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T Cooke

Publications and source records attributed to T Cooke.

At least 55 records · Page 3Linked to original sources
PubMed1989

Prognostic value of nucleolar organizer regions and ploidy values in advanced colorectal cancer.

The prognostic value of nucleolar organizer regions and ploidy status in patients with Dukes' C colorectal cancer was determined. In addition, nucleolar organizer regions and ploidy status were compared with the established prognostic indices age, sex, tumour location and degree of histological differentiation. Fifty-one patients (27 men, 24 women) aged 35-81 years (median 64.8 years) were studied. Five years after presentation, 16 patients were alive and well. Survivors had significantly lower nucleolar organizer region counts (median value and range) in primary tumours 12 (8-15) and lymph node metastases 11 (8-15) than non-survivors 17 (14-25) and 18 (13-25) respectively (P less than 0.05). Fewer survivors had aneuploid tumours than non-survivors: four survivors compared with 17 non-survivors. In a regression analysis model, nucleolar organizer regions were the most important individual variable for predicting survival (chi2 = 15, P less than 0.01) while ploidy values (chi2 = 6, P less than 0.2) were equivalent to histological differentiation.

Adult↗
PubMed1988

Proliferation patterns and aneuploidy in adenomatous polyps of the colon.

The frequency of aneuploidy and the proliferative activity of 57 colorectal adenomatous polyps was investigated by static cytophotometry and compared with 43 adenocarcinomas and 60 samples of normal mucosa. Twenty per cent of the adenomas contained aneuploid cells compared with 63 per cent of the adenocarcinomas. Except in the case of villous adenomas, there was a general increase in the proliferative activity of the diploid adenomas with increasing degrees of dysplasia. All of the adenomas showed an increase in proliferation compared with normal mucosa. There was a positive correlation between the size of the diploid adenomas and proliferative activity (P less than 0.001).

Adenocarcinoma↗
PubMed1988

Experimental colonic carcinogenesis: changes in faecal bile acids after promotion of intestinal tumours by small bowel resection in the rat.

Small bowel resection promotes the development of colonic tumours in azoxymethane treated rats. As high faecal bile acid concentrations are associated with colonic cancer and may be altered by resection, we have studied changes in faecal bile acid concentrations during promotion of colonic carcinogenesis by increasing small bowel resection. Twenty rats in each group underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg by 12 weekly subcutaneous injections, and faecal bile acid concentrations were measured at six and 16 weeks. Colonic tumour number rose from 0.6 per rat in the transection group to 1.6 per rat in the 50% resection group (p less than 0.01) but were not significantly different to transection values at 0.8 per rat in the 80% resection group. Total daily faecal bile acid excretion and bile acid concentrations fell with increasing resection from 14.2 (1.6) mg/rat/day and 5.8 (0.7) mg/g dry faeces respectively in the transection group to 6.5 (0.5) mg/rat/day and 2.9 (0.2) mg/g respectively in the 80% resection group (p less than 0.001). The greatest reduction was seen in the concentration of deoxycholic acid which has been particularly associated with the aetiology of colonic cancer. The promotion of colonic tumours following small bowel resection in carcinogen treated rats is unlikely to be mediated by changes in faecal bile acid concentration or composition.

Animals↗
PubMed1987

Alteration in colonic epithelial cell DNA associated with intestinal neoplasia: selection of high risk patients.

The proliferative activity of the colonic crypts of patients who are at high risk of developing colonic tumours has been assessed. Cells from the upper parts of the colonic crypts were collected at colonoscopy, and were stained for DNA by the Feulgen technique. Using a microdensitometer the DNA content of the cells was measured and a proliferative index calculated. Patients with single neoplasms had a proliferative index similar to controls although individual patients with hyperplastic mucosa could be identified. Patients with multiple neoplasms had an elevated proliferative index. These results may form the basis of a screening programme for colonic tumours.

Adenoma↗
PubMed1987

Predictive power of progesterone receptor status in early breast carcinoma.

Progesterone receptor status (PgR) and oestrogen receptor status (ER) were examined in 332 women with stage I-II breast carcinoma treated at a single centre either by simple mastectomy with (n = 283) or without (n = 6) axillary clearance, or by segmental mastectomy with (n = 18) or without (n = 25) axillary clearance and radiotherapy; median follow-up time was 40 (range 10-60) months. Neither the concentration nor the presence of PgR related to either disease-free interval or survival. However both the presence and the concentration of ER were found to be associated with a longer disease-free interval amongst patients with stage II tumours (P less than 0.01). From this study it appears that progesterone receptor status does not predict outcome in early breast carcinoma.

Adult↗
PubMed1987

Importance of cellular DNA content in pre-malignant breast disease and pre-invasive carcinoma of the female breast.

