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S R Bloom

Publications and source records attributed to S R Bloom.

At least 1,081 records · Page 60Linked to original sources

Subcellular localization of serotonin and motilin in the human jejunum.

1. Analytical subcellular fractionation techniques have been applied to human jejunal homogenates to study the localization of serotonin and motilin. 2. Serotonin, detected by a fluorimetric assay, showed two distinct particulate distributions in the density gradients with modal densities of 1.14 and 1.20. Motilin, whether detected by N-terminal or C-terminal specific antibodies showed similar density distributions with a modal density of 1.20, coinciding with the denser peak of serotonin. 3. These results lend support to the histochemical suggestions that motilin is located in a a serotonin-containing granule.

Centrifugation, Isopycnic↗

Effects of pancreatic polypeptide on motilin and circulating metabolites in man.

Pancreatic polypeptide was infused intravenously in healthy fasting subjects at 1 pmol kg-1 (n = 7) and 4 pmol kg-1 min-1 (n = 10) producing plasma PP concentrations of 223 +/- 37 pmol/l (mean +/- SEM) and 891 +/- 64 pmol/l respectively. These levels are similar to and four-fold higher than those seen after a normal mixed breakfast in healthy young adults. In a separate study five healthy subjects ingested a small breakfast during infusion of PP on different days at 1 pmol kg-1 min-1 and 2 pmol kg-1 min-1 respectively. PP at 1 pmol kg-1 min-1 caused a marked reduction in fasting plasma motilin concentrations to 20% of the basal level (p less than 0.001). There were, however, no significant changes in plasma concentrations of insulin, glucagon, gastrin, secretin, enteroglucagon, gastric inhibitory peptide or neurotensin. Despite previous reports possibly implicating PP in metabolism, there were no significant effects on blood levels of glucose, alanine lactate, 3-hydroxybutyrate, glycerol or non-esterified fatty acids, either in the fasting state or after the ingestion of food. Although it seems unlikely that PP is a major hormonal regulator of intermediary metabolism in man, its ability to suppress motilin at physiological concentrations suggests the possibility of an indirect influence on digestive motor function.

Adult↗

Plasma secretin in neonates.

Plasma secretin has been measured in 96 normal 6-day-old term infants and in 158 healthy preterm infants whose mean post-partum ages were 2 1/2, 6, 13 or 24-days. At birth, plasma secretin levels in both term and preterm infants were high compared with those seen in healthy fasting adults (p less than 0.001), but subsequently declined towards adult values. In contrast, preterm infants who had not been fed for the first 6 days of life, had presistently high basal plasma secretin values. In term infants at 6 days of age and in preterm infants up to 13 days, there was no secretin response to a feed. However, by 24 days, preterm infants showed a marked postprandial secretin elevation (p less than 0.02). No correlations were found between plasma secretin concentrations and either blood glucose or plasma insulin concentrations following a feed. Significant adjustments in plasma secretin levels occur in the early weeks of life which may be influenced by enteral feeding.

Adult↗

Plasma pancreatic polypeptide in the human neonate.

Plasma pancreatic polypeptide (PP) concentrations have been studied in 197 healthy term and preterm infants. At birth plasma concentrations were lower than those found in the young fasting adult (p less than 0.01), but by the sixth postnatal day in both term and preterm infants basal concentrations had risen to adult levels. In preterm infants, who were studied at two further postnatal ages, 13 and 24 days, basal plasma PP concentrations peaked at 13 days with levels that were over twice those seen in fasting adults (p less than 0.005). However, the marked PP elevations following feeding that have been reported in adults, were not seen in any of the groups of neonates studied. PP physiology thus appears to differ in neonates and adults. These findings may be relevant to adaptation to postnatal life.

Adult↗

Developmental aspects of gastric inhibitory polypeptide (GIP) and its possible role in the enteroinsular axis in neonates.

