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D R Appleton

Publications and source records attributed to D R Appleton.

At least 55 records · Page 3Linked to original sources
PubMed1987

A trophic effect of epidermal growth factor (EGF) on rat colonic mucosa in organ culture.

The development of an organ-culture system for rat colonic mucosa has enabled a direct assessment of the effect of epidermal growth factor (EGF) on cell division. An augmented mitotic index (AIm) has been employed to identify changes in cell proliferation. Explants of colonic mucosa from four animals were maintained in a medium containing serum for five days. On the fifth day of culture, half of the explants received fresh medium containing EGF (40 ng/ml) and the remainder (controls) fresh medium only. At 6, 12, 24 and 48 hr thereafter groups of both experimental and control explants received the metaphase-arresting drug vincristine (4 micrograms/ml) for 3 hr prior to fixation. The proportions of vincristine-arrested metaphases within the explants were determined. Analysis of the data indicates that when serum is present exogenous EGF exerts a trophic effect which increases with time (P less than 0.001). In a second experiment colonic explants from four animals were maintained for five days in a serum-free medium and were then divided into groups, each of which received one of a range of concentrations of EGF. The AIm was determined for each group after 36 hr. It was found that increasing concentrations of EGF produce a small but significant increase in cell proliferation (P less than 0.01). This effect, however, was less pronounced than that seen when serum was present. These results suggest that EGF has a trophic action on the colon and interacts with additional factors found in serum.

Animals↗
PubMed1987

Sugars consumption of Northumbrian children aged 11-14 years.

In order to investigate the relationships between diet and tooth decay the authors recently completed the first longitudinal study of diet and dental caries increment in children. 405 children initially aged 11.5 years each recorded their intake of foods and drinks for a total of 15 days over a period of 2 years. This is a review of some of the findings.

Child↗
PubMed1986

A cytokinetic study of small-intestinal and colonic mucosa after resection of 70% of the small intestine.

Pulse-labelling with tritiated thymidine and a fraction of labelled mitoses experiments have been performed in order to investigate the proliferative changes induced at various sites in the hyperplastic small-intestinal mucosa of rats previously subjected to resection of 70% of the small intestine. Proliferative activity in the colon was also studied. In the distal ileum there is a significant reduction in cell cycle time (Tc) of cells at all levels within the crypt and the growth fraction falls. In the jejunum and proximal ileum the crypts contain an increased number of proliferating cells, but as the size of the maturation zone is also increased, there is no significant alteration in the relative number of proliferating cells per crypt. Nor does the distribution of proliferating cells in these crypts seem to alter. There is no general reduction in Tc at these sites, but there does appear to be a significant reduction in Tc on the part of the cells in the stem-cell zone at the crypt base. In neither proximal nor distal colon was there any significant proliferative change apparent after small-intestinal resection.

Animals↗
PubMed1986

Interpreting the correlation coefficient when one of the variables is discrete.

The effect on the correlation coefficient of discretizing data was investigated in two ways. First, the theoretical effect of dichotomizing data was calculated, and it was shown that the resulting correlation coefficient is considerably less than that between the underlying bivariate normally distributed variables. Second, computer simulations were performed of a model in which a continuous variable (measured with some error) gives rise to a counting variable through a mechanism in which the count is zero below a certain threshold value for the continuous variable and then increases linearly as the continuous variable increases. It was shown that the correlation coefficient between the observed values of the continuous and counting variables decreased as (a) the measurement error increased, (b) the slope of the relationship decreased, and (c) the number of counts decreased. It is concluded that caution is required when interpreting correlation coefficients when one or both of the variables consist of a few (say only four or five) discrete scores.

Computer Simulation↗
PubMed1986

Dietary sources of energy, protein, fat and fibre in 375 English adolescents.

The aim of this report of the dietary sources of energy, protein, fat and fibre in 375 English adolescents aged 11-14 years is to contribute to the development of health education. Each child recorded their dietary intake five times over a 2-year period using a 3-day diary with interview. Food tables (Paul & Southgate, 1978) were used to calculate nutrient intake. The results are the mean of all 15 days intake. Potatoes (chips and crisps) were the largest single source of energy but 'meat' was the main source of protein and fat, other important sources of fat were the spreading fats, milk, chips and crisps. Chips were the main source of fibre but white bread, crisps and baked beans also contributed similar proportions of fibre. Some differences between the sexes and social classes were observed; the lower social class children appeared to have more undesirable eating habits.