The risk of malignant change in pre-invasive breast disease such as proliferative atypia (PA) or the risk of invasive carcinoma arising from ductal carcinoma in situ (DCIS) remains uncertain in individual women because of the absence of any prognostic criteria. In order to clarify this, the cellular DNA content (ploidy) of 51 screen-detected lesions has been investigated. Cellular DNA measurements were made by static cytometry following Feulgen staining of disaggregated tissue sections and the resulting histograms classified as either diploid or aneuploid. Thirteen cases of PA and twelve of DCIS were compared with twenty-six biopsies showing DCIS with adjacent invasive carcinoma (DCIS + Ca). In the latter group, ploidy of the invasive carcinoma was compared with the associated DCIS in 16 cases. Aneuploid cells were found in approximately 30 per cent of PA and DCIS lesions but in 23 of 26 cases of DCIS + Ca. Of 16 assessable cases of co-existing DCIS and micro-invasive carcinoma both were aneuploid in 11, both diploid in 1, and in 4 cases the DCIS was aneuploid whereas the invasive carcinoma was diploid. These results suggest that aneuploidy may be of value in predicting the most biologically aggressive of these pre-invasive lesions.

Aged↗
PubMed1987

Kinetic changes in experimental colonic urinary diversion.

An experimental model of colonic urinary diversion was performed on male Wistar rats to see if faeces, urine or a faeces and urine mixture produces tumours. Cell kinetic techniques, including the crypt cell production rate, and cellular DNA measurement were used to examine the effect of urine and of faeces on the colonic mucosa. Urinary diversion into the colon significantly increased colonic crypt activity. Tumours were found at the anastomosis when urine and faeces were mixed at 4 months, and at 6 months with urine alone.

Animals↗
PubMed1987

Effect of a long-acting analogue of somatostatin, SMS 201-995, on the development of intestinal tumours in azoxymethane-treated rats.

The effect of daily parenteral administration of a long-acting analogue of somatostatin (SMS 201-995) on the development of intestinal tumours and the rate of crypt cell proliferation in azoxymethane-treated rats has been studied. SMS 201-995 had no significant effect on the number of colonic tumours induced. In the duodenum, SMS 201-995 administration was associated with a change in the number of tumours from 1.4/rat in saline-treated animals to 2.4/rat in animals treated for the last third of the study and 2.8/rat in animals treated with SMS for the entire duration of the study (P less than 0.02). SMS had no significant effect on the rate of cell proliferation in the duodenum, ileum or colon. The inhibition of release of gastrointestinal trophic hormones by this analogue of somatostatin thus does not appear to reduce the number of tumours in the intestine of azoxymethane-treated rats.

Animals↗
PubMed1987

Metal-responsive elements act as positive modulators of human metallothionein-IIA enhancer activity.

The human metallothionein IIA (hMT-IIA) gene contains two enhancer elements whose activity is induced by heavy-metal ions such as Cd2+. To determine the nature of the relationship between the metal-responsive elements and the element(s) responsible for the basal activity of the enhancers, the basal-level enhancer element(s), the hMT-IIA enhancers were subjected to mutational analysis. We show that deletion of the metal-responsive elements had no effect on the basal activity of the enhancer but prevented further induction by Cd2+. On the other hand, replacement of the basal-level enhancer element with linker DNA led to inactivation of the enhancer both before and after treatment with Cd2+. Therefore, the metal-responsive elements seems to act as a positive modulator of enhancer function in the presence of heavy-metal ions. In addition to the two enhancers, the hMT-IIA promoter contained one other element, the GC box, required for its basal expression. Unlike deletion of the basal-level enhancer element, replacement of the GC box with linker DNA had no effect on the ability of the promoter to be induced by Cd2+.

Base Sequence↗
PubMed1987

Effects of birth weight, gestational age, and maternal obstetric history on birth prevalence of cerebral palsy.

A register of children with cerebral palsy born to mothers resident in the Mersey region from 1966 to 1977 was compiled from health service records. Frequency distributions and prevalences of birth weight and gestational age differed for those with hemiplegia, diplegia, and quadriplegia. In particular, the children with diplegia showed a bimodal frequency distribution. Children of normal birth weight with diplegia had a higher prevalence of severe mental retardation than those of low birth weight. These differences may be due to survival bias and may not be of aetiological importance. Furthermore, the mothers of diplegic infants had a significantly higher proportion of spontaneous abortions, stillbirths, and low birthweight infants in their obstetric history. This suggests that prenatal factors predominate in the aetiology of diplegia.

Abortion, Spontaneous↗
PubMed1987

Trends in birth prevalence of cerebral palsy.

