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Biomedical subjects

L H Rees

Publications and source records attributed to L H Rees.

At least 145 records · Page 8Linked to original sources
PubMed1984

The role of endogenous opioids in the chlorpropamide alcohol flush.

The response of plasma immunoreactive met-enkephalin (IR-met-enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non-insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR-met-enkephalin was observed in all three groups. When the two groups of flushers were re-tested with the addition of an infusion of naloxone a rise in plasma IR-met-enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR-met-enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR-met-enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR-met-enkephalin.

Administration, Oral↗
PubMed1984

Measurement of immunoreactive gamma-MSH in human plasma.

A radioimmunoassay for immunoreactive gamma-MSH (IR-gamma-MSH) in human plasma has been developed. The assay is capable of detecting normal basal circulating levels which range from less than 20-100 ng/1 at 0900 h. Plasma levels are raised concomitantly with ACTH during insulin induced hypoglycaemia and CRF stimulation and suppressed with dexamethasone. Chromatographic characterisation of IR-gamma-MSH in plasma demonstrates a major peak of IR-gamma-MSH, corresponding to purified glycosylated N-terminal pro-opiomelanocortin 1-76, when IR-gamma-MSH is secreted from the pituitary. In contrast IR-gamma-MSH produced ectopically appears to be heterogeneous.

ACTH Syndrome, Ectopic↗
PubMed1984

Response of circulating somatostatin, insulin, gastrin and GIP, to intraduodenal infusion of nutrients in normal man.

We have studied the effect of direct infusion of nutrients into the duodenum of normal subjects on circulating plasma somatostatin, insulin, gastrin and gastric inhibitory polypeptide (GIP) levels. Six normal subjects were given on four separate occasions 150 ml of isotonic solutions containing 100 calories of carbohydrate, protein, or fat, and a control solution of saline, by infusion into the second part of the duodenum. Plasma somatostatin rose slightly after carbohydrate, mean basal 30 +/- 3 pg/ml, peak 46 +/- 16 pg/ml at 15 min; and more markedly after protein, peak 57 +/- 9 pg/ml at 30 min. However, fat was the most potent intraduodenal stimulus to plasma somatostatin release into circulation, peak 101 +/- 11 pg/ml at 30 min. The plasma insulin rise was greatest after carbohydrate, peak 68 +/- 10 i.u., but there was a significant rise after protein also, peak 34 +/- 6 i.u. Plasma gastrin rose significantly after protein only, peak 70 +/- 22 pg/ml. Plasma GIP rose markedly after carbohydrate, basal 506 +/- 50 pg/ml, peak 1480 +/- 120 pg/ml. Protein was also a potent stimulus of circulating plasma GIP release, peak 1200 +/- 190 pg/ml, while fat was the least potent, peak 730 +/- 190 pg/ml. Thus, calorie for calorie, fat is the most potent intraduodenal nutrient stimulus of circulating somatostatin. We postulate therefore that somatostatin may be an enterogastrone--a circulating hormone released by intraduodenal fat which inhibits gastric acid secretion. Fat is the least potent intraduodenal nutrient stimulus of circulating GIP release. This is evidence against the hypothesis that circulating GIP acts as an enterogastrone.

Adult↗
PubMed1984

Responses to analogues of growth hormone-releasing hormone in normal subjects, and in growth-hormone deficient children and young adults.

Three analogues of growth hormone-releasing hormone (GHRH) have been compared in normal subjects. GHRH(1-29)NH2 is equipotent to GHRH(1-40); increasing doses from 10-200 micrograms per subject augments the duration of stimulated growth hormone (GH) release, but the peak serum GH shows only a poor correlation with dose. The derivative D-Ala2-GHRH(1-29)NH2 is no more potent than the unsubstituted GHRH(1-29)NH2. In 20 children and young adults with growth hormone deficiency by conventional criteria, eight showed normal or only slightly subnormal peak serum GH responses to GHRH(1-40) or GHRH(1-29)NH2. These included two patients with tumours of the hypothalamus, as well as six with idiopathic isolated growth hormone deficiency or panhypopituitarism. A poor response to GHRH was generally seen in patients on long-term GH therapy. Priming with GHRH, in either a single bolus or a continuous infusion, did not increase the GH response to GHRH. It is concluded that GHRH(1-29)NH2 is a useful analogue in the testing of GH reserve in patients with growth hormone deficiency, and has considerable potential for long-term therapy.

Adolescent↗
PubMed1984

Does gastric acid release plasma somatostatin in man?

