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Biomedical subjects

L H Rees

Publications and source records attributed to L H Rees.

At least 109 records · Page 6Linked to original sources
PubMed1985

A peptide that inhibits the mitogenic stimulation of Swiss 3T3 cells by bombesin or vasopressin.

The synthetic peptide [D-Arg1,D-Pro2,D-Trp7,9,Leu1]substance P inhibits the stimulation of DNA synthesis induced in Swiss 3T3 cells by bombesin or vasopressin, but not that induced by a wide range of other growth factors and mitogens. The stimulation induced by 10 pM-3 nM-bombesin is inhibited by 1-30 microM-antagonist in a manner consistent with competition at the bombesin receptor. The inhibition by the antagonist of the stimulation induced by vasopressin suggests a previously unrecognized interaction of the antagonist with vasopressin receptors. The antagonist should be useful in studies of cell proliferation both in vivo and in vitro.

Animals↗
PubMed1985

Effect of liver and renal dysfunction on circulating methionine-enkephalin immunoreactivity.

Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = -0.71, P less than 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.

Enkephalin, Methionine↗
PubMed1985

Comparison by gel filtration chromatography and reversed-phase high-performance liquid chromatography of the immunoreactive growth hormone composition of a human pituitary extract.

The immunoreactive growth hormone composition of a pituitary extract has been compared by conventional gel filtration chromatography (pH 8), and reversed-phase high-performance liquid chromatography (pH 2) on a wide-pore (300 A) short-chain column. By gel filtration chromatography, four peaks of immunoreactivity were obtained, labelled "monomer", "dimer", "aggregate" and "void". However, by high-performance liquid chromatography all of these fractions were themselves shown to be multicomponent mixtures. The "monomer" peak contained at least two forms (M1 and M2). The "dimer" fraction contained three peaks, two of which co-eluted with M1 and M2, and a third component, D. Similarly, the aggregate fraction contained M1, M2, D and a fourth component, A. The "void", in contrast, contained mostly M1 and M2 with very little D. One interpretation of these results is that M1 (the 22K molecular weight monomeric form) and M2 (a chemically modified form of M1) are present in all molecular weight fractions in loosely bound aggregates which break up under acidic conditions. D and A are probably oligomeric forms of growth hormone (possibly a dimer and higher molecular weight species, respectively).

Chromatography, Gel↗
PubMed1985

Effect of histamine infusion on circulating methionine-enkephalin and catecholamine concentrations.

In 5 normal adult men, histamine was infused i.v. for 5 min at 20 micrograms/kg/h and at 80 micrograms/kg/h on two occasions one week apart. Diastolic blood pressure fell and heart rate, plasma adrenaline and noradrenaline all rose in a dose-dependent manner, but plasma methionine-enkephalin (Met-Enk) concentrations were unchanged. These results indicate that while Met-Enk may be co-stored with catecholamines (CAs) in the adrenal medulla in at least this paradigm, circulating concentrations of CAs may be altered without similar changes in plasma Met-Enk immunoreactivity.

Adrenal Medulla↗
PubMed1985

The effect of surgery on plasma beta-endorphin and methionine-enkephalin.

Seven women undergoing abdominal hysterectomy under halothane and nitrous oxide analgesia had plasma samples taken before, during and after surgery for assay of adrenocorticotrophin (ACTH), beta-endorphin, beta-lipotrophin and methionine (Met)-enkephalin immunoreactivity. Plasma ACTH, beta-endorphin and beta-lipotrophin all rose in parallel from the start of surgery and were unaffected by postoperative opiate analgesia. Plasma Met-enkephalin concentrations did not change significantly during the course of the surgery and immediate post-operative period, although the variance of the samples increased at the time of the first skin incision. These data indicate that the stress of surgery and post-operative pain, while producing marked elevations of proopiomelanocortin-derived peptides, are not associated with changes in plasma Met-enkephalin. These data exclude a role for circulating Met-enkephalin in the modulation of surgical pain but do not exclude such a role for beta-endorphin.

Analgesics, Opioid↗
PubMed1985

The role of endorphins in septicaemic shock: a pilot study in burned patients.

There is recent evidence that circulating opioid peptides, or 'endorphins', act as chemical messengers responsible for the induction of the complex cardiovascular changes leading to hypotension in septicaemic shock. The pilot study of an investigation of opioid peptides in septicaemia in burned patients is presented. Serial measurements of plasma beta-endorphin and metenkephalin were performed throughout the recovery of six patients with large burns (20-70 per cent BSA). Our preliminary findings concur with previous evidence that opioid peptides may play a role in the hypotension of septicaemic shock.

Adolescent↗
PubMed1985

Cushing's syndrome.

