Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 325 records · Page 18Linked to original sources

PubMed1986

Morphological changes in red blood cells of calves caused by Leptospira interrogans serovar pomona.

Haemoglobinaemia is seen in certain hosts infected by certain serovars of Leptospira interrogans, but is absent from other serovar-host associations. Comparisons were made between calves infected with serovar pomona and those receiving a crude "toxin" prepared from the same organism. Red blood cells from "toxin"-injected calves showed discocyte-echinocyte transformation and contained portions of cytoplasm segregated within vacuoles. These animals showed increased sequestration of RBCs within the spleen but no overt haemoglobinaemia. Red blood cells from infected and haemoglobinaemic animals were spherical and pitted. They also showed vacuoles and tracts under the cell membrane in fully haemoglobinized RBCs and dark granular inclusions within the cytoplasm of those which were only partially haemoglobinized. Intracellular leptospires were not seen within the RBCs. Red blood cell sequestration and erythrophagocytosis were very pronounced within the spleen, liver and bone marrow. The changes in the RBCs are not easily explained by the previously proposed theory that RBC destruction is due to a phospholipase-like toxin acting directly upon the RBC membrane. A more appropriate hypothesis is that the RBC lesions are due to the adverse effects of leptospiral "toxin(s)" on the metabolism of the RBC causing the formation of defective portions of cytoplasm. These are then either degraded and expelled, leaving empty vacuoles, or are degraded and left within the cytoplasm as dark granular inclusions.

Animals↗

PubMed1986

Pathogenesis and red blood cell destruction in haemoglobinaemic leptospirosis.

Sequential morphological changes were seen in RBCs, spleen and liver from hamsters during the development of haemoglobinaemia following infection with Leptospira interrogans serovar ballum. Spleens from pre-haemoglobinaemic hamsters showed sequestration of RBCs and erythrophagocytosis but to a lesser degree than was seen in the haemoglobinaemic hamsters. Erythrophagocytosis and RBC sequestration were also seen in the liver, particularly in the haemoglobinaemic animals. None of these changes was seen in the RBCs, spleens and livers from moribund and dead hamsters suffering from non-haemoglobinaemic disease resulting from infection with Leptospira interrogans serovar pomona. Intracellular leptospires were readily identifiable within the spleens and livers of hamster infected with both ballum and pomona. It is suggested that leptospiral toxins affect RBC metabolism and eventually RBC morphology. The affected cells are detected and removed by the reticulo-macrophage system, usually before intravascular haemolysis can take place. If the toxins affect a certain enzyme or biochemical pathway, there are sufficient normal metabolic differences in RBCs between animals of different species and, in the same species of animal, between the same and different aged animals, to explain the differing susceptibilities of the RBCs to leptospiral toxins.

Animals↗

PubMed1986

Neurotensin stimulates pancreatic exocrine secretion in rats.

Neurotensin (NT) stimulates pancreatic exocrine secretion in dogs and humans. The purpose of this study was to examine the effect of exogenous neurotensin on pancreatic exocrine secretion in rats. Five Sprague-Dawley male rats were prepared with pancreatic, gastric and duodenal fistulas. Bile was shunted into the duodenum in order to collect pure pancreatic juice. 24 h later, neurotensin (0.05, 0.1, 0.2, 0.3, 1.0 nmol/kg) was infused intravenously in a random fashion. Pancreatic juice was collected every 10 min, and the volume was recorded and protein and bicarbonate were measured. Neurotensin stimulated, in a dose-related manner, the pancreatic secretion of water, protein and bicarbonate. Neurotensin may be involved in the physiologic control of pancreatic secretion in rats.

Animals↗

PubMed1986

In vitro studies of haemolysis by Leptospira interrogans serovars pomona and ballum.

