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Biomedical subjects

I Taylor

Publications and source records attributed to I Taylor.

At least 271 records · Page 15Linked to original sources
PubMed1985

Cell kinetics and in vitro clonogenicity of primary colorectal cancer: clinicopathological relationships and the implications for chemotherapy.

Cells with the capacity for clonogenic growth in vitro can be isolated from primary human colorectal carcinomas. In this study colonies were grown, composed of cells which expressed epithelial membrane antigen and CEA, confirming their neoplastic character. Adequate growth for assessing the cytotoxicity of drugs for use in clinical chemotherapy regimes was obtained from 64% of the specimens. Colony forming efficiency of the tumour cells was not related to clinical stage or pathological grade of the parent tumour. The S-Phase fraction of the tumour was established in vitro using pulse thymidine labelling. The thymidine labelling index for Dukes' stage A and B tumours was significantly higher (median 15.7%, range 10.1-23.6%) than for Dukes' stages C and D (median 11.7%, range 0.1-13.6%). Colony forming efficiency in vitro was independent of the thymidine labelling index of the tumour. These findings are discussed with reference to the known heterogeneity of colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1985

Effect of warfarin on cell kinetics, epithelial morphology and tumour incidence in induced colorectal cancer in the rat.

The effect of low dose warfarin and high dose warfarin on epithelial cell kinetics (as determined by stathmokinetic techniques), and preneoplastic morphological changes was studied during azoxymethane induced carcinogenesis in the rat. Warfarin, at either low or high dose, had no effect on crypt cell production rate (CCPR) at any time interval whereas tumour incidence in both low dose warfarin and high dose warfarin groups was significantly reduced. Morphological changes were observed using scanning electron microscopy, which by conventional histology were shown to be adenoma precursors. In the control group the number of microadenomas increased with time after starting azoxymethane. In warfarin treated animals, the number of microadenomas also increased with time, but the actual incidence was reduced when compared with controls. These results suggest that the effects of warfarin on tumour development is unrelated to its anticoagulant effect, because increased dose did not result in greater tumour reduction. Furthermore, there was no overall change in CCPR when warfarin was administered. Warfarin may exert a specific effect, by preventing neoplastic change in cells which have undergone morphologically undetectable changes associated with early carcinogenesis.

Adenoma↗
PubMed1985

Effect of deoxycholic acid on the tumour incidence, distribution, and receptor status of colorectal cancer in the rat model.

It has previously been observed that 25% of human colorectal cancers contain specific receptors to deoxycholic acid (DCA). In the present study, the effect of intrarectal instillation of DCA on tumour number, distribution, size, and DCA receptor status was measured in rats receiving the colorectal carcinogen, azoxymethane. Rats treated with azoxymethane and intrarectal DCA developed significantly more colorectal cancers than rats receiving azoxymethane and intrarectal saline (median 11.5, range 8-17 vs. median 6.0, range 3-9 tumours/rat, respectively, p less than 0.01). This reflected a significantly higher number of tumours in the distal colon of the DCA-treated group (median 8.0, range 5-10 tumours/rat) compared to the saline-treated group (p less than 0.01). In those rats receiving DCA and azoxymethane, 5 of 12 tumours tested were found to be DCA receptor-positive, compared with only 1 of 11 in the saline and azoxymethane group. These results confirm the belief that DCA acts as a tumour promoter, and suggest a possible role for DCA receptors.

Animals↗
PubMed1984

Correlations between clonogenicity and prognostic factors in human breast cancer.

The pursuit of more effective systemic treatments in breast cancer has been limited by a failure to maintain or grow tumour cells in vitro. This study reports our experience in obtaining clonogenic growth in 54 primary breast cancers obtained at mastectomy. Of 47 assays free of infection, clonogenic growth was achieved in 22 (41 per cent). Only 5 of 23 oestrogen receptor positive tumours grew compared to 14 of 21 oestrogen receptor negative tumours chi 2 = 9.03; P less than 0.01). None of the 5 cytosolic receptor positive tumours contained a nuclear receptor for oestrogen. Growth was not related to tumour stage, menopausal status, age or histological grade. Receptor negative tumours had higher thymidine labelling indices, but these were no different to the tumours grown in the assay.

Breast Neoplasms↗
PubMed1984

Changes in intestinal blood flow during the development of chronic large bowel obstruction.

