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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 631 records · Page 35Linked to original sources
PubMed1986

Studies on cardiac distribution and function of neuropeptide Y.

High concentrations of a novel peptide, neuropeptide Y, have been demonstrated in the guinea-pig and canine heart and in the latter, a particularly high concentration was found in the region of the coronary vasculature (126 +/- 31 pmol g-1). Intra-arterial infusion of neuropeptide Y for 30 s into the coronary artery of the intact, innervated dog heart resulted in a rapid and short-lasting reduction of blood flow from 38 +/- 4 to 31 +/- 3 ml min-1 (P less than 0.05) to resume control level, 39 +/- 5 ml min-1, within 5 min. These injections were unaccompanied by changes in heart rate and aortic pressure, while there was an associated small reduction in dP/dt, used as a measure for changes in contractility. In vitro studies using the isolated, paced papillary muscle from cat, guinea-pig and rat, and spontaneously beating right atria from the guinea-pig, demonstrated no effect of NPY on active tension or beating frequency. The results indicate that NPY has vasoconstrictor properties, but under the test circumstances to lack both positive and negative inotropic and chronotropic effects.

Animals↗
PubMed1986

Jejunal mucosal enzyme activities, regulatory peptides and organelle pathology of the enteropathy of common variable immunodeficiency.

Jejunal biopsies from six patients having the small bowel enteropathy associated with common variable immunodeficiency have been subjected to analytical subcellular fractionation and enzymic and regulatory peptide microassay to define the organelle pathology of this syndrome. Compared with normal subjects, the immunodeficient patients had decreased activities of the three brush border enzymes: alkaline phosphatase, gamma-glutamyl transferase and alpha-glucosidase. The other organelle marker enzyme activities and all the regulatory peptide concentrations did not differ from the controls. Density gradient experiments showed a complete loss of particulate beta-glucosidase (lactase) with activity entirely located in the cytosol. The integrity of other organelles was normal. These data indicate that the enteropathy of common variable immunodeficiency is associated with abnormalities in the jejunal brush border analogous to those present in tropical malabsorption syndrome.

Adult↗
PubMed1986

Occurrence and distribution of a newly discovered peptide, galanin, in the mammalian enteric nervous system.

Galanin, a newly discovered peptide, was found throughout the gastrointestinal tract of man, pig, and rat, exclusively in nerves. The concentrations of immunoreactive galanin ranged from 3.7 +/- 0.7 (mean +/- SEM) pmol/g in rat antrum to 76.5 +/- 14.3 pmol/g in pig colon. The predominantly intrinsic origin of the galanin nerves was shown by the finding of the peptide in submucosal ganglion cells, the majority of which also contained VIP. Furthermore, neither extrinsic denervation of the gut nor administration of capsaicin, which selectively destroys extrinsic afferent fibres, had any significant effect on the galanin innervation. The caudal projection of galanin-immunoreactive fibres was demonstrated by complete transection of the gut, which led to their reduction in the 1 to 2 cm distal to the cut. The abundance of galanin in the innervation of the mammalian gut and its reported action on smooth muscle contractility suggest this peptide to be a novel regulatory factor in the control of bowel function.

Animals↗
PubMed1986

Electrophysiological actions of somatostatin on the atrioventricular junction in sinus rhythm and reentry tachycardia.

Because somatostatin, a neuroregulatory peptide, is found in abundance in the atria and atrioventricular node, its electrophysiological and antiarrhythmic properties were compared with those of verapamil in ten patients with paroxysmal atrioventricular tachycardia. During sinus rhythm, intravenous somatostatin slowed the heart rate whereas verapamil increased it. Though both agents prolonged atrioventricular conduction time and refractoriness, verapamil was more potent. They were equally effective at terminating reentry atrioventricular tachycardia, restoring sinus rhythm in six of seven patients. Whereas verapamil consistently blocked conduction in the atrioventricular node, somatostatin usually induced ventricular extrasystoles at the time of conversion. Somatostatin may have physiological importance in the neurohumoral control of cardiac impulse formation and conduction.

Adult↗
PubMed1986

Effect of infused vasoactive intestinal peptide on airway function in normal subjects.

