Search PubMed⌕ Search

Biomedical subjects

A J Watson

Publications and source records attributed to A J Watson.

At least 271 records · Page 15Linked to original sources
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↗
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

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↗
PubMed1977

Liver function and structure in survivors of acetaminophen poisoning. A follow-up study of serum bile acids and liver histology.

A series of 30 patients, hospitalized with acetaminophen overdose, were studied during initial admission and again three months later. The quantity of acetaminophen ingested varied from 5 to 50 g and 19 patients developed raised transaminase levels in the serum during the initial period. Liver damage, on the basis of needle biopsy findings, was categorized as severe in 5, moderate in 7, and mild or minimal in 18 patients. At three months' follow-up all but one of the biochemical indicants of liver damage had reverted to normal in all patients. The exception was the serum total bile acids. Residual changes found on liver biopsy at three months were minimal and nonspecific, apart from one previously severely affected patient in whom there was evidence of scarring. It is concluded that in the usual spectrum of acetaminophen poisoning requiring hospitalization there is no evidence of lasting liver damage.

Acetaminophen↗
PubMed1977

The effect of a single injection of hydroxyurea on cell population kinetics in the small bowel mucosa of the rat.

The effect of a single injection of hydroxyurea (HU) on cell population kinetics in the jejunal crypt of the rat was studied using autoradiography with tritiated thymidine and metaphase arrest with vincristine. HU appeared to act selectively on cells in the S phase producing inhibition of DNA synthesis and cell death. The deficit in proliferating cells was made good by a decrease in cell cycle time and an increase in growth fraction. Particular attention was paid to the basal, slowly cycling (and possibly clonogenic) crypt cells; early in the recovery sequence an increase in cell production rate was found in the base of the crypt. It is proposed that basal crypt cells, having survived cycle-specific insult because of long cell cycle times, proceed to repopulated the depleted proliferative compartment.

Animals↗
PubMed1976

Diagnosis of Giardia lamblia infection as a cause of diarrhoea.

Retrospective analysis of the records of 31 patients diagnosed as having Giardia lamblia infection in our hospital over a five-year period suggests that the condition is not considered often or early enough. Adult patients particularly "suffer" more, having to endure more investigations (mean of 16) than do symptomatic children (mean of 6) before a diagnosis is made. The length of time to reach the diagnosis from first referral further supports this view, being almost seven weeks in adults and three weeks in children--both groups having had symptoms for an average of seven months before referral.

Adult↗
PubMed1976

Evaluation of paracetamol-induced damage in liver biopsies. Acute changes and follow-up findings.

In 100 patients who had taken an acute overdose of paracetamol the liver was biopsied percutaneously on the 4th day or as soon thereafter as recovery of the clotting mechanism allowed. A system for grading the histological changes in the liver is described. The hallmark of severe (grade III) damage is centrizonal necrosis, for which there is probably a dosage threshold. Consequent changes include phagocytosis of cell debris, reticulin collapse, and an inflammatory infiltration; acidophil degeneration of hepatocytes is sometimes prominent; regenerative growth is already evident after 4 days. Mild (grade I) damage is characterized by excess of lipofuscin pigment in centrizonal hepatocytes, sparse focal necrosis of liver cells, and some phagocytosis of lipofuscin. The findings in moderate (grade II) damage are similar but more pronounced. Five patients died in acute hepatic failure, and 22/100 showed severe (grade III) changes but survived. Forty-nine patients representing all three grades of liver damage were rebiopsied after 3 months. Central necrotic zones were found to have been completely reconstituted leaving only minor abnormalities except for one patient who showed mild centrilobular fibrosis and scarring of a nonprogressive nature.

Acetaminophen↗
PubMed1976

Studies on the mechanism of diurnal variation of proliferative indices in the small bowel mucosa of the rat.

In the rat small bowel mucosa significant variation was found in both the labelling and the mitotic indices with time of day. The zenith and the nadir of labelling and mitotic activity coincided at 15.00 and 02.00 hours respectively. Small changes were found in the "cut-off" position, but this variation in proliferative compartment size was insufficient to account for the comparatively wider fluctuations in proliferative indices. Measurements of the rate of entry into mitosis, using metaphase arrest with vincristine at three widely separated times during the day, showed no significant change. Changes in the growth fraction or in the birth rate as measured cannot account for diurnal variation in the proliferative activity of the small bowel mucosa. We propose a hypothesis which involves diurnal fluctuations in the transit times through G1 and through G2.

Animals↗