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Biomedical subjects

E B Thompson

Publications and source records attributed to E B Thompson.

At least 181 records · Page 10Linked to original sources
PubMed1978

The relation between estrogen receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer.

In a retrospective study we determined the relation between estrogen receptors and the response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer. Thirty-four of 45 patients with low or absent estrogen-receptor values (less than 10 fmol per milligram of cytoplasmic protein) had objective responses to chemotherapy, whereas only three of 25 patients with higher values (greater than 10 fmol per milligram of cytoplasmic protein) responded (P less than 0.0001). There were no statistically significant differences between the two groups in age, menopausal status, disease-free interval, Karnofsky index or prior therapy. Differences in sites of involvement or type of chemotherapy did not account for the increased response rate in receptor-negative patients. We conclude that estrogen-receptor values are an important predictor of response to cytotoxic chemotherapy in metastatic breast cancer.

Adult↗
PubMed1978

Cardiovascular effects of Azadirachta indica extract.

A crude extract of the leaves of Azadirachta indica was studied for its effects on the cardiovascular system of anesthetized guinea pigs and rabbits. These effects include profound hypotension and a minimal negative chronotropic effect, which increased at higher doses. In one rabbit, 200 mg of extract/kg decreased the heart rate from 280 to 150 beats/min. The extract also exhibited a weak antiarrhythmic activity in rabbits against ouabain-induced dysrhythmia.

Animals↗
PubMed1978

Isolation and characterization of L-cell variants with altered sensitivity to glucocorticoids.

Stable glucocorticoid-resistant receptor-containing (R+) variants of L cells have been obtained and characterized. Five clones of such cells were obtained after chemical mutagenesis of the A9HT cell line. These clones and an additional, spontaneously resistant subclone of the LB82 cell line all contain glucocorticoid receptors which appear normal with regard to quantity, affinity for steroids, and in vivo localization in subcellular compartments. Somatic cell hybrids were formed between two of these R+-resistant clones, a previously isolated R-resistant clone, and three different sensitive L cell parents. In no case was steroid resistance dominant. Thus, these resistant L cells appear to be candidates for complementation analysis. The R+-resistant clones may be hindered in as yet undefined steps of glucocorticoid action.

Cell Division↗
PubMed1978

Association between steroid hormone receptors and response rate to cytotoxic chemotherapy in metastatic breast cancer.

The influence of steroid hormone receptors on response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer was determined in a retrospective study. We have previously reported that 34 of 45 patients with tumors containing low or absent estrogen-receptor values had objective responses to chemotherapy while three of 25 patients with positive estrogen-receptor tumors responded. In the present study, 22 of 34 patients with low or absent progesterone-receptor tumors had an objective response to cytotoxic chemotherapy, while none of eight patients with a positive progesterone-receptor tumor responded (P less than 0.05). Patients having tumors with a negative estrogen receptor and a negative progesterone receptor had a response rate of 88% (21 of 24 patients). There were three patients whose tumors were estrogen-receptor negative but progesterone-receptor positive; none had a response to chemotherapy. Chemotherapy response was not associated with the presence or absence of either androgen or glucocorticoid receptor. We conclude that progesterone-receptor values in addition to estrogen-receptor status may prove to be important correlates of response to cytotoxic chemotherapy in metastatic breast cancer. Androgen- and glucocorticoid-receptor analyses are not helpful in predicting response to chemotherapy.

Adult↗
PubMed1977

Interaction of glucocorticoid hormones and cyclic nucleotides in induction of tyrosine aminotransferase in cultured hepatoma cells.

Reproducible induction of the enzyme tyrosine aminotransferase by dibutyryl cAMP (Bt2cAMP) in a line of HTC hepatoma cells in suspension culture requires that the cells be preinduced with dexamethasone, a synthetic glucocorticoid which itself induces tyrosine aminotransferase. Concentrations of dexamethasone that do not induce tyrosine aminotransferase fail to support Bt2cAMP induction, removal of the steroid from the medium leads to a loss of the Bt2cAMP effect, and an HTC cell line whose aminotransferase is not steroid-inducible does not respond to the cyclic nucleotide. We show that the further induction of tyrosine aminotransferase by Bt2cAMP in dexamethasone-treated cells is due to an increased rate of enzyme synthesis. The cyclic nucleotide has no effect on aminotransferase synthesis in cells grown in the absence of steroid. Several lines of evidence suggest that dexamethasone acts at a step beyond the activation of protein kinase by cAMP: (a) basal levels of cAMP are not altered by growth of HTC cells in dexamethasone; (b) accumulation of cAMP from the medium is not enhanced; (c) the glucocorticoid does not induce cAMP-dependent protein kinase in HTC cells; and (d) there is no augmentation of cAMP binding to the regulatory protein, nor is there any change in cAMP activation of protein kinase caused by growth in dexamethasone. These results help define a system that should be useful in studying the interaction of cyclic nucleotides and steroid hormones.

