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Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 235 records · Page 13Linked to original sources
PubMed1989

Uptake of 131I-metaiodobenzylguanidine by 6-23 rat medullary thyroid carcinoma.

Uptake of 131iodine-metaiodobenzylguanidine (131I-MIBG) by 6-23 rat medullary thyroid carcinoma (MTC), was studied in vitro and in vivo. In vitro, there was an 8-fold increase in 131I uptake by 6-23 cells when labeled with 131I-MIBG (131I 24 +/- 15 cpm/10(6) cells, 131I-MIBG 196 +/- 9 cpm/10(6) cells). MIBG uptake in vitro was the same at 4 degrees C and 37 degrees C. In contrast, 131I-MIBG uptake by PC-12 rat pheochromocytoma cells were 200 times greater (131I-MIBG 42,412 +/- 6,755 cpm/10(6) cells). 131I-MIBG uptake by rat MTC cells in vitro were of a comparable magnitude to the uptake of 131I-MIBG by rat ileal enterochromaffin cells (RIE-1) and mouse colon cancer cells (MC-26). In vivo, uptake of 131I-MIBG by 6-23 MTC tumor was considerably less than in the normal tissues (muscle, liver, spleen, kidney, adrenal and thyroid). Gamma camera studies of 131I-MIBG uptake by 6-23 MTC tumors growing in Wag-Rij rats were only transiently positive in 1 out of 4 rats studied. We conclude that 131I-MIBG is poorly taken up by rat medullary thyroid carcinoma and is an unpredictable marker for localization of rat MTC.

3-Iodobenzylguanidine↗
PubMed1989

Role of protein kinase C and phosphorylation in bombesin-evoked gastrin release from isolated perfused rat stomach.

We have recently reported that bombesin (BBS)-stimulated gastrin release is principally dependent on a Ca2+/calmodulin intracellular pathway, and that it is independent of the cyclic AMP-mediated pathway. Recently it was demonstrated that stimulation of protein kinase C (PK-C) resulted in increased gastrin release from the isolated canine G-cells in cultures. The role of PK-C in the BBS-evoked gastrin release, however, remains unexamined. In this study we examined a possible role of PK-C in the secretion of BBS-stimulated gastrin from isolated perfused rat stomach. The effect of phosphorylation on gastrin release, in response to BBS, was also determined. Administration of phorbol ester (PMA 10-100 nM, a PK-C activator) alone significantly provoked gastrin release, but markedly inhibited the BBS (1 nM) stimulated gastrin secretion in a dose-dependent manner. Molybdic acid (phosphatase inhibitor), caused an enhancement of BBS-evoked gastrin response at doses of 5 or greater than 5 mM. These results suggest that: (1) diacylglycerol/PK-C pathway may exert a negative feedback control over BBS-induced gastrin release; (2) phosphorylation step is required for gastrin secretion in response to BBS.

Animals↗
PubMed1989

Intracerebroventricular administration of calcitonin enhances glucose-stimulated release of insulin.

Intracerebroventricular (i.c.v.) administration of salmon calcitonin (500 ng) augmented glucose-stimulated release of insulin in rats. Vagotomy increased this enhancement effect of i.c.v. calcitonin significantly, whereas peripheral atropine treatment did not change it. Adrenal catecholamines did not participate in the centrally mediated insulinotropic effect of calcitonin since acute adrenalectomy did not modify the enhancement effect of i.c.v. calcitonin. Destruction of the sympathetic ganglia by neonatal treatment with 6-hydroxydopamine abolished the enhancement effect of i.c.v. calcitonin, which suggests that the sympathetic nervous system participates in the central action of calcitonin to enhance glucose-stimulated release of insulin.

Animals↗
PubMed1989

Effect of gamma-aminobutyric acid on bombesin-evoked release of somatostatin and gastrin from isolated rat stomach.

The effect of gamma-aminobutyric acid (GABA) on basal and bombesin (BBS)-stimulated release of somatostatin (SLI) and gastrin from isolated perfused rat stomach was examined. In the control study, BBS at a dose of 10 nM significantly stimulated release of SLI and gastrin. Infusion of GABA (1-1000 nM) caused a depression of SLI release induced by BBS (10 nM) in a dose-dependent fashion. However, at doses used in this study GABA had no effect on either basal level of SLI and gastrin or BBS-elicited gastrin release. These results indicate that GABA can specifically modulate BBS-induced SLI release from rat stomach.

