| 31. |
- Brilakis, Emmanouil S., et al.
(författare)
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Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery : Insights from the PLATelet inhibition and patient outcomes (PLATO) trial
- 2013
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 166:3, s. 474-480
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. Methods Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. Results Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P-interaction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P-interaction =.46) prior CABG. Conclusions Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.
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| 32. |
- Böhm, Johann, et al.
(författare)
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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.
- 2012
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 33:6, s. 949-59
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
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| 33. |
- Caridis, Konstantina-Anna, et al.
(författare)
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Simultaneous production of glucose oxidase and catalase by Alternaria alternata
- 1991
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Ingår i: Applied Microbiology and Biotechnology. - 0175-7598 .- 1432-0614. ; 34:6, s. 794-797
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Tidskriftsartikel (refereegranskat)abstract
- A number of factors affecting simultaneous production of cell-bound glucose oxidase and catalase by the fungus Alternaria alternata have been investigated. Consecutive optimization of the type and concentration of nitrogen and carbon source, the initial pH and growth temperature resulted in a simultaneous increase in glucose oxidase and catalase by 780% and 68% respectively. Two second-order equations, describing the combined effect of pH and temperature on the activity of each enzyme, revealed that glucose oxidase had its optima at pH 7.9 and 32.3°C and catalase at pH 8.5 and 18.1°C. Under certain growth conditions, yields as high as 23.5 and 18,100 units/g carbon source for glucose oxidase and catalase, respectively, were simultaneously obtained.
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| 34. |
- Christakopoulos, Paul, et al.
(författare)
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Direct conversion of sorghum carbohydrates to ethanol by a mixed microbial culture
- 1993
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Ingår i: Bioresource Technology. - 0960-8524 .- 1873-2976. ; 45:2, s. 89-92
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Tidskriftsartikel (refereegranskat)abstract
- The carbohydrates of sweet sorghum were directly converted to ethanol by a mixed culture of Fusarium oxysporum F3 and Saccharomyces cerevisiae 2541. A number of factors affecting this bioconversion was studied. Optimum ethanol yields of 33·2 g/100 g of total sorghum carbohydrates, corresponding to 10·3 g/100 g of fresh stalks, were obtained. These values represented 68·6% of the theoretical yield based on total polysaccharides and exceeded that based on oligosaccharides of sorghum by 53·7%. The results demonstrated that more than half of the sorghum polysaccharides were directly fermented to ethanol, thus making the process worthy of further investigation.
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| 35. |
- Christakopoulos, Paul, et al.
(författare)
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Enhancement of pH-stability of a low molecular mass endoglucanase from Fusarium oxysporum by protein pegylation
- 1998
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Ingår i: Carbohydrate Research. - 0008-6215 .- 1873-426X. ; 314:1-2, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- The stability of the low molecular mass endoglucanase (23.2 kDa) from Fusarium oxysporum at alkaline pH was enhanced by chemical modification. Two distinct types of amino acid-specific modifiers were used. The first, either cyanuric chloride activated polyethylene glycol (CC–PEG) or polyethylene glycol succinimidyl succinate active ester (SS–PEG), react (more or less specifically) with protein amino groups. The second type, maleimide polyethylene glycol (Mal–PEG), is specific for cysteinyl residues. The enzyme lost almost all of its activity when modified with CC–PEG, whereas no inactivation was observed with SS–PEG and Mal–PEG. The modified endoglucanase showed remarkably enhanced alkaline pH stability. When acting upon cello-oligosaccharides and 4-methylumbelliferyl cello-oligosaccharides, the enzyme preferentially cleaved the internal glycosidic bonds. The modified enzymes mediated a decrease in the viscosity of carboxymethyl cellulose (CMC) associated with the release of only small amounts of reducing sugar. Thus, the modified enzyme retains the endo character of the native enzyme
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| 36. |
- Christakopoulos, Paul, et al.
(författare)
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Optimization of β-glucosidase catalysed synthesis of trisaccharides from cellobiose and gentiobiose
- 1994
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Ingår i: Biotechnology letters. - 0141-5492 .- 1573-6776. ; 16:6, s. 587-592
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Tidskriftsartikel (refereegranskat)abstract
- Purified β-Glucosidase from Fusarium oxysporum catalysed the hydrolysis and transglycosylation reactions in the presence of cellobiose and gentiobiose. The product of the latter reaction was mainly a triose. The time of incubation, pH and substrate concentration for transglycosylation reaction were optimised. Under optimal conditions, the concentration of glucose and triose reached approximately 15–20 % of the initial substrate concentration. These results suggested that β-glucosidase from F.oxysporum is an ideal enzyme for the synthesis of triose in reasonable quantities.
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| 37. |
- Christakopoulos, Paul, et al.
(författare)
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Production and characterization of extracellular lipase from Calvatia gigantea
- 1992
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Ingår i: Applied Microbiology and Biotechnology. - 0175-7598 .- 1432-0614. ; 38:2, s. 194-197
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Tidskriftsartikel (refereegranskat)abstract
- A number of factors affecting production of extracellular lipase by the edible fungus Calvatia gigantea were investigated. Consecutive optimization of carbon and nitrogen sources, initial pH of culture medium and growth temperature resulted in an increase in lipase activity of 87%. Under optimum conditions, activities as high as 22.4 units ml−1 of culture medium were obtained, competing favourably with most activities reported for other lipase hyperproducing microorganisms. The enzyme was optimally active at pH 7.0 and 30°C and had, at optimum pH, half-lives of 75.7 and 22.9 min at 45 and 55°C. Both high activity and kinetic characteristics of the enzyme make this process worthy of further investigation.