The effect of chronic progressive distal large bowel obstruction on intestinal blood flow was studied in 12 mini-pigs. Blood flow was measured by the techniques of xenon133 clearance and intracardiac injections of radiolabelled microspheres. Intestinal blood flow was increased in the left colon and ileum but decreased in the caecum. Blood was shunted from the mucosa to the muscle layers. The results suggest that primary anastomosis of the obstructed left colon is not contraindicated by haemodynamic considerations.

Animals↗
PubMed1984

Prognostic factors and in vitro cytotoxic sensitivity in colorectal cancer.

The poor response rates to chemotherapy for colorectal cancer justify attempts to rationalize selection of patients for treatment, and the development of systems to evaluate new cytotoxic agents. Refinement of prognostic indices may identify colorectal cancer patients at a higher risk of recurrence who merit more aggressive treatment. We report our experience with the stem cell assay and pulse thymidine labelling in 43 primary colorectal cancers. Thirty-six tumours were evaluable, and clonogenic growth was obtained in 30 (83 per cent). In 24 tumours (67 per cent) growth was adequate for meaningful interpretation of a cytotoxic drug assay. Frequency of growth and colony forming efficiency did not correlate with histopathological grade, Dukes' stage or tumour cell kinetic indices. Thymidine labelling indices correlated with Dukes' stage (A and B versus C and D, P less than 0.01, Mann-Whitney U test). Cytotoxic assays with 5-fluorouracil and 5'-deoxy-5-fluorouridine were undertaken in 18 cases (14 primary carcinomas, 4 malignant ascites), of which 14 were evaluable and 3/14 (21.5 per cent) were chemosensitive in vitro. Both drugs were equally effective in vitro at clinically attainable plasma concentrations. This is in accordance with the response rates observed clinically with 5-FU chemotherapy in colorectal cancer.

Antineoplastic Agents↗
PubMed1984

Transferrin receptor expression during exponential and plateau phase growth of human tumour cells in culture.

Transferrin receptor expression by the human tumour cell lines CCRF-CEM leukaemia and PMC-22B melanoma was studied, measuring the specific binding of fluorescein isothiocyanate (FITC)-labelled transferrin using a fluorescence-activated cell sorter. By measuring the fluorescence of cells stained at subsaturating concentrations of conjugate it was possible to calculate the average numbers of receptors per cell and the binding affinity by Scatchard analysis. These values (1.9 X 10(5) binding sites/cell, KA 1.2 X 10(9) M-1 for CCRF-CEM during exponential growth and 6.9 X 10(4) binding sites/cell, KA 1.4 X 10(-9) M-1 for PMC-22B) are in close agreement with previously published data obtained using radiolabelled transferrin. The present method, however, allowed the transferrin receptor expression of individual cells within a population to be measured and thus it has been possible to test the hypothesis that transferrin receptor is a marker for cycling cells. Frequency-distribution histograms of transferrin receptor showed a wide range of values for both cell lines during exponential growth. When the extreme ranges were sorted and the cells examined for cellular DNA content it was found that those with the highest transferrin receptor expression were enriched with cells in S, G2, and M phases of the cell cycle, whereas those with low transferrin receptor expression were mainly in G1. However, two-parameter-correlated dot plots of transferrin receptor expression versus DNA content showed there was considerable overlap between the ranges of receptor expression for the different cell cycle compartments. Using a stathmokinetic method we have measured the proportion of quiescent cells in fed plateau phase cultures. Transferrin receptor expression was downgraded under these growth conditions but, contrary to expectation, the decline affected the population uniformly, without the emergence of a distinct, transferrin receptor-negative subpopulation corresponding to the increasing proportion of quiescent cells. Thus, although transferrin receptor expression bears some relation to cell cycle phase and reflects the proliferative activity of populations of cells, it is incapable of identifying individual cells which are out of cycle.

Apoproteins↗
PubMed1984

The effect of vasopressin and hepatic artery ligation on the blood supply to normal and metastatic liver tissue.

