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Biomedical subjects

A Grenier

Publications and source records attributed to A Grenier.

At least 37 records · Page 2Linked to original sources
PubMed1984

Biochemical studies of a patient with hereditary hepatorenal tyrosinemia: evidence of glutathione deficiency.

Metabolic and enzymatic studies in a patient with hereditary tyrosinemia demonstrated for the first time a deficiency of erythrocyte and hepatic glutathione. Markedly decreased hepatic fumarylacetoacetate hydrolase activity was demonstrated in this patient. The activities of hepatic enzymes not involved in tyrosine metabolism were also determined. Assay of mixed function oxidase activity demonstrated low levels of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase, suggesting decreased hepatic detoxification capacity. 5-Aminolevulinic acid dehydratase activity was undetectable. Succinylacetone (4,6-dioxoheptanoic acid), an abnormal metabolic product secondary to fumarylacetoacetate hydrolase deficiency was found in serum and urine. Succinylacetone was demonstrated to inhibit 5-aminolevulinic acid dehydratase in vitro, as did the urine, plasma, and red cell lysates of the patient.

Erythrocytes↗
PubMed1982

Detection of succinylacetone and the use of its measurement in mass screening for hereditary tyrosinemia.

A technique designed to measure quantitatively succinylacetone (4,6-dioxoheptanoic acid) is presented. It essentially involves the inhibition of delta-aminolevulinate dehydratase (EC 4.2.1.24) by succinylacetone. Prior to their use in the assay, the samples are heated at 100 degrees C for 30 min in order to transform all succinylacetoacetate (3,5-dioxooctanedioic acid) to succinylacetone. By this transformation of the first abnormal metabolite specific to hereditary tyrosinemia to the second and last one, which is a powerful inhibitor of delta-aminolevulinate dehydratase, we determine in one sensitive assay the total amount of both. Succinylacetone was measured in sera and urines from 19 patients with hereditary tyrosinemia. All sera and urines contained succinylacetone at concentrations ranging, respectively, from 2 to 100 mumol/l and from 190 to 6000 mumol/g creatinine. The technique was also adapted to dried blood spots on paper and was used as a test complementary to blood tyrosine determination in mass screening for hereditary tyrosinemia. A total of 2412 samples having concentrations of 60 mg/l or more of tyrosine were assayed, and ten showed the presence of succinylacetone. These were all from newborns with hereditary tyrosinemia. The test has proven to virtually eliminate false positives, and, thereby, much clerical work and parental anxiety.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Prenatal diagnosis of hereditary tyrosinaemia: measurement of succinylacetone in amniotic fluid.

A method is proposed for prenatal diagnosis in pregnancies at risk of hereditary tryosinaemia. Affected fetuses were detected on the basis of the abnormal presence in the amniotic fluid of succinylacetone, a metabolite previously identified in sera and urines of patients suffering from hereditary tyrosinaemia. Our data show that the forty amniotic control samples had no detectable succinylacetone, while succinylacetone was found in three out of the thirteen cases at risk. Following the parents' decision, these three fetuses were aborted. The ten other mothers who brought their pregnancies to term had normal infants. Enzymatic analysis from two of their aborted fetuses' livers revealed an absence or a low activity of fumarylaceto-acetate hydrolase (EC 3.7.1.2) compared with control fetal livers of the same age.

Amniotic Fluid↗
PubMed1982

Maternal alphafetoprotein screening by the polypropylene tube immunoradiometric assay on dried blood.

The polypropylene tube immunoradiometric assay for alphafetoprotein (AFP) determination was applied to maternal serum along with a radioimmunoassay technique during the second trimester of pregnancy. Blood from pregnant women was collected by finger prick on strips of chromatography paper (Schleicher and Schuell No. 903C) and air dried. A 4.75 mm disc spot was eluted in anti-AFP coated tubes containing 1.0 ml of assay medium. After one hour the medium was vortexed and the tubes washed and counted on a Concept 4tm (Micromedic Systems, Horsham, PA. 19044). The sensitivity of the technique is about 9 micrograms/l (35 ng/l in the assay) by the Rodbard formula. The concordance between the dried blood and the serum RIA tests in normal pregnancies was over 90 per cent at the 95th and 97th percentiles. This assay on dried blood spotted on chromatography paper was tested on 1003 patients and proved to be an ideal alternative to whole serum screening techniques: it minimizes sample manipulations and can easily be integrated into an existing newborn screening programme.

