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R N Barnes

Publications and source records attributed to R N Barnes.

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Alterations in the distribution and activity of transglutaminase during tumour growth and metastasis.

Transglutaminase activity and subcellular distribution have been examined in both normal and tumour tissue. Subcellular fractionation of rat liver demonstrated a bimodial distribution for transglutaminase between the particulate (approximately 40%) and cytosol (approximately 60%) fractions. Isolation of enriched plasma membrane fractions indicated the presence of membrane associated transglutaminase activity which co-distributed with that of 5'-nucleotidase and Na+/K+-ATPase. Induction of hepatocellular carcinomas in rats by treatment with either diethylnitrosamine or 6-p-dimethylaminophenylazobenzothiazole resulted in a reduction in transglutaminase activity which was accompanied by redistribution of the enzyme to the particulate fraction of the cell. The tumour bearing liver appeared to represent an intermediate stage between the hepatocellular carcinoma and control liver when assayed for content and distribution of transglutaminase activity. The transglutaminase activity of four transplantable rat sarcomas (P7, P8, MC3 and CC5) was found to be greatly reduced when compared with the normal tissues of rat liver, lung and spleen. A further reduction in this activity occurred in the primary growths of the sarcomas P7 and P8 following detection of metastases. Our data suggest that such changes in the distribution and content of transglutaminase may be a feature of tumour tissue and may be of value in both monitoring and investigating the carcinogenic process.

Acyltransferases↗

Detection of early atherosclerosis in M. fascicularis with transcutaneous ultrasonic measurement of the elastic properties of the common carotid artery.

The elastic properties of 22 common carotid arteries from 13 male cynomolgus monkeys (M. fascicularis) that were fed either a high cholesterol (test) diet or a standard monkey chow (control) diet for 18 months were measured noninvasively with 5 MHz ultrasound. A B-mode image of the artery was obtained with a 32-element linear array transducer, and a single line of video ultrasonic information was selected for tracking the echoes from the adventitial side of the near wall to the lumen-intima interface of the far wall. This technique measured lumen diameter plus anterior wall thickness. The diastolic diameter (Dd) (mean +/- SEM) of the test arteries was slightly larger than controls (2.9 +/- 0.1 vs 2.5 +/- 0.1 mm), whereas the fractional diameter change from diastole to systole (DeltaD/Dd, where DeltaD = diameter change) was slightly less (0.062 +/- 0.010 vs 0.082 +/- 0.011). Direct subclavian artery pulse pressure (DeltaP) in the test animals (63 +/- 4 mm Hg) was significantly greater than in the controls (41 +/- 2 mm Hg), whereas there was no difference in diastolic pressure (85 +/- 3 vs 81 +/- 2), respectively. The pressure-strain elastic modulus Ep = (DeltaP/DeltaD) Dd was significantly greater in the test monkeys (182 +/- 33 kPa) than in the controls (73 +/- 9 kPa). Morphometric analysis of atherosclerosis revealed more connective tissue and intra- and extracellular lipids in the test arteries than in the controls. Based on the average of three cross-sections equally spaced along each common carotid artery, the intimal area and the maximal intimal thickness averaged 0.89 +/- 0.16 mm2 and 0.26 +/- 0.04 mm for the test monkeys compared to negligible intimae from the controls. Medial area also was significantly greater in the test monkeys (0.71 +/- 0.03 mm2) compared to controls (0.57 +/- 0.04 mm2). Percentage stenosis defined as intimal area/IEL area, where IEL area is that within the internal elastic lamina, showed the test arteries to have 30 +/- 5% stenosis compared to 0% for the controls. However, dilatation appeared to compensate for any loss in lumen area due to intimal thickening. In this study, significant carotid artery stiffening associated with diet-induced atherosclerosis is demonstrated. This noninvasive technique may be useful in pediatrics and in preventive medicine for the detection of arterial stiffening associated with early progressive atherosclerotic lesions.

Journal Article↗