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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 847 records · Page 47Linked to original sources
PubMed1983

Kinetics of regulation of neurotensin content in PC12 cells.

The mechanism by which nerve growth factor (NGF) and dexamethasone synergistically increase the content of neurotensin (NT) in PC12 cells can be partially separated into NGF and dexamethasone-mediated components by study of cultures pre-treated with either agent. The detectable early response of NGF-treated cells to dexamethasone is at least 24 hours faster than that of dexamethasone-treated cells to NGF, and is also greater in both absolute and relative magnitude. Both in NGF-treated cultures exposed to dexamethasone and in dexamethasone-treated cultures exposed to NGF, however, the rates of increase in NT content are initially low and then accelerate, suggesting periods of enzyme induction preceding NT accumulation. This suggestion is further supported by the absence of increases in the presence of actinomycin D, but an apparently paradoxical increase in NT content is observed in the presence of camptothecin. The findings are consistent with a complex interaction between NGF and dexamethasone, which might involve induction of multiple enzymes.

Adrenal Gland Neoplasms↗
PubMed1983

Intracellular topography of immunoreactive gastrin demonstrated using electron immunocytochemistry.

Gastrin (G)-producing cells from the mammalian gastric antrum have been investigated using computer-assisted morphometry and a novel double colloidal gold-labeled-immunoglobulin electron immunocytochemical procedure. Correlation analysis of human antral G-cells indicates (p less than 0.001) that a single population of granules exists with small (160 nm) electron-dense and large (240 nm) electron-lucent forms representing the extremes. Non-crossreacting region-specific antisera have been used to visualize G-17 and G-34 (progastrin) to the small electron-dense granules and G-17 to the other intermediate forms. From the results we propose a topographic segregation of immunoreactive gastrins within 2 apparently distinct granule subclasses and suggest that this may represent the pathway of granule maturation.

Adult↗
PubMed1983

Distribution of bombesin, somatostatin, substance-P and vasoactive intestinal polypeptide in feline and porcine skin.

The content and distribution of several regulatory peptides in the skin of cats and pigs, freshly obtained at surgery, have been investigated. Immunoreactive bombesin was evenly distributed at low concentrations in both species, being below the detection limit in the body and nose of the cat, and showing a peak value of 1.6 +/- 0.7 pmol/g in the tip of the pig's ear. Similar concentrations of somatostatin-immunoreactivity (-IR) were found but greater regional variation occurred in the pig with a low in the mid back of 0.4 +/- 0.1 and the highest value in the snout of 3.1 +/- 0.8. Substance-P-IR in the pig showed a marked variation in concentration, apparently parallelling skin sensitivity, with a low in the back of 0.4 +/- 0.7 and higher values around the anus (8.1 +/- 1.6), legs (6.8 +/- 1.8) and snout (13.5 +/- 3.6) whilst in the cat values ranged from 0.3 +/- 0.06 in the body to 5.0 +/- 0.9 in the front footpads. In contrast, vasoactive intestinal polypeptide (VIP)-IR showed greater variability in the cat, being below the assay's detection in the body and highest in the front and rear footpads (17 +/- 7 and 29 +/- 6 respectively), but in the pig most regions exhibited low concentrations with the exception of the snout which peaked at 12.0 +/- 5.0. Immunocytochemical localisation showed the peptides to be present in nerve fibres. Substance-P-IR was particularly localised in the snout of the pig just below the epithelium while VIP-IR was more concentrated in deeper layers, often associated with sweat glands and blood vessels.

Animals↗
PubMed1983

Abnormalities of growth hormone release in response to human pancreatic growth hormone releasing factor (GRF (1-44) ) in acromegaly and hypopituitarism.

Human pancreatic growth hormone releasing factor (GRF (1-44)) is the parent molecule of several peptides recently extracted from pancreatic tumours associated with acromegaly. A study was conducted to examine its effects on the release of growth hormone in normal volunteers and in patients with hypopituitarism and acromegaly. GRF (1-44) dose dependently stimulated the release of growth hormone in normal people and produced no appreciable side effect. This response was grossly impaired in patients with hypopituitarism and, although similar to the growth hormone response to hypoglycaemia, was of quicker onset and a more sensitive test of residual growth hormone function. Patients with acromegaly appeared to fall into (a) those with a normal response to GRF, whose growth hormone suppressed significantly with oral glucose, and (b) those who had an exaggerated response to GRF (1-44), whose growth hormone had not suppressed previously after oral glucose. Present methods for testing growth hormone deficiency entail using the insulin stress test, which is time consuming, unpleasant, and sometimes dangerous. A single intravenous injection of GRF now offers the possibility of an easier, safer, and more reliable routine test for growth hormone deficiency. It has the further advantage of being free of side effects and readily performed in outpatients. Hence it seems likely to become the standard test and take the place of the insulin stress test.

