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Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 289 records · Page 16Linked to original sources
PubMed1988

Cross-reaction of two different somatostatin antisera with calcitonin gene-related peptide.

Two different anti-somatostatin antisera, R-101 and OAL-273, cross-react with rat calcitonin gene-related peptide (1-37) (CGRP). CGRP amounts, in excess of 6.25 x 10(-9) M, cross-react with R-101 in the somatostatin radioimmunoassay. CGRP amounts, in excess of 1.6 x 10(-9) M, cross-react with OAL-273. Both CGRP displacement curves are parallel to that of synthetic somatostatin (1-14). Comparison of ID50's shows that the cross-reactivity of CGRP with R-101 and OAL-273 are 0.02 and 0.1% of somatostatin, respectively.

Amino Acid Sequence↗
PubMed1988

Inhibition of gastric acid secretion by peptide YY is independent of gastric somatostatin release in the rat.

The purpose of this study was to determine whether the inhibitory action of peptide YY (PYY) on gastric acid secretion is attributable to the release of gastric somatostatin in rats. Two groups of rats (six rats/group) were anesthetized with urethane and prepared with gastric fistulas and jugular catheters. Pentagastrin (18 micrograms/kg-h) was given intravenously for 150 min to stimulate gastric acid secretion. Intravenous PYY (130 micrograms/kg-h) inhibited pentagastrin-stimulated gastric acid secretion significantly (P less than 0.05). Administration of iv PYY resulted in a 41% reduction (P less than 0.05) in pentagastrin-stimulated gastric acid secretion. In another group of anesthetized rats, administration of PYY (10(-7), 10(-8) M) failed to stimulate a release of somatostatin from the isolated-perfused rat stomach. Our findings indicate that PYY can inhibit gastric acid secretion independently of release of gastric somatostatin in the rat.

Animals↗
PubMed1988

Calcitonin gene-related peptide inhibits gallbladder contractility.

Calcitonin gene-related peptide (CGRP), a 37-amino acid peptide, is widely distributed in the gastrointestinal tract where it is colocalized with substance P. The effect of CGRP on gallbladder motility is unknown. The objective of this study was to examine the effect of CGRP on cholecystokinin-octapeptide (CCK-8) and substance P-stimulated gallbladder contraction in vivo and in vitro. In in vivo studies intragallbladder pressure was measured in response to bolus administration of CCK-8 (10(-15) to 10(-9) mol/kg) or substance P (10(-12) to 10(-7) mol/kg), either alone or with a continuous infusion of CGRP (10(-9) mol/kg/hr), in anesthetized guinea pigs. In in vitro studies the contractile force of guinea pig gallbladder muscle strips was examined in response to CCK-8 (10(-12) to 10(-7) mol/L) and substance P (10(-9) to 10(-6) mol/L), alone or with CGRP (10(-10) to 10(-6) mol/L). CGRP (10(-9) mol/kg/hr) inhibited in vivo gallbladder contraction that was stimulated by CCK-8, but not by substance P. CGRP alone produced a significant (p less than 0.05) dose-related decrease in the resting tension of gallbladder strips in vitro. CGRP (10(-6) mol/L) inhibited gallbladder muscle tension in vitro, stimulated by both CCK-8 and substance P. These studies show that CGRP can affect gallbladder motor activity by decreasing smooth muscle tone and that CGRP can antagonize the action of CCK and substance P. CGRP may be involved in the physiologic control of gallbladder emptying and refilling.

Animals↗
PubMed1988

The time course of beta cell dysfunction in chronic ethanol-induced pancreatitis: a prospective analysis.