Adolescent↗
PubMed1986

A comparison of crypt-cell proliferation in rat colonic mucosa in vivo and in vitro.

The successful development of a long-term organ culture system has made it possible to perform experiments on rat colonic mucosa in vitro. However, the effect of trauma or the withdrawal of trophic influences in culture may result in the disturbance of proliferation within the tissue. In this paper we describe an investigation designed to characterise the culture system by a comparison of the proliferative parameters in vitro with those in vivo. Stathmokinetic experiments were performed in vivo and in vitro to estimate cell birth rate. Mitotic indices were also calculated. The in vivo birth rate (7.8 +/- 0.8 cells/1000 cells/hour) and the in vitro birth rate for the whole explant (7.7 +/- 0.5 cells/1000 cells/hour) were found to be similar. A study of crypts in the centre and at the edge of the cultured explants, however, indicated that proliferation at the two sites differed markedly, the birth rate at the edge (7.5 +/- 0.9 cells/1000 cells/hour) being approximately twice that at the centre (3.2 +/- 0.9 cells/1000 cells/hour). Provided that this topological difference in proliferation within the explant is recognised the in vitro model, in particular the basal level found at the centre, may still be regarded as a valid system for studying tissue responses to carcinogens and trophic factors.

Animals↗
PubMed1986

The dietary intake of added and natural sugars in 405 English adolescents.

A number of reports have urged a reduction in sugars intake. Implementing this advice depends upon knowledge of sugars intake by target groups. This paper reports the added and natural sugars intake by one target group--young adolescents. The diet of 405 children was recorded using a 3-day diary with interview repeated five times between September 1979 and July 1981. Food tables (Paul & Southgate, 1978) were used and the values for the sugars content of the food items altered to provide both added sugars and natural sugars concentration. The mean daily intake of added and natural sugars respectively, for the 193 boys was 85 g (s.d. 22), 39 g (s.d. 12), and for the 212 girls was 78 g (s.d. 24), 35 g (s.d. 12). Added sugars contributed, on average, 69 per cent of total sugars and 15 per cent of energy intake. Confectionery, table sugar and soft drinks together contained 71 per cent of the added sugars intake, while milk, fruit and their products provided the majority of the natural sugars. It is considered that major reductions of sugars intake would be possible in these children by restricting the intake of a small number of groups of foods of low nutrient density. Food labelling of sugars content would enable consumers to make sensible choices of foods.

Adolescent↗
PubMed1985

Transplantation of a segment of ileum to the external abdominal wall: an animal model of intestinal mucosal hyperplasia.

When a segment of small intestine is transplanted to the external abdominal wall in rats adaptive changes occur in the exposed mucosa. These probably represent an extreme example of a physiological response to one type of trophic influence--the effect of mechanical trauma. The nature of the changes has been studied at 7 weeks after externalization using simple morphometry and a number of cytokinetic techniques (thymidine labelling, vincristine-induced metaphase arrest and the fraction-of-labelled-mitoses method), and comparisons drawn with the normal ileum. The exteriorized mucosa showed marked villus atrophy and hyperplasia of the crypts to three times normal size as a result of increases both in crypt length and crypt circumference. Neither metaplastic nor dysplastic epithelial abnormalities were observed. Crypt-cell production rate doubled in the hyperplastic crypts due to an increase in the size of the proliferation zone within the crypt, and the distribution of proliferating cells within the crypt changed. But cell cycle times were prolonged and more maturing cells were retained in the hyperplastic crypts. The potential usefulness of this model, particularly in carcinogenicity studies is considered.

Abdominal Muscles↗
PubMed1985

Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'.

A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P less than 0.001). The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%. Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.

Animals↗
PubMed1985

Aspects of statistics in studies of cell proliferation. IV. Simulation.

