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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 505 records · Page 28Linked to original sources
PubMed1988

7B2, a new protein secreted by human functionless pituitary tumours, in vitro.

A novel pituitary protein, 7B2, of approximately 180 amino acids has been suggested to colocalise with LH in the pituitary gonadotropes. Increased secretion of LH is known to occur in functionless pituitary tumours. We have therefore measured 7B2 immunoreactive equivalents in the 24-h medium of explant pituitary cultures prepared from 17 functionless, 20 somatotropic, 16 PRL secreting and 8 corticotropic adenomas. A synthetic fragment corresponding to amino acids 23-39 of 7B2 was used to raise antisera (rabbits), prepare radiolabel (chloramine T iodination) and also serve as the assay standard. 7B2-immunoreactive equivalents in the medium from the functionless tumours was 517 +/- 149 pmol/l, significantly higher than that of the somatotropic tumours (248 +/- 90 pmol/l, P less than 0.05), prolactinomas (108 +/- 37 pmol/l, P less than 0.001) and corticotropin producing adenomas (107 +/- 77 pmol/l, P less than 0.001) (one-way analysis of variance). Gel permeation chromatography of medium obtained from functionless tumours revealed two immunoreactive 7B2 peaks one eluting at a coefficient of 0.28 corresponding to that of normal human pituitary extract and another eluting at a coefficient of 0.59. Gel chromatography profiles of medium obtained from somatotropic tumours contained similar immunoreactive 7B2 peaks (elution coefficient 0.28 and 0.57). These findings demonstrate that 7B2-like material is secreted by pituitary adenomas in explant culture with the highest level from functionless tumour cultures.

Adenoma↗
PubMed1988

Opioid peptides do not modulate atrial natriuretic peptide or aldosterone release under basal conditions in man.

The effect of two analogues of [Met]-enkephalin, [D-Ala2,N-Phe4,Met(0)-ol5]-enkephalin and its guanyl derivative, on plasma concentrations of atrial natriuretic peptide (ANP) and serum aldosterone in six normal subjects was investigated. All subjects were given a 1 litre water load to inhibit vasopressin release. Both analogues, when injected i.v. at a dose of 100 micrograms, stimulated release of prolactin and GH and inhibited serum cortisol; there was no significant change in blood pressure, pulse rate or urine output. Neither plasma concentrations of ANP nor serum aldosterone levels changed significantly after injection of either analogue at a low or high dose. Naloxone, given i.v. as an 8 mg bolus, also failed to alter concentrations of either ANP or aldosterone, while it significantly stimulated the release of serum LH and cortisol. It was concluded that under basal conditions opiate receptors are unable to modulate plasma ANP or serum aldosterone concentrations.

Adult↗
PubMed1988

Galanin abolishes the inhibitory effect of cholinergic blockade on growth hormone-releasing hormone-induced secretion of growth hormone in man.

In five healthy normal male volunteers, pretreatment with the cholinergic muscarinic antagonist pirenzepine (30 mg i.v.) almost abolished the growth hormone (GH) response to a maximal dose (120 micrograms i.v.) of growth hormone-releasing hormone (GHRH) (GH response at 40 min 5.6 + 1.3 mU/l with GHRH and pirenzepine vs 40.8 +/- 5.3 mU/l with GHRH alone, P less than 0.02). Concomitant i.v. infusion of galanin (40 pmol/kg/min) with pirenzepine not only restored but significantly potentiated the GH response to GHRH (GH at 40 min 72.2 +/- 10.5 mU/l, P less than 0.001 vs GHRH and pirenzepine, P less than 0.02 vs GHRH alone). Previous studies have proposed that cholinergic pathways control GH release via somatostatin and this study suggests that galanin may act by modulating hypothalamic somatostatinergic tone either directly or, possibly, by facilitating cholinergic neurotransmission.

Adult↗
PubMed1988

Increased hypothalamic neuropeptide Y concentrations in diabetic rat.

Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) and matched control rats between 1 day and 14 wk after diabetes induction. After 2 wk, both central and lateral hypothalamic neuropeptide Y (NPY) concentrations in STZ-D rats were consistently higher than those found in control rats, with significant 30-50% increases at 4 wk in the central hypothalamus, and at 6 and 14 wk in both central and lateral hypothalamus. Immunocytochemical studies in 4- and 6-wk STZ-D animals showed the appearance of intensely NPY-positive swollen cell bodies in the supraoptic nucleus and a subjective increase in NPY staining of medial hypothalamic nerve fibers. Central hypothalamic concentrations of three other peptides were significantly greater in STZ-D animals than those in control animals at single points (neurotensin, 1 day; calcitonin gene-related peptide, 2 wk; neurokinin, 4 wk). Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time. However, galanin immunostaining in the supraoptic and magnocellular paraventricular nuclei was strikingly concentrated in a reduced number of distended cell bodies. Hypothalamic peptide changes in STZ-D could be related to metabolic disturbance, changes in energy and water balance, altered pituitary function, or other factors. Persistently elevated concentrations of NPY, a very potent central stimulant of eating and drinking, may mediate the hyperphagia and polydipsia characteristic of STZ-D.