Insulin-glucose homeostasis was examined in 62 patients with chronic pancreatitis (CP). All patients were graded on the basis of test results from five studies: (1) endoscopic retrograde cholangiopancreatography, (2) fat-stimulated release of pancreatic polypeptide (PP), (3) NBT-bentiromide PABA test, (4) 72-hour fecal fat test, and (5) oral glucose tolerance test (OGTT). Patients with CP were graded as either mild/moderate or severe by means of a scoring system that we devised and have previously reported. Nineteen patients were graded as mild/moderate and 43 patients were graded as severe. The endocrine function of non-beta and beta islet cells was compared by assessing release of PP after fat and by release of insulin during OGTT. Release of PP was depressed in 58%, and the depressed output was found in only patients with a severe grade of CP. Forty-four of 62 patients (71%) with CP had abnormal OGTT findings; the distribution of this abnormality was not greatly different between mild/moderate and severe grades. Depressed release of insulin was seen in 58% (36 of 62)--more commonly in patients with a severe grade (10%) but also in 32% of patients with a mild/moderate grade. A subset of patients with CP sustains early beta-cell dysfunction. We conclude that decreased output of PP is a more reliable measure of functional deficit and stage in CP.

Adult↗
PubMed1988

Establishment of a human gastrinoma in nude mice.

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 micrograms/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 micrograms/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 +/- 93 mg) was significantly greater than control fundic weight (180 +/- 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.

Adult↗
PubMed1988

Interaction of neurotensin, secretin and cholecystokinin on pancreatic exocrine secretion in conscious dogs.

The results of previous studies from our laboratory have shown that neurotensin can stimulate pancreatic secretion of bicarbonate and protein. This study was done to compare the stimulatory action of neurotensin on pancreatic exocrine secretion in conscious dogs to those of secretin and cholecystokinin (CCK). Six dogs with chronic pancreatic and gastric fistulas were given hydrochloric acid intraduodenally or CCK-8 intravenously to produce maximal bicarbonate or protein secretion. Neurotensin was then given intravenously in combination with intraduodenal hydrochloric acid or intravenous CCK-8. Incremental bicarbonate outputs in response to intraduodenal hydrochloric acid alone were measured and compared with intraduodenal hydrochloric acid plus intravenous neurotensin. Intravenous administration of neurotensin augmented pancreatic bicarbonate and protein secretory responses to a maximal dose of intraduodenal hydrochloric acid. Incremental protein responses to intravenous CCK-8 alone were measured and compared to intravenous CCK-8 plus intravenous neurotensin. Incremental bicarbonate responses to intravenous CCK-8 alone were compared with intravenous CCK-8 plus intravenous neurotensin. Similarly, intravenous neurotensin augmented pancreatic protein and bicarbonate secretory responses to a maximal dose of intravenous CCK-8. The results of this study indicate that neurotensin may stimulate pancreatic secretion of protein and bicarbonate by mechanisms which are different from those of CCK and secretin. Neurotensin apparently exerts its action through specific neurotensin receptors.

Animals↗
PubMed1988

The mechanism of the inhibitory action of neurotensin on pentagastrin-stimulated gastric secretion in dogs.

Neurotensin is a potent inhibitor of pentagastrin-stimulated gastric acid secretion. This study was done to investigate the possible role of vagal innervation and of prostaglandins on this inhibitory effect. Five dogs with gastric cannulas were infused with pentagastrin (1 microgram per kilogram of body weight each hour) for 210 minutes. In the 60 to 150 minute period, neurotensin (5.5 micrograms per kilogram of body weight each hour) was infused. Neurotensin significantly decreased pentagastrin-stimulated gastric acid output, while the simultaneous administration of indomethacin (bolus of 1 milligram per kilogram of body weight plus infusion of 0.5 milligrams per kilogram each hour) abolished the effect of neurotensin. After truncal vagotomy, the inhibitory effect of neurotensin was again studied. Since the sensitivity of the stomach to pentagastrin decreased after vagotomy, the dose of pentagastrin was doubled (2 micrograms per kilogram of body weight each hour) in order to achieve acid stimulation comparable with the levels before vagotomy. After vagotomy, neurotensin inhibited the effect of pentagastrin in a manner similar to that shown before vagotomy. The inhibitory potency of neurotensin on gastrin-stimulated gastric secretion is independent of the vagus, but requires intact synthesis for prostaglandins.

Animals↗
PubMed1988

Role of vagal hyperactivity in gastric stress ulceration after acute injury to the cervical cord.

