Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 433 records · Page 24Linked to original sources

PubMed1989

Studies of the entero-insular axis following pancreas transplantation in man: neural or hormonal control?

To study the role of hormonal and neural factors in the control of the entero-insular axis the insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) responses to oral and intravenous glucose were investigated in 5 patients who had received a combined kidney and paratopic pancreas transplant, with physiological portal venous drainage. The incremental areas under the insulin and C-peptide responses to oral glucose were significantly greater than the responses to intravenous glucose (insulin: patients 7983 +/- 1937 (+/- SE) vs 3513 +/- 2188 mU l-1 min, p less than 0.002, control subjects 5505 +/- 1035 vs 1066 +/- 484 mU l-1 min, p less than 0.004; C peptide: patients 440 +/- 80 vs 144 +/- 61 nmol l-1 min, p less than 0.01, control subjects 200 +/- 38 vs 63 +/- 16 nmol l-1 min, P less than 0.01). The incretin effects for insulin (patients 4.4 +/- 1.4, control subjects 7.7 +/- 1.8) and C-peptide (patients 4.4 +/- 0.9, control subjects 3.7 +/- 0.9) and the GIP responses to oral and intravenous glucose were not significantly different between transplant patients and control subjects. As the incretin effect was preserved, despite a denervated pancreas, hormonal rather than neural factors may be more important in mediating increased insulin secretion after oral carbohydrate. The normal GIP response is compatible with its proposed role as an insulinotropic hormone.

Adult↗

PubMed1989

Purification and characterisation of cerebellins from human and porcine cerebellum.

The primary human and porcine structure of the novel neuropeptide cerebellin is unknown. These peptides were, therefore, isolated by a combination of ion-exchange and reverse-phase chromatography using a specific radioimmunoassay against rat cerebellin. The sequences of the peptides were deduced by mass spectrometry (for both human and porcine cerebellins) and gas-phase Edman degradation (for porcine cerebellin). In both species, two molecular forms were identified. In the human, the major form corresponded to the pentadecamer [des-Ser1]-cerebellin (approximately 95% of the total) and the minor form, to the hexadecamer peptide. In the pig, however, both molecular forms were present in approximately equal amounts. The finding that the sequences of human and porcine cerebellin are identical to that of the rat suggests that strong evolutionary pressure has acted to conserve this sequence.

Amino Acid Sequence↗

PubMed1989

Endothelin-induced contractions of tracheal smooth muscle and identification of specific endothelin binding sites in the trachea of the rat.

1. The presence of specific binding sites and the contractile activity of the novel peptide, endothelin have been investigated in rat trachea. 2. Endothelin (10(-8)-10(-5) M) induced long-lasting contraction of rat tracheal rings superfused with Krebs solution (EC50 5.4 x 10(-6) M). Contractions of the tissue to 10(-6) M endothelin were attenuated in Ca2+-free medium containing 0.1 mM EGTA but unaffected by nicardipine (10(-7) M). 3. After equilibration in Ca2+-free medium (without EGTA) a return to normal Ca2+ concentrations (2.5 mM), 30 min or 60 min following endothelin (10(-6) M), produced a sustained contraction of the tissue. 4. Specific binding sites for endothelin were identified on rat tracheal smooth muscle (KD 1.34 x 10(-10) M, maximal binding 1.2 fmol mm-2). Specific binding sites were also identified on nerve trunks. Endothelin binding was unaffected by co-incubation with nicardipine (10(-7) M) or verapamil (10(-7) M). 5. The discrepancy between the apparent KD for endothelin binding and the EC50 for endothelin-induced contraction suggests that the endothelin binding sites identified in this study may not be associated with the receptors mediating contraction. 6. These results indicate that endothelin binding sites are present on tracheal smooth muscle. The mechanism of endothelin-induced contraction, whilst being dependent on extracellular calcium, does not appear to involve binding to the dihydropyridine- or verapamil-sensitive sites on the voltage-dependent Ca2+ channel. Its long duration of action may be associated with a sustained increase in Ca2+ permeability.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1989

Plasma enteroglucagon, gastrin and peptide YY in conventional and germ-free rats refed with a fibre-free or fibre-supplemented diet.

