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Biomedical subjects

J H Dussault

Publications and source records attributed to J H Dussault.

At least 19 recordsLinked to original sources
PubMed1999

Thyroid function in mothers of hypothyroid newborns.

OBJECTIVE: To assess etiologic significance of maternal autoimmune thyroid disease on incidence of transient congenital hypothyroidism in newborns. METHODS: Thyroid function was assessed in 259 mothers of hypothyroid newborns from the Quebec newborn screening program between 1984 and 1996. Maternal blood samples were taken routinely at the time of follow-up serum sampling of the infants, for measurements of free thyroxine, TSH, and antimicrosomal autoantibodies. Thyroid scans were conducted to characterize the type of thyroid dysfunction in affected infants. Results were compared with similar data from a control population of 1773 pregnant women recruited from Quebec City between 1991 and 1992. These samples were collected at routine second-trimester prenatal screenings. RESULTS: The mothers of congenitally hypothyroid infants had higher prevalence of suppressed serum TSH concentrations compared with the control population (6.1% versus 2.9%, P = .01), higher prevalence of increased serum TSH levels (7.0% versus 0.9%, P < .001), and similar prevalence of positive antimicrosomal antibodies (11.6% versus 12.1%, P = .90). The prevalence of transient congenital hypothyroidism in the study population of hypothyroid infants was 27%, which is significantly greater than the 15% observed in our overall population of 523 congenitally hypothyroid infants studied between 1974 and 1996 (P = .04). Antimicrosomal antibodies were demonstrable in ten (77%) of 13 mothers of infants with transient congenital hypothyroidism, and antimicrosomal antibodies or abnormal serum TSH levels in 13 of 13 (100%). CONCLUSION: These results indicate that most, if not all, cases of transient congenital hypothyroidism were attributable to maternal autoimmune thyroid disease, and presumably to maternal TSH receptor-blocking antibody. They suggest that maternal autoimmune thyroid disease is associated with much higher prevalence of transient congenital hypothyroidism than suspected. Because of the 20% prevalence of autoimmune thyroid disease and thyroid dysfunction in the mothers of congenitally hypothyroid infants, we recommend thyroid assessment of such women, if this information is not available.

Autoantibodies↗
PubMed1999

Relation of basic and clinical research on foetal and neonatal thyroid pathology to neonatal thyroid screening.

In this short review the importance is emphasized of basic and clinical research in regard to the interpretation of screening results. This review covers foetal thyroid physiology during the first 48 h of life, the importance of thyroid hormones for normal brain development, the definition of a critical period which might explain intellectual abnormalities in 10-15% of detected hypothyroid children and the importance of autoimmunity in the aetiology and diagnosis of transient congenital hypothyroidism.

Animals↗
PubMed1997

Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone.

The development of oligodendrocyte progenitor cells is regulated by epigenetic factors which control their proliferation and differentiation. When oligodendrocyte progenitor cells, purified on a Percoll centrifugation gradient from neonate rat brain, are cultured in serum-free medium in the presence of platelet-derived-growth factor (PDGF), they divide and their differentiation is delayed. Triiodothyronine (T3) treatment of progenitor cells blocks their proliferation and induces their differentiation into oligodendrocytes. T3 also induces morphological differentiation of oligodendrocytes as indicated by the marked increase in the length of oligodendrocyte processes. To determine whether the effects of T3 on progenitor cell proliferation and oligodendrocyte maturation are causally related, or instead, are independent, we examined the influence of T3 on secondary cultures of postmitotic oligodendrocytes. We show that T3 increases morphological and functional maturation of postmitotic oligodendrocytes as indicated by a well developed network of branched processes and by the expression of myelin/oligodendrocyte glycoprotein (MOG) and glutamine synthetase (GS). T3 increases glutamine synthetase activity and its message level after a lag period of 24-48 h, and these levels increase through a posttranscriptional event. In contrast, no effect of T3 was observed on myelin basic protein (MBP) gene expression as determined by Northern blot analysis. Our results indicate that thyroid hormones participate in the control of the progenitor cell proliferation and differentiation as well as in oligodendrocyte maturation and that these two T3-regulated events are independent.

Animals↗
PubMed1996

Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment.

