)222), whereas that with Lubrol WX affected the secondary structure of the membrane proteins more strongly. UDPGT activation also occurred in phospholipase A2-treated microsomes. Maximal activation was obtained after 1--5 min of incubation and was stable throughout the experiment. Phospholipase A2 at the ratio of microsomal protein to phospholipase 250 : 1 (w/w) slightly increased (theta)222 after 10 min of incubation and did not change it further even after 30 min of incubation. Treatment of liver microsomes with a 10 : 90 (v/v) aqueous acetone solution removed 90% of the total membrane phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine. The UDPGT activity was decreased in lipid-depleted microsomes, and the enzyme was not reactivated when phosphatidylcholine-lysophosphatidylcholine liposomes were added at a low temperature. An even greater decrease was obtained when the lipid binding was carried out at 37 degree C. Lipid-depleted microsomes had a high (theta)222 associated with a red-shift of 2 nm, indicating partial aggregation of membrane proteins and an increase in the alpha-helical content of the protein after acetone extraction. However, this particular protein structure was partially reversible, since a binding of phospholipids to lipid-depleted microsomes gave a (theta)222 close to that found in control microsomes. The UDPGT activity was not dependent on the secondary structure of the membrane proteins.

Acetone↗