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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 1,009 records · Page 56Linked to original sources
PubMed1981

The peripheral substance P-ergic system.

In this review we have described the distribution, precise quantities and physico-chemical characteristics of Substance P in the central nervous system and in 7 peripheral organs. In keeping with the main reported actions of substance P as a modulator of both smooth muscle tone and blood vessel diameter, nerve fibres containing the peptide are frequently seen in close proximity to smooth muscle fibres and blood vessels. The postulated role of substance P as a sensory transmitter has been fully supported by the finding of significant concentrations of the peptide not only in primary sensory neurons but also in their central and peripheral branches. Its transport and release at afferent terminals is further validated by the significant depletion of substance P which occurred in the corresponding tissue after ligation of a sensory nerve (vagus), destruction of a ganglion (i.e., Gasserian ganglion leading to depletion from ocular structures) and treatment with capsaicin. The ultrastructural secretory granules containing Substance P are shown here by a novel immunocytochemical procedure using gold-labelled antibodies on ultrathin sections to correspond to a sub-class of the large, dense, p-type neurosecretory vesicles, with characteristic size (mean 85 +/- 15 nm), electron density and limiting membrane.

Animals↗
PubMed1981

Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.

Gastrointestinal Hormones↗
PubMed1981

The mechanism of abnormal pancreatic beta cell response to food following acute hypoglycaemia in man.

Following acute insulin-induced hypoglycaemia, an abnormal pattern of insulin secretion in response to a meal has been demonstrated in six healthy volunteers. This is characterized by an initial impairment in insulin secretion and late hyperinsulinaemia. Postprandial gastrointestinal hormone levels were normal following hypoglycaemia in these subjects. In four other subjects, the administration of intravenous glucose prior to the meal partially reversed the abnormal pattern of secretion. In two patients with a total pre-ganglionic sympathectomy, the pattern of blood glucose, plasma insulin and C-peptide was similar to that observed following hypoglycaemia in normal subjects. It is unlikely that an abnormal entero-insular axis or an elevation of plasma catecholamine levels are primarily responsible for this phenomenon. This effect of hypoglycaemia on postprandial insulin secretion may be caused by glucopenia of the pancreatic beta cells.

Blood Glucose↗
PubMed1981

Abnormalities of the colonic regulatory peptides in Hirschsprung's disease.

We describe here a depletion of peptide containing nerves and cells in Hirschsprung's disease, in comparison with specimens of bowel taken from age-matched neonates with no evidence of chronic constipation. VIP content in the diseased specimens was reduced by almost 80%, from 110/+-10.6 (mean +/- SEM) pmol VIP/g wet weight of tissue in controls to 23.8 +/- 3.5 pmol/g in the mid-portion of the diseased specimens. In addition, the numbers of enteroglucagon and somatostatin cells in the mucosa were significantly reduced in the aganglionic portions. Enteroglucagon cells were reduced from 55 +/- 7 in controls to 27 +/- 2 in proximal portions rising to 44 +/- 3 and 49 +/- 4 cells/mm2 in middle and distal areas. Somatostatin cell numbers also fell, from 5.5 +/- 1.9 to 1.8 +/- 0.8, 2.5 +/- 0.7 and 3.8 +/- 0.9 cells/mm2 in similar areas. Further investigation of the abnormalities of the diffuse neuroendocrine system in Hirschsprung's disease may help in understanding the nature of this condition and provide additional information on the role of these peptides in the control of gut function.

Bombesin↗
PubMed1981

Metabolic and endocrine responses to a milk feed in six-day-old term infants: differences between breast and cow's milk formula feeding.

There is little information on the metabolic and endocrine responses to milk feeding in the neonatal period particularly in relation to the model of nutrition and composition of the milk. Plasma concentrations of insulin, glucagon and gastric inhibitory polypeptide (GIP) together with blood levels of glucose, ketone bodies, pyruvate, lactate and glycerol were measured pre- and post-prandially in 79 health six-day-old term infants who had been either breast fed or fed on a modified cow's milk formula (Cow and Gate Premium) from birth. Formula fed infants had a greater insulin and GIP response to feeding and their basal and postprandial blood ketones were considerably lower than in breast fed infants. In addition a significantly greater post feed rise in both lactate and pyruvate concentrations was observed with formula feeding. These results may have significant implications regarding infant feeding and postnatal metabolism.

Animals↗
PubMed1981

Plasma neurotensin in term and preterm neonates.

