Starvation of phosphorylase kinase deficient rats is accompanied by partial hepatic glycogen depletion.
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Biomedical subjects
Publications and source records attributed to R Geddes.
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Rat liver glycogen was freed of non-covalently bound protein. The backbone protein was purified from the pure glycogen. This protein had a molecular weight of 60,000 daltons and amino acid analysis showed it to be rich in glutamate, serine and the hydrophobic amino acids. In both size and amino acid content it differed from the corresponding rabbit muscle protein. An O-type glycoprotein linkage is suggested.
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The incorporation of radioactivity into liver glycogen has been shown not only to be a metabolically inhomogeneous process but also to depend critically on the nature of the precursor. D-Galactose is incorporated into glycogen by a mechanism which is separate from that associated with the incorporation of D-glucose. D-Galactose is favoured for incorporation into high-molecular-weight glycogen and consequently is affected more by treatment of the animal with the antibiotic tunicamycin, since high-molecular-weight glycogen is preferentially found in the lysosomal compartment.
The 1,4-alpha-glucosidase inhibitor. Acarbose, when injected intraperitoneally disturbs liver lysosome metabolism, causing distinct and persistent inhibition of the enzymes and acute disturbances of lysosomal glycogen metabolism. A feedback control mechanism appears to operate, affecting cytosolic carbohydrate metabolism. A model is suggested for the adult form of lysosomal storage disease. The biochemical effects closely resemble those occurring in glycogenosis type II (Pompe's disease), and these have been confirmed by electron microscopy.
Glycogen of high molecular weight has been isolated from mammalian muscle, in contrast to the material of low molecular weight commonly described. The large polysaccharide is similar to liver glycogen in the structure of its individual beta-particles and also, partially, in the mode of assembly into the gross alpha-particles. The large particles may be disrupted by 2-mercaptoethanol, but not to the same extent as their liver counterparts.
Rats with a gentic deficiency of phosphorylase kinase have been treated with the 1,4-alpha-glucosidase inhibitor, Acarbose. Lysosomal glycogen metabolism has been markedly altered and the results support the concept of a feedback control mechanism operating on the uptake mechanism into the lysosomal compartment.
We report the complication of cardiac tamponade occurring secondary to a pericardial effusion in a patient with persistently seronegative rheumatoid arthritis. The frequency and presenting features of this potentially life threatening complication of rheumatoid arthritis are reviewed and management of this complication is discussed.
The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression.
The incorporation of 2-amino-2-deoxy-D-glucose from precursor 2-amino-2-deoxy-D-galactose into liver glycogen has been shown to be a metabolically inhomogeneous process after starvation. The protein-to-polysaccharide ratio is also heterogeneous with respect to molecular size, and enhanced overall as compared to normal glycogen. The results are discussed from the viewpoint of a molecular order in the synthesis and degradation of liver glycogen.
The size-distribution of liver glycogen was shown to be distinctly affected by the anti-inflammatory drugs salicylate and indomethacin. By measurement of the incorporation of radioactive glucose into glycogen, salicylate was shown to have a depressing effect on overall liver glycogen metabolism. These effects appear to arise from the stabilizing of the lysosome by the drugs. The incorporation, via liposomes, of purified anti-1,4-alpha-glucosidase activity and in the content of high-molecular-weight glycogen. These changes are increased by prolonged liposomal antibody treatment and suggest that a possible feedback control mechanism operates in the incorporation of glycogen into lysosomes. These experiments may be useful as a model of glycogen turnover and its failure in glycogenosis type II (Pompe's disease).
Glycogen has been carefully isolated from rabbit brain tissue and found to be of significantly greater molecular size (up to approx. 100 MDa) and heterogeneity than previously reported. The incorporation of radioisotope from glucose, pyruvate or acetate precursor has been shown to be non-uniform, being similar to the metabolic inhomogeneity observed in other tissues. Physicochemical studies have shown the gross hydrodynamic structure of the glycogen to be inhomogeneous and to differ significantly from that of liver glycogen.
Aortic root abnormalities including cusp thickening, subvalvular stenosis, and mild aortic root dilatation are the most common cardiac complications in patients with long standing ankylosing spondylitis (AS). Twenty-three patients with definite idiopathic AS (New York Criteria 1966) and twenty-two matched controls were studied with M-mode echocardiography. Only one of the AS patients had clinical aortic incompetence. Six of the AS patients had mildly dilated aortic roots (normal less than 3.7 cm) with a mean diameter of 3.9 cm (range 3.8 to 4.00 cm). None of the twenty-two controls matched for age, sex and blood pressure had dilated aortic roots, with a mean diameter of 3.3 cm (range 2.9 to 3.6 cm). No correlation existed between aortic dilatation and severity of disease estimated by acute phase proteins--caerulo plasmin, alpha 1-antitrypsin, alpha 1 acid glycoprotein, ferritin and C Reactive protein. Contrary to a previous report, mild aortic root dilatation occurs in long standing cases of AS. Although it is a non-specific finding, it does not appear to be related to age or blood pressure and may therefore be the forerunner of aortic incompetence.
Forty patients with arthritis (26 rheumatoid and 14 osteoarthrosis) entered a five-week double-blind crossover trial of diclofenac and ibuprofen. Four patients failed to complete the 10-week trial. There was no statistically significant difference in parameters of disease activity for the rheumatoid arthritis patients, but patients with osteoarthrosis fared significantly better on diclofenac. There was a low incidence of side effects on both regimens.
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Low temperature NMR spectra have been obtained of the water bound to glycogen. These data have allowed the evaluation of the amount of water bound and the energy and entropy associated with this bonding. High molecular weight glycogen (approx. 1 - 10(9)) exhibits water binding properties analogous to those previously found for other glycoproteins. Low molecular weight glycogen (approx. 1 - 10(7)), however, shows anomalous binding characteristics, with large amounts of associated "non-freezing" water. These findings are discussed in terms of previously proposed molecular architecture.
Lysosome-rich fractions were isolated from rat liver homogenates. In some fractions the lysosomes were separated from the contaminating mitchondria by the use of discontinuous Ficoll/sucrose gradients. Some glycogen was associated with lysosome fractions. This glycogen was of very large molecular size and of a quite different molecular-weight distribution from that isolated from the cytosol. It is suggested that appreciably more than 10% of cellular glycogen is located within the lysosome.