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Biomedical subjects

J Letarte

Publications and source records attributed to J Letarte.

At least 19 recordsLinked to original sources
PubMed1991

Differential synthesis of 5-lipoxygenase in peripheral blood and synovial fluid neutrophils in rheumatoid arthritis.

In order to investigate 5-lipoxygenase enzyme regulation in neutrophils during an inflammatory reaction, we studied 5-lipoxygenase mRNA levels, as well as de novo enzyme synthesis, in resting and activated neutrophils isolated from normal individuals and patients with rheumatoid arthritis. The approach used was to analyze these activities in resting peripheral blood neutrophils of normal individuals on the one hand and in peripheral blood and matched synovial fluid neutrophils isolated from patients with rheumatoid arthritis on the other hand. Our first observation was that resting peripheral blood neutrophils of either normal individuals or patients show detectable levels of 5-lipoxygenase mRNA and are able to synthesize the enzyme de novo. Our second observation was that inflammatory activated neutrophils from synovial fluid reveal lower 5-lipoxygenase mRNA levels and enzyme synthesis than do the patient-matched peripheral blood cells. This is in spite of the fact that, for other proteins, synovial fluid neutrophils are equally or more active than their peripheral blood counterparts. We conclude that peripheral blood neutrophils are capable of synthesizing the enzyme, thus ensuring the turnover of the protein. Furthermore, complex regulatory mechanisms appear to take place in response to inflammation as it occurs in synovial fluids of patients with rheumatoid arthritis, leading to decreased mRNA levels and enzyme synthesis. Possible mechanisms of regulation are discussed and are presently under investigation.

Arachidonate 5-Lipoxygenase↗
PubMed1990

Mechanisms of hypercholesterolaemia in glycogen storage disease type I: defective metabolism of low density lipoprotein in cultured skin fibroblasts.

Hyperlipidaemia is a feature of glycogen storage disease type I (GSD-I) (Levy et al.). High levels of LDL cholesterol (200 +/- 25 mg dl-1) and apo B (387 +/- 44 mg dl-1) were found in association with hypercholesterolaemia in GSD-I. Related causative factors might be attributed to overproduction and/or delayed removal of LDL. In this study, a possible alteration in the clearance of LDL was examined. Using cultured fibroblasts for LDL receptor activity, the following observations were made: 1. GSD-I fibroblasts revealed only a slight decrease in LDL binding (65 +/- 7) when compared with controls (74 +/- 4 ng mg-1 protein), however, LDL internalization (382 +/- 24 vs. 570 +/- 52 ng mg-1 protein) and proteolytic degradation (2082 +/- 280 vs. 2916 +/- 12.5 ng mg-1 protein) were significantly affected (P less than 0.01). 2. Binding, internalization and proteolytic degradation of LDL from GSD-I were compared with that of controls, and were found to be significantly lower (P less than 0.01). 3. Substitution of control lipoprotein-deficient serum (LPDS) by GSD-I LPDS further diminished the above processes (P less than 0.05). Our results demonstrate that increased plasma cholesterol in GSD-I is due to a decreased catabolism of LDL. The data suggest that the problem may well be multifactorial, due to diminished receptor expression, abnormal LDL composition and impaired LDL receptor interaction due to a circulating inhibitory factor.

Adolescent↗
PubMed1989

Detection of beta-1,3-glucanase activity after native polyacrylamide gel electrophoresis: application to tobacco pathogenesis-related proteins.

Beta-1,3-Glucanase (laminarinase) activity was detected after polyacrylamide gel electrophoresis under native conditions by using laminarin as substrate. Following incubation of gels, laminarin was stained with Aniline Blue. Under UV illumination, lysis zones appeared as dark bands against a fluorescent background. As low as 0.001 unit of commercial Penicillium laminarinase could be observed after incubating the polyacrylamide gel for 45 min at pH 5.0. Extracts of commercial Penicillium laminarinase exhibited four bands with lytic activity towards laminarin. Analysis of intercellular fluid extracts of tobacco mosaic virus-infected tobacco leaves revealed four beta-1,3-glucanases corresponding to three acidic pathogenesis-related proteins, b4 (2), b5 (N) and b6b (0), and one basic protein. The presence of laminarin in gels retarded the migration of some proteins with beta 1,3-glucanase activity. This change in electrophoretic mobility could be used as a complementary affinity test for identifying proteins with beta-1,3-glucanase activity.