Germ-free rats and conventional rats were starved and then refed with either an elemental diet (Flexical), or Flexical plus 30% kaolin, or Flexical plus 30% of a fibre mixture. Plasma levels of enteroglucagon, gastrin and peptide YY (PYY) were all significantly affected by diet. Enteroglucagon and especially PYY were significantly increased by the addition of fermentable fibre to the diet, but only in the conventional, not in the germ-free rats. Gastrin was not affected by the addition of fermentable fibre, but was increased by kaolin. Enteroglucagon and PYY were, however, both very much elevated in the germ-free animals, in which there is no proliferative response to fibre. Enteroglucagon and PYY levels were similar to those usually associated with extreme hyperproliferative states, indicating that it is unlikely that these hormones are involved in the proliferative response of the gastrointestinal tract to dietary fibre, and casting doubt on their role in other responses.

Animals↗

PubMed1989

Adrenal responses to calcitonin gene-related peptide in conscious hypophysectomized calves.

1. Right adrenal and various cardiovascular responses to an intra-aortic infusion of calcitonin gene-related peptide (CGRP; 4 micrograms min-1) have been investigated in the presence and absence of exogenous adrenocorticotrophin ACTH1-24 (2 or 5 ng min-1 kg-1, I.V.). The adrenal clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-7 days previously. 2. At the higher dose (5 ng min-1 kg-1) the I.V. infusion of ACTH raised mean plasma ACTH concentration by about 1000 pg ml-1 and mean right adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal cortisol output by about 750 ng min-1 kg-1. Under these conditions the intra-aortic infusion of CGRP had no apparent effect on adrenal function, other than to produce moderate adrenal vasodilatation. In contrast, in the absence of exogenous ACTH, the same dose of CGRP produced a substantial rise in cortisol output, which rose steadily to a peak mean value of 409 +/- 31 pg min-1 kg-1 at 10 min. It also significantly inhibited the release of free, but not of total, met5-enkephalin-like immunoreactivity from the gland (P less than 0.001) together with a significantly greater fall in adrenal vascular resistance (P less than 0.001). 3. At the lower dose of ACTH (2 ng min-1 kg-1, I.V.) CGRP raised mean plasma cortisol output from 314 +/- 31 to 486 +/- 44 ng min-1 kg-1 (P less than 0.01) and this effect was not attributable to an increase in the adrenal presentation rate of ACTH. 4. It is concluded that this peptide exerts a steroidogenic action on the adrenal cortex which is manifest in the absence of exogenous ACTH in the functionally hypophysectomized calf.

Adrenal Cortex↗

PubMed1989

Neuroendocrine responses to stimulation of the splanchnic nerves in bursts in conscious, adrenalectomized, weaned lambs.

1. Effects of stimulation of the peripheral ends of the splanchnic nerves below behavioural threshold at either 4 or 7 Hz continuously for 10 min, or at 40 or 70 Hz for 1 s at 10 s intervals for 10 min. have been compared in conscious adrenalectomized lambs. 2. Both patterns of stimulation resulted in an abrupt rise in mean aortic blood pressure of closely similar extent which was associated with reflex bradycardia. 3. At the lower frequencies both patterns of stimulation elicited a closely similar rise in mean plasma glucose, glucagon and pancreatic polypeptide concentration, but the fall in mean plasma insulin concentration was significantly greater during continuous stimulation. 4. Unlike other species in which the release of NPY and bombesin-like immunoreactivity (BLI) is potentiated by intermittent high-frequency stimulation, no significant differences were produced by changing the pattern of stimulation. The release of BLI was found to be frequency related over the ranges tested (4-7 Hz continuously and 40-70 Hz in bursts) whereas the release of NPY was not. 5. Splanchnic nerve stimulation also produced detectable rises in the mean plasma concentrations of noradrenaline and adrenaline. The mean average concentration of noradrenaline during stimulation in bursts was significantly higher than that during continuous stimulation (P less than 0.02). There was also a steady rise in mean plasma 3,4-dihydroxyphenylacetic acid (DOPAC) during stimulation followed by a further rise to significantly higher values (P less than 0.02) following stimulation in bursts at 40 Hz. 6. It is concluded that the pattern of stimulation is a less important determinant of autonomic responses to splanchnic nerve stimulation in sheep than in certain other species.