The new ileal peptide neurotensin has not been studied hitherto in the human neonate. Plasma concentrations of neurotensin were measured by radioimmunoassay in 276 healthy term or preterm infants either at birth or pre- or post-prandially during the neonatal period. In addition, a group of 10 6-day-old preterm infants were studied who had never been enterally fed on account of hyaline membrane disease. Plasma neurotensin values were obtained also in 12 healthy fasting adults. Term infants had higher plasma neurotensin concentration than preterm infants at birth. Both groups showed a significant postnatal surge in basal (pre-prandial) neurotensin concentrations exceeding adult values, but no postnatal neurotensin elevation was found in the unfed group. In preterm infants, who were studied further into the neonatal period than term infants, there was a progressive increase in the rise of neurotensin following a milk feed, with a massive neurotensin response by 24 days of age. In 6-day-old term infants, the neurotensin response to bottle feeding was significantly greater than to breast feeding. These findings add further weight to the concept that neurotensin may be of physiological importance as a gut hormone. The high neurotensin levels and large feed responses seen in neonates may indicate a unique role for neurotensin in early life.

Bottle Feeding↗
PubMed1981

Effect of somatostatin infusion on intermediary metabolism and entero-insular hormone release in infants with hyperinsulinaemic hypoglycaemia.

The hypoglycaemia of infantile hyperinsulinism is often exceedingly difficult to control. The use of somatostatin has been advocated recently in such infants because of its effect on inhibiting insulin release, but nothing is known of the wider effects of this potent hormone in the young child. Two infants presenting at 9 weeks and 5 days of age with severe hyperinsulinaemic hypoglycaemia were studied during an infusion of somatostatin. In both infants normoglycaemia was restored with suppression of insulin secretion. An increase in blood ketone bodies occurred, but no change was seen in blood pyruvate, lactate or alanine concentrations. The plasma concentrations of glucagon, cortisol, growth hormone, motilin, pancreatic polypeptide, gastric inhibitory of polypeptide, neurotensin, gastrin and vasoactive intestinal peptide decreased markedly during the somatostatin infusion. No consistent change occurred in plasma enteroglucagon or secretin values. We conclude that somatostatin effectively suppresses abnormal insulin secretion in infants, but it has profound effects on the release of nine other hormones. Further studies are needed to define the consequences of suppressing the release of these hormones before somatostatin can be used routinely in the management of infantile hyperinsulinism.

Adenoma↗
PubMed1981

Pancreatic endocrine responses to exogenous neurotensin in the conscious calf.

1. Responses to neurotensin have been investigated in conscious calves 2-5 weeks after birth given continuous I.V. infusions of the peptide for 15 min (5 pmol. kg-1 . min-1). 2. In control calves the concentration of the peptide in the arterial plasma had risen by 160 +/- 10 pmol/l at the end of the infusion,. after which it fell exponentially (t1/2: 1.4 min). 3. This dose of neurotensin produced no significant change in mean heart rate, aortic blood pressure, plasma gastrin or glucose concentration. 4. It was found that neurotensin could produce a pronounced rise in the concentration of both insulin and pancreatic polypeptide (PP) in the arterial plasma, together with a much smaller rise in pancreatic glucagon concentration. 5. Each of these three pancreatic endocrine responses was found to be glucose-sensitive within the range ca. 5.0-9.0 mmol/l. Hyperglycaemia potentiated insulin release and inhibited release of PP and glucagon. 6. The results are discussed in relation to the findings of other workers in other species.

Animals↗
PubMed1981

Developmental changes in pancreatic endocrine function in the young calf.

1. Pancreatic endocrine responses to 2-deoxyglucose (1.2 mmol/kg I.V.) known to be mediated via the autonomic innervation, have been investigated in calves 24 h after birth and the results compared with those obtained previously in older calves (Bloom, Edwards & Hardy, 1978). 2. Neurally mediated insulin release was found to be defective in the calf at 24 h, whereas the capacity to release both pancreatic glucagon and pancreatic polypeptide (PP) in response to 2-deoxyglucose appears to be fully developed at this age. 3. Both the release of glucagon and of PP from the pancreas which occurred under these conditions were suppressed by I.V. infusions of glucose (17 mumol . kg-1 . min-1) which raised the arterial plasma glucose concentration of unsuckled 24-h-old calves to the level normally encountered in suckled calves of the same age. 4. Closely similar changes in the haematocrit and plasma cortisol concentration occurred in both suckled and unsuckled 24-h-old calves in response to 2-deoxyglucose, suggesting that the intensity of the stimulus to the brain was equipotent and that glucose inhibits the release of glucagon and PP by a direct action on the alpha and PP cells respectively. 5. closely similar changes in plasma PP concentration were observed in suckled and unsuckled 24-h-old calves in response to 2-deoxyglucose, in spite of the higher plasma glucose concentration in the former group. It is concluded that the PP response is potentiated by some unidentified factor in suckled calves.

Aging↗
PubMed1981

The role of the parasympathetic system in the control of insulin release in the conscious calf.

