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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 595 records · Page 33Linked to original sources
PubMed1986

Effective and lasting growth-hormone suppression in active acromegaly with oral administration of somatostatin analogue SMS 201-995.

Oral administration of the long-acting somatostatin analogue, SMS 201-995 (Sandoz), was assessed in five patients with active acromegaly, four of whom had not responded to pituitary irradiation. Doses of 4-8 mg three times daily lowered mean 24 h growth-hormone concentrations by over 50% in every case, with suppression to below 10 mU/l for several hours after the morning dose. Despite effective suppression of serum insulin levels, deterioration in glucose tolerance was very slight, and the drug had no side-effects. Orally administered SMS 201-995 avoids the need for multiple daily injections and is potentially valuable in the medical treatment of acromegaly.

Acromegaly↗
PubMed1986

Characterization of a novel prepro VIP derived peptide.

A newly identified, large molecular weight form of peptide histidine methionine (PHM), has been found not only where it was first revealed, in the stomach, but also in high concentrations in the nasal mucosa and urogenital system, though not in the central nervous system, intestine and lung. An antibody to the spacer peptide sequence prepro-VIP 111-122, lying between PHM and VIP, also reacts directly with the large molecular form of PHM. It is suggested that the post-translational processing of prepro-VIP differs between tissues and in some, cleavage may not occur at the C-terminal end of PHM. The biological significance of this is currently unclear.

Amino Acid Sequence↗
PubMed1986

Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors.

Pancreatic polypeptide is often secreted by pancreatic endocrine tumors and is considered a marker for such tumors. To investigate the diagnostic value of this marker, we studied 323 patients with proved pancreatic endocrine tumors. We found plasma concentrations of pancreatic polypeptide to be elevated (more than 300 pmol per liter) in 144 patients (diagnostic sensitivity, 45 percent). However, plasma levels of pancreatic polypeptide can also be elevated in the absence of a pancreatic tumor. To ascertain whether the administration of atropine could distinguish between normal and tumor-associated polypeptide secretion, we studied 30 patients with pancreatic tumors and high plasma levels of pancreatic polypeptide, 18 patients without tumors who had elevated levels of pancreatic polypeptide, and eight normal controls. Polypeptide levels in the 18 patients without tumors were substantially lower than in the 30 patients with tumors. Atropine (1 mg intramuscularly) did not suppress polypeptide levels in patients with tumors, but did suppress plasma levels by more than 50 percent in all subjects without tumors. Thus, although its diagnostic sensitivity is low, pancreatic polypeptide appears to be a useful adjunctive marker of many pancreatic endocrine tumors, and the atropine suppression test can be used to distinguish normal from tumor-related secretion of the polypeptide. Identification of the type of pancreatic endocrine tumor still requires measurement of the hormone that is specific for the tumor.

Adenoma, Islet Cell↗
PubMed1986

Growth hormone release in man induced by galanin, a new hypothalamic peptide.

Galanin, a 29-aminoacid neuropeptide, was infused for 60 min into healthy volunteers at 7.8 pmol/kg/min (n = 4) or 33.2 pmol/kg/min (n = 6). During the infusion there was no change in heart rate or blood pressure and the only symptoms were a transitory bitter taste and slight hypersalivation. Plasma growth hormone levels rose during the high-dose galanin infusion from 2.8 +/- 0.8 mU/l to a mean peak of 48.5 +/- 19.8 mU/l; prolactin levels rose from 176 +/- 33 mU/l to 274 +/- 33 mU/l. A significant rise in growth hormone also occurred with the low-dose infusion (2.5 +/- 1.1 mU/l to a mean peak of 23.5 +/- 6.6 mU/l). There was no change in cortisol, thyroid-stimulating hormone, follicle-stimulating hormone, or luteinising hormone at either dose. 20 min after the start of the infusion a 25 g glucose bolus was given intravenously. Galanin reduced glucose clearance without significantly affecting plasma insulin concentrations. Pancreatic polypeptide levels were suppressed by the galanin infusion but levels of glucagon and gastric inhibitory peptide were unchanged.

Adult↗
PubMed1986

Chromatographic evidence for high-molecular-mass galanin immunoreactivity in pig and cat adrenal glands.

Galanin was measured by radioimmunoassay in extracts of pig, cat and rat adrenals using non-C- and mid to C-terminally directed antibodies. The extracts were fractioned by gel chromatography and HPLC. The non-C-terminal galanin immunoreactivity in pig was 92.8 +/- 11.7 pmol/g, in cat 9.1 +/- 0.9 pmol/g and in rat less than 1 pmol/g. Two higher molecular forms of galanin have been identified in both pig and cat adrenal. One major large form behaves as if it was N-terminally extended (Kav pig 0.58, cat 0.48) and the other, a very high-molecular-mass form (Kav pig 0.10, 0.24, cat 0.10), as if it had both N- and C-terminal extensions.

