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Biomedical subjects

K D Buchanan

Publications and source records attributed to K D Buchanan.

At least 199 records · Page 11Linked to original sources

Gastrin and glucagon responses to extensive distal small bowel resection: an experimental study in dogs.

The objectives of the present work were to study the role (and possible sources) of gastrin and glucagon, as measured by radioimmunoassay techniques, in the acute response to massive bowel resection in dogs. Four acute experimental models were designed for this purpose. Circulating portal and arterial hormone concentrations were estimated under basal conditions and after administration of an intraduodenal fat stimulus. Stimulated portal gastrin levels were significantly higher in animals with bowel resections than in intact animals (p less than 0.05 to p less than 0.01) but the depletion of N-terminal glucagon-like (GLI) reactivity or total GLI was only transiently significant (p less than 0.05). Pancreatectomy, with or without resection, resulted in depletion of circulating N-terminal and C-terminal GLI, although not to zero values, suggesting extra-pancreatic sources of the GLI. Portal-arterial differences were noted for GLI but not for gastrin.

Animals↗

Plasma glucagon and insulin concentrations in acromegaly.

Sixteen patients with clinically active acromegaly were investigated; four of these had insulin-independent diabetes mellitus. Those acromegalic subjects who were not diabetic exhibited excessive insulin responses to glucose and arginine stimulation. By contrast, plasma glucagon concentrations in these patients did not differ significantly from those in control subjects. Acromegalic patients who also had insulin-independent diabetes had a markedly reduced insulin response to glucose stimulation, while arginine-induced insulin secretion was relatively well preserved. Although there was a tendency for plasma glucagon concentrations to be higher in the diabetic than in the nondiabetic group of acromegalic subjects, this difference did not achieve statistical significance either in the basal state or during the glucose amd arginine infusion tests.

Acromegaly↗

A glycoside-hydrolase inhibitor in treatment of dumping syndrome.

BAY g 5421, a glycoside-hydrolase inhibitor, produced symptomatic improvement in ten patients with the dumping syndrome. 100 mg BAY g 5421, given before a 50 g sucrose meal, produced pronounced attenuation of both hyperglycaemic and hypoglycaemic phases of plasma glucose levels; and it greatly reduced the rise in plasma levels of gastric inhibitory polypeptide and insulin. Gastric emptying, studied simultaneously by an isotopic method, showed little difference between tests, suggesting that the improvement achieved was not mediated by slowing gastric emptying.

Adult↗

Physicochemical and biological properties of glucagon-like polypeptides from porcine colon.

Polypeptide material displaying glucagon-like immunoreactivity was isolated from porcine colon using immunoaffinity chromatography. The immunoreactive material was tightly bound to high molecular weight proteins but was dissociated by 0.1% w/v sodium dodecyl sulphate solution into immunoreactive components of approximate molecular weights 12,000,8000,5000 and 3000. These components reacted at least 50 times more strongly with antibodies specific for the N-terminal region of glucagon than with antibodies specific for the C-terminal region of glucagon. While the 8000 and 3000 dalton fractions were homogeneous, the 12,000 and 5000 dalton fractions were resolved into multiple bands by isoelectric focusing. The 12,000 dalton fraction was devoid of glycogenolytic and lipolytic activity, was not insulin releasing and showed no ability to bind to receptor sites specific for glucagon on hepatic plasma membranes and to active hepatic adenylate cyclase. The 8000 and 5000 dalton components showed weak lipolytic activity. The possible significance of colonic glucagon-like immunoreactivity relative to pancreatic glucagon and immunoreactivity from other tissues is discussed.

Adenylyl Cyclases↗

Starvation-induced changes in secretin-like immunoreactivity of human plasma.

Levels of secretin-like immunoreactivity in the plasma of 50 starved subjects were measured by radioimmunoassay and rose from 18 +/- 3 (S.E.) pg/ml after 12 h, to 103 +/- 12 pg/ml (P less than 0.005) after 36 h. The assay antibodies were found to be specific for a region of secretin located towards the C-terminal residue. Lactoperoxidase was used to label the secretin with 125I and ionexchange chromatography on SP-Sephadex C-25 was used to purify the labelled product. The plasma immunoreactivity was purified by immunoaffinity chromatography on antibody-Sepharose conjugates and characterised by gel-filtration on Sephadex G-50 calibrated with molecular weight markers. After a 12-h fast, 10-20% of the immunoreactivity had a molecular weight of about 12 000, possibly due to precursors of secretin. Most of the remainder was smaller than secretin with molecular weight of less than 3000. This material comprised over 90% of the plasma immunoreactivity after a 36-h fast and may be due to degradation products.

Antibody Specificity↗

The use of perfused rat intestine to characterise the glucagon-like immunoreactivity released into serosal secretions following stimulation by glucose.