Adrenalectomy↗

PubMed1989

Studies on the pathogenesis of the early dumping syndrome induced by intraduodenal instillation of hypertonic glucose.

A reaction indistinguishable from the early dumping syndrome was induced in four of nine normal volunteers by intraduodenal instillation of a hypertonic glucose meal. Tachycardia and marked peripheral vasodilatation were demonstrated in 'dumpers' by Doppler ultrasound measurements of the arterial blood flow signal. The dumping reaction was not detectably altered by the addition of guar to the meal. Plasma VIP concentration rose and plasma volume fell to a similar degree in 'dumpers' and 'non-dumpers', suggesting that neither event is an integral component of the dumping mechanism. In contrast, the rates of rise of blood glucose and enteroglucagon concentration were markedly greater in 'dumpers'. The results are inconsistent with the conventional explanation that the early dumping syndrome is caused by a large osmotic fluid shift, but are compatible with a mechanism involving an initial period of intestinal hypermotility.

Blood Flow Velocity↗

PubMed1989

Atrial natriuretic peptide concentrations in hypoxic secondary pulmonary hypertension: relation to haemodynamic and blood gas variables and response to supplemental oxygen.

Plasma atrial natriuretic peptide concentrations, measured in samples drawn from the pulmonary artery, were raised in nine of 17 patients with hypoxic pulmonary hypertension but normal right atrial pressures at rest. No relationship was seen between atrial natriuretic peptide concentrations and mean pulmonary artery or right atrial pressure, or calculated pulmonary or systemic vascular resistance. Patients with the most severe hypoxaemia tended to have higher plasma atrial natriuretic peptide concentrations; three patients with no past history of oedema had concentrations more than twice the upper limit of normal. Treatment with supplementary oxygen for 30 minutes reduced pulmonary vascular resistance in all patients but had no significant effect on plasma atrial natriuretic peptide concentration. These findings suggest that atrial natriuretic peptide may be a factor in the control of sodium and water balance in hypoxic cor pulmonale, where the determinants of individual susceptibility to peripheral oedema are not well understood.

Aged↗

PubMed1989

Effects of acute and chronic ethanol administration on the gastrointestinal hormones gastrin, enteroglucagon, pancreatic glucagon and peptide YY in the rat.

The effect of acute and chronic ethanol administration on the gastrointestinal hormones gastrin, enteroglucagon (EG), pancreatic glucagon (PG) and peptide YY (PYY) was studied in the rat alcohol model. Plasma levels of gastrin and PYY were not significantly changed under chronic and/or acute alcohol, while PG was stimulated by acute intraperitoneal ethanol injections in control animals as well as in chronically ethanol-fed rats (8 +/- 1 vs. 28 +/- 6 pmol/l, p less than or equal to 0.05, and 7 +/- 1 vs. 21 +/- 4 pmol/l, p less than or equal to 0.05). EG levels were significantly raised after chronic ethanol feeding (45 +/- 5 vs. 73 +/- 8 pmol/l, p less than or equal to 0.01) and even further elevated if an acute dose of alcohol was given to chronically ethanol-fed rats (73 +/- 8 vs. 168 +/- 29 pmol/l, p less than or equal to 0.05). The immunohistologically evaluated numbers of the respective hormone-producing cells were not significantly changed by alcohol feeding. The ethanol-dependent elevations of EG and PG may contribute, at least in part, to the intestinal hyper-regeneration, motility disturbances and altered glucose metabolism observed after alcohol consumption.

Animals↗

PubMed1989

Effect of enprostil on gastric emptying, intestinal transit time and post-prandial release of gastro-intestinal peptides.

