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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 1,027 records · Page 57Linked to original sources

Effects of vasoactive intestinal peptide and pancreatic polypeptide in rabbit intestine.

The effects of porcine vasoactive intestinal peptide (VIP) and bovine pancreatic polypeptide (PP) on jejunal, ileal, and colonic fluid transport were studied in the rabbit. VIP produced secretion in the small intestine (jejunum greater than ileum) but did not affect absorption in the colon. PP had no secretory effects in jejunum, ileum, or colon. The small intestinal secretion induced by VIP was not associated with raised cAMP concentrations in the mucosa; this suggests that the secretory effects of VIP in vivo are mediated by a mechanism other than stimulation of adenylate cyclase.

Animals↗

Gut-hormone profile in totally pancreatectomised patients.

In eight totally pancreatectomised patients the release of the relevant gut hormones was determined after a standard test meal. Plasma levels of pancreatic glucagon were not significantly different from zero in our series of pancreatectomised patients. Pancreatic polypeptide was undetectable. These findings imply the absence of a significant number of normally functioning alpha cells and pancreatic polypeptide cells in extrapancreatic sites in man. Consistent with the antrectomy, duodenectomy, and resection of the upper jejunum that are performed in conjunction with a total pancreatectomy the gastrin release was significantly impaired. In contrast there was a striking post-prandial rise in enteroglucagon probably induced by the rapid intestinal transit time often seen after partial gastrectomy. In contrast plasma motilin and GIP levels were normal. Pancreatectomised man thus presents an interesting model of total deficiency of endogenous insulin, pancreatic polypeptide, and pancreatic glucagon and, in addition, greatly diminished gastrin. The considerable derangement of metabolic and intestinal function that follows total pancreatectomy may, in part, be explained by this gross disturbance of the normal physiology of gut hormone.

Adult↗

Mixed pancreatic apudoma with symptoms of excess vasoactive intestinal polypeptide and insulin: improvement of diarrhoea with metoclopramide.

A female patient is described with a single pancreatic tumour producing vasoactive intestinal polypeptide (VIP), insulin, and pancreatic polypeptide. The initial presentation was with diarrhoea and hypokalaemia and a raised plasma VIP was demonstrated. Her symptoms improved with metoclopramide administration and absolute concentrations of 28 aminoacid (peak IV) VIP were found to have fallen. She then developed hypoglycaemia with hyperinsulinism. All symptoms resolved after surgical excision. This case emphasises the potential of these tumours to contain more than one endocrine cell type synthesising different biologically active peptides.

Apudoma↗

Somatostatin, gastrointestinal peptides, and the carcinoid syndrome.

During a control infusion noradrenaline and alcohol each provoked carcinoid flushing in four of five patients and pentagastrin in two of five patients. When tetradecapeptide somatostatin was infused on another day no patient flushed at any time, even when 16 microgram of either noradrenaline or pentagastrin were administered. Carcinoid flushing was not associated with release of gastrin or any of the other vasoactive or postprandially released gut regulatory peptides measured. In a sixth patient with severe prolonged carcinoid flushing, subcutaneous Des AA1, 2, 4, 5, 12D Trp8 somatostatin markedly reduced the incidence and severity of flushing for two days. Somatostatin is thus a potent inhibitor of carcinoid flushing, but no evidence has been found for the gut hormones measured to be mediators of flushing.

Aged↗

Lack of effect of pancreatic polypeptide in the rate of gastric emptying and gut hormone release during breakfast.

Bovine pancreatic polypeptide (PP) was infused intravenously in 5 healthy subjects on two separate occasions with mean doses of 1 and 2 pmol kg-1 min-1, respectively, which achieved plasma levels equal to and twice those observed after a normal mixed breakfast. The gastric emptying rate of a carbohydrate-rich breakfast 20 min after the start of each PP infusion was not significantly different from a control infusion of 0.15 M saline. PP is unlikely to be an important physiological modulator of gastric emptying rate in man.

Adult↗

Gut hormone responses in the irritable bowel syndrome.

