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Biomedical subjects

J Dawson

Publications and source records attributed to J Dawson.

At least 199 records · Page 11Linked to original sources

Mucosal enzyme activities, peptide hormone concentrations and hormone secretory granule properties in functioning proximal jejunum after shunt operation for obesity.

Crosby capsule biopsies were obtained from functioning jejunum in 6 patients between 7 and 15 months after jejuno-ileal for morbid obesity and compared with 6 normal control biopsies. Brush border and other mucosal enzyme activities and seven regulatory peptide concentrations were measured in each biopsy. Analytical subcellular fractionation by sucrose density gradient centrifugation was used to investigate brush border and peptide secretory granule properties. Specific activities of all the brush border enzymes assayed in the bypass patients were similar to the normal controls and subcellular fractionation studies showed no change in brush border properties. Similarly, properties of other mucosal organelles and their associated enzyme activities were unchanged in the bypass patients. The mucosal regulatory peptide concentrations in the bypass patients showed no significant difference from the normal controls and no changes were detected in peptide storage granule properties. These studies therefore support the concept that the adaptive changes occurring after jejuno-ileal bypass are due to changes in cell numbers or other parameters of function rather than changes in the specific activities of the brush border enzymes themselves. They also show that the marked abnormalities of plasma hormone release after bypass surgery are not in themselves due to alterations in mucosal hormone concentrations, or of the secretory granule properties.

Adult↗

Psychoses of epilepsy: a radiological evaluation.

Computerized axial tomography (CAT) scanning was carried out on 57 patients who had received a hospital diagnosis of psychoses associated with epilepsy, and 78 epileptic patients with psychiatric illness other than epilepsy. Abnormal scans were reported in approximately half of the cases in both groups. An excess of left hemisphere abnormality was noted in the psychotic group, but this was not significant. These findings failed to provide firm support for the hypothesis that lateralized structural damage to the cerebral hemispheres plays a major part in determining the specific pattern of associated psychotic illness.

Adult↗

Characterisation of gut hormone storage granules from normal human jejunum using metrizamide density gradients.

Analytical subcellular fractionation techniques using metrizamide density gradients have been used to investigate the properties of the gut hormone storage granules and the principal organelles from homogenates of normal human jejunal mucosa obtained by peroral mucosal biopsy. The individual hormones, detected by radioimmunoassay, each showed single discrete peaks in the density gradient experiments indicating localisation to single granules each with characteristic modal densities. Thus motilin showed a modal density of 1.15, gastrin 1.16, gastric inhibitory polypeptide (GIP) 1.17, enteroglucagon 1.18 and somatostatin and vasoactive intestinal peptide (VIP) 1.10 g/ml. The following organelles, characterised by their marker enzymes were located in the density gradients; plasma membrane (5'-nucleotidase) brush border (alpha-glucosidase, pH 6.0) mitochondria (particulate malate dehydrogenase), peroxisomes (catalase), lysosomes (N-acetyl-beta-glucosaminidase), endoplasmic reticulum (alpha-glucosidase, pH 8.0), cytosol (lactate dehydrogenase). These studies provide biochemical evidence of the distinct nature of the individual gut hormone storage granules and provide a basis for studying dynamic changes in the granules in response to physiological stimuli and pathological processes.

Adult↗

Subcellular fractionation studies of human gastric antrum: localization of the mucosal peptide hormones.

1. Analytical subcellular fractionation techniques have been applied to endoscopic human gastric antral biopsies to study the localization of gastrin, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles. 2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for somatostatin (modal density 1.23) and vasoactive intestinal peptide (modal density 1.17). Gastrin showed a more complex distribution with a distinct peak (modal density 1.18) and a substantial shoulder extending into the denser regions of the gradient. 3. The following organelles, characterized by their marker enzymes, were located in the density gradients: plasma membrane (5'-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (beta-N-acetyl-D-glucosaminidase), endoplasmic reticulum (neutral alpha-aminidase), cytosol (lactate dehydrogenase). 4. This technique can be applied to investigate disease of the gastric antrum at a subcellular level.

Acetylglucosaminidase↗

Subcellular fractionation studies of human rectal mucosa: localization of the mucosal peptide hormones.

1. Analytical subcellular fractionation techniques have been applied to endoscopic human rectal biopsies to study the localization of enteroglucagon, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles. 2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for enteroglucagon (modal density 1.25) and somatostatin (modal density 1.23). Vasoactive intestinal peptide showed a less discrete localization but demonstrated a major peak (modal density, 1.17) with a small subsidiary peak (modal density 1.24). 3. The following organelles, characterized by their marker enzymes, were located in the density gradients; plasma membrane (5'-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (beta-N-acetyl-D-glucosaminidase), endoplasmic reticulum (neutral alpha-D-glucosidase) and cytosol (lactate dehydrogenase). 4. This technique can be used to investigate disease of the human rectum at a subcellular level.

