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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 937 records · Page 52Linked to original sources
PubMed1982

[The effect of calcium on the release of gastric inhibitory polypeptide (GIP) - with reference to the release of GIP in patients with hyperparathyroidism (author's transl)].

Plasma gastric inhibitory polypeptide (GIP), insulin, glucagon concentrations and blood glucose levels in response to the ingestion of 100 g glucose were measured in 5 patients with hyperparathyroidism in order to elucidate the effect of hypercalcemia on the release of these hormones. In addition, the effect of acute hypercalcemia on the release of these hormones in response to glucose ingestion was investigated in normal subjects. Fasting plasma GIP concentration in patients with hyperparathyroidism was significantly greater than the value in seventeen normal subjects. Significantly higher responses of plasma GIP and insulin were observed after the glucose ingestion in the patients with hyperparathyroidism as compared with the values in the normal subjects, and integrated GIP and insulin responses to the glucose ingestion for 120 min in the patients with hyperparathyroidism were significantly greater than the values in the normal subjects. On the other hand, plasma glucagon concentration after the glucose ingestion in the patients with hyperparathyroidism remained unchanged, although plasma glucagon concentrations after the glucose ingestion decreased significantly from the basal value in the normal subjects. Blood glucose levels after the glucose ingestion in two groups increased significantly from the basal value in the same manner. In nine normal subjects calcium infusion (4 mg/kg bolus injection followed by continuous infusion of 4 mg/kg/hr for 3 hr) caused a significantly high concentration of plasma calcium (11.5 approximately 13.0 mg/dl) from the basal value. Significantly higher responses of plasma GIP and insulin to the glucose ingestion were observed during calcium infusion as compared with the values during saline infusion. On the other hand, plasma glucagon concentration after the glucose ingestion was not significantly changed during calcium infusion in contrast with a significant decrease of plasma glucagon after the glucose ingestion during saline infusion. Consequently, calcium was considered to play a major part in the release of GIP and insulin. The characteristic response of plasma glucagon during calcium infusion was considered, at least in part, to protect the hypoglycemia caused by hyperinsulinemia.

Adult↗
PubMed1982

Developmental changes in bombesin, substance P, somatostatin and vasoactive intestinal polypeptide in the rat brain.

The regional distribution of the 4 neuropeptides, bombesin, substance P, somatostatin and vasoactive intestinal polypeptide (VIP) were investigated in the developing rat brain. Specific radioimmunoassay and immunocytochemistry were employed. VIP and bombesin were undetectable in the foetal brain whereas substance P and somatostatin were shown to be present in all regions as early as 14 days postcoitus. There was a dramatic postnatal increase in all 4 peptides in most regions. These results are discussed and compared with results of previous investigations of the ontogeny of the classic neurotransmitters.

Aging↗
PubMed1982

The effect of altered luminal nutrition on cellular proliferation and plasma concentrations of enteroglucagon and gastrin after small bowel resection in the rat.

Luminal nutrition is known to have a trophic effect on small bowel mucosa after intestinal resection. Humoral agents, however, may also contribute to this process. Two of the proposed humoral agents, enteroglucagon and gastrin, were therefore investigated after intestinal resection and transection in the rat, and changes in their concentration in the plasma were related to cellular proliferation. Forty-eight male Wistar rats had either 75 per cent proximal small bowel resection or jejunal transection. The animals were further divided into three groups, each with a different nutritional intake. The first group were allowed food ad libitum. The second group were kept under hypothermic conditions which resulted in hyperphagia, while the last group were nourished intravenously. A further 8 animals had a laparotomy only (sham operation). All animals were killed 12 days after operation, plasma enteroglucagon and gastrin were measured, while determination of the crypt cell production rate (CCPR) was used to denote cellular proliferation. In each group resected rats had significantly higher crypt cell production rates and greater enteroglucagon levels compared with transected animals. However, only in the normally fed group was plasma gastrin increased in resected animals, there being no significant difference in the plasma concentration of this peptide in transected compared with resected rats, in both the intravenously fed and hyperphagic groups. In the models studied enteroglucagon appears to be a more likely candidate for a humoral trophic agent than gastrin in intestinal adaptation.

