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Biomedical subjects

F B Williamson

Publications and source records attributed to F B Williamson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Inhibition by heparin-modulated antithrombin III of amidolysis catalysed by m beta-acrosin.

Purified m beta-acrosin catalysed amidolysis of several p-nitroanilides with C-terminal arginine residues. Antithrombin III inhibited amidolysis catalysed by the enzyme. This effect of antithrombin III was potentiated by heparin, and to a modest extent by heparan sulphate, cellulose sulphate, dextran sulphate and xylan sulphate. De-N-sulphated heparin, de-N-sulphated N-acetylated heparin, heparin of low relative molecular mass, chondroitin 4-sulphate, chondroitin 6-sulphate, dermatan sulphate and hyaluronic acid were ineffective.

Acrosin↗
PubMed1984

Heparan structure and the modulation of angiogenesis.

It is postulated that the angiogenic potential of tissues is influenced by the fine structure of heparan glycosaminoglycans present in the tissues. Possible mechanisms involved are discussed. It is suggested that compounds chemically related to heparans might usefully act as inhibitors of pathological angiogenesis.

Capillaries↗
PubMed1983

Beta-agarases I and II from Pseudomonas atlantica. Substrate specificities.

Beta-Agarase I and II were characterised by their action on agar-type polysaccharides and oligosaccharides. Beta-Agarase I, an endo-enzyme, was specific for regions containing a minimum of one unsubstituted neoagarobiose unit [3,6-anhydro-alpha-L-galactopyranosyl-(1 leads to 3)-D-galactose], hydrolysing at the reducing side of this moiety. Yaphe demonstrated that agar was degraded by this enzyme to neoagaro-oligosaccharides limited by the disaccharide but with a predominance of the tetramer [Yaphe, W. (1957) Can. J. Microbiol. 3, 987-993]. Beta-Agarase I slowly degraded neoagarohexaose but not the homologous tetrasaccharide. [1-3H]Neoagarohexaitol was cleaved to neoagarotetraose and [1-3H]neoagarobiitol. The highly substituted agar, porphyran was degraded to methylated, sulphated and unsubstituted neoagaro-oligosaccharides which were invariably terminated at the reducing end by unsubstituted neoagarobiose. The novel enzyme, beta-agarase II, was shown to be an endo-enzyme. Preliminary evidence indicated this enzyme was specific for sequences containing neoagarobiose and/or 6(1)-O-methyl-neoagarobiose. It degraded agar to neoagaro-oligosaccharides of which the disaccharide was limiting and predominant. Beta-Agarase II rapidly degraded isolated neogarotetraose and neoagarohexaose to the disaccharide. With [1-3H]neoagarohexaitol, exo-action was observed, the alditol being cleaved to neoagarobiose and [1-3H]neoagarotetraitol. Neoagarotetraitol was hydrolysed at 4% of the rate observed for the hexaitol. Porphyran was degraded to oligosaccharides, the neutral fraction comprising 24% of the starting carbohydrate. This fraction was almost exclusively disaccharides (22.4%) containing neoagarobiose (7.4%) and 6(1)-O-methyl-neoagarobiose (15%). Beta-Agarase II is probably the 'beta-neoagarotetraose hydrolase' reported by Groleau and Yaphe as an exoenzyme against neoagaro-oligosaccharides [Groleau, D. and Yaphe, W. (1977) Can. J. Microbiol. 23, 672-679].

Agar↗
PubMed1983

Effect of alpha 1-proteinase inhibitor and sulphated polysaccharides on the activity of m beta-acrosin.

Purified m beta-acrosin catalysed amidolysis in vitro of several p-nitroanilides with C-terminal arginine residues. alpha 1-proteinase inhibitor inhibited amidolysis catalysed by the enzyme. This effect of alpha 1-Proteinase inhibitor was not prevented by pre-incubation of the enzyme with heparin or any other glycosaminoglycan. Pre-incubation of the enzyme with sulphated dextran or sulphated cellulose alleviated the effect of alpha 1-proteinase inhibitor. These results are discussed in terms of possible in vivo modulation by alpha 1-proteinase inhibitor of acrosin activity.

