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Biomedical subjects

J P Chanoine

Publications and source records attributed to J P Chanoine.

At least 19 recordsLinked to original sources
PubMed2001

Modulation of steroidogenesis by selenium in a novel adrenal cell line developed using targeted tumorigenesis.

UNLABELLED: Glutathione peroxidase (GPx-1) is a selenoenzyme that metabolizes H(2)O(2), a source of potentially toxic free radicals. Steroidogenesis is markedly inhibited by H(2)O(2) in vitro. OBJECTIVE: to study the effects of selenium deficiency on GPx activity and adrenal steroidogenesis in a novel adrenal cell line developed using targeted tumorigenesis. METHODS: AN4Rppc7 cells were grown for 7 days in serum-free medium. 8-Br-cAMP-stimulated concentrations of steroid hormones were measured by RIA. StAR (Steroid Acute Reactive Protein) mRNA was measured by Northern blot. RESULTS: selenium deficiency caused a 99% There was a 51%, progesterone, corticosterone and aldosterone production, respectively (p<0.05 by ANOVA). StAR mRNA was not affected by selenium. CONCLUSIONS: selenium deficiency causes a marked decrease in GPx activity. Decreased steroid hormone production occurs for selenium concentrations equal or lower than 5 nM. The absence of changes in StAR mRNA content suggests that selenium deficiency does not affect cholesterol access to the mitochondria.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia. PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed. RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy. CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.

Adolescent↗
PubMed2001

Should the definition of micropenis vary according to ethnicity?

OBJECTIVE: We determined whether the existing reference values for the diagnosis of micropenis are appropriate for optimal care of neonates in a multiethnic environment like Vancouver. METHODS: The stretched penile length and width were measured in 105 full-term newborn males of Caucasian (n = 40), Chinese (n = 40) and East-Indian origin (n = 25). RESULTS: Mean length -2.5 SD was used for the definition of micropenis and was 2.6, 2.5 and 2.3 cm for Caucasian, East-Indian and Chinese babies, respectively (p < 0.05). This is close to the widely accepted recommendation that a penile length of 2.4- 2.5 cm be considered as the lowest limit for the definition of micropenis. CONCLUSION: Mean penile length and diameter are slightly but significantly smaller in newborns of Chinese origin compared to newborns of Caucasian and East-Indian origins.

Asian People↗
PubMed2001

Selenium decreases thyroglobulin concentrations but does not affect the increased thyroxine-to-triiodothyronine ratio in children with congenital hypothyroidism.

Compared with euthyroid controls, patients with congenital hypothyroidism (CH) who are receiving L-T(4) treatment show elevated serum TSH relative to serum T(4) concentrations and increased T(4)/T(3) ratio. These abnormalities could be the consequence of impaired activity of the selenoenzymes deiodinases on which patients with CH rely to convert the ingested L-T(4) into active T(3). Eighteen patients (0.5-15.4 yr), diagnosed with CH in infancy, received selenomethionine (SeM, 20-60 microg selenium/day) for 3 months. The study took place in Belgium, a country where selenium intake is borderline. Compared with the values observed in age- and sex-matched euthyroid controls, patients with CH had decreased selenium, thyroglobulin and T(3) concentrations and increased TSH, reverse T(3), and T(4) concentrations and T(4)/T(3) ratio at baseline. Selenium supplementation caused a 74% increase in plasma selenium values but did not affect the activity of the selenoenzyme glutathione peroxidase used as a marker of selenium status. SeM abolished the TSH difference observed between CH patients and euthyroid controls at baseline and caused a significant decrease in thyroglobulin values. Thyroid hormone concentrations were not affected by SeM. In conclusion, our data suggest that selenium is not a limiting factor for peripheral T(4)-to-T(3) conversion in CH patients. In contrast, we find indirect evidence that SeM improves thyroid hormones feedback at the hypothalamo-pituitary level and decreases stimulation of the residual thyroid tissue, possibly suggesting greater intracellular T(4)-to-T(3) conversion.

Adolescent↗
PubMed2001

Lipodystrophy in patients with juvenile dermatomyositis--evaluation of clinical and metabolic abnormalities.

