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Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 199 records · Page 11Linked to original sources
PubMed1986

Peptide YY abnormalities in gastrointestinal diseases.

Plasma concentrations of peptide YY (PYY), a newly isolated peptide produced by ileal and colonic endocrine cells, were measured in several groups of patients with digestive disorders after a standardized normal breakfast. Peptide YY levels were found to be grossly elevated in patients with steatorrhea due to small intestinal mucosal atrophy (tropical sprue). Basal levels in these patients were 79 +/- 18 pM, which was nearly 10-fold higher than those seen in healthy controls (8.5 +/- 0.8 pM). Patients with steatorrhea due to chronic destructive pancreatitis also had substantially increased basal PYY levels (47.5 +/- 6.3 pM), and their postprandial response was also greater than that of normal subjects. Moderately elevated plasma PYY concentrations were seen in patients with inflammatory bowel disease and patients recovering from acute infective diarrhea. In contrast, patients with diverticular disease, duodenal ulcer, and functional bowel disease had normal PYY responses. These changes in the secretion of PYY responses. These changes in the secretion, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.

Adult↗
PubMed1986

Electrophysiological actions of somatostatin on the atrioventricular junction in sinus rhythm and reentry tachycardia.

Because somatostatin, a neuroregulatory peptide, is found in abundance in the atria and atrioventricular node, its electrophysiological and antiarrhythmic properties were compared with those of verapamil in ten patients with paroxysmal atrioventricular tachycardia. During sinus rhythm, intravenous somatostatin slowed the heart rate whereas verapamil increased it. Though both agents prolonged atrioventricular conduction time and refractoriness, verapamil was more potent. They were equally effective at terminating reentry atrioventricular tachycardia, restoring sinus rhythm in six of seven patients. Whereas verapamil consistently blocked conduction in the atrioventricular node, somatostatin usually induced ventricular extrasystoles at the time of conversion. Somatostatin may have physiological importance in the neurohumoral control of cardiac impulse formation and conduction.

Adult↗
PubMed1986

Elevated plasma peptide YY in human neonates and infants.

Plasma concentrations of peptide YY (PYY) were measured in cord blood and at 6, 12, and 18 days of postnatal life in 24 healthy preterm neonates, from cord blood of eight full-term neonates, and from peripheral blood of 13 infants 9 months old. Concentrations were high in cord blood (73 +/- 9 pmol/liter versus adult fasting 10.4 +/- 1.3, p less than 0.001) and rose postnatally in the premature infants to 399 +/- 48 pmol/liter at 6 days, 489 +/- 42 at 12 days, and fell to 414 +/- 43 at 18 days. Plasma PYY concentrations were much lower in infants 9 months old (32 +/- 3 pmol/liter), suggesting that the postnatal surge of plasma PYY is a feature of early adaptation to extrauterine life. Gel permeation chromatograms revealed that the major circulating form of PYY in the neonate eluted in a position identical to that of the pure 36 amino acid peptide. There was, however, evidence of two larger molecular forms that may be precursor molecules. Because PYY is a peptide that exhibits potent effects on gastrointestinal secretion and motility in humans, these observations suggest that this candidate gut hormone may be important in the adaptation to enteral nutrition in the neonate.

Fetal Blood↗
PubMed1986

Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man.

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.

Adult↗
PubMed1986

Localization and molecular forms of galanin in human adrenals: elevated levels in pheochromocytomas.

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.

Adrenal Gland Neoplasms↗
PubMed1985

Ontogeny of a novel pituitary protein (7B2) in the human fetal intestine.

The developmental profile of the concentration of a novel pituitary protein (7B2) was studied immunochemically in the human gastrointestinal tract from 12 weeks of gestation to 4 months after birth and was compared to the distribution in the adult. 7B2-like immunoreactivity (IR-7B2) was detected in all segments studied, but no gross changes were seen through fetal life. At term higher concentrations of IR-7B2 were found in the duodenum and the antrum, which is similar to the distribution of adult man. Gel permeation chromatography revealed that the main peak of 7B2 immunoreactivity in the fetal intestinal extract eluted with a Kav of 0.3. Similar elution profiles were also observed in extracts of human adult intestine.

Adult↗
PubMed1985

Effect of long acting somatostatin-analogue, SMS 201 995, on gut hormone secretion in normal subjects.

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s.c. injection of 50 micrograms it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.

Adult↗
PubMed1985

Somatostatin and the dumping syndrome.

Infusion of somatostatin reduced the symptoms of the early dumping syndrome after oral glucose was given and also reduced the associated tachycardia and rise in packed cell volume. It inhibited the secretion of enteroglucagon, neurotensin, and vasoactive intestinal polypeptide, which are raised in patients with the dumping syndrome and may have an aetiological role. It also prevented the reactive hypoglycaemia of late dumping by inhibiting the release of gastric inhibitory polypeptide and insulin. Somatostatin, possibly through its inhibitory effects on hormonal secretion, may have a role in the management of patients with the early and late dumping syndrome.

