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Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 469 records · Page 26Linked to original sources

Rate of disappearance of circulating endogenous gastrin in dogs.

In five awake mongrel dogs, endogenous gastrin was released by continuous irrigation of the antrum with acetylcholine. After 60 minutes of antral perfusion, the entire vascular supply of the antrum was suddenly and totally occluded, and serial samples of peripheral blood were taken for measurement of gastrin. The rate of disappearance of endogenous gastrin was caluclated by standard linear regression analysis; the calculated half-life of endogenous gastrin was 8.62 minutes. Analysis of the data suggests that the disappearance rate of endogenous gastrin could be explained by two distinct half-lives: one of 2.8 minutes (which is similar to the half-time in dogs of both 14- and 17 -amino acid gastrin), and another of 15.4 minutes (which is similar to the half-time of 34 -amino acid gastrin). Physiologically released gastrin is a mixture of three or more molecular forms of gastrin and the half-life of 8.62 minutes probably represents the disappearance half-time of this mixture.

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Effect of alcohol on the release of secretin and pancreatic secretion.

The effect of alcohol on the release of secretin was studied in man by radioimmunoassay, and in dogs and cats by radioimmunoassay and bioassay (secretion of water and bicarbonate by the pancreas). In man plasma secretin levels increased significantly from a basal of 121 +/- 14 to 164 +/- 24 pg/ml at 60 minutes after oral ingestion of alcohol. Intraduodenal administration of alcohol in man, dogs, and cats did not release secretin or affect pancreatic water and bicarbonate secretion in dogs and cats, but a moderate increase in pancreatic protein output was observed in these two species. Plasma gastrin levels rose significantly from a basal of 52 +/- 4 to 64 +/- 3 pg/ml after ingestion of alcohol in man and from 33 +/- 5 to 51 +/- 8 pg/ml after administration of alcohol into the stomach of dogs. Administration of alcohol into the duodenum in man, dogs, and cats did not release gastrin. We conclude that alcohol probably does not release secretin directly. The mechanism of release of secretin in man is unknown; it clearly involves the stomach and may be mediated via the release of gastric acid.

Adult↗

Suppression of gastric secretion and serum gastrin by gastrin antibody.

Fourteen dogs received varying doses of antigastrin antibody; after a single dose of 0.07 ml/kg, circulating gastrin levels could not be measured for as long as forty-seven days. Gastric secretion in response to food was not diminished by antigastrin antibody doses as high as 0.07 ml/kg daily for ten days. Larger doses, 0.2 and 0.4 ml/kg, were required to produce a temporary reduction in gastric-stimulated gastric acid secretion. Mucosal levels of gastrin in the antrum, fundus, and duodenum were greatly increased ten days after injection of antigastrin antibody. The therapeutic use of antigastrin antibody to control gastric secretion seems at the present time not feasible because of the scarcity of the antigastrin antibody and because large doses aare required to obtain only a temporary effect.

Animals↗

The effects on gastrin and gastric secretion of five current operations for duodenal ulcer.

We have measured serum gastrin and gastric acid secretion in 66 duodenal ulcer patients before and after vagotomy and pyloroplasty (V + P--15 patients), selective proximal vagotomy without drainage (SPV - D--11 patients), and with drainage (SPV + D--19 patients), and vagotomy, antrectomy, and either gastroduodenostomy (V + BI--15 patients) or gastrojejunostomy (V + BII--6 patients). Basal and peak postprandial gastrin levels were increased in postoperative V + P, SPV - D, and SPV + D patients. Basal and peak postprandial levels of gastrin were unchanged after V + BII, indicative of duodenal release of gastrin. Gastrin response to food was abolished in V + BII patients. Acid output was reliably reduced after all five operations; reduction was greatest in patients after antrectomy and least in patients after SPV. No beneficial results were found with drainage in SPV patients. Acid secretion increased with time in SPV patients, especially those with drainage.

Adult↗

Suppression of gastrin release and gastric secretion by gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP).