Fasting and postprandial levels of gastrin, insulin, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, enteroglucagon and neurotensin were measured in 42 patients with irritable bowel syndrome (IBS). No overall major abnormalities of secretion of any of these peptides were found, although minor differences from normal of pancreatic polypeptide and neurotensin were observed. It is doubtful whether abnormalities of gut hormone secretion play an important role in the pathophysiology of IBS.

Adult↗

Pancreatic tumours produce neurotensin.

Tumour tissue may secrete substances which are not normally secreted by the original tissue. We have found that 6 out of 21 pancreatic tumours producing vasoactive intestinal peptide also produce neurotensin-like peptides. These are sometimes secreted and very high plasma levels of neurotensin-like immunoreactivity may be found in the circulation.

Female↗

The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.

The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.

Adult↗

Bombesin, somatostatin and neurotensin-like immunoreactivity in bronchial carcinoma.

Bombesin, a regulatory peptide found in adult lung and in higher concentration during development in the foetal lung, has potent biological actions which include the ability to stimulate the release of a number of hormones. Radioimmunoassay of extracts of tumour, lung and plasma from patients with bronchial carcinoma revealed very high tissue bombesin concentrations in two oat cell carcinomas, with lower levels in two out of six adenocarcinomas exceeding the concentrations found in normal lung. The oat cell carcinomas also contained significant amounts of somatostatin and in one case neurotensin. Neurotensin was further detected in two out of seven squamous tumours and three adenocarcinomas. Secretion of regulatory peptides by bronchial carcinomas may account for some of their ill-understood non-metastatic clinical manifestations.

Adenocarcinoma↗

Scope and specificity of acarbose in slowing carbohydrate absorption in man.

Fifty-gram carbohydrate tolerance tests were performed on healthy volunteers to test the activity and specificity of an alpha-glucoside hydrolase inhibitor, acarbose (BAY g 5421). Two hundred milligrams acarbose reduced the area under the blood glucose response curve by 89% (P less than 0.001) after sucrose by 80% (P less than 0.002) after starch, by 19% (N.S.) after maltose, with no effect on glucose. Breath hydrogen measurements indicated an almost complete malabsorption of the sucrose. At 50 mg acarbose, some reduction in blood glucose and insulin response to sucrose was still seen, but no significant hydrogen production. It is suggested that at lower doses, acarbose may prolong the time course over which carbohydrate is absorbed as does dietary fiber; as with fiber, it may be a useful adjunct to diabetic therapy.

Acarbose↗

Decrease of pancreatic somatostatin in neonatal nesidioblastosis.

The inappropriate insulin release that is characteristic of severe neonatal hypoglycemia and nesidioblastosis was thought to be principally due to a marked proliferation of B-cells. A possible deficiency of somatostatin, one of the factors controlling insulin release, has only recently been considered. We report have a significant decrease of pancreatic somatostatin cells and somatostatin content in nesidioblastosis, as compared with appropriate controls. Pancreatic tissue from five babies with severe hypoglycemia, hyperinsulinemia, and nesidioblastosis was examined for insulin, somatostatin, and glucagon by immunocytochemistry and radioimmunoassay. There was a variable insulin cell hyperplasia among the nesidioblastotic specimens but no significant difference from controls was detected. In contrast, there was a consistent and highly significant (P less than 0.02) decrease (of more than 50%) of somatostatin cells (controls, 1.29 +/- 0.22%; nesidioblastosis, 0.53 +/- 0.14%, mean +/- SEM). Similarly, there was no significant alteration in insulin content, although a slight increase was found in non-microadenomatous areas of the diseased pancreata (controls, 42.3 +/- 4.1; nesidioblastosis, 58.6 +/- 9.4 nmol/g wet weight of tissue, mean +/- SEM). However, somatostatin content was almost 60% below control values (controls, 0.365 +/- 0.038; nesidioblastosis, 0.16 +/- 0.039 nmol/g), a statistically significant difference (P less than 0.01). Thus, a marked reduction in the content of somatostatin was present in the pancreata of these infants with nesidioblastosis, resulting in a distinct alteration of the normal pancreatic hormone balance.