Bucladesine↗
PubMed1977

Effect of concanavalin A on tyrosine aminotransferase in rat hepatoma tissue culture cells. Rapid reversible inactivation of soluble enzyme.

Concanavalin A added to intact cells at 37 degrees caused rapid and reversible inactivation of a soluble enzyme, tyrosine aminotransferase, in two lines of rat hepatoma tissue culture cells grown in monolayer culture. This temperature-dependent process was independent of de novo protein and RNA synthesis and independent of increased uptake of Ca2+ and Mg2+ or glucose. The inactivation could be reversed by adding alpha-methyl-D-mannopyranoside a competing sugar for concanavalin A binding. Other lectins known to bind to different sugars did not bring about the inactivation of tyrosine aminotransferase. Addition of concanavalin A did not result in the inactivation of another soluble enzyme, lactic dehydrogenase. The maintenance of tyrosine aminotransferase in an inactive form after the binding of concanavalin A to the cells required the continued presence of concanavalin A. This effect of concanavalin A could not be mimicked either by dibutyryl cyclic adenosine or guanosine monophosphoric acid. Incubation of cell extracts with concanavalin A did not result in inactivation nor did mixing of extracts from concanavalin A-treated cells with extracts from untreated cells. On the basis of these results we conclude that the following are the essential requirements for concanavalin A to bring about the inactivation of tyrosine aminotransferase: (a) the binding of native concanavalin A to the cells; (b) integrity of certain structural elements of the cells.

Alanine Transaminase↗
PubMed1977

Delayed malignancy and altered growth properties of somatic cell hybrids between rat hepatoma and mouse L-cells.

Somatic cell hybrids of mouse L-cells with rat HTC cells were studied for their growth properties in vitro and tumorigenicity in vivo. Three hybrid clones were selected for detailed study. All were delayed in tumor formation in nude mice compared with the parent lines despite their varied growth properties in vitro. One clone was sensitive to density dependent inhibition of growth (DDIG) and had a relatively low saturation density. A second clone was not sensitive to DDIG and had a higher saturation density. The third clone had atypical morphology, was insensitive to DDIG, and had a relatively high saturation density. All of the clones studied produced colonies suspended in agarose gel which were much smaller than those of the parents incubated for the same period of time. Only the pattern of growth in agarose gel corresponded to the delayed tumor formation in vivo of the hybrids. Sensitivity to DDIG and saturation density were not consistent with tumor growth. The hybrid clone that was sensitive to DDIG was the only one of the three that had a nearly complete set of chromosomes derived from each of the parents. The chromosome numbers of all three clones were unchanged after growth in agarose or as tumors in the nude mice.

Animals↗
PubMed1977

The stability of tyrosine aminotransferase and other proteins in enucleated rat hepatoma tissue culture cells.

The role of the nucleus in bringing about the induction of tyrosine aminotransferase (TAT) by glucocorticosteroid hormone and its deinduction upon steroid removal has been studied in enucleated rat hepatoma tissue culture cells (FU5-5). Both processes require the presence of the nucleus. However, cytoplasts from preinduced cells show an initial rapid decline in enzyme activity immediately after enucleation followed by maintenance of a constant level of activity. This initial decline in enzyme activity can be partially prevented by trypan blue, an inhibitor of lysosomal activity. This suggests that the early fall in enzyme activity could be due to an increase in the level of lysosomal activity immediately after enucleation. The subsequent constant level of activity seems due to maintenance rather than synthesis and degradation since it is not affected by cycloheximide. The absence of degradation applies to other kinds of proteins in enucleated FU5-5 cells and enucleated mouse fibroblast L cells. These experiments suggest that some kind of labile RNA or protein dependent on the presence of the nucleus is required for the degradation of all classes of proteins in different kinds of cells.

Cell Fractionation↗
PubMed1977

Extinction of hemoglobin inducibility in Friend erythroleukemia cells by fusion with cytoplasm of enucleated mouse neuroblastoma or fibroblast cells.

Friend mouse erythroleukemia cells (T3c1-2 and its subline 5000) can be induced to synthesize hemoglobin after treatment with 1.5% (vol/vol) dimethylsulfoxide. When these cells are fused with nonerythroid cells (namely, mouse neuroblastoma or L cells) hemoglobin induction is extinguished. In order to determine if the nucleus of the nonerythroid cell is necessary for this extinction, fusions were performed between mouse erythroleukemia cells and enucleated neuroblastoma or L cells. Hemoglobin induction was reduced or eliminated in clones of these hybrids even after 6 months of continuous culture. These results suggest that the cytoplasm of nonerythroid cells contains factor(s) that extinguish hemoglobin inducibility in erythroleukemic cells and that this new phenotype can be inherited.