Adrenal Glands↗
PubMed1986

Regional distribution of a novel peptide (P7 of 1B236) immunoreactivity in the human central nervous system.

The regional distribution of a novel peptide (P7 of 1B236) in the human central nervous system (CNS) was examined. P7-like-immunoreactivity (p7-LI) was shown to be distributed throughout the CNS, with a chromatographic pattern closely similar to that previously described in rat. In the brain the concentrations of P7-LI were higher in the globus pallidus and substantia nigra than in any other regions. Considerable amounts of P7-L1 were also found in the cerebellum. In the spinal cord the concentration of P7-L1 was slightly higher in the ventral than in the dorsal cord, though no difference in concentration was found between cervical, thoracic, lumbar and sacral regions. The distribution pattern of this novel peptide reveals its predominance in sub-cortical motor areas. Studies of its pharmacological effects and possible role in movement disorders are awaited with interest.

Adult↗
PubMed1986

Remission of symptoms during long term treatment of metastatic pancreatic endocrine tumours with long acting somatostatin analogue.

Five patients with metastatic pancreatic endocrine tumours injected a long acting somatostatin analogue (SMS 201-995) 50 micrograms subcutaneously every 12 hours and were followed up for three to six months. Treatment aimed at controlling excess secretion of hormone by the tumours thereby bringing symptomatic relief. Four patients showed a significant reduction in tumour related hormone concentrations but in none did values return to normal. All five patients, however, noted definite symptomatic improvement and in one this was dramatic (disappearance of life threatening diarrhoea and correction of metabolic acidosis and hypokalaemia within 48 hours). Mild worsening of symptoms and increasing fasting tumour related hormone concentrations after three to six months of treatment were reversed by doubling the 12 hourly dose. The treatment was well tolerated and had no deleterious effect on fasting blood glucose concentrations. This somatostatin analogue seems a promising non-invasive treatment for metastatic pancreatic endocrine tumours.

Adult↗
PubMed1986

Effectiveness of SMS 201-995, a synthetic, long-acting somatostatin analogue, in treatment of quinine-induced hyperinsulinaemia.

SMS 201-995, a new long-acting, synthetic somatostatin analogue, dose 50 micrograms/h, given as a continuous intravenous infusion, completely abolished quinine-induced insulin release in 9 healthy Thai volunteers. Hyperinsulinaemia, which caused sustained hypoglycaemia in a 32-year-old post-partum Thai patient who was receiving intravenous quinine for falciparum malaria, was suppressed within 30 min of starting SMS 201-995, and the patient became fully conscious. This octapeptide antagonises the stimulatory effect of quinine on the pancreatic beta cell and is a specific therapy for life-threatening hyperinsulinaemic hypoglycaemia complicating falciparum malaria.

Adult↗
PubMed1986

Combined use of vasopressin and synthetic hypothalamic releasing factors as a new test of anterior pituitary function.

Nine normal volunteers and 15 patients with pituitary disorders were given a combined test of anterior pituitary function using four hypothalamic releasing factors and arginine vasopressin. Rapid sequential intravenous infusions of human corticotrophin releasing factor 100 micrograms, growth hormone releasing factor 100 micrograms, luteinising hormone releasing hormone 100 micrograms, and thyrotrophin releasing hormone 200 micrograms were administered. Arginine vasopressin (10 pressor units) was given intramuscularly at the same time. Plasma or serum samples were assayed for concentrations of cortisol, growth hormone, luteinising hormone, follicle stimulating hormone, prolactin, and thyroid stimulating hormone at multiple times for 120 minutes. No troublesome side effects occurred. The results of the releasing factor combined test with arginine vasopressin were compared in the same subjects with a conventional combined test using insulin together with thyrotrophin releasing hormone and luteinising hormone releasing hormone. No difference was observed in the basal and peak concentrations of luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone, and prolactin. Both cortisol and growth hormone responses to the releasing factors with arginine vasopressin were much greater than those seen with insulin induced hypoglycaemia or the combined releasing factors without arginine vasopressin. Patients with pituitary hypo-function were similarly recognised in both studies. There was a rapid increase in all hormone values with a peak usually by 60 minutes. In most people adequate assessment of individual hormone reserves may be achieved using basal, 30 minute, and 60 minute samples. This new combined releasing factor test appears to be a safe, rapid, and useful test of anterior pituitary function.

Adult↗
PubMed1986

Calcitonin gene-related peptide-immunoreactive nerves in the tongue, epiglottis and pharynx of the rat: occurrence, distribution and origin.