The effect of low (0.08 microU g-1 body wt min-1) and high (0.16 microU g-1 body wt min-1) rates of vasopressin infusion on blood flow to normal liver tissue and to liver metastases derived from azoxymethane induced colorectal carcinomas was studied in 36 male Wistar rats. Portal venous flow was measured by electromagnetic flowmetry and blood flow to normal and metastatic liver tissue by the clearance of xenon-133 injected directly into the liver parenchyma or metastasis. The low rate of vasopressin infusion decreased portal venous flow but increased blood flow to normal and metastatic liver tissue while at the higher rate of infusion these effects were reversed. Hepatic artery ligation (HAL) immediately following a low rate of vasopressin infusion abolished the observed increase in blood flow to both normal liver tissue and metastases. HAL immediately following the higher rate of vasopressin infusion further reduced blood flow to metastases but did not further alter blood flow to normal liver tissue. HAL prior to the infusion of the vasoactive drug significantly reduced blood flow to metastatic liver tissue, increased portal venous flow and was without effect on blood flow to normal liver tissue. Following HAL, blood flow to metastatic liver tissue was not further altered by either the low or high rates of vasopressin infusion. However, blood flow to normal liver tissue after HAL was reduced by a low rate of infusion of vasopressin and increased by the higher rate of infusion. The results of this study indicate that blood flow to normal or metastatic liver tissue can be increased or decreased by differential rates of infusion of vasopressin. These observations may have important implications in the treatment of liver metastases in man where different rates of vasopressin infusion may potentiate the effects of hepatic artery ligation or cytotoxic therapy.

Animals↗
PubMed1984

Detection of early neoplastic changes in experimentally induced colorectal cancer using scanning electron microscopy and cell kinetic studies.

Colonic tumours were induced in Wistar rats using 12 consecutive subcutaneous injections of azoxymethane at a dose of 10 mg/kg/week. Pairs of rats were killed at five weekly intervals after initial injection until 25 weeks. Colonic mucosa was sampled from five standard areas along the length of the colon and examined by both scanning electron microscopy and conventional light microscopy. The crypt cell production rate was measured by stathmokinetic techniques. Scanning electron microscopy showed microadenomas as early as five weeks and consistently after 15 weeks. They were found predominantly in the distal colon and increased in size with time. The lesions showed a progressive increase in the number of crypts per adenoma and increasingly disorganised slit shaped crypt orifices. The presence of epithelial dysplasia in the microadenomas and of invasion of the colonic wall by carcinoma was confirmed histologically, although fewer lesions were identified in tissue sections than by scanning electron microscopy. Crypt cell production rate increased with time, particularly in the distal colon. This increase was significant between five and 25 weeks. The results of these observations suggest that there is an adenoma-carcinoma sequence in this animal model. The value of scanning electron microscopy in identifying and quantifying the mucosal changes during carcinogenesis is emphasised.

Adenoma↗
PubMed1984

Effect of vasopressin on liver blood flow in the hypophysectomised rat.

Liver blood flow (xenon-133 clearance method) and portal venous flow were measured in hypophysectomised rats following the infusion of vasopressin at a range of infusion varying from 0.0125 to 0.8 microU/g b.w./min over the range 0.0125-0.1 microU/g b.w./min, portal venous flow was reduced, the reduction being linearly related to the logarithm of the dose (r = -0.88). Following the infusion of 0.8 microU/g b.w. of vasopressin, portal venous flow significantly increased above pre-infusion levels (p less than 0.05). Liver blood flow was increased significantly (p less than 0.05) when vasopressin was infused over the range 0.0125-0.2 microU/g b.w. At higher rates of infusion, liver blood flow was progressively reduced, and at 0.8 microU/g b.w./min liver blood flow was less than pre-infusion levels (p less than 0.05). These data suggest that the effects of vasopressin on hepatic haemodynamics is related to the rate of infusion with a reversal of effects at higher rates of infusion. The implications of these findings in relation to the use of vasopressin in the management of portal hypertension and bleeding oesophageal varices is discussed.

Animals↗
PubMed1984

Colonic motility in the postoperative period.

The effect of a laparotomy on postoperative motility in the colon has been studied in dogs. Movement has been recorded by an electrical impedance method each day after a standard laparotomy. Mean values of movement in the descending colon were reduced, not abolished, for 3 days after operation (preoperative: 34.0%; day 1: 17.9%; day 2: 22.1%; day 3: 23.9%). In contrast, there was no reduction in motility in the transverse colon but a rise in activity on the first postoperative day (preoperative: 39.1%; day 1: 63.3%). It is concluded that a laparotomy does not abolish colonic movement postoperatively and that there is a reduction which affects the distal colon for 3 days.