Animals↗
PubMed1988

Chronic pancreatitis and diabetes mellitus: plasma and gastroduodenal mucosal profiles of regulatory peptides (gastrin, motilin, secretin, cholecystokinin, gastric inhibitory polypeptide, somatostatin, VIP, substance P, pancreatic polypeptide, glucagon, enteroglucagon, neurotensin).

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Manipulation of gut hormone response to food by soluble fiber and alpha-glucosidase inhibition.

Preliminary data indicated that viscous fiber (guar) and alpha-glycosidase inhibition (acarbose) used in combination to slow carbohydrate absorption have an apparently additive effect in reducing the postprandial glycemic response. The full endocrine data reported here also demonstrate that reductions in insulin and gastric inhibitory polypeptide are most significant when guar and acarbose are used in combination. The results are divergent for enteroglucagon when guar and acarbose were given singly. Raised enterglucagon levels seen after acarbose are in keeping with inhibition of proximal absorption resulting in more distal absorption of carbohydrate. However, with viscous fiber, the enteroglucagon response was reduced, and this reduction was maintained even after addition of acarbose. The results demonstrate that the gut endocrine response can be manipulated by pharmacological interventions which alter the pattern of carbohydrate absorption.

Acarbose↗
PubMed1988

A case of somatostatinoma: responses to food and SMS 201-995 administration.

Plasma somatostatin response to food and the administration of the long-acting somatostatin analogue SMS 201-995, as well as pituitary responses to insulin-induced hypoglycemia, growth hormone-releasing hormone (GHRH) and thyrotropin-releasing hormone (TRH), were assessed in a 60-year-old woman with biopsy-proven metastatic somatostatinoma. SMS 201-995 alone did not change plasma somatostatin-like immunoreactivity (SRIF), but levels of low-molecular-weight forms (SRIF-14 and SRIF-28) more than doubled in response to a standard meal. This postprandial response was not affected by pretreatment with SMS 201-995. Although a growth hormone response to insulin-induced hypoglycemia and supramaximal GHRH was absent, the patient's thyroid-stimulating hormone response to TRH was normal. These results suggest that somatostatin analogues may not influence tumor autonomy and that a SRIF response to food may contribute to early satiety in patients with somatostatinoma. In addition, the long-term use of somatostatin analogues to suppress hormone production by other peptide-secreting tumors may not have predictable results.

Adenoma, Islet Cell↗
PubMed1988

The relationship of the renin-angiotensin-aldosterone system to atrial natriuretic peptide and the natriuresis of volume expansion in diabetics with and without proteinuria.

Atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system are important regulatory hormones in sodium homeostasis. We have measured these hormones during volume expansion produced by water immersion in diabetic subjects without and with microalbuminuria or frank proteinuria and compared the response with normal controls. Diabetic subjects excreted about half the amount of sodium that was excreted by the normal subjects (39 vs 21 mmol) over 4 h. Diabetic subjects and normal ones showed a twofold rise in ANP during immersion and a marked suppression of both plasma renin activity and aldosterone. There was no difference in the hormonal response between diabetic and normal subjects or between those diabetic subjects with and those without incipient (microalbuminurics) or established nephropathy.

Adult↗
PubMed1988

Hypergastrinaemia of sheep infected with Haemonchus contortus.

Radioimmunoassay of plasma gastrin has shown that a hypergastrinaemia occurs in yearling sheep, after infection with 10(6) infective third stage larvae of Haemonchus contortus. Plasma gastrin concentrations began to rise two to four days after infection, that is, at about the same time as, or slightly before, the abomasal pH was observed to increase.

Abomasum↗
PubMed1988

Circulating concentrations of immunoreactive peptide 7B2 in certain pathophysiological conditions, and response to oral glucose load.

A peptide, 7B2, originally isolated from pituitary, is present in endocrine tumors, with high concentrations in pancreatic islet tumors. Plasma from most of these patients showed very high immunoreactivity to 7B2 (IR-7B2). To assess whether or not there is any alteration in circulating 7B2 concentrations due to age, sex, etc., we measured concentrations in plasma in 96 fasting healthy subjects, ages three months to 91 years; in patients with various other conditions, including pregnancy; and in cord blood. The response of circulating IR-7B2 to oral glucose was also evaluated. We found particularly high IR-7B2 concentrations in cord blood. Postnatally the concentrations were lower and decreased gradually with age to values for adults [15.6 (SE 2.9) pmol/L], increasing again significantly (P less than 0.01) in persons older than 70 years [37.1 (SE 32) pmol/L]. There was no significant sex-related difference in values for plasma. For the pathological conditions studied, we observed significantly supranormal values in patients with chronic renal failure [175.1 (SE 35.9) pmol/L]. Some of the pregnant patients in their third trimester also showed high values. A small but significant increase in plasma IR-7B2 was observed after a glucose load, both in control subjects and diabetics. Perhaps the kidney plays a major role in 7B2 degradation.

