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Biomedical subjects

W Y Chey

Publications and source records attributed to W Y Chey.

At least 145 records · Page 8Linked to original sources

Cause-and-effect relationship between motilin and migrating myoelectric complexes.

We investigated the cause-and-effect relationship between plasma motilin levels and migrating myoelectric complexes (MMCs). Each dog was implanted with a set of eight bipolar electrodes on the small intestine. Premature phase IIIs were initiated by morphine bolus injections. Plasma samples were assayed for motilin and gastrin. All spontaneous and morphine-initiated phase IIIs were associated with peaks of plasma motilin, which always occurred after phase IIIs had started in the proximal duodenum. The plasma motilin level decreased consistently during phase I and started to increase again only after phase II had started in the duodenum. Either a meal or somatostatin infusion disrupted MMC cycling, but morphine boluses overcame this disruption and initiated phase IIIs that propagated distally. The phase IIIs thus initiated were associated with peaks in plasma motilin levels. In contrast, bolus injections of motilin did not initiate phase IIIs during the fed state or during somatostatin infusion. Our findings suggest that endogenous motilin does not initiate spontaneous MMCs. Instead, MMC contractions release motilin. The physiological role of motilin, thus released, may be to act as an endocrine agent to coordinate secretory and motor events with the start of phase III activity in the upper small intestine.

Animals↗

Effect of motilin on the opossum upper gastrointestinal tract and sphincter of Oddi.

We studied the effect of motilin on myoelectric activity of the sphincter of Oddi (SO) and upper gastrointestinal tract in conscious opposums. In 17 animals, bipolar electrodes were implanted on the gastric antrum, SO, duodenum, and jejunum. Subsequent 8-h recordings reconfirmed our previous findings that SO spike burst rate changed with interdigestive cycles of the gastrointestinal migrating myoelectric complex (MMC), becoming maximal during passage of phase III activity through the duodenum. In eight animals, peak motilin levels were shown to occur concurrently with maximal SO spike burst rate and MMC phase III activity in the duodenum. Motilin infusion (0.3 and 0.9 micrograms X kg-1 X h-1), given for 30-60 min starting 10 min after duodenal phase III, elicited premature MMC activity that originated in the stomach. Maximal SO activity occurred coincident with passage of premature phase III activity through the duodenum. Pulse intravenous doses of motilin (25-1,600 ng/kg) generally caused an immediate increase in spike burst activity in the gastric antrum, duodenum, and SO that lasted 3-5 min and was often followed by a premature MMC, usually starting in the antrum and progressing through the duodenum and jejunum. Increases in SO spike burst rate also occurred concurrent with motilin-induced, premature duodenal phase III. Motilin given at 5-60% of the duodenal MMC cycle length elicited premature MMCs at 10-60% of the cycle, but no premature MMCs were elicited by any of the motilin doses at the 5% intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampulla of Vater↗

Effect of rabbit antimotilin serum on myoelectric activity and plasma motilin concentration in fasting dog.

It is known that a cyclic increase in plasma motilin concentration occurs during the interdigestive state of dog and the increase coincides with migrating myoelectric complexes (MMCs) of the antrum as well as proximal duodenum. The purpose of the present study is to determine the role of endogenous motilin in the occurrence of MMCs in 10 dogs prepared with a gastric cannula and platinum monopolar electrodes in the gastric antrum, duodenum, jejunum, and ileum. After recording at least two consecutive cycles of MMCs from the proximal duodenum, each dog received an intravenous infusion of highly specific rabbit antimotilin sera in varying doses ranging from 3.5 to 15 ml for a period of 60 or 90 min. During the motility recording period ranging from 6 to 30 h following the administration of the antimotilin serum, several changes in the motility were observed. 1) The occurrence of MMCs in the antrum, duodenum, jejunum, and ileum was temporarily interrupted for varying periods depending on the individual dog studied and the amount of antiserum administered. When the higher dose of antimotilin was administered, a more profound and prolonged inhibition occurred. 2) Phase I activity rarely occurred. Instead, a phase II-like activity continued throughout the recording period. 3) MMCs in the jejunum or ileum occurred at irregular intervals without aboral propagation of MMCs from the duodenum or jejunum. 4) The plasma motilin concentration decreased to levels lower than that observed during phase I of the duodenum and exhibited no cyclic increase until the MMCs reappeared in the proximal duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Secretin-like immunoreactivity and biological activity in the antral mucosa.

