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Biomedical subjects

G Siest

Publications and source records attributed to G Siest.

At least 325 records · Page 18Linked to original sources
PubMed1984

Kinetic properties of UDP-glucuronosyltransferase(S) in different membranes of rat liver cells.

Glucuronidation of 4-nitrophenol, borneol and morphine occurred in rough and smooth endoplasmic reticulum, Golgi apparatus and plasma membranes of rat liver cells. In all fractions, prior fixation of either substrate (UDP-glucuronic acid or the aglycone) enhanced the affinity for the second substrate. Whatever the membrane, glucuronidation of 4-nitrophenol was characterized by high Vmax and high affinity for UDP-glucuronic acid. On the other hand, glucuronidation of borneol exhibited a lower Vmax and a lower affinity for UDP-glucuronic acid. In the endoplasmic reticulum, conjugation of morphine had a low Vmax, but the enzyme had high affinities for both UDP-glucuronic acid and the aglycone.

Animals↗
PubMed1984

Complexes of serum gamma-glutamyltransferase with apolipoproteins and immunoglobulin A.

We have detected complexes between gamma-glutamyltransferase and apolipoproteins or immunoglobulin A in sera from patients with hepatobiliary diseases but not in sera from healthy individuals. An average of 52.4% of the enzymic activity was precipitated by antiserum against apolipoprotein A, 29.9% by antiserum against apolipoprotein B, and 9.7% by antiserum against immunoglobulin A. Fifty to 60% of the enzyme activity was inhibited in the immunoprecipitates from the transferase fraction bound to apolipoprotein A or immunoglobulin A, and 21% in the fraction bound to apolipoprotein B. We identified the complexed transferase fractions by electrophoresis.

Aged↗
PubMed1984

Associations between serum gamma-glutamyltransferase and apolipoproteins: relationships with hepatobiliary diseases.

We studied the association between gamma-glutamyltransferase (GGT) and apolipoproteins A or B in serum of 42 patients with various hepatobiliary diseases. Binding of the enzyme to apolipoprotein A is not related to a clearly defined disease, but appears to be mainly influenced by the ratio of total cholesterol to GGT activity. An important fraction of GGT activity is associated with apolipoprotein B in patients with icteric or anicteric cholestasis. Conversely, in noncholestatic patients, the percentage of apolipoprotein B-bound GGT activity is low. Addition of the "heavy" form of GGT, obtained by solubilizing the membrane-bound enzyme with detergents, to a serum with low GGT activity led to the binding of the enzyme only to apolipoprotein A. The "light" form of GGT, obtained by limited proteolysis of the "heavy" form and added to the same serum, did not bind to either apolipoprotein A or apolipoprotein B. Thus, the association between the serum enzyme and apolipoprotein A apparently results from nonspecific aggregation of the amphiphilic "heavy" form of the enzyme. The origin of the apolipoprotein B-GGT complexes found in cholestatic patients needs further investigation.

Adult↗
PubMed1984

[Multiple molecular forms of serum gamma-glutamyltransferase: characterization and clinical significance].

Heterogeneity of serum gamma-glutamyltransferase was described for the first time about thirty years ago. It seems to result from post-translational modifications of a single type of molecule. The study of that heterogeneity is based upon the use of separation techniques such as gel filtration, ion-exchange chromatography, affinity chromatography with lectines, and especially electrophoresis on various supports. The most promising clinical applications concern hepatology. In particular, appearance of certain fractions observed by electrophoresis on polyacrylamide gel could evoke the existence of malignant phenomena.

Animals↗
PubMed1984

[Effects of Aldatense on laboratory tests. Comparison with a reference population].

Aldatense effects on laboratory test results were studied in two subjects groups. - A treated group was paired with an untreated hypertensive group. In these conditions, some parameters were increased by 10 to 20 p. cent (creatinine, urea, phosphate, urate) or by 30 p. cent (triglycerides), others decreased by 40 p. cent (alkaline phosphatases) and 80 p. cent (gamma glutamyltransferase). The treated population was characterized either by values near to reference values (urea, creatinine, phosphate, calcium, albumin, gamma glutamyltransferase), by decreased values (alkaline phosphatases, triglycerides) or by increased values (urate).

