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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 829 records · Page 46Linked to original sources

The influence of modified sham feeding on plasma polypeptide (CCK, gastrin, motilin, neurotensin and somatostatin) concentrations in duodenal ulcer disease.

Changes in gastric acid secretion and plasma levels of CCK, gastrin, motilin, neurotensin and somatostatin in response to modified sham feeding (MSF) were investigated in 8 asymptomatic duodenal ulcer patients. MSF caused a significant increase in gastric acid secretion whereas the peripheral plasma concentrations of the various polypeptides remained unchanged. The study gives further support for the notion that MSF activates the vagal innervation to the parietal cells more selectively than insulin hypoglycaemia.

Adult↗

Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species.

Calcitonin gene-related peptide (CGRP) immunoreactivity was found throughout the entire spinal cord of man, marmoset, horse, pig, cat, guinea pig, mouse, rat, and frog. CGRP-immunoreactive fibers were most concentrated in the dorsal horn. In the ventral horn of some species large immunoreactive cells, tentatively characterized as motoneurons, were present. Pretreatment of rats with colchicine enhanced staining of these large cells but did not reveal CGRP-immunoreactive cell bodies in the dorsal horn. In the dorsal root ganglia, CGRP immunoreactivity was observed in most of the small and some of the intermediate sized cells. Substance P immunoreactivity, where present, was co-localized with CGRP to a proportion of the small cells. In the cat the ratio of substance P-immunoreactive to CGRP-immunoreactive ganglion cells was 1:2.7 (p less than 0.001). The concentration of CGRP-immunoreactive material in tissue extracts was determined by radioimmunoassay. In the dorsal horn of the rat spinal cord the levels of peptide were found to range from 225.7 +/- 30.0 pmol/gm of wet weight in the cervical region to 340.6 +/- 74.6 pmol/gm in the sacral spinal cord. In the rat ventral spinal cord, levels of 15.7 +/- 2.7 to 35.1 +/- 10.6 pmol/gm were found. The concentration in dorsal root ganglia of the lumbar region was 225.4 +/- 46.9 pmol/gm. Gel permeation chromatography of this extractable CGRP-like immunoreactivity revealed three distinct immunoreactive peaks, one eluting at the position of synthetic CGRP and the others, of smaller size, eluting later. In cats and rats, rhizotomy induced a marked loss of CGRP-immunoreactive fibers from the dorsal horn of the spinal cord. In the cat, unilateral lumbosacral dorsal rhizotomy resulted in a significant (p less than 0.05) reduction of extractable CGRP from the ipsilateral lumbar dorsal horn (5.6 +/- 1.2 pmol/gm of wet weight) compared to the contralateral side (105.0 +/- 36.0 pmol/gm of wet weight). We conclude that the major origin of CGRP in the dorsal spinal cord is extrinsic, from afferent fibers which are probably derived from cells in the dorsal root ganglia. The selective distribution of CGRP throughout sensory, motor, and autonomic areas of the spinal cord suggests many putative roles for this novel peptide.

Animals↗

Experience with an LHRH analogue in the management of relapsed progressive prostatic cancer.

Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics.

Acid Phosphatase↗

Effect of single dose of omeprazole on the gastrointestinal peptide response to food.

The gastrointestinal peptide response to food was assessed in 6 healthy subjects following oral administration of 40 mg omeprazole. There was a small but statistically significant increase in basal plasma gastrin six hours after the dose of omeprazole, but the post-prandial plasma gastrin was not significantly increased. There was no significant effect on basal or post-prandial levels of somatostatin, insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, neurotensin, cholecystokinin, secretin, vasoactive intestinal peptide and gastrin-releasing peptide or blood glucose concentration.

Adult↗

Pancreatic exocrine and endocrine responses in chronic pancreatitis.