Blood Glucose↗
PubMed1985

Bile exclusion from the duodenum. Its effect on gastric and pancreatic function in the dog.

The effect of diverting bile from the duodenum in four dogs with cholecystojejunostomy was studied using a double-marker perfusion technique. After the diversion procedure, a liquid meal increased acid secretion from 0.8 mmol H+/min to 1.48 mmol H+/min (P less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 min after feeding (P less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (P less than 0.01, paired t test), and the level of CCK was significantly lower 60 min after feeding (P less than 0.05, paired t test). There was no significant change in the rate of gastric emptying after bile diversion, but the pH of duodenal contents was lower in the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum, and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

Amylases↗
PubMed1985

Plasma peptide YY (PYY) in dumping syndrome.

The newly isolated hormonal peptide PYY is mainly localized to endocrine cells of the lower intestinal mucosa. The release of PYY by oral glucose was studied in six patients with the dumping syndrome to ascertain the effect of this condition on PYY release. Plasma PYY concentrations were greatly increased following oral glucose in patients with the dumping syndrome compared with healthy controls. In a separate series of experiments, the effect of somatostatin infusion on the PYY release by glucose in these patients was investigated. The release of PYY was completely blocked by infusion of somatostatin, and its release from the bowel in normal subjects may therefore be modulated by local somatostatin in the gut. PYY has been shown to inhibit gastric acid secretion and emptying, at plasma concentrations similar to those seen after glucose, in patients with the dumping syndrome. PYY may therefore be a factor involved in the pathophysiological changes associated with this condition.

Chromatography, Gel↗
PubMed1985

Human distribution and release of a putative new gut hormone, peptide YY.

A radioimmunoassay has been developed for the new intestinal hormonal peptide tyrosine tyrosine [peptide YY (PYY)]. Peptide YY concentrations were measured in separated layers of the human gastrointestinal tract, where PYY was found exclusively in the mucosal epithelium which contained the endocrine cells. Peptide YY was found throughout the small intestine, in very low concentrations (5 pmol/g) in duodenum (6 pmol/g) and jejunum (5 pmol/g), but in higher concentrations in the terminal ileum (84 pmol/g). High concentrations were found throughout the colon (ascending 82 pmol/g, sigmoid 196 pmol/g), being maximum in the rectum (480 pmol/g). The major molecular form of PYY-like immunoreactivity in human intestine appeared to be identical to pure porcine hormone, both as judged by gel permeation chromatography and by reverse-phase high-pressure liquid chromatography. Basal plasma concentrations of PYY were low but rose in response to food, remaining elevated for several hours postprandially. The known potent biologic actions of PYY, its high concentrations in gut endocrine cells, and its release into the circulation after a normal meal suggest that this peptide may function physiologically as a circulating gut hormone.

Adult↗
PubMed1985

Effect of peptide YY on gastric, pancreatic, and biliary function in humans.

The effect of peptide YY (PYY) on gastric and pancreatico-biliary secretion was studied in humans. Peptide YY was infused into groups of 6 healthy volunteers at doses of 0.59, 0.20, and 0.064 pmol X kg-1 X min-1. The two higher doses caused a significant suppression of gastric acid and pepsin output during background stimulation with pentagastrin. The middle dose of PYY (0.20 pmol X kg-1 X min-1) that increased plasma PYY levels by 27 +/- 2 pM caused a 90% +/- 18% (mean +/- SEM; p less than 0.001) reduction in the incremental gastric volume response to pentagastrin. Similarly this dose of PYY caused a substantial inhibition of the acid (77% +/- 14%; p less than 0.005) and pepsin (96% +/- 22%; p less than 0.01) response to pentagastrin; in 2 subjects, pepsin output fell to below basal levels. In contrast, the highest dose of PYY (0.62 pmol X kg-1 X min-1) had no significant influence on duodenal juice volume, output of bicarbonate, trypsin, or bilirubin during low dose stimulation with secretin (0.25 pmol X kg-1 X min-1) and cholecystokinin-8 (0.15 pmol X kg-1 X min-1). Thus PYY concentrations in the circulation similar to those seen after the ingestion of food cause a marked reduction in gastric secretion. This peptide should therefore be considered as one of the possible candidates for the classical enterogastrone.

Adolescent↗
PubMed1985

Rat immunoreactive cholecystokinin (CCK): characterization using two chromatographic techniques.