Acromegaly↗
PubMed1983

Advanced carcinoma of the prostate: treatment with a gonadotrophin releasing hormone agonist.

Ten patients with advanced progressive adenocarcinoma of the prostate were treated with a long acting analogue of gonadotrophin releasing hormone. Eight of these patients responded to treatment in terms of pain relief and clinical regression of tumour. Serum gonadotrophin and testosterone concentrations were significantly suppressed by the end of the second week of treatment, testosterone concentrations being comparable with those achieved by castration. The two patients who failed to respond had both relapsed previously when receiving conventional treatment, and neither showed any endocrine response to the analogue. Superagonists of gonadotrophin releasing hormone may be the treatment of choice in adenocarcinoma of the prostate, but further trials are required to establish long term safety and efficacy.

Acid Phosphatase↗
PubMed1983

Neuropeptide tyrosine (NPY)--a major cardiac neuropeptide.

A newly discovered bioactive peptide, neuropeptide tyrosine (NPY), has been found in the human cardiac nervous system. Dense concentrations of NPY-immunoreactive nerve fibres were found in association with nodal tissue (atrioventricular node 22.1 +/- 3.7 pmol/g). NPY nerve fibres were seen in close contact with cardiac muscle fibres and were also found around the coronary vessels (19.6 +/- 6.2 pmol/g). Analysis of the peptide by high-performance liquid chromatography demonstrated that it was present in a single molecular form, closely similar or identical to that of the isolated bioactive peptide. Cardiac function in man has long been known to be influenced by cholinergic and adrenergic nerves. There now appears to be a further component of the nervous system in the human heart, involving peptidergic nerves containing NPY.

Basal Ganglia↗
PubMed1983

Vagal origin of substance P-containing nerves in the guinea pig lung.

This study reports on the possible origin and putative sensory nature of substance P-containing fibres in the lung. Following vagal ligation experiments, carried out on adult guinea pigs, the vagi, nodose ganglia and lungs were investigated by immunocytochemistry and radioimmunoassay. After ligation the lung showed a marked depletion of substance P-immunoreactivity; concomitantly there was an accumulation of immunoreactive material proximal to the ligature, indicating a peripheral direction of the peptide axonal flow. Several substance P-immunoreactive neuronal cell bodies were observed in the nodose ganglion. These results suggest that substance P-immunoreactive fibres in the lung might originate from primary sensory neurones in the nodose ganglion, which is compatible with other evidence that substance P has a sensory role.

Animals↗
PubMed1983

Ontogeny of PHI in the rat brain.

The regional distribution of immunoreactive PHI (IR-PHI) was investigated in rat brain between postcoitum (pc) and day 60 postpartum (pp). IR-PHI was undetectable in all regions of the foetal brain, and only very small amounts were found at day 7 pp. However, there was a dramatic increase thereafter reaching a peak at day 20 pp (e.g. in the hippocampus there was a 12-fold increase in the PHI concentration). Highest concentrations were found in the cortex (40 +/- 5 pmol/g) and hippocampus (35 +/- 8 pmol/g), with lower concentrations in the diencephalon (11 +/- 4 pmol/g) and mesencephalon (10 +/- 3 pmol/g). The brainstem and cerebellum contained very low amounts of IR-PHI. Permeation analysis of brain extracts, on Sephadex G50-superfine, indicated the presence of one major form of IR-PHI which eluted in a similar position to pure intestinal porcine PHI and human intestinal PHI.

Animals↗
PubMed1983

Glucagonomas. Ultrastructure and immunocytochemistry.

Pancreatic tumors harboring glucagon immunoreactive cells were found in four patients with diabetes mellitus. Alpha-cell (glucagon) granules were present in three tumors; pancreatic polypeptide (PP) immunoreactive cells were detected in two. In two patients the tumors were malignant and one of these had the glucagonoma syndrome; the other was a member of a family with MEN-type I syndrome. These cases illustrate three clinical subtypes of glucagonoma.

Adenoma, Islet Cell↗
PubMed1983

Plasma neurotensin release and gastric emptying in the dumping syndrome.

