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Biomedical subjects

G M Besser

Publications and source records attributed to G M Besser.

At least 379 records · Page 21Linked to original sources
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

Response of luteinizing hormone from columns of dispersed rat pituitary cells to a highly potent analogue of luteinizing hormone releasing hormone.

The response of LH from a perfused column of dispersed rat anterior pituitary cells to LH releasing hormone (LH-RH) and the analogue, D-Ser(But)6-desGly10-Proethylamide9-LH-RH (Hoe 766), was investigated. Dose-response curves showed non-parallelism between LH-RH and the analogue. but it was evident that the analogue was considerably more potent. After a single pulse of LH-RH, LH output returned to basal values in 8 min; this was prolonged to 20 min in the case of the analogue. During this 20 min the cells were refractory to pulses of LH-RH but pulses of the analogue maintained output of LH. During constant-dose perfusion with either synthetic LH-RH or the analogue, output of LH rapidly reached a peak and then gradually fell over several hours to approach baseline values. However, a pulse of 50 mmol potassium chloride/l was still able to release LH at this time. The data are consistent with the view that this analogue of LH-RH is highly potent and is strongly bound by the LH-RH receptor. Furthermore, since it desensitizes the LH-RH receptor, it appears that continued turnover of either LH-RH or the analogue at the receptor is necessary for output of LH to be maintained.

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↗
PubMed1981

In vitro studies on the effects of ranitidine on isolated anterior pituitary and adrenal cells.

The effects of ranitidine on anterior pituitary and adrenal function have been studied using isolated perfused rat anterior pituitary and zona glomerulosa cells. Ranitidine did not have pituitary hormone releasing activity with respect to LH, TSH, GH and ACTH. It also did not alter prolactin secretion in experiments designed to test whether it acted as a dopamine agonist or antagonist. In the adrenal cell studies ranitidine infusion stimulated basal aldosterone secretion and inhibited the release of aldosterone in response to angiotensin II, but not to ACTH. These experiments suggest that ranitidine is unlikely to alter pituitary hormone secretion by a direct action on the pituitary. The drug, however, can affect aldosterone secretion in vitro and further in vivo studies are required to elucidate the significance of this.

Adrenal Cortex↗
PubMed1980

Inhibition of vasopressin release in man by an opiate peptide.

The opiate control of vasopressin secretion in man was investigated with a long-acting analogue of met-enkephalin, DAMME (FK33-824, Sandoz). Infusion of 1 mg DAMME into water-deprived volunteers produced a diuresis which was attenuated by naloxone; there was no change in water excretion when subjects were hydrated. Plasma-immunoreactive-vasopressin failed to rise after DAMME administration, despite osmotic stimulation with hypertonic saline infusion. Opiates appear to be involved in mechanisms which suppress the osmotically mediated release of vasopressin, while opiate involvement in baroceptor-mediated release may be quite different.

Adolescent↗
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

A cytochemical section-bioassay for thyrotropin.

A cytochemical section-bioassay of thyrotropin has been developed which retains the sensitivity of the earlier segment-assay (10(-4) microunits/ml) and allows a considerable increase in the rate at which these within-animal bioassays can be done. The index of precision (n=23) was 0.11 +/- 0.06; intra-assay variation was 1.3%; inter-assay variation was 10.9 +/- 6%. Fiducial limits (p = 0.95) ranged from 65-150% to 78-127%. The system is also capable of detecting thyroid-stimulating immunoglobulins.

Aminopeptidases↗
PubMed1980

The effect of cyproterone acetate on serum testosterone, LH, FSH, and prolactin in male sexual offenders.

The anti-androgen, cyproterone acetate, was administered in a dose of 100 mg/day to eight adult male sexual offenders for 21-31 days. Serum testosterone fell to subnormal levels within 7 days and remained low for 6-28 days after treatment was stopped. The fall in testosterone was accompanied by a fall in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), and a rise in serum prolactin. All subjects experienced a decrease in libido and in frequency of masturbation. The probable mechanisms of action of cyproterone acetate are discussed, as is its potential role in the management of sexual offenders. These studies suggest that measurement of serum testosterone could be used as an index of compliance in sexual offenders treated with cyproterone acetate who are released on parole.

Adult↗
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↗