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- Kohl, S, et al.
(författare)
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CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
- 2005
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 13:3, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
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- Hrmova, Maria, et al.
(författare)
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Substrate specificity and catalytic mechanism of a xyloglucan xyloglucosyl transferase HvXET6 from barley (Hordeum vulgare L.)
- 2009
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 276:2, s. 437-456
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Tidskriftsartikel (refereegranskat)abstract
- A family 16 glycoside hydrolase, xyloglucan xyloglucosyl transferase (EC 2.4.1.207), also known as xyloglucan endotransglycosylase (XET), and designated isoenzyme HvXET6, was purified approximately 400-fold from extracts of young barley seedlings. The complete amino acid sequence of HvXET6 was deduced from the nucleotide sequence of a near full-length cDNA, in combination with tryptic peptide mapping. An additional five to six isoforms or post-translationally modified XET enzymes were detected in crude seedling extracts of barley. The HvXET6 isoenzyme was expressed in Pichia pastoris, characterized and compared with the previously purified native HvXET5 isoform. Barley HvXET6 has a similar apparent molecular mass of 33-35 kDa to the previously purified HvXET5 isoenzyme, but the two isoenzymes differ in their isoelectric points, pH optima, kinetic properties and substrate specificities. The HvXET6 isoenzyme catalyses transfer reactions between xyloglucans and soluble cellulosic substrates, using oligo-xyloglucosides as acceptors, but at rates that are significantly different from those observed for HvXET5. No hydrolytic activity could be detected with either isoenzyme. Comparisons of the reaction rates using xyloglucan or hydroxyethyl cellulose as donors and a series of cellodextrins as acceptors indicated that the acceptor site of HvXET can accommodate five glucosyl residues. Molecular modelling supported this conclusion and further confirmed the ability of the enzyme's active site to accommodate xyloglucan and cellulosic substrates. The two HvXETs followed a ping-pong (Bi, Bi) rather than a sequential reaction mechanism.
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- Vánky, Farkas B., et al.
(författare)
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Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?
- 2006
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 25:6, s. 913-922
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims Glutamate plays an important role for myocardial metabolism in association with ischaemia. Patients with coronary artery disease characteristically demonstrate increased uptake of glutamate. Improved recovery of myocardial metabolism and haemodynamic state after coronary surgery has been reported in patients treated with glutamate infusion. However, the effect of glutamate has not been studied after other cardiac surgical procedures. In addition, the effects of glutamate on peripheral tissue metabolism remain to be described. Methods Twenty patients undergoing surgery for aortic stenosis were studied after randomisation to blinded infusion of glutamate or saline during 1 h immediately after skin closure. Myocardial and leg tissue metabolism were assessed with organ balance techniques. Results Postoperative glutamate infusion induced a marked increase in myocardial and leg tissue uptake of glutamate. This was associated with a significant uptake of lactate in the heart. The negative arterial–venous differences of amino acids and free fatty acids across the leg were significantly smaller in the glutamate group. Haemodynamic state remained stable and did not differ between groups. Conclusion The heart and peripheral tissues consumed the exogenously administered glutamate after surgery for aortic stenosis. Potentially favourable effects of glutamate on myocardial and peripheral tissue metabolism are suggested.
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- Vanky, Farkas B, et al.
(författare)
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Long-Term Consequences of Postoperative Heart Failure After Surgery for Aortic Stenosis Compared With Coronary Surgery
- 2007
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 83:6, s. 2036-2043
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although postoperative heart failure is a major determinant of operative mortality in cardiac surgery it has received little attention in the literature, and long-term consequences remain to be addressed. Therefore, the impact of postoperative heart failure on long-term survival in relation to other risk factors was studied. Methods: All patients undergoing aortic valve replacement (AVR) for aortic stenosis from 1995 through 2000 in the southeast region of Sweden (n = 398) were compared with a cohort, matched for age and sex, undergoing coronary artery bypass grafting (CABG [n = 398]). Risk factors for 5-year mortality were analyzed. Results: Forty-five AVR and 47 CABG patients required treatment for postoperative heart failure. Thirty-day, 1-year, and 5-year mortality in patients with and without postoperative heart failure after AVR were 6.7% versus 1.4% (p = 0.05), 8.9% versus 4.0% (p = 0.13), and 42.2% versus 14.2% (p < 0.0001) respectively. Corresponding results in the CABG group were 21.3% versus 1.1% (p < 0.0001), 25.5% versus 3.1% (p < 0.0001), and 36.2% versus 11.1% (p = 0.0015). Postoperative heart failure, preoperative renal dysfunction, procedure-associated stroke, body mass index less than 19 kg/m2, older age, preoperative atrial fibrillation, and preoperative anemia turned out as independent risk factors for 5-year mortality after AVR. In the CABG group, postoperative heart failure, diabetes mellitus, older age, and procedure-associated stroke emerged as independent risk factor for 5-year mortality. Conclusions: Postoperative heart failure was associated with high early mortality after CABG whereas the grave consequences of postoperative heart failure after AVR for aortic stenosis became evident only with time. © 2007 The Society of Thoracic Surgeons.