Isolated perfused intestine of rat was used to demonstrate the glucose-stimulated release of glucagon-like immunoreactivity (GLI) into serosal secretions. The released GLI was characterised using immunoaffinity chromatography on columns of immobilised antibodies specific for the N (residues 1 to 18) and for the C (residues 19-29) terminal portions of glucagon followed by gel-filtration. The immunoreactivity was present in a variety of molecular species. These include a large GLI which has a molecular weight about 12000 and binds to antibodies specific for the N-terminal portion of glucagon and two polypeptide fractions with molecular weight closer to that of glucagon. While one fraction of the small GLI boun both to antibodies specific for the C-terminal and N-terminal portions of glucagon the other bound only to the former antibodies. The relevance of these findings to the origins of circulating GLI and the possible precursor relationship between large and other forms of GLI is discussed.

Animals↗

Hypercalcaemia in rheumatoid arthritis: investigation of its causes and implications.

When correction was made for hypoalbuminaemia, 23 of 50 ambulant patients with definite or classical rheumatoid arthritis were found to have hypercalcaemia. When these 23 patients were studied 6 months later, 7 had hypercalcaemia as defined by the correction factor for a low serum albumin level, and 6 of these patients had raised serum ionised calcium concentrations. Biochemical studies in the 23 patients indicated evidence of hyperparathyroidism, namely, hypophosphataemia, increased serum alkaline phosphatase, hyperchloraemia, and reduced tubular reabsorption of calcium. However, serum immunoreactive parathyroid hormone concentrations were normal. Only one patient had an abnormally low serum 25-hydroxy-vitamin D result: this patient had a high level of urinary D-glucaric acid and was receiving phenobarbitone for treatment of epilepsy. The biochemical features suggestive of parathyroid overactivity were particularly found in patients with raised serum calcium levels. The cause of hypercalcaemia in rheumatoid arthritis remains to be explained.

Adult↗

A histological study of the effect of chronic gastritis on gastrin cell distribution in the human stomach.

To determine the effect of varying degrees of gastritis on the distribution of immuno-reactive gastrin cells 38 partial gastrectomy specimens have been studied. Routinely stained histological sections of mucosa were compared with serial and adjacent sections stained by specific immunohistochemistry using peroxidase and fluorescent techniques. While chronic superficial gastritis had no obvious effect, mild atrophic gastritis was associated with an uneven distribution of gastrin cells which became more marked with increasing severity of gastritis. In the region of intestinal metaplasia gastrin cells were almost totally absent. Small numbers of gastrin cells were found within areas of pseudopyloric metaplasia in the fundus, a region where those cells are not normally seen. Similarly, gastrin cells were detected within regenerative gastric polypi in both antrum and fundus.

Chronic Disease↗

The gastro-entero-pancreatic hormone secretion after a mixed meal in normal subjects before and after a 72 hour period of starvation.

The responses of plasma gastro-entero-pancreatic (GEP) hormones and free fatty acids (FFA) to a standard mixed meal before and after starvation have been measured. Raised insulin, glucose and FFA levels were found following refeeding after starvation and levels of secretin and C-terminal glucagon-like-immunoreactivity (C-GLI), raised by starvation, were rapidly suppressed on refeeding. The responses of gastrin and N-terminal glucagon-like-immunoreactivity (N-GLI) to a standard mixed meal were not altered by starvation. Although this study does not directly support that secretin and glucagon are responsible for the hyperglycaemia or hyperinsulinaemia of starvation diabetes, a role for both hormones in the raised FFA levels is proposed, as well as a role for glucagon in the initial hyperglycaemic response to a meal after starvation.

Adult↗

Effect of catecholamines on gastrin release.

In vivo and in vitro techniques have been used to study the effect of catecholamines on gastrin release. The i.v. infusion of epinephrine in dogs produced a significant rise in plasma gastrin concentration. This response was prevented by the administration of propranolol to block beta-adrenergic receptors. The infusion of isoproterenol, a beta-adrenergic agonist, produced a significant rise in gastrin levels, while phenylephrine, an alpha-adrenergic agonist, had no effect. In in vitro studies using isolated pieces of rat antrum, isoproterenol stimulated acute phase release of gastrin, whereas phenylephrine was again without effect. The studies indicate that catecholamines directly influence G cell function.

Animals↗

On the relationship between gastrin, gastric secretion, and adjuvant arthritis in rats.

The elevation of plasma immunoreactive gastrin known to occur during the induction of adjuvant-induced arthritis (Rooney et al., 1973) has been shown to be maximal at 7 days after injection. Gastrin administered exogenously accelerated and exacerbated the inflammatory joint disease. Some evidence has been presented that the endogenous immunoreactive gastrin had biological activity in terms of gastric acid secretion.

Animals↗