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| 2. |
- Dumanski, Jan P., et al.
(författare)
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Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 98:6, s. 1208-1219
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Tidskriftsartikel (refereegranskat)abstract
- Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.
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| 3. |
- Egge-Jacobsen, Wolfgang, et al.
(författare)
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O-Linked glycosylation of the PilA pilin protein of francisella tularensis : identification of the endogenous protein-targeting oligosaccharyltransferase and characterization of the native oligosaccharide
- 2011
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Ingår i: Journal of Bacteriology. - Baltimore : Williams & Wilkins. - 0021-9193 .- 1098-5530. ; 193:19, s. 5487-5497
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Tidskriftsartikel (refereegranskat)abstract
- Findings from a number of studies suggest that the PilA pilin proteins may play an important role in the pathogenesis of disease caused by species within the genus Francisella. As such, a thorough understanding of PilA structure and chemistry is warranted. Here, we definitively identified the PglA protein-targeting oligosaccharyltransferase by virtue of its necessity for PilA glycosylation in Francisella tularensis and its sufficiency for PilA glycosylation in Escherichia coli. In addition, we used mass spectrometry to examine PilA affinity purified from Francisella tularensis subsp. tularensis and F. tularensis subsp. holarctica and demonstrated that the protein undergoes multisite, O-linked glycosylation with a pentasaccharide of the structure HexNac-HexHex-HexNac-HexNac. Further analyses revealed microheterogeneity related to forms of the pentasaccharide carrying unusual moieties linked to the distal sugar via a phosphate bridge. Type A and type B strains of Francisella subspecies thus express an O-linked protein glycosylation system utilizing core biosynthetic and assembly pathways conserved in other members of the proteobacteria. As PglA appears to be highly conserved in Francisella species, O-linked protein glycosylation may be a feature common to members of this genus.
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| 4. |
- Forsberg, Lena M, et al.
(författare)
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Differences in recovery of left and right ventricular function following aortic valve interventions : a longitudinal echocardiographic study in patients undergoing surgical, transapical or transfemoral aortic valve implantation
- 2013
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 82:6, s. 1004-1014
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo evaluate longitudinal left and right ventricular function (LVF and RVF) after transcatheter aortic valve implantation (TAVI) as compared to surgical aortic valve replacement (SAVR) and LVF and RVF after TAVI by the transfemoral (TF) or transapical (TA) approach.BackgroundKnowledge about differences in recovery of LVF and RVF after TAVI and SAVR is scarce.MethodsSixty patients (age 81 ± 7 years, logistic EuroSCORE 16 ± 10%), undergoing TAVI (TF: n = 35 and TA: n = 25), were examined by echocardiography including atrioventricular plane displacement (AVPD) and peak systolic velocities (PSV) by tissue Doppler at basal RV free wall, LV lateral wall and septum preprocedurally, 7 weeks and 6 months postprocedurally. Twenty-seven SAVR patients were matched to 27 TAVI patients by age, gender and LVF.ResultsEarly postintervention, TAVI patients had improved longitudinal LVF. However, when analyzed separately, only TF, but not TA patients, had improved LV lateral and septal AVPD and PSV (all P ≤ 0.01). All TAVI patients, as well as the TF and TA group had unchanged longitudinal LVF between the early and late follow-ups (all P > 0.05). The SAVR group had higher septal LVF than the matched TAVI group preprocedurally, while postoperatively this difference was diminished. Longitudinal RVF was better in the TF group than in the TA group pre- and postprocedurally. Although the SAVR group had superior longitudinal RVF preoperatively, this was inferior to TAVI postoperatively.Conclusions Postprocedural longitudinal LVF and RVF in patients undergoing TF-TAVI, TA-TAVI, or SAVR differ considerably. Preservation of longitudinal RVF after TAVI might influence the selection of aortic valve intervention in the future.
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| 5. |
- Forsberg, Lena M, et al.
(författare)
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Exercise echocardiography predicts postoperative left ventricular remodeling in aortic regurgitation
- 2014
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Ingår i: SCANDINAVIAN CARDIOVASCULAR JOURNAL. - : Informa Healthcare. - 1401-7431 .- 1651-2006. ; 48:1, s. 4-12
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Tidskriftsartikel (refereegranskat)abstract
- Objective. We aimed to investigate if preoperative left ventricular (LV) function assessed by exercise echocardiography could predict late postoperative LV function in aortic regurgitation (AR) patients and to evaluate how LV long-axis function is affected late after aortic valve surgery. Design. A total of 21 male chronic AR patients, aged 49 (12) years, accepted for surgery were examined preoperatively, 6 months-, and 4 years postoperatively, at rest and during exercise. Besides conventional echocardiographic parameters, the atrioventricular plane displacement (AVPD) by M-mode and peak systolic velocity (s) in the basal LV by color tissue Doppler were measured. Results. Preoperatively EFrest and EFexercise, were 55(7)% and 54(9)%, respectively, and Delta EF 0(8)%. LV dimensions and volumes indexed to BSA had decreased at the 6-month follow-up and were stable at late follow-up. s(rest), s(exercise), AVPD(rest), and AVPD(exercise) were unchanged at both the postoperative examinations (all P >= 0.05). Preoperative EFexercise and AVPD(exercise) showed inverse correlation to late postoperative indexed LV enddiastolic volume (r = -0.68, p < 0.004 and r = -0.86, P < 0.001) and indexed LV endsystolic volume (r = -0.68, P = 0.004 and r = -0.81, P < 0.001), while there was no correlation to preoperative EFrest and AVPD(rest) (all r < 0.2). Conclusions. Preoperative exercise echocardiography can detect AR patients with suboptimal LV remodeling late postoperatively.
