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Biomedical subjects

J Ruel

Publications and source records attributed to J Ruel.

32 records · Page 2Linked to original sources

Regional distribution of nuclear T3 receptors in rat brain and evidence for preferential localization in neurons.

We examined the distribution of nuclear T3 in mature rat brain with the aim of determining specific targets of thyroid hormones within this tissue. Saturation experiments, performed in 9 different structures of the brain and in 4 parts of the cortex, revealed the presence of a single class of binding sites with a mean Ka of 0.53 X 10(10) M-1. The highest concentrations of receptors were found in the amygdala (0.523 +/- 0.025 ng T3/mg DNA, Mean +/- SE) and the hippocampus (0.438 +/- 0.071 ng T3/mg DNA) while the lowest were in the brain stem (0.058 +/- 0.003 ng T3/mg DNA) and the cerebellum (0.079 +/- 0.026 ng T3/ml DNA). The receptor was not uniformally distributed within the cerebral cortex, its concentration being relatively high in the central sections and intermediate in the remaining portions. The cell type distribution of the T3 receptor was studied by separating glial and neuronal nuclei on a discontinuous sucrose gradient. There was no detectable specific T3 binding in the fraction of oligodendrocyte nuclei (approximately 95% pure). Conversely, the neuron-enriched fraction (approximately 60%) showed a significant increase in receptor concentration compared to total nuclei (35-40% neurons): 0.857 +/- 0.196 vs 0.511 +/- 0.095 ng T3/mg DNA (p less than 0.01) in the cortex and 0.425 +/- 0.018 vs 0.234 +/- 0.24 ng T3/mg DNA (p less than 0.01) in the forebrain. The absence of nuclear T3 receptors in oligodendrocytes may have important implications on the mechanism of action of thyroid hormone in myelination.

Animals↗

Triiodothyronine increases glutamine synthetase activity in primary cultures of rat cerebellum.

Dissociated cells from 2-3 day-old rat cerebella were cultured in absence of thyroid hormones using conditions yielding mainly glial cells. After 7, 14 and 21 days in vitro, triiodothyronine (60 nM) was added to a set of dishes and glutamine synthetase activity was measured after 24, 48, and 72 h in both control and triiodothyronine-treated cultures. Basal glutamine synthetase activity increased more than 6 X between 7 and 21 days of culture. Triiodothyronine produced significant increases of glutamine synthetase activity after 72 h in 7-day-old cultures (+ 16%), after 48 h in 14-day-old cultures (+ 45%) and after 24 h in 21-day-old cultures (+ 27%). This effect depends on the initial plating density and is not observed if cells are plated at less than 1 cerebellum equivalent per 60 mm dish. Dose-response experiments indicated that 10(-8) M of triiodothyronine induces maximal response whereas half-maximal response is achieved around 10(-10) M. These results show that physiological amounts of thyroid hormone can influence the maturation of astrocytes in culture.

Animals↗

Thyroid hormones modulate ornithine decarboxylase in the immature rat cerebellum.

In this study, we measured ornithine decarboxylase (ODC) activity as a potential parameter to evaluate the response of the developing rat brain to thyroid hormones. In cerebellum, neonatal hyperthyroidism (40 micrograms thyroxine/100 g body weight daily from birth) increased ODC activity at 2 and 5 days of age and then accelerated its developmental decline. Conversely, ODC activity was decreased in 2- and 5-day-old hypothyroid rats (propylthiouracil to the mother), but it was not significantly different from normal thereafter. No significant differences were observed in the forebrain following either treatment. In hypothyroid rat cerebellum, a single injection of triiodothyronine (T3, 100 micrograms/100 g 18 h before sacrifice) increased significantly ODC activity at all ages. A dose-response study showed that 0.5 micrograms T3/100 g is sufficient to obtain maximal stimulation. Finally, administration of antiserum against rat growth hormone had no significant effect on ODC response to T3. These results show that ODC is a useful marker of thyroid state and tissue response in the neonatal rat cerebellum.

Aging↗

Pituitary nuclear triiodothyronine receptors during development in the rat.