Five dogs prepared with Heidenhain pouches received infusions of saline, GIP and VIP before and after a standard meat meal. Blood samples were obtained under basal conditions and at subsequent intervals for measurement of gastrin, insulin, GIP and VIP by radioimmunoassay. GIP and VIP infusions had no effect on basal levels of gastrin. GIP and VIP (in common with secretin and glucagon) were found to suppress food-stimulated release of gastrin and gastrin-stimulated acid secretion from the Heidenhain pouch. Insulin levels were significantly elevated during GIP and VIP infusions. Food released GIP (and perhaps VIP.

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Plasma levels of secretin in man and dogs: validation of a secretin radioimmunoassay.

We have developed and validated a secretin radioimmunoassay that is sufficiently sensitvie to measure circulating levels of secretin in the plasma of man and dogs. At a final dilution of 1:50,000, the antibody bound 30 percent to 40 percent of radioiodinated (125 I) 6-tyrosyl synthetic secretin. Pure natural porcine secretin was used as a reference standard and a linear dose-response curve was generated with 10 to 1,000 pg. of the polypeptide. Little or no cross-reactivity was found when graded doses of other gastrointestinal polypeptides were assayed in the radioimmunoassay and immunoreactive secretin (IRS) in volumes of serum up to 300 mul could be measured accurately.

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Catabolism of secretin by the liver and kidney.

We have investigated the roles of the liver and the kidney in the catabolism of secretin, using a specific and sensitive radioimmunoassay. Dogs were prepared with sampling catheters in the aorta, hepatic vein, portal vein, and renal vein and with electromagnetic flow probes on the portal vein, hepatic artery, and renal artery. Secretin levels in the vessels entering and leaving the liver and kidney were determined by radioimmunoassay and the total mass of secretin [concentration (picograms per milliliter) X plasma flow rate (milliliter per minute)] was calculated during an intravenous infusion of exogenous secretin and during release of endogenous secretin by acidification of the proximal intestine. The total masses of secretin entering and leaving the liver were the same during secretin infusion and during the release of endogenous secretin. Under conditions of elevation of plasma secretin, however, the kidney extracted 30 percent of arterial secretin during secretin infusion and 45 percent during release of endogenous secretin. Clearly the kidney is a major site of secretin catabolism.

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Identification of cholecystokinin-secreting cells.

Cholecystokinin (C.C.K.)-producing cells were identified in the mucosa of the upper small intestine in man and other mammals by immunocytochemical techniques and electron microscopy on semi-thin and serial thin sections. Ultrastructural studies suggested that the C.C.K.-producing cells resemble I cells of the modified Wiesbaden classification. The combination of these techniques provides a simple and reliable method of identifying C.C.K. cells in human biopsy material and will be useful in the investigation and diagnosis of gut endocrine dysfunctions.

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Depletion of antral gastrin after food in rats.

The results of these studies indicate that in fasting rats, there is an abrupt and prolonged rise in circulating gastrin after feeding. This increase in serum gastrin is accompanied by an early (five minutes) diminution in antral gastrin which is followed by slightly higher and more variable antral gastrin values. These findings suggest that feeding triggers the release of gastrin with early depletion of antral gastrin and that, subsequently, gastrin syhthesis and release interact cyclically to maintain antral and serum concentrations of gastrin. Antral, fundic, and duodenal gastrin values in rats are similar to those reported in dogs and cats. The jejunum of the rat contains little, if any, gastrin.

Animals↗

Effect of antrectomy and subsequent vagotomy on the serum gastrin response to food in dogs.

The effect of food on serum gastrin and gastric acid secretion has been studied in dogs with denervated pouches before and after antrectomy and subsequent vagotomy. A Billroth I anastomosis was used in one group of dogs and a Billroth II in the other. Serum gastrin was measured by radioimmunoassay. In both groups of dogs antrectomy significantly depressed mean basal levels of serum gastrin and abolished the rise in serum gastrin in response to a meat meal. Meal-induced pouch acid secretion was considerably lowered by antrectomy after either Billroth I or Billroth II anastomosis. Vagotomy after antrectomy increased basal levels of gastrin, but did not restore the serum gastrin response to a meat meal in either group of dogs. It is suggested that biologically active forms of gastrin are released from the antrum in response to a meal. Biologically inactive basal levels of gastrin apparently originate from extra-antral sources. The post-vagotomy increase in basal (static) gastrin suggests vagal control of the metabolism of static, extra-antral gastrin.

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