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Biomedical subjects

G M Besser

Publications and source records attributed to G M Besser.

At least 397 records · Page 22Linked to original sources

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↗

Pituitary and testicular fibrosis in association with retroperitoneal fibrosis.

A patient is discussed who originally presented with retroperitoneal fibrosis, and subsequently developed both pituitary fibrosis and testicular fibrosis. Replacement of testicular tissue by fibrosis has not previously been described in this condition, while we have only been able to find a single previous report of pituitary fibrosis. Fibrous replacement of testis and pituitary should be considered as a further manifestation of the midline fibrosing syndrome.

Adult↗

Endocrine function in the Prader-Willi syndrome.

Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader-Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous ater 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormonal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader-Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities.

Adolescent↗

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↗

Two new dopamine agonists that are long acting in vivo but short acting in vitro.

The effects of two new ergolines, pergolide and CH29-717, on prolactin secretion in vitro and in vivo were compared with those of bromocriptine. Both ergolines had in vitro potencies similar to that of bromocriptine, but had a shorter duration of action. However, in vivo both were longer acting than bromocriptine after a single dose of 100 micrograms, and effectively suppressed prolactin secretion for greater than 24 h. It would appear that the pharmacokinetics of these ergolines are different to those of bromocriptine, and this may have considerable therapeutic importance.

Animals↗

Somatostatin secretion by lung and thymic tumours.

Ectopic secretion of somatostatin in one patient with a thymic tumour and in two patients with lung tumours is described. All three patients also had ectopic ACTH secretion. Gel filtration chromatography under dissociating conditions showed the two lung tumour extracts to contain predominantly 1600 MW somatostatin monomer while the thymic tumour contained predominantly a 3000-3500 MW form of somatostatin, 77% of which was not converted to 1600 MW somatostatin by dithiothreitol (an agent which reduces disulphide bridges). This form may therefore represent a covalently-bound precursor of somatostatin rather than a dimer of two somatostatin monomers. Plasma from all three tumour patients and from normal subjects contained both 1600 and 3000--3500 MW somatostatin. It is suggested that somatostatin secretion may frequently be associated with multiple hormone producing tumours.

ACTH Syndrome, Ectopic↗

Metergoline and cyproheptadine suppress prolactin release by a non-5-hydroxytryptaminergic, non-dopaminergic mechanism.

A dispersed rat anterior pituitary cell system has been used to investigate the effects of cyproheptadine and metergoline on prolactin secretion. Both drugs were potent inhibitors of prolactin secretion. However, the inhibition was not antagonized by either 5-hydroxytryptamine or a variety of dopamine antagonists. We conclude that both drugs act through mechanisms that are neither 5-hydroxytryptaminergic nor dopaminergic.

Animals↗

Chlorpromazine, haloperidol, metoclopramide and domperidone release prolactin through dopamine antagonism at low concentrations but paradoxically inhibit prolactin release at high concentrations.

1. The effects of chlorpromazine, haloperidol, metoclopramide and domperidone on the release of prolactin from perfused columns of dispersed rat anterior pituitary cells were studied. 2. Chlorpromazine, haloperidol, metoclopramide and domperidone antagonized the dopamine-mediated inhibition of prolactin release at low concentrations. 3. Each dopamine antagonist displaced the dose-response curve for dopamine-induced suppression of prolactin release to the right in a parallel manner. 4. At higher concentrations, the four drugs became less effective as dopamine antagonists. 5. At high concentrations in the absence of dopamine, chlorpromazine, haloperidol, metoclopramide and domperidone paradoxically suppressed prolactin secretion by an unknown mechanism.

Animals↗

Chromatographic characterization of adsrenocorticotrophin in human plasma.

A chromatographic procedure has been developed for the characterization of ACTH- and lipotrophin- (LPH) related peptides in human plasma under acid-dissociating conditions to minimize artifacts of protein binding. The recovery and sensitivity of this method permits identification of ACTH at normal physiological levels in the circulation. Plasma profiles obtained from normal subjects and patients with pituitary dependent Cushing's disease, Addison's disease and Nelson's syndsrome showed only one significant peak of ACTH activity eluting in the position of purified native human 1--39 ACTH. However, the plasma profiles obtained from all the patients with the ectopic ACTH syndrome demonstrated a second peak of immunoreactive larger-molecular-weight ACTH and in some plasma samples this was the only form of ACTH observed. This larger-molecular-weight ACTH eluted midway between the void volume and 1--39 ACTH and co-eluted with a protein marker of molecular weight 22 000.

ACTH Syndrome, Ectopic↗

Development of a specific extracted radioimmunoassay for methionine enkephalin in human plasma and cerebrospinal fluid.

A sensitive extracted radioimmunoassay for methionine enkephalin (met-enkephalin) has been developed which allows measurement of its concentration in human plasma and cerebrospinal fluid (CSF). The first evidence for the existence of met-enkephalin in the circulation of man is described and its presence in CSF confirmed. The susceptibility of the methionine residue in met-enkephalin to undergo oxidation to the methionine sulphoxide analogue was utilized. All extracted samples were oxidized by hydrogen peroxide before assay and this allowed measurement of total met-enkephalin. The assay had unique specificity with no cross-reaction with leucine enkephalin, purified human beta-endorphin or beta-lipotrophin (beta-LPH). A purification method for radio-iodinated enkephalin has been developed with octadecasilyl-silica (ODS-silica) (10 micrometers) yielding a high-affinity mono-iodinated tracer stable on storage for up to 3 months at 4 degrees C. A method to extract met-enkephalin from acidified plasma or CSF has been developed with larger particle size ODS-silica (35-70 micrometers) suitable for extracting repeated samples. Met-enkephalin immunoreactivity was detectable in plasma of all subjects tested and ranged from 14 to 140 pg/ml. In CSF, however, the range was 5-29 pg/ml. Met-enkephalin immunoreactivity was not generated by incubating exogenous or endogenous beta-LPH and beta-endorphin in plasma or CSF. Two hypopituitary subjects and one dexamethasone-suppressed subject, all with undetectable immunoreactive plasma adrenocorticotrophic hormone and NH2- and CO2H-terminal beta-LPH, had measurable met-enkephalin in their plasma suggesting met-enkephalin was not of pituitary origin nor a breakdown product of secreted beta-LPH or beta-endorphin.

Endorphins↗

A comparison of the effects of four ergot derivatives on prolactin secretion by dispersed rat pituitary cells.

The inhibitory effects of dopamine and various ergot alkaloids on prolactin secretion were studied using continuously perfused columns of dispersed rat anterior pituitary cells. Bromocriptine (5 nmol/l) and lisuride hydrogen maleate (5 nmol/l) both inhibited prolactin secretion, the effects persisting for more than 3 h after the end of the administration of the drugs. A similar although less long-lasting effect was observed with lergotrile (50 nmol/l) and the new ergoline derivative, pergolide (5 nmol/l). These effects contrasted with the rapid disappearance of the action of dopamine. The potency estimates of the ergots relative to that of dopamine were: lergotrile, 2.3; bromocriptine, 13; lisuride, 15; pergolide, 23. Ther dopamine-receptor blocking drugs, metoclopramide and haloperidol, antagonized the prolactin release-inhibiting activity of the compounds; bromocriptine and lisuride showed the highest resistance to this dopaminergic blockade. The results suggested that the direct effect of the ergot derivatives on dispersed pituitary cells was mediated through dopamine receptors and emphasized the long-lasting action of bromocriptine and lisuride in vitro.

Animals↗