Electrophoresis, Polyacrylamide Gel↗
PubMed1989

The importance of glyoxylate and other glycine precursors in the hepatic and renal conjugation of benzoate in normal and hyperammonemic mice.

Benzoate conjugation, represented by hippurate synthesis, was measured in hepatocytes isolated from normal and sparse-fur (spf) mutant mice, with X-linked ornithine transcarbamylase deficiency, to compare the effects of glyoxylate and piridoxylate (a hemiacetal of glyoxylate and pyridoxine), substituted for glycine. Various amino acid precursors of glycine described in the literature, including serine, threonine, glutamine, and glutamate, were studied in a similar manner. The role of glyoxylate and piridoxylate was also assessed in the renal cortex, in comparison with liver homogenates from normal and hyperammonemic mice. The results indicate the importance of glyoxylate and piridoxylate to completely substitute for glycine (96-115%) in isolated hepatocytes of spf/Y mice, as compared with 53-69% (p less than 0.05) in normal +/Y controls. The mean value of amino acid precursors to substitute for glycine in spf mice was serine 51%, threonine 29% (p less than 0.05), and glutamine 9%. In normal mice, only serine (21%) (p less than 0.01) partly substituted for glycine, whereas threonine, glutamine and glutamate gave negative values of net hippurate synthesis. The specific activity of renal cortex for hippurate synthesis from glycine, glyoxylate and piridoxylate was 3-4 times that of liver homogenates (p less than 0.01 - less than 0.001). A scheme for the transamination of glyoxylate by alanine is presented. Besides alanine, the excess of glycine, serine, and threonine is readily deaminated in the body to take part in gluconeogenic reactions, thus contributing to hyperammonemia. The cumulative effect of benzoate conjugation to drain these ammoniagenic precursors through glycine may be the basis of its therapeutic effect in hyperammonemia.

Ammonia↗
PubMed1987

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. II. A cross-sectional study in childhood. Correlations with hormonal levels and developmental quotients.

We report the results of somatosensory evoked potentials (SEPs) and auditory brain-stem responses (ABRs) done in 48 congenital hypothyroid (CH) treated children, early detected and aged 18 months, 3 and 5-9 years of age. We report also the results of SEP and ABR done in 9 3-year-old CH children, before and after a 1 month therapy interruption to reassess the thyroid status. The more frequent abnormalities were increased wave I latencies for 18 month and 3-year-old CH children. In some children, these increases were not associated with signs of otitis media. No significant difference was seen between CH children and controls for SEP latencies and ABR and SEP interpeak latencies (IPLs). Similarly, no significant difference was seen between the two recording sessions in the 9 3-year-old CH children for ABR and SEP. On an individual basis, we observed abnormalities of central conduction time for ABR and SEP in several CH children. Moreover, significant partial correlations were found between ABR and SEP IPLs and thyroxine (T4) serum levels at diagnosis and thyrotropin (TSH) serum levels at the time of recording. There was also a significant partial correlation between N19-P22 IPLs and the practical reasoning scale of the Griffiths test considering the whole group of CH children. These results indicate that SEP might eventually be used to detect CH children at risk of presenting developmental abnormalities.

Brain Stem↗
PubMed1986

Somatosensory evoked potentials and auditory brain-stem responses in congenital hypothyroidism. I. A longitudinal study before and after treatment in six infants detected in the neonatal period.