Cushing's syndrome remains one of the most challenging problems in clinical endocrinology. Cushing's disease is caused in the majority of cases by basophil pituitary microadenomas which may be successfully treated by trans-sphenoidal hypophysectomy. Treatment with metyrapone or o,p'-DDD can always induce a clinical remission but not a cure, and neurotransmitter therapy may be effective in a minority of cases. Pituitary irradiation cures about half of cases in the long-term and may be used for surgical failures. Tumours producing ectopic ACTH are frequently benign, small and occult and may produce a syndrome clinically indistinguishable from Cushing's disease. Biochemical investigations cannot absolutely distinguish pituitary from ectopic sources of ACTH and therefore body CT scanning and percatheter venous sampling are essential diagnostic investigations. Tumour localization may result in resection and complete cure, although even small tumours may have a malignant potential. Adrenal tumours are readily diagnosed by plasma ACTH measurement and adrenal CT scanning. Adrenal adenomas are cured by adrenalectomy. Carcinomas may be treated by a combination of adrenalectomy, radiotherapy and o,p'-DDD, but long-term prognosis is poor.

Adrenal Cortex Hormones↗
PubMed1985

Peri-operative endocrine effects of etomidate.

This study investigated the effects of etomidate on endocrine responses to anaesthesia and surgery. Patients undergoing abdominal hysterectomy received standard anaesthetics of either etomidate for induction with etomidate infusion, or thiopentone and halothane. Etomidate suppressed the secretion of cortisol and aldosterone for between 8 and 22 hours after the end of the etomidate infusion; 11-deoxycortisol secretion was not suppressed during the etomidate infusion, but rose postoperatively; 17 alpha-hydroxyprogesterone suppression also lasted only as long as the etomidate infusion. There were no effects on plasma oestradiol, ACTH, or prolactin, but growth hormone concentrations were elevated in the etomidate group. Etomidate was concluded to have influenced adrenocortical function only, where it probably inhibits 11 beta-hydroxylation, 17 alpha-hydroxylation and other intramitochondrial hydroxylation reactions. There were no clinical sequelae attributable to adrenocortical suppression. The relationship of chemical structure of etomidate and other phenylated imidazoles to inhibition of steroidogenesis is discussed.

17-alpha-Hydroxyprogesterone↗
PubMed1985

A case of pituitary dependent Cushing's disease with clinical and biochemical features of the ectopic ACTH syndrome.

A case of atypical pituitary dependent Cushing's disease is reported. The patient presented with clinical symptoms similar to those of the ectopic ACTH syndrome; notably a marked hypokalaemic alkalosis, widely fluctuating plasma cortisol levels, greatly elevated plasma ACTH levels, and failure to suppress both plasma cortisol and ACTH levels following high dose oral dexamethasone. However, a large aggressive pituitary tumour was detected by skull X-ray and computed tomography. Removal of the pituitary tumour led to full remission of the patient's Cushing's syndrome. Pro-opiomelanocortin (POMC) related peptides in the plasma and tumour tissue extract of this patient have been characterized by gel-filtration and Concanavalin-A Sepharose affinity chromatography, indicating processing of POMC in a manner more usually associated with ectopic tumours.

ACTH Syndrome, Ectopic↗
PubMed1985

The relationship between serum prolactin and immunocytochemical staining for prolactin in patients with pituitary macroadenomas.

We have studied the relationship between mean pretreatment levels of serum prolactin and the presence of positive immunohistochemical staining for prolactin in the pituitary tumours of 55 patients. Pretreatment serum prolactin was significantly higher in patients with tumours showing many prolactin immunostaining cells than in those with none (P less than 0.001). When the pretreatment serum prolactin exceeded 6000 mU/l, the tumours contained over 90% of prolactin positive cells; one patient was an exception who had received long-term high dose bromocriptine therapy, and her tumour showed only occasional cells with positive staining. When the pretreatment serum prolactin level was under 2500 mU/l, a tumour was found which showed either no cells or fewer than 1% of cells which stained for prolactin. There was no significant difference in pretreatment serum prolactin levels between 11 patients with craniopharyngiomas and 34 patients with pituitary macroadenomas showing no prolactin immunostaining. Seventy-one percent (32) of the 45 patients with craniopharyngiomas or tumours with negative immunostaining for prolactin, had raised pretreatment serum prolactin levels (above 360 mU/l) although this was usually only slightly elevated; the levels exceeded 2500 mU/l in six (13%) of them (two craniopharyngiomas, four pituitary tumours) but in none did the levels exceed 6000 mU/l. Four of the 55 pituitary tumours showed occasional cells (less than 1%) that stained positively for growth hormone. In none of the patients with these tumours was there evidence of acromegaly or pathologically elevated circulating growth hormone levels.

Adenoma↗
PubMed1985

Pituitary ACTH dependent Cushing's syndrome due to ectopic production of a bombesin-like peptide by a medullary carcinoma of the thyroid.

A 41-year-old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin-like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin-like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin-like peptide, causing excessive pituitary ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1985

Comparison of the clinical activity of mesulergine and pergolide in the treatment of hyperprolactinaemia.

