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Biomedical subjects

L A Smallman

Publications and source records attributed to L A Smallman.

46 records · Page 3Linked to original sources

Ultrastructural abnormalities of cilia in the human respiratory tract.

Primary ciliary dyskinesia is thought to be caused by a primary defect of ciliary ultrastructure and function. However, atypical cilia have also been described in humans with and without acquired respiratory tract disease. With few exceptions, these abnormalities have not been quantified. Ciliary ultrastructure was therefore studied in 21 specimens of bronchial mucosa from patients with a variety of respiratory problems and in five specimens of nasal mucosa from asymptomatic nonsmokers. The incidence of microtubular abnormalities and compound cilia was generally less than 10 per cent, and there was no correlation between the incidence of these abnormalities and the presence of lung carcinoma or smoking habits. Transposition of ciliary microtubules and radial spoke defects, specific microtubular abnormalities thought to be pathognomonic for primary ciliary dyskinesia, were observed in a number of specimens, and visualization of dynein arms, particularly inner dynein arms, was extremely difficult. It is concluded that ultrastructural abnormalities of cilia should be carefully quantified in patients with primary ciliary dyskinesia and control subjects before it can be assumed they have pathologic significance.

Adolescent↗

Pituitary adenomas producing growth hormone in acromegalic patients.

Growth hormone was shown in histological sections of 25 pituitary adenomas from acromegalic patients by means of the unlabelled peroxidase-antiperoxidase (PAP) technique. On the basis of the numbers of cytoplasmic granules, the cells of the adenomas were of two types: densely granulated and sparsely granulated. The densely granulated cells had abundant cytoplasm containing numerous granules, whereas the sparsely granulated cells had little cytoplasm with scanty granules. Depending on the predominant cell type the adenomas were also classified as densely granulated or sparsely granulated: 21 of the 25 adenomas (84%) were densely granulated and four (16%) sparsely granulated. There was some variation, however, in the relative numbers of the two types of cell from one part of an adenoma to another, a feature consistent with one type of cell in different phases of activity. There was no significant difference in mean serum growth hormone concentrations between the two groups, and granularity of the adenomas in histological sections did not therefore correlate with secretory activity. Nine adenomas showed extrasellar extension. The mean serum growth hormone concentration in these cases was lower than the mean of the adenomas confined to the sella turcica. Thus the size of the tumour did not correlate with the serum growth hormone concentration. Three of the four adenomas in the sparsely granulated group showed extrasellar extension, compared with 6 of 21 classified as densely granulated. This suggests that sparsely granulated adenomas have a more aggressive pattern of behaviour, but histological evidence for this was lacking.

Acromegaly↗

Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: a serine proteinase effect.

We have examined the effect of adding elastase positive sputum from six patients with purulent bronchiectasis on the ciliary beat frequency of nasal epithelium from normal subjects. Control studies of cilia suspended in tissue culture medium showed little change in ciliary beat frequency over six hours. Cilia incubated in elastase positive secretions, however, showed a considerable decrease in ciliary beat frequency over the period, falling from a mean of 13 X 40 beats/second to 6 X 78 beats/second (p less than 0.001). Inhibition of the elastase activity with pure human alpha 1 antitrypsin abolished this effect (mean at start 13 X 75 beats/second, mean at six hours 11 X 64 beats/second). The patients were then treated with amoxycillin for two weeks and sputum was collected at the end of the course. These secretions showed no detectable elastase activity and also had little effect on ciliary beat frequency. The results suggest that serine proteinase activity associated with elastase can decrease mucociliary function in vitro and that antibiotic treatment even in the apparently stable state may have a beneficial effect.

Bronchiectasis↗

The mechanism of healing of tympanic membrane perforations. A two-dimensional histological study in guinea pigs.

The healing of small perforations, made in 60 tympanic membranes (30 guinea pigs) with either a thermal myringotome or a needle was observed over a 10-day period using an operating microscope. Thirty-six of these were sectioned either parallel with the handle of the malleus, or at right angles to it, and the closing perforations studied by light microscopy. The epidermis closed the perforations first, in the direction of surface migration. This process began within 48 hours and was complete within 9 days. A fibrous reaction occurred, starting at 3 days, and this was seen on the side of the perforation adjacent to the malleus or bony tympanic annulus. There was no response visible in the middle ear mucosa. The conclusion of this study is that the epidermis is the first layer to close a perforation because of its migratory function, and the direction of closure is the direction of migration. Healing of the fibrous layer occurs secondarily, and the site of the response in this layer is related to the vascular distribution in the tympanic membrane.

Animals↗

Computerized measurement of ciliary beat frequency.

We describe how ciliary beat frequency (CBF) of human respiratory epithelium in vitro can be robustly and quickly measured. The proven photometric technique has been improved by using a microcomputer to calculate and display the results. The software, which runs on an IBM-compatible PC, was developed using Borland Turbo Pascal and employs a fast Fourier transform routine to derive the CBF. Results are displayed almost as soon as a cell is identified under the microscope, and are in accordance with previous work. The technique can now be used diagnostically and for a variety of drug trials on respiratory epithelium.

Adult↗