Search PubMed⌕ Search

Biomedical subjects

L H Rees

Publications and source records attributed to L H Rees.

At least 199 records · Page 11Linked to original sources
PubMed1981

Angiotensin II stimulates the release of ACTH from dispersed rat anterior pituitary cells.

In a rat anterior pituitary dispersed cell system, angiotensin II was found to stimulate the release of ACTH at concentrations ranging from 100 pmol/l to 1 mumol/l, with a maximal response being given by 10 nmol/l. The angiotensin II antagonist, saralasin, was able to block completely at a concentration of 1 mumol/l the stimulation of ACTH induced by 10 nmol/l angiotensin II, but had no effect on the basal release. The log dose-response curve for ACTH release by angiotensin II was shifted to the right in a parallel fashion by saralasin 10 nmol/l, suggesting competitive antagonism. The stimulation of ACTH release by a rat stalk-median eminence extract or by arginine vasopressin was unaffected by saralasin. The data are interpreted as suggesting that rat corticotrophs contain angiotensin II receptors, and that these may be involved in ACTH release in response to hypovolaemic stress.

Adrenocorticotropic Hormone↗
PubMed1981

Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease.

Although impaired growth hormone secretion in response to pharmacological stimuli occurs in some growth retarded children with Crohn's disease, its relationship to past and future th is uncertain. We have therefore determined the growth hormone and gonadotrophin response to the physiological stimulus of sleep by continuous venous sampling in five severely gonadotrophin profiles, the mean plasma hormone concentrations during the first five hours of sleep were determined. In three of the five patients, five hour mean growth hormone levels were reduced (3.8, 5.0, and 8.5 mU/l) compared with levels reported previously in normal short children (10-43 mU/l), although the pulsatile pattern of growth hormone secretion was preserved in all. Nocturnal growth hormone secretion was unrelated to the growth velocities of these children during both pre- and post-treatment assessment periods but a significant correlation was found between growth hormone concentration and a disease activity score (r = 0.79, P less than 0.05), suggesting that growth hormone release by the pituitary was influenced by the severity of the disease. Nocturnal growth hormone secretion was also correlated with gonadotrophin secretion (luteinising hormones, r = 0.99, and follicle stimulating hormone, r = 0.96; p less than 0.01) indicating more extensive hypothalamic-pituitary disturbance. These findings suggest that hypothalamic-pituitary function is depressed in growth retarded children with Crohn's disease, but that abnormalities of growth hormone secretion are unlikely to be directly involved in the growth retardation seen in this condition.

Adolescent↗
PubMed1981

Characterisation of the pro opiocortin family of peptides in human cerebrospinal fluid.

Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinal fluid. Samples of cerebrospinal fluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing's disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column fractions were assayed for N- and C-terminal beta-lipotropin, N-terminal ACTH and gamma-MSH immunoreactivity. Elution profiles obtained from chromatography on Sephadex G-50 demonstrated peaks of immunoreactivity corresponding to the elution positions of synthetic human beta-endorphin, highly purified beta-lipotropin and highly purified gamma-lipotropin in all CSF samples. A peak of a large molecular weight material with N and C terminal beta-lipotropin immunoreactivity was also detected. Chromatography of CSF on Sephadex G-75 showed this large molecular weight peak to be comprised of peptides eluting in the positions of a 31K molecular weight marker with beta-lipotropin and ACTH immunoreactivity and a 16K molecular weight marker with gamma-MSH immunoreactivity. This suggests the presence of the common precursor to ACTH and LPH in the CSF.

Chromatography, Gel↗
PubMed1981

Correlation of endogenous somatostatin, gastric inhibitory polypeptide, glucagon and insulin with gastric function in the conscious calf.