The clinical activity of the new ergoline, mesulergine, was compared to pergolide in the treatment of hyperprolactinaemia. Mesulergine was given to 22 women and five men with hyperprolactinaemia. Serum prolactin was substantially lowered in 10 women; two subsequently conceived and completed normal pregnancies. Twelve women stopped treatment due to side-effects, usually nausea and vomiting, or inadequate responses. The side-effects were generally similar to those on bromocriptine; in one patient they were better and in four worse than on bromocriptine. The male patients were more tolerant of mesulergine, and substantial falls in serum prolactin were seen with evidence of tumour shrinkage. Twenty-seven women with hyperprolactinaemia received pergolide; serum prolactin was lowered or normalized in 16. Side-effects necessitating cessation of treatment were similar to those seen with bromocriptine. Nevertheless, four women tolerated pergolide better than bromocriptine and two women adequately treated with mesulergine had previously been intolerant of pergolide. We conclude that both pergolide and mesulergine may be useful and effective drugs in the treatment of hyperprolactinaemia as alternatives to bromocriptine.

Adenoma↗
PubMed1985

Stimulation by food of peripheral plasma immunoreactive growth hormone releasing factor.

A highly specific radioimmunoassay has been used to study changes in peripheral human plasma growth hormone releasing factor (GRF) following the ingestion of food. From a mean basal plasma concentration of 11.8 pg/ml (range less than 7-15.4 pg/ml) in six normal individuals following overnight fast, the circulating concentration of GRF-like immunoreactivity increased to a mean maximum of 36.7 pg/ml (range 20.2-77.0 pg/ml) sampled 120 min after a mixed breakfast. This increase in GRF was accompanied by suppression rather than stimulation of circulating growth hormone. The predominant source of peripheral circulating GRF-like immunoreactivity may therefore by extrahypothalamic and responds to an oral food stimulus.

Adult↗
PubMed1985

Autonomic regulation of postprandial plasma somatostatin, gastrin, and insulin.

To evaluate the neural regulation of postprandial somatostatin release we studied the effect of blockade of (a) alpha-adrenergic and beta-adrenergic and (b) cholinergic receptors on the plasma somatostatin, gastrin and insulin responses to a standard meal in two groups of five fasting healthy male volunteers. Thymoxamine (0.1 mg/kg iv over two minutes then 10 mg/hour for two hours) and propranolol (0.15 mg/kg iv over two minutes, then 0.75 mg/kg/hour for two hours) were started just before eating while atropine (0.04 mg/kg/im) was given at 15 minutes on completion of the meal. There was a prompt and sustained rise in plasma somatostatin after a control meal in all experiments. This rise was arrested by atropine but not altered by either thymoxamine or propranolol. The plasma gastrin response to a meal was moderately enhanced by thymoxamine and markedly enhanced by atropine. Postprandial insulin release was not affected by alpha- or beta-adrenergic blockade but was abolished by atropine. The effect of atropine on the postprandial plasma somatostatin rise might have been mediated through reduction in gastric acidity or delay in gastric emptying. Hence we gave five fasting male volunteers and intraduodenal infusion of fat emulsion (25 calories in 30 minutes) on two occasions both alone and after atropine. Plasma somatostatin rose during the fat infusion alone and this rise was abolished by atropine. These data suggest that (a) cholinergic but not adrenergic mechanisms are important modulators of plasma somatostatin release after orally ingested and intraduodenally infused nutrients (b) atropine abolishes plasma somatostatin release independently of its effects on gastric acidity and motility and (c) are consistent with the hypothesis that atropine potentiates postprandial gastrin release through reduction of somatostatin mediated inhibition.

Adult↗
PubMed1985

Bombesin-like peptides in human endocrine tumors: quantitation, biochemical characterization, and secretion.

Bombesin-like immunoreactivity (BLI) in 20 human endocrine tumors was studied using an antiserum directed toward the C-terminal region of bombesin. Additionally, plasma BLI was assayed in normal subjects and patients with known BLI-containing tumors. In 7 tumors (medullary carcinoma of the thyroid, n = 2; carcinoid of the lung, n = 3; hepatic carcinoid, n = 1; pheochromocytoma, n = 1), the BLI content ranged from 6-2000 pg/mg wet wt of tissue. Sephadex G-50 gel chromatography of tumor extracts under acid-dissociating conditions revealed 2 peaks of BLI: 1 coeluting with porcine gastrin-releasing peptide (GRP) and 1 with bombesin. Reverse phase ODS silica HPLC analysis of the G-50 peaks using a methanol-trifluoroacetic acid gradient showed that human tumor BLI more closely resembled porcine GRP and its C-terminal fragment GRP-(14-27) than bombesin itself. Partial tryptic digestion of the tumor GRP-like peptide generated a product which, on HPLC, was similar to GRP-(14-27). Elevated plasma BLI was detected in the peripheral circulation of three subjects and in the vessels draining the tumor metastases of one of these patients. BLI was undetectable in normal subjects. These results indicate 1) that BLI is present in and may be secreted by various human endocrine tumors, and 2) that human tumor BLI closely resembles porcine GRP and its C-terminal fragment GRP-(14-27).

Animals↗