1. The effect of atropine (0.2 mg/kg) on the release of insulin from the pancreas, in response to both exogenous and endogenous hyperglycaemia, has been investigated in conscious 2- to 5-week-old calves. 2 The rise in mean plasma insulin concentration in response to infusions of glucose, which raised the concentration of glucose in the plasma by about 4.0 mmol/l, was significantly depressed in calves with cut splanchnic nerves by prior administration of atropine. 3. The rise in plasma insulin concentration, which normally follows stimulation of the splanchnic nerves in the conscious calf (Bloom & Edwards, 1980), was almost completely suppressed by prior administration of atropine. 4. These findings are discussed in relation to those of other workers with other species. The results indicate that the parasympathetic innervation to the pancreas plays an important part in the control of insulin release in response to hyperglycaemia.

Animals↗
PubMed1981

Pancreatic endocrine responses to stimulation of the peripheral ends of the vagus nerves in conscious calves.

1. The effects of stimulation of the peripheral ends of both vagus nerves below the heart (10 Hz for 10 min) were investigated in conscious calves 2-5 weeks after birth. 2. Stimulation was invariably below behavioural threshold and caused a prompt increase in the concentrations of pancreatic glucagon, insulin and pancreatic polypeptide (PP) in the arterial plasma. Each of these responses was blocked by pretreatment with atropine (0.2 mg/kg). 3. Administration of exogenous glucose by continuous I.V. infusion (ca. 0.08 mmol kg-1 min-1) greatly enhanced the release of insulin in response to vagal stimulation without significantly changing that of pancreatic glucagon or PP. 4. Vagal stimulation also caused a significant rise in the concentration of vasoactive intestinal peptide (VIP) in the intestinal lymph and this response was found to persist in the presence of atropine.

Animals↗
PubMed1981

Pancreatic endocrine function in cortisol-treated thyroidectomized calves.

1. Pancreatic endocrine function has been investigated in thyroidectomized calves given exogenous cortisol (2.0 mg.kg-1.day-1) in order to produce overt signs of diabetes. 2. Whenever this diabetic syndrome was induced it was associated with falling plasma insulin concentrations. A few days later, there was a significant rise in the post-absorptive concentration of both pancreatic glucagon and pancreatic polypeptide (PP) in the arterial plasma. Elevated levels of both hormones invariably persisted until the animals were given thyroxine. 3. Each of the pancreatic endocrine responses to cortisol was reversed by daily administration of thyroxine (25 microgram.kg-1. day-1) and the plasma glucose concentration was restored to normal within a few days. 4. Starvation was found to be an extremely effective way of reducing both the plasma glucose and glucagon concentration of diabetic calves without apparently affecting the concentration of either insulin of PP. 5. Neurally mediated release of insulin in response to 2-deoxyglucose, but not of either pancreatic glucagon or PP, was found to be defective in diabetic calves and recovered in response to thyroxine. 6. These results suggest that the primary defect that leads to the development of this diabetic syndrome in cortisol-treated thyroidectomized calves is failure of insulin release but that this is associated with consequential changes in the rates at which both glucagon and PP are released from the pancreas.

Animals↗
PubMed1981

Pancreatic endocrine responses to physiological changes in plasma neurotensin concentration in the calf.

1. Plasma neurotensin concentration was found to increase by between 3 and 18 pmol/l 20 min after feeding in conscious 2-6 week old calves. 2. Synthetic bovine neurotensin was infused I.V. at a dose which reproduced the rise in the plasma concentration (1 pmol. kg-1 min-1), in calves of the same age, which were also receiving a continuous I.V. infusion of glucose (0.03 mmol. kg-1. min-1) to mimic alimentary hyperglycaemia. Under these conditions neurotensin caused a significant rise in the mean concentration of both insulin and pancreatic polypeptide (PP), but not that of glucagon, in the arterial plasma. 3. The rise of plasma insulin concentration, but not that of PP, in response to the same dose of neurotensin was strongly potentiated during infusions of exogenous amino acids. There was also a significant rise in plasma glucagon concentration in response to neurotensin in the calves given amino acids. 4. It is concluded that neurotensin is a physiological incretin in the calf.

Animals↗
PubMed1981

Nesidioblastosis of the pancreas: definition of the syndrome and the management of the severe neonatal hyperinsulinaemic hypoglycaemia.

Three newborn infants are reported who developed severe non-ketotic hypoglycaemia (blood glucose less than 1.1 mmol/l; 19.8 mg/100 ml) within 6 hours of birth. All had inappropriately raised plasma insulin concentrations for the level of glycaemia, and required high rates of glucose infusion (less than 15 mg glucose/kg per minute) to prevent symptoms of hypoglycaemia. Medical treatment (hydrocortisone, diazoxide, chlorothiazide, phenytoin, propranolol, and depot glucagon) was ineffective in preventing hypoglycaemia and all 3 infants were subjected to partial and then total pancreatectomy. The pathological features of nesidioblastosis are reported from quantitative immunohistochemical studies on the pancreata. These results together with those from metabolic and endocrine studies performed on the 3 infants during the investigation of the cause of the hypoglycaemia and during the preoperative and postoperative period are presented in detail in order to define a practical approach to the management of this difficult clinical problem in the neonate.

Diazoxide↗