Levels of endogenous somatostatin, gastric inhibitory polypeptide (GIP), glucagon and insulin were measured during gastric (abomasal) emptying in the conscious calf. Isotonic NaHCO3 infused into the duodenum increased rates of emptying of a saline test meal and of gastric acid secretion, but had no effect on basal levels of blood glucose, somatostatin, GIP, insulin or glucagon. By contrast, intraduodenal infusion of 60 mM-HCl caused complete inhibition of gastric emptying, reduction of acid secretion, and an immediate increase in plasma somatostatin from 121.3 +/- 9.4 (S.E.M.) to 286.3 +/- 16.3 pg/ml (P less 0.01) but levels of GIP, insulin, glucagon and glucose were unaltered. Intravenous injection of somatostatin (0.5 microgram/kg) suppressed the antral electromyographic recording and gastri efflux so long as plasma somatostatin levels remained above approx. 200pg/ml. This suggest that somatostatin can be released by intraduodenal acidification and that it inhibits gastric function by an endocrine effect. Since somatostatin retards gastric emptying it may therefore have an indirect role in nutrient homeostasis by limiting discharge of gastric chyme to the duodenum.

Animals↗
PubMed1981

Response of circulating immunoreactive somatostatin to nutritional stimuli in normal subjects.

We have previously reported that in normal subjects plasma immunoreactive somatostatin levels rise after a mixed meal. The contribution of individual nutrients to this rise, and the molecular nature of the somatostatin immunoreactivity measured, have now been studied. Six normal healthy subjects received, on separate occasions, isocaloric (520 calories) and isovolumetric (260 ml) quantities of carbohydrate, protein, and fat. The mean fasting plasma somatostatin level was 29 +/- 5 pg/ml. After carbohydrate a peak of 48 +/- 7 pg/ml was reached at 30 min, and after protein and fat there were more sustained rises with peak levels of 74 +/- 8 pg/ml and 80 +/- 9 pg/ml, respectively. Sephadex G50 chromatography of extracts of fasting peripheral plasma showed two main peaks of somatostatin immunoreactivity, one coeluting with cyclic somatostatin and a larger peak of approximately 3500 molecular weight (mol wt). Levels of both 1600 and 35000 mol wt somatostatin were increased 60 min after a mixed meal. Approximately 80% of the 3500 mol wt form of somatostatin could be converted to the 1600 mol wt form by treatment with dithiothreitol (an agent which reduces disulphide bonds). It is concluded that: (a) in normal subjects fat and protein are potent stimuli for somatostatin release; (b) somatostatin in normal peripheral plasma exists in multiple forms, and that both 1600 and 35000 mol w forms of somatostatin immunoreactivity are stimulated by feeding; (c) the 3500 mol wt form could represent a dimer of somatostatin or a somatostatin molecule linked to a second peptide chain by disulphide bonds.

Adult↗
PubMed1980

Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain.

Low-frequency electroacupuncture effectively alleviated recurrent pain in 10 patients. Basal levels of beta-endorphin and met-enkephalin in the lumbar cerebrospinal fluid (CSF) of these patients were not different from those in pain-free control subjects. After electroacupuncture in the patients with pain CSF beta-endorphin levels rose significantly in all subjects, but met-enkephalin levels were unchanged. These results suggest that the analgesia observed after electroacupuncture in patients with recurrent pain may be mediated by the release into the CSF of the endogenous opiate, beta-endorphin.

Acupuncture Therapy↗
PubMed1980

Ectopic production of methionine enkephalin and beta-endorphin.

Immunoreactive methionine enkephalin and beta-endorphin were sought by serial dilution of tissue extracts and assay of chromatographic fractions in non-endocrine tumour tissue from three patients with the ectopic adrenocorticotrophin syndrome associated with carcinoid tumours and in normal lung tissue and thymic tissue from a patient with myasthenia gravis. In all cases serial dilution of extracts showed parellelism to standard radioimmunoassay curves. The two peptides were found in high concentration in the three tumours but were undetectable in the control tissues. In a single case tested the methionine enkephalin concentration in a vein draining the tumour was twice that in a peripheral vein. In view of their profound effect on behaviour in animals and potent analgesic activity in animals and man the ectopic secretion of methionine enkephalin and beta-endorphin may modify the clinical features of a wide variety of tumours and produce some of the diverse clinical syndromes associated with malignancy.