Adaptation, Physiological↗
PubMed1982

The effect of glucose-dependent insulinotropic polypeptide infused at physiological concentrations on the release of insulin in man.

Blood glucose and the responses of insulin and glucose-dependent insulinotropic polypeptide (GIP) were measured in 12 healthy, normal weight subjects after drinking 50 g glucose. On a subsequent occasion each subject was given a simultaneous infusion of GIP and glucose to mimic the plasma concentrations observed in the first test. The peak GIP concentration after oral glucose was 22.3 +/- 1.9 pmol/l (mean +/- SEM), but was higher after GIP infusion at 36.3 +/- 4.6 pmol/l, (p less than 0.005). The blood glucose levels following oral glucose peaked at 6.3 +/- 0.5 mmol/l which was the same as seen after intravenous glucose. The insulin response to oral glucose was, however, far higher (431.3 +/- 58.2 pmol/l) than that obtained after GIP and glucose infusion (191.6 +/- 30.9 pmol/l, p less than 0.001). Thus it has not proved possible to explain completely the oral enhancement of insulin release by the action of GIP alone.

Administration, Oral↗
PubMed1982

Neuron specific enolase (NSE) immunostaining detection of endocrine cell hyperplasia in adult rats exposed to asbestos.

Hyperplasia of endocrine cells in the lung of the adult rat exposed to asbestos has only been characterised so far by electron microscopy as there is a lack of reliable staining techniques for their demonstration at light microscopical level. Neuron specific enolase (NSE), an isoenzyme of the glycolytic enzyme enolase has recently been shown to be present in lung endocrine cells. In this study we reveal a marked endocrine cell hyperplasia at light microscopical level in the lungs of adult rats exposed to asbestos using antibodies to NSE. Very large groups of NSE-immunoreactive cells (20-80) were only observed in the lungs of rats exposed to asbestos for 12 months. In addition smaller groups of cells (2-10) known to be present normally and to decrease with age, were rarely noted in the controls but were frequently detected in the treated rats. Immunoreactive NSE is therefore a very good marker for endocrine cell hyperplasia and thus of early neoplastic changes.

Animals↗
PubMed1982

Pancreatic glucagon in human foetal stomach.

A combination of immunocytochemistry at light and electron microscopic levels, direct radioimmunoassay and measurement after gel chromatography have been used to identify and characterise a glucagon-like peptide detected in human foetal stomach. Immunocytochemistry, with region specific antisera, demonstrated that the glucagon-containing cells were indistinguishable from pancreatic A cells. Radioimmunoassay of tissue extracts confirmed the presence of significant quantities of glucagon, mean 21 pmol/g wet weight (range 14-29) in 16-26 week old foetuses, increasing to 41 pmol/g wet weight (range 31-52) in 33-30 week old foetuses and after gel chromatography the peptide was found to elute at the same position as standard porcine glucagon. It is apparent, therefore, that the human foetal fundus contains significant quantities of true pancreatic-type glucagon.

Female↗
PubMed1982

Mapping, quantitative distribution and origin of substance p- and VIP-containing nerves in the uvea of guinea pig eye.

VIP- and substance P-like immunoreactivities were found in considerable concentrations (VIP: 17.3 +/- 4.8 pmol/g, mean +/- SEM; substance P:11.1 +/- 1.8 pmol/g) in the uveal portion of the guinea pig eye. Immunocytochemistry localised these two regulatory peptides to nerve fibres found principally in a plexus in the iris (substance P) and in an extensive network surrounding the blood vessels of the choroid (VIP). A remarkable anatomical demarcation of the two types of peptide-containing nerves was established by the staining of substance P-containing nerves, which stops at the level of the ciliary body. This uveal area is known to be involved in the ocular responses to nociceptive stimuli. At the ultrastructural level, immunoreactivity for both peptides was localised to distinct subpopulations of p-type nerves, distinguishable by the size of their large dense-cored vesicles. Those immunoreactive for VIP were significantly larger (p less than 0.0005) than those immunoreactive for substance P (95 +/- 7 nm and 82 +/- 9 nm respectively; mean +/- SD). Interruption of the trigeminal pathway produced a remarkable decrease of substance P immunoreactivity in the anterior portion of the uvea (9.1 +/- 1.5 pmol/g, mean +/- SEM, control; 5.3 +/- 1.3 pmol/g, denervated), but not of VIP immunoreactivity in the choroid. Following colchicine treatment, VIP-immunoreactive neuronal cell bodies were localised in the choroid. The separate anatomical localisations and distributions of the two uveal peptides appear to be related to their different origins and functional roles in the response of the eye to noxious stimuli.