Food and insulin hypoglycaemia raise plasma concentrations of somatostatin. Both also stimulate gastric acid secretion but it is not clear whether gastric acid itself has any effect on somatostatin secretion. We, therefore, studied the effect on plasma concentrations of somatostatin of infusion of 0.1 N HC1 into the stomach and duodenum of healthy subjects. Plasma somatostatin did not rise with a small dose of HC1 given intragastrically (15 mmol) or intraduodenally (4 mmol). After an intraduodenal infusion of 60 mmol HC1 over 30 minutes, sufficient to reduce intraluminal pH to 2, plasma somatostatin rose moderately in five subjects from a mean value (+/- SEM) of 32 +/- 3 pg/ml to a peak at 10 minutes of 54 +/- 11 pg/ml. It is concluded that: (a) intragastric acid infusions do not release circulating somatostatin in man; and (b) that intraduodenal acidification albeit at grossly supraphysiological doses is a moderate stimulus of plasma somatostatin release. Therefore, gastric acid is unlikely to be a major factor mediating postprandial plasma somatostatin release in man.

Adult↗
PubMed1984

CRF-41 stimulates the release of beta-lipotrophin and beta-endorphin in normal human subjects.

A prompt rise in circulating immunoreactive N- and C-terminal lipotrophin (LPH) accompanied the increase in ACTH when 100 micrograms CRF-41 was given to 6 normal male subjects. Chromatography of the basal and peak 15-min values showed that there was an equimolar increase in beta-LPH and beta-endorphin, to cause parallel release of ACTH, beta-endorphin and beta-LPH from the pro-opiocortin precursor.

Adult↗
PubMed1984

Glucose modulation of somatostatin and LHRH release from rat hypothalamic fragments in vitro.

In the rat, hypoglycaemia inhibits growth hormone secretion, but the mechanism is unclear. To investigate this further, we have studied the effects of glucose and 2-deoxy-D-glucose on somatostatin and LHRH release from rat hypothalamic fragments incubated in vitro. Glucose (1.35-22 mM) was added to glucose-free medium and 5 and 50 mM 2-deoxy-D-glucose were added to medium containing 5.5 mM glucose. Medium somatostatin and LHRH levels were measured by RIA. Somatostatin and LHRH released diluted in parallel with synthetic somatostatin and LHRH. Sephadex gel filtration demonstrated two molecular forms of somatostatin, 70% coeluting with somatostatin-14 and 30% with somatostatin-28; LHRH coeluted with synthetic LHRH. KCl (30-100 mM) resulted in release of somatostatin and LHRH; this was reduced in calcium-free medium. Basal and K+-stimulated somatostatin release were significantly increased by reducing glucose levels (r = -0.6, p less than 0.001). Basal LHRH was not influenced by glucose. Basal and K+-induced somatostatin release were significantly increased by 2-deoxy-D-glucose (p less than 0.05), while LHRH levels remained unchanged. Our results demonstrate that basal and K+-induced somatostatin release from rat hypothalamic fragments are modulated by local glucose concentrations, and this effect is specific as it is not paralleled by LHRH changes. We suggest that the reduction in growth hormone secretion during hypoglycaemia in the rat might be mediated, at least in part, via a direct effect of glucose on somatostatin release.

Animals↗
PubMed1984

Corticotrophin-releasing factor--mediated adrenocorticotrophin release from rat anterior pituitary cells is potentiated by C-terminal gastrin-releasing peptide.

The remission of Cushing's syndrome following surgical removal of a tumour containing bombesin-like immunoreactivity (BLI), but insignificant levels of ACTH, is described. However, an acid extract of the tumour tissue caused the release of ACTH from isolated rat anterior pituitary cells in vitro. These observations led to an investigation of the effects of synthetic C-terminal gastrin-releasing peptide (GRP(14-27] on ACTH release from isolated rat anterior pituitary cells. GRP(14-27) (10-1000 ng/ml) directly stimulated the release of ACTH in vitro, whereas lower doses (10-1000 pg/ml), ineffective themselves in eliciting ACTH release, potentiated the CRF-mediated in-vitro release of ACTH.

ACTH Syndrome, Ectopic↗
PubMed1983

Endorphin-related peptides in rat cerebrospinal fluid.

Cerebrospinal fluid (CSF) samples were taken from rats implanted with chronic cisternal cannulae and assayed for methionine-enkephalin, beta-endorphin and corticotropin (ACTH). Immobilization stress had little apparent effect on immunoreactive levels of the peptides in the CSF. Gel chromatographic analysis of the beta-endorphin- and ACTH-immunoreactive profiles in rat CSF revealed several peaks. beta-Endorphin-immunoreactive peaks were present at the expected positions of pro-opiocortin, beta-lipotropin and beta-endorphin. ACTH-immunoreactive peaks eluted at positions corresponding to pro-opiocortin, the 20-23K ACTH biosynthetic intermediate, 14K ACTH, and 4.5K ACTH. These results suggest that rat CSF contains peptides of the pro-opiocortin family similar to those previously described in rat pituitary.