Animals↗
PubMed1989

Preoperative endoscopic retrograde cholangiopancreatography (ERCP) in patients with pancreatic pseudocyst associated with resolving acute and chronic pancreatitis.

Experience with patients with pancreatic pseudocysts has led the authors to the hypothesis that preoperative evaluation of the pancreatic and bile ducts by ERCP will define those patients who may be inadequately treated by pseudocyst drainage alone without attention to associated pancreatic and biliary ductal abnormalities. In patients with certain ductal abnormalities, the pseudocyst operation was combined with a definitive operative drainage of the pancreatic duct and/or of the biliary tree where appropriate. A prospective evaluation of routine preoperative ERCP was undertaken over a 36-month period in all patients scheduled for operative treatment of pseudocyst of the pancreas. From an initial group of 44 patients with pseudocysts, three patients who had spontaneous regression of the pseudocyst were excluded. ERCP was successful in 39 of the remaining 41 patients. Among 41 operated patients, 24 were admitted with a diagnosis of pseudocyst that arose after an episode of acute pancreatitis, and 17 had chronic pancreatitis with pseudocyst. Nine patients, initially assumed to have acute pancreatitis, were recognized to have chronic pancreatitis on the basis of ERCP findings. Communication with the main pancreatic duct (MPD) was demonstrated in 18 of 41 pseudocysts, and the rate of communication was similar in patients with acute and chronic pancreatitis. Dilatation of the MPD was seen in 23 of 41 patients and was associated with chronic pancreatitis in 21. Dilatation of the common bile duct was found in 12 patients with chronic pancreatitis. The operative plan was altered by ERCP findings in 24 of 41 patients; 22 of the 24 patients had chronic pancreatitis. There were no complications of ERCP. These data suggest that ERCP should be performed in all patients with pseudocysts to establish correct diagnosis and to allow optimal choice of operation.

Acute Disease↗
PubMed1989

Endogenous cholecystokinin regulates growth of human cholangiocarcinoma.

Exogenous administration of cholecystokinin (CCK) or caerulein inhibits growth of SLU-132, a human cholangiocarcinoma that we have shown to possess receptors for CCK. Chronic administration of cholestyramine, a resin that binds bile salts, increases release of CCK and growth of the pancreas in guinea pigs. Feeding the bile salt, taurocholate, inhibits meal-stimulated release of CCK. The purpose of this study was to determine whether endogenous CCK affects growth of the human cholangiocarcinoma, SLU-132. We implanted SLU-132 subcutaneously into athymic nude mice. The bile salt pool was depleted by feeding 4% cholestyramine for 40 days, either alone or enriched with 0.5% taurocholate for 32 days. When the mice were killed, tumors and pancreas were removed. Cholestyramine significantly inhibited the growth of SLU-132 and stimulated growth of the normal pancreas. Feeding of taurocholate acted to stimulate tumor growth. These results demonstrate that endogenous levels of CCK regulate growth of this human cholangiocarcinoma. Our findings suggest that manipulation of levels of endogenous gut hormones may, in the future, play a role in management of patients with certain gastrointestinal cancers.

Adenoma, Bile Duct↗
PubMed1989

Pancreatic juice enhances fat-stimulated release of enteric hormones in dogs.

The presence of pancreatic juice in the intestinal lumen results in the hydrolysis of dietary fat. The hydrolytic products of dietary fat are potent stimulants of pancreatic exocrine secretion and potent inhibitors of gastric acid secretion. In this study, residual pancreatic enzyme activity in the intestinal lumen may account for the observed increase of triglyceride-stimulated pancreatic exocrine secretion and the release of peptides during diversion of pancreatic juice. The presence of pancreatic juice enhanced the pancreatic protein output that was stimulated by the intraduodenal administration of a triglyceride (corn oil, 2 g/kg/h) by 240% (p less than .05). The presence of pancreatic juice during the intraduodenal administration of a triglyceride nearly abolished the output of gastric acid as well as the release of gastrin (p less than .05) that had been stimulated by the intragastric placement of a 10% peptone meal. Pancreatic juice in the duodenum significantly enhanced the triglyceride-stimulated release of cholecystokinin-33/39, secretin, neurotensin, peptide YY, pancreatic polypeptide, and insulin (p less than .05) when compared with the release of these enteropancreatic hormones during the diversion of pancreatic juice. This study shows that the presence of pancreatic juice in the duodenal lumen enhances the fat-stimulated release of enteric hormones that have a stimulatory action on the enteroacinar and enteroinsular axis as well as an inhibitory action (enterogastrone-like activity) on the postprandial regulation of gastric function.