Adult↗
PubMed1984

[Reference values of plasma and lipoprotein cholesterol and triacylglycerols in healthy children].

A sample of a reference population was selected from an all-inclusive population by a method based on strict physiological and clinical criteria. Sociological and ethnic factors as well as the biological plasma evaluation of the parents were used as family exclusion parameters. Cholesterol and triacylglycerols were measured in total plasma as well as in each lipoprotein fraction isolated by ultracentrifugation. The values are described as functions of sex and age. Total cholesterol varied little with age and sex. It is higher in girls except for HDL values. The maximum difference between boys and girls (age group 15-19 yrs) is mainly due to LDL-bound cholesterol. Plasma triacylglycerol values are generally higher in girls than in boys, particularly for VLDL. The minimum difference is in the age group 15-19 yrs.

Adolescent↗
PubMed1983

Plasma lecithin:cholesterol acyltransferase -- reference values and effects of xenobiotics.

Plasma lecithin:cholesterol acyltransferase (LCAT) has been measured by an enzymatic method. We did not observe any significant sex variations, but age variations were found. In females, LCAT activities are stable up to 40 years (60 mumol . 1.1 . h-1 at the 50th centile). Also, from 50 years the median increased progressively to 76 mumol . 1-1 . h-1. In males, the activity increased from 52 to 71 mumol . 1-1 . h-1 at the 50th centile in two age groups (15-20 years and 50 years). The effect of some xenobiotics on LCAT activity was studied. We observed an increase in activity of 33% in males when the daily alcoholic beverage consumption ranged from 0 to more than 0.5 litre of wine or beer. LCAT activity increased in children who were treated with hypolipidemic drugs (fenofibrate, Lipanthyl). In boys, the mean enzyme activity increased to 35% (p less than 0.05). The increase was greater in girls (75%, p less than 0.01). Treatment with anticonvulsant drugs gave a decrease in LCAT activity of 32-46%.

Adolescent↗
PubMed1983

Pressure effects on the apparent viscosity of artificial dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine membranes using intramolecular excimer probe.

Emission spectroscopy of intramolecular excimer probes allows the determination of 'equivalent viscosity' of membranes. While increasing the pressure on artificial membrane suspensions, variations in viscosity - essentially related to an increase in the order parameter in the membranes - are observed. In the case of mixed phospholipids, the effect of pressure is amplified, probably due to the existence of holes on the molecular scale between the two lipidic layers.

Dimyristoylphosphatidylcholine↗
PubMed1983

Studies of UDP-glucuronosyltransferase activity toward eugenol, using a gas chromatographic method of measurement.

A method for the assay of uridine diphosphate (UDP)-glucuronosyltransferase activities toward some phenolic compounds and monoterpenoid alcohols is described. The method is based on the disappearance of the free substrate after incubation with microsomes and UDP-glucuronate. This disappearance is recorded using a gas chromatographic process. This method has been used, for example, to characterize the glucuronidation process of eugenol (4-allyl-2-methoxyphenol). The method could be extended to other substrates. Analytical conditions are given for some of them, especially monoterpenoid alcohols since the studies of their conjugations are a growing field of interest in evaluation of heterogeneity of UDP-glucuronosyltransferase. The method could also be used with other biological materials including cell suspension and crude liver biopsies.

Animals↗
PubMed1983

Induced hepatotoxicity in female rats by aflatoxin B1 and ethynylestradiol interaction.

