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G Greeley

Publications and source records attributed to G Greeley.

8 recordsLinked to original sources
PubMed1994

Characterization of a human pancreatic carcinoid in vitro: morphology, amine and peptide storage, and secretion.

The study of functioning human endocrine tumors has been hampered by a lack of suitable in vitro models. We have established the first permanent cell line of a human pancreatic carcinoid tumor (BON) in culture. BON cells grow in monolayer culture and form colonies in soft agar. Injection of BON cells into nude mice produces transplantable tumors in a dose-dependent fashion. The histology of tumors in athymic mice from injection of dispersed, cultured BON cells is similar to the original histology of the resected tumor. Significant amounts of neurotensin, pancreastatin, and serotonin (5-HT) are demonstrated in the cells by radioimmunoassay (RIA) and the presence of chromogranin A, bombesin, and 5-HT is confirmed by immunocytochemistry. Numerous round and pleomorphic dense-core neurosecretory granules are present on electron microscopy. Functional receptors for acetylcholine, 5-HT, isoproterenol, and somatostatin are present on cultured cells. BON cells possess a specific transport system for uptake of 5-HT from the medium; this uptake system may be a route for regulation of autocrine effects of 5-HT on carcinoid cells. This unique human carcinoid tumor cell line should provide the opportunity for new insight into the biology of carcinoid tumors and of specific intracellular mechanisms for secretagogue action in the release of amines and peptides.

Adult↗
PubMed1989

Protein meal-stimulated pancreatic polypeptide secretion in Prader-Willi syndrome of adults.

Children with Prader-Willi syndrome (PWS) are characterized by obesity, hyperphagia, hypogonadism, and mental retardation with underlying hypothalamic dysfunction and are known to have blunted or absent pancreatic polypeptide (PP) secretion in response to protein meals. In this communication, adults (26 +/- 3 years of age) with PWS were compared with age-matched normal obese and normal weight controls in regards to plasma glucose, insulin, PP, cholecystokinin (CCK), cholesterol, and triglyceride after a high protein meal. Compared with normal weight controls, adults with PWS showed a smaller and delayed rise in plasma insulin, and relatively smaller and delayed PP elevation whereas obese controls revealed hyperglycemia, markedly higher insulin, and moderately higher PP, cholesterol, and triglyceride levels than those with PWS. There was a small increment of CCK levels after a protein meal in all groups of adults. After a protein meal, the molar ratio of PP to CCK doubled in normal weight and PWS groups, and this ratio tripled in the normal obese group, suggesting no reduced PP secretion in PWS in response to CCK stimulation. PP hyposecretion in PWS thus appears to be a part of multiple endocrinopathy associated with hypothalamic dysfunction.

Adult↗
PubMed1984

Plasma concentrations of cholecystokinin in patients with duodenal ulcer disease.

Cholecystokinin (CCK) is structurally similar to gastrin and is known to competitively inhibit the action of gastrin on the parietal cell, but little information has been accumulated about circulating levels of CCK in patients with duodenal ulcer (DU). In a group of 18 healthy volunteers (controls) and 22 DU patients (13 with active DU, nine with inactive DU), we stimulated endogenous release of CCK with oral administration of Lipomul corn oil. Plasma concentrations of CCK were measured by radioimmunoassay; ultrasonographic measurements of gallbladder volume were used as a biologic correlate for CCK in control patients and in patients with active DU. No significant difference was found in fasting plasma concentrations of CCK between controls (107 +/- 8 pg/ml) and DU patients (123 +/- 15 pg/ml), or in their total integrated release of CCK during the first hour after Lipomul ingestion (3.7 +/- 0.7 ng-min/ml in controls, 2.8 +/- 0.4 ng-min/ml in DU patients). Furthermore, no significant difference was found in integrated release of CCK between patients with active DU (2.9 +/- 0.6 ng-min/ml) and those with inactive DU (2.8 +/- 0.6 ng-min/ml). Gallbladder volume was highly correlated with plasma concentrations of CCK in controls (r = -0.91) and in active DU patients (r = -0.98). Patients with active DU had significantly smaller volumes of their resting gallbladders, they emptied less of their resting gallbladder contents in response to fat, and they showed diminished sensitivity to endogenously released CCK compared to controls. In six patients with active DU who underwent truncal vagotomy and drainage, integrated release of CCK increased significantly, from 1.9 +/- 0.6 ng-min/ml before vagotomy to 9.3 +/- 3.0 ng-min/ml after vagotomy. We found no evidence to suggest that abnormalities in release of CCK contributes to the development of duodenal ulcers. We speculate, however, that the increased release of endogenous CCK after truncal vagotomy may possibly play an etiologic role in the syndrome of postvagotomy diarrhea.

Adult↗
PubMed1983

Correlation of release and actions of cholecystokinin in dogs before and after vagotomy.