Seventy-three patients were studied after ingesting a liquid glucose meal, tagged with 113Indium. Nineteen of these patients were awaiting surgery for their duodenal ulcer, while 54 were studied postoperatively, 25 of whom experienced troublesome postprandial (dumping) symptoms in their daily lives. The radioactive marker emptied significantly faster in the symptomatic patients than in the symptomfree, pre and post-operative groups (initial emptying rate 3.45 +/- 0.23, compared with 1.16 +/- 0.19 and 1.27 +/- 0.15% fall in counts/min respectively; p less than 0.01). Initial (20 min) rises in the plasma concentrations of neurotensin-like immunoreactivity measured during the test correlated significantly with the rate of gastric emptying in all patients, being greatest in patients with dumping symptoms. Physiological concentrations of neurotensin have been shown to delay gastric emptying. The excessive rise in plasma neurotensin-like immunoreactivity in patients with dumping symptoms, presumably occurring as a result of the rapid passage of nutrients to the neurotensin-rich ileum, may possibly have a compensatory role in slowing further emptying from the stomach.

Computers↗
PubMed1983

Radioimmunoassay of substance P and its stability in tissue.

A sensitive and specific radioimmunoassay for substance P has been developed and its full characterisation is described. The assay was used to investigate the stability of substance P in tissue in order to establish the optimal conditions of tissue storage for maximal recovery of the peptide. The results indicate unexpected post-mortem changes in tissue substance P content and suggests its existence in at least two separate pools, which differ in their susceptibility to degradation. These results highlight the need for careful consideration of both extraction technique and assay characteristics in radioimmunological investigations of substance P.

Animals↗
PubMed1983

Human pancreatic growth-hormone-releasing factor selectively stimulates growth-hormone secretion in man.

A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.

Acromegaly↗
PubMed1983

The role of pancreatico-biliary secretions in intestinal adaptation after resection, and its relationship to plasma enteroglucagon.

Two groups, each containing 16 male Wistar rats, had either 75 per cent small bowel resection or jejunal transection; 8 animals from each group; had previously been subjected to pancreatico-biliary diversion. All animals were killed 12 days after the operation, plasma enteroglucagon levels were measured and crypt cell production rate (CCPR) at different sites of the remaining small intestine was measured using a metaphase arrest technique with vincristine. In each of the resected groups there was a significant increase in the CCPR and enteroglucagon levels compared with the transected groups. Furthermore it was found that the CCPR and enteroglucagon levels were higher in the resected group without the pancreatico-biliary diversion compared with the resected group with the diversion. This study, although it confirms the importance of pancreatico-biliary secretions in intestinal adaptation, could also indicate that a humoral factor may be important in the control of intestinal cell proliferation. Our findings do not exclude the possibility that enteroglucagon could be a candidate for such a role.

Adaptation, Physiological↗
PubMed1983

The presence of peptide histidine-isoleucine in human, dog, guinea-pig and rat pancreas.

Peptide histidine isoleucine-like immunoreactivity has been detected in the pancreas of man (10.3 +/- 2.6 pmol/g), dog (6.5 +/- 1.1 pmol/g), guinea-pig (5.8 +/- 0.9 pmol/g) and rat (0.7 +/- 0.1 pmol/g) using a specific radioimmunoassay. Chromatographic analysis of the pancreatic extracts by high performance liquid chromatography indicated that both guinea-pig and rat have a molecular form of the immunoreactivity which is distinct from the porcine intestinal peptide histidine-isoleucine.

Animals↗
PubMed1983

Disparity between glucose-dependent insulinotropic polypeptide and insulin responses in obese man.

Studies were carried out in 32 obese patients and 30 normal-weight control subjects to ascertain the response of glucose-dependent insulinotropic polypeptide (GIP) and insulin to (1) oral and intravenous glucose (10 obese and 10 control subjects), (2) oral fat and intravenous glucose (eight obese and six control subjects) and (3) mixed test meal (14 obese and 14 control subjects). Basal mean insulin was higher in the obese (99 pmol/l) than in the control group (40 pmol/l), but fasting blood glucose and GIP were not significantly different from normal. The total integrated response of insulin in obese subjects after oral glucose was 54.1 versus 33.3 nmol . l-1 . h-1 in control subjects; glucose and GIP responses were similar in both groups. After intravenous glucose the integrated insulin response was 8.8 in the obese versus 5.0 nmol . l-1 . h-1 in control subjects; GIP was unaffected by intravenous glucose and glucose levels were similar. Following oral fat and intravenous glucose, insulin secretion was again abnormal in the obese, 24.5 versus 7.3 nmol . l-1 . h-1 in controls, but GIP responses were normal. However, the control subjects became hypoglycaemic after this test: blood glucose 2.8 mmol/l at 150 min compared with 4.6 mmol/l in the obese group. The insulin response to a mixed meal was also abnormal in obesity.

Administration, Oral↗