OBJECTIVE: Lipodystrophy and associated metabolic abnormalities are being increasingly recognized as complications of juvenile dermatomyositis (JDM). We investigated the prevalence of lipodystrophy and the extent of metabolic abnormalities related to lipoatrophic diabetes mellitus in patients with JDM. METHODS: Twenty patients with JDM were evaluated for evidence of lipodystrophy and associated lipoatrophic diabetes mellitus. All patients underwent clinical assessment, laboratory investigations, and metabolic studies (oral glucose tolerance test, lipid studies, insulin antibodies). RESULTS: We found clinical evidence of lipodystrophy and lipoatrophic diabetes mellitus in 4 of 20 patients with JDM and metabolic abnormalities known to be associated with lipodystrophy in another 8 patients. The 20 patients with JDM were categorized as follows: Group 1 (Patients 1-4) consisted of patients with lipodystrophy and either diabetes mellitus (2 patients) or impaired glucose tolerance (2 patients); Group 2 (Patients 5-12): no lipodystrophy but abnormal glucose and/or lipid studies; Group 3 (Patients 13-20): no lipodystrophy and no abnormalities of glucose and lipid studies. CONCLUSION: We found 25% of patients with JDM have lipodystrophy, and 50% present with hypertriglyceridemia and insulin resistance. Screening for metabolic abnormalities in JDM should be included in routine followup because of the effect of lipodystrophy on longterm prognosis.

Adolescent↗
PubMed2000

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.

Adolescent↗
PubMed1998

Decreased growth hormone response to glucagon in infants after an apnea of infancy.

We studied glucagon-induced growth hormone secretion in 9 patients with apnea of infancy and in 55 siblings of children who had died of sudden infant death syndrome, who were included as a comparison group. We observed a 33% decrease in growth hormone secretion in patients with apnea of infancy. However, linear growth remained normal. This finding could be related to either repeated episodes of hypoxia or to abnormal maturation of the autonomous nervous system.

Apnea↗
PubMed1998

Age-related perception of stature, acceptance of therapy, and psychosocial functioning in human growth hormone-treated girls with Turner's syndrome.

This study evaluated the perception of stature, acceptance of therapy, and psychosocial functioning in relation to age at onset and time on treatment during 2 yr of GH therapy in 31 girls with Turner's syndrome grouped by age (group A: 3.7-5.8 yr, n = 9; group B: 7.2-11.8 yr, n = 13; group C: 12.5-16.4 yr, n = 9). The growth response after 2 yr was significant in the 3 groups when calculated in terms of growth norms for untreated Turner girls (mean increase in height SD score: +1.2, +1.5, and +1.1, respectively). The effect was less marked in terms of growth norms for normal girls, particularly in group B (+0.5 SD score). Height was perceived as a problem by most patients, except in the youngest girls at the start of treatment (group A) and in the majority of the adolescents after 2 yr of GH therapy (group C), without evidence of relation to growth response during therapy. The GH injections were fairly well accepted by all patients, except those younger than 6 yr. In all patients, expected adult height was unrealistic and became more realistic with age, whereas no consistent changes were observed in relation to growth response to GH therapy. The Child Behavior Checklist revealed elevated mean scores at the behavioral subscales of attention problems (group A and B), social problems, withdrawal, and anxiety-depression (most obviously in group B). No significant changes were seen during GH therapy. In group C, an elevated mean social problem score at the Youth Self Report and a low mean social self-esteem score at the Self-Esteem Inventory were observed before therapy and showed a significant improvement during 2 yr of GH treatment. These results, however, might be biased due to an increase in social desirability during therapy. We conclude that the perception of height, acceptance of GH therapy, and psychosocial functioning in girls with Turner's syndrome show important differences between age groups, with only slight changes observed during GH therapy.

Adolescent↗
PubMed1996

Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5'-deiodinase type I inhibitor 6-anilino-2-thiouracil.

Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5'D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5'D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5'D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17: antibiotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl; ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/- 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0.7 and T3S = 9.7 +/- 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5'D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5'D-I activity is markedly decreased.

Aniline Compounds↗
PubMed1995

Glucose, growth hormone, cortisol, and insulin responses to glucagon injection in normal infants, aged 0.5-12 months.