Adolescent↗
PubMed1987

Glucagon-like peptide-1 7-36: a physiological incretin in man.

The physiological role of glucagon-like peptide-1 7-36 amide (GLP-1 7-36) in man was investigated. GLP-1 7-36-like immunoreactivity was found in the human bowel; its circulating level rose after oral glucose and after a test breakfast. When it was infused into seven volunteers at a rate to mimic its postprandial plasma concentration in the fasting state, plasma insulin levels rose significantly and glucose and glucagon concentrations fell. During an intravenous glucose load, it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations, compared with a control saline infusion, even inducing postinfusion reactive hypoglycaemia. By comparison, infusion of glucose-dependent insulinotropic peptide (GIP) to physiological levels was less effective in stimulating insulin release. These observations suggest that GLP-1 7-36 is a physiological incretin and that it is more powerful than GIP. The observation of greatly increased postprandial plasma GLP-1 7-36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder.

Adult↗
PubMed1987

Increase of substance P-like immunoreactivity in the peripheral nerve of the axolotl after injury.

That substance P may be a neurotrophic factor in urodele limb regeneration was investigated in the axolotl (Ambystoma mexicanum). Two weeks after section of the peripheral nerves to the forelimb, there was a marked increase in substance P-like immunoreactivity (IR) content of the nerves proximal to the lesion. A smaller increase occurred as early as 3 days after section of nerves innervating a regrowing limb bud (blastema), and substance P-IR fibres were observed by immunocytochemistry to innervate blastema tissue. As substance P-IR by applying capsaicin to peripheral nerve--capsaicin had no effect on substance P-IR in either intact or injured axolotl nerves. Substance P fulfills a number of criteria of a trophic substance in axolotl limb regrowth.

Ambystoma mexicanum↗
PubMed1987

Distribution of vasoactive intestinal polypeptide binding sites in guinea pig genital tissues.

Vasoactive intestinal polypeptide (VIP) binding sites were localised in sections of guinea pig genital tissues using [125I]VIP and quantitative in vitro receptor autoradiography. A moderate density of binding was demonstrated in the epithelium of the prostate gland, seminal vesicles and in the testes. Moderate to high VIP binding also occurred in the epithelial lining of the oviduct, uterine glands, cervix and vagina. The binding sites appear to have a dissociation constant (Kd) of 0.36 nM and maximum receptor density (Bmax) of 60.5 x 10(-3) fmol/mm2 in sections of the uterine horn. The results indicate that VIP may have a role in the secretory functions of the guinea pig genital tract.

Animals↗
PubMed1987

Isolation, characterization, and pharmacological actions of peptide histidine valine 42, a novel prepro-vasoactive intestinal peptide-derived peptide.

The primary structure and biological activity of a novel prepro-vasoactive intestinal peptide (prepro-VIP)-derived peptide has been determined from an adrenal pheochromocytoma. The peptide was purified sufficiently for characterization by fast atom bombardment mapping after cation-exchange and reverse-phase fast protein liquid chromatography. The sequence of this novel peptide corresponds exactly to prepro-VIP-81-122 and has been designated peptide histidine valine 42 (PHV-42). Synthetic PHV-42 reduced both the force and frequency of spontaneous contractions of isolated rat uterus and was at least 12 times more potent than peptide histidine methionine (prepro-VIP-81-107), and over a hundred times more potent than noradrenaline. PHV-42 was also more potent than peptide histidine methionine in relaxing smooth muscle preparations of rat stomach and guinea pig trachea, but was approximately 4-fold less potent in reducing blood pressure than VIP. PHV-42 thus forms a separate subsystem in the VIP family of peptides and may be the most biologically active product of prepro-VIP in certain tissues such as the uterus and trachea.

Adrenal Gland Neoplasms↗
PubMed1987

Neuromedin N: presence and chromatographic characterization in the rat.

The distribution of neuromedin N and its structurally related peptide, neurotensin, was investigated in the rat and found to be remarkably similar with highest concentrations in the ileum. However, neuromedin N but not neurotensin was found in the kidney. Chromatographic analysis of immunoreactive neuromedin N demonstrated a single peak of immunoreactivity which was distinguishable from the single peak of immunoreactive neurotensin. Neuromedin N is likely to be a naturally occurring peptide and is distinct from neurotensin in rat peripheral tissues.

Animals↗
PubMed1987

Somatostatin.

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Humans↗