Computer simulation of an experiment can help to reveal how effective that experiment might be in estimating cell kinetic parameters, or in elucidating the nature of a proliferative response to a perturbation of the steady state, such as a carcinogenic or therapeutic treatment. Writing a simulation also clarifies one's thoughts about possible mechanisms of the proliferative response.

Cell Division↗
PubMed1985

Vindesine as a stathmokinetic agent in human rectal tumours in organ culture.

Organ culture, using human colorectal mucosa and tumours, is a good system in which to test a new stathmokinetic agent such as vindesine. Using this system we have found that vindesine has similar metaphase-arresting properties to vincristine, including at least a 6-fold dose response difference in its ability to arrest mitosis in mucosa and tumour, mucosa being the more sensitive. Vindesine is a satisfactory stathmokinetic agent, but in view of its greater cost offers no particular advantages over vincristine.

Carcinoma↗
PubMed1985

Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer.

Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.

Breast Neoplasms↗
PubMed1985

Some influences on the measurement of food intake during a dietary survey of adolescents.

Data are presented from a recent longitudinal study of dietary habits of English children aged 11-13 y, in relation to various factors which may have influenced the estimations of intake. A knowledge of such relationships may aid the design and interpretation of this and other dietary surveys. The factors studied included survey fatigue, learning effect, season of the year, day of the week and the subjects' knowledge of the study's purpose. Generally the relationships found were of minor importance, but the variable influence of some of these factors is apparent from a study of the relevant literature. This is one reason why dietary survey methodology is resistant to simplification. It is concluded that the dietary survey method used was adequate for the purpose of the study.

Adolescent↗
PubMed1985

Cell proliferation in human colorectal mucosa in organ culture: the early adaptive changes.

In organ culture tissues undergo adaptive changes which complicate the assessment of proliferative indices. In the present study, a technique devised to preserve collagen metabolism and mesenchymal stroma in tissues of mixed origin was employed to investigate the kinetic behaviour of human colorectal mucosa over the first 24 hours in culture. During this period the structural preservation of tissue is good. The mitotic index in mucosa is profoundly depressed throughout the explants during the first 2-6 hours in culture. During this same period, however, heavy uptake of tritiated thymidine, indicating DNA synthesis, is observed within 150 micron of the cut edge of the samples but not centrally. This phenomenon has been described previously and assumed to be the result of inadequate diffusion of oxygen into the tissue. The 'edge labelling' phenomenon is followed by a wave of mitosis in the tissue edge at 8-18 hours in culture. This delay between tritiated thymidine uptake and the appearance of mitoses in the tissue edge may simply represent the duration of the S + G2 phase of the cell cycle, but is more likely to be due to cells in G1 moving into the S phase followed by cells hitherto blocked in G2 being stimulated into the M phase. After 18 hours the mitotic and labelling indices become more uniform throughout the samples suggesting that 'edge labelling' is partly due to local stimulation of cell proliferation by trauma rather than central inhibition due to diffusion problems. These results suggest that in this organ culture system, assessment of proliferative indices should be carried out after these adaptive changes have settled.

Adaptation, Physiological↗
PubMed1984

Relationship between dietary habits and caries increment assessed over two years in 405 English adolescent school children.

The study was conducted in seven schools on children initially aged 11.5 years. They recorded their diet on five occasions, each of three days, and received an annual dental examination, including radiography. Caries increments were low, mostly (58 per cent) in fissure surfaces. Correlations between caries increment and dietary factors were low due to the low caries increments observed and the large error associated with dietary data where analyses attempt to discriminate between individuals. The highest correlation was between caries increment and weight of daily intake of sugars (+0.143, p less than 0.01). Multivariate analyses revealed that this relationship could not be explained by differences in sex, social class, tooth-brushing habits or level of plaque as measured by gingival inflammation. Weight of sugar intake appeared to be more strongly correlated to caries than frequency of intake; concentration of sugars in foods was positively related, and sugars in snacks were more strongly related to caries than total dietary sugars. The 31 children who consumed most sugar (greater than 163 g/day) developed 5.0 DMFS during the 2 years, 0.9 DMFS per year more than the 31 children (3.2 DMFS during 2 years) who had the lowest sugar intake (less than 78 g/day).

Adolescent↗