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S R Bloom

Publications and source records attributed to S R Bloom.

At least 217 records · Page 12Linked to original sources
PubMed1994

Atrial natriuretic peptide and glucagon release in experimental intestinal ischaemia and reperfusion.

Intestinal ischaemia and reperfusion cause changes in cardiovascular and pulmonary function. In a rat model, the plasma concentrations of atrial natriuretic peptide (ANP) and pancreatic glucagon rose on reperfusion after 20 min of intestinal ischaemia, coinciding with significant arterial hypotension: mean(s.e.m.) ANP 79(13) versus control 36(4) fmol ml-1 (P < 0.01); and mean(s.e.m.) glucagon 22(2) versus control 10(1) fmol ml-1 (P < 0.001). Glucagon was also released on reperfusion after 5 min of ischaemia: mean(s.e.m.) 18(2) fmol ml-1 (P < 0.001 versus control). In a second experiment, pretreatment of rats with allopurinol did not prevent arterial hypotension but abolished ANP release (mean(s.e.m.) 36(2)fmol ml-1 versus no pretreatment 70(7) fmol ml-1, P < 0.05), while glucagon release was unaffected. The release of ANP, but not that of glucagon, is therefore mediated by oxygen free radicals and may signify cardiac and/or pulmonary injury or dysfunction. The actions of these peptides may be relevant in the pathophysiological perturbation of intestinal ischaemia-reperfusion.

Allopurinol↗
PubMed1994

Localization and surgical management of insulinoma.

Over a 14-year period 34 patients were referred for surgical treatment of insulinoma. The diagnosis was confirmed by demonstrating hypoglycaemia with inappropriate hyperinsulinaemia during prolonged fasting. Selective visceral angiography localized 30 solitary benign insulinomas and two carcinomas. In two patients with islet cell hyperplasia, angiography demonstrated a single lesion only. Ultrasonography had a sensitivity of 15 per cent and computed tomography a sensitivity of 24 per cent in the localization of tumours. All patients but one were treated by operation. Eighteen tumours were enucleated and 13 (including both patients with islet cell hyperplasia) were treated by distal pancreatectomy. Two patients underwent negative primary exploration; both had single adenomas removed at re-exploration. There were no operative deaths but nine patients (predominantly those undergoing pancreatic resection) had complications. Thirty-one patients were symptom-free following operation at a mean follow-up of 16 months.

Adolescent↗
PubMed1994

Amylin tonally regulates arginine-stimulated insulin secretion in rats.

To assess the effect of naturally-present amylin in the control of insulin release we infused a novel amylin antagonist, its 8-37 fragment, or amylin in anaesthetized rats for 60 min, and 30 min after the start arginine was infused for 14 min. Amylin8-37 decreased the blood glucose concentration by 18% whereas the plasma insulin concentration was 90% higher following arginine treatment. In contrast amylin infusion raised both glucose and insulin concentrations. These results suggest that while amylin added at high dose can induce peripheral insulin resistance, naturally present amylin tonally controls insulin secretion.

Amyloid↗
PubMed1994

Lack of acute effect of amylin (islet associated polypeptide) on insulin sensitivity during hyperinsulinaemic euglycaemic clamp in humans.

It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeostasis and on insulin sensitivity using the euglycaemic hyperinsulinaemic clamp. The amylin used opposed insulin-mediated glucose disposal in rat soleus muscle at concentrations of 10 nmol/l. Seven subjects were studied on two occasions and infused with either amylin or placebo for 6 h, initially when postabsorptive and then during a euglycaemic hyperinsulinaemic clamp. Mean plasma amylin concentrations during the first 3 h were 2006 +/- 327 pmol/l during amylin infusion and 20 +/- 9 pmol/l during the control infusion. Amylin infusion had no effect on postabsorptive plasma concentrations of insulin (control: 32 +/- 16 vs amylin: 25 +/- 8 pmol/l) or glucose (5.1 +/- 0.1 vs 5.3 +/- 0.1 mmol/l). During the clamp, amylin concentrations were 1636 +/- 422 pmol/l when it was infused and 24 +/- 6 during control infusions. Plasma glucose and insulin concentrations were well matched during the control and amylin infusions (glucose: 4.7 +/- 0.1 vs 4.8 +/- 0.1 mmol/l; insulin: 198 +/- 37 vs 195 +/- 22 pmol/l). Exogenous glucose infusion rates were a mean of 13% lower than control values during the amylin infusion but were not statistically different (p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Naloxone-induced anorexia increases neuropeptide Y concentrations in the dorsomedial hypothalamus: evidence for neuropeptide Y-opioid interactions in the control of food intake.