Acetylcholinesterase↗
PubMed1982

Peptide-containing innervation of the human intestinal mucosa. An immunocytochemical study on whole-mount preparations.

The three-dimensional distribution of the peptide-containing innervation in the human intestinal mucosa was studied by fluorescence immunohistochemistry on whole-mount mucosal preparations. An extensive VIP-immunoreactive nerve supply was demonstrated at all levels, but was markedly increased in density in the distal intestine, where it formed a particularly rich network in close contact with the luminal epithelium. In contrast, substance P-containing nerve fibres formed a looser and evenly distributed innervation at all levels. The muscularis mucosae was richly supplied by VIP- and substance P-containing fibres. Met-enkephalin immunoreactivity was confined to a few scattered nerve bundles running in the muscularis mucosae and around the bottom of epithelial crypts.

Animals↗
PubMed1982

PHI stimulates intestinal fluid secretion.

Regulatory peptides are likely to have a role in the control of net intestinal fluid transport. PHI is a peptide recently isolated from porcine duodenum which has been shown to have sequence homologies with other peptides of the glucagon-secretin family. We have studied the effect of intravenous infusion of synthetic PHI on net intestinal fluid transport in the rat small intestine. During PHI infection net absorption was reduced in the duodenum and jejunum and net secretion was observed in the ileum. Thus synthetic PHI appears to be capable of strongly stimulating intestinal secretion in the rat.

Animals↗
PubMed1982

Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man.

The role of pancreatic polypeptide (PP) and motilin in the regulation of the migrating motor complex (MMC) was studied in normal subjects. Both plasma motilin and PP levels changed cyclically in the fasted state and were highest in the late phase II period preceding the activity front in the duodenum. A continental breakfast invariably disrupted the MMC and induced a fed pattern of motility. After the meal plasma motilin levels decreased whereas PP levels rose significantly. Infusion of pure porcine motilin during the fasted state induced an activity front and a rise in plasma PP levels. Infusion of bovine PP in doses producing plasma PP levels above the postprandial values neither induced an activity front nor prevented its occurrence. During PP infusion, however, plasma motilin levels were low, although the activity front was not inhibited. PP seems to have no clear role in the regulation of the motor component of the MMC of man. The role of motilin in the production of the activity front of the MMC is discussed.

Duodenum↗
PubMed1982

Content and release of neurotensin in PC12 pheochromocytoma cell cultures: modulation by dexamethasone and nerve growth factor.

The production of neurotensin-like immunoreactivity was investigated in cultured PC12 rat pheochromocytoma cells with and without the addition of nerve growth factor (NGF) and dexamethasone. Both monolayer cultures and spinner cultures contained measurable amounts of neurotensin. In the monolayer cultures supplemented with NGF and dexamethasone, cell and medium concentrations of neurotensin increased approx. 100-fold. In the spinner cultures the effect of the additives was less potent and the increase in neurotensin content, while still considerable, was approximately an order of magnitude less. Chromatographic analysis of medium and extracts of the cells from monolayer cultures indicated that the majority of the immunoreactivity coeluted in the same position as synthetic neurotensin, with recoveries of 68 and 85%, respectively. The effect of NGF and dexamethasone on neurotensin production differs significantly from their effect on catecholamine production in PC12 cells, and this suggests the possibility of independent regulation.

Adrenal Gland Neoplasms↗
PubMed1982

Bombesin production by human small cell carcinoma of the lung.