Adrenocorticotropic Hormone↗
PubMed1983

Gonadal function in men treated for acute leukaemia.

Gonadal function was assessed in eight men in remission of leukaemia who had completed treatment eight months to eight years previously. All four men treated for acute myeloid leukaemia had normal sperm counts and motility, compared with only one of the four with acute lymphatic or undifferentiated leukaemia. Hormonal studies indicated that the sterility resulted from gonadal failure rather than pituitary dysfunction after cranial irradiation. These findings are important in the counselling of patients with leukaemia.

Acute Disease↗
PubMed1983

Raised plasma metenkephalin in patients who habitually mutilate themselves.

Mean plasma metenkephalin concentration was significantly higher in ten patients who habitually mutilated themselves than in matched, healthy controls. No differences were found in corticotropin, N-lipotropin or C-lipotropin (beta-endorphin). Plasma metenkephalin was raised only in the five patients receiving hospital treatment because of their behaviour disorder. It was not raised in those patients sufficiently well to have been discharged from hospital.

Adult↗
PubMed1983

Chlorpropamide-ethanol induced met-enkephalin secretion in dogs: release mechanisms and biochemical characterisation.

Circulating met-enkephalin-like immunoreactivity (MLI) rises in man after chlorpropamide and ethanol although the origin and molecular forms of circulating MLI are not well defined. We have studied the response to oral ethanol in conscious and anaesthetised dogs pretreated with chlorpropamide. In conscious dogs MLI rose from a basal level of 29 +/- 7 pg/ml to a peak of 55 +/- 14 pg/ml 10 min after ethanol (P less than 0.001). In anaesthetised animals, following ethanol, plasma MLI rose in caval (35 +/- 6 pg/ml to a peak of 70 +/- 10 pg/ml), in portal (28 +/- 6 pg/ml to 51 +/- 6 pg/ml) and in adrenal blood (897 +/- 316 pg/ml to 1483 +/- 298 pg/ml; P less than 0.001). Biogel P-4 chromatography of caval and portal basal plasma showed 87% of MLI measured coeluted with the synthetic pentapeptide, while chromatography of peak plasma showed that only 65% coeluted with the pentapeptide and the remaining 35% was of larger molecular size. Sephadex G75 chromatography of adrenal vein plasma revealed three peaks of MLI of differing molecular sizes (8 k = 69.7%; 3-5 k = 12.1% and the pentapeptide = 18.2%). Treatment of the column fractions with trypsin and carboxypeptidase B resulted in the generation of new MLI with peaks of approximate molecular sizes 31 k (10.4%), and 18 k (37.1%) in addition to 8 k (40.0%), 3-5 k (5.0%) and the pentapeptide (7.5%). Acetaldehyde involvement in MLI release was investigated. Following acetaldehyde infusion, plasma MLI rose both in caval (35 +/- 9 pg/ml to 86 +/- 8 pg/ml) and adrenal vein (417 +/- 121 pg/ml to 1768 +/- 433 pg/ml) bloods. Thus we have established an animal model which enables further study of the mechanisms of MLI release and characterisation of the molecular forms. The adrenal medulla, unlike the gut, may be an important source of circulating met-enkephalin and acetaldehyde formation an essential intrinsic component of chlorpropamide-ethanol induced met-enkephalin release.

Acetaldehyde↗
PubMed1983

Characterisation of bombesin-like immunoreactivity in human fetal lung.

A sensitive radioimmunoassay for bombesin-like immunoreactivity (BLI) was developed and utilised in conjunction with G50 gel chromatography and reverse-phase HPLC, to study the content and molecular characteristics of bombesin-like peptides in acid extracts of human fetal lung. The antiserum, (B5), is directed towards the C-terminal region of the bombesin molecule and cross-reacts 70% with synthetic porcine GRP and the synthetic GRP fragment, GRP (14-27). Specimens of lung were collected from fetuses of gestational ages 15-22 weeks, following prostaglandin termination of pregnancy. The tissue was extracted into 0.1 N HCl at 90 degrees C. The mean BLI content was 50.2 pg/mg wet weight of tissue (range 15.5-136 pg/mg; n = 13). No correlation between gestational age and BLI content could be established. G50 gel chromatography of acid extracts, under dissociating conditions, revealed two peaks of BLI, one in the position of synthetic porcine GRP and the second, constituting greater than 90% of the immunoreactivity, eluting with synthetic amphibian bombesin. Reverse-phase ODS silica HPLC of this major G50 peak, utilising a methanol/trifluoroacetic acid gradient, indicated that this peptide was similar to the GRP C-terminal fragment, GRP (14-27). We have therefore (1) confirmed the presence and heterogeneity of BLI in human fetal lung, and (2) shown, for the first time, that the majority of this BLI more closely resembles a fragment of GRP than amphibian bombesin itself.

