Distribution of arylsulphatase C in subcellular membranes of rat liver.
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Biomedical subjects
Publications and source records attributed to F A Rose.
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The metabolic fate of dipotassium 2-hydroxy-5-nitrophenyl [(35)S]sulphate ([(35)S]NCS), a chromogenic substrate for lysosomal arylsulphatases A and B, has been studied in rats. Intraperitoneal injection of [(35)S]NCS into free-ranging animals is followed by excretion of the bulk of the radioactivity in the urine within 24hr., less than 13% being eliminated as inorganic [(35)S]sulphate. Most of the urinary radioactivity can be accounted for as [(35)S]NCS, but small amounts of a labelled metabolite are also present. Experiments in which [(35)S]NCS was injected intravenously into anaesthetized rats with bile-duct and bladder cannulae confirm that the ester is rapidly excreted in the urine. However, small amounts of radioactivity appear in bile, mainly in the form of the metabolite detected in urine. When [(35)S]NCS is perfused through the isolated rat liver, about 35% of the dose is hydrolysed within 3hr. Similar results are obtained if [(35)S]NCS is injected into anaesthetized rats in which kidney function has been eliminated by ligature of the renal pedicles. The labelled metabolite has been isolated from bile obtained by perfusing several rat livers with blood containing a total of 100mg. of [(35)S]NCS. It has been identified as 2-beta-glucuronosido-5-nitrophenyl [(35)S]sulphate. The implications of the various findings are discussed. The Appendix describes the preparation of [(35)S]NCS.
1. Rat tissues have been shown to possess an aminotransferase that is active towards l-tyrosine O-sulphate and dependent on 2-oxoglutarate and pyridoxal phosphate. 2. Kidney, liver and pancreas have the greatest activity and the enzyme is localized mainly in the mitochondrial fraction in the liver and kidney cell. 3. The enzyme was shown to be distinct from l-tyrosine-2-oxoglutarate aminotransferase but its true identity was not established. 4. A procedure for the assay of the enzyme in crude tissue preparations was developed.
1. l-Tyrosylglycine O[(35)S]-sulphate is metabolized by the rat to yield the O[(35)S]-sulphate esters of l-tyrosine, p-hydroxyphenylpyruvic acid and p-hydroxyphenylacetic acid. 2. The proportion of the administered peptide which is excreted as l-tyrosine O[(35)S]-sulphate is greater at a higher dose. 3. An enzyme capable of hydrolysing the peptide bond of l-tyrosylglycine O[(35)S]-sulphate to yield l-tyrosine O[(35)S]-sulphate has been detected in rat liver and kidney. 4. The activity of this enzyme is completely inhibited by a large excess of l-tyrosylglycine.
A sensitive method using the Technicon Amino Acid Autoanalyzer was developed for the determination of l-tyrosine O-sulphate in mammalian urine. Normal rabbit urine was shown to contain a material that has properties identical with l-tyrosine O-sulphate. The material is also a normal constituent of rat, sheep, calf and mouse urine and is excreted by these animals in quantities ranging from 0.1 to 0.8mg./day/kg. body wt.
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Rats inhaled a paste polymer polyvinyl chloride dust at an aerosol concentration of 10 mg/m3 for 6 hr/day, 5 days/wk for a 15-wk period. A small number of randomly scattered lung lesions were detected at 15 wk; these lesions were also present 15 wk after exposure to polyvinyl chloride had ceased. Few if any biochemical changes were detected at the alveolar surface in lung tissues or other organs of polyvinyl chloride-exposed rats. It is therefore concluded that at "nuisance" dust level this form of polyvinyl chloride polymer exhibits a weak biological reactivity.
The present report is an analysis of the course of peripheral vascular disease (PVD) in 619 patients with non-insulin-dependent diabetes (NIDDM) recruited within 1 yr of diagnosis and followed quarterly for up to 14 yr (X = 10.5 yr). At 13 yr duration, the actuarially determined cumulative risks for intermittent claudication (IC), nonpalpable dorsalis pedis pulse (NPUL), and arterial calcification (CALC) were, respectively, 37.9%, 34.5%, and 60.9% for men and 24.3%, 37.6%, and 32.2% for women. Major amputations (AMP) occurred in only 1.3% of the patients, equivalent to approximately one case per 1000 patients per year. The corresponding incidences of IC, NPUL, and CALC were, respectively, 29, 27, and 47 per 1000 men and 19, 27, and 25 per 1000 women per year. CALC and NPUL were strongly related to mortality. Baseline risk factors with probability levels that suggest a relationship to PVD were, in women, age versus CALC (P less than 0.01), age versus NPUL (P less than 0.05), weight versus NPUL (P less than 0.05), systolic BP versus CALC (P less than 0.01), summed glucose tolerance test versus CALC (P less than 0.01), and triglyceride level versus CALC (P less than 0.05). In men, the only significant risk factors were diminished vibration perception, which was related to NPUL (P less than 0.05), and the serum triglyceride level, which was related to IC (P less than 0.05). In patients who are carefully followed prospectively, IC is far more common, but AMP is far less common than has been generally appreciated. Further studies are needed to clarify the roles of the diverse risk factors that are possibly related.