To test the discriminatory potential of certain indices of pancreatic function we performed duodenal perfusion studies and measured trypsin, bicarbonate, and lactoferrin outputs, and plasma concentrations of pancreatic polypeptide and motilin in the basal state and during continuous intravenous stimulation with 100 ng kg-1h-1 Ceruletide and 1 CU kg-1h-1 secretin. The following groups were studied: 12 normal volunteers (NV), seven patients with chronic pancreatitis with steatorrhea (CPS), and seven without steatorrhea (CP). Stimulated trypsin outputs, after 45 min of stimulation, were the best discriminant among the groups (NV versus CPS, p less than 0.0005; NV versus CP, p less than 0.005; CP versus CPS, p less than 0.05). Basal trypsin outputs showed similar patterns but failed to discriminate between NV and CP. Bicarbonate outputs were less discriminatory than trypsin outputs. Lactoferrin outputs failed to discriminate, but transient high peak outputs occurred in the initial stimulation period in all four patients with calcific chronic pancreatitis, suggesting a washout phenomenon. Basal motilin levels were elevated in both groups of pancreatitis (p less than 0.05). Stimulated pancreatic polypeptide levels were lower in CPS (NV versus CPS, p less than 0.05) but higher in CP (NV versus CP, p less than 0.005). These differences were also apparent in the basal state. We conclude that the best discrimination among the three groups was achieved by measurement of trypsin outputs, after 45 min of stimulation. In addition, the pancreatic polypeptide response may be used as a marker of residual pancreatic function in chronic pancreatitis.

Adult↗

Production of "ectopic" vasoactive intestinal peptide-like and neurotensin-like immunoreactivity in human pheochromocytoma cell cultures.

Neoplastic chromaffin cells from human pheochromocytomas can exhibit extensive spontaneous and nerve growth factor (NGF)-induced outgrowth of neurite-like processes in vitro, despite the absence of such processes in vivo. To determine whether acquisition of neuron-like features by human pheochromocytoma cells in culture is accompanied by functional alterations, process outgrowth, vasoactive intestinal peptide-like immunoreactivity ( VIPLI ), neurotensin-like immunoreactivity (NTLI), and catecholamine content were studied in freshly dissociated cells and in 21-day-old cultures from six human pheochromocytomas. All of the cultures produced VIPLI and exhibited spontaneous process outgrowth. NGF stimulated process outgrowth and enhanced production of VIPLI . Dexamethasone inhibited process outgrowth and tended to decrease production of VIPLI . NTLI was detected in cells from only one of the tumors, and its production appeared to be regulated comparably to that of VIPLI . Catecholamine content decreased markedly in all of the cultures and was not regulated in parallel with either VIPLI or NTLI. The findings suggest that human pheochromocytoma cultures may help to elucidate cellular and molecular mechanisms regulating ectopic and normal VIP production.

Adrenal Gland Neoplasms↗

Peptide histidine isoleucine- and vasoactive intestinal polypeptide-like immunoreactivity coexist in rat hypophysial portal blood.

Plasma immunoreactive peptide histidine isoleucine (PHI) and vasoactive intestinal polypeptide (VIP) levels were measured by specific radioimmunoassays in urethane-anesthetized rats. Basal levels of plasma PHI-like immunoreactivity (PHI-LI) in the hypophysial portal blood were 414 +/- 180 pmol/l (means +/- S.E.), about 7 times higher than in the peripheral blood. VIP-like immunoreactivity (VIP-LI) was also high in the portal blood (399 +/- 139 pmol/l). The correlation coefficient between PHI-LI and VIP-LI was 0.76. These findings suggest that PHI and VIP are co-released from the median eminence into the hypophysial portal blood in rats.

Animals↗

Neuropeptide Y-immunoreactive nerves in the uvea of guinea pig and rat.