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| 38. |
- Christakopoulos, Paul, et al.
(författare)
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Purification and characterisation of a major xylanase with cellulase and transferase activities from Fusarium oxysporum
- 1996
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 289, s. 91-104
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Tidskriftsartikel (refereegranskat)abstract
- A major xylanase from Fusarium oxysporum was purified to homogeneity by gel filtration, affinity, and ion-exchange chromatographies. It has a molecular mass of 60.2 kDa and pl of 6.6 and was optimally active at pH 7.4 and at 50 °C. The enzyme was stable over the pH range 5.8–8.2 at 40 °C for 24 h and lost 45% of its original activity at pH 9.0 under the identical conditions. The enzyme rapidly hydrolysed xylans from oat spelts (husks) and birchwood, but the activities on carboxymethylcellulose (CMC), filter paper, and Avicel were very low. Determination of kcat/Km revealed that the enzyme hydrolysed oat spelts and birchwood xylans, 15–30 times more efficiently than CMC. In a 24 h incubation, at pH 7.0 and 9.0, the enzyme hydrolysed oat spelts and birchwood xylans by 75 and 65%, respectively. However, at pH 7.0, the enzyme released almost equal amounts of xylose and xylobiose from both xylans, whereas at pH 9.0, the concentration of xylobiose was twice as muchi as that of xylose and xylotriose. Xylanase attacked preferentially the internal glycosidic bonds of xylo- and 4-methylumbelliferyl cello-oligosaccharides [MeUmb(Glc)n]. The enzyme catalysed transglycosylation reaction with xylotriose, xylotetraose, and xylopentaose as donors and 4-methylumbelliferyl β-d-glucoside (MeUmbGlc) as an acceptor.
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| 39. |
- Christakopoulos, Paul, et al.
(författare)
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Purification and Characterisation of an Extracellular β-Glucosidase with Transglycosylation and Exo-glucosidase Activities from Fusarium oxysporum
- 1994
-
Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 224:2, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- An extracellular β-glucosidase from Fusarium oxysporum was purified to homogeneity by gel-filtration and ion-exchange chromatographies. The enzyme, a monomeric protein of 110 kDa, was maximally active at pH 5.0–6.0 and at 60°C. It hydrolysed 1→4-linked aryl-β-glucosides and 1→4-linked, 1→3-linked and 1→6–linked β-glucosides. The apparent Km and kcat values for p -nitrophenyl β-d-glucopyranoside (4-NpGlcp) and cellobiose were 0.093 (Km), 1.07 mM (kcat) and 1802 (Km), 461.5 min-1 (kcat), respectively. Glucose and gluconolactone inhibited the enzyme competitively with Ki values of 2.05 mM and 3.03 μM, respectively. Alcohols activated the enzyme; butanol showed maximum effect (2.2-fold at 0.5 M) while methanol increased the activity by 1.4-fold at 1 M. The enzyme catalysed the synthesis of methylglucosides, ethylglucoside and propylglucosides, as well as trisaccharides in the presence of different alcohols and disaccharides, respectively. In addition, the enzyme hydrolysed the unsubstituted and methylumbelliferyl cello-oligosaccharides [MeUmb(Glc)n] but the rate of hydrolysis decreased with increasing chain length. Analysis of products released from MeUmb(Glc)n as a function of time revealed that the enzyme attacked these substrates in a stepwise manner and from both ends. Thus, β-glucosidase from F. oxysporum, with the above interesting properties, could be of commercial interest.
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| 40. |
- Christakopoulos, Paul, et al.
(författare)
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Purification and mode of action of an alkali-resistant endo-1,4-β-glucanase from Bacillus pumilus
- 1999
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Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861 .- 1096-0384. ; 364:1, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Alkaline endo-1,4-β-d-glucanase was secreted byBacillus pumilusgrown in submerged culture on a combination of oat spelt xylan and corn starch as carbon sources. The enzyme was purified to homogeneity by Sephacryl S-200 and Q-Sepharose column chromatography. The protein corresponded to molecular mass and pIvalues of 67 kDa and 3.7, respectively. The enzyme was optimally active at pH 7.0–8.0 and 60°C and retained 50% of its optimum activity at pH 12. The most notable characteristic of the endoglucanase was its high stability up to pH 12 for 20 h at 30°C. The enzyme hydrolyzed carboxymethylcellulose (CMC) and cello-oligosaccharides but was inactive on cellobiose, cellotriose, Avicel, xylan, 4-nitrophenyl-β-d-glucoside, 4-nitrophenyl-β-d-cellobioside, and 4-nitrophenyl-β-d-xyloside. Analysis of reaction mixtures by HPLC revealed that the enzyme produced almost exclusively cellotriose when acted on CMC and appeared to hydrolyze cello-oligosaccharides by successively releasing cellotriose. The use of 4-methylumbelliferyl cello-oligosaccharides and the determination of bond cleavage frequency revealed that the enzyme preferentially hydrolyzed the third glycosidic bond adjacent to the glycon. The enzyme mediated a decrease in the viscosity of CMC associated with a release of only small amounts of reducing sugar. The enzyme activity was not inhibited by metal ions, surfactants, and chelating agents used as components of laundry detergents.
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