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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 343 records · Page 19Linked to original sources
PubMed1990

The hormonal responses to repetitive brief maximal exercise in humans.

The responses of nine men and nine women to brief repetitive maximal exercise have been studied. The exercise involved a 6-s sprint on a non-motorised treadmill repeated 10 times with 30 s recovery between each sprint. The total work done during the ten sprints was 37,693 +/- 3,956 J by the men and 26,555 +/- 4,589 J by the women (M greater than F, P less than 0.01). This difference in performance was not associated with higher blood lactate concentrations in the men (13.96 +/- 1.70 mmol.l-1) than the women (13.09 +/- 3.04 mmol.l-1). An 18-fold increase in plasma adrenaline (AD) occurred with the peak concentration observed after five sprints. The peak AD concentration in the men was larger than that seen in the women (9.2 +/- 7.3 and 3.7 +/- 2.4 nmol.l-1 respectively, P less than 0.05). The maximum noradrenaline (NA) concentration occurred after ten sprints in the men (31.6 +/- 10.9 nmol.l-1) and after five sprints in the women (27.4 +/- 20.8 nmol.l-1). Plasma cardiodilatin (CDN) and atrial natriuretic peptide (ANP) concentrations were elevated in response to the exercise. The peak ANP concentration occurred immediately post-exercise and the response of the women (10.8 +/- 4.5 pmol.l-1) was greater than that of the men (5.1 +/- 2.6 pmol.l-1, P less than 0.05). The peak CDN concentrations were 163 +/- 61 pmol.l-1 for the women and 135 +/- 61 pmol.l-1 for the men. No increases in calcitonin gene related peptide (CGRP) were detected in response to the exercise. These results indicate differences between men and women in performance and hormonal responses. There was no evidence for a role of CGRP in the control of the cardiovascular system after brief intermittent maximal exercise.

Adult↗
PubMed1990

The effect of splanchnic nerve stimulation on the uptake of atrial natriuretic peptide by the adrenal gland in conscious calves.

A technique has been developed with which it has been possible to quantify the output of a wide variety of agonists including catecholamines, glucocorticoids, mineralocorticoids, enkephalins and various peptides, from the adrenal gland in the conscious unrestrained calf; also to investigate responses to electrical stimulation of the peripheral end of the splanchnic nerve below any behavioural threshold. In the present study this methodology has been employed to investigate the extent to which stimulation of the splanchnic sympathetic innervation affects adrenal handling of atrial natriuretic peptide as this peptide has been identified within the adrenal medulla in this species. Stimulation of the splanchnic nerve at frequencies which raised the concentration of atrial natriuretic peptide like-immunoreactivity (ANP) by 25% led to an abrupt increase in the uptake of the peptide by the right adrenal gland by about 250%. During nerve stimulation more than 20% of the ANP that was estimated to be presented to the gland was taken up, by comparison with less than 13% of the amount presented which was taken up before and after stimulation. These results suggest that stimulation of the splanchnic nerve may specifically enhance the uptake of ANP by the adrenal gland and represent the first report of such a mechanism in respect of any biologically active peptide so far as we are aware.

Adrenal Glands↗
PubMed1990

Endothelin in the gastrointestinal tract. Presence of endothelinlike immunoreactivity, endothelin-1 messenger RNA, endothelin receptors, and pharmacological effect.

The possible production and role of endothelin in the gastrointestinal tract was investigated in rats by radioimmunoassay, Northern-blot hybridization, receptor assay using membrane preparations, and pharmacological study using gut strips. Endothelinlike immunoreactivity was detected in all regions (from stomach to colon) of the rat gastrointestinal tract (13-48 fmol/g wet tissue) including the mucosal layer of the ileum and colon (8.4 +/- 2.0 fmol/g wet tissue and 18.4 +/- 2.1 fmol/g wet tissue, respectively, mean +/- SEM; n = 5). Fast protein liquid chromatographic analysis of the endothelinlike immunoreactivity in jejunum, ileum, colon, and colon mucosa extracts showed peaks in the positions of endothelin-1 and endothelin-3. The presence of endothelin-1 messenger RNA was demonstrated by Northern-blot hybridization in the whole colon and pooled ileal and colonic mucosa, but not in the whole jejunum. Specific binding in the rat gastrointestinal tract was particularly high in the fundus of stomach, jejunum, ileum, and colon. In the ileum, many binding sites were found in the circular and longitudinal muscle layers, but few in the mucosal layer. Endothelin-1 and endothelin-3 caused contraction of rat stomach strips, rat colon, and guinea pig ileum. These findings indicate that endothelin is present in the rat gastrointestinal tract, perhaps produced by both vascular endothelial cells and mucosal epithelial cells, and can cause contraction of gastrointestinal smooth muscle. Thus, endothelin may have a physiological role in the control of gastrointestinal function.