We report the results of a longitudinal study of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) performed in 6 children with congenital hypothyroidism. These infants were detected by the Quebec Network for Genetic Medicine and treated early. ABRs and SEPs were recorded both before and 2 weeks after the initiation of therapy and at 6 months of age. Before treatment, for SEP, we found increased wave N19, P22 latencies and N13-N19, N19-P22 interpeak latencies (IPLs) in congenital hypothyroid (CH) children. For ABR, there were increased wave I latencies with normal I-V IPLs. Substitutive therapy improved these abnormalities although this improvement was more evident after a shorter period of time for ABRs than for SEPs. Even at 6 months, 2 CH children still showed increased N13-N19 IPLs. Both had very low serum T4 levels at the time of diagnosis and one had also a very small knee surface area, both criteria indicating a severe hypothyroidism. It will be interesting to verify if initial and persisting increase of N13-N19 IPL is associated with later neuropsychological problems.

Congenital Hypothyroidism↗
PubMed1978

Modification of a screening program for neonatal hypothyroidism.

From our experience in the screening of 212,000 newborn infants, we have devised a flow chart for processing T4 and TSH measurements obtained from initial filter paper blood spots. To date, all infants with thyroid dysfunction or TBG deficiency have been detected. Of the population screened, 1.84% require a spot TSH determination, and 1.1% require repeat determinations of T4.

Filtration↗
PubMed1978

Effects of clofibrate on plasma tryptophan, growth hormone, and prolactin and on brain tryptophan and serotonin in prepubertal rats.

The effects of clofibrate administration (200 mg/kg, po) on somatic growth, plasma levels of lipids, tryptophan, growth hormone (GH), and prolactin (PRL), as well as on brain concentrations of tryptophan and 5-hydroxytryptamine (5-HT) were studied in prepubertal male rats. The drug did not significantly alter ponderal growth, but an appreciable reduction of tail length was observed in rats treated for 30 days. Triglyceride concentrations in plasma showed a 43% diminution after 30 days of treatment, whereas free fatty acid (FFA) levels were not modified. Clofibrate administration for 7, 15, or 30 days caused a fall in total tryptophan and a significant increase of the free fraction in plasma with no change in brain tryptophan levels. Brain 5-HT was generally unaffected but a marked elevation of this parameter was noted in rats treated for 15 days. Plasma GH and PRL concentrations remained unaltered. It may be concluded from these findings that the slight reduction of somatic growth, the diminution of triglycerides, and the increase of free tryptophan in plasma, induced by chronic clofibrate treatment, are not associated with variations in brain tryptophan and 5-HT levels or with modifications of plasma GH and PRL titers.

Animals↗
PubMed1978

Reevaluation of levodopa-propranolol as a test of growth hormone reserve in children.

The growth hormone (GH) reserve of 15 short children was evaluated with the levodopa-propranolol test (DPT) and the sequential arginine-insulin test (AIT). Four patients failed to respond to both tests and were classified as hyposomatotropic. In the other 11 children, the mean GH peak response to the DPT was significantly higher than that to the AIT, mainly because five subjects who had a normal response to the DPT failed to respond to the AIT. These children had a generally poor yearly growth increment prior to testing associated in three with an obvious emotional problem, and were found at follow-up to have resumed a normal growth pattern. These data confirm the effectiveness of the DPT as a test of GH reserve. Although hypoglycemia can occur occasionally during test, this procedure is safer and easier to perform than the widely used AIT. Finally, the DPT seems to detect a category of children who have a temporary growth failure and nonresponse to the usual GH tests but who are not hyposomatotropic and consequently do not require human GH.

Adolescent↗
PubMed1978

Study of enzyme defect in a case of ornithine transcarbamylase deficiency.

Activity of liver ornithine transcarbamylase was measured in a biopsy obtained from a seven years old girl, suffering from chronic hyperammonemia and orotic aciduria. The activity of the defective enzyme was only 17% of that of a control. pH optimum was 8.1 in the patient and the control. However, the pH curves were different between 7.0 and 8.1. Km (ornithine) of the patient's ornithine transcarbamylase was within the normal range (0.41 nM), but the Km (carbamyl phosphate) was low (0.18 mM). The girl seems to be a heterozygote carrier of ornithine transcarbamylase deficiency due to an abnormal liver enzyme.

