Biomedical subjects

M Saji

Publications and source records attributed to M Saji.

126 records · Page 7Linked to original sources

PubMed1987

Biological activities of human growth hormone and its derivatives estimated by measuring DNA synthesis in Nb2 node rat lymphoma cells.

Nb2 cell is a rat lymphoma cell line that responds to lactogens such as prolactin and human growth hormone (hGH) with an increased rate of proliferation. We explored the relationship between the biochemical events induced by hGH and its derivatives and their receptor binding activities. hGH stimulated RNA, DNA and protein synthesis of Nb2 cells as a function of time. Stimulation of RNA and protein was maximal at 2-3 h and 12 h, respectively, after the addition of hGH. DNA synthesis, measured by the rate of [3H]thymidine incorporation, reached a maximum after 18-h incubation with hGH. Stimulation of DNA synthesis was elicited by hGH in a dose-dependent manner between 0.45 and 45 pmol/l. The activity of the 20 K hGH variant in stimulating DNA synthesis was approx 30% of that of hGH. In contrast, S1-hGH, which lacks a sequence of ten amino acids (140-149) of hGH, showed a 3.2-fold greater activity than hGH. F1 (amino-terminal sequence 1-134 of hGH) was only 0.06% as active as hGH, and the activity of F2 (C-terminal 42 amino acid residue of hGH) was less than 0.01%. Both fragment 1-15 and 32-46 were without effect. The relative potencies of these hGH derivatives in stimulating DNA synthesis were similar to their relative abilities to inhibit [125I]hGH binding to lactogenic receptors on Nb2 cell. Nb2 cells provide a suitable model to study the relationship between receptor binding and the biochemical events induced by lactogens.

Animals↗

PubMed1987

Ibotenic acid-induced lesions of striatal target and projection neurons: ultrastructural manifestations in dopaminergic and non-dopaminergic neurons and in glia.

The cytological changes elicited by central microinjections of the excitotoxin, ibotenic acid (IBO) were examined in the adult rat striatonigral system using electron microscopic immunocytochemistry. The chemical markers included tyrosine hydroxylase (TH), a biosynthetic enzyme in dopaminergic neurons, and glial fibrillary acidic protein (GFAP). Both short (1-7 day) and long (30-60 days) term effects were evaluated at the site of IBO-injections in the striatum and more distally in the substantia nigra, which both contributes afferents and receives efferents from the striatum. In the neostriatum at every survival period examined, TH-labeled axonal processes appeared equally numerous in the control and IBO-injected hemispheres. However, the TH-labeled axons in the striatum ipsilateral to the IBO-injection were slightly enlarged, and generally lacked synaptic densities. In the early period the remaining neuropil showed signs of edema and contained perikarya and dendrites with vacuolar or dense cytoplasm as well as intact, unlabeled terminals. Numerous astrocytes, and apparently demyelinated axons were more commonly seen at the 7 day period. At 30 and 60 days, bundles of myelinated axons, unlabeled axon terminals, and astrocytes containing a variety of cytosomes and other cytoplasmic inclusions were in close apposition to TH-labeled axon terminals. These results suggest that the dopaminergic terminals may serve neuromodulatory functions with respect to glia or other afferent axons remaining after IBO-injections in the striatum. In the substantia nigra, homolateral to the injection, a dense type of degeneration was seen in a few perikarya and dendrites at 7 days of survival. At this stage, electron dense anterograde degeneration also was seen in terminals contacting both TH-labeled and unlabeled dendrites. The secondary long term changes in nuclear groups located distal to the primary lesion are characteristic of certain types of progressive human neuropathological disorders.

Animals↗

PubMed1986

Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 alpha in fetal mouse bones.

Recombinant human interleukin 1 alpha (rhIL-1 alpha) stimulates prostaglandin E2 and bone resorption in cultured forearm bones of fetal mouse in a dose-dependent manner: the minimal rhIL-1 alpha to elicit a significant bone resorption was 1.6 ng/ml (89 pM). The half maximal concentrations to elicit bone resorption and thymocyte proliferation were 3.3 ng/ml (183 pM) and 0.31 ng/ml (17 pM), respectively. The bone resorbing activity induced by IL-1 was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL 1-antibody. There was a good correlation between PGE2 production and bone resorption induced by IL-1 alpha. These results suggest that rhIL-1 alpha stimulates bone resorption at approximately 10 times the concentrations necessary for thymocyte proliferation and that PGE2 produced in the bone is at least in part involved in osteoclastic bone resorption.

Animals↗

PubMed1985

Thyroid-stimulating antibody bioassay using porcine thyroid cells cultured in follicles.

Isolated porcine thyroid cells were cultured in agarose-coated dishes and allowed to reform follicles with normal polarity. The thyroid cells reaggregated into follicles were compared with cells cultured in monolayer for cAMP responsiveness to TSH and thyroid-stimulating antibody (TSAb). The cells in follicles were sensitive to TSH stimulation and responded to the hormone at concentrations as low as 3.3-10 microU/ml with an increase in cAMP production. In contrast, 10-50 microU/ml TSH were required to elicit a cAMP response in cells cultured in monolayer using identical conditions. cAMP responsiveness to TSAb also was greater in the cells organized into follicles. TSAb was detected in serum from 89.4% of 66 untreated patients with hyperthyroid Graves' disease using thyroid follicles, but TSAb was detected in serum from only 60% of the patients when assayed using cells in monolayer. The assay using thyroid follicles was used to measure TSAb in 27 euthyroid patients who were euthyroid while receiving thionamide therapy and compared with 20-min thyroid 131I uptake after T3 suppression. TSAb was present in 11 of 12 nonsuppressible patients and in 5 of 15 suppressible patients. TSAb was positively correlated with 20-min 131I thyroid uptake. We conclude that thyroid cells cultured in follicles are suitable for measuring TSAb.