Abdomen↗
PubMed1984

Assessment of anorectal motility measurements in the management of adult megacolon.

Anorectal motility was studied in 23 patients with adult megacolon. A balloon was used for rectal distension, and electrical signals from the anal canal or rectal mucosa were monitored with a silver/silver chloride electrode. Intraluminal pressure was measured by a pressure transducer linked to the vicinity of the electrode via a polythene tube. Responses to rectal distension provided a means of distinguishing patients with adult Hirschprung's disease from ones with idiopathic megacolon. Some patients with the latter condition showed an elevation of mean anal canal pressure relative to that in normal subjects. There was no statistically significant difference in slow-wave frequency in the anal canal between patients and adult megacolon and normal subjects. The fall in anal canal pressure associated with rectal distension was correlated with a decline in the amplitude of slow-wave electrical activity. The measurement of anorectal motor parameters was of value in the management of adult megacolon.

Anal Canal↗
PubMed1984

Assessment of a scoring scheme for the preoperative diagnosis of breast lumps.

The value and accuracy of a scoring system applied to clinical examination, aspiration cytology and mammography has been assessed in the diagnosis of 224 consecutive 'new' patients attending a breast clinic with a breast lump. In 72 of 99 patients with breast cancer (80%) the scores were high enough to allow definitive surgery without formal histology; all were subsequently confirmed as breast carcinomas. Cytology proved the most accurate investigation with no false positives and a correct diagnosis in 146 of 148 adequate specimens (98.6%). This system reduced the frozen section rate by 74% and allowed for a more appropriate counselling of patients prior to mastectomy.

Adult↗
PubMed1983

Pulmonary carcinoids. Immunohistochemical demonstration of brain-gut peptides.

Antisera raised against serotonin, gastrin, somatostastin, motilin, bombesin, calcitonin, secretin, glucagon, ACTH, neurotensin, and pancreatic polypeptide carboxyterminal hexapeptide were employed to immunohistochemically stain seven pulmonary carcinoids. Argentaffin and argyrophil stains were also performed on all cases. Serotonin-like immunoreactivity was present in four tumors, pancreatic polypeptide-like immunoreactivity in four tumors, bombesin-like immunoreactivity in two tumors and ACTH-like immunoreactivity in one tumor. The cells shown to contain neuroendocrine products constituted a minority cell population in all tumors except the ACTH-immunoreactive tumor. This study suggests that pulmonary carcinoids, like their abdominal counterparts, contain a variety of neuroendocrine products, and may produce more than one neuroendocrine product. Serotonin and pancreatic polypeptide-like immunoreactivity were the most prevalent neuroendocrine products demonstrable in this study.

Adult↗
PubMed1983

Changes in small bowel myoelectrical activity following laparotomy.

Recordings of the myoelectrical activity have been obtained from the small intestine of 4 dogs by means of serosally implanted electrodes. The occurrence of the activity front (phase III) of the migrating myoelectrical cycle (MMC) in the recordings obtained each day after abdominal surgery have been compared. No activity fronts were seen on postoperative days 1 and 2. From days 3 to 6 there was a slightly reduced incidence, but from day 7 onwards an activity front was observed in each recording. It is concluded that the normal pattern of cyclic myoelectrical activity in the small intestine is disrupted for at least 2 days following a laparotomy, and the view that small bowel motility returns to normal soon after routine abdominal surgery may be inaccurate.

Animals↗
PubMed1983

Bile acid receptors in colorectal cancer.

Bile acids are thought to be involved in both the aetiology and development of colorectal cancer. In this study the existence of specific bile acid receptor proteins has been postulated. A receptor assay which involved labelling with 14C-deoxycholic acid was performed as well as autoradiography using 3H-deoxycholic acid. In an initial study resected colorectal cancer and adjacent histologically normal colorectal mucosa from 39 patients were studied, as were samples of normal gastric mucosa, cancers and benign colorectal tumours. Specific receptors to deoxycholic acid were detected in 12 (30.8 per cent) of the colorectal cancers, but in only 1 (2.6 per cent) of the samples from normal colorectal mucosa (X2 = 11.16, P less than 0.005). No deoxycholic acid receptors were detected in any other tissue studied. Autoradiographs of colorectal cancers showed binding of 3H-deoxycholic acid in receptor-positive tumour tissue. These findings might provide some explanation for the evidence linking bile acids with the disease.

Autoradiography↗