We performed glucagon stimulation tests in 59 normally growing siblings of children who died from sudden infant death syndrome. These investigations were performed to exclude a possible metabolic disorder (found in 4 siblings) as an underlying cause of sudden infant death syndrome. The remaining 55 siblings (32 boys and 23 girls) provide control data for this age range. Testing was performed at 0800 h after a 15-h fast. The median age was 98 days (range, 13-349 days). Plasma glucose and serum cortisol, insulin, and GH were determined before and 30, 60, 90, 120, 150, and 180 min after im injection of 0.1 mg/kg glucagon. No side-effects were observed during the procedure. Asymptomatic hypoglycemia was noted in 11% of the infants at least once between 120-180 min. Basal and peak GH concentrations were greater than 10 micrograms/L in 31% and 80% of the infants, respectively. There was a significant negative correlation between age and basal GH concentration [Spearman's rank correlation coefficient (rs) = -0.37; P < 0.01]. There was a significant correlation between age and glucagon-stimulated cortisol at 120, 150, and 180 min (rs) = 0.41; P < 0.005), but not between age and changes in glucose levels. There was no significant correlation between age and basal cortisol or peak GH concentrations and no difference between boys and girls for any of the variables studied. In conclusion, the glucagon stimulation test is well tolerated in very young subjects. The peak GH response to glucagon injection is independent of age between 0.5-12 months. The age-related increase in the glucagon-stimulated cortisol response despite a similar decrease in glucose suggests the existence of a postnatal maturation in the response of the pituitary-adrenal axis to stress.

Aging↗
PubMed1995

No apparent mineralocorticoid receptor defect in a series of sporadic cases of pseudohypoaldosteronism.

Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C944-->T944, Ala241-->Val241) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A760-->G760, Ileu180-->Val180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone.

Adolescent↗
PubMed1993

The thyroid gland is a major source of circulating T3 in the rat.

In rats, the respective contribution of the thyroid and peripheral tissues to the pool of T3 remains unclear. Most, if not all, of the circulating T3 produced by extrathyroidal sources is generated by 5'-deiodination of T4, catalyzed by the selenoenzyme, type I iodothyronine 5'-deiodinase (5'D-I). 5'D-I in the liver and kidney is almost completely lost in selenium deficiency, resulting in a marked decrease in T4 deiodination and an increase in circulating T4 levels. Surprisingly, circulating T3 levels are only marginally decreased by selenium deficiency. In this study, we used selenium deficiency and thyroidectomy to determine the relative contribution of thyroidal and extrathyroidal sources to the total body pool of T3. Despite maintaining normal serum T4 concentrations in thyroidectomized rats by T4 replacement, serum T3 concentrations remained 55% lower than those seen in intact rats. In intact rats, restricting selenium intake had no effect on circulating T3 concentrations. Decreasing 5'D-I activity in the liver and kidney by > 90% by restricting selenium intake resulted in a further 20% decrease in serum T3 concentrations in the thyroidectomized, T4 replaced rats, suggesting that peripheral T4 to T3 conversion in these tissues generates approximately 20% of the circulating T3 concentrations. While dietary selenium restriction markedly decreased intrahepatic selenium content (> 95%), intrathyroidal selenium content decreased by only 27%. Further, thyroid 5'D-I activity actually increased 25% in the selenium deficient rats, suggesting the continued synthesis of this selenoenzyme over selenoproteins in other tissues in selenium deficiency. These data demonstrate that the thyroid is the major source of T3 in the rat and suggest that intrathyroidal T4 to T3 conversion may account for most of the T3 released by the thyroid.

Animals↗
PubMed1993

Placental 5-deiodinase activity and fetal thyroid hormone economy are unaffected by selenium deficiency in the rat.

In adult male rats, selenium deficiency results in a near complete loss in the selenoprotein 5'-deiodinase in the liver, resulting in decreased peripheral deiodination of thyroxine (T4) and increased serum T4 concentrations. Serum 3,5,3'-triiodothyronine concentrations are normal or slightly decreased, and serum 3,3',5'-triiodothyronine concentrations are normal or slightly increased in selenium-deficient rats. We now report the effects of selenium deficiency on maternal and fetal thyroid hormone economy and on placental 5-deiodinase activity in the rat. Weanling female rats were fed either a selenium-deficient or selenium-supplemented diet for 4 wk before mating and then throughout gestation. Rats were killed at 21 d of gestation. Selenium deficiency was confirmed by a 95 and 94% decrease in glutathione peroxidase and a 84 and 56% decrease in liver type I outer ring 5' deiodinase activity in the mother and the fetus, respectively. In contrast to the increase in circulating T4 observed in selenium-deficient male and nonpregnant female adult rats, serum T4 was not affected by selenium deficiency in pregnant rats, but there was a 3-fold increase in serum 3,3',5'-triiodothyronine concentrations associated with a 70% decrease in maternal brain type II outer ring 5' deiodinase activity. Maternal serum 3,5,3'-triiodothyronine concentrations were decreased by 21%. Placental 5-deiodinase activity was unaffected by selenium deficiency. In the fetus, serum T4, 3,3',5'-triiodothyronine, and TSH concentrations were not affected by selenium deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The postnatal serum 3,5,3'-triiodothyronine (T3) surge in the rat is largely independent of extrathyroidal 5'-deiodination of thyroxine to T3.