Neuropeptide Y (NPY)-immunoreactivity has been localized to a rich network of fibres in the uvea of guinea pig and rat. In the iris, NPY-immunoreactive nerves were present in iridial smooth muscle and around blood vessels; similarly throughout the choroid a dense network of NPY-immunoreactive fibres was found surrounding the choroidal vascularization. Following sympathectomy a marked decrease of NPY-immunoreactivity, in particular in the iris and less marked in the choroid, was noted, indicating that these fibres may originate at least in part from neuronal cell bodies in the superior cervical ganglion. The close relationship of the NPY-immunoreactive fibres to blood vessels in both anterior and posterior uvea is consistent with the established vasoconstrictor action of this peptide.

Animals↗

Diarrhoea in vipoma patients associated with cosecretion of a second active peptide (peptide histidine isoleucine) explained by single coding gene.

Peptide histidine isoleucine (PHI), first isolated from pig intestine, is distributed identically to vasoactive intestinal peptide (VIP) in all mammals. 42 patients with high plasma VIP secondary to VIPoma also had very high plasma PHI-like immunoreactivity, in a constant ratio to VIP. None of 125 patients with other endocrine tumours had high levels of either peptide. VIPoma tissue from 20 patients also contained PHI shown by immunocytochemistry to be produced by the same cell as VIP. Messenger RNA(mRNA) from one of these tumours contained the codes for VIP and a separate PHI-like sequence. Human PHI-like sequence differed from porcine PHI in only two aminoacid residues. A single cell thus produces two separate regulatory peptides with apparently similar potencies but different spectra of activity. In normal tissue the constant coproduction of two active neuropeptides by a single neuron provides further evidence against the doctrine of one neuron producing only one neurotransmitter.

Adenoma, Islet Cell↗

Morphologic patterns and diagnostic criteria of VIP-producing endocrine tumors. A histologic, histochemical, ultrastructural, and biochemical study of 32 cases.

Thirty-two tumors (31 pancreatic and one jejunal) all associated with severe watery diarrhea, increased VIP levels in blood and most with hypokalemia, were investigated. The VIP content of tumor tissue ranged from 23 to 15,000 pmol/g. VIP immunoreactive cells were detected histochemically in 24 of 28 tumors investigated, PP immunoreactive cells in 11 of 28 tumors, hCG (alpha chain) immunoreactive cells in 12 of 25 tumors, and neuron specific enolase (NSE) immunoreactive cells in 24 of 26 tumors (the 2 negative results were due to inadequate fixation). All cases showed light microscopic features of epithelial endocrine tumors. Electron microscopy demonstrated a prevalence of agranular, poorly granulated and a minority of well granulated cells. Most secretory granules were round, small (150+/- 30 nm diameter) and of moderate electron density, resembling those of the so-called D1 cells. By electron immunocytochemistry, PP was directly localized in a subpopulation of relatively larger granules (154 +/- 22 nm core diameter) showing closely applied membranes. VIP-storing granules, directly identified only in the jejunal tumor, appear to correspond to a subpopulation of slightly smaller P-type granules (126 +/- 37 nm core diameter) showing a narrow, clear halo. The origin, behavior, and diagnostic criteria of VIPomas are discussed.

Adult↗

Bombesin and calcitonin secretion by pulmonary carcinoma is modulated by cholinergic receptors.

Three established cell lines derived from human small cell carcinoma of the lung, and known to produce significant amounts of peptide hormones were used to evaluate the regulation of hormone secretion by cholinergic agonists. In two of the cell lines (DMS 53, DMS 153) acetylcholine chloride, bethanechol chloride, and carbamylcholine at the concentrations of 10(-3)M to 10(-5)M stimulated secretion of bombesin and calcitonin as measured by RIA. The third cell line, DMS 406, was not significantly stimulated. Inhibition of induced stimulation by the cholinergic antagonist atropine, but not hexamethonium, indicated the presence of muscarinic rather than the nicotinic type of cholinergic receptors on the stimulatable cells. These receptors appear to mediate hormone secretion comparably to normal endocrine cells.

Acetylcholine↗

Neuropeptide Y in neuroblastoma X glioma hybrid cells. Response to dexamethasone and nerve growth factor.