We have previously reported that despite neonatal screening, children with severe congenital hypothyroidism treated at 5 weeks of age with 6 micrograms/kg.day levothyroxine have clinically significant intellectual impairment, whereas those with the moderate form of the disease are indistinguishable from controls. The developmental outcome of children with severe congenital hypothyroidism treated earlier with higher initial doses of levothyroxine remained to be determined. In the present study, 45 infants with permanent congenital hypothyroidism detected by neonatal screening are described. For the group, the median age at starting treatment was 14 days, and the median initial dose of levothyroxine was 11.6 micrograms/kg.day. Based on the area of their knee epiphyses at diagnosis, the patients were divided into 2 subgroups: severe (< 0.05 cm2; n = 10) and moderate (> or = 0.05 cm2; n = 35). The psychomotor development of 8 patients in each subgroup, matched for the socioeducational level of their families, was assessed at 18 months. Mean plasma free T4 levels were supraphysiological during the first few months of life, but mean plasma T3 levels remained within the normal range, and there were no signs or symptoms of hyperthyroidism. The mean plasma TSH concentration was less than 4.5 mIU/L 4 weeks after starting treatment. Bone maturation remained delayed at 12 months in the severe cases and was not unduly advanced in the moderate cases. The mean (+/- SD) developmental quotients at 18 months were similar in severe and moderate cases (107 +/- 10 and 110 +/- 5, respectively). We conclude that with earlier treatment and a higher initial dose of levothyroxine, the early developmental outcome of infants with severe congenital hypothyroidism is now indistinguishable from that of infants with the moderate form of the disease who were used as controls.

Child Development↗
PubMed1995

Thyroid hormones stabilize acetylcholinesterase mRNA in neuro-2A cells that overexpress the beta 1 thyroid receptor.

We investigated the intracellular events involved in the 3,3',5-triiodo-L-thyronine (T3)-induced accumulation in acetylcholinesterase (AChE) activity in neuroblastoma cells (neuro-2a) that overexpress the human thyroid receptor beta 1 (hTR beta 1). Treatment of these cells with T3 increased AChE activity and its mRNAs after a lag period of 24-48 h, and these levels increased through stabilization of the transcripts by T3. T3 had no effect on the transcriptional rate or processing of AChE transcripts. The protein kinase inhibitor H7 inhibited T3-induced accumulation in AChE activity and its mRNAs, whereas okadaic acid (a potent inhibitor of phosphatases 1 and 2A) potentiated the effect of T3. Okadaic acid and H7 have no effect on the binding of hTR beta 1 to T3 or the transcriptional rate of the AChE gene. Finally, treatment of cells with T3 stimulated cytosolic serine/threonine, but not tyrosine kinase, activities. The time course analysis reveals that the increase in serine/threonine activity precedes the effect of T3 on AChE mRNAs. These results suggest that activation of a serine/threonine protein kinase pathway might be a link between nuclear thyroid hormone receptor activation and stabilization of AChE mRNA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Outcome in three siblings with antibody-mediated transient congenital hypothyroidism.

A woman receiving thyroxine substitution therapy for acquired hypothyroidism caused by autoimmune thyroiditis gave birth to three babies who had transient primary hypothyroidism. All three babies had elevated thyrotropin levels on neonatal screening, but one had normal thyroxine values. Thyrotropin receptor-blocking antibodies were present in maternal serum and in the three neonates. Each baby also had a different congenital malformation. The neurodevelopmental outcome of the children appeared related in part to maternal thyroxine levels, which suggests that transplacental transfer of thyroxine may protect the fetal brain.

Adult↗
PubMed1994

Expression of alpha and beta thyroid receptors during oligodendrocyte differentiation.

To determine which thyroid receptor (TR) isoforms are expressed during oligodendrocyte differentiation, we studied the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2) and one beta (beta 1) TR isoforms in a bipotential oligodendrocyte-type 2-astrocyte (O-2A) progenitor cell line (CG-4) as well as in rat O-2A progenitor cells and oligodendrocytes. O-2A progenitor cells expressed only TR alpha-mRNAs, whereas oligodendrocytes and type 2-astrocytes also expressed TR beta 1-mRNAs. The differential expression of alpha 1 and beta 1 TRs suggests specific functions for both types of TRs during oligodendrocyte differentiation. We present evidence for a possible role of TR alpha 1 in the effect of thyroid hormones on the proliferation of CG-4 cells maintained as progenitor cells.

Animals↗
PubMed1994

Overexpression of the beta 1 thyroid receptor induces differentiation in neuro-2a cells.

To determine the functions of the alpha 1 and beta 1 thyroid hormone receptors (TRs) in neural differentiation, we have established stable transfected neuronal cell lines (Neuro-2a) that overexpress either TR alpha 1 or TR beta 1. 3,5,3'-Triiodothyronine (T3) treatment of cells that overexpress TR beta 1 blocks proliferation by an arrest of cells in G0/G1 and induces morphological and functional differentiation of Neuro-2a cells as indicated by the marked increase in the number of perisomatal filopodia-like neurites and in acetylcholinesterase (AChE) activity. The effect on AChE activity was dose-dependent, and the time-course analysis reveals that this effect occurs after 24 hr of T3 treatment, with a maximal increase occurring after 48 hr of treatment. The increase of AChE activity is paralleled by an increase of AChE mRNAs. Last, we present evidence that shows that the effects of T3 on differentiation are independent of its effect on proliferation. T3 had no effect on the differentiation of Neuro-2a cells that overexpressed TR alpha 1. Our results indicate that TR beta 1 may play a key role in the effects of T3 in neuroblastoma cell differentiation.