Bombesin↗
PubMed1983

Characterisation of immunoreactive somatostatin in human fetal hypothalamic tissue.

Levels of immunoreactive somatostatin (IRS) were measured in extracts of hypothalamic tissue from human fetuses of 12-26 weeks gestation. The IRS contents (0.7-22.5 ng) and concentrations (2.7-118.0 pg/mg wet weight tissue) both increased slightly with gestation. Sephadex G-50 chromatography of 11 extracts showed up to four peaks of IRS, one co-eluting with synthetic somatostatin-14 (S14), a second co-eluting with synthetic somatostatin-28 (S28) and two other peaks having approximate molecular weights of 6000 and 10 000, respectively. The levels of S14 and S28 increased significantly during gestation, while the levels of 6000 molecular weight IRS decreased with age. We suggest that the increase in S14 and S28 levels may be the cause of the fall in circulating growth hormone (GH) in the fetus in later gestation.

Female↗
PubMed1983

Evidence for direct production of somatostatin-14 from a larger precursor than somatostatin-28 in a phaeochromocytoma.

Gel-filtration chromatography of an acid-extract of a phaeochromocytoma, under dissociating conditions, revealed 4 peaks of immunoreactive somatostatin (IRS) of approx. 8-10 kilodaltons (K), 6K, 3.5K and 1.6K as detected by an antiserum (R9) directed against the central region of tetradecapeptide somatostatin (S14). The 3.5K and 1.6K forms of IRS co-eluted with synthetic cyclic S28 and S14 respectively on reversed phase HPLC. Using another radioimmunoassay for the 1-14 sequence of S28 (N-peptide) a peak of immunoreactive N-peptide (IRN) with a molecular weight of approx. 4500 was observed. The antiserum (N3) used in the N-peptide assay was raised against N-Tyr N-peptide and cross-reacts less than 5% with synthetic S28. Two peaks were further characterised by partial tryptic digestion and gel-filtration chromatography. The 3.5K IRS peak was partially converted to a 1.6K IRS form together with an approximately equimolar amount of IRN with apparent molecular weight of 2500. This 2.5K IRN co-eluted both with N-Tyr N-peptide and with the IRN generated by tryptic digestion of synthetic cyclic S28. No IRN peak of this size was observed in the original extract. Tryptic digestion of the 6K IRS peak generated 3.5K and 1.6K IRS and 2.5K IRN. These results suggested that (1) this human phaeochromocytoma contains IRS very similar to the known structure of ovine and porcine S28 and S14. (2) The 6K IRS is composed of an unknown peptide sequence attached via trypsin-susceptible bond to the N-terminus of S28. (3) In this tumour S14 is being generated directly from 6K IRS and not via S28.

Adrenal Gland Neoplasms↗
PubMed1983

Distribution and characterisation of immunoreactive somatostatin in human gastrointestinal tract.

Immunoreactive somatostatin (IRS) was measured in acid extracts of human gastrointestinal tissue. The highest levels were found in the duodenum, pancreas, jejunum and stomach with lower levels in the ileum and colon. In the antrum, pylorus, duodenum and pancreas the main peak of IRS (1.6K IRS) coeluted with synthetic somatostatin-14 on both gel filtration chromatography and HPLC. In the body of stomach, jejunum, ileum and colon, a large peak coeluting with synthetic somatostatin-28 (3.5K IRS) on both chromatographic systems was also identified, while minor peaks of IRS assigned molecular weights of 6000 (6K) and greater than 15 000 (15K) were seen in some extracts. The total IRS content and pattern of molecular forms were similar in tissues obtained from adults at surgery or rapid post mortem, and in tissue taken from human fetuses after prostaglandin termination of pregnancy. When tissues were divided into mucosal and muscle layers, greater than 90% of the IRS was in the mucosa with less than 10% in the muscle layer. In the muscle layer the IRS was almost entirely the 1.6K form in all tissues. Immunohistochemical studies showed the IRS in the mucosa to be localised in endocrine-type cells, while in the muscle layer the IRS is present in nerve fibres and neurones of the myenteric plexus. It is suggested that (1) different mechanisms may control the biosynthesis of somatostatin-14 and somatostatin-28 in mucosal cells in different parts of the gut, (2) different biosynthetic controls may operate in endocrine-like and neuronal cells in the same region of the gut.

Chromatography, High Pressure Liquid↗