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Biomedical subjects

A W Goode

Publications and source records attributed to A W Goode.

At least 19 recordsLinked to original sources
PubMed1992

Progesterone receptor induction by danazol in cultured cancer cells and the rat uterus.

We have previously reported that clinical trials relating to the use of danazol in the management of benign breast disease show a positive correlation between favourable clinical response and an induction of progesterone receptors in the affected tissue which is maintained for a period of at least 6 months subsequent to the cessation of treatment. Further studies designed at elucidating more clearly the actions of danazol at the cellular and molecular levels have confirmed that progesterone receptors are down-regulated by short-term progestin action at the level of the mRNA transcript, but that danazol is subsequently able to produce an enhanced cellular response, inducing progesterone receptors in the presence of oestrogenic agents. Uteri from danazol-treated rats showed a doubling of progesterone receptor concentrations compared with the control uteri. In the mammary cancer cell line T-47D, cells treated with danazol had increased progesterone receptor concentrations of 558.4 +/- 32.0 compared with 152.6 +/- 7.0 fmol/mg protein in the control cells. In both cases, these inductions were observed following a period of progesterone receptor suppression. Short-term molecular studies on T-47D cells indicated that progesterone and danazol initially inhibit mRNA transcription, but that 24 h after treatment an induction is observed. This is especially marked in the danazol-treated cells.

Animals↗
PubMed1992

Oestrogen receptor isoforms, their distribution and relation to progesterone receptor levels in breast cancer samples.

Oestrogen receptors (ER) in breast cancer tumours are highly heterogeneous. In this study, the variability in the profile of ER isoforms and its relation to progesterone receptor (PgR) levels in breast tumours has been studied. Using high resolution isoelectric focusing (IEF) 4 ER isoforms can be detected with pI values of 6.1 (corresponding to the 8S ER), and 6.3, 6.6 and 6.8 (all of which have a sedimentation pI values of 6.1 (corresponding to the 8S ER), and 6.3, 6.6 and 6.8 (all of which have a sedimentation coefficient of approximately 4S in sucrose density gradients). Data were obtained on the soluble receptors from supernatants of 66 ER-positive primary breast tumour homogenates using high resolution IEF. In 43 of these samples PgR levels were also measured. The isoform at pI 6.6 was present in 97.0% of tumours, the isoform at pI 6.1 in 83.3%, the pI 6.3 isoform 39.4% of tumours and the pI 6.8 isoform in only 33.3% of tumours. Only 12.1% of tumours studied contained the full complement of ER isoforms (pI 6.1, 6.3, 6.6 & 6.8). The ER isoforms at pI 6.1 & 6.8 were only found in PgR-positive (> 10 fmol PgR/mg protein) tumours. Some tumours contained only a single ER isoform at pI 6.6 or 6.1, but those at pI 6.3 and 6.8 were never found singly. Tumours containing 3 or 4 ER isoforms had significantly higher levels of PgR (> 90 fmol/mg protein) than those with only 1 or 2 (P < 0.001). The presence of ER isoforms at pI 6.3 and pI 6.8 also significantly correlated with high levels of PgR (P < 0.001). This variability in the ER isoform profile of breast tumours and their correlation with PgR levels may have a bearing on prognosis and tumour response to endocrine therapy.

Breast Neoplasms↗
PubMed1991

Significance of the 8S complex in oestrogen receptor recognition.

Previous studies from this laboratory have drawn attention to discrepancies between enzyme-linked immunoassay (EIA) and steroid binding assay (SBA) in the analysis of oestrogen receptors (ER) in breast tumours. In particular, EIA values were at least 3-fold higher than SBA values in tumours which also contained progesterone receptors (PR) when both 4 and 8S isoforms of the ER are present. To test the influence of these isoforms on the two assay systems, the relationships between the oestrogen receptor (ER) values obtained by EIA and SBA were examined in tumour cytosols prepared in the presence of molybdate and protease inhibitors to prevent degradation of the 8S form. Under these conditions, values for ER were the same by EIA and SBA (slope = 1.08, r = 0.886, n = 25) when EIA was performed using low salt phosphate buffer instead of the high salt-containing Abbott-diluent provided with the kit. However, after disruption of the 8S assembly using high K+ concentration, the slope of the regression was 6.37, r = 0.865, n = 25. Using ER from rat uterus, EIA was also performed on intact 8S oligomers, on 8S ER dissociated by high salt, and on glycerol density gradient-fractionated 4S ER. The identity of the ER oligomers and components was confirmed by glycerol density gradient fractionation, and by isoelectric focussing. For the 4S ER, EIA gave similar values whether using low or high salt phosphate buffer. However EIA values for the 8S form were 2-fold higher when the supplied diluent was used than when the assay was performed in low salt buffer. The amount of oestradiol which could be extracted was affected by the different conditions used. Addition of KCl or trypsin to disrupt the 8S ER caused an increase in the amount of extractable oestradiol compared with control values (control = 52 +/- 4.0, high KCl = 91 +/- 4.4, trypsin = 152 +/- 7.5, pg oestradiol/mg protein). We conclude that further antibody binding sites are revealed from the 8S ER form after its disaggregation by high salt. The steroid extraction data also suggests the possibility that tightly bound steroid is retained within the 8S ER structure, and released by 8S disaggregation. Both of these may contribute to the differences between EIA and SBA values.

