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Biomedical subjects

M Lakshmanan

Publications and source records attributed to M Lakshmanan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Bifurcation, chaos and suppression of chaos in FitzHugh-Nagumo nerve conduction model equation.

We study the effect of constant and periodic membrane currents in neuronal axons described by the FitzHugh-Nagumo equation in its wave form. Linear stability analysis is carried out in the absence of periodic membrane current. Occurrence of chaotic motion, (i) in the absence of both constant and periodic membrane currents, (ii) with constant current only, (iii) with periodic membrane current only, and (iv) with both constant and periodic currents is investigated for specific parametric choices. We show how chaos sets in through a cascade of period doubling bifurcations. We then demonstrate the possibility of control of chaos using various control mechanisms. Specifically, we show the control of chaos by (i) adaptive control mechanism, (ii) periodic parametric perturbation and (iii) stabilization of unstable periodic orbits.

Animals↗
PubMed1993

Effects of dexamethasone on L-type calcium currents in the A7r5 smooth muscle-derived cell line.

Patch clamp experiments were used to characterize the effect of dexamethasone on calcium currents in A7r5 cells. Pretreatment for 48 h with 200 nM dexamethasone did not affect the single channel conductance, the voltage dependence of channel opening, or the voltage-dependent inactivation of L-type channels. However, dexamethasone caused an approximately 2-fold increase in the amplitude of L-type calcium currents in 5 out of 9 experiments, suggesting an increase in the number of active channels. The effect of dexamethasone appeared to be greatest on batches of cells with low control current density. The amplitude of T-type calcium current was not affected by dexamethasone.

Animals↗
PubMed1992

Differential effect of a new thyromimetic on triiodothyronine transport into myoblasts and hepatoma and neuroblastoma cells.

3,5-Dibromo-3'-pyridazinone-L-thyronine (L-94901), a member of a novel class of thyromimetics, reduces cholesterol plasma levels with little effect on cardiac function in rats. Because receptor binding of L-94901 in isolated heart and liver nuclei is similar but binding in liver nuclei in vivo was 50-fold higher than in cardiac nuclei, we studied its effect on triiodothyronine (T3) transport across the plasma membrane of myoblasts, hepatoma cells and neuroblasts. Previously, we had demonstrated saturable, stereospecific and energy dependent transport of T3 into the three cell lines. After equilibrium of intact cells with hormone, nuclear binding of T3 was decreased by L-94901 in all three cell lines. While whole cell uptake and whole cell binding of T3 was only slightly affected by L-94901, kinetic analysis of the initial rate of uptake showed uncompetitive or noncompetitive inhibition and a differential decrease in Vmax. Furthermore, the Ki for the liver and brain derived cells was 10-fold lower than for the muscle derived cells. This effect on the plasma membrane transport of T3 may explain the differential effect reported in the intact animal.

Animals↗
PubMed1992

Pelvic radioiodine uptake in a rectal wall teratoma after thyroidectomy for papillary carcinoma.

A 30-yr-old woman with previously resected papillary thyroid carcinoma was found to have a pelvic lesion which concentrated radioiodine. By performing simultaneous 131I whole-body and 99mTc-methylene diphosphonate bone scans, we found the lesion to be in soft tissue between the sacrum and bladder. Radioiodine therapy was postponed so that the lesion, a benign teratoma of the rectal wall, could be surgically removed. Prior to laparotomy, the patient received a second tracer dose of 131I so that the lesion could be located at surgery with a hand-held gamma detector. A postoperative whole-body 131I scan confirmed that the lesion had been removed, thus reducing the absorbed radiation that would have been received by the ovaries during radioiodine therapy. Although the lesion contained both thyroid and gastric epithelium, accumulated 131I was limited to the area with thyroid follicles.

Adult↗
PubMed1992

The movement of thyroid hormones in the central nervous system.

Thyroid hormones in the central nervous system (CNS) present a number of complexities which include a marked difference in hormone effects on the developing brain compared to the mature brain, extensive regional heterogeneity within the brain, and alternate ways by which the hormones gain entry to the CNS and its cells. Furthermore, most of the T3 found within brain cells is derived from the T4 that they have accumulated. This brief review concerns the movement of the thyroid hormones as they leave the bloodstream and make their way into and through the CNS. There are many sites for potential control of thyroid hormone transport into the central nervous system. The blood brain barrier and the choroid plexus may work in tandem as two parallel resistors subjected to different controls to maintain brain interstitial levels of thyroid hormone at near constant levels. Thyroid hormone may enter neurons directly from the interstitial fluid or indirectly from the glial cells. Nonetheless, both neurons, perhaps at the synaptosome, and glial cells are capable of transporting and concentrating thyroid hormones at physiological levels.

Animals↗
PubMed1990

High-affinity binding of thyroid hormones to neuroblastoma plasma membranes.

The binding of thyroid hormones to isolated plasma membranes was studied in NB41A3 neuroblasts. Saturable binding of L-T3, D-T3 and L-T4 was observed. Binding was time-dependent, with equilibrium reached in less than 60 min and maximal binding occurring between pH 7.4 and 7. Saturation experiments demonstrated two classes of sites for L-T3: a high-affinity site with Ka 8.4 X 10(9) M-1 and a low-affinity site with Ka 7.3 X 10(6) M-1.L-T3 and D-T3 inhibited each other's binding, L-T3 being several-times more potent. Affinity labeling of isolated membranes with bromoacetylated thyroid hormones disclosed stereospecific binding to SDS-PAGE bands with approximate molecular masses of 27 kDa (preferentially labeled by BrAc-L-T3), 32 kDa (preferentially labeled by BrAc-D-T3), and 48 and 87 kDa (preferentially labeled by BrAc-L-T4). Binding of BrAc-L-T3 to the 27 kDa band accounted for 3.4% of total binding, was selectively inhibited by excess L-T3, and may be involved in intracellular transport of L-T3.