The role of vagal hyperactivity in the pathogenesis of gastric stress ulceration that occurs after acute trauma to the cervical cord is controversial. We have used a rat model of transection of the cervical cord to induce gastric stress ulceration and to examine the cause of the ulcers. Cervical cord transection did not increase gastric acid output or plasma levels of gastrin or pancreatic polypeptide, either immediately or up to eight hours later. However, gastric stress ulceration showed a time-related increase in ulceration. Vagal stimulation with 2-deoxy-glucose enhanced the gastric acid output in rats with cervical cord transection but failed to change the quantity or characteristics of the gastric ulceration. We conclude that there is no evidence to support the vagal hyperactivity hypothesis in the pathogenesis of gastric stress ulceration after acute cervical cord injury.

Acute Disease↗
PubMed1987

Inhibition of pentagastrin-stimulated up-regulation of gastrin receptors and growth of mouse colon tumor in vivo by proglumide, a gastrin receptor antagonist.

We have recently demonstrated that gastrin stimulates growth of mouse colon cancer (MC-26) in vivo by regulation of gastrin receptors (GR). In the present study, we have tested the effect of proglumide (PGL), a GR antagonist, on the trophic and GR-regulatory effects of gastrin on MC-26 tumors. Four groups of 12 mice each were inoculated with 5 X 10(4) MC-26 cells and given injections of either normal saline (control), pentagastrin (PG), PGL, or both PG + PGL for 21 days. At the end of the treatment period, body, tumor, fundic, and colon weights were noted and GR measured. Two types of specific gastrin-binding sites were found on tumor cell membranes of control mice, one with high binding affinity (Kd = less than 1.0 nM) and low capacity (GR), and the other with a very high capacity and a low affinity (Kd = greater than 0.1 microM) (type 2 gastrin-binding sites). Only the type 1 GR were observed on the fundic mucosal and colon membranes. PG treatment resulted in a significant weight increase of the tumors with an up-regulation of only type 1 GR. On the other hand, PG had no significant effect on fundic mucosal and colonic GR levels, but caused a significant increase in fundic mucosal weights. PGL completely inhibited both the trophic and GR up-regulatory effects of PG on tumors, but incompletely reduced the PG-stimulated fundic mucosal weight gain, indicating differential sensitivity of tumor and normal tissues to PGL. PGL, in the absence of PG, was slightly trophic for normal fundic mucosa, but had no effect on MC-26 tumors and normal colon. The one striking effect of PGL, in the presence of PG, was the significant lowering of the binding affinity of type 1 GR for gastrin on both the tumor and normal gastrointestinal tissues. This effect may be another mechanism by which PGL interferes with the actions of PG on MC-26 tumors and fundic mucosa of mice.

Animals↗
PubMed1987

Peptide YY interacts with secretin and duodenal acidification to inhibit gastric acid secretion.

Previous studies have indicated that plasma levels of peptide YY (PYY) increase significantly after a meal. The purpose of this study was to characterize the interaction of PYY and secretin in the inhibition of gastric acid secretion, and to determine whether PYY can influence acid-induced inhibition of gastric acid secretion in conscious dogs. I.v. administration of PYY at 200 pmol/kg/h inhibited pentagastrin (1 microgram/kg/h)-stimulated gastric acid output (P less than 0.05). PYY further augmented i.v. secretin-induced inhibition of pentagastrin-stimulated gastric acid output by 32 +/- 7%, and intraduodenal hydrochloric acid-induced inhibition of pentagastrin-stimulated gastric acid output by 40 +/- 12%. The mean integrated release of secretin response to duodenal acidification (3.9 +/- 1.0 ng-[0-60] min/ml) was not affected by PYY (3.3 +/- 0.9 ng-[0-60] min/ml). The present study demonstrates that PYY can interact with secretin and duodenal acidification in an additive fashion to inhibit pentagastrin-stimulated gastric acid secretion. Our results suggest that several hormones that are released postprandially can interact with each other to inhibit gastric acid secretion.

Animals↗
PubMed1987

Effects of cyclosporine and alpha-difluoromethylornithine on the growth of mouse colon cancer in vitro.