The effect of an oral dose of 70 micrograms enprostil (a prostaglandin E2 analogue) on the post-prandial hormone response to a test breakfast was examined in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers. Enprostil markedly reduced the post-prandial rises in insulin and glucose-dependent insulinotropic peptide (GIP) but plasma glucose remained unchanged. To study the effects on gut motility 8 healthy volunteers ingested a liquid meal containing 75 g glucose, 20 g lactulose and 99mTc colloid after taking placebo or 70 micrograms enprostil. Gastric emptying, measured using a gamma camera, was unchanged but mouth-to-caecum transit time was significantly longer on enprostil; time to half maximal breath hydrogen: placebo 119 min, enprostil 200 min (p less than 0.05). This delay was associated with a reduced and delayed post-prandial rise in GIP and insulin and with other changes in the gut hormone profile.

Adult↗

PubMed1989

Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

GAWK (chromogranin-B 420-493) is a 74 amino acid peptide recently isolated from human pituitaries. Using two different antibodies (directed against GAWK [1-17] and [20-38] fragments) GAWK-LI was measured in tumors from 194 patients and in the plasma of 434 patients by RIA. The highest tissue concentrations of GAWK-LI were found in pheochromocytoma (GAWK [1-17]-LI, 18,173 +/- 3,915; GAWK [20-38]-LI, 17,852 +/- 2,763 [mean +/- SEM] pmol/g wet wt tissue; n = 9), which were at least ten times higher than any other tumors producing GAWK-LI. High concentrations of GAWK-LI were also found in other types of endocrine tumors including carcinoid, medullary carcinoma of thyroid, pancreatic, and ACTH-producing lung tumors. On the other hand, low concentrations of GAWK-LI were found in nonendocrine tumors. Plasma concentrations of GAWK-LI were found to be elevated in patients with endocrine tumor, but more so in those with pancreatic tumors than with pheochromocytomas. Plasma concentrations returned to normal after successful tumor removal. Chromatographic profiles of GAWK-LI in extracts of pheochromocytomas and normal adrenals showed high molecular weight peaks that were absent in the extracts of other endocrine tumors and normal pancreas, suggesting differential tissue-specific processing. Thus GAWK-LI is produced by a variety of endocrine tumors and may serve as a plasma tumor marker, especially in patients with pancreatic endocrine tumors.

Adrenal Gland Neoplasms↗

PubMed1989

Evidence for neuropeptide Y synthesis in the rat anterior pituitary and the influence of thyroid hormone status: comparison with vasoactive intestinal peptide, substance P, and neurotensin.

Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.

Animals↗

PubMed1989

A new pituitary protein 7B2 is increased in patients with high alpha- or beta-hCG.

The presence of 7B2 (a 180 amino acid peptide first extracted from the porcine pituitary) was investigated by a specific radioimmunoassay and gel filtration chromatography in the plasma of three groups of patients known to have increased levels of alpha- and beta-hCG subunits. Plasma 7B2 immunoreactive equivalents (7B2-IE) were increased in postmenopausal women (range 67-143 pmol/l, median: 94 pmol/l, N = 20, P less than 0.05), in patients with Klinefelter's syndrome (range 195-230 pmol/l), median 213 pmol/l, N = 4, P less than 0.01) and in 17 patients with malignant endocrine gastrointestinal tumours (range 66-20,000 pmol/l, N = 32) compared with healthy controls (range 23.6-98.2 pmol/l, median 41.5 pmol/l, N = 40). Tumour tissue from 4 patients with endocrine pancreatic tumours had significantly higher 7B2-IE concentrations than normal pancreatic tissue, with the highest concentration in an insulinoma (449 pmol/g, normal: 28 pmol/g). During therapy almost parallel changes in plasma 7B2 and other hormones were noted and 7B2-IE therefore might be an additional marker for cancers of the APUD system.

Adolescent↗

PubMed1989

Expression of the rat amylin (IAPP/DAP) gene.