Using immunohistocytochemical techniques, secretin cells are again demonstrated in the antral mucosae of both dogs and rats. Secretin-like immunoreactivity was found in the crude extracts of antral mucosae in 15 dogs [1.18 +/- 0.48 (+/- SE) ng/g wet wt of mucosae], and a similar amount of SLI was also found in 82 rat antral mucosae. Upon ion exchange chromatography, the extracts of dog antral mucosae exhibited a predominant species eluted by the same salt concentration as porcine secretin. The rat antral mucosal extract also produced a chromatogram exhibiting the same predominant species on the ion exchanger. The main immunoreactive secretin peak, when gel filtrated on a Sephadex G-50 (superfine) column, produced an elution profile identical to that of standard natural porcine secretin. These results indicated that antral mucosae of both animal species contain an immunoreactive secretin-like material of the same charge and size as natural porcine secretin. Intravenous injection of a preparation of partially purified secretin from the extracts of canine antral mucosae resulted in a significant increase in the pancreatic flow in anesthetized rats. We conclude that a small number of secretin cells are, therefore, present in the antral mucosae of dog and rat, and this observation is supported by the presence of an immunologically and biologically active secretin-like molecule with charge and size similar to those of porcine secretin in the canine mucosal extracts.

Animals↗

Somatostatinoma syndrome: does a clinical entity exist?

We report here 2 patients with somatostatin-secreting tumours and hypersomatostatinaemia. One subject, a 36 year old woman with diabetes, flushing, labile blood pressure and diarrhea, had elevated basal plasma levels of somatostatin-like immunoreactivity (SLIR) and calcitonin. Plasma SLIR increased further following tolbutamide administration. Plasma levels of prostaglandin E2 (PGE2) and pancreatic polypeptide (PP), normal in the basal state, showed exaggerated responses to pentagastrin and secretin, respectively. Immunocytochemistry of the tumour tissue revealed cells containing somatostatin-, calcitonin-, PGE2- and PP-like immunoreactivity. The other patient, a 52 year old male, had an SLIR-secreting tumour of the proximal duodenum and elevated basal and post-tolbutamide SLIR levels but no signs or symptoms suggestive of increased SLIR production. Tumour tissue revealed cells containing somatostatin- and calcitonin-like immunoreactivity. We conclude that patients with somatostatinomas do not always exhibit a predictable syndrome. Patients with these tumours may exhibit a range of clinical, biochemical and immunocytochemical features typical of endocrine tumours of mixed-cell origin, such that the dominant signs and symptoms associated with these neoplasms cannot readily be ascribed to overproduction of any single hormone.

Adenoma, Islet Cell↗

Liver injury with alcoholiclike hyalin after gastroplasty for morbid obesity.

Hepatic damage resembling alcoholic hepatitis has been described after jejunoileal bypass surgery for morbid obesity, but has not been previously reported as a complication of gastric partitioning operations (gastric bypass and gastroplasty). A patient who developed an alcoholic hepatitislike clinical picture 8 mo after gastroplasty is described, suggesting that malnutrition superimposed on obesity may be responsible for the injury in both settings. Reversal of the gastroplasty was associated with clinical and biochemical improvement.

Adult↗

Potentiation effect of cholecystokinin-octapeptide on pancreatic bicarbonate secretion stimulated by a physiologic dose of secretin in humans.

We studied the potentiation effect of cholecystokinin-octapeptide and secretin on pancreatic secretion of bicarbonate and trypsin in humans. The pancreatic bicarbonate and trypsin outputs were determined by using a triple-lumen duodenal tube and indicator dilution technique while gastric juice was completely aspirated. When cholecystokinin-octapeptide in varied doses, 2.6, 5.3, 10.9, 26.3, 52.6, and 109.4 pmol . kg-1 . h-1, was added to i.v. infusion of secretin in a physiologic dose, 0.03 clinical units (CU) . kg-1 . h-1, the bicarbonate outputs were significantly greater than those achieved by secretin or cholecystokinin-octapeptide alone or the sum of the bicarbonate outputs produced by each hormone. The potentiation effect of cholecystokinin-octapeptide occurred at the dose of 10.9 pmol . kg-1 . h-1. No further further augmentation on the bicarbonate output occurred when the dose of cholecystokinin-octapeptide was increased in the dose range greater than 10.9 pmol . mg-1 . h-1. No potentiation on pancreatic secretion of trypsin was apparent when the two hormones were given simultaneously. Thus, cholecystokinin-octapeptide in a relatively small dose range potentiated the pancreatic bicarbonate secretion stimulated by a physiologic dose of secretin. The pancreatic enzyme secretion does not appear to be potentiated by two hormones.

Adult↗

Effect of 1-phenylpentanol on release of secretin and exocrine pancreatic secretion in dogs and humans.