Studies were undertaken to measure the pituitary nuclear triiodothyronine (T3) binding capacity (BC) during development in the rat. BC was measured in 0.4 M NaCl-solubilized receptors in 5-, 14-, 20-, 27-, 30-, 40-, 50-day-old rats and in adult animals. Results indicate that BC is lower in 5-day-old rats than in adult animals (0.397 +/- 0.02 vs. 0.797 +/- 0.06 pmol T3/mg protein) (mean +/- SE) (P less than 0.01). Hypothyroidism, induced during the neonatal period or in the adult animal, results in a significant decrease in BC (P less than 0.01) when compared with control rats. However, treatment of hypothyroid animals with T3 (0.4 micrograms/100 g body wt) for a period of 7-14 days significantly increased BC as compared with hypothyroid rats without apparent changes in Ka. The relative affinities of various thyroid hormone analogues for the nuclear receptor were also measured in the adult animal. The affinities of these analogues are in the following order: TRIAC greater than L-T3 greater than D-T3 greater than L-T4 greater than D-T4 greater than DIMIT greater than L-T2 greater than rT3. The present findings demonstrate the presence of high affinity nuclear T3 binding sites in the pituitary of neonatal rat and could thus account for the effects of thyroid hormones on GH synthesis and TSH secretion observed in these animals.

Aging↗

Thyroid hormones, malnutrition, and biochemical composition of developing rat lung.

We studied the effects of thyroid hormones and malnutrition on protein, DNA, and phospholipid content of the developing rat lung during the first month of life. Neonatal hypothyroidism significantly decreases the lung phospholipid content by 30-45% between 5 and 30 days of age whether the results are expressed per milligram DNA or per gram tissue. Administration of thyroxine for 3 days to hypothyroid rats increases significantly (20%) their total phospholipid content, mainly through its preferential effect on phosphatidylcholine (50% increase). Adult animal response to thyroid hormones is markedly different from that observed in young rats for most parameters examined. In malnourished rats, lung tissue phospholipids are decreased per cell but not per unit cell mass after 11 days of age. These results show that hypothyroidism has a specific effect on lung phospholipids during the neonatal period.

Animals↗

Characterization of nuclear 3,5,3'-triiodothyronine receptors in the developing rat lung: effects of hypo- and hyperthyroidism.

In this study, we measured the changes in binding characteristics of T3 to its nuclear receptor in lungs of rats from 2 days of age to adulthood. In all ages studied, we found a single class of binding sites with a mean Ka of 1.16 +/- 0.05 x 10(10) M-1. The specificity of the nuclear receptor, as judged by the relative affinities of thyroid hormone analogs, is in general agreement with data previously reported for lung and other organs. A significant decrease in the maximum binding capacity of the lung T3 receptor occurs between 30 and 40 days of age: 0 to 30 days, 0.208 +/- 0.005 pmole T3/mg protein; 40 days to adulthood, 0.111 +/- 0.007 pmole T3/mg protein. Our experiments showed that this reduction is not due to differential recovery of nuclei or efficiency of extraction at various ages. The relative saturation of the nuclear receptor increases from 26% at 2 days of age to 48% in the adult animal. Thyroid status has no significant effect on the nuclear T3 binding capacity of developing rat lung up to 11 days of age. However, hyperthyroidism substantially increased the binding capacity in lungs of adult animals (0.157 +/- 0.009 versus 0.108 +/- 0.006 pmole T3/mg protein), without a corresponding reduction in hypothyroidism (0.116 +/- 0.007 pmole T3/mg protein). These findings suggest that thyroid hormones play a yet unspecified important role in lung physiology during the first month of life in the rat.

Age Factors↗

Effect of retraction procedures on the periodontium in humans.

On the basis of wound healing and gingival recession caused by the three procedures, the copper-band retraction method was the most satisfactory. This tentative conclusion is based on the following reasons: 1. Retraction methods must be evaluated relative to the impression procedure and fit of the restoration. The long-range effects of the marginal fit are probably the most important factor for enhancing periodontal health. 2. This study involved only healthy periodontia of adolescent patients. Different healing might be observed in tissues characterized by gingivitis or periodontitis. 3. A broader study involving a greater range of procedures and conditions is recommended to evaluate each retraction technique. 4. This study involved teeth which had an adequate zone of attached gingiva. More complicated healing and perhaps altered sequences might be observed if the procedures were performed on gingival margins of alveolar mucosa, thin gingival walls, or areas of root prominence and thin cortical bone.

Adolescent↗

Residual visual capacities in a case of cortical blindness.