Animals↗
PubMed1990

Impact of conventional and three-dimensional thallium-technetium scans on surgery for primary hyperparathyroidism.

Twenty-nine patients with primary hyperparathyroidism underwent double-tracer subtraction scanning after injection of 201Tl as thallous chloride for thyroid and parathyroid images followed by 99mtechnetium as sodium pertechnetate for thyroid images prior to surgical exploration of the neck. The operative findings were correlated with the scans. All 23 adenomas (100%) and 13 of 18 (72%) hyperplastic glands were correctly localized. The ability of the scan to identify abnormal parathyroids was determined by the gland mass rather than whether the tissue was adenomatous or hyperplastic as all 32 (100%) abnormal glands weighing more than 180 mg were successfully localized in contrast to four of nine (44%) glands weighing less than 180 mg. An additional technique, in which emission tomography was carried out after subtraction scintigraphy, was used on 11 patients in the series. In all 11, the site of a single abnormal gland was predicted by the conventional subtraction scan: in nine of these patients, emission tomography provided additional localization of the gland in the anteroposterior plane.

Humans↗
PubMed1989

Epidermal growth factor receptor and oestrogen receptors in the non-malignant part of the cancerous breast.

Fifty-one samples of non-malignant tissue from four mastectomies were analysed to assess oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) status across the cancerous breast. No significant relationship was found between the presence of EGFR and ER. Eighty-four per cent of these samples were EGFR positive and 29% expressed both receptor types. EGFR and ER expression was not affected by histological sub-group. In contrast, analysis of 44 primary cancers showed, in agreement with the literature, a significant inverse relationship between the presence of ER and EGFR (Fisher's exact test P less than 0.002). The difference between malignant and non-malignant tissue appeared to result from the prevalence of co-expression of EGFR and ER in the non-malignant specimens. This suggests different regulation of receptor expression in malignant and non-malignant tissue.

Adult↗
PubMed1989

Diet-induced thermogenesis in patients with gastrointestinal cancer cachexia.

1. Indirect calorimetry has been used to measure resting energy expenditure (REE) and the thermogenic response to a test meal (diet-induced thermogenesis) in groups of weight-stable and weight-losing patients with gastrointestinal adenocarcinoma. Average daily intakes of energy and protein were computed from dietary assessment for the week before hospitalization. Results were compared with a control group of patients with benign gastrointestinal disease. 2. Weight-losing cancer patients had a significantly reduced mean total energy and protein intake. 3. There was no significant difference in REE between the groups when results were normalized in terms of metabolic body size (kJ/kg 0.75) and lean body mass (kJ/kg). 4. Diet-induced thermogenesis was reduced in weight-losing cancer patients. 5. It is suggested that the reduction of diet-induced thermogenesis in weight-losing cancer patients is another element of starvation adaptation, subsequent to their weight loss, and that altered thermogenesis does not contribute to the weight loss seen in cancer cachexia.

Adenocarcinoma↗
PubMed1989

Insulinoma.

Explore the source record for details and available documents.

Adenoma, Islet Cell↗
PubMed1988

The relationship between changes in lipid fuel availability and tissue fructose 2,6-bisphosphate concentrations and pyruvate dehydrogenase complex activities in the fed state.

An elevated concentration of non-esterified fatty acids in the fed state elicited inhibition of cardiac, but not hepatic, pyruvate dehydrogenase complex (PDH). There was a modest decline in fructose 2,6-bisphosphate (Fru-2,6-P2) concentration in heart, and, to a lesser extent, in liver. Surgical stress decreased PDH activities and Fru-2,6-P2 concentrations in both heart and liver. Only the former response was abolished if postoperative lipolysis was inhibited. Surgery also decreased the [Fru-2,6-P2] in gastrocnemius: this response was abolished if lipolysis was inhibited.

Animals↗
PubMed1988

Acute effects of surgery on carbohydrate production and utilization in the fed rat.