Animals↗
PubMed1989

The effects of 2-deoxy-D-glucose and alpha-difluoromethylornithine on the growth of pancreatic cancer in vivo.

The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), inhibits growth of some cancers. alpha-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. We and others have previously shown that DFMO inhibits cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on the growth of H2T hamster pancreatic ductal adenocarcinoma. Twenty-eight male Syrian golden hamsters were inoculated with 500,000 H2T cells, and then randomized into four groups of seven each: group 1 served as control; group 2 received DFMO (3% in drinking water); group 3 received 2-DG (500 mg/kg/day) intraperitoneally; group 4 received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation and continued for 28 days. At the end of the treatment period, the area of the H2T tumor was reduced 31% by DFMO compared with a 22% reduction caused by 2-DG. Tumor weight was significantly reduced (31%) by DFMO but not by 2-DG. Tumor contents of DNA, RNA, and protein were also reduced by DFMO but not 2-DG. Tumor concentration of the polyamines, putrescine and spermidine, were reduced by DFMO, but 2-DG did not alter levels of polyamines. The combination of DFMO and 2-DG caused a significantly greater reduction in tumor weight and putrescine content compared with DFMO alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of pancreastatin on pancreatic endocrine and exocrine secretion.

Pancreastatin is a novel peptide that was recently purified from extracts of the porcine pancreas. The present study shows that pancreastatin (10(-9)-10(-8) M) can stimulate release of insulin from both the isolated perfused rat pancreas and from cultured rat islet cells in the presence of a low, non-insulinotropic concentration of glucose (4.2 mM). Pancreastatin (10(-9) M) can also inhibit release of insulin stimulated by a high concentration of glucose (16.7 mM). Pancreastatin, at 10(-8) M, can enhance glucose (8.3 mM) induced release of insulin in the static islet cell incubation. In addition, pancreastatin (10(-9)-10(-8) M) can inhibit, in a dose-dependent fashion, cholecystokinin (CCK)-8 stimulated release of amylase from dispersed guinea pig pancreatic acini. Pancreastatin alone, however, did not affect basal release of amylase. Our study shows that pancreastatin can exert a direct effect on both pancreatic endocrine and exocrine secretion.

Amylases↗
PubMed1989

Effect of galanin on glucose-, arginine-, or potassium-stimulated insulin release.

We have examined the effect of galanin infusion on glucose-stimulated release of insulin from the isolated perfused pancreas of the rat to better characterize the effect of galanin on the first and second phases of insulin release. The effects of galanin on insulin release stimulated by L-arginine or high concentrations of potassium were also examined. When perfusion of galanin was started 4 min before the start of perfusion of high glucose (16.7 mM), galanin (10(-8)-10(-11) M) inhibited both the first and second phases of insulin release in a dose-dependent manner. When perfusion of galanin (10(-8) or 10(-9) M) was started simultaneously with high glucose (16.7 mM), only the second phase of insulin release was suppressed (P less than 0.05). Galanin (10(-9) M) failed to inhibit insulin release stimulated by L-arginine (10 and 5 mM) or potassium (25 and 20 mM). These findings suggest that the inhibitory action of galanin on glucose-stimulated insulin release is exerted on early intracellular events that occur during the stimulation of insulin release and that are common to both phases. Because galanin does not inhibit insulin release stimulated by L-arginine or potassium, galanin may inhibit glucose-stimulated closure of potassium channels.

Animals↗
PubMed1989

Inhibition of glucose-stimulated insulin release in the perfused rat pancreas by parathyroid secretory protein-I (chromogranin-A).

The effect of graded doses (10(-10)-10(8) M) of highly purified bovine parathyroid secretory protein-I (SP-I; chromogranin-A) or synthetic porcine pancreastatin on glucose-stimulated insulin release in the perfused rat pancreas was examined. SP-I (10(-9) M) inhibited the first phase of glucose-stimulated insulin release, and 10(-8) M SP-I inhibited both the first and second phases of glucose-stimulated insulin release; 10(-10) M SP-I was inactive. In comparison, pancreastatin at 10(-10) M inhibited the first phase of insulin release, and at 10(-9) and 10(-8) M, pancreastatin inhibited both phases of insulin release. The inhibition by SP-I was achieved at concentrations that normally exist in the general circulation of man. These and other data suggest that circulating SP-I plays a physiological role in the regulation of insulin secretion.