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| 6. |
- Forsberg, Lena M, et al.
(författare)
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Left and right ventricular function in aortic stenosis patients 8 weeks post-transcatheter aortic valve implantation or surgical aortic valve replacement
- 2011
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Ingår i: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; 12:8, s. 603-611
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Tidskriftsartikel (refereegranskat)abstract
- Aims Knowledge of longitudinal left and right ventricular (LV and RV) function after transcatheter aortic valve implantation (TAVI) is scarce. We hypothesized that the longitudinal systolic biventricular function in aortic stenosis (AS) patients is affected differently by TAVI and surgical aortic valve replacement (SAVR). less thanbrgreater than less thanbrgreater thanMethods and results Thirty-three AS patients (all-TAVI group, age 81 +/- 9 years, 18 female), with EuroSCORE 18 +/- 9%, were accepted for TAVI. Seventeen of these patients were matched (by gender, age, and LV function) to 17 patients undergoing SAVR. Conventional echocardiographic parameters, systolic atrioventricular plane displacement (AVPD) at standard sites and peak systolic velocity (PSV) by pulsed tissue Doppler at basal RV free wall, LV lateral wall, and septum were studied before and 8 weeks after the procedure. Procedural success was 100%, and 30-day mortality 9%. In all TAVI patients, AVPD(lateral), PSV(lateral), AVPD(septal), and PSV(septal) increased (P andlt; 0.001, 0.003, 0.006 and 0.002). When studying the matched patients postoperatively, both the SAVR and TAVI patients had increased PSV(lateral) and AVPD(lateral) (SAVR: P = 0.03 and P = 0.04, TAVI: P = 0.04 and P = 0.01). The PSV(RV) increased in the all-TAVI group (P = 0.007), while the AVPD(RV) was unchanged. SAVR patients had decreased AVPD(RV) (P = 0.001) and PSV(RV) (P = 0.004), while the matched TAVI patients had unchanged RV function parameters. less thanbrgreater than less thanbrgreater thanConclusion An improvement in regional longitudinal LV function in the septal and lateral wall could be seen after TAVI. Among the matched patients, both the TAVI and SAVR patients seemed to improve LV function in the lateral wall. RV systolic function increased in TAVI patients, but was impaired in the matched SAVR group at the 8-week follow-up.
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| 7. |
- Schmidt, Linnéa, et al.
(författare)
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Case-specific potentiation of glioblastoma drugs by pterostilbene
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 73200-73215
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.
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| 8. |
- Tijani, Muyideen Kolapo, et al.
(författare)
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How to Detect Antibodies Against Babesia divergens in Human Blood Samples
- 2024
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Ingår i: Open Forum Infectious Diseases. - : OXFORD UNIV PRESS INC. - 2328-8957. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Background. Today only indirect fluorescent antibody assays (IFAs) are commercially available to detect antibodies against Babesia divergens in humans. IFA is subjective and requires highly experienced staff. We have therefore developed an enzyme-linked immunosorbent assay (ELISA)-based method for measuring anti-B. divergens immunoglobulin G antibodies in human blood samples. Methods. Crude merozoite extract from in vitro cultures of a new B. divergens isolate was used in ELISA to detect antibodies in different sets of samples: Borrelia burgdorferi-positive samples, healthy individuals, tick-bitten individuals including follow-up samples 3 months later, positive control samples from patients with an active Babesia infection, and samples from malaria-endemic regions. As a reference, IFA was used to detect antibodies in the tick-bitten samples. Western blot was used to evaluate reactions against specific bands in extracts with/without parasites. Results. Using IFA as the reference method, the sensitivity and specificity of the ELISA were 86% (12/14) and 100% (52/52). There was a very high correlation (r = -0.84; P = .0004) between IFA dilution factors and ELISA absorbances among the samples classified as positive. Five percent of the B. burgdorferi-positive samples were judged as weakly positive and 5% as strongly positive in our ELISA. Western blot showed that the immunodominant antigens (∼120 kDa) were from merozoites and not from erythrocytes. Conclusions. This ELISA can detect antibodies directed against B. divergens, and it can be a useful and easy assay to handle compared with IFA. The ELISA can also measure high and low levels of antibodies, which could give insight into the recency of a B. divergens infection.
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| 9. |
- Åström, E., et al.
(författare)
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Precision measurements of linear scattering density using muon tomography
- 2016
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing. - 1748-0221. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that muon tomography can be used to precisely measure the properties of various materials. The materials which have been considered have been extracted from an experimental blast furnace, including carbon (coke) and iron oxides, for which measurements of the linear scattering density relative to the mass density have been performed with an absolute precision of 10%. We report the procedures that are used in order to obtain such precision, and a discussion is presented to address the expected performance of the technique when applied to heavier materials. The results we obtain do not depend on the specific type of material considered and therefore they can be extended to any application.
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