ACTH Syndrome, Ectopic↗
PubMed1980

Met-enkephalin circulates in human plasma.

The physiological roles of Met-enkephalin and Leu-enkephalin are still unknown. They may act as neurotransmitters in the central and peripheral nervous systems. Met-enkephalin has been detected in several species in a variety of tissues including brain, spinal cord and gut using bioassays, opiate receptor assays and radioimmunoassays (RIA). It has also been detected in human gut immunocytochemically and in human brain and cerebrospinal fluid by opiate receptor assay and RIA. However, all reported assays show some degree of cross-reaction with Leu-enkephalin and unequivocal differentiation between the two enkephalins and the larger endorphins has not always been possible. Thus the existence of Met-enkephalin in human tissues and fluids remains in doubt. Using a highly specific RIA, we have now obtained evidence that Met-enkephalin-like material circulates in the plasma of normal subjects and may be secreted by the adrenal gland. Chromatographically the material exists in plasma mainly as the intact pentapeptide and not as the biologically inactive degradation product Gly-Gly-Phe-Met as would be expected from metabolic studies.

Adrenal Glands↗
PubMed1980

In vivo and in vitro studies on the effect of metoclopramide on aldosterone secretion.

Metoclopramide, a dopamine antagonist drug, elevated plasma aldosterone and prolactin levels without significantly affecting plasma renin activity, ACTH or potassium. Studies with isolated perfused rat zona glomerulosa cells showed that metoclopramide could directly stimulate aldosterone release and that this action was blocked by dopamine. These results suggest that dopamine may play an important inhibitory role in the control of aldosterone secretion.

Adrenal Glands↗
PubMed1980

Secretion of ACTH, LPH and beta-endophin from human pituitary tumours in vitro.

Basal and stimulated secretion of immunoreactive ACTH, LPH and beta-endorphin from four human pituitary tumours has been studied in vitro using a superfused, isolated cell system. Chromatography of cell secretions under acid-dissociating conditions demonstrated that the human tumor cells released immunoreactive peptides with the elution profiles of alpha h (1-39) ACTH, beta h-LPH, gamma h-LPH and beta h-endorphin confirming that beta h-endorphin is secreted by human pituitary tumour cells and is not formed by enzymic cleavage from beta h-LPH in blood. No alpha- or beta h-MSH, nor any higher molecular weight forms of ACTH or LPH were detected. The cells from all four tumours responded to stimulation with rat stalk-median eminence extract (SME) and synthetic AVP with a concomitant release of ACTH, beta-LPH, gamma-LPH and beta-endorphin. In contrast to the isolated rat anterior pituitary cells, the pattern of responses to SME and AVP were indistinguishable and the release provoked by rat SME could be accounted for virtually entirely by its vasopressin content. No stimulation of release was observed when the cells were exposed to a variety of biogenic amines. Addition of hydrocortisone to the perfusion buffer of two tumours resulted in a slow inhibition of both basal and stimulated ACTH and LPH release. These data demonstrate that human pituitary tumour tissue from patients with Cushing's disease and Nelson's syndrome can be studied in vitro and that such studies may contribute to a greater understanding of the aetiology of these diseases.

Adrenocorticotropic Hormone↗
PubMed1980

CSF and plasma somatostatin levels in acromegaly.

Cerebrospinal fluid (CSF) and plasma levels of somatostatin have been measured in patients with active acromegaly and the results compared to those obtained in patients with non-endocrine diseases. Plasma levels have also been studied in acromegalics given oral glucose. The mean CSF somatostatin level in twenty patients without endocrine disease was 76 pg/ml (range 46-112) which did not differ significantly from that found in eight acromegalics (mean 87 pg/ml, range 48-160). Plasma somatostatin in twenty-two acromegalic patients on no medical treatment was 43 pg/ml (range 9-113), not significantly different from values in a normal control population. There were no differences in the somatostatin levels of non-diabetic acromegalics. After oral glucose, there was a rise in circulating somatostatin in eleven out of twelve acromegalic patients, and this rise did not differ from that seen in normal subjects. It is probable that altered somatostatin secretion is neither the cause nor the result of acromegaly; however it is possible that local changes in somatostatin concentration which are not reflected in peripheral plasma or CSF levels may occur near the site of its production.