Animals↗
PubMed1990

Thyroid hormone transport in a human glioma cell line.

The uptake of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) was studied in human glioma cells (Hs 683) and compared with that in several other neural cell lines. At 25 degrees C or 37 degrees C, total cell uptake rose rapidly and reached equilibrium within 60 min. The glioma cells had the highest uptake: 47.6 fmol of L-T3 and 43.4 fmol of L-T4 per 10(6) cells at 37 degrees C. These were inhibited 77% and 72%, respectively, by excess unlabeled hormone. Uptake in the nuclei reached equilibrium between 90 and 120 min and was also highest in glioma cells: 1.46 fmol of L-T3 and 0.49 fmol of L-T4 per 10(6) cells. When expressed as percent of total cell uptake, however, glioma cells had the lowest values (3.1% for L-T3 and 1.1% for L-T4). Also in contrast to other cell lines, glioma cells transported L-T4 almost as effectively as L-T3. D-T3 and D-T4 total cell uptake was 86% and 96% lower than that of the respective L-isomers, and the nuclear uptake as a fraction of the cell uptake was similar. Kinetic analysis of the initial rate of cell uptake gave Vmax values for D-T3 and D-T4 that were 97% and 98% lower than for the L-isomers. Antimycin and monodansylcadaverine decreased the Vmax as well as the equilibrium cell and nuclear uptake of the L-isomers. The apparent nuclear affinity constant for L-T4 in intact cells was inhibited 90% in the presence of antimycin, whereas no effect was observed in isolated nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoisobutyric Acids↗
PubMed1990

The transport of thyroxine into mouse neuroblastoma cells, NB41A3: the effect of L-system amino acids.

Thyroid hormones must cross the plasma membrane to interact with nuclear or other intracellular receptors. In brain cells, most of the T3 in the nucleus is derived intracellularly from T4. While a saturable transport system has been demonstrated for T3 in a number of cell types, the evidence for such a system for T4 is less well established. In a mouse neuroblastoma cell line (NB41A3) the transport of T4 was found to be stereospecific, saturable, and energy dependent. When cells were incubated with radiolabeled hormone, the nuclear accumulation of L-T4 was 3.8-fold higher than that of D-T4, whereas isolated nuclei had a similar Ka for both enantiomers. Exposure of cells to antimycin and monodansylcadaverine decreased nuclear uptake of L-T4 (Ki of 197 and 55 microM, respectively), but had little effect on D-T4 uptake. Furthermore, L-system neutral amino acids, in particular L-phenylalanine at physiological concentrations, were shown to be competitive inhibitors of both T3 and T4 transport. In the presence of 0.1 mM L-phenylalanine the Km of the saturable plasma membrane transport of L-T3 increased 2.3-fold, and that of L-T4 increased 2.1-fold. In contrast, 1.0 mM L-serine or D-phenylalanine had little effect on L-T4 transport. This interaction of L-system amino acid and thyroid hormone transport may be of physiological importance.

Amino Acids↗
PubMed1989

Triiodothyronine transport into differentiated and undifferentiated mouse neuroblastoma cells (NB41A3).

The mechanism of T3 entry into cells was studied in undifferentiated NB41A3 neuroblasts and after differentiation with 0.5 mM sodium butyrate. In undifferentiated neuroblasts, cell uptake of labeled L-T3 at 2 h was reduced to 43% of the control value by excess L-T3, whereas only 5.9% of D-T3 uptake was saturable. After incubation of intact cells with labeled hormone, the nuclei contained 3.8% of the total cellular L-T3 and 4.3% of D-T3. Thus, L-T3 nuclear uptake was 3 times higher than D-T3. Kinetic analysis of the initial rate of uptake of L-T3 by the cells gave a Km of 1.25 nM and a maximum velocity of 2.38 fmol/min.10(6) cells. The initial rate of D-T3 uptake was not saturable. Inhibitors of ATP production (antimycin and oligomycin) as well as monodansylcadaverine virtually abolished saturable cell uptake and decreased nuclear uptake more than total cell uptake, suggesting that the saturable component of uptake into the cells is the major source of nuclear L-T3. After differentiation by butyrate, both cell uptake and nuclear uptake of L-T3 increased. The apparent affinity (Ka) of the nuclear T3 receptors was determined in intact cells and compared with the Ka measured with isolated nuclei. In undifferentiated cells, the apparent Ka was 3-fold higher than the true Ka, presumably due to a step-up in the free T3 concentration in the cytosol compared to that in the incubation medium. After butyrate exposure, the apparent nuclear Ka was decreased to less than 1.5 times the control value, but Ka in isolated nuclei was unchanged. The number of nuclear receptors, however, was increased by butyrate in both intact cell and isolated nuclei experiments. These results indicate that butyrate exerts separate effects on the number of nuclear receptors and saturable T3 transport in mouse neuroblasts.

Adenosine Triphosphate↗