A register of children with cerebral palsy born in the period 1966-77 to mothers resident in the Mersey region was compiled from several different data sources. There were 685 cases, with a male:female ratio of 1.4:1. The birth prevalence of cerebral palsy ranged from 1.18 to 1.97 per 1000 live births each year, with a mean of 1.51 per 1000 live births. There was no discernible trend in overall prevalence, but there was a highly significant upward trend in the prevalence of cerebral palsy among low birthweight infants, which was evident for all the major types of cerebral palsy. It is postulated that this is due to improved survival rather than a real change in incidence. Alternatively, because the register was compiled from health service records, a diagnostic access bias from improved follow up of low birthweight infants may have led to an apparent increase in prevalence.

Birth Weight↗
PubMed1987

Enteroglucagon and experimental intestinal carcinogenesis in the rat.

To assess the association between the putative intestinal trophic hormone enteroglucagon and the development of intestinal tumours, four groups of 20 rats underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg weekly for 12 weeks. At 26 weeks there was a promotion of colonic neoplasia from a median of 0.5 (range 0-3) per rat in the transection group to 1.0 (0-3) in the 50% resected group (p less than 0.01) but no significant promotion in the 80% resection group. In the small bowel, increasing resection resulted in a progressive promotion of tumours from a median of 1.0 (range 0-3) per rat in the transection group to 2.0 (0-5) in the 50% resection group (p less than 0.001) and 3.0 (0-11) in the 80% group (p less than 0.01). Plasma enteroglucagon was measured at 2, 16, and 26 weeks and was raised seven-fold in the 80% resected group (p less than 0.001). There was a significant correlation between enteroglucagon concentrations and number of duodenal tumours but not colonic tumours. Crypt cell production rate in the duodenum increased from 11.5 +/- 1.9 to 29.2 +/- 1.4 cells/crypt/h in the 80% resected group (p less than 0.001) and showed a close correlation with both enteroglucagon levels and tumour promotion in the small bowel. There were no changes in crypt cell production rate in the colon with resection. This study shows a close association between enteroglucagon concentrations, promotion of tumours and crypt cell production rate in the duodenum but not in the colon.

Animals↗
PubMed1986

Prostatic carcinoma cell DNA content measured by flow cytometry and its relation to clinical outcome.

DNA content of prostate tumour cells has been measured by flow cytometry of cell suspensions prepared from fixed tissue by an enzyme disaggregation technique. Two classes of tumours have been identified: diploid tumours, with a DNA content similar to benign cells and aneuploid tumours with grossly abnormal DNA values. The prognosis for the aneuploid tumours was significantly worse than diploid tumours (P less than 0.001). When ploidy is combined with histological grading, here using the Gleason numerical system, it is possible to predict which patients, whatever their age at diagnosis, will die from their tumour and which patients will probably die before their tumour kills them. With these facts it is possible to select patients for active or expectant treatment.

Aged↗
PubMed1986

Human chorionic gonadotrophin expression in colorectal adenocarcinoma.

The presence of human chorionic gonadotrophin (HCG) in colorectal adenocarcinoma was studied histologically in 45 tumors using immunoperoxidase technique. Ten neoplasms (22.2 percent) contained HCG-positive tumor cells. These cells were present mostly at the periphery of the tumors. Many formed parts of glands, while some were arranged in syncytial clumps or columns, or singularly. Thus, these tumor cells resembled trophoblastic tissue not only in being HCG-positive but also in their peripheral distribution and occasionally in morphologic appearance. HCG-positive tumors were seen more commonly in the rectosigmoid region (90 percent) and were more aggressive than HCG-negative tumors. In this study, lymph node or liver metastases were present in 70 percent of HCG-positive tumors compared with 29 percent of negative tumors--a difference which is statistically significant.

Adenocarcinoma↗
PubMed1986

Changes in crypt cell DNA content during experimental colonic carcinogenesis.

Changes in colonic crypt cell DNA content have been monitored during experimental carcinogenesis. Colonic tumours were induced in Wistar rats using 12 consecutive subcutaneous injections of azoxymethane at a dose of 10 mg kg-1. Ten rats were killed at each of 10, 15, 20 and 25 weeks after the initial injection. On sacrifice the descending colon, plus any polyps or tumours with their adjacent mucosa, was removed, fixed and processed to paraffin wax. Sections were stained for DNA by the Feulgen reaction. Using an integrating microdensitometer the DNA content of the proliferative and functional cells was measured and expressed as a percentage of the stem cell DNA content. As carcinogenesis progressed there was an increase in the mean amount of DNA in the proliferative and functional cells in the distal colon although the tissue was histologically normal. The transitional mucosa adjacent to tumours showed the same increases as the 25 week distal colon. In the adenomas, there was a further increase in the DNA content of the functional cells. These results are probably a reflection of the increase in the number of dividing cells in the higher positions of the colonic crypts during carcinogenesis.

Animals↗