Biomedical subjects
Publications and source records attributed to M Meredith-Brown.
Intralobar pulmonary sequestration is a relatively rare congenital anomaly. The commonest clinical presentation is with chronic cough, expectoration and recurrent attacks of pneumonia. An unusual presentation with a psoas abscess is reported.
A very large variation (44-fold) was observed in the ability of short-term organ cultures of peripheral lung tissue from lung-cancer patients to metabolize the environmental carcinogen benzo(alpha)pyrene to organic solvent-soluble metabolites. The amounts of benzo(alpha)pyrene (2 microM) metabolized ranged from little (1%) to almost total (96.2%) metabolism within 24 h of culture. Previous work by Kellerman et al. (1973) has suggested a relationship between susceptibility to lung cancer and the indicibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. The metabolic fate of carcinogenic polycyclic aromatic hydrocarbons in the respiratory tract in vivo is undoubtedly more closely mimicked by short-term organ culture of human lung than by cultured lymphocytes. Thus the very wide interindividual variation observed in pulmonary metabolism of benzo(alpha)pyrene in this study and the large variations in covalent binding to human bronchial DNA observed by Harris et al. (1976) strongly suggest that there may be little basis for screening humans for variations in lymphocyte aryl hydrocarbon hydroxylase activity as a means of assessing their susceptibility to lung cancer.
Short-term organ cultures of peripheral lung from lung cancer patients metabolise benzo[alpha]pyrene to ethylacetate-soluble metabolites, which covalently bind to tissue macromolecules. The nature and quantities of metabolites formed and the extent of covalent binding are dependent upon the time of incubation, the substrate concentration and interindividual variability in the metabolic activity of the lung. Individuals whose lungs rapidly metabolise the carcinogen exhibit more extensive further metabolism of primary metabolites and higher levels of covalent binding. Certain striking differences in the relative retention in the tissue or release into the extra-cellular medium of different metabolites have been found as illustrated by the observation that the ratio of 7,8-dihydro-7,8-dihydroxybenzo[alpha]-pyrene to 9,10-dihydro-9,10-dihydroxybenzo[alpha]pyrene was always significantly higher in the tissue than in the extracellular medium.