1-Phenyl-1-hydroxy-N-pentane is a synthetic derivative of an ingredient of Curcuma longa that is used as a condiment and dye. The effects of 1-phenyl-1- hydroxy-N-pentane on release of secretin, gastrin, and pancreatic secretion of bicarbonate and protein were studied in both dogs and humans. In fasting dogs with gastric fistulas and modified Herrera's pancreatic fistulas, intraduodenal administration of 1-phenyl-1-hydroxy-N-pentane (pH 6.7) in three different doses (25, 50, and 100 mg/kg) resulted in significant increases in both plasma secretin concentration and bicarbonate output. The increases in the two variables were dose related. The bicarbonate output and plasma secretin concentration produced by the doses of 1-phenyl-1-hydroxy-N-pentane correlated well. No significant change occurred in either protein output or plasma gastrin concentration. The effect of intragastric 1-phenyl-1-hydroxy-N-pentane on release of secretin and pancreatic secretion was also studied in the digestive state. While gastric pH was maintained at 5.5 by intragastric titration with 1 N NaOH after intragastric administration of 5% liver extract solution, intragastric administration of 1-phenyl-1-hydroxy-N-pentane (100 mg/kg) resulted in significant increases in both plasma secretin concentrations and pancreatic bicarbonate output. In the same experiment, the plasma gastrin concentration did not change significantly, whereas gastric acid secretion decreased significantly after the 1-phenyl-1-hydroxy-N-pentane administration. In 6 human volunteers, both plasma secretin concentration and pancreatic bicarbonate output significantly increased when 2% 1-phenyl-1-hydroxy-N-pentane solution, 30 ml/30 min, was infused in the upper jejunum. Again, no increase in the protein output was apparent. These studies indicate that endogenous secretin is released by an agent other than acid and suggest strongly that the increased pancreatic bicarbonate secretion is attributed to the increased plasma concentration of secretin. 1-Phenyl-1-hydroxy-N-pentane may be a useful agent for release of secretin in subjects with achlorhydria, severe hyposecretory state, or total gastrectomy.

Adult↗

Plasma secretion and pancreatic secretion in response to liver extract meal with varied pH and exogenous secretin in the dog.

1. In dogs with chronic gastric and pancreatic fistulas, a liver extract meal adjusted to various pH levels ranging from 7.0 to 2.0, was introduced into the stomach and the increments in plasma secretin levels were correlated with the pH of the liver extract meal and pancreatic bicarbonate outputs. 2. The pH threshold for both bicarbonate secretion and secretin release was found to be about 4.5. With a stepwise decrease in the pH of the meal below pH 4.5, there were stepwise increments in the plasma secretin concentrations and pancreatic bicarbonate outputs. 3. Exogenous secretin, given in graded doses ranging from 0.03 to 2.0 clinical unit/kg per hr, increased the plasma secretin concentrations and bicarbonate secretion in a dose-dependent fashion. 4. These results indicate that the pH threshold for release of endogenous secretin is 4.5 and suggests that, at pH levels below 4.5, pancreatic bicarbonate secretion depends upon the duodenal acid load and is linearly correlated to an increment in plasma secretin concentrations. 5. It is concluded that endogenous secretin is a major determinant of pancreatic bicarbonate secretion after a meal. 6. Pancreatic protein secretion by intragastric liver extract meal was greatly increased both in experiments with liver extract meal, pH 4.0 or below, and I.V. infusion of secretin at a dose of 0.12 u./kg per hr. It is questioned, however, whether this effect of secretin is physiological.

Animals↗

Effects of atropine on the action and release of secretin in humans.

Using two groups of volunteers, we investigated the effects of atropine on pancreatic secretion of bicarbonate, protein, and trypsin stimulated by secretin. Secretin given intravenously in graded doses of 0.03, 0.06, and 0.125 clinical units.kg-1.h-1 produced significant increases in pancreatic secretion of bicarbonate in a dose-related manner. Pancreatic secretion of bicarbonate and protein was significantly suppressed by intravenous atropine, despite the dose of secretin infused. Intrajejunal perfusion of HCl at a rate of 3.3 mM/h, producing plasma secretin concentration comparable with that of the postprandial state, resulted in significant increases in the pancreatic secretion of bicarbonate. The increase in the pancreatic secretion of bicarbonate and trypsin was significantly suppressed by atropine. However, atropine did not affect the increase in the plasma secretin concentration produced by jejunal acidification or intravenous secretin. These studies indicate that atropine inhibits the pancreatic effect but not the intestinal release of secretin.

Atropine↗

Bethanechol or cimetidine in the treatment of symptomatic reflux esophagitis: a double-blind control study.