Acrosin↗
PubMed1983

beta-agarases I and II from Pseudomonas atlantica. Purifications and some properties.

The agarose-degrading system of Pseudomonas atlantica has been re-examined. In addition to the previously reported extracellular endo-beta-agarase [Yaphe, W. (1966) in Proceedings 5th International Seaweed Symposium, pp. 333-335] a second, membrane-bound endo-enzyme activity, beta-agarase II has been discovered. These two enzymes act in concert to degrade agarose to neoagarobiose [3,6-anhydro-alpha-L-galactopyranosyl-(1 leads to 3)-D-galactose] and also to degrade partially 6-O-methylated agarose to neoagarobiose and 6(1)-O-methyl-neoagarbiose. Novel assays were devised for beta-agarase II and the associated disaccharidase, neoagarobiose hydrolase. These allowed the critical purification of beta-agarase I and II. beta-Agarase I was purified 670-fold from the bacterial medium by a new method using ammonium sulphate precipitation and gel filtration on Sephadex G-100. The enzyme was resolved from the small amount of extracellular beta-agarase II. Dodecylsulphate/polyacrylamide gel electrophoresis indicated a homogeneous protein and a molecular weight of 32000. Activity was observed against agar over the pH range 3.0-9.0 and optimally at pH 7.0. The enzyme could be used indefinitely at 30 degrees C but only for up to 2 h at 40 degrees C. beta-Agarase II was partially purified (5-fold) from the soluble fraction of disrupted cells by chromatography on Sephadex G-100, hydroxyapatite and DEAE-Sepharose CL-6B. This preparation was free of beta-agarase I and disaccharidase. beta-Agarase II was stimulated by NaCl, optimally in the range 0.10-0.20 mol dm-3 (2.4-fold the activity at 0.010 mol dm-3 NaCl). Alkali earth metal (0.002 mol dm-3 CaCl2 or 0.005 mol dm-3 MgCl2) gave 1.2-fold the normal activity. Optimum activity was over pH 6.5-7.5.

Chemical Phenomena↗
PubMed1983

Porphyran primary structure. An investigation using beta-agarase I from Pseudomonas atlantica and 13C-NMR spectroscopy.

Porphyran, a highly substituted agarose from Porphyra umbilicalis was degraded by highly purified beta-agarase I from Pseudomonas atlantica. This enzyme cleaved at the reducing side of units of beta-neoagarobiose (3,6-anhydro-alpha-L-galactopyranosyl-(1 leads to 3)-beta-D-galactopyranose). The oligosaccharides were divided into fractions of low and high molecular weight by dialysis. The permeate (23% of total starting carbohydrate) was separated by ion-exchange into neutral and anionic fractions. Gel filtration of the neutral fraction (19%) resolved two major oligosaccharides. These were shown by 13C-NMR spectroscopy to be 6(3)-O-methyl-neoagarotetraose and 6(3),6(5)-di-O-methyl-neoagarohexaose. Gel filtration of the anionic oligosaccharides (3.3%) revealed two novel monosulphated tetrasaccharides, 6-O-sulphato-alpha-L-galacto-pyranosyl-(1 leads to 3)-beta-D-galactopyranosyl-(1 leads to 4)-3,6-anhydro-alpha-L-galactopyranosyl-(1 leads to 3)-D-galactopyranose and its 6(3)-O-methylated derivative. The 13C-NMR data from the sulphated tetrasaccharides provided a novel reference which was used to characterise higher, partially sulphated fragments in the dialysis permeate. The fraction retained on dialysis (77%) had an average degree of polymerisation of 40 and was homologous with the high-molecular-weight anionic permeate. From 13C-NMR spectroscopy porphyran was found to comprise 49% sulphated disaccharide units and these were calculated to occur in stretches averaging 2.0-2.5 contiguous units.

Chemical Phenomena↗
PubMed1983

Effect of antithrombin III, alpha 1-proteinase inhibitor and heparin on amidolytic activity of nerve growth factor (7S-NGF).