Animals↗
PubMed1977

Variants of HTC cells with low tyrosine aminotransferinase inducibility and apparently normal glucorticoid receptors.

Variants of HTC cells showing little or no induction of tyrosine aminotransferase in response to glucorticoids have been isolated by repeated cloning without deliberate selective pressures. In this paper, the derivation and some properties of these cells, compared with both high-inducing clones and wild-type cells, are described. The non-inducing cells all grew well, and were not induced even by unusually high concentrations of steroid. The enzyme activity had a normal half-life of decay and heat inactivation. It was inactivated by antiserum against authentic tyrosine aminotransferase, and no evidence for antigenically active, enzymatically inactive enzyme was found. No great variability was seen in the few other enzyme activities tested. Glucorticoid receptors were present in all the clones, With respect to concentration, cellular uptake, cell-free binding to nuclei and intracellular localiztion, no differences were found between the receptors of inducible and non-inducible clones. These are the first cells derived from an inducible type to be characterized as having normal receptor while becoming steroid resistant. They appear to be blocked in a late step of the response to the steroid, and therefore may prove useful in analyzing these later steps.

Aspartate Aminotransferases↗
PubMed1977

Characterization of a glucocorticoid-sensitive human lymphoid cell line.

A human lymphoblastoid cell line (CEM), the growth of which is inhibited by glucocorticoids, is described. Although growth of the original uncloned cell line is only slightly retarded by dexamethasone, sensitive clones were isolated in which growth is completely blocked by 2 to 3 days of exposure to 10(-6) M dexamethasone. After 4 to 5 days, these cells become pyknotic and lyse. The inhibitory affect of dexamethasone first become apparent in suspension culture at a concentration of about 5 X 10(-8) M. Receptor analysis showed the presence of specific glucocorticoid receptors with an apparent dissociation constant for dexamethasone of about 1.3 X 10(-8) M both in the sensitive and in one resistant clone analyzed. Ability to displace dexamethasone from the receptor is correlated with the known glucocorticoid activity of all steroids tested, as is their ability to inhibit cloning of sensitive cells in agarose. These results indicate that the specificity of inhibitory effects is related to receptor specificity of inhibitory effects is related to receptor specificity. Dexamethasone is a potent inhibitor when cells are cloned in agarose, having a marked effect even at a concentration of 7 X 10(-9) M. CEM cells thus provide human cell lines suitable for in vitro analysis of steroid effects on leukemic cells.

Animals↗
PubMed1976

A radioautographic analysis in the light and electron microscope of identified Aplysia neurons and their processes after intrasomatic injection of L-(3H)fucose.

We have studied radioautographically the distribution and fate of 3H-glycoproteins within the single identified neurons L10 and R12 of Aplysia californica after intrasomatic pressure injection of [3H]fucose. Silver grains were localized to intracytoplasmic membranes in both cell body and axon 3 h after injection of the cholinergic neuron L10. Grains also appear at this time over presumptive synapses. In the cell body the Golgi apparatus was labeled, as were vesicles, multivesicular bodies, pigment granules, smooth endoplasmic reticulum, mitochondria and peroxisomes. The Golgi apparatus is the most intensely labelled organelle (relative specific activity 9,5). Over 50% of the silver grains are associated with the Golgi apparatus and with vesicles. In the axons, vesicles were labeled most intensely, having a relative specific activity of 40.4 (% silver grains/% area), an intensity 10 times that of similar appearing somatic vesicles, and 4.5--10 times that of other organelles (multivesicular bodies, mitochondria, smooth endoplasmic reticulum) in the axon. At least 32% of the silver grains are associated with vesicles. It appears that the biosynthetic machinery of these neurons is heavily involved in the production of vesicle membrane destined for transport along axons and to terminals. The preponderant labeling of vesicles in the axon parallels the rapid and perferential transport of glycoprotein components described by Ambron et al. and may indicate that specific glycoprotein molecules can be identified as components of these vesicles. After injection of the cholinergic neuron R2 transport of radioactivity was restricted to the axonal tree of the injected neuron. After injection of L10, one other neuron was invariably labeled. By varying the conditions of injection, as many as 5 other neuron cell bodies could be labeled. These are located in the position of cells known to be electrically coupled to L10, and they probably became labeled by transneuronal movement of fucose across electrotonic junctions. Since restriction of label to the injected neuron is easily determined in each experiment, this technique makes possible the identification of chemical and perhaps electrical synapses of identified cells with optimal preservation of fine structure.

Animals↗