Acetylcholinesterase↗
PubMed1994

Transient expression of 3,5,3'-triiodothyronine nuclear receptors in rat oligodendrocytes: in vivo and in vitro immunocytochemical studies.

It is generally accepted that the action of thyroid hormones is mediated through specific nuclear receptors. Recent studies have demonstrated the homology of the thyroid receptor with the cellular product of the oncogen v-erbA. So far, two genes have been identified and classified as alpha and beta subtypes. In this study, the expression of nuclear triiodothyronine (T3) receptors (NT3Rs) was examined in secondary cultures containing 85-90% oligodendrocytes (OL) prepared from newborn rat brain primary cultures enriched in OL. These cultures, which are able to produce myelin membranes, were examined by double immunolabelling with a monoclonal antibody (2B3) raised against purified rat liver NT3Rs and with antibodies against two maturation markers of OL: an early marker, galactocerebroside (GC), and myelin basic protein (MBP), which is expressed later than GC. 2B3 recognized three nuclear proteins with the same molecular weights as beta 1, alpha 1, and alpha 2 subtypes with different capacities for binding T3. In 5-day-old OL secondary cultures (25 days, total time in culture), 2B3-NT3R immunoreactivity was located in 77% of morphologically immature OL (GC)+ cells, whereas only 44% of morphologically mature OL were immunoreactive. Only 35% of the MBP+ cells co-expressed NT3Rs. In the corpus callosum of developing rat brain, at all ages studied from 7-60 days postnatal, the total absence of NT3Rs in dark OL (morphologically mature), confirmed by ultrastructural immunocytochemistry, indicates an even more dramatic decrease during maturation. Furthermore, the percentage of medium OL (less mature) stained by 2B3 is reduced by approximately half in 60- compared to 20-day-old rat brain. It is of interest to note that the in vitro observation with maturation markers mirrors the in vivo decrease of NT3R expression during development. It is interesting that NT3Rs are absent in vivo before the critical period of active myelination. These data indicate the presence of a nuclear T3 binding protein in the nuclei of OL at the time of myelination both in vitro and in vivo. The transient expression of these NT3Rs during active myelination argues in favour of a direct effect of thyroid hormones on OL.

Animals↗
PubMed1994

Thyroid hormones and thyrotropin variations during long term overfeeding in identical twins.

The aim of this study was to evaluate variations in plasma thyroid hormones and TSH during a standardized long term overfeeding protocol (4.2 megajoules/day [corrected] during a 100-day period) in 24 lean adults (12 pairs of monozygotic twins) and to assess their relationships with body composition and resting metabolic rate (RMR) changes. Compared to preoverfeeding values, basal plasma T3 concentrations were increased on day 25, but not later; basal plasma T4 and free T4 (FT4) concentrations were unchanged; basal plasma rT3 concentrations were persistently decreased throughout the entire protocol; and the TSH response to TRH stimulation was persistently enhanced. The TSH response to TRH before overfeeding was positively correlated with the changes in RMR with overfeeding (r = -0.53; P < 0.01). No association was found between changes in basal plasma T3 concentrations and changes in RMR. However, changes in basal T3 were positively related to changes in body weight (r = 0.46; P < 0.05). A significant within-pair similarity was found for changes in T4 and FT4 with overfeeding (P < 0.05). We conclude that 1) during overfeeding, the early increase in T3 concentrations is a transitory phenomenon, whereas the decrease in rT3 concentrations and the increased TSH response to TRH are more sustained; 2) the TSH responsiveness to TRH stimulation could be a predictor of the changes in RMR during times of increased energy intake; 3) there is no evidence for a direct role of T3 in the adaptation of resting energy expenditure during a long term overfeeding protocol; and 4) the genotype could be involved in the changes in T4 and FT4 during a prolonged positive energy balance period.

Adult↗
PubMed1993

Thyroid hormone up-regulates thyroid hormone receptor beta gene expression in rat cerebral hemisphere astrocyte cultures.