In the rat, selenium deficiency causes a near-complete loss of the selenoenzyme type I 5'-deiodinase (5'D-I), resulting in a marked decrease in hepatic T4 to T3 conversion. In adult rats, serum T4 concentrations are consistently increased, whereas serum T3 and rT3 concentrations are unaffected or slightly decreased and increased, respectively. In rat fetuses near term, serum T4 and rT3 concentrations are not affected by selenium deficiency. We have now studied the effect of selenium deficiency on thyroid function in the neonatal rat. Weanling female rats were fed either a selenium-supplemented or a selenium-deficient diet for 4 weeks before mating and then throughout gestation and lactation. Neonatal rats were killed at 7, 14, 21, and 28 days. Selenium deficiency was confirmed by a more than 89% decrease in liver 5'D-I activity in mothers and pups. Selenium deficiency resulted in significant increases in serum T4 concentrations in 3- and 4-week-old pups. In contrast, selenium deficiency led to a striking increase in serum rT3 concentrations. The normal postnatal serum T3 surge was not affected by selenium deficiency at any age. In 2- and 4-week-old selenium-deficient pups obtained from a second litter from the same mothers, liver 5'D-I activity was markedly decreased, but thyroid 5'D-I activity was not affected. The increased serum rT3 and, less so, T4 concentrations observed in selenium-deficient pups were associated with a significant decrease in brain 5'D-II activity in 14- and 28-day-old pups and in brown adipose tissue 5'D-II activity in 14-day-old pups. In conclusion, the present study demonstrates that the increase in serum T4 concentrations consistently observed in selenium-deficient adult rats occurs only after the second week of life. The normal physiological postnatal 12-fold increase in serum T3 concentrations observed in selenium-deficient pups despite the marked decreases in liver 5'D-I and brain and brown adipose tissue 5'D-II activities suggests that T4 to T3 conversion by peripheral tissues may not be a major source of T3 in the neonate. In contrast, the thyroid gland, whose 5'D-I activity is not affected by selenium deficiency, is probably the principal source of circulating T3 in the neonate. Finally, the early and marked increase in serum rT3 concentrations observed in selenium-deficient pups suggests that liver 5'D-I is important in rT3 deiodination.

Adipose Tissue, Brown↗
PubMed1993

Circulating calcitonin levels in healthy children and subjects with congenital hypothyroidism from birth to adolescence.

Using an extraction-concentration technique of circulating calcitonin (exCT) that permits a sensitive and specific assessment of circulating CT monomer levels, we measured exCT levels in 115 healthy children (59 girls and 56 boys), aged 0-16 yr, and 25 patients (15 girls and 10 boys), aged 2 months to 22 yr, with congenital hypothyroidism (CH), a condition characterized by a marked CT deficiency in adults. We found a significant negative correlation between CT levels and age in healthy children (girls, r = -0.83; boys, r = -0.63; P < 0.001). There was a 5-fold decrease in CT levels from the neonatal period to adolescence. The fall in CT levels was particularly marked in early infancy (e.g. for the age category 1 day to 1 yr, 19.0 +/- 1.9 vs. 7.3 +/- 1.2 ng/L for the group 1-5 yr, P < 0.01), but less pronounced thereafter (for the group 5-10 yr, 4.7 +/- 0.8 ng/L; P < 0.001 vs. the group 1 day to 1 yr). The well established sex difference in CT levels in adults was significant only for the age category above 10 yr (2.7 +/- 0.4 ng/L for girls vs. 4.5 +/- 0.7 ng/L for boys, P < 0.05). In patients with CH, the mean exCT level was 2.0 +/- 0.3 ng/L under 3 yr of age (n = 9), whereas all CT values were undetectable after the age of 3 yr, which could contribute to the lower bone mass of adult CH patients. CT values were normal in 3 children with metabolic goiter. In healthy children, our results demonstrate the existence of an age-related decrease in circulating CT levels, which was particularly marked in infancy. The sex difference in CT levels progressively appeared in childhood, but was significant only after 10 yr of age. Such changes in CT levels could be important for neonatal calcium metabolism and contribute to the lower bone mass in females.

Adolescent↗