A case of cortical blindness resulting from a dense ischemic lesion of both calcarine cortices (as seen on CAT Scan) was studied up till the seventh month after the initial stroke. By using mainly forced-choice procedures, similar to those previously used for testing hemianopic subjects, we were able to demonstrate the reappearance of some visual capacities, even though the patient still behaved as if completely blind in everyday life and the lesion remained as it was first seen. First, an ability to detect moving stimuli reappeared then bright flashes could be detected. At last, the patient could localize flickering spots approximately, by pointing with his hand, despite the fact that he did not really see them. As was hypothesized in cases of unilateral occipital lesions, such residual vision would likely to be subserved by extrageniculostriate pathways.

Aged↗

Effects of neonatal hypo- and hyperthyroidism on pituitary growth hormone content in the rat.

Thyroid hormones play an important role in growth and development. Therefore, we investigated the effects of neonatal hypo- and hyperthyroidism on pituitary GH content in the rat. In control rats, pituitary GH content increased from 4.16 +/- 0.34 at 2 days to 43.7 +/- 4.2 microgram/gland (mean +/- SE) at 15 days of age, with a t 1/2 of increment of 3.48 +/- 0.40 days. Between 18-60 days of age, pituitary GH content increased from 56.9 +/- 4.0 to 300 +/- 28 microgram/gland, with a t 1/2 of 18.2 +/- 1.5 days. The administration of T3 had no significant effect on the pituitary GH content of these animals. In neonatal hypothyroid rats, pituitary GH content was significantly lower than that of controls at 2 days of age (P < 0.01) and decreased from 8 days on, with a t 1/2 of 3.71 +/- 0.25 days. However, 24 h after the administration of T3 (100 microgram/100 g BW), pituitary GH content was significantly increased in these animals. Similarly, the administration of T3 (0.4 microgram/100 g BW) to 14-day-old hypothyroid rats restored the pituitary GH content to 70-80% of normal after 5 days of therapy. Conversely, hyperthyroidism induced in 14-day-old normal or hypothyroid rats resulted in a significant decrease in their pituitary GH contents after 5 days of treatment. Therefore, the present results indicate that during the neonatal period, thyroid hormones play a primary role in the control of GH accumulation in the pituitary. Furthermore, the lack of increase in pituitary GH content after the administration of T3 during development might suggest that the rate of formation of GH is already maximum during this period of life in the rat, or, alternatively, that the pituitary nuclear T3 receptors are near full saturation during development. Finally, a generally similar effect of T3 on pituitary GH response was observed in the neonatal rat as well as in the adult animal.

Aging↗

Development of a flow simulator to study haemodynamic behaviour of natural and artificial blood vessels under physiologic flow conditions.

A new computer-controlled flow simulator has been designed to study the haemodynamic behaviour of natural and artificial blood vessels under physiologic flow conditions. The simulator can generate well characterized and fully developed laminar flow properties. It includes a unique perfusion case that imposes an axial tension on the vessel segment, and a commercial programmable pump to reproduce pulsatile flow rates. Response to high frequency commands was greatly attenuated and displayed a frequency dependent phase angle. Thus, for complex pulsating flow rates containing different frequency components, the system response was significantly distinct from the command. To reproduce physiologic waveforms, the transfer function of the whole system was determined for different amplitudes and frequencies of flow rate excitations. Each input command was compared to the measured flow rate, and the values of the gain and phase angle were evaluated. If the desired flow rate was composed of a sum of n sine wave components, each has a frequency fj and an amplitude Aj, a corrected command signal was then reconstructed by amplifying the attenuated components and advancing those lagged in time. The corrected signal was finally applied as the new command to the pump. The results showed an excellent agreement with physiologic waveforms. Examples of different pulsatile flow experiments to investigate the effects of frequency, pressure, and wall elasticity are presented.

Blood Flow Velocity↗

Development of a parallel plate flow chamber for studying cell behavior under pulsatile flow.

The design of a new parallel plate perfusion chamber for cell behavior studies involving pulsatile flowrates is presented. It was based on fluid mechanical considerations to ensure a region of regular and uniform shear stress at the wall. A numeric solution of the flow was performed to study the effect of pulsating flow on the entrance length. Dye injection investigations in the chamber showed laminar and uniform flow in the culture region under steady state conditions.

Cell Adhesion↗