Washed and unwashed red blood cells (RBC) from young calves, adult cattle, hamsters and humans were incubated with Leptospira interrogans serovars pomona and ballum. Washed cells suspended in saline were always haemolysed while unwashed cells and those which were washed and resuspended in plasma were never haemolysed, despite the presence of large numbers of organisms within the culture supernatant. Pomona produced greater haemolysis of cattle and human RBC than did ballum, but with hamster RBC ballum produced greater haemolysis than did pomona. A group of 6- to 9-month-old cattle infected with pomona showed no signs of clinical disease and RBC taken from them before infection and during the development of antibodies to pomona were haemolysed by pomona only after the cells were washed. Plasma therefore appears to have a protective function. This in vitro protective function of plasma even extended to plasma from young seronegative calves.

Animals↗

PubMed1986

Gastrinoma.

Although there are multiple etiologies of clinical hypergastrinemia, the most important cause is gastrinoma [Zollinger-Ellison (ZE) syndrome]. The most significant advance in the management of patients with the ZE syndrome has been the development of the ability to establish firmly the correct preoperative diagnosis by radioimmunoassay. We believe that all patients who have the ZE syndrome should undergo operation for two reasons: to identify and resect all tumor and because in patients in whom no tumor is found or in whom all tumor cannot be resected, the most reliable relief of hypersecretory symptoms for the life of the patient can be achieved by total gastrectomy.

Cimetidine↗

PubMed1986

Diagnostic role of gastrointestinal hormones in patients with chronic pancreatitis.

Thirty-three patients with chronic pancreatitis were studied in an effort to correlate release of gastrointestinal hormones (GIH) with the degree of pancreatic insufficiency. A prospective examination was conducted of fat-stimulated release of pancreatic polypeptide (PP), cholecystokinin (CCK), and neurotensin. Seventy-two-hour fecal fat determination, endoscopic retrograde pancreatography (ERP), and the bentiromide-PABA test were used to correlate the clinical stage of disease. The ERP was classified as positive only if the changes were advanced (or "marked") according to the Cambridge Classification. Five patients were defined to have mild disease, 13 moderate, and 15 severe. Any patient with clinical evidence of chronic pancreatitis and ERP changes that were less than advanced and had normal fecal fat and bentiromide tests received a grade of mild. Patients with one abnormal test were graded moderate, and those with two or three abnormal results were graded severe. In the 33 patients, the integrated 60-minute release of pancreatic polypeptide (PP) was 37.4 +/- 6.1 ng-60 min/ml in those five patients with mild disease, 102.3 +/- 10.3 ng-60 min/ml in the 13 patients with moderate disease, and 7.6 +/- 2.2 ng-60 min/ml in the 15 patients with severe disease. The integrated 60-minute release of neurotensin was 3.8 +/- 0.4 ng-60 min/ml in mild disease, 2.0 +/- 0.3 ng-60 min/ml in moderate disease, and 0.2 +/- 0.1 ng-60 min/ml in severe disease. CCK release did not correlate with the severity of disease. Enhanced release of PP appeared to correlate well with moderate stage of chronic pancreatitis, and depressed PP release with severe disease. Stimulated levels of PP and neurotensin appear to be useful in the diagnosis and staging of chronic pancreatitis. It is concluded that measurement of fat-stimulated release of PP and neurotensin may be useful to assess severity of disease in patients with chronic pancreatitis.

Adult↗

PubMed1986

Presence of estradiol-binding proteins in gastrointestinal tract of male rats.

In the cytosol from pancreas, fundus, and antrum of rats, two classes of specific, estradiol (E2)-binding proteins (EBPs) were observed, with 5- to 10-fold differences in their binding affinities, and 10- to 20-fold differences in their binding capacities. EBPs, both type I [high affinity, dissociation constant (Kd) less than 1.0 nM] and type II (low affinity, Kd greater than 5 nM), in the fundus were found to be specific for estrogens. None of the corticoids, or androgenic and progestogenic steroids tested demonstrated any significant inhibition of binding of radiolabeled E2 to EBP at doses as high as 5 X 10(-6) to 5 X 10(-5) M. At high concentrations of E2 (greater than 2-5 nM), nonsaturable EBPs were additionally observed in the pancreatic cytosol. In the intestine, however, EBP was not detected at E2 concentrations of less than 2 5 nM. Similarly, progesterone-binding proteins were nonmeasurable in either pancreas or gastrointestinal tissues at less than 5 nM concentrations of the ligand, indicating questionable physiological significance of the latter binding sites. The two classes of EBPs in the pancreas and stomach of rats, measured at near physiological E2 concentrations of less than 2 nM, however, may play a significant role in gastric and pancreatic functions, since sex steroids have been documented to have specific effects on structure and function of pancreas and stomach.