Little is known on the development of the release of gastric inhibitory polypeptide (GIP) in neonates or on its potential role in the enteroinsular axis. Using cross-section data collection we studied: (a) 100 preterm neonates either at birth (cord blood), or before or after a feed on the sixth or 24th day and (b) 63 term neonates at birth or on the sixth day. Blood samples were assayed for GIP, insulin and glucose. At birth plasma GIP concentrations were low compared with fasting adults (p less than 0.01). Basal plasma levels were significantly higher at six days in fed infants, but not in a group of sick preterm infants who had never been fed orally. On the sixth day there was no GIP response to a feed, but by 24th day there was a marked postprandial elevation (p less than 0.01). In preterm infants the insulin response was 68% greater at 24 days than at six days in spite of a similar glycaemic response. We hypothesize that this increasing postnatal insulin response to enteral feeding may be due to the commencement of the postprandial release of GIP, thought to be an important effector in the enteroinsular axis.

Blood Glucose↗

Effects of autonomic stimulation on the release of vasoactive intestinal peptide from the gastrointestinal tract in the calf.

1. The effects of autonomic stimulation on the release of vasoactive intestinal peptide (VIP) from the gastrointestinal tract have been investigated in adrenalectomized claves 2-5 weeks after birth.2. Stimulation of the peripheral ends of the splanchnic nerves (10 Hz for 10 min) caused a small fall in the concentration of VIP in portal and arterial plasma, together with a rise in the concentration in intestinal lymph. None of these changes achieved statistical significance.3. The effects of stimulation of the peripheral ends of the thoracic vagi, below the heart (10 Hz for 10 min), were found to depend in part upon the integrity of the splanchnic sympathetic innervation. A substantial rise in the concentration of VIP in intestinal lymph occurred whether or not the splanchnic nerves had been cut whereas an associated rise in arterial plasma VIP was only observed in calves in which the splanchnic nerves had been sectioned.4. The rise in the concentration of VIP in intestinal lymph, in response to vagal stimulation, was unaffected by concomitant stimulation of the splanchnic nerves, although the associated rise in arterial plasma VIP concentrations was suppressed. The response was also found to be resistant to atropine.5. The minimum estimated concentration of VIP in the extracellular fluid of the gastrointestinal tract was estimated to be about 60 p-mole/l. at rest and to rise by 70-120 p-mole/l. in response to vagal stimulation.6. Intravenous infusions of VIP at a dose of 50 ng kg(-1) min(-1) (16 p-mole kg(-1) min(-1)), which raised the minimum estimated concentration of VIP in the gastro-intestinal tract to the highest range encountered during stimulation, produced no significant changes in the concentrations of glucose, insulin, pancreatic glucagon or pancreatic polypeptide in the arterial plasma.7. It is concluded that a small amount of VIP is released from the gastrointestinal tract in response to vagal stimulation. In contrast, release of VIP is unaffected by stimulation of the splanchnic nerves except in so far as the rate at which the peptide passes into the circulation is reduced by adrenergic vasoconstriction.

Animals↗

Vasoactive intestinal peptide in relation to atropine resistant vasodilatation in the submaxillary gland of the cat.

1. Release of VIP from the submaxillary gland, in response to stimulation of the chorda tympani, and its vasodilator action at the site of release have been investigated in anaesthetised cats. 2. Chorda stimulation at 20 Hz produced an abrupt rise in the concentration of VIP in the submaxillary venous effluent plasma, accompanied by a substantial increase in submaxillary blood flow, in the presence or absence of atropine. 3. Intra-arterial infusions of VIP which reproduced the rise in submaxillary venous plasma concentration that occurred during chorda stimulation at 20 Hz, also produced a rise in submaxillary blood flow of the same order of magnitude. 4. Direct comparison of the responses of the submaxillary vasculature to intraarterial infusions of VIP, ACh and bradykinin showed that the vasodilator potency of VIP far exceeded that of either of the other agonists. 5. Intra-arterial infusion of ACh, sufficient to elicit a maximal submaxillary vasodilator response, caused no detectable release of VIP from the gland. 6. The results are discussed in relation to the proposition that VIP is released from post-ganglionic parasympathetic neurones, in the submaxillary gland of the cat, and acts, as a transmitter, to cause vasodilatation, which is resistant to atropine.

