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Biomedical subjects

A G Heppleston

Publications and source records attributed to A G Heppleston.

At least 37 records · Page 2Linked to original sources
PubMed1977

Cell kinetics of urethane-induced murine pulmonary adenomas: III. Implications of the disparity between the rates of entry into DNA synthesis and into mitosis.

Metaphase arrest by vincristine in urethane-induced murine pulmonary adenomas became linear after an interval of 60 min. The rate of entry into metaphase was 0-191%/h, which was considerably less than the 1%/h for the rate of entry into DNA synthesis obtained previously by double labelling. The duration of prophase plus metaphase was calculated to be 1-7 h. A growth fraction of 9% and a cell-loss factor of 52% were derived. The disparity between rates of entry into DNA synthesis and into metaphase was investigated by microdensitometry on Feulgen-stained squash preparations of tumours of varying ages. Tne DNA profiles showed an increasing frequency of hyperdiploid nuclei with age. Circumstantial evidence for polyploidy was provided by the presence of many binucleate cells in the tumours. By analogy with the liver, these cells may well represent a stage in the development of polyploidy, and the possible relevance of these findings to the neoplastic process is considered.

Adenoma↗
PubMed1977

Effect of inhaled plutonium dioxide on development of urethan-induced pulmonary adenomas.

Mice were exposed to plutonium dioxide (PuO2) aerosols 2 weeks before or after urethan injection. Both exposures reduced the number and size of adenomas. The incidence of arrested metaphases showed no consistently significant differences between plutonium-exposed and mock-exposed animals. The results are discussed in relation to recent electron microscopic evidence of degenerative changes in the type II epithelial cells of the mouse lung following PuO2 inhalation. It is concluded that damage at the cellular level may account for the observed reduction in growth of pulmonary adenomas in mice whose lungs contained plutonium particles.

Adenoma↗
PubMed1976

Cell kinetics of urethane-induced murine pulmonary adenomata: II, the growth fraction and cell loss factor.

Continuous labelling of urethane induced pulmonary adenomata in adult male A2G mice at intervals up to 20 weeks showed that the growth fraction fell progressively from 18% at 7 weeks to 7% at 20 weeks. This fall appears to be wholly responsible for the decrease in production of adenoma cells with age. A fraction labelled mitoses curve was constructed for pulmonary adenomata at 14 weeks post urethane. Only the first peak was apparent, giving median t2 and ts values of 2 and 9 h respectively. The cell cycle time was calculated at 45 h and the growth fraction at 6-2%, whilst the cell loss factor was estimated at 31%. Other cell loss values were calculated from data on the rate of entry into DNA synthesis obtained previously by double labelling. These values remained constant with time at 83-95%, suggesting that cell loss is in some way linked to cell production. However, the development of polyploidy in adenoma cells could not be eliminated. No areas of necrosis were seen in the adenomata at any time although karyorrhexis occurred in isolated cells. The labelling characteristics of alveolar wall cells in the same lung sections as the adenomata did not vary with time and the continuous labelling curve gave a growth fraction of 1-8%, a DNA synthetic time of 10 h and a cell cycle time of 30 h.

Adenoma↗
PubMed1975

Cell kinetics of urethane induced murine pulmonary adenomata: I. The growth rate.

A single injection of urethane into adult male A2G mice produced an increase in the proliferative rate of alveolar wall cells, reaching a peak at 2 weeks post urethan (PU) and declining to control levels by 2 months PU. During this urethane induced proliferative response the single and double labelling indices and the native metaphase index were all elevated although there was no corresponding alteration in the arrested metaphase index. This proliferative response may not be restricted to hyperplasia of potentially neoplastic cells, such as type II epithelium, but may also include type I epithelial cells and alveolar macrophage precursors. However, it was impossible to identify individual cell populations by methods used. The growth rate of adenomata decrease with time and cell kinetic techniques showed that the rates of entry of adenoma cells into DNA synthesis and into metaphase were decreasing concurrently with the growth rate. Thus the rate of cell production falls as adenomata age but how much cell loss contributes to the decrease in growth rate is not yet known. Decreasing cell production could be due to an increased cell cycle time and/or a decreased growth fraction. The duration of DNA synthesis in adenomata increased markedly as the mice survived, suggesting that the cell cycle time might be increased, but further experiments are required to determine whether the growth fraction changes. Attention is drawn to a complication that Colcemid introduces into kinetic studies on alveolar wall cells.

Adenoma↗
PubMed1975

The surface properties of the lung in rats with alveolar lipo-proteinosis.