Ammonia↗
PubMed1977

Increase in plasma growth hormone levels following thyrotropin-releasing hormone injection in children with primary hypothyroidism.

Thyrotropin-releasing hormone (TRH) induced a significant increase in plasma growth hormone (GH) levels in 4 of 8 children with primary hypothyroidism, while a slight decrease was observed in 8 control children. Base-line plasma prolactin (PRL) levels and peak responses to TRH were higher in hypothyroid children than in controls. These data may indicate the existence of dysfunction of central nervous system mechanisms of control of GH and PRL secretion in subjects with primary hypothyroidism.

Adolescent↗
PubMed1976

Thyroid function in neonatal hypothyroidism.

Various aspects of the thyroid function have been measured in 28 cases of neonatal hypothyroidism detected by means of the Quebec Screening Program for Metabolic Diseases. In all instances the T4 value in the blood of filter paper spot was below 2 SD of the mean of the day, averaging 0.39 +/- 0.04 ng/40 mul (mean +/- SEM) of eluted blood. The T4 value of a second similar sample averaged 0.22 +/- 0.04 ng/mul of eluted blood; this value was significantly lower than the first one. The serum T4 concentration was decreased in all the infants, whereas three of them had a normal serum TSH concentration. At least three groups of patients could be identified: (1) patients with primary thyroid failure, (2) those with secondary or tertiary hypothyrodism, and (3) those with abnormal synthesis of thyroid hormone.

Female↗
PubMed1976

TSH measurements from blood spots on filter paper: a confirmatory screening test for neonatal hypothyroidism.

A sensitive radioimmunoassay for the measurement of TSH in the eluate of blood spotted on filter paper has been developed. The method is consistently sensitive to 0.1 to 0.25 muU of TSH and enables the detection of values equivalent to 6 to 15 muU/ml of serum. The measurement of TSH in the filter paper spot in all infants with low filter paper spot T4 has permitted rapid confirmation of 10 cases of neonatal hypothyroidism. However, cases of hypothalamic hypothyroidism with low or normal filter paper spot TSH concentrations would have been missed using only this method. Since these patients represent approximately 10% of our neonatal hypothyroid population, we do not recommend this method as a primary screening procedure, but rather as a confirmatory test which will accelerate the diagnosis and therefore the onset of therapy.

Filtration↗
PubMed1976

Catecholamines metabolism in thyroid diseases. I. Epinephrine secretion rate in hyperthyroidism and hypothyroidism.

We have measured the secretion rate of epinephrine in 6 euthyroid, 6 hyperthyroid, and 6 hypothyroid subjects infused at a constant rate for a one hour period with tritiated epinephrine (.01 muc/kg/min) (New England Nuclear Inc.). Plasma and urinary levels of epinephrine were measured by modifying the fluorometric method of Anton and Sayre. Plasma levels of epinephrine were 3.0 +/- 3.0 ng/100 ml (mean +/- SD) in normal subjects, compared to 4.4 +/- 3.5 ng/100 ml (mean +/- SD) in hyperthyroid subjects. In urine, epinephrine values ranged from 1.3 mug/day to 6.1 mug/day in normal subjects. Mean value observed in hyperthyroidism was 4.9 +/- 2.6 mug/day and 3.8 +/- 1.0 mu/day in hypothyroidism. Plasma secretion rates averaged 48 +/- 27 mug/kg/day in normal subjects, compared to 54 +/- 18 mu/kg/day in hyperthyroidism and 43 +/- 20 mug/kg/day in hypothyroidism. Likewise, the mean urinary secretion rate was 55 +/- 27 mug/kg/day in normal subjects compared to 60 +/- 22 mug/kg/day in hyperthyroidism and 50 +/- 28 mug/kg/day in hypothyroidism. There is no statistical difference between the values found in the three groups of subjects (plasma and urine). Therefore, these results would indicate that the signs and symptoms encountered in hyperthyroidism are not secondary to a high secretion rate of epinephrine.

Epinephrine↗