Amidolysis catalysed by nerve growth factor (7S-NGF) and by a glandular kallikrein, unlike that catalysed by thrombin, was not inhibited by antithrombin III, either in the presence or absence of heparin. Inhibition by alpha 1-proteinase inhibitor of thrombin-, but not of 7S-NGF- or kallikrein-catalysed amidolysis was alleviated by incubation of enzyme and heparin before addition of inhibitor. These data are discussed in terms of a possible control of growth factor activity by antiproteinases and glycosaminoglycans.

Animals↗
PubMed1983

Glycosaminoglycans and the control of cell surface proteinase activity.

It is postulated that the metabolically variable fine structure of pericellular heparan glycosaminoglycans affects the ability of these molecules to influence cell proliferation-associated proteinase-catalysed reactions occurring at cell surfaces. Evidence suggesting the possibility of a wide repertoire of glycosaminoglycan-mediated positive and negative effects on such reactions is reviewed. It is suggested that clinical administration of compounds related chemically to heparins might usefully modulate cell proliferation-associated proteinase activity.

Animals↗
PubMed1982

Fragmentation and modification of iota-carrageenan and characterisation of the polysaccharide order-disorder transition in solution.

A procedure is described in detail by which the algal polysaccharide, iota-carrageenan, can be modified and fragmented to products of more regular structure and shorter chain length. Since most chains of this product can form uninterrupted helices they undergo the disorder-order transition without the gelation that is a feature of the behaviour of the natural polymer. The disorder-order transition becomes much sharper and occurs at higher temperatures with increasing chain length. The sign and magnitude of the accompanying shift in optical rotation can be estimated satisfactorily from the solid-state geometry of the helix using our semi-empirical method for correlating optical rotation with the conformations at glycosidic linkages. In solutions of the helical form, but not the coil form, cationic dyes such as methylene blue or acridine orange show induced optical activity and a changed visible spectrum which we attribute to binding and stacking on the helix. This also causes a shift in the temperature of the helix-coil transition. We discuss the possibility that the tendency of dyes to stack could drive polysaccharides into conformations that they would not otherwise adopt, with implications for their use as 'conformational probes'.

Carrageenan↗
PubMed1981

The anticoagulant activity of dermatan sulphates: evidence against the involvement of antithrombin III.

Anticoagulant activity of dermatan sulphates is unaffected by antiserum specific for antithrombin III (AT III) unless the glycosaminoglycan preparation contains demonstrable heparin. 2 Only dermatan sulphate preparations of considerable heparin content potentiate AT III inhibition of thrombin, factor Xa and plasmin. 3 These data suggest that dermatan sulphates exert anticoagulant activity which, unlike that of heparin, is largely or totally independent of AT III.

Animals↗
PubMed1981

Effect of sulphated polysaccharides on the alpha 1-antitrypsin inhibition of amidolysis catalysed by coagulation cascade proteinases.

1 The ability of several sulphated polysaccharide anticoagulants to prevent alpha 1-antitrypsin inhibition of thrombin paralleled their ability to potentiate antithrombin III inhibition of thrombin. None of the compounds examined altered the ability of alpha 1-antitrypsin to inhibit activated coagulation factor X (Xa). 2 These results are consistent with the possibility that a direct polysaccharide-proteinase interaction may be involved in the sulphated polysaccharide-modulated inhibition of thrombin by antithrombin III.

Amides↗
PubMed1980

Sulphated glycosaminoglycans in regenerating rat liver.

The total weight percentage glycosaminoglycan content of rat liber was found to increase by 50% in the first 30 h after partial hepatectomy. The content returned to near normal by the third day, but then increased again to a second maximum at 5-6 days, only to gradually decline to normal by the ninth day, when regeneration was nearly complete. This biphasic pattern was most marked in the chondroitin sulphate A/C component, with a 6-fold increase by the sixth day. Dermatan sulphate showed the same temporal trend, whereas heparan sulphate remained relatively unaltered. No such changes were detected in the livers of rats subjected to sham operation. The possible molecular mechanisms underlying the apparent link between cellular glycosaminoglycan content and proliferative tendency are discussed.

Animals↗