We measured neuropeptide Y (NPY) concentration in microdissected hypothalamic nuclei, by radioimmunoassay, and NPY mRNA in the hypothalamus in rats treated systemically with the nonspecific opioid antagonist, naloxone, to produce mild anorexia. Twenty rats were treated with daily SC injections of naloxone (7.5 mg/kg); 20 were treated with vehicle alone. Naloxone produced a 7% reduction in food intake (p < 0.01) and a reduction in weight gain (p < 0.002). Neuropeptide Y concentrations were increased specifically in the dorsomedial nucleus of the hypothalamus (DMN) in rats treated with naloxone (6.8 +/- 0.7 fmol/micrograms protein vs. 3.1 +/- 1.0 fmol/micrograms protein, p < 0.05, n = 10 per group). Total hypothalamic NPY mRNA was unchanged. Neuropeptide Y-opioid interactions may be important in the control of food intake.

Animals↗
PubMed1994

Solubilization of binding sites for IAPP and CGRP from rat lung.

Functional binding sites for [125I]IAPP and [125I]CGRP were solubilized from rat lung membranes with CHAPSO (10 mM). Rat IAPP had a higher affinity (Ki = 22.9 nM) for [125I]IAPP binding and rat alpha CGRP (Ki = 0.904 nM) had a higher affinity for [125I]CGRP binding over related peptides. [125I]IAPP binding was unaffected by GTP gamma S, but [125I]CGRP binding was 50% inhibited, indicating solubilization of a G-protein-receptor complex for CGRP but not IAPP binding. Wheat germ agglutinin affinity columns gave a 25-fold purification of IAPP binding sites, but no CGRP binding sites were eluted from the column, indicating different patterns of glycosylation of the two sites.

Amyloid↗
PubMed1994

The effects of PACAP and VIP on guinea pig tracheal smooth muscle in vitro.

Neither pituitary adenylate cyclase activating polypeptide-38 (PACAP) nor its homologue, vasoactive intestinal polypeptide (VIP), contracted guinea pig isolated trachea (GPT), but on preparations contracted with KCl (40 mM), both caused concentration-related relaxation (3 nM-3 microM, VIP IC50 = 72 nM, PACAP IC50 = 224 nM). Relaxant curves to PACAP were slower in reaching a maximum than those to VIP (approximately 150 and 50 min, respectively). The protease inhibitors, phosphoramidon (1 microM), leupeptin (50 microM), bestatin (100 microM), soya bean trypsin inhibitor (1 microM), and aprotinin (5 microM), together caused a small enhancement of relaxations to VIP, but not to PACAP. The VIP antagonist, [4-Cl-D-Phe6, Leu17]VIP (1-10 microM), did not inhibit the relaxation to either peptide, but did cause large contractions, which were enhanced by protease inhibition. These findings demonstrate that PACAP relaxes GPT in a similar manner to VIP.

Animals↗
PubMed1994

The effects of IAPP and CGRP on guinea pig tracheal smooth muscle in vitro.

Neither the novel peptide, islet amyloid polypeptide (IAPP), nor its homologue, calcitonin gene-related peptide (CGRP), contracted guinea pig isolated trachea (GPT), but on preparations contracted with KCl (40 mM), both caused concentration-related relaxation (1 nM-3 microM). Relaxant curves to both were shallow and slow in development, with clear maxima not being obtained. The protease inhibitors, phosphoramidon (1 microM), leupeptin (50 microM), bestatin (100 microM), soya bean trypsin inhibitor (1 microM), and aprotinin (5 microM), together had no effect on relaxations to CGRP, but depressed those to IAPP. Aprotinin appeared to be responsible for this depression. The specific CGRP antagonist, CGRP(8-37), 1-10 microM, had no effect on relaxations to either peptide. These findings demonstrate that IAPP relaxes GPT in a similar manner to CGRP.

Amyloid↗
PubMed1994

Absence of mutations in the Gs alpha and Gi2 alpha genes in sporadic parathyroid adenomas and insulinomas.

1. Activating mutations of the alpha-subunits of the Gs and Gi2 proteins give rise to the oncogenes gsp and gip2, respectively, which are found in a variety of endocrine tumours. 2. In this study the polymerase chain reaction and direct sequencing have been used to screen a small sample of parathyroid adenomas and insulinomas for these mutations. 3. No mutations were identified in nine insulinomas and 13 parathyroid adenomas screened for gsp, and 11 parathyroid adenomas and four insulinomas screened for gip2. In addition, two gastrinomas from patients with multiple endocrine neoplasia type 1 were found to be negative for both oncogenes. 4. This is the first report of screening for gip2 in parathyroid adenomas and gsp/gip2 in insulinomas, and it extends the range of tumours examined for these oncogenes.