High concentrations of a newly-identified biologically potent peptide, neuropeptide Y, have been demonstrated in 3 related mouse neuroblastoma-derived clonal cell lines, N18TG2 0.35 pmol/mg protein, NG108-15 0.44 pmol/mg protein and NCB-20 0.39 pmol/mg protein. The NG108-15 cell line was chosen for further evaluation. Dexamethasone (10 microM) and nerve growth factor (10 ng/ml) resulted in a 2-fold increase in cellular neuropeptide Y concentrations. The response to dexamethasone was demonstrated to be dose-dependent. Exposure to both agents in combination resulted in a more than additive effect, indicating synergism.

Animals↗

Infusion of a novel peptide, PHI, in man. Pharmacokinetics and effect on gastric secretion.

PHI, infused in man, achieved plateau plasma levels of 297 pmoles/1. The plasma half life was 3.1 min, metabolic clearance rate was 16.4 ml/kg/min and estimated volume of distribution was 73.2 ml/kg. No subjective side effects were noted during the infusion and there was no significant alteration in submaximal pentagastrin stimulated gastric acid or pepsin secretion.

Adult↗

Bombesin-like immunoreactivity in the pituitary gland.

Bombesin has been shown to stimulate release of anterior pituitary hormones both in vivo and in vitro. The aim of this study was to determine whether bombesin-like immunoreactivity could be detected in the human pituitary. Significant concentrations were found in the human anterior gland (4.6 +/- 1.5 pmoles/g), posterior gland (1.5 +/- 0.4 pmoles/g) and stalk (8.1 +/- 0.8 pmoles/g). Significant amounts were also observed in the guinea-pig pituitary. Gel permeation chromatography revealed the presence of 2 major molecular forms of bombesin-like immunoreactivity, one co-eluting with porcine gastrin-releasing peptide and the other with amphibian bombesin.

Adult↗

Neuropeptide Y in phaeochromocytomas and ganglioneuroblastomas.

Tumour tissue from nineteen patients with phaeochromocytomas and nine with ganglioneuroblastomas contained large numbers of neuropeptide Y (NPY) producing cells and extracts of these tumours had very high concentrations of immunoreactive NPY. Plasma NPY concentrations were also raised, averaging 460 pmol/l in patients with tumours of the sympathetic chain and 55 pmol/l in healthy controls. Since plasma NPY is straightforward to measure and relatively stable, its estimation may prove helpful as a screening tests for phaeochromocytoma.

Adrenal Gland Neoplasms↗

Neuropeptide Y distribution in the rat brain.

A massive neuronal system was detected by immunocytochemistry and radioimmunoassay with antibodies to neuropeptide Y, the recently isolated peptide of the pancreatic polypeptide family. Immunoreactive cell bodies and fibers were most prevalent in cortical, limbic, and hypothalamic regions. Neuropeptide Y was extracted in concentrations higher than those of any other peptide hitherto discovered in the mammalian brain. Column chromatography of brain extracts and double immunostaining experiments indicate that neuropeptide Y is the endogenous brain peptide responsible for immunostaining of pancreatic polypeptide-like immunoreactivity in the mammalian brain.

Animals↗

Reduced cholecystokinin-like and somatostatin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia.

Cholecystokinin-like immunoreactivity (CCK) and somatostatin-like immunoreactivity (SRIF) were determined in fourteen brains from patients dying with a diagnosis of schizophrenia and in twelve brains from control cases. The schizophrenics had been rated during life and were divided into two groups on the basis of the presence or absence of negative symptoms (affective flattening and poverty of speech). CCK was reduced in temporal cortex of the schizophrenics and in hippocampus and amygdala of those patients with negative symptoms. SRIF was reduced in the hippocampus in samples from the latter group. The selectivity of these changes to limbic lobe may reflect the presence of a degenerative process in that area. The association of changes in hippocampus and amygdala with negative symptoms of schizophrenia suggests a separate mechanism underlying these symptoms.

Aged↗