Acetylcholine↗

The effect of somatostatin on pancreatic endocrine responses mediated via the parasympathetic innervation in the conscious calf.

1. The effect of somatostatin on the responses to moderate insulin hypoglycaemia and to 2-deoxyglucose has been examined in 2--3 week-old calves with cut splanchnic nerves. 2. Intravenous infusions of somatostatin (150 p-mole . kg-1 . min-1) completely suppressed release of glucagon, pancreatic polypeptide (PP) and insulin from the pancreas in response to 2-deoxyglucose (1.1 m-mole/kg I.V.). 3. The same dose of somatostatin completely blocked the rise in plasma PP concentration that normally occurs in response to moderate insulin hypoglycaemia and significantly delayed the rise in plasma pancreatic glucagon concentration. The hypoglycaemic response to insulin was also found to be intensified by the administration of somatostatin. 4. It is concluded that each of the pancreatic neuroendocrine responses, that are now known to be mediated via the parasympathetic innervation, is suppressed in the presence of somatostatin in the young calf.

Animals↗

Pancreatic endocrine responses to stimulation of the peripheral ends of the splanchnic nerves in the conscious adrenalectomized calf.

1. Certain effects of stimulation of the peripheral ends of both splanchnic nerves have been investigated in unanaesthetized calves, given appropriate adrenal steroid replacement therapy. 2. Splanchnic nerve stimulation at frequencies within the physiological range produced prompt rises in the concentration of glucose, pancreatic glucagon and pancreatic polypeptide in the arterial plasma. These responses were followed by a rapid rise in plasma insulin concentration when the stimulus was terminated. The extent of this rise was related to the plasma glucose concentration at that precise point in time. 3. Stimulation at all frequencies tested had no effect on the concentration of vasoactive intestinal peptide in lymph collected from the intestinal duct. 4. The results are discussed in relation to those obtained in previous studies in anaesthetized calves of the same age.

Adrenalectomy↗

Plasma motilin, gastrin, and enteroglucagon and feeding in the human newborn.

Plasma concentrations of motilin, gastrin, and enteroglucagon were measured in cord blood and during the first 24 days of life before feeding in 45 term and 63 preterm, healthy infants. Levels of these hormones rose steeply after birth, reaching concentrations that were much higher than those in fasting adults. These increases in hormone concentration were not present in a group of 10 preterm infants who had received only intravaenous dextrose from birth because of hyaline membrane disease. Our findings suggest that early enteral feeding may trigger the postnatal increase in plasma concentrations of gut hormones and that this could play an important role in the physiologaical adaptations to extrauterine nutrition.

Fetal Blood↗

Development of gut hormone responses to feeding in neonates.

The development of the effects of a human milk feed on plasma concentrations of motilin, neurotensin, gastric inhibitory polypeptide, enteroglucagon, gastrin, and secretin were studied in 158 healthy preterm neonates (mean gestation 33 1/2 weeks) at mean postnatal ages of 2 1/2, 6, 13, or 24 days. Pronounced progressive changes occurred in postprandial hormone responses; these were absent or small in the first days of life and were large by age 24 days. These changes may have important consequences in the adaptation to postnatal life.

Age Factors↗

Separation of the gut hormone endocrine-cell storage granules of human jejunum using analytical subcellular fractionation.

Analytical subcellular fractionation techniques in combination with specific radioimmunoassays have been used to investigate the properties of the hormone-containing granules in human jejunal biopsy specimens. After gentle homogenisation, for all hormones except VIP, over 90% of the immunoreactivity was released in intact granules into the post-nuclear supernatant. Approximately 50% of the VIP immunoreactivity sedimented with the low speed pellet, probably reflecting the presence of this peptide in nerve fibres. The following hormone granules (equilibrium densities between parentheses) were separated by isopycnic centrifugation on the sucrose density gradients: VIP (1 x 17), motilin (1 x 20), and secretin (1 x 24). Gastrin and GIP granules were not resolved, both having the same modal density of 1 x 22 g/cm3. This combination of procedures thus provides a new quantitative technique for studying the properties of the gastrointestinal hormone-containing granules, and should therefore be of value in investigating pathophysiological problems in a variety of gastrointestinal diseases.