We conducted a double-blind study to compare the effectiveness of oral bethanechol chloride or cimetidine in treating reflux esophagitis to evaluate the drugs' effects on the symptoms of esophagitis and its verification by endoscopy. Forty-three patients were treated with either 300 mg of cimetidine or 25 mg of bethanechol chloride, each administered four times a day for six weeks. In addition to this drug treatment, the patients all received conventional medical therapy. Patients who were treated with either of the two drugs experienced a decrease in symptoms and less severe endoscopic lesions. While cimetidine treatment resulted in complete endoscopic healing in 15 of 22 patients, bethanechol treatment resulted in the same healing in 11 of 21 patients. During therapy, neither endoscopic lesions or symptoms worsened. Our study indicated that either cimetidine or bethanechol is an effective drug in treating reflux esophagitis. The effects of the two drugs can be favorably compared.

Administration, Oral↗

Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases.

Plasma secretin concentrations were determined in healthy subjects and patients with duodenal ulcer, achlorhydria, and celiac sprue. Mean fasting plasma secretin concentrations in 26 healthy subjects and 26 duodenal ulcer patients were 6.7 +/- 0.5 and 10.2 +/- 1.2 pg/ml, respectively, and were significantly different (P less than 0.02). After ingestion of a standard meat meal, pyloric pH decreased to less than 4.5 within 15 min and plasma secretin concentrations significantly increased in all 52 subjects. In 14 subjects (seven healthy subjects and seven patients with duodenal ulcer), no significant rise in plasma secretin concentration occurred when pyloric pH was maintained at greater than 5.0 by intravenous cimetidine (600 mg) and intragastric antacid. In 10 achlorhydric patients, intragastric pH remained greater than 5.0 after the meal and plasma secretin concentrations did not change. However, plasma secretin concentrations increased significantly when 0.1 N HCl was infused in the stomach (25 mEq/hr) during the postprandial period. In all eight adult patients with celiac disease (seven untreated, one partially treated), pyloric pH remained less than 4.0 after a meal. Postprandial secretin concentrations did not increase significantly in six and showed a transient rise in two. These studies show that (1) plasma secretin concentration increases significantly after meals in healthy subjects and patients with duodenal ulcer; (2) neutralization of gastric acid and the achlorhydric state show no significant postprandial rise in plasma secretin concentration; (3) achlorhydric patients do not have a defect in secretin release in response to acid; and (4) failure of postprandial rise in plasma secretin in patients with celiac disease is attributed to impaired release of secretin and in achlorhydric patients it is attributed to lack of acid secretion.

Achlorhydria↗

Motilin-antimotilin reaction reveals two antigenic determinants in motilin.

The reaction of motilin with four rabbit antimotilin sera raised by immunization with synthetic porcine motilin-bovine serum albumin conjugate was studied with respect to various binding parameters and specificity. All four antisera exhibited an extremely high degree of specificity and high affinity (K greater than 10(11) M-1) for porcine motilin. Studying the various synthetic motilin fragments. These antisera appeared to contain binding sites reacting strongly with the N-terminal sequence in which the first three amino acid residues are essential for high affinity binding. One of the antisera, R-3-6, appeared to contain approximately 20% of its binding sites with high affinity for C-terminus-containing fragments. These results suggest that motilin possesses two antigenic domains along its primary structure; one contains the N-terminal tripeptide and the other contains the C-terminal nanopeptide as essential parts. Thus, in addition to heterogeneity in affinity, a given antibody preparation may be heterogenous with respect to the specificity along the sequence of a peptide. Gel filtration studies of the methanol extracts of human and dog plasma indicated that an immunoreactive motilin-like material with a molecular size similar to natural porcine motilin was measured by our routine radioimmunoassay.

Animals↗

Identification, characterization and distribution of motilin immunoreactivity in the rat central nervous system.

Motilin-immunoreactivity was evaluated in rat brain using 15 different antisera and by combining gel filtration, high pressure gel filtration and reverse phase high pressure liquid chromatography with radioimmunoassay. Gel filtration chromatography demonstrated a high molecular weight and low molecular weight form of immunoreactive motilin. The high molecular weight form predominated in brain while the low molecular weight peptide was the predominant form of duodenum. The low molecular weight immunoreactive motilin was indistinguishable from synthetic porcine motilin by gel filtration and high molecular weight gel filtration. Low molecular weight rat motilin could, however, be distinguished from synthetic porcine motilin by high pressure liquid chromatography and certain antisera. Immunological results suggest that the slight structural difference may be in the N-terminal portion of the molecule. Immunoreactivity was measured in grossly and microdissected regions of the rat brain. The peptide had quite a unique distribution as highest concentrations are observed in the cerebellum. High concentrations were also observed in hypothalamic nuclei. Particularly high concentrations were noted in the organum vasculosum lamina terminalis. Lowest motilin concentrations in the rat brain were in the pons and the medulla. The distribution of motilin in rat brain suggests that it may have roles in regulating both neuroendocrine and neurological processes.

Animals↗