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Biomedical subjects

D J Sutherland

Publications and source records attributed to D J Sutherland.

At least 55 records · Page 3Linked to original sources

Rapid assays for evaluating the drug sensitivity of tumor cells.

Assays that assess the ability of cells to incorporate labeled precursors into acid-precipitable material in the presence of adriamycin, daunorubicin, puromycin, vinblastine, melphalan, or methotrexate were investigated as an approach to the detection of resistant cells in human tumor samples. Each assay was evaluated with suitable drug-resistant Chinese hamster ovary cell lines and normal human fibroblasts to determine whether the assays reflected the drug sensitivity of these lines. Moreover, the ability to detect the presence of drug-resistance cells in a mixed population was evaluated. Validated assays were then used to measure the drug sensitivity of cell samples from pleural and peritoneal effusions of patients, mainly with carcinoma of the breast or ovary. Though the responsiveness of the majority of the samples in these assays was similar to that of a human fetal lung fibroblast line, 37 of 142 samples displayed responses consistent with the presence of a significant proportion of drug-resistant cells. Of these 37 nonresponsive samples, 12 displayed nonresponsiveness to three drugs.

Antineoplastic Agents↗

Androgen-dependent fibrinolytic activity in a murine mammary carcinoma (Shionogi SC-115 cells) in vitro.

Physiological concentrations of dihydrotestosterone (DHT) can specifically induce the release of fibrinolysin from androgen-dependent mammary carcinoma (Shionogi SC-115) cells in vitro. No fibrinolytic activity was observed in cells cultured either in the absence of DHT or presence of pharmacological concentrations of estrogen. Furthermore, an autonomous tumor derived from the Shionogi SC-115 cells produced fibrinolytic activity independent of added DHT or estrogen. These observations suggest a close correlation between fibrinolytic activity of a tumor and its ability to grow in vivo.

Aminocaproates↗

Uptake of the mosquito larvicide Temefos by the salt marsh snail, New Jersey--1973-1974.

Uptake of the mosquito larvicide temefos (Abate) by the salt march snail (Melampus bidentatus Say) in New Jersey was measured by gas-chromatographic analysis. Measurable quantities of temefos were found in the snails within 1 day after the first treatment with a 2% granular formulation but 3 weeks elapsed before uptake occurred following treatment with a temefos emulsion. Residues in the snails exposed to the granular formulation were generally more than 10 times higher than those in snails exposed to the emulsion although application rates of the granular formulation were only about three times higher than those of the emulsion. Residues in snails exposed to the emulsion fell below detectable levels less than 3 weeks after cessation of treatments although measurable amounts were found in snails exposed to the granular formulation for more than 5 weeks after the last treatment. The persistence of temefos in M. bidentatus suggests the potential for its movement through food webs exposed to the granular formulation.

Animals↗

Androgen receptors: relationship to growth response and to intracellular androgen transport in nine variant lines of the Shionogi mouse mammary carcinoma.

Aspects of the biological significance of androgen receptors have been studied in nine variant lines of the Shionogi carcinoma, two of which are androgen dependent and seven of which are autonomous. The dependent lines, and two of the seven autonomous lines, contain androgen receptors; this finding demonstrates that the presence of receptors is not an accurate marker of hormonal dependence in vivo. Since the ability to transport androgens into the nucleus, as judged from the relative maximal rates of transport, is virtually restricted to dependent and autonomous lines which possess cytoplasmic receptors, it is clear that such receptors may play a role in regulating the intranuclear concentration of androgens. The absence of cytoplasmic receptors and the comparative lack of perceptible transfer of androgens across the nuclear membrane are features peculiar to the autonomous condition.

Animals↗

Persistence of cadmium-induced metabolic changes in liver and kidney.

Daily intraperitoneal injection of cadmium chloride (1 milligram per kilogram) for 45 days enhanced gluconeogenesis as evidenced by significant increases in the activities of liver and kidney cortex pyruvate carboxylase, phosphopyruvate carboxylase, hexosediphosphatase, and glucose-6-phosphatase, the quartet of key, rate-limiting enzymes involved in the biotransformation of noncarbohydrate precursors into glucose. Whereas cadmium treatment decreased the level of hepatic glycogen, the concentration of blood glucose and urea was significantly elevated by this heavy metal. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with cadmium for 45 days, failed to restore the observed biochemical alterations in hepatic and renal carbohydrate metabolism to control values. Evidence indicates that cadmium augments the glucose-synthesizing capacity of liver and kidney cortex and that various metabolic changes persist even after a 4-week period of withdrawal from exposure to the heavy metal.

Animals↗