Animals↗

PubMed1986

Calcitonin inhibition of insulin release from isolated rat pancreatic islets.

Calcitonin is known to inhibit secretion of gastrin and insulin in vivo. The objective of this study was to determine whether calcitonin can act directly on pancreatic islets in vitro to inhibit insulin release. Isolated islets were obtained from collagenase-treated rat pancreas, and three peptides (gastrin-releasing peptide, cholecystokinin-8, bombesin) and glucose were used to stimulate insulin release. All agents caused a significant increase in insulin secretion and calcitonin inhibited these responses, but had no consistent effect on basal release. This study provides evidence that calcitonin is an effective inhibitor of insulin secretion and acts directly on islet tissue.

Animals↗

PubMed1986

Effect of bombesin and gastrin-releasing peptide on the release of gastric inhibitory polypeptide and insulin in rats.

The objective of this study was to determine whether bombesin- or gastrin-releasing peptide-induced release of insulin occurs before or after the release of gastric inhibitory polypeptide (GIP) in rats. The present results demonstrate that GIP release occurs before insulin release and suggest that bombesin-like peptides and GIP interact to stimulate insulin secretion.

Animals↗

PubMed1986

Comparison of the actions of bombesin, gastrin-releasing peptide-27, neuromedin B, and gastrin-releasing peptide-10 in causing release of gastrin and gastric inhibitory peptide in rats.

The objective of this study was to compare the gastrin- and gastric inhibitory peptide (GIP)-releasing actions of bombesin, gastrin-releasing peptide (GRP)-27, neuromedin B, and GRP-10 in rats. Both bombesin and GRP-27 are potent stimulants of gastrin and GIP release, whereas neuromedin B and GRP-10 are less effective, on a molar basis.

Animals↗

PubMed1986

Effect of substance P on contractions of the gallbladder.

The effect of substance P on contractions of the gallbladder in dogs (in vivo) and rabbits (in vitro) was examined. Substance P stimulated contraction of the gallbladder, both in vivo and in vitro; however, substance P was not as effective as cholecystokinin. Stimulation of gallbladder contractions in vivo by substance P was not affected by atropine. Stimulation of gallbladder strips in vitro by substance P was not affected by adrenergic antagonists or tetrodotoxin. These findings suggest that substance P may be a direct stimulant of contraction of the smooth muscle of the gallbladder.

Animals↗

PubMed1986

Role of gastrin and gastrin receptors on the growth of a transplantable mouse colon carcinoma (MC-26) in BALB/c mice.

We recently reported trophic response of transplantable mouse colon cancer cells (MC-26) to pentagastrin, in vivo, and demonstrated gastrin receptors on MC-26 cells, in vitro. In the present study, growth of MC-26 cells in mice, in response to pentagastrin, was studied in relation to binding kinetics and capacity of gastrin receptor. Gastrin receptor levels on mouse fundic and colonic membranes and on MC-26 cellular membranes were determined before MC-26 cell inoculation and designated as Day 0 levels. Four groups of mice were next inoculated with MC-26 cells and given injections of either pentagastrin (treated) or normal saline (control) for 10 or 15 days. At the end of the treatment periods, body, tumor, fundic, and colon weights were noted and gastrin receptor measured. tumor and fundic weights increased significantly within 15 days of pentagastrin treatment, compared to control values. In control (non-pentagastrin treated) mice, the binding affinity of gastrin receptor on tumor membranes was significantly decreased and associated with the complete loss of high-affinity gastrin receptor (Kd = less than 0.5 nM) by Day 15 of tumor growth. On the other hand, both the binding affinity and gastrin receptor levels of tumor membranes were maintained at Day 0 values by pentagastrin treatment. Endogenous gastrin was therefore ineffective in maintaining high-affinity gastrin receptor on control tumors. A significant number of low-affinity gastrin-binding sites (Kd = less than 2 nM) appeared in control tumors by Day 15, which could reflect rapid dedifferentiation or conformational changes of gastrin receptor in the absence of high levels of normal regulatory hormones. These studies demonstrate that the trophic effects of gastrin on MC-26 cells are probably mediated by its regulation and maintenance of the binding affinity and capacity of gastrin receptor on the cancer cells, in vivo.

