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Biomedical subjects

G Neale

Publications and source records attributed to G Neale.

At least 73 records · Page 4Linked to original sources

Functional and biochemical evidence of damage to enterocytes induced by triparanol: role of lysosomes and the effect of gluten-free diet.

1. Functional and biochemical studies were performed on the small intestine of control rats, and the results were compared with similar studies on animals given triparanol at a dosage of 0.114 mmol/kg daily for 10 days. The animals given triparanol were fed with either standard rat food or a gluten-free diet. 2. By using a recirculating-perfusion technique in vivo, it was shown that absorption of galactose from an 8 mmol/l solution was impaired in the ileum but not in the jejunum of the triparanol-treated rats. 3. Assays of marker enzymes for the principal subcellular organelles were performed on isolated jejunal and ileal enterocytes. In the ileum there was a striking decrease in lysosomal enzyme activities and a smaller but significant decrease of lactate dehydrogenase, catalase and malate dehydrogenase activities. In the jejunum there was no significant change in the activities of these enzymes. 4. Measurements of lysosomal integrity indicated that ileal lysosomal fragility was markedly increased and that jejunal lysosomes were affected to a much smaller extent. 5. These effects of triparanol could not be ameliorated by feeding with a gluten-free diet.

Acetylglucosaminidase

A familial abnormality of circulating vitamin B12 binding proteins: occurrence in a family of high serum concentrations of transcobalamin II.

A family is described in which two members (a father and a daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE-23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti-TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the beta, gamma region. This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed.

Blood Proteins

Studies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia.

Detailed studies of protein metabolism were undertaken in a patient with pellagra and hypoproteinemia associated with the carcinoid syndrome both before and after treatment. The synthesis of albumin improved from 82 mg per kg per day to 135 mg per kg per day with little change in the daily excretion of 5-hydroxyindole acetic acid. After treatment with nicotinamide the patient made good progress with a complete resolution of the signs of pellagra and protein malnutrition. These results support the hypothesis that a reduced availability of the essential amino acid L-tryptophan may limit the synthesis of albumin and nicotinic acid in patients with the carcinoid syndrome who become anoretic.

Adult

Some properties of alkaline-phosphatases in parenchymal and biliary tract cells separated from rat liver.

Livers of both normal and bile-duct ligated rats have been separated into parenchymal cells and fractions enriched in biliary tract cells. The specific activity of alkaline phosphatase increases in both types of cells after occlusion of the bile duct but the increase is more marked in the case of parenchymal cells. The enzyme from parenchymal cells migrates as a single zone on electrophoresis, whereas additional zones of lower anodal mobility occur in extracts of biliary tract preparations. The alkaline phosphatase activity of the slower zones is significantly less stable to heat than that of the zone characteristic of parenchymal cells. It is postulated that the increase in heat stability of alkaline phosphate in extracts of whole rat liver after bile-duct ligation is due to an increase in the proportion of the more stable form of the enzyme predominant in parenchymal cells.

Alkaline Phosphatase

Effect of bile-duct ligation on organelle marker enzymes in the liver and serum of rats.

1. Marker enzymes for the principal subcellular organelles of rat liver were asayed in the liver of rats 1 day and 8 days after bile-duct ligation or after laparotomy as a control procedure. 2. The microsomal enzymes in liver tissue showed complex changes. Benz[alpha]pyrene hydroxylase activity, predominantly found in the smooth endoplasmic reticulum, was decreased. Glucose 6-phosphatase activity and ribonucleic acid, which are localized predominantly in the rough endoplasmic reticulum, were increased. 3. The plasma membrane enzyme, alkaline phosphatase, increased in activity after bile-duct ligation. 4. No changes in mitochondrial enzyme activities were noted after 1 day but there was a 50% reduction 8 days after ligation. Lysosomal enzyme activities did not change in the liver tissue. 5. Liver catalase and D-amino acid oxidase activities showed a slight increase at 1 day postligation but a significant fall by 8 days. 6. Lactate dehydrogenase, a cytosol enzyme, showed a decrease in activity after 1 day but an increase in tissue activities 8 days after ligation. 7. Serum activities of mitochondrial, plasma membrane, microsomal, lysosomal and cytosol marker enzymes tended to increase post-ligation, particularly at 8 days. 8. Monoamine oxidase, a predominantly mitochondrial enzyme, was greatly elevated in the serum after 1 day but had returned to normal activities by 8 days.