We have used the polymerase chain reaction with mixed sequence primers to generate a probe for rat amylin and have used this to detect expression in various rat tissues. Amylin mRNA is found in greatest concentrations in the pancreas where a single mRNA species can be detected giving a hybridisation signal intensity approximately 10% that of insulin mRNA. When the beta cell population was depleted with streptozotocin, both amylin and insulin mRNAs were reduced to a similar extent. Consistent with its supposed role in the control of carbohydrate metabolism, amylin mRNA was also found in the stomach. Unlike the related peptide, CGRP, amylin mRNA is not present in the thyroid and is not widely distributed in the central nervous system. The only nervous tissue in which it could be detected was the dorsal root ganglion. Surprisingly, amylin mRNA was also found in the lung though only at very low levels.

Amino Acid Sequence↗

PubMed1989

The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women.

Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose.

Adrenal Cortex Hormones↗

PubMed1989

The anterior pituitary content of neuromedin U-like immunoreactivity is altered by thyrotrophin-releasing hormone and thyroid hormone status in the rat.

In this study we have examined the effects of TRH, thyroid hormones and dopamine on the rat anterior pituitary content of neuromedin U-like immunoreactivity. Oral administration of TRH (20 mg/100 g per day) to euthyroid animals evoked a fivefold increase in peptide content after 12 days of treatment. This effect was found to be dependent upon circulating levels of thyroid hormone, since administration of TRH to thyroidectomized animals failed to show a similar effect without simultaneous treatment with tri-iodothyronine. The possibility that the TRH-induced increase in anterior lobe neuromedin U content reflected alterations in prolactin secretion or synthetic rate was also examined. Treatment of euthyroid animals with a dopamine agonist and antagonist was, however, without effect. These results demonstrate a unique relationship between TRH and thyroid hormone levels in increasing the anterior lobe content of neuromedin U immunoreactivity.

Animals↗

PubMed1989

Increased neuropeptide Y concentrations in specific hypothalamic regions of streptozocin-induced diabetic rats.

Untreated streptozocin-induced diabetic (STZ-D) rats have previously been shown to have significantly increased hypothalamic concentrations of neuropeptide Y (NPY), a regulatory peptide that powerfully stimulates eating and drinking and inhibits secretion of several pituitary hormones when injected centrally. Tissue NPY concentrations have been measured by radioimmunoassay in selected hypothalamic regions microdissected from fresh, unfixed brain slices to localize diabetes-associated NPY changes precisely within the hypothalamus. Significant (35-200%) increases in NPY concentrations (P less than .01 vs. matched nondiabetic controls) were found in specific hypothalamic regions between 3 and 14 wk after induction of STZ-D. These regions included the paraventricular and ventromedial nuclei and lateral hypothalamic area, major appetite-regulating areas that are sensitive to the hyperphagic and polydipsic actions of NPY. Increased NPYergic activity in these areas may, at least partly, drive the increased eating and drinking characteristic of STZ-D. NPY concentrations were also increased in the arcuate nucleus and medial preoptic area. Because both of these regions are important in modulating pituitary hormone secretion, local NPY increases may be involved in the impaired secretion of luteinizing hormone, thyroid-stimulating hormone, growth hormone, and prolactin known to occur in STZ-D. Our finding of NPY increases in specific hypothalamic nuclei associated with functional changes found in STZ-D suggests that this peptide may have a role in the altered metabolic and neuroendocrine regulation of the syndrome.

Animals↗

PubMed1989

High-dose porcine galanin infusion and effect on intravenous glucose tolerance in humans.

The neuropeptide galanin inhibits glucose-stimulated insulin release in dogs and rodents and has been proposed as having a role in the control of insulin release in humans. The effect of infused galanin on intravenous glucose tolerance in humans was investigated by giving an intravenous glucose tolerance test (0.5 g glucose/kg body wt) alone and with infusions of synthetic porcine galanin at high-dose levels (80 and 160 pmol.kg-1.min-1) to seven healthy male volunteers. The results showed no effect of galanin infusion on plasma glucose or serum insulin, although a rise in serum growth hormone even in the face of the intravenous glucose load confirmed the potent growth hormone-stimulating effect of galanin. These results suggest that caution should be exercised in extrapolating a physiological role for galanin in humans from the results of animal studies.

Animals↗