Female↗
PubMed1981

["Liberated" motricity by holding the head during the first weeks of life (author's transl)].

The instability of the head disturbs neonatal motricity. However, when the head is held during a long period of observation (30 minutes) a motricity called "liberated" motricity, probably cortical in origin can be induced. 246 children, less than 8 weeks of age, have been examined while they were sitting on a bench and while their attention was kept in alert by the examinator who was holding their heads. In 97% of cases, the reflex motricity calms down and the following signs can be observed: (a) a stage of intense communication with the examinator, (b) then, the trunk straights up and the limbs become quiet and make movements which recall those of an older infant (43,5%), at least, there is a real interest for a toy, either looked at without gestures (39%), or touched and taken in an intentional way (19%). The theorical interest of this study is to get a new aspect of the normality of neonatal motricity. The clinical knowledge is still too recent to help detecting brain damage.

Head↗
PubMed1980

Toxicity, pharmacokinetics, and cholesterol-inhibitory effect of 7-ketocholesterol.

The possible toxic effect of intravenous 7-ketocholesterol (7-KC), a steroid which has been shown to inhibit cholesterol flux in the arterial wall, was investigated in rabbits. The histology, hematology and blood chemistry were compared in 4 control animals, 3 animals receiving high doses (5.50 +/- 0.33 mg/kg/day) and 4 animals injected with lower doses 1.85 +/- 0.28 mg/kg/day) of the oxygenated sterol. Each animal received a total of 16 injections at the rate of 2 injections per day. Pharmacokinetic studies on the disappearance rate of [4-(14)C]7-KC were also carried out. Pathologic changes in the organs of animals injected with 7-KC were few. In one animal exposed to the higher concentration of 7-KC, some granulomatous angiitis in the lung was noticed. Changes in the liver were not significantly different from those observed in the control animals. Inhibition of arterial flux of cholesterol (inhibition of 55%) was noticed with high and low doses of the oxidized sterol. The disappearance curves of [14C]cholesterol in blood and plasma were characteristic of a 2-compartment model. The rate constant determining tissue uptake of 7-KC was higher than tissue efflux and there was no appreciable reflux into red cells. The results indicate that it is possible to reduce cholesterol flux in the arterial wall of rabbits without causing major toxic changes and that both red cells and tissue act as a reservoir for the oxygenated sterol.

Animals↗
PubMed1980

Cord-blood tyrosine levels in the full-term phenylketonuric fetus and the "justification hypothesis".

The "justification hypothesis" attributes mental retardation in phenylketonuria (PKU) to an inability of the heterozygous mother to deliver an appropriate amount of tyrosine to the PKU fetus who, in turn, is unable to correct for this deficiency because of its genetic constitution. We tested this hypothesis by measuring concentrations of tyrosine and phenylalanine in cord blood obtained at delivery from nine infants with PKU and five infants with persistent (non-PKU) hyperphenylalaninemia (PHP). For each of these specimens there were four control cord-blood specimens from infants born on the same day and, generally, in the same hospital. PKU and PHP groups were similar with respect to cord-blood tyrosine and phenylalanine values. There was no biologically significant deficiency of tyrosine in cord blood of the pooled PKU and PHP deficiency of tyrosine in cord blood of the pooled PKU and PHP groups (54 +/- 10 microM, mean +/- SD) compared with controls (61 +/- 16 microM, P = 0.13). On the other hand, phenylalanine in cord blood of the pooled PKU and PHP groups was significantly increased (144 +/- 30 microM, mean +/- SD) compared with controls (128 +/- 24, P = 0.004). The mangitude of the differences in cord-blood tyrosine and phenylalanine between control and PKU subjects are so small that it is unlikely that they have any consequences for physical and mental development. The justification hypothesis, as it pertains to blood tyrosine at term, is not upheld.

Female↗
PubMed1978

Polystyrene tube immunoradiometric assay for human alpha1-fetoprotein, and its use for mass screening.

We describe a two-site immunoradiometric assay for human alpha1-fetoprotein, with use of antibody-coated polystyrene tubes as solid phase. The sensitivity, precision, and simplicity of this system make it eminently suitable for mass-screening purposes. We currently use it for neonatal detection of hereditary tyrosinemia in the Province of Quebec; measurements are made on blood spotted and dried on paper. This system could be well suited for other mass surveys, such as prenatal screenings for fetal abnormalities.

Amino Acid Metabolism, Inborn Errors↗