Animals↗

PubMed1986

Effects of cyclosporin A and alpha-difluoromethylornithine on the growth of hamster pancreatic cancer in vitro.

The growth and survival of hamster H2T pancreatic ductal adenocarcinoma in vitro are known to be significantly reduced by inhibitors of polyamine biosynthesis. alpha-Difluoromethylornithine (alpha-DFMO) is a specific and irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. alpha-DFMO treatment inhibits the growth of H2T pancreatic cancer cells and decreases H2T cell survival in vitro and in vivo. In the present study, the effects of cyclosporin A (CsA) were examined on growth, survival, and polyamine levels in H2T pancreatic ductal adenocarcinoma in vitro. CsA had inhibitory effects on H2T pancreatic cancer growth similar to those of alpha-DFMO; these effects were blocked by the addition of the polyamine putrescine. Polyamine levels were found to be significantly altered in cells treated with CsA and/or alpha-DFMO. The combination of CsA (8.3 X 10(-4) mM) and alpha-DFMO (0.5 mM or 1.0 mM) inhibited H2T cell survival to a greater extent than either agent alone. These results suggest that CsA in combination with other agents that inhibit polyamine synthesis may be useful for the treatment of pancreatic cancer.

Animals↗

PubMed1986

Cholecystokinin-destroying activities of canine tissue homogenates.

We have studied the capacity of different canine tissue homogenates to destroy cholecystokinin in vitro. Tissues from the kidney cortex, lung, pancreas, and small bowel contained significant cholecystokinin-destroying activity. Only small amounts of activity were found in the liver, and no activity was detected in the kidney medulla, the gastric antrum, gallbladder, spleen, or in serum or plasma. The kidney cortex was the richest source of activity. The cholecystokinin-destroying enzyme isolated from the kidney cortex was heat-labile, non-dialyzable, and trypsin-resistant, with an optimum pH between 7 and 7.4. The enzyme was inhibited by chelating agents and by phenylalanine amide, although it was little affected by phenylalanine itself or proteinase inhibitors. The enzyme required divalent cation cofactors for its activity. After inhibition by EDTA, the enzyme could be reactivated completely with Mn2+, but not with Ca2+ or Mg2+ alone. The cholecystokinin-destroying enzyme was bound strongly to membranes, and during differental centrifugation, was sedimented with mitochondrial fractions of kidney cortex. The supernatant fraction of the solubilized enzyme obtained at 105,000 X g had a molecular weight of about 480,000 dalton. Since the enzyme could be inhibited by phenylalanine-amide, it would appear to act at the C-terminal end of the cholecystokinin molecule.

Animals↗

PubMed1986

Bile inhibits release of cholecystokinin and neurotensin.

We have investigated the effect of bile on fat-stimulated release and basal plasma levels of cholecystokinin-33/39 (CCK) and neurotensin in six awake dogs prepared with chronic gastric and duodenal cannulas. Experimental bile diversion was achieved by catheterization of the common bile duct through the duodenal cannula; the gallbladder was undisturbed. Bile diversion significantly enhanced the release of both CCK and neurotensin that was stimulated by intraduodenal (ID) infusion of a triglyceride suspension (corn oil) (0.5 gm/kg-hr). The integrated release with ID triglyceride (ng [0 to 90 min]/ml) for CCK was control 5.58 +/- 0.83, bile diversion 14.47 +/- 2.81, bile excess 1.68 +/- 0.56, and for neurotensin was control 0.35 +/- 0.19, bile diversion 1.26 +/- 0.35, and bile excess 0.45 +/- 0.31. ID infusion of excessive bile (bile collected during bile diversion) significantly inhibited both the release and basal levels of CCK. Bile diversion alone did not modify plasma levels of CCK or neurotensin. We conclude that: endogenous bile exerts a negative feedback effect on release of CCK and neurotensin induced by triglyceride and on basal plasma levels of CCK; bile is unnecessary for the stimulation of endocrine cells in the intestinal mucosa by dietary fat; and measured basal levels of CCK and neurotensin represent a real amount of circulating peptide in the fasting state, that is, the basal levels are real and not artifactual.