Animals↗
PubMed1990

Effects of preprovasoactive intestinal polypeptide-derived peptides on ileal output.

Tumors associated with the Verner Morrison syndrome secrete peptide histidine methionine, its C-terminally extended variant peptide histidine valine, and vasoactive intestinal peptide. There is evidence that vasoactive intestinal peptide mediates diarrhea, but recent evidence suggested that peptide histidine methionine and peptide histidine valine may be at least as important. Infusion of vasoactive intestinal peptide, peptide histidine methionine, and peptide histidine valine into patients with ileostomies produced mean plateau plasma levels of 163, 1301, and 2106 pM, respectively, which are within the range seen in the Verner Morrison syndrome. Vasoactive intestinal peptide produced an integrated ileal output of 174 (53) g (mean [SEM]), compared with only 20 (7) g with peptide histidine methionine and 10 (3) g with peptide histidine valine. These results suggest that vasoactive intestinal peptide is substantially more important than peptide histidine methionine or peptide histidine valine in mediating diarrhea in the Verner Morrison syndrome.

Adult↗
PubMed1990

Increased pressor effect of repeated doses of rat or porcine endothelin in the anaesthetised rat.

Rat and porcine endothelin differ by 6 amino acids. Porcine and rat endothelin were equiactive at producing the transient fall in blood pressure in the anaesthetised rat but porcine endothelin was three times more potent at producing the subsequent sustained rise. Repeated doses of either peptide in the same rat produced a larger pressor response with each repetition, the peak response being reached more rapidly. The magnitude of the blood pressure fall did not change significantly but the first response in each rat was of longer duration than subsequent responses, especially with rat endothelin.

Animals↗
PubMed1990

Neuropeptide Y (NPY)-containing nerves in mammalian ureter.

The distribution of neuropeptide Y in the ureter of the rat, rabbit, and man has been determined by radioimmunoassay and chromatographic analysis of the tissue extract. The localization of neuropeptide Y-immunoreactivity has been identified by immunocytochemistry. A regional distribution of neuropeptide Y was found; highest concentrations being present in the ureterovesical junction. Throughout the ureter, neuropeptide Y-immunoreactive nerve fibers were identified to surround the blood vessels and a few plexuses of neuropeptide Y-containing nerves were present within the muscle layers. Neuropeptide Y was not present within ganglion cells. Treatment of rats with 6-hydroxydopamine resulted in a significant reduction of neuropeptide Y concentrations in the upper, middle, and lower thirds of the ureter. This depletion in extractable neuropeptide Y was associated with morphologic changes typical of axonal degeneration of the neuropeptide Y-containing nerve fibers.

Animals↗
PubMed1990

Combined use of immunocytochemistry and in situ hybridization to study beta thyroid-stimulating hormone gene expression in pituitaries of hypothyroid rats.

Immunocytochemistry and in situ hybridization were used to demonstrate beta thyroid-stimulating hormone (TSH) immunoreactivity and beta TSH messenger RNA (mRNA) in the same tissue section of rat pituitary. Sections (10 micronsP of 4% paraformaldehyde-fixed pituitaries from surgically thyroidectomized and intact male rats were first hybridized with a 32P-labelled complementary RNA beta TSH probe and were then immunostained for beta TSH. In both sets of animals beta TSH mRNA and beta TSH immunoreactivity were simultaneously localized to many thyrotrophs, although there was considerable heterogeneity in mRNA labelling intensity between individual cells. In hypothyroid rats more cells were positive with both probe and antiserum, and the intensity of mRNA labelling in most quantified by direct apposition of hybridized sections to autoradiography film, and the image grey levels were measured using an image analyser to convert them into equivalent amounts of radioactivity. In hypothyroid rats this amount was 22 times greater than in controls (control 4.77 +/- 0.84 attomoles mm-2; hypothyroid 107.06 +/- 14.2 attomoles mm-2; mean +/- SEM p less than 0.001). In situ hybridization has been used in combination with immunocytochemistry, to demonstrate beta TSH and mRNA and immunoreactivity at a cellular level in rats with different thyroid status.