Animals↗
PubMed1989

Evidence for regulation of peptide-YY release by the proximal gut.

Peptide-YY (PYY) is a novel enteric peptide that is structurally related to pancreatic polypeptide and neuropeptide-Y. The objectives of the present experiments were to characterize the following aspects of PYY metabolism: the distribution of PYY in the canine gastrointestinal tract, the release of PYY in response to oral ingestion of a mixed meal or intraduodenal (ID) administration of oleic acid, the effect of ileocolectomy on the release of PYY in response to ID administration of oleic acid when transit of chyme to the distal ileum and colon is prevented, the effect of interruption of intramural neural pathways of the small bowel on the release of PYY, and the effect of iv cholecystokinin on the release of PYY. The results of these experiments demonstrate that PYY immunoreactivity is distributed primarily in the terminal ileum, colon, and rectum. Circulating levels of PYY increase significantly (P less than 0.05) within 10-30 min after ingestion of a meal or to ID administration of a fatty acid. Complete interruption of the flow of chyme to the site of PYY-containing cells (i.e. ileum-colon) did not block the release of PYY; however, ileocolectomy abolished the release of PYY in response to ID administration of oleic acid. Severance of intramural neural pathways along the small bowel did not alter the release of PYY in response to an oral meal. Intravenous administration of graded doses of cholecystokinin stimulated the release of PYY in a dose-related manner. The results of these experiments indicate that the release of PYY from the distal ileum and colon is controlled, at least in part, by an extramural neural, endocrine, or a combination of both types of mechanisms which originate in the foregut.

Animals↗
PubMed1989

A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog.

The objective of this study was to compare the effects of various nutrients (fats, proteins, amino acids, and carbohydrates), given directly into the duodenum or the colon, on the release of peptide-YY (PYY) in conscious dogs. As reported previously, this study showed that plasma levels of PYY increased significantly (P less than 0.05) within 15 min in response to an oral mixed meal. Intraduodenal (ID) administration of a fatty acid (oleic acid; 100 mmol/L; 100 ml/h) stimulated a robust release of PYY, whereas ID administration of an amino acid mixture (phenylalanine plus tryptophan; 100 mmol/L each; 100 ml/h), glucose (1 g/kg), or a liver extract (10%; 100 ml/h) failed to elevate plasma levels of PYY. ID administration of glucose at 2 g/kg caused a mild but significant elevation in plasma PYY levels. Intracolonic administration of saline, a fatty acid, an amino acid mixture, glucose, or a liver extract significantly stimulated PYY release. This study suggests that as chyme moves from the stomach to the proximal bowel, fat is the primary constituent of food that stimulates the prompt release of PYY. However, unabsorbed nutrients can release PYY by a direct contact with the PYY-containing cells lining the intestinal lumen of the terminal ileum, colon, and rectum. Both mechanisms probably participate in the release of PYY.

Amino Acids↗
PubMed1989

Pancreatic secretion and the release of cholecystokinin after a meal in dogs with and without exclusion of pancreatic juice.

Pancreatic secretion and plasma levels of cholecystokinin-33/39 (CCK) were measured for 5 h after a meal in dogs with and without exclusion of pancreatic juice. Significant and prolonged increases in pancreatic secretion and plasma CCK levels were observed irrespective of pancreatic juice exclusion. The integrated responses of pancreatic protein output (2.6 +/- 0.6 g/300 min), plasma CCK (1.3 +/- 0.5 nmol.l-1 .300 min) with exclusion of pancreatic juice showed no significant differences from those without exclusion (2.8 +/- 0.3 g/300 min and 1.3 +/- 0.3 nmol.l-1.300 min for protein output and CCK, respectively). These results suggest that the CCK-mediated feedback mechanism of pancreatic enzyme secretion does not work, at least not in the postprandial state in dogs.

Animals↗
PubMed1989

DNA synthetic activity in tumor-bearing mice.