Centrifugation, Isopycnic↗

Subcellular localization of serotonin and motilin in the human jejunum.

1. Analytical subcellular fractionation techniques have been applied to human jejunal homogenates to study the localization of serotonin and motilin. 2. Serotonin, detected by a fluorimetric assay, showed two distinct particulate distributions in the density gradients with modal densities of 1.14 and 1.20. Motilin, whether detected by N-terminal or C-terminal specific antibodies showed similar density distributions with a modal density of 1.20, coinciding with the denser peak of serotonin. 3. These results lend support to the histochemical suggestions that motilin is located in a a serotonin-containing granule.

Centrifugation, Isopycnic↗

Separation of the gut hormone endocrine-cell storage granules of human jejunum using analytical subcellular fractionation.

Analytical subcellular fractionation techniques in combination with specific radioimmunoassays have been used to investigate the properties of the hormone-containing granules in human jejunal biopsy specimens. After gentle homogenisation, for all hormones except VIP, over 90% of the immunoreactivity was released in intact granules into the post-nuclear supernatant. Approximately 50% of the VIP immunoreactivity sedimented with the low speed pellet, probably reflecting the presence of this peptide in nerve fibres. The following hormone granules (equilibrium densities between parentheses) were separated by isopycnic centrifugation on the sucrose density gradients: VIP (1 x 17), motilin (1 x 20), and secretin (1 x 24). Gastrin and GIP granules were not resolved, both having the same modal density of 1 x 22 g/cm3. This combination of procedures thus provides a new quantitative technique for studying the properties of the gastrointestinal hormone-containing granules, and should therefore be of value in investigating pathophysiological problems in a variety of gastrointestinal diseases.

Cell Fractionation↗

gamma-Glutamyltransferase in human and mouse breast tumours.

A series of experimental mouse tumours were assayed for their gamma-glutamyltransferase activities. Significantly raised activities were found in a transplantable spontaneous mammary carcinoma compared to normal or lactating mouse breast. A study was therefore undertaken of human breast tumours. Carcinomas showed significantly elevated enzyme levels when compared with normal tissue or histologically uninvolved tissue from a breast containing a carcinoma. Fibroadenoma and chronic mastitis also showed significantly elevated levels when compared with normal tissue and did not differ significantly from carcinoma tissue. Benign breast cyst fluid showed very high levels of enzyme activity. Binding properties of the enzyme to Con A-Sepharose suggested that while normal tissue and fibroadenomas contained only asialated enzyme, carcinomas, chronic mastitis and cyst fluid contained a substantial proportion of sialated enzyme.

Animals↗

Immunodeficiency, malabsorption and secretory diarrhea. A new syndrome.

Described here is a patient with severe watery diarrhea associated with common variable immunodeficiency. Malabsorption for fat, bile acids, vitamin B12 and xylose was demonstrated, but the patient failed to respond to all the usual therapeutic maneuvers. The diarrhea responded only to high dose steroid therapy. Intestinal perfusion studies showed a hitherto undescribed, presumably acquired, glucose-stimulated water, sodium and chloride secretion in the jejunum and ileum, whereas normal fluid and electrolyte transport occurred from bicarbonate and mannitol solutions. Glucose absorption itself was normal and no hormonal, morphologic or biochemical defect was demonstrated to account for the phenomenon. The patient was also interesting when compared with other patients with common variable immunodeficiency in having normal plasma cells in the intestinal mucosa and an extensive family involvement.

Adult↗

Effects of gastrointestinal hormones on fasting gallbladder storage patterns in man.

Gallbladder storage and emptying patterns were studied in fasting normal subjects by a duodenal perfusion technique using indocyanine green as a biliary marker. Fasting gallbladder storage patterns were very variable but a more uniform biliary output with net storage of about 40% of the biliary marker was observed during a simulated interprandial state (2--4 h after meals) produced by a low dose intravenous infusion of secretin and caerulein. With this background hormonal stimulation, infusion of bovine pancreatic polypeptide to achieve physiological interprandial levels promoted further gallbladder storage of bile. Bovine pancreatic polypeptide produced storage by a major effect on the gallbladder rather than on the liver, common bile duct or sphincter of Oddi since a reduction of biliary output was not observed during bovine pancreatic polypeptide infusion in cholecystectomized subjects. Bovine pancreatic polypeptide had a separate effect on the pancreas, reducing trypsin output in both normal and cholecystectomized subjects.

Adult↗