Animals↗
PubMed1990

Peptide histidine valine: its haemodynamic actions and pharmacokinetics in man differ from those of vasoactive intestinal peptide and peptide histidine methionine.

1. The effects of intravenous and intra-arterial infusion of the peptides derived from prepro-vasoactive intestinal peptide, vasoactive intestinal peptide, peptide histidine methionine and peptide histidine valine, were examined in six healthy volunteers. 2. Vasoactive intestinal peptide given intravenously caused a significant increase in heart rate and a decrease in diastolic, but not systolic, blood pressure, whereas peptide histidine valine caused an increase in heart rate alone, despite higher achieved circulating peptide concentrations. Peptide histidine methionine did not affect heart rate or blood pressure. Forearm blood flow was increased by vasoactive intestinal peptide and peptide histidine valine when infused locally intra-arterially, although vasoactive intestinal peptide was more potent than peptide histidine valine. 3. Plasma concentrations of cardiodilatin (the N-terminal peptide derived from pro-atrial natriuretic peptide) were increased by intravenous infusion of vasoactive intestinal peptide, but were unaffected by peptide histidine methionine or peptide histidine valine. Circulating plasma concentrations of adrenaline and noradrenaline did not change during infusion of vasoactive intestinal peptide, peptide histidine methionine or peptide histidine valine. 4. Peptide histidine valine had a long half-life when compared with peptide histidine methionine and vasoactive intestinal peptide. 5. We conclude that peptide histidine valine is active in the human cardiovascular system and has a similar, though less potent, vasodilating action to vasoactive intestinal peptide. The higher circulating levels of peptide histidine valine found in man suggest that it may be important in modulating vascular tone.

Adult↗
PubMed1990

Endothelin immunoreactivity in mice with gram-negative bacteraemia: relationship to tumour necrosis factor-alpha.

1. To investigate the role of endothelin in Gram-negative bacteraemia and the possible involvement of tumour necrosis factor-alpha in its pathophysiology, we measured plasma and tissue (lung, kidney and spleen) immunoreactive endothelin levels in Gram-negative bacteraemic mice, with and without passive immunization by anti-(tumour necrosis factor-alpha) antibody. 2. Plasma immunoreactive endothelin levels were greatly increased after the Escherichia coli injection. Pretreatment with anti-(tumour necrosis factor-alpha) antibody did not suppress elevated plasma immunoreactive endothelin levels (P greater than 0.1). 3. Lung tissue immunoreactive endothelin levels in mice were increased 16 h after the E. coli injection and were not affected by prior passive immunization with anti-(tumour necrosis factor-alpha) antibody. Immunoreactive endothelin in spleen and kidney was undetectable (less than 34 fmol/g wet weight). 4. Injection of rMu tumour necrosis factor-alpha into mice did not increase plasma immunoreactive endothelin levels. 5. Antibody to endothelin given 30 min after a 90% lethal dose challenge with E. coli did not affect mortality. 6. We conclude that the rise in plasma and tissue endothelin that occurs in Gram-negative bacteraemia is independent of tumour necrosis factor-alpha.

Animals↗
PubMed1990

Intussusception in the Syrian golden hamster.

Of a series of ninety-six young male Syrian Golden hamsters, 13% developed lethargy, anorexia, diarrhoea and colocolic intussusception when their diet was changed from a basal laboratory-grade rodent chow to a nutritionally complete semi-purified diet. Histologically, the colon of the hamsters with intussusception had markedly reduced mucus production. Plasma levels of gastric inhibitory polypeptide (GIP) were reduced 80% (P less than 0.01) but peptide tyrosine/tyrosine and enteroglucagon in plasma were increased 290 and 526% respectively in hamsters with intussusception. Variations in dietary fatty acid composition had no effect but intussusception was not observed after changing the dietary carbohydrate from sucrose to starch.

Animals↗
PubMed1990

Hormonal responses to cardiac surgery: effects of sufentanil, somatostatin and ganglion block.