A series of continuous cell lines of human small cell carcinoma of the lung (SCCL) have been evaluated for the production of bombesin (BN). In early established cultures BN was detected in the medium of 9 out of 11 cell lines and in 6 out of 7 cell homogenates examined. Levels in the medium were frequently higher in cultures of later passages compared to earlier passages of the same line and low levels developed in the two previously negative cell lines. Plasma concentrations were greater than 80 pmol/l in 2 out of 27 (7%) randomly selected patients with SCCL. A culture (DMS 406) established from the tumor of a patient with the highest plasma level (1240 pmol/l) was the highest producer in vitro. The results indicate that BN, which has been demonstrated immunocytochemically to be present in normal bronchial mucosal cells, is frequently produced by SCCL in vitro but elevated plasma levels are infrequently found in patients with this neoplasm.

Bombesin↗
PubMed1982

Local application of capsaicin to one sciatic nerve of the adult rat induces a marked depletion in the peptide content of the lumbar dorsal horn.

In an earlier study we have shown that local application of capsaicin directly to one sciatic nerve induces a decrease of substance P and cholecystokinin octapeptide (CCK8)-like peptide from the dorsal spinal cord using immunocytochemical analysis. Here the effect of locally applied capsaicin on seven peptides known to be present in the L4 segment was assessed by radioimmunoassay and immunocytochemistry. The peptides investigated were substance P, somatostatin and CCK8-like peptide (which are present in small diameter primary afferent fibres), neurotensin, enkephalin (which are intrinsic to the spinal cord), neurophysin (of supraspinal origin) and bombesin (whose origin is unknown). Fourteen days after a single application of 49 mM solution of capsaicin a significant depletion of substance P and somatostatin was detected. These results were confirmed by parallel immunocytochemical analysis which localised the dramatic decreases of substance P and somatostatin to lamina 1 and lamina 2. In addition a depletion of CCK8-like immunoreactivity was observed by immunocytochemistry in this area, but quantitative radioimmunoassay of CCK8-like peptide did not detect this depletion. The capsaicin-induced changes were dose-dependent and reversible. Small decreases were noted with concentrations of capsaicin as low as 0.1 mM. The changes were apparent from day 9 onwards, maximal depletion seen by day 14. By 200 days post-operatively, a recovery to normal peptide levels in the ipsilateral dorsal horn was observed. In addition, a significant depletion of cutaneous substance P was noted in the area of the skin innervated by the capsaicin-treated nerve. These changes were accompanied by a significant increase in noxious thermal response (hind paw immersion test, T = 49 degrees C, ipsilateral leg 9.11 +/- 1.3 seconds, contralateral leg: 5.1 +/- 1.3 seconds, P = less than 0.005). The peptides neurotensin, enkephalin, neurophysin and bombesin were not affected by capsaicin treatment. These findings suggest that local application of capsaicin induces an indiscriminate depletion of peptide-containing primary sensory afferent fibres which is dose-dependent, long-lasting, but reversible.

Administration, Topical↗
PubMed1982

Duodenal perfusion with sodium taurocholate inhibits biliary but not pancreatic secretion in man.

1. A standard duodenal perfusion technique was used to study the effects of luminally perfused sodium taurocholate on basal and stimulated biliary and pancreatic secretion and gastrointestinal hormone release in man. 2. During duodenal perfusion with sodium taurocholate alone, both basal and caerulein/secretin-stimulated bilirubin secretion were suppressed. A successive perfusion with a mixture of the bile salt and essential amino acids in combination overcame the biliary suppression and biliary secretion rose above basal levels. A further increase in bilirubin secretion was not observed in a subsequent perfusion with essential amino acids alone in these studies. 3. No inhibitory effect on basal or caerulein/secretin-stimulated trypsin secretion was observed during the bile salt perfusion; basal trypsin secretion was in fact slightly increased during a prolonged (4 h) perfusion of the bile salt. 4. During bile salt perfusion, basal bicarbonate secretion remained unchanged but caerulein/secretin-stimulated bicarbonate secretion was slightly increased. 5. Plasma levels of pancreatic polypeptide, gastric inhibitory peptide and gastrin did not change significantly during duodenal perfusion with bile salt, but plasma levels of motilin were suppressed. 6. These results support the view that bile salts in the duodenum may regulate biliary and pancreatic secretion in man and affect plasma levels of motilin.

Adult↗
PubMed1982

Slow release dietary carbohydrate improves second meal tolerance.

Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or "lente" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.

Adult↗