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- Kihlberg, K., et al.
(author)
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Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B
- 2017
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In: Haemophilia. - : Wiley. - 1351-8216. ; 23:4, s. 620-627
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Journal article (peer-reviewed)abstract
- Introduction: Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in approximately one third of patients with non-severe haemophilia A. Whether assay discrepancy may also occur in patients with haemophilia B remains unknown. Aim: This study compared the results from the one-stage and the chromogenic assays in patients with haemophilia B. Methods: Plasma samples from patients with haemophilia B attending the haemophilia centre in Malmö, Sweden, were collected after a wash-out period of more than 7 days and analysed with both assays. Results: Fifty samples from 36 patients were analysed. No discrepancy was found in patients with severe haemophilia B. Among the 44 plasma samples from patients with non-severe disease, 15 showed a twofold or greater difference between the results of the two methods, with the chromogenic method presenting the higher value (mean FIX:Cone-stage 0.02 vs. FIX:Cchromo 0.06 IU mL-1). Of these 15 samples, 14 were from seven individuals from five families with the same mutated amino acid at the N-terminal cleaving site of the activation peptide (FIX: c.572G>A; p.Arg191His or FIX: c.571C>T; p.Arg191Cys). These mutations were not observed in any patients with non-discrepant results. The reported bleeding frequency for these patients was low and indicative of a mild bleeding phenotype. Conclusion: Our findings imply that assay discrepancy occurs for factor IX activity and that both type of assays are needed for a correct diagnosis and classification of haemophilia B. The underlying mechanism by which the mutation influences the assays remains to be determined.
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| 2. |
- Koppal, Sandeep, et al.
(author)
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Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis
- 2017
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In: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 78:1, s. 285-296
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Journal article (peer-reviewed)abstract
- Purpose: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. Methods: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60×0.60×0.70mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. Results: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64±0.2737% versus 9.294±0.1762% (mean±standard error of the mean [SEM]; P<0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81±1.276 s-1 versus 56.94±0.9095 s-1 (mean±SEM; P<0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2=0.92) as well as between cumulative R2* and IPH (R2=0.94). Conclusion: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH.
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| 4. |
- Over, Bjorn, et al.
(author)
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Structural and conformational determinants of macrocycle cell permeability
- 2016
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In: Nature Chemical Biology. - New York : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 12:12, s. 1065-1074
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Journal article (peer-reviewed)abstract
- Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 nonpeptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.
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