We have investigated the effect of the addition of somatostatin and trimetaphan to sufentanil 20 micrograms kg-1 on the hormonal responses to cardiac surgery and compared the changes with a control group receiving sufentanil and sodium nitroprusside. Eighteen patients undergoing elective valve replacement surgery were studied. Patients who received somatostatin and trimetaphan in addition to sufentanil had significantly smaller serum growth hormone and plasma glucagon concentrations compared with those who received sufentanil and sodium nitroprusside. The cortisol response to surgery was inhibited in both groups. There were no significant differences in catecholamine concentrations between the two groups. There was no effect of the additional inhibition of glucagon and growth hormone on circulating concentrations of glucose and lactate, but plasma concentrations of non-esterified fatty acids increased significantly. Thus the addition of somatostatin increased the suppression of the hormonal response to cardiac surgery by sufentanil.

Aged↗
PubMed1990

Massive histamine release in a patient with systemic mastocytosis.

We have measured plasma histamine concentrations, systemic vascular resistance, cardiac output and arterial pressure during laparotomy in a patient with systemic mastocytosis. The patient developed vasodilation and hypotension during surgery, associated with a massive increase in plasma histamine concentration.

Anesthesia, General↗
PubMed1990

Endothelin in renal failure.

Endothelin is a 21-residue peptide vasoconstrictor produced by endothelium. Using a radioimmunoassay, endothelin values were measured in four groups of individuals: normal controls (0.54 +/- 0.12 pmol/l, n = 20); undialysed patients with chronic renal failure (CRF) (0.82 +/- 0.13 pmol/l, n = 38); chronic renal failure patients on continuous ambulatory peritoneal dialysis (CAPD) (2.81 +/- 0.63 pmol/l, n = 20); and patients with CRF on haemodialysis (HD) (4.52 +/- 1.21 pmol/l, n = 14). The endothelin values were significantly greater in undialysed patients with CRF when compared with controls (P less than 0.001) and significantly greater in both dialysis groups when compared with controls and the undialysed CRF group (P much less than 0.001). The difference between the two dialysis groups was not significant (P = 0.07). There was no correlation between endothelin and serum creatinine, mean arterial pressure, presence of chronic hypertension and/or diabetes, use of calcium-channel blockers and/or ACE inhibitors, or primary renal diagnostic category. A single haemodialysis session had no significant effect on endothelin values in the ten patients in whom this was assessed. Fast protein liquid chromatography (FPLC) appeared to confirm that the molecular species found in chronic renal failure were the same as those found in diabetic patients.

Adolescent↗
PubMed1990

Pharmacokinetics of the long-acting somatostatin analogue octreotide (SMS 201-995) in acromegaly.

A single-dose study was performed to examine the pharmacokinetics of subcutaneous octreotide in acromegalic patients and to investigate the relationship between growth hormone and the elimination half-life of the drug. Fourteen acromegalic patients (six men and eight women; age range 35-59 years) who had previously received conventional treatment were studied. Two subjects were on long-term octreotide which had been discontinued 72 h before the study. Octreotide 100 micrograms was administered subcutaneously and plasma samples taken every 10 min for 1 h and then hourly for up to 8 h. Growth hormone was measured at 0, 2 and 8 h. Octreotide was rapidly absorbed with a mean (+/- SEM) t1/2abs of 5.4 min (+/- 0.8) peaking at a mean plasma concentration of 3.4 nmol/l (+/- 0.2) in 27.4 min (+/- 3.7). The monoexponential elimination phase had a mean half-life of 110 min (+/- 9.6). The apparent volume of distribution was 29.4 1 (+/- 1.9) and total clearance was 172 ml/min (+/- 10.4). These results were similar to those obtained in normal volunteers. There was no simple relationship between the level of growth hormone and the half-life of octreotide. Growth hormone levels ranged from 2.5 to 34.0 mIU/l but were only greater than 10 mIU/l in three subjects. Further studies of octreotide pharmacokinetics are needed in untreated patients with acromegaly with raised growth hormone levels.

Acromegaly↗
PubMed1990

Effect of octapeptide somatostatin analogue (SMS 201-995) on plasma 7B2 (a neuroendocrine polypeptide) levels in patients with acromegaly.