Oligonucleotide probes complementary to specific regions of three thyroid receptor cDNAs were used to study the effects of thyroid hormone on the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2) and one beta-thyroid (beta 1) receptors isoforms in rat cerebral hemisphere astrocyte cultures. Both genes are expressed by type 1 astrocytes. The levels of the alpha 1-, alpha 2-, and beta 1-mRNAs did not significantly change between day 8 and day 22, in cultures grown in the absence of thyroid hormone. L-triiodothyronine (L-T3) treatment of the cultures increased the levels of beta 1-mRNAs by fivefold without changing either the levels of the alpha 1- and alpha 2-mRNAs or L-T3 binding capacity. The effect of L-T3 on beta 1-mRNAs was observed after 4 h of treatment and was independent of protein synthesis, suggesting that this effect is likely to be a direct one. Treatment of the cultures by cytosine arabinosine, a drug that kills dividing cells, specifically decreased level of the alpha 1- and alpha 2-mRNAs by 60% and 38%, respectively. Finally, by immunocytochemistry, we showed that the beta 1 receptor-immunoreactivity was either located in the perinuclear region and the cytoplasm or in the nuclei of astrocytes. Taken together with previous data obtained in neuronal cultures where no effect of L-T3 was observed on the levels of the beta 1-mRNAs, our findings indicate that the beta 1 gene is differentially regulated in neurons and astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Expression of thyroid hormone receptors mRNAs in rat cerebral hemisphere neuronal cultures.

We have studied the expression of the alpha and beta thyroid receptors mRNAs (TR-mRNAs) in cerebral hemisphere neuronal cultures, initiated from 15-day-old rat embryos, by northern analysis. In the cultures grown in the absence of L-triiodothyronine (L-T3), the alpha 2 TR-mRNAs were the predominant form of TR-mRNAs and were approximately 8 to 20-fold higher than the levels of the alpha 1 TR-mRNAs, depending on the age of the cultures. The levels of alpha 2 TR-mRNAs significantly increased by 1.8 fold between day 8 and 15 and remained on a plateau value thereafter until day 22. Over the same time period, there were no significant changes on the levels of alpha 1 TR-mRNAs. The ratio alpha 1/alpha 1 + alpha 2 TR-mRNAs decreased between day 8 and 15. The beta 1 TR-mRNAs increased by 8 fold between day 8 and day 22. On day 8, the beta 1 TR-mRNAs were 1.8 fold lower than the levels of the alpha 1 TR-mRNAs while they were 6 fold higher on day 22. L-T3 treatment of the cultures had no effect on the levels of the alpha 1, alpha 2 and beta 1 TR-mRNAs. The differential temporal expression of the alpha 1 and beta 1 TR-mRNAs suggests distinct functions for both types of T3 receptors in neuronal maturation.

Animals↗
PubMed1992

Immunocytochemical localization of beta thyroid receptor in the rat cerebellum.

Using a specific antibody, we report here the immunocytochemical localization of the beta thyroid receptor (TR beta) in the adult rat cerebellum. We show that the immunoreactivity is specifically located in the Purkinje cells while the internal granular layer and the molecular layer are devoid of staining. In Purkinje cells, the immunoreactivity is either limited in the nuclei, or predominantly located in the perinuclear region and the cytoplasm. The presence of thyroid receptor is correlated with the presence of TR beta mRNAs as determined by Northern analysis.

Animals↗
PubMed1992

The expression of nuclear 3,5,3' triiodothyronine receptors is induced in Schwann cells by nerve transection.

The effects of thyroid hormones on the nervous system are mediated by the presence of nuclear T3 receptors (NT3R). In this study, the expression of NT3R was investigated in spinal cord, dorsal root ganglia (DRG), or sciatic nerve of adult rats after immunostaining with a 2B3-NT3R monoclonal antibody which recognizes both alpha and beta types of NT3R. The specificity of this monoclonal antibody was confirmed by Western blots. The 2B3-NT3R monoclonal antibody recognized one band corresponding to a molecular weight of 57 kDa in extract of spinal cord or DRG. No staining was observed on immunoblot of intact sciatic nerve. In the spinal cord, the nuclei of the neurons and glial cells including both astrocytes and oligodendrocytes exhibited 2B3-NT3R immunoreactivity. While all the nuclei of the DRG sensory neurons expressed the NT3R, all the nuclei of the satellite and Schwann cells were devoid of any immunoreaction. In the sciatic nerve, the nuclei of the Schwann cells also lacked 2B3-NT3R-immunoreactivity. After sciatic nerve transection in vivo, Schwann cell nuclei, which never expressed NT3R in intact nerves of adult rats, displayed a clear 2B3-NT3R immunoreaction in proximal and distal stumps adjacent to the section. Double immunostaining with antibodies raised to 3-sulfogalactosylceramide or S100 confirmed that most of the NT3R containing nuclei belong to Schwann cells. In dissociated cell cultures grown in vitro from sciatic nerves, Schwann cells exhibited 2B3-NT3R immunoreactivity. These data suggest that the inhibition of NT3R expression in Schwann cells ensheathing axons in intact nerve is reversed when the axons are degenerating or lacking.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