1. The work utilized a model of uncomplicated abdominal surgery (laparotomy under ether anaesthesia) to delineate the effects of abdominal trauma on glucose homoeostasis in the fed rat. 2. Regulation of glucose production and utilization was investigated by observing the response to the administration of glucose, insulin plus glucose and 5-methylpyrazole 3-carboxylic acid. 3. Glucose administration suppressed hepatic glucose output as assessed by portal-venous concentration differences in control or surgically stressed rats. In contrast, glycaemia was increased and lactaemia decreased in the latter group. Portal-venous concentrations differences for lactate were unaffected. 4. Surgery increased plasma fatty acid concentrations and the antilipolytic response to glucose or glucose plus insulin was diminished. Post-operative increases in fatty acid concentrations were associated with inhibition of hepatic pyruvate dehydrogenase complex which was reversed by insulin, indicating a differential sensitivity of adipose tissue and liver to the hormone. 5. The model of surgical stress utilized, while affecting extrahepatic glucose disposal, did not elicit depletion of liver glycogen or inactivation of L-pyruvate kinase. 6. It is concluded that the initial response to uncomplicated abdominal surgery involves carbohydrate conservation rather than increased glucose production, with effects to decrease extrahepatic glucose uptake and hepatic glucose oxidation.

Animals↗
PubMed1988

A prospective controlled trial of topical irrigation in the treatment of delayed cutaneous healing in human leg ulcers.

1. Topical irrigation with normal saline is known to produce rapid healing in chronic leg ulcers. This study was designed to determine if the rate of healing could be improved by the addition of topical nutrition to the irrigating solution. 2. Forty-eight patients with chronic leg ulcers were admitted to hospital for a minimum of 6 weeks bed-rest. During this time the ulcers were continuously irrigated by one of four test solutions. The solutions were: normal saline; a dilute amino acid solution isotonic with the normal saline; a hyperosmolar saline solution; a hyperosmolar amino acid solution. There were 12 ulcers in each group. 3. The amino acid solutions produced significantly faster healing than the saline solutions (P less than 0.01). Concentration had no significant effect on healing (P greater than 0.15). 4. The application of amino acids does appear to enhance healing in this model of delayed wound healing. This effect does not depend only on the osmolarity of the solution used.

Amino Acids↗
PubMed1988

Regional injection of 5-fluorouracil and starch microspheres in colorectal cancer.

Experiments were undertaken to examine the effect of degradable starch microspheres (DSM) on the local distribution of 5-fluorouracil (5-FU) given by mesenteric arterial injection. Tritiated 5-FU (200 microCi) was injected into the inferior mesenteric artery of 8 perfused specimens of human large bowel containing adenocarcinoma and the concentration of 5-FU in local tissues and venous effluent was measured by scintillation counting. Metabolites of 5-FU were detected by radiochromatography. DSM (6 X 10(7)/mean diameter 40 micron) were injected in suspension with 5-FU (n = 7) and separately: before (n = 7) and after 5-FU (n = 7). Specimens given DSM retained 20% more cytotoxic than specimens given 5-FU alone (p less than 0.05). The concentration of 5-FU in tissues next to the primary tumour was increased when DSM were given in suspension with 5-FU, but higher concentrations were obtained when DSM were given last (p less than 0.05). Low concentrations were produced when DSM were given first. Concentrations in tumour tissue were not significantly increased by DSM.

Adenocarcinoma↗
PubMed1987

Effects of danazol on incidence of progesterone and oestrogen receptors in benign breast disease.

Results from a continuing clinical trial in benign breast disease indicate that danazol may induce progesterone receptors and that this effect persists after treatment. In women given danazol the number of biopsy specimens that were positive for progesterone receptors rose from 14 out of 31 before treatment to 23 out of 30 at the end of six months' treatment and remained raised at 21 out of 31 six months later. The number of biopsy specimens that were positive for oestrogen receptors rose transiently from eight out of 31 to 12 out of 30 and then fell to six out of 31. A satisfactory clinical response was achieved in 26 of the 31 patients but was maintained in only 11 six months or more after the end of treatment. It was only in this group that a significant and long-standing increase in progesterone receptors was observed. These findings suggest that in some women with benign breast disease who have been treated with danazol changes occur that may have long term benefit.

Adult↗
PubMed1987

Oestrogen and progesterone receptor distribution in the cancerous breast.

To test the hypothesis that steroid hormone receptor expression is particularly pronounced in breast tumours when compared with non-neoplastic tissue, mastectomy samples were divided into 16 sectors. Multifocal tumours, of varying receptor phenotype were found in 4 patients and in addition different regions of large tumours also showed varying receptor contents. Remaining samples were found to consist of normal tissue, with fat, connective tissue and some benign breast disease. In the 9 patients with oestrogen receptor positive tumours (ER), ER content was invariably much greater in the tumours than in the remainder of the breast. Progesterone receptor (PR) content was not closely related to ER, and was lowest in the poorly differentiated tumours. This relation to differentiation was not seen in ER. The data support the view that ER concentration in ER positive tumours may reflect the transformed nature of neoplastic tissue.

Adult↗