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| 2. |
- Myhrinder, Anna Lanemo, 1975-, et al.
(författare)
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Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia
- 2013
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 54:8, s. 1769-1779
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.
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| 3. |
- Rosén, Anders, et al.
(författare)
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Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection
- 2012
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:1, s. 18-27
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.
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| 4. |
- Rundqvist, Håkan Claes, et al.
(författare)
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Influence of nutrient ingestion on amino acid transporters and protein synthesis in human skeletal muscle after sprint exercise
- 2017
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 123:6, s. 1501-1515
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Tidskriftsartikel (refereegranskat)abstract
- Nutrient ingestion is known to increase the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Less is known about the effect of nutrients on muscle protein synthesis following sprint exercise. At two occasions separated by one month, twelve healthy subjects performed three 30-s sprints with 20-min rest between bouts. In randomized order, they consumed a drink with essential amino acids and maltodextrin (nutrient) or flavored water (placebo). Muscle biopsies were obtained 80 and 200 min after the last sprint and blood samples were taken repeatedly during the experiment. Fractional synthetic rate (FSR) was measured by continuous infusion of L-[(2)H5]-phenylalanine up to 200 min postexercise. The mRNA and protein expression of SNAT2 were both 1.4-fold higher (P < 0.05) after nutrient intake compared to placebo at 200 min postexercise. Phosphorylated Akt, mTOR and p70S6k was 1.7- to 3.6-fold higher (P<0.01) 80 min after the last sprint with nutrient ingestion as compared to placebo. In addition, FSR was higher (P<0.05) with nutrients when plasma phenylalanine (FSRplasma) was used as a precursor, but not when intracellular phenylalanine (FSRmuscle) was used. Significant correlations were also found between FSRplasma on the one hand and plasma leucine and serum insulin on the other hand in the nutrient condition. The results show that nutrient ingestion induces the expression of the amino acid transporter SNAT2, stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis following sprint exercise.
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| 5. |
- Aasa, Ulrika, et al.
(författare)
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The Swedish physical activity and fitness cohort born in 1958 - dropout analysis and overview at 36-year follow-up
- 2017
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 27:4, s. 418-429
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Tidskriftsartikel (refereegranskat)abstract
- The main aim of the Swedish physical activity and fitness cohort study (SPAF-1958) was to describe physical fitness, physical activity, health, and lifestyle across part of the lifespan, and to assess the influences on these factors from the environment, personal factors, and genetics. There is inevitable dropout from longitudinal studies, and it may be systematic. The aim of this first paper of the second follow-up of SPAF-1958 was to provide a dropout analysis to consider to what extent the participants, at 52 years of age, remain a representative sample of the original adolescent study population. Additional aims were to provide an overview of the study protocol and the ongoing study population. Ongoing study participants in SPAF born in 1958 were, at the second follow-up at the age of 52, still representative of the study cohort in terms of sex, adolescent geographical area, upper secondary school program, adolescent body composition, muscular strength, and muscular endurance. However, a higher physical activity and, among women, a higher aerobic capacity in adolescence decreased the risk for dropout. It is important when interpreting results from longitudinal studies to adjust for the systematic dropout that could bias the conclusions drawn from the results.
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| 6. |
- Ahlsson, Anders, 1962-, et al.
(författare)
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Adenosine in cold blood cardioplegia : a placebo-controlled study
- 2012
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - Oxford, United Kingdom : Oxford University Press. - 1569-9293 .- 1569-9285. ; 14:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Adenosine as an additive in blood cardioplegia is cardioprotective in animal studies, but its clinical role in myocardial protection remains controversial. The aim of this study was to investigate whether the addition of adenosine in continuous cold blood cardioplegia would enhance myocardial protection.Methods: In a prospective double-blind study comparing adenosine 400 μmol l(-1) to placebo in continuous cold blood cardioplegia, 80 patients undergoing isolated aortic valve replacement were randomized into four groups: antegrade cardioplegia with adenosine (n = 19), antegrade cardioplegia with placebo (n = 21), retrograde cardioplegia with adenosine (n = 21) and retrograde cardioplegia with placebo (n = 19). Myocardial arteriovenous differences in oxygen and lactate were measured before, during and after aortic occlusion. Myocardial concentrations of adenine nucleotides and lactate were determined from left ventricular biopsies obtained before aortic occlusion, after bolus cardioplegia, at 60 min of aortic occlusion and at 20 min after aortic occlusion. Plasma creatine kinase (CK-MB) and troponin T were measured at 1, 3, 6, 9, 12 and 24 h after aortic occlusion. Haemodynamic profiles were obtained before surgery and 1, 8 and 24 h after cardiopulmonary bypass. Repeated-measures analysis of variance was used for significance testing.Results: Adenosine had no effects on myocardial metabolism of oxygen, lactate and adenine nucleotides, postoperative enzyme release or haemodynamic performance. When compared with the antegrade groups, the retrograde groups showed higher myocardial oxygen uptake (17.3 ± 11.4 versus 2.5 ± 3.6 ml l(-1) at 60 min of aortic occlusion, P < 0.001) and lactate accumulation (43.1 ± 20.7 versus 36.3 ± 23.0 µmol g(-1) at 60 min of aortic occlusion, P = 0.052) in the myocardium during aortic occlusion, and lower postoperative left ventricular stroke work index (27.2 ± 8.4 versus 30.1 ± 7.9 g m m(-2), P = 0.034).Conclusions: Adenosine 400 μmol l(-1) in cold blood cardioplegia showed no cardioprotective effects on the parameters studied. Myocardial ischaemia was more pronounced in patients receiving retrograde cardioplegia.
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| 7. |
- Bergenfelz, Anders, et al.
(författare)
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Impact of modern techniques on short-term outcome after surgery for primary hyperparathyroidism: a multicenter study comprising 2,708 patients.
- 2009
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Ingår i: Langenbeck's archives of surgery / Deutsche Gesellschaft für Chirurgie. - : Springer Science and Business Media LLC. - 1435-2451 .- 1435-2443. ; 394:5, s. 851-60
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Tidskriftsartikel (refereegranskat)abstract
- Preoperative localization procedures and the use of intraoperative parathyroidism (iOPTH) have led to a shift of paradigm from bilateral neck exploration to focused parathyroidectomy in primary hyperparathyroidism (pHPT). However, only a small number of randomized trials from specialized centers have been published. The main purpose of the study was to analyze the impact of localization procedures and iOPTH on short-term outcome after pHPT surgery in a multi-institutional setting.
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| 8. |
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| 9. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 10. |
- Borggren, Marie, et al.
(författare)
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Increased Sensitivity to Broadly Neutralizing Antibodies of End-Stage Disease R5 HIV-1 Correlates with Evolution in Env Glycosylation and Charge.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Induction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is the objective of most antibody-based HIV-1 vaccine undertakings. However, despite the relative conserved nature of epitopes targeted by these antibodies, mechanisms underlying the sensitivity of circulating HIV-1 variants to broadly neutralizing antibodies are not fully understood. Here we have studied sensitivity to broadly neutralizing antibodies of HIV-1 variants that emerge during disease progression in relation to molecular alterations in the viral envelope glycoproteins (Env), using a panel of primary R5 HIV-1 isolates sequentially obtained before and after AIDS onset.
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