Adenoma↗
PubMed1994

Elevated plasma endothelin concentrations in heart failure; an effect of angiotensin II?

Endothelin is a powerful vasoconstrictor that may be partly responsible for the increases in venous and arterial tone characteristic of heart failure. The release of endothelin from endothelial cells in culture is stimulated by angiotensin II. We investigated the relationship between plasma concentrations of immuno reactive endothelin-1 and angiotensin II in 25 patients with heart failure and eight with ischaemic heart disease but normal left ventricular function. Plasma concentrations of endothelin and angiotensin II were correlated (Spearman rank correlation coefficient of 0.72; P < 0.0001) in patients with heart disease. Plasma concentrations of angiotensin II and endothelin were higher in those patients with heart failure. Angiotensin II was infused over a 3 h period in eight healthy volunteers. Infusion of angiotensin II increased plasma concentrations of angiotensin II to levels greater than those usually found in patients with severe heart failure but induced only a modest rise in plasma concentrations of immunoreactive endothelin-1 (0.77 +/- 0.16 to 1.03 +/- 0.03 pmol.l-1, P < 0.02). Increased plasma concentrations of angiotensin II and endothelin-1 both appear to reflect the presence and severity of heart failure. Although a significant correlation exists between plasma concentrations of angiotensin II and endothelin in patients with heart failure, the relationship may not be causal.

Adult↗
PubMed1994

Intrapulmonary shunting causing hypoxaemia in a case of carcinoid syndrome.

A case of metastatic carcinoid syndrome with hypoxaemia is described. The hypoxaemia appeared to be due to intrapulmonary shunting. There was improvement in resting and exercise arterial oxygen saturations following chemotherapy with streptozotocin and 5-fluorouracil. This was followed by a decrease in the tumour bulk which may have led to a reduction in the secretion of the vasodilator products responsible for shunting. Some features of this case suggest that the hypoxaemia might have been due to dilatation of precapillary and capillary vessels of the pulmonary micro-circulation. These features are part of the so-called 'hepatopulmonary syndrome', of which this case appears to represent a less severe form.

Adult↗
PubMed1994

Islet amyloid polypeptide: does it play a pathophysiological role in the development of diabetes?

There is suggestive evidence that amylin acts physiologically in an autocrine manner within the islet to restrain insulin secretion, but conversely there is little indication that this action of amylin plays any role in the development of NIDDM. Deposition of amylin within pancreatic islets is a feature in patients with NIDDM but is of sufficient degree to disrupt beta-cell function in only a small minority of individuals. Current evidence suggests that amylin does not have any physiologically important extra-islet metabolic effects. The potential exists for the development of amylin antagonists as pharmacological agents to enhance insulin secretion in NIDDM but antagonism of systematic CGRP would need to be avoided. There is little, if any, indication that either replacement of amylin or treatment with amylin agonists are likely to have any beneficial role in patients with IDDM.

Amyloid↗
PubMed1994

Release of vasodilator, but not vasoconstrictor, neuropeptides and of enteroglucagon by intestinal ischaemia/reperfusion in the rat.

Reperfusion of ischaemic intestine is characterised by an initial hyperaemia with ensuing mucosal repair. This study investigated possible roles for gut vasoactive neuropeptides and trophic peptides in these phenomena. Groups of rats were monitored during superior mesenteric artery occlusion for five or 20 minutes, with or without subsequent reperfusion for five minutes. Peptide concentrations (fmol/ml) in arterial blood, were measured using specific radioimmunoassays. Intestinal ischaemia alone did not cause haemodynamic disturbance or peptide release. Reperfusion, after five minutes of ischaemia, resulted in arterial hypotension and a rise in plasma vasoactive intestinal polypeptide (mean (SEM)) (37 (3), control 11 (4), p < 0.001). After 20 minutes of ischaemia, reperfusion resulted in greater hypotension (p < 0.05) and release of both vasoactive intestinal polypeptide (31 (3), p < 0.05 v control) and the more potent vasodilator beta-calcitonin gene related peptide (49 (3), control 23 (1), p < 0.001). By contrast, the vasodilators alpha-calcitonin gene related peptide and substance P and the vasoconstrictors neuropeptide Y, peptide YY, and somatostatin were not released. Bombesin, a stimulatory neuropeptide, was released after 20 minutes of ischaemia/reperfusion (13 (2), control 7 (3), p < 0.05). Plasma enteroglucagon rose from control (51 (4)) to 110 (16) (p < 0.001) and to 158 (27) (p < 0.005) after five and 20 minutes of ischaemia/reperfusion. The potent enteric vasodilators vasoactive intestinal polypeptide and beta-calcitonin gene related peptide, unopposed by vasoconstrictors, may promote post-ischaemic intestinal hyperaemia. The rise in plasma enteroglucagon may point to diffuse mucosal injury and is consistent with the putative trophic role of this peptide.