Acetylglucosaminidase

Indices of granulocyte activity in inflammatory bowel disease.

In conditions with increased neutrophil production, the serum total vitamin B(12)-binding capacity (TBBC) is considered to correlate with the blood pool size of neutrophil granulocytes. The serum lysozyme, on the other hand, is a measure of neutrophil (and monocyte) turnover. The mean serum TBBC was significantly raised in patients with ulcerative colitis (range 1.23-5.51 ng/ml; mean 2.64 ng/ml) and patients with Crohn's disease (range 1.58-9.29 ng/ml; mean 2.93 ng/ml). The elevated values were shown to be due to rises in the granulocyte-secreted binding proteins, transcobalamins I and III. The TBBC was shown to rise with increasing activity of disease and to correlate roughly with the blood neutrophil granulocyte count. Patients with inflammatory bowel disease also had a significantly raised mean level of serum lysozyme (range 3.1 to 10.4 mug/ml; mean 6.8 mug/ml), but there was no correlation in individual patients between serum lysozyme and total B(12)-binding capacity. These results are taken to indicate an enlarged granulocyte pool and increased granulocyte turnover in inflammatory bowel disease.

Adolescent

Changes in plasma -glutamyl transpeptidase activity associated with alterations in drug metabolism in man.

A significant rise in plasma gamma-glutamyl transpeptidase activity (GGT) was observed on 13 out of 14 occasions on which patients on long-term treatment with the oral anticoagulant warfarin were given amylobarbitone, quinalbarbitone, or phenazone (antipyrine) for 30 days. In 13 of these 14 studies there was evidence that drug administration had stimulated the rate of warfarin metabolism. One patient showed no increase in plasma GGT activity, yet a significantly increased rate of warfarin metabolism, and another patient showed an increase in plasma GGT activity without a change in warfarin metabolism. When alterations in both plasma GGT activity and plasma warfarin concentration occurred together in response to drug administration the changes followed a similar time course, occurring after about one week of drug administration with maximal changes at about 10 or 15 days. Administration of chlordiazepoxide, diazepam, nitrazepam, and methaqualone did not stimulate the rate of warfarin metabolism in four patients studied, but plasma GGT activity increased significantly in two of these four instances. The implications of these observations in the interpretation of plasma GGT activities are discussed.

Acyltransferases

Liver structure and function following small bowel resection.

The observation that patients with extensive small bowel resection have impaired hepatocellular function with reduced BSP clearance and fatty change in biopsies from the liver led to a systematic study of liver structure and function following proximal and distal small bowel resection in the rat. While anaesthesia and surgery impaired BSP clearance per se, small bowel resection further reduced BSP clearance with impairment of both uptake and excretion phases of BSP excretion. The increased BSP retention was more marked after distal than after proximal small bowel resection, but in both experimental groups the abnormalities of BSP excretion spontaneously returned to normal three to four weeks after surgery. Circulating liver enzymes were normal but serum alkaline phosphatase was significantly depressed, particularly after distal resection. Isoenzyme studies showed that the depression of serum AP was due to a reduced intestinal isoenzyme. While serum levels remained consistently depressed up to eight weeks after proximal resection, in parallel with mucosal regeneration, serum AP returned to normal two to four weeks after ileectomy. While these minor changes in hepatic structure and function would normally be of little clinical importance, the additional insult of hepatic dysfunction may well be important in malnourished patients after extensive small bowel resection.

Adult