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Biomedical subjects

D R Appleton

Publications and source records attributed to D R Appleton.

At least 91 records · Page 5Linked to original sources
PubMed1981

Kinetics of the non-neoplastic mucosa of the large bowel of dimethylhydrazine-treated rats.

Administration of 1,2 dimethylhydrazine (DMH) to rats by weekly s.c. injections causes the development of multiple epithelial tumours of the large bowel. These appear to arise as localized dysplastic abnormalities in hitherto apparently morphologically normal crypts. This study was undertaken in order to examine cell proliferation in such apparently normal crypts of DMH-treated animals. A number of proliferative abnormalities are evident, including changes in the size of the crypts, changes in the disposition of proliferating cells within them and reduced cell-cycle times. The nature and the extent of the abnormalities vary from site to site along the length of the bowel, and reflect the vulnerability of the different segments of the bowel, not only to the carcinogenic effects of DMH, but also to short-term toxicity.

1,2-Dimethylhydrazine↗
PubMed1980

Breast-feeding and respiratory syncytial virus infection.

The pattern of breast-feeding in 127 infants admitted to hospital with respiratory syncytial virus infection was compared with that in 503 age-matched controls. Thirty per cent of children with infection had been breast-fed compared with 49% of controls. The approximate relative risk of being admitted to hospital with respiratory syncytial virus infection if not breast-fed was 2.2. Several other factors were also considered, including an assessment of maternal care and home environment; the mother's age, marital state, and smoking habits; the number of siblings; and gestation. Adverse factors were all associated with an increased risk of admission with infection, but breast-feeding still appeared to provide protection after controlling for these other factors in turn. These findings provide further support for encouraging mothers to breast-feed their infants and should prompt further studies into the immune status of mothers and into the nature of the protective factors in their breast milk.

Breast Feeding↗
PubMed1980

The effect of a single injection of cytosine arabinoside on cell population kinetics in the mouse jejunal crypt.

The early effects of a single injection of cytosine arabinoside (ara-C) on cell population kinetics in the jejunal crypt of the mouse were studied using autoradiography with tritiated thymidine, and metaphase arrest with vincristine. Ara-C had three main effects on crypt cells: a block of cells near the transition from G1 to S, death of nearly all cells in S, and a temporary block of the survivors, which remained viable and were able to proceed through the cell cycle. Throughout the crypt there was a decrease in cell cycle time and an increase in growth fraction. Although changes in proliferative rate were highest in the lowest part of the crypt it was not possible to show that crypt repopulation originated only from basal crypt cells, and the data are consistent with repopulation from the faster cycling cells in the proliferative compartment.

Animals↗
PubMed1980

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats.

We have measured mitotic indices and 3H-thymidine-labelling indices for the colonic epithelial tumours induced in rats by the administration of dimethyl-hydrazine (DMH). The fraction-of-labelled-mitoses (FLM) technique has been used to estimate the duration of the cell-cycle phases. In general, mitotic and labelling indices in the tumours are similar to those in the proliferation zone of the normal crypt epithelium; lesions considered to be least well differentiated on histological grounds appear to have the lowest mean labelling index. Benign tumours and the different types of malignant tumours have mean cell-cycle times about half those of the normal mucosa.

Animals↗
PubMed1980

The metaphase arrest technique. A critical review.

The accuracy and precision of the stathmokinetic experiment for the determination of cell birth rate are discussed from practical and theoretical viewpoints. Topics covered include the determination of the optimal dosage of the metaphase arresting agent, the times at which observations should be taken and which cells should be counted, the correct method of estimating cell birth rate and the dependence of any derived estimate of the turnover time on the age distribution of cycling cells. Failure to consider any of these points can lead to considerable inaccuracy. It is further shown that the stathmokinetic method is a rather imprecise one for measuring the turnover time and the duration of mitosis. Data are present comparing the results of using the technique with those obtained from autoradiographic studies.

