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Biomedical subjects

E Costello

Publications and source records attributed to E Costello.

8 recordsLinked to original sources

Overexpression of Mos, Ras, Src, and Fos inhibits mouse mammary epithelial cell differentiation.

Mammary epithelial cells terminally differentiate in response to lactogenic hormones. We present evidence that oncoprotein overexpression is incompatible with this hormone-inducible differentiation and results in striking cellular morphological changes. In mammary epithelial cells in culture, lactogenic hormones (glucocorticoid and prolactin) activated a transfected beta-casein promoter and endogenous beta-casein gene expression. This response to lactogenic hormone treatment was paralleled by a decrease in cellular AP-1 DNA-binding activity. Expression of the mos, ras, or src (but not myc) oncogene blocked the activation of the beta-casein promoter induced by the lactogenic hormones and was associated with the maintenance of high levels of AP-1. Mos expression also increased c-fos and c-jun mRNA levels. Overexpression of Fos and Jun from transiently transfected constructs resulted in a functional inhibition of the glucocorticoid receptor in these mouse mammary epithelial cells. This finding clearly suggests that glucocorticoid receptor inhibition arising from oncogene expression will contribute to the block in hormonally induced mammary epithelial cell differentiation. Expression of Src resulted in the loss of the normal organization and morphological phenotype of mammary epithelial cells in the epithelial/fibroblastic line IM-2. Activation of a conditional c-fos/estrogen receptor gene encoding an estrogen-dependent Fos/estrogen receptor fusion protein also morphologically transformed mammary epithelial cells and inhibited initiation of mammary epithelial differentiation-associated expression of the beta-casein and WDNM 1 genes. In response to estrogen treatment, the cells displayed a high level of AP-1 DNA-binding activity. Our results demonstrate that high cellular AP-1 levels contribute to blocking the ability of mammary epithelial cells in culture to respond to lactogenic hormones. This and other studies indicate that the oncogene products Mos, Ras, and Src exert their effects, at least in part, by stimulating cellular Fos and probably cellular Jun activity.

Animals

Cardiac smokers: beliefs and values about smoking, and attitudes toward the risk of smoking to health.

Many cardiac patients continue to smoke, although this greatly increases their risk of health complications. This study explored cognitive and social factors which may discriminate between cardiac smokers who will be successful in quitting smoking and those who relapse to smoking following hospitalization for a myocardial infarction or coronary artery bypass graft surgery. Patients were interviewed prior to discharge from hospital and when they returned to clinic. Few patients were found to have resumed smoking when they returned to clinic. However, patients who had only recently quit smoking were found to be susceptible to relapse to smoking on the basis of their attitudes towards the risk of smoking to their health and the reduced social pressure from significant others not to smoke. Data suggested that nurses did not take full advantage of opportunities to influence cardiac patients about smoking.

Coronary Disease

The pathogenicity of Mycobacterium tuberculosis during chemotherapy.

We used the guinea pig as an experimental model to investigate the pathogenicity of Mycobacterium tuberculosis. Sputum samples were injected subcutaneously into guinea pigs and the animals were killed and an autopsy performed after eight weeks. The likelihood of the sputum samples producing tuberculosis in the guinea pig was related to culture positivity rather than to duration of chemotherapy. This study does not support the belief that a change in pathogenicity occurs during treatment of pulmonary tuberculosis.

Animals

Body fat deposition in adult obese women. II. Changes in fat distribution accompanying weight reduction.

This study examined changes in body fat distribution in 68 women who lost an average of 12.3 kg from an initial weight of 103.6 kg. Weight reduction was accompanied by a small but statistically significant reduction of 1.2% in the waist-to-hip ratio, suggestive of a reduction in upper-body obesity. Subjects with greater upper-body obesity tended to achieve greater reductions in the waist-to-hip ratio. Changes in five circumference measures were highly correlated with losses of fat and showed that subjects with lower-body obesity tended to lose large amounts of fat from both their upper and lower fat depots while subjects with upper-body obesity lost fat primarily from their upper depots. Women with lower-body obesity tended to lose more total body fat than did women with upper body obesity (r = -0.26, p less than 0.04).

Adipose Tissue

The partogram: a graphic guide to progress in labour.

The use of the partogram of Philpott, Studd, has proved to be a very valuable aid in the early detection of abnormal progress in labour. The graphic representation of all the relevant data of the labour on one sheet of paper has been received enthusiastically by the nursing and medical staff alike and has allowed the earlier detection of abnormal patterns of labour. It is considered that the partogram should become an essential part of the documentation of labour in all patients.

Attitude of Health Personnel