Vasoactive intestinal peptide, one of the putative neurotransmitters of non-adrenergic inhibitory nerves in human airways, is a potent relaxant of human airways in vitro. Previous in vivo studies of infused vasoactive intestinal peptide in asthmatic subjects have shown only a small bronchodilator effect, which may have been secondary to the cardiovascular effects of the peptide. The effect on airway function of infused vasoactive intestinal peptide was studied in normal subjects, who readily develop bronchodilation in response to a beta agonist. Separate experiments were designed to assess whether there is any synergy between this peptide and the beta agonist isoprenaline. Incremental doses of 1, 3, and 6 pmol/kg/min of vasoactive intestinal peptide were infused for 15 minutes. At 6 pmol/kg/min it caused a mean fall in systolic blood pressure from 108 to 88 mm Hg and a rise in heart rate from 71 to 95 beats/min. There was no significant change in specific airways conductance (sGaw) at any dose of vasoactive intestinal peptide. No significant changes were found with placebo. Isoprenaline (400 microgram) given by inhalation at the end of the infusion produced a mean increase in sGaw of 50%. Infused peptide caused no significant change in the cumulative dose-response curve for inhaled isoprenaline. The lack of effect of vasoactive intestinal peptide on airway responses in vivo may be due to rapid enzymatic breakdown of the peptide or to the fact that dosage has to be limited by the cardiovascular effects.

Adult↗
PubMed1986

Effects of decapeptide of mammalian bombesin and neuromedin B on pancreatic exocrine secretion in the rat.

The effects on pancreatic exocrine secretion of intravenous bolus injections of decapeptide of mammalian bombesin (also called neuromedin C) and neuromedin B, recently isolated mammalian bombesin-like peptides, have been studied and compared with those of amphibian bombesin in anaesthetized rats. Decapeptide of mammalian bombesin and neuromedin B stimulated the volume output from the pancreas with the same potency as that with which they stimulated protein output, as did amphibian bombesin. The maximal peak rates of volume and protein secretion observed in the 5- to 10-min period after the injection of 3 X 10(-10) mol/kg decapeptide of mammalian bombesin were 24.5 +/- 1.2 microliters/5 min and 8.5 +/- 0.5 mg bovine serum albumin equivalents per 5 min (mean +/- SEM, n = 5). These rates were equivalent to those produced by the same dose of amphibian bombesin, but the duration of responses to decapeptide of mammalian bombesin were shorter than those of equimolar doses of amphibian bombesin. The relative potencies of decapeptide of mammalian bombesin and neuromedin B, calculated from the doses producing 50% of maximum effect on total responses, were, respectively, 100 and 0.5% of that of amphibian bombesin. The results suggest that decapeptide of mammalian bombesin, and possibly neuromedin B, could play a regulatory role in the control of exocrine pancreatic secretion.

Animals↗
PubMed1986

Gastric regulatory peptides in rats with reduced acid secretion.

Gastric acid secretion is known to be controlled by a complex system of interacting factors. Amongst these, regulatory peptides make a significant contribution. In the present study, immunocytochemistry and radioimmunoassay were used to investigate gastric regulatory peptides in animals with pharmacologically reduced gastric acid secretion. Increased numbers of densely immunostained antral gastrin-immunoreactive (G) cells were seen in rats which had been rendered virtually achlorhydric by administration of high-dose (400 mumol/kg daily) omeprazole over a 10-week period. These morphological changes were accompanied by increases in the plasma, antral and fundic concentrations of gastrin, as measured by radioimmunoassay. In contrast, antral somatostatin-containing cells were reduced, and there was a corresponding fall in the tissue content of the peptide. Ten weeks after treatment had ceased, the peptide profiles had returned to normal. No other regulatory peptide, whether endocrine or neural, appeared to alter during treatment with high-dose omeprazole. Treatment with high-dose (700 mumol/kg daily) ranitidine also caused an elevation in the G cell population and the antral and plasma content of gastrin, but to a lesser extent than that observed during omeprazole treatment. Somatostatin cells and tissue levels did not alter in these animals, and no other morphological changes could be detected. Radioimmunoassay, however, measured reduced quantities of vasoactive intestinal peptide, peptide histidine isoleucine and calcitonin gene-related peptide. Achlorhydria, induced by omeprazole at a dosage of 250-500 times that required for effective acid inhibition in man and animals, therefore resulted in reciprocal changes in gastrin and somatostatin cells. These changes are support for the postulated roles of these peptides in the control of gastric acid secretion.

Achlorhydria↗
PubMed1986

Elevated plasma peptide YY in human neonates and infants.

