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Biomedical subjects

A M Houghton

Publications and source records attributed to A M Houghton.

6 recordsLinked to original sources
PubMed2006

K-ras activation generates an inflammatory response in lung tumors.

Activating mutations in K-ras are one of the most common genetic alterations in human lung cancer. To dissect the role of K-ras activation in bronchial epithelial cells during lung tumorigenesis, we created a model of lung adenocarcinoma by generating a conditional mutant mouse with both Clara cell secretory protein (CC10)-Cre recombinase and the Lox-Stop-Lox K-ras(G12D) alleles. The activation of K-ras mutant allele in CC10 positive cells resulted in a progressive phenotype characterized by cellular atypia, adenoma and ultimately adenocarcinoma. Surprisingly, K-ras activation in the bronchiolar epithelium is associated with a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils. These mice displayed early mortality in the setting of this pulmonary inflammatory response with a median survival of 8 weeks. Bronchoalveolar lavage fluid from these mutant mice contained the MIP-2, KC, MCP-1 and LIX chemokines that increased significantly with age. Cell lines derived from these tumors directly produced MIP-2, LIX and KC. This model demonstrates that K-ras activation in the lung induces the elaboration of inflammatory chemokines and provides an excellent means to further study the complex interactions between inflammatory cells, chemokines and tumor progression.

Animals↗
PubMed1996

Vitamin D receptor and growth inhibition by 1,25-dihydroxyvitamin D3 in human malignant melanoma cell lines.

The expression of vitamin D receptors (VDR) and growth inhibition induced by 1,25-dihydroxyvitamin D3 have been noted in certain human malignant melanoma cell lines. In this study, widely disparate levels of VDR mRNA expression were demonstrated in a panel of eight human malignant melanoma cell lines. Quantitation of receptor level by ligand binding assay showed a similar pattern. Proliferation and growth curve analysis was performed in two cell lines: RPMI 7951 (high VDR) and SK-MEL-28 (low VDR). Significant growth inhibition was noted in RPMI 7951 cells at 10(-9) M 1,25-dihydroxyvitamin D3. SK-MEL-28 cells, which express much lower levels of VDR, did not show any growth inhibition except at extremely high concentrations of 1,25-dihydroxyvitamin D3, namely 10(-5) M. These findings suggest a receptor-mediated mechanism of growth inhibition for 1,25-dihydroxyvitamin D3 and a role for this hormone in the growth of malignant melanoma cells.

Calcitriol↗
PubMed1989

Pre-employment screening: use or ornament?

Pre-employment screening (PES) in an occupational health department (OHD) in Inner London was evaluated by establishing its resource implications and devising methods to estimate its efficiency and effectiveness. The attitudes of those involved in PES were also examined. While coverage of student nurses applicants was in the region of 100 per cent, only 43 per cent of all other new employees were screened. Student nurse applicants were more likely to be referred to an occupational health nurse or doctor than other employees (45 per cent nurses, 18 per cent others), but only one person had been rejected on health grounds, as a result, during the previous 15 months. The majority of reasons for sickness absence or early retirement could not have been predicted by PES. Opinions as to the purpose of PES varied from employees who in general thought that PES was designed to protect their interests, to managers, who thought it was to protect theirs.

Attitude↗