| 11. |
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| 12. |
- Gneiss, C, et al.
(författare)
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Comparative study of four different assays for the detection of binding antibodies against interferon-beta
- 2008
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 14:6, s. 830-836
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Tidskriftsartikel (refereegranskat)abstract
- Background Binding antibodies (BAB) against interferon-β (IFNβ) are often determined as screening assays before performing an expensive and elaborate neutralizing antibody (NAB) test. Methods In this study, we compared four BAB tests, a western blot (WB), a direct binding enzyme-linked immunosorbent assay (ELISA) (dELISA), a capture ELISA (cELISA), and a commercial enzyme immuno-assay (EIA) in 325 multiple sclerosis patients with and without neutralizing antibodies to evaluate the sensitivity and specificity to detect NAB by receiver operating characteristics analysis. Results The area under the curve (AUC) values were 0.907 for the dELISA, 0.925 for the cELISA, and 0.776 for the EIA ( P < 0.0001 for all). At a sensitivity of 95%, the specificity was approximately 30% in the dELISA, 55% in the cELISA, and 13% in the EIA. The WB as a qualitative BAB detection method had a given sensitivity of 97% and a specificity of 55%. There was a strong and significant correlation between high NAB titers (>500 neutralizing units [NU]) and titers obtained by all quantitative BAB assays. However, low to medium NAB titers (20–500 NU) did not significantly correlate with BAB titers. Conclusion We conclude that the cELISA seems to be most suitable for NAB screening, but BAB titers cannot reliably predict NAB titers.
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| 13. |
- Görgens, Johann F, et al.
(författare)
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Amino acid supplementation, controlled oxygen limitation and sequential double induction improves heterologous xylanase production by Pichia stipitis
- 2005
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Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1364 .- 1567-1356. ; 5:6-7, s. 677-683
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Tidskriftsartikel (refereegranskat)abstract
- Heterologous endo-beta-1,4-xylanase was produced by Pichia stipitis under control of the hypoxia-inducible PsADH2-promoter in a high-cell-clensity culture. After promoter induction by a shift to oxygen limitation, different aeration rates (oxygen transfer rates) were applied while maintaining oxygen-limitation. Initially, enzyme production was higher in oxygen-limited cultures with high rates of oxygen transfer, although the maximum xylanase activity was not significantly influenced. Amino acid supplementation increased the production of the heterologous endo-beta-1,4-xylanase significantly in highly aerated oxygen-limited cultures, until glucose was depleted. A slight second induction of the promoter was observed in all cultures after the glucose had been consumed. The second induction was most obvious in amino acid-supplemented cultures with higher oxygen transfer rates during oxygen limitation. When such oxygen-limited cultures were shifted back to fully aerobic conditions, a significant re-induction of heterologous endo-beta-1,4-xylanase production was observed. Re-induction was accompanied by ethanol consumption. A similar protein production pattern was observed when cultures were first grown on ethanol as sole carbon source and subsequently glucose and oxygen limitation were applied. Thus, we present the first expression system in yeast with a sequential double-inducible promoter. (c) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.
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| 14. |
- Görgens, Johann F, et al.
(författare)
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Amino acid supplementation improves heterologous protein production by Saccharomyces cerevisiae in defined medium
- 2005
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 67:5, s. 684-691
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Tidskriftsartikel (refereegranskat)abstract
- Supplementation of a chemically defined medium with amino acids or succinate to improve heterologous xylanase production by a prototrophic Saccharomyces cerevisiae transformant was investigated. The corresponding xylanase production during growth on ethanol in batch culture and in glucose-limited chemostat culture were quantified, as the native ADH2 promoter regulating xylanase expression was derepressed under these conditions. The addition of a balanced mixture of the preferred amino acids, Ala, Arg, Asn, Glu, Gln and Gly, improved both biomass and xylanase production, whereas several other individual amino acids inhibited biomass and/or xylanase production. Heterologous protein production by the recombinant yeast was also improved by supplementing the medium with succinate. The production of heterologous xylanase during growth on ethanol or glucose could thus be improved by supplementing metabolic precursors in the carbon- or nitrogen-metabolism.