Adolescent↗

PubMed1985

Triiodothyronine binding immunoglobulin in a euthyroid man without apparent thyroid disease; its properties and effects on triiodothyronine metabolism.

A 54 year old man with markedly elevated serum T3, but without an apparent thyroid disease, was found to have a specific antibody to T3. His serum thyroxine, TBG and TSH were in normal range, but T3-RSU was markedly low. Antibodies to thyroglobulin and microsome were negative. He was judged euthyroid because of a normal basal metabolic rate and a normal thyroidal 123I uptake which was suppressed by T3 administration. When serum was extracted with ethanol prior to assay, serum T3 was found to be in the upper border of normal range. Several experiments revealed the presence of an antibody to T3 in his serum with an affinity constant of 3.3 X 10(9) M-1. The binding capacity of the antibody was 7.6 ng/mg of IgG. The binding of [125I]T3 was almost specific to T3, and potencies of T4 and fT3 in displacing [125I]T3 binding were only 1.0 and 0.3%, respectively, of that of T3. The antibody contained both kappa and lambda chains and was therefore polyclonal. The T3 metabolic clearance rate, which was determined by disappearance of injected [125I]T3 from serum, was lower in this patient (7.44 1/day) than in normal. The T3-production rate was decreased to 14.9 micrograms/day, and serum free T3 concentration as well as urinary T3 excretion rate were also reduced. Since both serum total and free T4 concentrations were normal, the supply of T4 to peripheral tissues would be sufficient to keep this patient in a euthyroid state in spite of the anti-T3 antibody.

Chemical Precipitation↗

PubMed1983

Action of angiotensin II on cultured brain stem neurons of the rat.

Following the application of angiotensin II to cultured lower brain stem neurons of rat embryos, the facilitatory response was mostly seen in small-sized oval, fusiform, and polygonal neurons, while the inhibitory response was seen in medium-sized pyramidal and multipolar neurons. Saralasin blocked both facilitatory and slow inhibitory responses, but had no effect on the fast inhibitory response.

Action Potentials↗

PubMed1982

Transmitter sensitivities among various types of cultured brain stem neurons.

We prepared cultures of dissociated cells from the lower brain stem of 14- to 15- day-old rat fetuses, and studied how neuronal activities of various types of neurons were influenced by application of various transmitters or transmitter-like substances. Unit discharges of the cultured neurons were recorded extracellularly, using suction micropipette, while the test substances were applied iontophoretically to the surface membrane of the cell body. We selected for testing 4 types of neurons with the typical appearance, i.e. multipolar, pyramidal, polygonal and fusiform one. Each type of neuron had specific sensitivities to acetylcholine and leucine-enkephalin. Amino acids and substance P acted to 4 types of neurons as either unanimous excitant or inhibitor. Monoamines and leucine-enkephalin had both inhibitory and facilitatory effect on unit discharges, although the inhibitory effect was dominant. These findings suggest that there is a specific relation between morphological properties of the brain stem neurons and their sensitivities to transmitters.

Acetylcholine↗

PubMed1982

Nicotinic and muscarinic property of ACh receptors on cultured brain stem neurons.

Explore the source record for details and available documents.

Acetylcholine↗

PubMed1981

Stimulus-dependent labeling of cultured ganglionic cell with [14C]2-deoxyglucose.

We prepared cultures of dissociated cells from the ciliary (CG) and dorsal root ganglion (DRG) of 10--12-day-old chick embryos, and applied [14C]2-deoxyglucose ([14C]2-DG) to the cultured cells to examine the effects of stimulation on the labeling with [14C]2-DG at the single cell level. Electrical current stimulation increased [14C]2-DG uptake in CG and DRG neurons. The increase depended on frequency of the stimulation. These effects were potentiated by the application of tetraethylammonium, but suppressed by tetrodotoxin. Externally applied potassium ions increased the [14C]2-DG uptake in the CG cell, depending logarithmically on the concentration of applied KCl. The concentration-dependent increase agreed with potassium effect on the equilibrium potential. For CG cells, acetylcholine (ACh), glutamate, gamma-aminobutyric acid (GABA) and glycine induced remarkable increases of the [14C]2-DG uptake, while dopamine did not induce any change. For DRG cells, GABA and glycine facilitated the [14C]2-DG uptake, while ACh, glutamate and dopamine did not have any significant effects on it. These facilitatory actions of neurotransmitters on the [14C]2-DG uptake are mostly consistent with the excitatory effects of the substrates on both CG and DRG cells in culture. The results suggest that the [14C]2-DG uptake in single cells is intimately correlated with action potential generation and change in the testing potential.

Animals↗

PubMed1981