The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. alpha-Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and polyamine levels in MC-26 colon cancer in vitro. CsA had inhibitory effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3 X 10(-4) mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer.

Adenocarcinoma↗
PubMed1987

Norfloxacin: clinical pharmacology and clinical use.

Norfloxacin, a nalidixic acid analog, is the first of the fluorinated quinolinecarboxylic acids to be marketed in the United States. It demonstrates potent antibacterial activity against aerobic, gram-negative bacteria including the Enterobacteriaceae, gentamicin-resistant Pseudomonas aeruginosa, and penicillin-resistant Neisseria gonorrhoeae. Norfloxacin exhibits good activity against methicillin-resistant and -sensitive Staphylococcus aureus, but less activity against most other aerobic, gram-positive organisms. Anaerobic bacteria are resistant to the drug. Resistance to norfloxacin is not plasmid mediated, but is secondary to bacterial mutation, and occurs less frequently than nalidixic acid resistance. Its pharmacokinetic properties after a 400-mg oral dose consist of a peak serum concentration of 1.3-1.58 micrograms/ml, an elimination half-life of 3-7 hours, and good penetration into kidney and prostatic tissues. Renal excretion is the major route of elimination. Norfloxacin is highly effective in the treatment of uncomplicated and complicated urinary tract infections, and gonococcal urethritis. Adverse effects are generally well tolerated and usually do not require discontinuation of therapy.

Bacteria↗
PubMed1987

Relaxation of rat gastrointestinal smooth muscle by parathyroid hormone.

In this study we investigated whether parathyroid hormone (PTH) can produce relaxation of gastrointestinal (GI) smooth muscle as it has been reported to do for vascular and uterine smooth muscle. Muscle tissue preparations from rat stomach, duodenum, ileum, or colon were mounted in a 37 degrees C tissue bath and perfused with oxygenated medium. Changes in isometric tension were recorded with a force-displacement transducer connected to a polygraph. Decreases in either resting tension or agonist-induced tension (0.5-1.0 microM acetylcholine or carbachol) were observed within 1-2 min of PTH addition and were reversible upon removal of the peptide. All GI regions tested were responsive to PTH. Synthetic rPTH-(1-34) (0.1-100 nM) produced a dose-dependent relaxation of both fundic (ED50 = 5.2 nM) and colonic (ED50 = 2.5 nM) muscle strips. At 100 nM, a 90% decrease in fundic tension and a 70% decrease in colonic tension were seen. At 100 nM, bPTH-(1-34), but not bPTH-(7-34) or rat calcitonin gene-related peptide, also was effective in relaxing fundic or colonic muscle. Similarly, in the fundic muscle, 500 nM bPTH-(3-34) alone was ineffective, but it inhibited the effect of 5 nM rPTH-(1-34) when both peptides were tested in combination. Likewise, 100 nM bPTH-(3-34) also inhibited the relaxation induced by 5, 10, or 100 nM bPTH-(1-34). The results show PTH to be highly effective in nanomolar concentrations in causing relaxation of GI smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cyclosporine and alpha-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro.

alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and polyamine levels in mouse colon cancer (MC-26) and hamster pancreatic cancer (H2T) cells in vitro. The growth and survival of MC-26 and H2T cells were inhibited by both DFMO and CsA. However, H2T cells were observed to be significantly more sensitive than MC-26 cells to both CsA and DFMO. The inhibitory effects of CsA were blocked by the addition of the polyamine, putrescine, in both MC-26 and H2T cells. Polyamine levels were altered significantly in both MC-26 and H2T cells treated with CsA and DFMO. However, the profile of these alterations differed between MC-26 and H2T cell lines. Putrescine and spermidine levels in MC-26 cells were more sensitive to DFMO inhibition than were H2T cells. Spermine levels were consistently elevated in MC-26 cells exposed to CsA or DFMO, while the level of spermine in H2T cells decreased significantly in response to the same drugs. These results suggest that CsA and DFMO exhibit different effects on colon and pancreatic cancer growth in vitro. In addition, the differences in the sensitivity of pancreatic and colon cancer to CsA and DFMO indicate potentially important differences in polyamine metabolism between the two cell lines.