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| 15. |
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| 16. |
- Neubauer, Bernd A., et al.
(författare)
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KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes
- 2008
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 71:3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore the involvement of M-type potassium channels KCNQ2, Q3, and Q5 in the pathogenesis of common idiopathic epilepsies. METHODS: Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case-control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls. RESULTS: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004). CONCLUSION: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.
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| 17. |
- Ringden, O, et al.
(författare)
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The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 113:13, s. 3110-3118
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Tidskriftsartikel (refereegranskat)abstract
- Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]–matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P < .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.
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| 18. |
- Sjostrand, F., et al.
(författare)
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The osmotic link between hypoglycaemia and hypovolaemia
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68:2, s. 117-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective . Hypoglycaemia is regularly accompanied by hypovolaemia. To suggest a mechanism for this phenomenon, we reviewed data from eight studies conducted by our group and examined the circumstances under which rebound hypoglycaemia develops after intravenous infusion of glucose solutions. Material and methods. Forty healthy volunteers and 40 patients received a total of 122 infusions of glucose solutions at different rates, volumes and concentrations. Plasma glucose and the haemodilution were measured repeatedly during and for at least 2 h after the infusions ended. Glucose kinetics was calculated using a one-compartment turnover model and the plasma volume expansion was estimated from changes in Hb. Results . A strong linear correlation was found between the glucose level and the plasma volume expansion in all series of experiments (p<0.001). After infusion, there was a risk of hypoglycaemia and hypovolaemia developing in healthy volunteers with a high glucose clearance and when infusing glucose solutions of higher concentrations than 2.5 %. Few and mild hypoglycaemic events occurred in patients with insulin resistance, such as in diabetics and in those undergoing surgery. The immediate linear relationship between hypoglycaemia and hypovolaemia suggests an osmotic link between the two parameters. More specifically, infused fluid accompanies glucose during uptake into the cells, while volume expansion by the same fluid has already elicited an effective diuretic response. Conclusion . Hypovolaemia is a consequence of hypoglycaemia after intravenous infusion of glucose solution and is caused by the osmotic translocation of fluid from the extracellular to the intracellular fluid space that occurs despite effective renal elimination.
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| 19. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 20. |
- Sominanda, A, et al.
(författare)
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Interferon beta preparations for the treatment of multiple sclerosis patients differ in neutralizing antibody seroprevalence and immunogenicity
- 2007
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:2, s. 208-214
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Tidskriftsartikel (refereegranskat)abstract
- Development of neutralizing antibodies (NAbs) reduces the clinical efficacy of interferon beta (IFNβ) treatment in multiple sclerosis (MS) patients. The aim of this study was to evaluate NAb seroprevalence (frequency of patients with NAbs) and immunogenicity (titer levels) of IFNβ preparations in a clinical setting. We analysed 1115 consecutive MS patients, treated with one of the three available IFNβ preparations, for an average of 40 months (1 – 120 months), for the presence of NAbs with the MxA protein induction assay. Overall, 32% of patients were positive for NAbs with neutralizing titers above 10. The frequency of NAbs, ie, the seroprevalence, was 13% in Avonex-treated patients, 43% for Betaferon, 39% for Rebif22 and 30% for Rebif44. In addition, the potential to induce high titer levels, ie, the immunogenicity, was observed to differ between preparations. Avonex, showing the lowest seroprevalence, also showed low immunogenicity and typically induced low titers. Betaferon, showing the highest seroprevalence when inducing NAbs, induced lower titers compared to Rebif22 and Rebif44. Treatment duration over five years only marginally correlated with decreased seroprevalence and titer levels. In conclusion, NAbs to IFNβ are common in a clinical setting and the IFNβ preparations differ not only in NAb seroprevalence, but also in immunogenicity. Multiple Sclerosis 2007; 13: 208–214. http://msj.sagepub.com
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