Animals↗
PubMed1980

Propranolol and giving up smoking.

A placebo-controlled double-blind clinical trial was conducted to determine whether propranolol helps cigarette smokers to stop smoking; 73 subjects entered the trial but at the end of eight weeks only six had stopped smoking, three in the propranolol and three in the placebo group. There was no evidence of any helpful effect of propranolol in subjects trying to stop smoking.

Adult↗
PubMed1979

Estimating the proportion of proliferating cells in a population.

In a population of cells that proportion which is actively engaged in the proliferative cycle is often estimated from the ratio of the observed labelling index to an expected labelling index, calculated, on the basis of all cells being in cycle, from the cell cycle phase durations and the age distribution. Ignoring the variability in cell cycle times may lead to large overestimates or underestimates in the expected labelling index. A method is given of obtaining a more accurate estimate of this variable, and hence of the proliferative proportion.

Animals↗
PubMed1979

Variation in the cell cycle time in the crypts of Lieberkühn of the mouse.

The durations of the phases of the cell cycle were measured at different levels in the jejunal crypts of male Balb/c mice. A mean cell cycle time of 12.3 h was found for the whole crypt. In cell positions 1 and 2, the cell cycle time was 16.7 h, and this time steadily decreased to a value of between 10 and 11 h for cell positions above 11. It is concluded that basally situated crypt cells in the mouse are cycling relatively slowly, and that they form the functional stem cell pool for the crypt. These cells may also compose the potential stem cell pool which repopulates the crypt after death of proliferative cells.

Animals↗
PubMed1979

Cytokinetic studies of crypts in convoluted human small-intestinal mucosa.

Forty-seven peroral biopsy specimens of duodenojejunal mucosa showing convolutions were obtained from patients with a variety of clinical disorders. These mucosal samples were divided into three groups according to the extent of the convolutions and the severity of the accompanying histopathological changes; the cytokinetic status of the crypts in the three groups was then analysed and compared. Those in which the mucosae were predominantly or totally convoluted (group 3) showed the most notable cytokinetic changes: crypts were hyperplastic and crypt cell production rate was markedly increased compared with the other two groups and with morphologically normal control mucosae. In the case of one patient with mucosal changes of group 3 severity, additional studies were carried out using vincristine to produce metaphase arrest. The cell cycle time of 27 hours was greatly shortened compared with a control value of 45 hours.We find that the presence of convolutions in small-intestinal mucosal biopsy specimens is accompanied by an increase in the rate of cell production from the crypts, which is presumably related directly or indirectly to the rate of loss of mature enterocytes from the surface of the mucosa. Furthermore, an increase in the proportion of convolutions may reflect an increase in the rates of cell production and cell loss. In the group 3 convoluted mucosae the cytokinetic profile of the crypts resembled that of some of the flat avillous coeliac mucosae previously studied although the rates of cell production did not reach the levels attained by the most productive of the flat coeliac mucosae.

Adult↗
PubMed1979

A comparison of cell proliferation at different sites within the large bowel of the mouse.

This study was undertaken in order to compare cell proliferation at different sites along the length of the large bowel of the mouse. Simple morphometry has been used along with 3HTdR labelling studies and metaphase arrest with vincristine. Differences have been described in the shape and size of crypts, the distribution of proliferating cells, the duration of the cell cycle, as well as in the rate of cell production by the crypts. The findings explain some of the apparent inconsistencies in the literature.

Animals↗
PubMed1978

Pathological features of the colonic tumours induced in rats by the administration of 1,2-dimethylhydrazine.