Acromegaly↗
PubMed1980

Circulating somatostatin after food and glucose in man.

Using a recently validated radioimmunoassay, changes in circulating somatostatin have been measured in normal subjects after food (a standard breakfast), and oral and intravenous glucose. After the standard breakfast, a clear and sustained rise in plasma somatostatin was seen in all subjects from a mean value (+/-1 SE) of 28 +/- 7 pg/ml to a mean peak value, at 60 min of 57 +/- 11 pg/ml. When glucose was taken by mouth a significant but smaller rise was seen, but intravenous glucose caused no significant change in plasma somatostatin. A rise in circulating somatostatin after feeding has not previously been demonstrated in normal man and it is suggested that somatostatin may have an important endocrine role in the gut.

Adult↗
PubMed1980

Molecular forms of somatostatin in normal subjects and in patients with pancreatic somatostatinoma.

Two patients with somatostatin-secreting pancreatic tumours are described, one presenting with hypoglycaemia due to hyperinsulinism, and the other with Cushing's syndrome due to ectopic ACTH production. When plasma from these patients was subjected to gel chromatography under conditions designed to prevent somatostatin binding to larger proteins, a peak of monomeric immunoreactive somatostatin was observed as well as several large molecular weight forms. These larger forms of somatostatin could be dissociated into monomeric somatostatin by dithiothreitol. Similar studies on plasma obtained from normal subjects also showed heterogeneity of circulating somatostatin. Extracts of tumour tissue from both patients contained predominantly monomeric somatostatin, but only small amounts of high molecular weight somatostatin which differed from the profile seen in plasma. The site(s) of origin of the large molecualr weight forms of somatostatin seen in plasma and their relative biological activities remain to be established.

Adenocarcinoma↗
PubMed1980

Immunoreactive somatostatin changes during insulin-induced hypoglycaemia and operative stress in man.

Little is currently known about the factors controlling somatostatin secretion. A radioimmunoassay has been developed that is sufficiently specific and sensitive to be used for physiological studies of circulating levels in man. During insulin-induced hypoglycaemia a rise in plasma somatostatin was seen in each of ten subjects studies. Although this paralleled the rise in circulating glucagon and growth hormone, no individual relationships were found either between these variables or to any change in cortisol or insulin C-peptide. In contrast no rise in somatostatin was seen during surgical stress. Thus, contrary to expectation, circulating somatostatin levels can be altered by metabolic stimuli. It seems likely that this peptide may serve an endocrine as well as a paracrine role since its modulating effects may occur not only near to but also at a distance from the site of secretion. It is not yet clear whether the somatostatin measured comes from the hypothalamus, any other part of the central nervous system or the gastrointestinal tract.

Adult↗
PubMed1980

beta-Endorphin and beta-MSH in human plasma.

The aim of this study was to establish whether or not a peptide with chromatographic and immunological properties of beta-endorphin exists in human plasma. Using direct chromatography under conditions designed to minimize generation of beta-endorphin and beta-MSH from beta-LPH, we invariably found a peptide with beta-endorphin immunoreactivity eluting in the position of beta h-endorphin on gel chromatography in samples of plasma from patients with elevated ACTH and LPH levels. beta-MSH was only found in the plasma of one patient with the ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗
PubMed1980

ACTH LPH and related peptides in the ectopic ACTH syndrome.

Adrenocorticotrophin, lipotrophin and the related peptides alpha-MSH, CLIP, beta-endorphin and met-enkephalin have been measured, and characterized chromatographically in tumour extracts from seven patients with the ectopic ACTH syndrome. Four of the seven tumours contained the complete family of peptides, although the proportion of one to another varied between tumours. In addition, large molecule weight forms of ACTH and met-enkephalin were seen. The potential clinical importance of these observations is discussed.

ACTH Syndrome, Ectopic↗