Pancreatic secretion of enzymes and gallbladder contraction in response to intestinal stimulants are thought to be mediated through the vagus nerve and by means of release of cholecystokinin (CCK). The effect of truncal vagotomy on the release of CCK, pancreatic protein secretion, and gallbladder pressure (all stimulated by intraduodenal instillation of oleate) was studied in five dogs. Each dog was prepared with chronic pancreatic and gastric fistulas and catheter cholecystostomies. Simultaneous measurements were made of plasma CCK (by radioimmunoassay), pancreatic protein secretion, and gallbladder pressure (by perfused catheter technique) before and during intraduodenal administration of oleate. Before truncal vagotomy, intraduodenal oleate caused increases in plasma CCK (from 82 +/- 6 to 208 +/- 32 pg/ml), pancreatic protein secretion (from 83 +/- 8 to 165 +/- 15 mg/15 min), and gallbladder pressure (from 11 +/- 2 to 27 +/- 2 cm H2O) (all measured from basal state to 120 minutes). Truncal vagotomy caused a 45% decrease in the output of pancreatic protein in response to oleate and completely abolished the increase in gallbladder pressure, but it caused no change in release of CCK. The correlations between plasma CCK and pancreatic protein secretion before truncal vagotomy (r = 0.86) and after truncal vagotomy (r = 0.77) were highly significant. The correlation between plasma CCK and gallbladder pressure was highly significant before (r = 0.91) but not after (r = 0.42) truncal vagotomy. This study demonstrates that truncal vagotomy inhibits pancreatic protein secretion and gallbladder pressure in response to fat but does not interfere with release of CCK. The effects may be due to interruption of vagus-mediated reflexes between the intestine and the pancreas and gallbladder. The good correlation between plasma concentrations of CCK and both pancreatic protein secretion and gallbladder pressure provides evidence that the radioimmunoassay measures biologically active CCK.

Animals↗
PubMed1982

Pancreatic protein secretion and gastrointestinal hormone release in response to parenteral amino acids and lipid in dogs.

Parenteral nutrition has been advocated for and used in clinical situations in which provision of calories without stimulation of pancreatic secretion is desired. A recent report, however, provided evidence for substantial stimulation of pancreatic secretion after parenteral administration of amino acids and fat. We have studied the effect of intravenous administration of crystalline amino acids and lipid on pancreatic protein secretion and release of gastrointestinal hormones in five dogs with chronic pancreatic fistulas. The amino acids were given as a 4.25% solution in 5% glucose at 2 gm/hr. Parenteral fat was administered as Intralipid 10% at 3.5 ml/kg/hr. Plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and serum concentrations of gastrin, measured by radioimmunoassay, were determined before, and at intervals during, infusion of amino acids and fat. Pancreatic juice was collected simultaneously with blood sampling, and volume and protein output were measured. Basal concentrations of CCK, PP, and gastrin were not affected by intravenous infusion of amino acids. Pancreatic protein secretion and volume were also unaffected by parenteral amino acids. Parenteral infusion of fat resulted in a significant inhibition of integrated gastrin release but had no effect on plasma concentrations or integrated release of CCK or PP. Neither the volume nor protein output of pancreatic secretion was affected by intravenous fat administration. In summary, no stimulation of pancreatic secretion or release of CCK, PP, or gastrin occurred as a result of parenteral amino acid or fat administration. There is, therefore, no contraindication to the use of parenteral nutrition in situations in which it is desirable to keep the pancreas at rest.

Amino Acids↗
PubMed1978

The effect of castration, thyroidectomy and haloperidol upon the turnover rates of dopamine and norepinephrine and the kinetic properties of tyrosine hydroxylase in discrete hypothalamic nuclei of the male rat.

Adult male rats were either castrated, thyroidectomized, or treated with haloperidol and the rates of turnover of dopamine (DA) and norepinephrine (NE) in the median eminence (ME), the arcuate and dorsomedial nuclei of the hypothalamus were estimated from the rate of decay of DA and NE concentrations as determined by radioenzymatic assay following blockade of catecholamine synthesis by alpha-methyl-p-tyrosine. The ME of animals similarly prepared was also examined for changes in the total activity and kinetic properties of tyrosine hydroxylase (TH). Four days following the administration of haloperidol (400 microgram/kg) or 10 days after castration, there was a significant increase in the rate of turnover of DA but not NE in the ME accompanied by an increase in the Vmax but not Km for the substrate or cofactor of TH. Furthermore, the administration of haloperidol to hypophysectomized rats also significantly increased the TH activity in the ME, indicating that such changes may occur independently of any changes in serum prolactin levels. Ten days after thyroidectomy, or three weeks after treatment with prophylthiouracil, there was a significant increase in the turnover rate of DA in both the ME and dorsomedial nucleus but not in the arcuate nucleus. No changes in the turnover rates of NE in any of the three areas were observed following thyroidectomy. In the ME, the increase in turnover of DA was accompanied by an increase in the total TH activity (Vmax) as welll as a decrease in Km for tetrahydrobiopterin but not tyrosine. From these results 4 conclusions were drawn: (1) following halperidol, castration, and thyroidectomy there are increases in the activity of dopaminergic terminals within the ME; (2) castration, haloperidol and thyroidectomy may influence the activity of dopaminergic terminals within the ME by different mechanisms; (3) changes in tyrosine hydroxylase and turnover of catecholamines within the ME may occur independently of changes in prolactin levels; and (4) local recurrent afferent circuits may exist in the arcuate nucleus region of the hypothalamus.

Animals↗