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- Vánky, Farkas B., et al.
(författare)
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Myocardial metabolism before and after valve replacement for aortic stenosis
- 2006
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Ingår i: Journal of Cardiovascular Surgery. - 0021-9509 .- 1827-191X. ; 47:3, s. 305-313
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Post ischemic disturbances of myocardial metabolism that may contribute to postoperative heart failure and are accessible to metabolic treatment have been identified early after coronary surgery. Knowledge derived from these studies may not be applicable to other patient groups. Therefore we studied myocardial energy metabolism in patients operated for isolated aortic stenosis. METHODS: Twenty patients undergoing isolated aortic valve replacement (AVR) because of aortic stenosis without significant regurgitation were studied before and immediately after surgery. Myocardial uptake of oxygen and energy substrates was assessed with coronary sinus catheter technique. RESULTS: Free fatty acids (FFA) were the main source of myocardial energy before and after AVR. A significant uptake of lactate was only recorded preoperatively. A significant uptake of glutamate of the same magnitude as previously described in coronary patients was found pre- and postoperatively. Postoperatively a relative decrease of myocardial oxygen extraction ratio (P<0.001) and oxygen consumption (P=0.14) by approximately 20% was observed. CONCLUSION: Preoperative and postoperative metabolic adaptation with substantial uptake of glutamate, previously claimed to be due to chronic or repetitive ischemia, was demonstrated. The results indicate that oxidative metabolism had not fully recovered when the procedure was completed. However, the potentially unfavorable postoperative metabolic state with predominant reliance on FFA as energy source was out-balanced by the unloading effect of AVR with a reduction in myocardial oxygen extraction.
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| 9. |
- Vánky, Farkas B., et al.
(författare)
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Risk factors for postoperative heart failure in patients operated on for aortic stenosis
- 2006
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Ingår i: The Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975. ; 81:4, s. 1297-1304
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Tidskriftsartikel (refereegranskat)abstract
- Background Risk factors for postoperative heart failure (PHF) have not been specifically studied in valve surgery although it has been acknowledged that patient variables may have a more profound influence on postoperative outcome than valve-related factors. Methods All patients undergoing isolated aortic valve replacement for aortic stenosis from January 1995 to December 2000 in the southeast region of Sweden were studied (n = 398). Forty-five patients with aortic valve replacement required treatment for PHF. Univariate and multivariate logistic regression analysis was carried out to identify risk factors for PHF. Results Thirty-day mortality was 6.7% versus 1.4% for patients with and without PHF, respectively (p = 0.05). With regard to clinical presentation of aortic stenosis, angina was associated with reduced risk, whereas history of congestive heart failure increased the risk for PHF. Five preoperative (hypertension, history of congestive heart failure, severe systolic left ventricular dysfunction, pulmonary hypertension, preoperative hemodynamic instability) and two intraoperative (aortic cross-clamp time, intraoperative myocardial infarction) variables were identified as independent risk factors for PHF. Patient–prosthesis mismatch did not influence the risk of PHF significantly. Conclusions Postoperative heart failure was associated with a marked increase in postoperative mortality and morbidity. Risk factors for PHF were variables indicating preexisting myocardial dysfunction, increased right or left ventricular afterload, and intraoperative myocardial injury. Our results highlight issues concerning cross-clamp time and myocardial protection, particularly for patients with preoperatively compromised myocardial function. Asymptomatic patients with significant aortic stenosis should be considered for surgery before substantial echocardiographic evidence of left ventricular dysfunction or increased pulmonary artery pressure develops.
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