Fluorescent Antibody Technique↗

GIP and insulin responses to oral glucose in coeliac patients before and after treatment.

The responses of plasma gastric inhibitory polypeptide (GIP) and insulin to oral glucose were studied in five patients with untreated coeliac disease. These patients were restudied after one year on a gluten-free diet. In the untreated patients, the blood glucose, serum insulin, and GIP levels were significantly lower than in the controls. After gluten withdrawal there was an improvement towards normality in the responses of blood glucose, serum insulin, and GIP. The results show that untreated coeliac disease is associated with abnormalities of intestinal and pancreatic hormone secretion and that these abnormalities are improved by gluten withdrawal.

Administration, Oral↗

Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity.

The treatment of obesity by intestinal bypass provides a unique model for the investigation of gut hormone release from the functionally deranged bowel. We have examined the postprandial response of eight circulating gut or pancreatic peptide hormones in 16 preoperative obese patients, 20 patients with jejunoileal bypass, 38 patients with biliopancreatic bypass and 13 age and sex-matched controls. Basal and post-meal hormone concentrations were determined by specific radioimmunoassay methods. Reductions of the upper small intestinal hormones, motilin and gastric inhibitory polypeptide were found in both types of surgery. Conversely, the ileal hormones neurotensin and enteroglucagon were elevated following surgery. This pattern is consistent with the known distribution of these hormones. Variations of response due to surgical differences were noted for gastrin and the enteropancreatic axis, which was more markedly disturbed after biliopancreatic bypass. The alterations of hormone release closely reflect the anatomical changes induced by each particular surgical technique.

Adult↗

The control of the adaptation of the human neonate to postnatal nutrition.

Major changes occur in the function of several physiological systems after birth which enable the neonate to adapt to postnatal nutrition. It is suggested that the secretion of gut and pancreatic hormones in response to enteral feeding has a key role in triggering a cascade of developmental changes in gut structure and function, and in the relation of pancreatic endocrine secretion to intermediary metabolism. Evidence to support this hypothesis is presented.

Acclimatization↗

Regulatory peptides in endocrine cells and autonomic nerves: electron immunocytochemistry.

Advances in immunocytochemistry, particularly at the electron microscope level, have enabled us to establish further details of the ultrastructural appearance of endocrine cells and autonomic nerves of the gastrointestinal tract. Its contribution can be summarised as follows: a)validation of previously recognised endocrine cell types. b) Recognition of sub-groups within endocrine cells and autonomic nerve cell types previously included within one single type (e.g. D1 cells and p-type autonomic nerves). c) Discrimination of molecular forms now known to be stored in morphologically distinguishable secretory granules or parts thereof (e.g. pro-glucagon and glucagon in A cells and gut and antral gastrin-producing cells). Advances in the techniques and the accurate quantification of the end products will enable us to recognise changes in gastrointestinal tract diseases in man.

Animals↗

Effect of motilin on the gastric emptying of glucose and fat in humans.

The effect of natural motilin on the rate of gastric emptying of 200 ml 25% glucose was studied in seven subjects using a 99mtechnetium tin colloid marker. On the control day the subjects received intravenous saline while on the test day they received a motilin infusion of 0.2 pmol/kg/min. Infusions were blind and given in random order. Thirty minutes after glucose ingestion, 25.5 +/- 2% of the isotope had emptied during motilin infusion, compared with 11.0 +/- 1.5% with saline (p < 0.005). Plasma motilin concentrations rose from a basal value of 23 +/- 5 pM to 57 +/- 9 pM during the motilin infusion. The faster emptying rates after motilin were reflected in a faster rise of plasma glucose and insulin. The rate of emptying of 99mtechnetium-labeled double cream (200 ml, 24 g fat) was measured in 5 subjects. The rate of gastric emptying of the cream was unaffected by exogenous motilin. Gel chromatographic analysis of basal plasmas revealed two immunoreactive motilin peaks. After ingestion of cream during motilin infusion, there was an increase of the second peak but a reduction of the first peak whereas both peaks rose on the control day. Thus low-dose exogenous motilin stimulates the gastric emptying of glucose but not of fat.

Adult↗