The parenteral administration of 1,2-dimethylhydrazine to rats caused the development of colonic neoplasms in about 90% of animals by 24--30 weeks of treatment. Usually there were multiple tumours with a mean of 2.7 per rat. The lesions have been classified histologically into adenomata (26% of all tumours) and carcinomata, the latter showing varying degrees of differentiation. No completely anaplastic tumours were seen, and there were none originating in connective tissue. The distributions of the different tumour types along the length of the colon varied. The more benign lesions were situated predominantly in the distal half of the colon, while the poorly differentiated adenocarcinomata were concentrated in the proximal third of the colon. There was good evidence to suggest that adenomata often progressed to frank malignancy in the distal colon. In the proximal part, however, it appeared that tumours frequently developed de novo as poorly differentiated carcinomata. Perhaps regional variations in the kinetic organisation of the normal colonic mucosa somehow influence the nature of the neoplastic change induced by DMH, thus accounting for the differences in tumor distribution. After 24 weeks of DMH treatment there was only a small increase in the mean number of tumours per rat.

Adenocarcinoma↗
PubMed1978

The effect of single and of multiple doses of prednisolone tertiary butyl acetate on cell population kinetics in the small bowel mucosa of the rat.

The effect of single and of multiple doses of prednisolone upon cell population kinetics in the rat jejunal crypt was investigated, using autoradiography and stathmokinetic techniques with vincristine. Single injections of prednisolone (2.5 mg/kg body weight) induced a depression both flash thymidine labelling and mitotic indices; this change was shown to be due to a decreased cell production rate. Recovery of these proliferative indices occurred over seven days after injection; measurement of crypt size parameters showed a transient decrease in crypt population. Multiple daily injections of prednisolone (1 mg/kg body weight) produced a more sustained decrease in labelling and mitotic indices, which lasted as long as injections were continued (7 days); stathmokinetic techniques showed decreases in cell production rates, and the crypt population was also depressed throughout this period. It is concluded that prednisolone depresses cell proliferative rates in rat jejunal mucosa.

Animals↗
PubMed1978

Choosing the programme for an international congress.

The method of selecting abstracts for an international congress at which only 15% of submitted papers could be accepted entailed a panel of 12 assessors using their specialised knowledge, but presentation of the abstract was also important is selection. There was only a limited agreement between assessors in arranging abstracts in order of merit, so that a single assessor would be unacceptable. Use of the full panel to grade all abstracts was very expensive, but it could be replaced, without unacceptable injustice, by dividing the work randomly among groups of three selectors.

Congresses as Topic↗
PubMed1978

Cell population kinetics in the epithelium of the colon of the male rat.

The present study was undertaken in order to try to define some of the kinetic parameters in the colonic mucosa of normal Wistar rats. Preliminary observations showed considerable morphological differences in the mucosa from site to site along the length of the colon. In particular the height of the crypts (measured in cells) was variable. In addition labelling index studies demonstrated dramatic variations in the distribution of labelling along the length of the crypts from site to site in the bowel. A single site in the descending colon was selected for more detailed study using a stathmokinetic agent, vincristine, and the continous labelling technique with tritiated thymidine. The results of these investigations suggest that there exists at the base of the crypt a subpopulation of cells cycling more slowly than the cells in the rest of the proliferative compartment. Growth fraction appears to fall with rising cell positions within the crypt.

Animals↗
PubMed1978

Kinetics of changes in the crypts of the jejunal mucosa of dimethylhydrazine-treated rats.

When symmetrical 1,2 dimethylhydrazine was administered to rats by weekly s.c. injection, 37% of the animals had developed small intestinal carcinomas after 21-27 weeks. These lesions were largely localized to duodenum and upper jejunum. At the same time there was a diffuse crypt hyperplasia in the jejunum which affected all the treated animals, not just those with neoplasms. This marked hyperplasia was preceded by a modest sustained crypt elongation which was seen soon after DMH injections began. In these hyperplastic jejunal crypts the absolute size of the proliferative compartment was increased, but the growth fraction calculated from labelling studies appeared to fall, probably by reduction in relative size of the proliferating population within the proliferative compartment. No convincing alteration in actual cell-cycle time was observed in the abnormal crypts. There was a slight (25%) increase in cell-production rate in the abnormal crypts.

Animals↗