Acid and neutral extracts of rat cerebral cortex and upper small intestine were prepared and the endogenous concentrations of cholecystokinin-like immunoreactivity (CCK-LI) measured by three new CCK-specific radioimmunoassays. The characterization of the immunoreactive CCK molecular forms was undertaken using gel permeation chromatography in the presence of 6 M urea to minimise problems relating to peptide adsorption or aggregation. Reverse-phase high-performance liquid chromatography (HPLC) was also performed on the rat tissue extracts. Rat cortex contained 268 +/- 12 pmol/g CCK-LI, and over 90% resembled the sulphated CCK-8, which was preferentially extracted at neutral pH. In contrast, the rat upper small intestine (97 +/- 8 pmol/g of CCK-LI) contained less than 20% CCK-8, the majority of immunoreactive CCK being of larger molecular size and being preferentially extracted at acid pH. In the small intestine the predominant molecular form(s) was intermediate in size between CCK-33 and CCK-8. Large amounts of CCK-33 and of a molecular form larger than CCK-33 were also detected. It is concluded that post-translational cleavage of CCK differs in rat brain and gut.

Animals↗
PubMed1985

Effect of calcitonin on gastrointestinal regulatory peptides in man.

A major physiological role of calcitonin in humans appears to be regulation of skeletal turnover. It has been suggested that another function of calcitonin is to prevent post-prandial rises in calcium, particularly in animals, but the importance of such a function in man remains to be determined. Although it is known that calcitonin has an inhibitory effect on the secretion of gastrin and insulin, its actions on other gut and pancreatic hormones have not previously been studied. To investigate interrelations between calcitonin and gastrointestinal regulatory peptides, 0.5 mg synthetic human calcitonin was administered to 10 fasting patients. No changes in the plasma concentrations of glucose, somatostatin, neurotensin, enteroglucagon, vasoactive intestinal polypeptide or bombesin were observed. In contrast, profound falls in the circulating levels of gastrin, insulin and pancreatic glucagon were seen, reaching a maximum shortly after the peak of plasma calcitonin concentration. Marked changes were also observed in the levels of motilin, pancreatic polypeptide and, to a lesser extent, gastric inhibitory polypeptide, but the maximal falls occurred about 40 min later, coinciding with a significant fall in serum calcium. It is possible that the effect of calcitonin on these hormones was direct, perhaps receptor-mediated. The falls in levels of motilin and pancreatic polypeptide could have been further enhanced by changes in extracellular calcium ion concentrations. Whether any of these effects of calcitonin occur physiologically remains to be determined. However, these findings suggest new therapeutic possibilities for calcitonin.

Adult↗
PubMed1985

Positive correlation between symptoms and circulating motilin, pancreatic polypeptide and gastrin concentrations in functional bowel disorders.

Motilin, pancreatic polypeptide and gastrin blood concentrations in response to drinking water have been studied in 40 patients with functional bowel disease and compared with results in two groups of healthy control subjects. Patients with slow transit constipation and idiopathic megacolon showed impaired motilin release. Pancreatic polypeptide release was reduced in patients with slow transit constipation, but increased in those with functional diarrhoea. Gastrin release was impaired in all groups complaining of chronic constipation. Circulating motilin, pancreatic polypeptide and gastrin concentrations appear to bear some relationship to intestinal transit time in patients with functional bowel disorders.

Adult↗
PubMed1985

Is raised plasma peptide YY after intestinal resection in the rat responsible for the trophic response?

The relationship between the adaptive response and plasma PYY concentrations after small bowel resection has been investigated. Seventy five per cent proximal small bowel resection resulted in a rise in plasma PYY at six days from 28 +/- 3.1 to 85 +/- 12.3 pmol/l (p less than 0.001) and this difference was maintained to 48 days. Plasma PYY correlates both with crypt cell production rate (CCPR) in the ileum and with plasma enteroglucagon levels. In a second study, PYY or saline was infused over a 12 day period. There were no significant changes in intestinal wet weight or CCPR in any part of the bowel studied. This indicates that it is unlikely that PYY exerts a major trophic effect on the gastrointestinal tract.

Animals↗
PubMed1985

Treatment of patients with pancreatic endocrine tumours using a new long-acting somatostatin analogue symptomatic and peptide responses.

Seven patients with gut and pancreatic endocrine tumours have been treated with a long acting somatostatin analogue (SMS 201-995), given as a twice daily subcutaneous injection. This produced dramatic improvement in their endocrine related symptoms, in association with a fall in circulating tumour peptides. One of these patients has now been treated for seven months with this analogue which has controlled his previously life threatening diarrhoea caused by a malignant VIP secreting tumour. He gives his own injections twice daily, and has returned to a full and active life. This is a promising agent both for acute treatment of peptide hypersecretion, and for the long term management of some patients who are unresponsive to other available therapy.

Adult↗