Plasma concentrations of peptide YY (PYY) were measured in cord blood and at 6, 12, and 18 days of postnatal life in 24 healthy preterm neonates, from cord blood of eight full-term neonates, and from peripheral blood of 13 infants 9 months old. Concentrations were high in cord blood (73 +/- 9 pmol/liter versus adult fasting 10.4 +/- 1.3, p less than 0.001) and rose postnatally in the premature infants to 399 +/- 48 pmol/liter at 6 days, 489 +/- 42 at 12 days, and fell to 414 +/- 43 at 18 days. Plasma PYY concentrations were much lower in infants 9 months old (32 +/- 3 pmol/liter), suggesting that the postnatal surge of plasma PYY is a feature of early adaptation to extrauterine life. Gel permeation chromatograms revealed that the major circulating form of PYY in the neonate eluted in a position identical to that of the pure 36 amino acid peptide. There was, however, evidence of two larger molecular forms that may be precursor molecules. Because PYY is a peptide that exhibits potent effects on gastrointestinal secretion and motility in humans, these observations suggest that this candidate gut hormone may be important in the adaptation to enteral nutrition in the neonate.

Fetal Blood↗
PubMed1986

Production of pituitary protein 7B2 immunoreactivity by endocrine tumors and its possible diagnostic value.

7B2 is a protein originally isolated from pituitary, which has been shown to be present in the central nervous system and in certain peripheral tissues, with very high concentrations in pancreatic islets. Endocrine and nonendocrine tumors from 185 patients were investigated by RIA for the presence of immunoreactive pituitary protein 7B2. The highest mean concentration of 7B2 immunoreactivity was found in insulinomas [452 +/- 174 (+/- SEM) pmol/g wet wt tissue; n = 16], which was significantly higher than the concentration in normal adult pancreatic tissue (28.3 +/- 4.4 pmol/g; n = 7). High concentrations of 7B2 immunoreactivity also were found in other endocrine tumors. The cellular localization of 7B2 was studied in normal pancreas, pancreas with hyperplastic islets, and endocrine tumors. 7B2 immunoreactivity was localized to B-cells in the normal pancreas and to variable proportions of cells in islet cell hyperplasias, B-cell tumors, and pheochromocytomas. Plasma concentrations of 7B2 immunoreactivity also were determined in 255 patients with established diagnoses of endocrine or nonendocrine tumors. The proportion of patients with elevated plasma concentrations (arbitrarily set at more than 4 SD above the mean) were 42 of 72 with pancreatic islet cell tumors, 7 of 11 with midgut carcinoid tumors, and 5 of 13 with medullary carcinomas of the thyroid. Especially high values were found in patients with glucagonomas (14 of 20), vipomas (12 of 13), and pancreatic polypeptide-producing tumors (5 of 6). Thus, 7B2 immunoreactivity is produced by a variety of different tumors and may serve as a tumor marker, especially in patients with certain pancreatic islet tumors.

Adult↗
PubMed1986

Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man.

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.

Adult↗
PubMed1986

Localization and molecular forms of galanin in human adrenals: elevated levels in pheochromocytomas.

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.

Adrenal Gland Neoplasms↗
PubMed1986

Effect of ketoconazole on adrenocorticotrophic hormone secretion in vitro and in vivo.

The direct effects of ketoconazole on ACTH secretion have been investigated using a rat pituitary cell culture system. Ketoconazole had no significant effects on basal ACTH secretion, corticotrophin-releasing factor- or arginine vasopressin-stimulated ACTH secretion, nor did it affect dexamethasone inhibition of ACTH secretion. In-vivo studies demonstrated an increased ACTH level (168 vs 76 ng/l) accompanied by a fall in plasma corticosterone (193 vs 307 micrograms/l) in normal rats given ketoconazole (24 mg/kg, five oral doses given 8 hourly). No effects were seen in adrenalectomized rats or at lower doses (6 mg/kg) in normal or adrenalectomized rats. A high dose of ketoconazole (24 mg/kg, twice daily oral doses) also caused increased ACTH levels in normal rats (129 vs 86 ng/l) when given for 7 days. No effects were seen in adrenalectomized rats or on plasma corticosterone levels in normal rats. Our data suggest that ketoconazole at these doses has no direct effects on pituitary ACTH secretion but causes an increase in plasma ACTH due to its inhibition of adrenal steroid synthesis.

Adrenalectomy↗
PubMed1986

Pancreatic alpha cell function in the fetal and newborn pig.