Animals↗
PubMed1987

Role of cholecystokinin in canine pancreatic exocrine response to bombesin stimulation.

The role of cholecystokinin in bombesin-stimulated pancreatic secretion in dogs was examined by the use of a specific cholecystokinin antagonist, proglumide. The primary component of bombesin-stimulated pancreatic secretion at the lowest tested dose was due to cholecystokinin, with only 25 percent of bombesin-stimulated protein output preserved during proglumide infusion. Maximal stimulation of cholecystokinin release was achieved by even the lowest dose of bombesin, whereas dose-related increases in bombesin-stimulated protein secretion were observed. This increase in exocrine secretion is probably explained by increased direct bombesin stimulation. Our findings suggest that the maximal dose of bombesin is lower for cholecystokinin release than its effective dose for enzyme secretion. We conclude that, in all probability, postprandial release of bombesin (or its analogue, gastrin-releasing peptide) affects pancreatic function primarily through release of cholecystokinin.

Animals↗
PubMed1987

Distribution of peptide YY in the gastrointestinal tract of the rat, dog, and monkey.

The objective of this study was to characterize the distribution and concentration of peptide YY (PYY) in the gastrointestinal tract of the rat, dog, and monkey. In the rat, the greatest concentration of PYY was detected in the ileum and colon. The concentrations of PYY in the ileum and colon were 72 +/- 49 and 768 +/- 180 ng/g tissue, respectively. In the dog, PYY was found primarily in extracts of the mucosal layer of the ileum and colon, with smaller amounts in the distal jejunum. The concentration of PYY in the mucosal layers of the canine distal jejunum was 113 +/- 25 ng/g tissue, proximal jejunum 302 +/- 56, mid jejunum 507 +/- 151, distal ileum 691 +/- 184, and colon 1706 +/- 774 ng/g tissue. In the monkey gastrointestinal tract, PYY was detected predominantly in mucosal extracts of the jejunum, ileum, and colon. The concentration of PYY in the mucosal layer extract of the jejunum was 92 +/- 23, ileum 615 +/- 127, and colon 1013 +/- 243 ng/g tissue.

Animals↗
PubMed1987

Effect of peptide YY on cephalic, gastric, and intestinal phases of gastric acid secretion and on the release of gastrointestinal hormones.

The objective of this study was to investigate the effects of a novel gut peptide, peptide YY (PYY), on the cephalic, gastric, and intestinal phases of gastric acid secretion and to explore the mechanisms involved. The cephalic phase of gastric acid secretion, stimulated by the intravenous injection of 2-deoxyglucose (75 mg/kg), was found to be inhibited by intravenous PYY (100, 200, 400 pmol/kg X h) in a dose-related fashion. Peptide YY (200 and 400 pmol/kg X h) also resulted in a significant dose-dependent inhibition of the gastric phase of acid secretion. On the other hand, PYY (400 pmol/kg X h) failed to affect the intestinal phase of gastric acid output. Serum gastrin levels were increased on infusion of 10% liver extract into stomach, but were unaffected on instillation of liver extract into duodenum. Peptide YY did not inhibit the release of gastrin in either the gastric or intestinal phase studies. Furthermore, PYY had no significant effect on either the basal release of secretin, gastric inhibitory polypeptide, pancreatic polypeptide, or neurotensin, or on the stimulated release of pancreatic polypeptide by 2-deoxyglucose. The specific binding of gastrin to its receptors on the fundic mucosa was also unaffected by PYY. These results indicate that PYY inhibits the cephalic and gastric phases of acid secretion independently, and that its actions are not mediated by either a negative effect on gastrin release or a positive effect on the release of some of the known acid inhibitors, or by an inhibition of gastrin binding to its receptors on the fundic cells. Our present findings (in combination with our previous findings of inhibition of pentagastrin- and bethanechol-stimulated gastric acid secretion by PYY, independent of the vagal cholinergic mechanism) indicate that the action of PYY is either direct on the parietal cells or is mediated by yet another, unidentified, inhibitor.

Animals↗