Animals↗

PubMed1986

Gastrin stimulates growth of colon cancer.

Gastrin is trophic for normal gastric and colonic mucosa. We examined the potential trophic effects of chronic gastrin administration on the growth of mouse colon adenocarcinoma (MC-26). Thirty-three mice bearing transplantable MC-26 colon cancers were treated with varying doses (125, 250, or 500 micrograms/kg/day) of pentagastrin. Significant increases in tumor weight and DNA content were observed. Fundic mucosal weight and DNA content in these mice showed a dose-related trophic response. The weight of control fundic mucosa was 10 mg and rose to 20, 45, and 65 mg with increasing doses of gastrin. The DNA content of control fundic mucosa was 155 micrograms and rose to 220, 340, and 480 micrograms as the dose of gastrin was increased. Pentagastrin stimulated growth of the MC-26 colon cancer, but the threshold for gastrin-stimulated tumor growth was different from that of normal mucosal growth. The hyperplastic response of the fundic mucosa was increased by increasing gastrin doses; whereas, colon cancer hyperplasia was maximal at the lowest dose tested (125 micrograms/kg/day) and did not increase further with increasing doses of hormone. Mice bearing gastrin-stimulated tumors died at a significantly greater rate than did mice with untreated tumors (80% of control mice and none of the treated mice were alive at day 55). The effects of gastrin treatment on the growth of MC-26 colon cancer persist after treatment is discontinued; mice with tumors that were treated with gastrin for either 7 or 14 days and in which the treatment was stopped were all dead by 35 or 28 days, respectively, after the end of treatment.

Adenocarcinoma↗

PubMed1985

Regulation of gastric acid secretion by secretin and serotonin.

We have tested the interaction between serotonin and secretin in pentagastrin-induced gastric acid secretion in six dogs prepared with Thomas gastric and duodenal cannulas. We further examined the effect of methysergide, a serotonin antagonist, on gastric acid secretion. The intravenous administration of serotonin or secretin alone significantly inhibited pentagastrin-induced gastric acid secretion. The combined administration of serotonin and secretin inhibited gastric acid secretion to a greater magnitude than either secretagogue alone. The administration of methysergide diminished basal concentrations of secretin on gastric acid secretion. Methysergide also enhanced the stimulatory activity of pentagastrin-induced gastric acid secretion. The inhibitory action of intraduodenal acidification of pentagastrin-induced gastric acid secretion was reversed by methysergide.

Animals↗

PubMed1985

Effect of aging on pancreatic secretion in rats.

We have characterized the effects of aging on the pancreatic exocrine secretory response to the normal stimulatory hormones, secretin, and cholecystokinin. Young (6 month old) and aged (26 months old) male Sprague-Dawley rats were prepared with pancreatic fistulas and challenged with different doses of secretin (0.03, 0.06, and 0.12 nmol/kg) and cholecystokinin-8 (0.3, 0.6, and 1.2 nmol/kg) intravenously. The pancreatic secretion was measured for volume and bicarbonate and protein outputs. Our results show that in aged rats, the basal pancreatic secretion volume and protein and bicarbonate outputs were significantly reduced, and the pancreatic secretion volume and protein and bicarbonate responses to graded doses of secretin or cholecystokinin-8 were significantly reduced. This study demonstrates that pancreatic exocrine function in rats diminishes with age.

Aging↗