The rate of DNA synthesis in normal tissues exhibits circadian rhythmicity. However, there have been conflicting reports of the effects of tumor burden on the circadian rhythm of DNA synthesis in non-cancer tissues. We have developed a mouse colon cancer (MC-26) that exhibits different growth under different photoperiods. The purpose of this study was to analyze DNA synthetic activity in tissues removed from tumor-bearing and tumor-free mice maintained under two different photoperiods. Two groups each of approximately 80 male Balb/c mice were acclimated to one of two light-dark cycles, 12L:12D or 6L:18D. Half of each group were injected with 5.0 x 10(4) MC-26 cells. Twenty-two days later, all mice were killed in subgroups at 4-6 hr intervals over one 24-hr period. Colons and tumors were removed for measurement of DNA synthesis. Results were analyzed by means of one-way analysis of variance (ANOVA) in order to determine whether DNA synthesis varied significantly within groups over the 24-hr period. The DNA synthetic activity, as measured by uptake of tritiated thymidine, exhibited significant temporal variation in the colons of control (tumor-free) mice under both the 12L:12D and 6L:18D photoperiods. The colons of tumor-bearing mice failed to exhibit a fluctuation under a 12L:12D photoperiod but did show a significant 24-hr rhythm under the 6L:18D photoperiod. The subcutaneously growing cancers did not exhibit a circadian variation in DNA synthetic activity under either photoperiod. Both photoperiod and the presence of cancer appear to affect the DNA synthetic activity observed in mice bearing the MC-26 colon cancer.

Animals↗
PubMed1989

Parathyroid hormone and parathyroid hormone-related protein inhibit phasic contraction of pig duodenal smooth muscle.

Parathyroid hormone (PTH) and a newly discovered PTH-related protein (PTHrP), which has amino-terminal homology with PTH, are potent relaxants of rat gastrointestinal tissues. Since their gastrointestinal relaxant effects have been described only in the rat, we examined their actions in another mammalian species in order to evaluate whether the relaxant property was more generally applicable. Longitudinal smooth muscle strips were obtained from the pig duodenum. The mucosa was removed, the strips were mounted in a tissue chamber, and changes in phasic contraction were detected with a force-displacement transducer and recorded using a polygraph. Acetylcholine-induced phasic contraction was inhibited rapidly in a dose-related manner by [Nle8,18,Tyr34]-bPTH-(1-34)-amide, or hPTHrP-(1-34). The IC50 values for these peptides were 2.6 nM and 6.1 nM, respectively. The maximal effect of both peptides was observed at 60 nM with an 84% decrease of the acetylcholine-induced contraction. At 400 nM, the PTH antagonist, [Nle8,18,Tyr34]-bPTH-(3-34)-amide, had no effect by itself. However, the same 400 nM concentration of this peptide totally blocked the decrease in phasic contraction induced by 10 nM of the bPTH-(1-34) analogue or hPTHrP-(1-34). Our results show that receptors for PTH or PTHrP are present in the muscular layer of the pig duodenum and that activation of these receptors inhibits the phasic contraction of the tissue. Furthermore, the ability of PTH-related peptides to relax gastrointestinal smooth muscle is not restricted to the rat.

Acetylcholine↗
PubMed1989

Twenty-four-hour variations in ornithine decarboxylase and acid phosphatase in mice.

Polyamines are essential for cell growth and differentiation. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis. Acid phosphatases (AP) are lysosomal enzymes that are important in normal intracellular metabolism. Twenty-four-hour variations in these enzymes may be important in understanding the temporal responses of different tissues to various stimuli. The purpose of this study was to examine a variety of tissues for fluctuations in the levels of ODC and AP over a 24-hr period. Significant circadian variations in the amount of ODC activity were observed in all tissues examined. Activity of AP varied with time of day in the liver, kidney, and heart. The highest and lowest measurements of ODC activity were as follows: liver, 81.5 +/- 7.0, 47.9 +/- 4.4; colon, 11.7 +/- 1.2, 3.1 +/- 0.7; stomach 3.1 +/- 0.4, 0.9 +/- 0.1; kidney, 420.9 +/- 0.9, 67.5 +/- 0.8; and heart, 4.7 +/- 1.0, 2.5 +/- 0.2. The highest and lowest measurements of AP activity were as follows: liver 3.8 +/- 0.1, 2.8 +/- 0.1; kidney, 3.4 +/- 0.1, 1.9 +/- 0.1; and heart, 2.6 +/- 0.1, 2.0 +/- 0.1. These findings suggest that rhythmic fluctuations in polyamine biosynthesis and lysosomal enzymes may influence other metabolic pathways differentially throughout 24 hr.

Acid Phosphatase↗