We studied the sequential changes of plasma levels of immunoreactive '7B2' (IR-7B2), a neuroendocrine polypeptide, after a subcutaneous injection of 50 micrograms of synthetic octapeptide somatostatin analogue (SMS 201-995) in seven patients with acromegaly due to GH-producing pituitary adenoma. Compared to the basal levels, mean plasma IR-7B2 and GH levels significantly decreased, until 5 and 10 h respectively after the administration of SMS 201-995. The mean (+/- SEM) nadir levels of plasma IR-7B2 and GH were 68.1 +/- 10.1 and 13.1 +/- 6.9%, respectively, compared to mean plasma levels before treatment (100%). Plasma IR-7B2 as well as GH levels did not change significantly when saline was administered subcutaneously to three acromegalic patients. In addition, plasma IR-7B2 levels did not change significantly after the administration of SMS 201-995 in normal subjects or in patients with primary hypothyroidism in whom SMS 201-995 induced a decrease of plasma TSH levels. These results strongly suggest that SMS 201-995 has an unequivocal suppressive effect on the synthesis and/or the secretion of 7B2 in human somatotroph adenoma cells.

Acromegaly↗
PubMed1990

Effect of synthetic human glucose-dependent insulinotropic polypeptide (hGIP) on the release of insulin in man.

During an oral glucose tolerance test (oGTT) and an isoglycaemic intravenous glucose infusion, blood glucose and the responses of insulin and glucose-dependent insulinotropic polypeptide (GIP) were measured in six healthy volunteers. On a subsequent occasion a constant infusion of human synthetic GIP (2 pmol kg-1 min-1 for 30 min and 0.5 pmol kg-1 min-1 for another 30 min was given to each subject, again with a simultaneous infusion of glucose to maintain isoglycaemia to the oGTT. During the oGTT, plasma GIP concentrations rose from 92 +/- 18 pmol 1(-1) to 257 +/- 42 pmol 1(-1) 60 min after ingestion of glucose (mean +/- SEM). When glucose was administered intravenously plasma GIP levels did not rise significantly over basal. The infusion of hGIP mimicked the physiological plasma GIP response after oral glucose during the first 60 min of the study. Plasma insulin concentrations were significantly lower between 45 and 60 min than during the oGTT (438 +/- 67 vs. 200 +/- 48 pmol 1(-1); P less than 0.02; 465 +/- 96 vs. 207 +/- 48 pmol 1(-1); P less than 0.01). However, the total and incremental integrated insulin responses during the first 60 min of the study were, though lower, not significantly different from the oGTT experiment when glucose and hGIP were infused simultaneously. Thus, in the presence of mild physiological hyperglycaemia, human GIP is able to enhance the initial insulin response almost equivalently to the stimulus provided by oral glucose. Decreased insulin concentrations during porcine GIP infusions in previous experiments might be due to sequence differences between human and porcine GIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of alpha-glucosidase inhibition and viscous fibre on diabetic control and postprandial gut hormone responses.

Twelve sulphonylurea-treated Type 2 diabetic patients underwent treatment for 2-week periods with the absorbable alpha-glucosidase inhibitor BAY m1099 (50 mg thrice daily) and with guar granules (5 g thrice daily) separately and together in a sequence-randomized double-blind placebo-controlled study. BAY m1099 and guar reduced the mean fasting plasma glucose from 10.0 +/- 0.7 mmol l-1 to 8.7 +/- 0.5 (p less than 0.05) and 8.3 +/- 0.7 mmol l-1 (p less than 0.01), respectively. Both agents also lowered home-monitored postprandial blood glucose, with BAY m1099 exerting the greater effect. Guar, but not BAY m1099, lowered serum cholesterol from 5.43 +/- 0.52 to 5.29 +/- 0.31 mmol l-1 (p less than 0.05). BAY m1099 reduced the test breakfast plasma responses of glucose (p less than 0.001) and gastric inhibitory polypeptide (GIP, p less than 0.01) and increased those of peptide tyrosine-tyrosine (p less than 0.05) and motilin (p less than 0.01). Guar also reduced plasma glucose concentrations after a test breakfast (p less than 0.05) and increased the response of neurotensin (p less than 0.05). Combining treatments gave no further reduction of postprandial blood glucose concentration and was associated with an increased incidence and severity of gastrointestinal side-effects.

1-Deoxynojirimycin↗