Plasma glucagon concentrations were measured in chronically catheterized fetal pigs during the last third of gestation and compared with the values observed in anaesthetized fetuses of similar gestational age. The mean plasma concentration of glucagon in the chronically catheterized fetuses was 10.0 +/- 1.4 (S.E.M.) pmol/l (n = 11; term = 114 +/- 2 days). Concentrations were increased after catheterization and fell to baseline values within 48 h of surgery. Arginine infusion evoked a rapid release of glucagon in chronically catheterized fetuses between 105 and 108 days of gestation; the mean maximum increment in plasma glucagon was 15.4 +/- 4.5 pmol/l (n = 5). Plasma glucagon concentrations increased with increasing gestational age in both anaesthetized and chronically catheterized fetuses. Between 95 and 110 days of gestation, glucagon levels were significantly higher in anaesthetized fetuses than in chronically catheterized animals with similar normal pH values. Catheterization and prematurity had no apparent effect on plasma glucagon levels at birth. The plasma concentrations at birth were similar to those observed in the chronically catheterized fetuses in utero provided the piglets did not become acidotic during delivery. Significantly higher plasma levels of glucagon were found in newborn piglets with acidaemia (pH less than 7.3) than in piglets with normal pH values at birth (pH greater than 7.3). When all the data from the newborn piglets were combined, there was a significant negative correlation (r = -0.79, n = 39, P less than 0.01) between blood pH and the plasma concentration of glucagon at birth. These observations demonstrate that the fetal alpha cells are functional and responsive in utero and at birth.

Animals↗
PubMed1986

A novel pituitary protein (7B2)-like immunoreactivity is secreted by a rat phaeochromocytoma cell line (PC12).

High concentrations of a novel pituitary protein (7B2) have been shown to be present in the PC12 rat phaeochromocytoma cell line by radioimmunoassay. 7B2-like immunoreactivity (IR-7B2) was released from PC12 cells into the incubation medium in response to stimulation by a depolarizing concentration of K+, and this K+-evoked release was inhibited by Co2+. The major IR-7B2 in PC12 cell and medium appeared to be identical to that in porcine pituitary gland as judged by both gel permeation chromatography and by reverse-phase high performance liquid chromatography (HPLC). Gel permeation chromatography of extracts of cell and medium revealed two IR-7B2 peaks, the earlier eluting at a elution coefficient (Kav) of 0.30 and the later at a Kav of 0.54. In medium, over 90% of the IR-7B2 eluted as the earlier peak. Fractionation of extracts of cell and medium on reverse-phase HPLC showed three main IR-7B2 peaks eluting at 43, 44.5 and 46% acetonitrile/water with 0.1% trifluoroacetic acid. The findings suggest that IR-7B2 might be released by calcium-mediated exocytosis.

Adrenal Gland Neoplasms↗
PubMed1986

Plasma release of atrial natriuretic peptide in response to blood volume expansion.

The response of plasma atrial natriuretic peptide (ANP) concentration to acute intravascular volume expansion was measured in ten male Wistar rats. An infusion of 3 ml polygelene colloidal solution at 37 degrees C over 45 s produced peak venous pressure rises of 1.5 cm water. A highly significant (P less than 0.001) rise of immunoreactive plasma ANP from 24.4 +/- 2.2 (mean +/- S.E.M.) pmol/l to a peak of 70.0 +/- 10.5 pmol/l occurred within 2.5 min. Plasma ANP concentrations had virtually returned to basal levels (32.7 +/- 2.7 pmol/l) 30 min after this acute volume load. A further infusion of 10 ml polygelene colloidal solution in 2 min produced peak venous pressure rises of 10 cm water and caused a dramatic and significant (P less than 0.001) increase of plasma ANP concentration to a peak of 534.8 +/- 38.5 pmol/l, occurring 7.5 min after infusion. The plasma ANP concentration had fallen but remained above basal levels 30 min later (137.2 +/- 26.4 pmol/l). Similar results were obtained using an identical protocol but with whole rat blood instead of polygelene solution as the volume-expanding agent. Gel column chromatography suggested that the majority of the immunoreactive ANP in rat plasma was of similar molecular size to rat alpha-ANP (1-28). These results support the hypothesis that blood volume expansion is a potent stimulus for the release of ANP into plasma.

Animals↗
PubMed1986

Reduced adrenal cortical sensitivity to ACTH in lambs with cut splanchnic nerves.

The possibility that the sensitivity of the adrenal cortex to endogenous ACTH may be affected by splanchnic nerve activity has been investigated in conscious, weaned, 5- to 8-month-old lambs. The animals were atropinized (0.5 mg/kg) and tested with an i.v. infusion of noradrenaline (333 ng/kg per min for 10 min), which produced a significant rise in the mean concentration of both ACTH and cortisol in the arterial plasma. In lambs tested at least 7 days after section of both splanchnic nerves, just below the diaphragm, the rise in plasma ACTH concentration was significantly greater, and that in plasma cortisol significantly less, than in control lambs. The mean plasma ACTH and cortisol concentrations were linearly related to one another in both groups (r = 0.93 and 0.92) but the sensitivity of the adrenal cortex to the steroidogenic action of ACTH appeared to have been roughly halved 1 week after bilateral splanchnic nerve section.

Adrenal Cortex↗