Cell Fractionation↗

Pectin and complications after gastric surgery: normalisation of postprandial glucose and endocrine responses.

Pectin has been shown to minimise the fall in blood glucose seen in patients who are troubled by hypoglycaemia attacks after gastric surgery. We therefore performed 50 g glucose tolerance tests with and without 14.5 g pectin on 11 post-gastric surgery patients. After pectin, the high postprandial levels of glucose, insulin, and enteroglucagon were significantly reduced as was the fall in blood glucose between 90 and 120 minutes. These effects of pectin may reflect slower uptake of glucose from the gastrointestinal tract and provide evidence to support the use of unabsorbable carbohydrate gelling agents in treating hypoglycaemia after gastric surgery.

Adult↗

Response of plasma pancreatic and gastrointestinal hormones and growth hormone to oral and intravenous glucose and insulin hypoglycaemia in Chagas's disease.

Plasma hormonal responses to insulin hypoglycaemia and to oral and intravenous glucose were investigated in chagasic patients with severe bowel disease and compared with controls matched for age, sex, weight, and race. After intravenous insulin, plasma concentrations of pancreatic glucagon and pancreatic polypeptide (PP) were reduced in the patients with Chagas's disease. These subjects also showed a subnormal rise in plasma insulin after oral glucose. Other hormone responses did not differ significantly from those in the normal controls. These results are compatible with partial denervation of the pancreatic alpha, beta, and PP cells in patients with chronic gastrointestinal Chagas's disease.

Adolescent↗

Gastric stress ulcers and gastrointestinal hormones - response to hydrochloric acid and sodium chloride infused intraduodenally. Preliminary report.

Gastric stress ulcers were produced by restraint in nonsecretory rats, and the response of the ulcer index to intraduodenal hydrochloric acid (HCl) or sodium chloride (NaCl) was studied in a three-step dose-response trial. Both substances lowered the ulcer index dose-dependently (Km HCl 0.038 +/- Km NaCl 0.089 +/- 0.009 mM/kg/h, respectively) reaching a nadir in rats receiving HCl. The improvement in ulcerations was associated with elevated plasma secretin, glucose, and lowered gastrin in this protocol. In both experimental procedures plasma vasoactive intestinal peptide (VIP) was higher with the low and intermediate doses as compared with the high dose when a slight venous hyperosmolality was present. Glucagon and insulin remained essentially stable. It is concluded that stress ulcers of the restraint type may be prevented by intraduodenal HCl, suggesting that the interplay of gastrointestinal hormones is deranged by stress and partly restored by acid instillation.

Animals↗

Neurotensin infusion in man: pharmacokinetics and effect on gastrointestinal and pituitary hormones.

Synthetic neurotensin was infused into five healthy subjects at a mean dose of 2.3 pmol/kg . min for 30 min, producing a rise in plasma neurotensin concentrations, measured by RIA of 104 +/- 10 (mean +/- SEM) pmol/liter. The mean disappearance half-time on stopping the infusion was 3.8 +/- 0.2 min. The MCR was 16 +/- 1 ml/kg . min, and the apparent space of distribution was 88 +/- 6 ml/kg. During the neurotensin infusions, plasma pancreatic polypeptide rose by 145 +/- 54 pmol/liter. In contrast to results in experimental animals, there was no significant change in the pulse or blood pressure of the subjects or any significant change in blood glucose or plasma concentrations of insulin, glucagon, gastric inhibitory peptide, gastrin, motilin, or vasoactive intestinal peptide. Similarly, there was no change in plasma concentrations of TSH, GH, PRL, LH, and FSH.

Adult↗