Animals↗
PubMed1994

Pancreatic endocrine responses to substance P and calcitonin gene-related peptide in conscious calves.

Both substance P (SP) and calcitonin gene-related peptide (CGRP; 0.13 micrograms.min-1.kg-1 for 10 min) produced a significant rise in arterial plasma pancreatic polypeptide (PP) concentration, and additive responses were obtained when both peptides were infused simultaneously and/or with acetylcholine (0.7 micrograms.min-1.kg-1 ia). The PP response to SP was abolished by intravenous infusions of glucose, whereas those to CGRP and acetylcholine were not significantly affected. Neither SP nor CGRP had any effect on plasma insulin concentration, either in the presence or absence of exogenous glucose, whether infused singly or together, or in the presence of acetylcholine. SP, but not CGRP, produced a small but statistically significant rise in mean plasma glucagon concentration when infused together with acetylcholine. These results suggest that SP and CGRP may modulate the secretion of PP and glucagon in the normal conscious calf but not that of insulin. It is also possible that SP modulates secretion of pancreatic glucagon in these animals.

Acetylcholine↗
PubMed1994

Evidence of a paracrine role of neuropeptide-Y in the regulation of insulin release from pancreatic islets of normal and dexamethasone-treated rats.

Recent evidence suggests that a number of a paracrine regulatory peptides, including neuropeptide-Y (NPY), are synthesized within pancreatic islets. We have, therefore, assessed the role of NPY on insulin release from isolated perifused rat islets. NPY release was detectable at 2.1 (95% confidence interval, 1.6-2.6) attomoles/islet.min from the perifused islets of control rats when the glucose concentration was 2.8 mM and decreased by 62% (P = 0.01) on changing to 20 mM glucose. The initial insulin release was 0.7 (0.3-1.6) fmol/islet.min, and it was increased 4-fold (P < 0.001) by high glucose. Simultaneously, pancreatic glucagon release was decreased 85% (P < 0.001), and somatostatin release was decreased 25% (P = 0.06). In contrast, in islets from rats given dexamethasone (4 mg/kg.day) for 10 days, NPY release was 6-fold increased by high glucose. NPY (100 nM) decreased insulin release by 44% (P < 0.001). To determine the influence of naturally present islet NPY on insulin release, immunoneutralization with NPY antiserum was employed. With control rat islets, insulin release was increased 3-fold with NPY antiserum (P = 0.02) in the presence of 2.8 mM glucose and elevated 2-fold at 8 mM glucose (P < 0.001). NPY immunoneutralization similarly increased insulin release from the perifused islets of rats treated with dexamethasone. Our results suggest that NPY is produced by pancreatic islets, and its expression is dependent on the prevailing endocrine environment. Islet NPY appears to constrain insulin release under a variety of conditions. NPY may be an important intraislet paracrine hormone.

Animals↗
PubMed1994

Effect of a new oral somatostatin analog (SDZ CO 611) on gastric emptying, mouth to cecum transit time, and pancreatic and gut hormone release in normal male subjects.

Sixteen healthy male volunteers participated in a randomized, double blind, parallel groups study. Subjects received either 1 or 5 mg SDZ CO 611 (a new, orally active somatostatin analog) twice daily over a 14-day period and acted as their own controls. Gastric emptying of 99mTc and mouth to cecum transit time, as measured by the breath hydrogen technique, after a mixed meal containing lactulose and 99mTc-diethylenetriaminepentaacetate, were assessed once before, twice during, and once after the period of study medication. Gastric emptying of 99mTc was significantly accelerated by the higher dose of SDZ CO 611, whereas mouth to cecum transit time was prolonged by the drug in a dose-dependent manner. Both doses of SDZ CO 611 led to suppression of the fasting level and postprandial release of several gastrointestinal and pancreatic hormones. This effect was more marked in those subjects taking 10 mg/day of the study medication. Motilin and pancreatic polypeptide were the most sensitive to the inhibitory actions of the analog. Glucose tolerance was significantly impaired by the 10-mg dose of the drug. We conclude that this new, orally active derivative of somatostatin is as effective on the gastrointestinal tract as the sc somatostatin analog octreotide. It would, therefore, be a useful advance in the treatment of gastroenteropancreatic tumors.

Administration, Oral↗