Female Sprague-Dawley rats were treated with a single ip dose of aflatoxin B1 (AFB1) (3 or 6 mg/kg). Twenty-four hours later and weekly until killed, some of the rats treated with AFB1 were given ethynylestradiol (EE) by gavage at the dose of 13 mg/kg. One, three, six, and nine months following the beginning of the experiment, animals were killed. Light microscopy of liver and histochemical determinations of gamma-glutamyltransferase (GGT) as well as the measurement of hepatic drug-metabolizing enzyme activities were investigated. The results show that AFB1 induced only very weak changes in the levels of different constituents studied. Thus, the mycotoxin did not affect GGT activity and increased epoxide hydrolase activity by a maximum of 42%. In contrast, EE significantly and progressively decreased (20 to 50%) the activity of UDP-glucuronosyltransferase (UDPGT) as well as the concentration of cytochrome P-450 and microsomal proteins. However, the estrogen increased the activity of epoxide hydrolase up to 150% as well as the activity of the hepatic (400%) and plasma (175%) GGT. The results also indicate that AFB1 amplified the EE-induced increase in liver weight and enhanced the depressive effects of the estrogen on microsomal proteins, cytochrome P-450, and UDPGT. Foci of cellular alteration which consisted of clear, acidophilic and basophilic cell lesions were seen in the livers of treated rats examined by light microscopy. These lesions were more prominent in the livers of animals given combinations of AFB1 and EE; they were accompanied by a strong intensity of GGT staining in the periportal area and a marked increase of the enzyme activity in the plasma (324%). From the sixth month, the livers of some animals treated with the combinations of AFB1 and EE showed hyperplastic nodules. This study indicates that the interaction between chronic administration of EE and a single ip injection of AFB1 induces hepatic lesions considered as possible forerunners of liver cell carcinomas. It also shows that GGT is a potential marker of preneoplastic lesions and may be used, therefore, in epidemiologic surveys in humans exposed to liver carcinogens such as the aflatoxins.

Aflatoxin B1↗
PubMed1983

Drug effects on clinical laboratory tests.

Drugs and xenobiotics can affect clinical laboratory test results either by interfering with the analytical systems themselves, or by influencing endogenous constituents. National and international bodies have brought widespread recognition to this problem and have proposed protocols for its thorough scientific study. In this survey the authors discuss studies in their laboratories concerning the effects of drugs on thousands of patients undergoing a routine clinical screen. A database is described for storing both patient information and a detailed analysis of the published literature on drug effects. Analytical interferences in clinical tests must be examined in validating the procedure. However, highly specific analytical techniques are increasingly helping to reduce such interferences. Biological effects can be classified as physiological, pharmacological or toxicological. In some cases, biological effects can be used to advantage in monitoring treatment by potentially hazardous drugs, such as the cardiac glycosides. The requirement for a well-defined reference population for each drug and for access to all clinical and medical data for each patient is discussed. The need for greater awareness of the influence of drugs on clinical laboratory results is considered, together with the suggestion that the health professions should try to exploit such effects in monitoring possible toxicity problems, in defining genetic constitution and in designing medication programmes.

Journal Article↗
PubMed1983

Effect of pretreatment with hydroxylated xenobiotics on the activities of rat liver UDP-glucuronosyl-transferases.

Six hydroxylated substrates were examined as potential inducers of UDP-glucuronosyltransferases towards their conjugation and the conjugation of other 'model' aglycones with glucuronic acid. Time-dependence (4, 14 and 28 days) and dose-dependence of treatments (from 25 mg/kg to 1 g/kg) were examined for some of these compounds. Monoterpenoid alcohols (borneol and terpineol) did not enhance the glucuronidation of the ten substrates tested. p-Hydroxybiphenyl gives typical 'substrate-induction' towards its own conjugation. Eugenol, a previously described inducer of UDP-glucuronosyltransferase activities in mouse, and 4-methylumbelliferone, give a general enhancement of all activities tested, especially those of the '3-methylcholanthrene-inducible' group of aglycones. p-Nitrophenol at low dose (2.5 mg/kg) gives a limited 'polycyclic aromatic hydrocarbon'-like increase.

Animals↗