The physical behaviour of the intact lungs and of lung extracts from rats affected by alveolar lipo-proteinsosis as a consequence of silica inhalation, was studied by means of pressure volume relations and surface tension area loops. Air inflation of diseased lungs occurred at a lower pressure and collapse was less on deflation than in control specimens, although there appeared to be little change in elastic forces. When saline was used dusted rat lungs showed at higher lung volumes a peculiar hysteresis effect which is attributable to consolidation of alveoli by the lipid material. Extracts from affected lungs showed differences from controls in respect of maximum and minimum surface tensions and stability index but all the values fell within the accepted limits of normal. However, with extracts from pathological lungs the area of the hysteresis loop increased, the shape of the surface tension area curve was abnormal and the percentage compression required to reduce the surface tension to 120 muN/cm fell. Extracts from diseased lungs depressed the maximum surface tension of normal lung extracts and increased the hysteresis area but had little effect on the minimum tension, the stability index or the % compression to achieve 120 muN/cm. The response was thus mainly that of an extract from a dusted rat. The surface activity of phospholipids may be affected by neutral lipid, cholesterol and the products of cell breakdown, all of which occur in the alveolar material. The occurrence within the same lung of compunds which reduce surface tension and others which modify the same lung of compounds which reduce surface tension and others which modify this property suggests that their relative concentrations may determine the overall effectiveness of the lung lining.

Animals↗
PubMed1975

A cell kinetic study of the alveolar wall following dust deposition.

The stathmokinetic technique was used to study quantitatively the proliferative response of cells comprising the alveolar wall of inbred mice which had inhaled coal or quartz. The exposures occupied 4 weeks and the observations continued over an extended period thereafter. Control observations suggested that mitotic inhibition was induced solely by residence in the exposure chamber, since cessation of exposure was quickly followed by a temporary rise of proliferative activity. This feature was not apparent when dust was inhaled, though with comparable exposure to both coal and quartz there was an elevation in mitotoic incidence of alveolar wall cells in dust-free areas of lung at a later interval. In dust-laden areas the rise was less in evidence, a situation that persisted throughout the post-exposure survival. The difference in mitotic incidence between dust-free and dust-containing areas was more evident after coal than after quartz inhalation, whilst in higher concentration a quartz aerosol induced a continued depression of mitotic activity. The proliferative response seen in the alveolar walls of control and dusted mice is most likely to be contributed by the interstitial precursors of alveolar macrophages, cells which are recognized to be marrow derived. The changes observed in mitotic incidence are interpreted in terms of demand for alveolar macrophages according to the nature of the dust and the inintensity of the exposure.

Animals↗
PubMed1974

Correlation between the tissue response and asbestos fiber content.

Asbestos fiber concentration increases in proportion to the degree of pulmonary fibrosis as far as the moderate grade. No such correlation occurs with severe asbestosis, nor with the morphological form which the fibrosis assumes, and here secondary factors may be concerned. Electron microscopy suggests that optically visible fibers constitute a reasonably constant proportion of the total irrespective of the pathological reaction. Light microscopy may thus afford a guide to the total asbestos concentration. Finally, the development of mesothelioma, whether of the pleura or the peritoneum, appears to be unrelated to the concentration of coated or uncoated asbestos fibers residing in the lung.

Asbestos↗
PubMed1973

The optical and electron microscopic determination of pulmonary asbestos fibre concentration and its relation to the human pathological reaction.

The quantitative extraction of asbestos fibres from asbestotic lung by alkali digestion has been refined by maceration of the tissue without prior drying, the minimum use of centrifugation, and the adoption of phase contrast microscopy. Preliminary experiments suggested that, using this technique, asbestos fibre counts were accurate to within at least +/- 20% and in most instances to within +/- 10%. The method was used to assess asbestos concentrations in lung tissue showing various degrees and forms of fibrosis. The results, as determined by light microscopy, indicated that uncoated fibres generally outnumbered coated fibres. In mild and moderate asbestosis there was a progressive increase in concentration of asbestos fibres, both coated and uncoated, with increasing severity of fibrosis, whereas in severe asbestosis no correlation existed between the fibre concentration and the form or the extent of the pathological reaction. It is suggested that the severe fibrosis results from the supervention of non-specific inflammatory processes. Asbestos fibre diameter distributions, gauged by electron microscopy, were fairly constant irrespective of the degree of fibrosis. Optically visible fibres constituted between 12 and 30% of the total, so that an optical count may be said to give an approximate indication of the total asbestos concentration and, so far as asbestosis is concerned, may well serve for comparative purposes. The relation between asbestos and neoplasia will, however, require identification and quantitation of particular types of the mineral by microanalytical techniques.

Asbestos↗