The occurrence, distribution and nature of calcitonin gene-related peptide (CGRP) in the tongue, epiglottis and pharynx of the rat was investigated by immunocytochemistry and radioimmunoassay. Numerous CGRP-containing nerves were found to innervate and terminate freely within the epithelium of the tongue, epiglottis and pharynx. Immunoreactive fibres were also found in the muscle layer and around blood vessels in the tongue, and in motor end plates in the muscle of the epiglottis and pharynx. Section of the trigeminal nerve induced a marked reduction in the number of immunoreactive nerves in the anterior portion of the tongue, whereas glossopharyngeal denervation results in a depletion of CGRP immunoreactivity in the posterior portion of the tongue. Immunoreactive nerves of the epiglottis and pharynx were depleted only after superior laryngeal nerve section. A subpopulation of labelled primary sensory neurones were observed in trigeminal and glossopharyngeal ganglia following injection of True blue retrograde tracer in the tongue. Most of the labelled cells were also immunoreactive for CGRP. Following systemic treatment with capsaicin, a loss of intra- and subepithelial CGRP-immunoreactive nerves was observed in all investigated tissues, while immunoreactive motor end plates remained unchanged.

Animals↗
PubMed1986

Is the C-terminal flanking peptide of rat cholecystokinin double sulphated?

A specific radioimmunoassay was developed to the predicted nine amino acid C-terminal flanking peptide of cholecystokinin (peptide serine serine, PSS). In aqueous extracts of rat brain, PSS was undetectable unless the extracts were first treated with arylsulphatase, which also resulted in desulphation of cholecystokinin. The reverse-phase HPLC analysis of partially desulphated extracts showed the presence of two peaks intermediate to the naturally occurring and the completely desulphated forms. It is therefore proposed that the CCK-flanking peptide PSS has both tyrosine residues sulphated.

Animals↗
PubMed1986

Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin.

Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character.

Adrenocorticotropic Hormone↗
PubMed1986

The effect of atrial natriuretic peptide on plasma renin activity, plasma aldosterone, and urinary dopamine in man.

The acute natriuretic effect of human atrial natriuretic peptide (ANP) has been well described in man. We have now studied possible hormonal mediators of this effect. We studied six healthy volunteers on two occasions when they received either an infusion of ANP of 1.5 pmol X kg-1 X min-1 for 30 min followed by 15 pmol X kg-1 X min-1 for a further 30 min, or matching vehicle infusions in a randomized single-blind fashion. On the placebo day, plasma renin activity (PRA) rose from 1.26 +/- 0.08 to 1.57 +/- 0.14 ng A1 X ml-1 X h-1, while on the ANP study day PRA fell from 1.45 +/- 0.15 to 1.28 +/- 0.05 ng A1 X ml-1 X h-1 (p less than 0.01). No significant changes were found in plasma aldosterone concentrations or in urinary dopamine excretion. These results provide evidence that ANP suppresses renin release in man.

Aldosterone↗
PubMed1986

Distribution and molecular heterogeneity of galanin in human, pig, guinea pig, and rat gastrointestinal tracts.

Galanin was measured by radioimmunoassay in whole thickness extracts of the gastrointestinal wall from four species and in extracts from separate layers of human small intestine. The immunoreactivity was characterized using gel chromatography and high-pressure liquid chromatography. Two antibodies were employed, which were characterized as non-C-terminal (Gal 8) and C-terminal (Gal 9) using a C-terminal galanin 10-29 fragment. Substantial quantities of galanin immunoreactivity were found, mainly localized at the muscle layer. Both intramolecular and intermolecular heterogeneity was apparent. Two molecular forms exist in humans (Kav 0.58, 0.69). The molecular heterogeneity in humans, rats, and guinea pigs may be localized near the C-terminus of the galanin molecule. A C-terminal extension of one human galanin form is likely (Kav 0.58). These findings give radioimmunologic evidence for a neurocrine origin of galanin. The chromatographic variations suggest that extrapolation of experimental results between species should be treated with caution.

Animals↗
PubMed1986

Effect of inhibition of acid secretion on the regulatory peptides in the rat stomach.

The effect of inhibiting acid secretion by pharmacologic agents on the gastric content of regulatory peptides has been determined by radioimmunoassay and immunocytochemistry. Plasma, antral, and fundic concentrations of gastrin were elevated in rats rendered virtually achlorhydric by treatment with high-dose omeprazole (400 mumol/kg daily for 10 wk). This was associated with an increase in the number and staining intensity of gastrin immunoreactive cells. A clear reciprocal relationship was observed between antral gastrin and somatostatin as assessed by both quantitative and qualitative methods. These changes had disappeared 10 wk after treatment was stopped. No alteration was found in the concentrations of other regulatory peptides proposed as important in control of acid secretion. Plasma and antral gastrin concentrations were elevated in rats treated with high-dose ranitidine (700 mumol/kg daily), but to a lesser extent than during omeprazole therapy, and somatostatin concentrations were unchanged.

Animals↗