| 1. |
- Mustjoki, S, et al.
(författare)
-
Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients
- 2013
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 27:7, s. 1520-1526
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P = 0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P = 0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients.
|
|
| 2. |
- Ballantyne, Kaye N., et al.
(författare)
-
Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
-
Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
-
Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
|
|
| 3. |
- Björkman, Berit, et al.
(författare)
-
Plausible scenarios for the radiography profession in Sweden in 2025
- 2017
-
Ingår i: Radiography. - : Elsevier. - 1078-8174 .- 1532-2831. ; 23:4, s. 314-320
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Radiography is a healthcare speciality with many technical challenges. Advances in engineering and information technology applications may continue to drive and be driven by radiographers. The world of diagnostic imaging is changing rapidly and radiographers must be proactive in order to survive. To ensure sustainable development, organisations have to identify future opportunities and threats in a timely manner and incorporate them into their strategic planning. Hence, the aim of this study was to analyse and describe plausible scenarios for the radiography profession in 2025.Method: The study has a qualitative design with an inductive approach based on focus group interviews. The interviews were inspired by the Scenario-Planning method.Results: Of the seven trends identified in a previous study, the radiographers considered two as the most uncertain scenarios that would have the greatest impact on the profession should they occur. These trends, labelled "Access to career advancement" and "A sufficient number of radiographers", were inserted into the scenario cross. The resulting four plausible future scenarios were: The happy radiographer, the specialist radiographer, the dying profession and the assembly line.Conclusion: It is suggested that "The dying profession" scenario could probably be turned in the opposite direction by facilitating career development opportunities for radiographers within the profession. Changing the direction would probably lead to a profession composed of "happy radiographers" who are specialists, proud of their profession and competent to carry out advanced tasks, in contrast to being solely occupied by "the assembly line".
|
|
| 4. |
- Izadi, Arman, et al.
(författare)
-
Subclass-switched anti-Spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization
- 2023
-
Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 120:15
-
Tidskriftsartikel (refereegranskat)abstract
- Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and complement receptor-mediated phagocytosis, superior to even the most potent single IgG3 mAb when compared at equivalent concentrations. Finally, in an in vivo model, we show that opsonic mAbs of both subclasses can be protective against a SARS-CoV-2 infection, despite the antibodies being nonneutralizing. Our results suggest that opsonic IgG3 oligoclonal cocktails are a promising idea to explore for therapy against SARS-CoV-2, its emerging variants, and potentially other viruses.
|
|
| 5. |
- Lundman, Berit, et al.
(författare)
-
Sense of coherence (SOC) related to health and mortality among the very old : The Umeå 85+ study
- 2010
-
Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 51, s. 329-332
-
Tidskriftsartikel (refereegranskat)abstract
- We describe associations between sense of coherence (SOC) and sense of well-being, diseases, physical function and the predictive value of SOC on depression and mortality. The study included 190 participants, aged 85-103 years. Linear correlation analysis was used for relationships between SOC scores and continuous variables. The effects of SOC score on 1- and 4-year mortality, as well as on depression at the 5-year follow-up, were investigated using Cox regression models. The mean SOC score was 71.8+/-10.2 (+/-S.D.). SOC score was positively related to well-being (p
|
|
| 6. |
- Viglund, Kerstin, et al.
(författare)
-
Relationships among inner strength, health and function, well-being, and negative life events in old people : a longitudinal study
- 2022
-
Ingår i: European Journal of Ageing. - : Springer. - 1613-9372 .- 1613-9380. ; 19, s. 545-554
-
Tidskriftsartikel (refereegranskat)abstract
- Inner strength is a conceptualization of a human resource that is generally considered beneficial for health and well-being. Previously, it has been examined in qualitative and cross-sectional studies, but longitudinal data are lacking. The aim of this study was to examine how inner strength, health and function, well-being, and negative life events, namely crises and diseases, affect each other over time in old people. A longitudinal two-wave design was used with data from 2010 and 2016. A total of 4023 participants, living in Finland and Sweden, and born in 1930, 1935, 1940, or 1945 were included. Data were collected using the Inner Strength Scale, the Life Orientation Scale, a short version of the Geriatric Depression Scale, one item from the SF36, and five items from the Katz ADL-index. Structural equation modeling was used to test for cross-lagged effects. Crises and diseases were found to be a positive predictor of inner strength, a negative predictor of well-being, and to have no significant effect on health and function over time. Inner strength and well-being had a reciprocal positive relationship, and health and function was a positive predictor inner strength. The study expands findings by providing perspectives of inner strength across time indicating that inner strength in old people increases when they have to face a disease or crisis. From a health perspective, the present findings reinforce the importance of healthcare professionals' awareness and knowledge of the construct of inner strength.
|
|
| 7. |
- Porsch, Helena, et al.
(författare)
-
Platelet-derived Growth Factor beta-Receptor, Transforming Growth Factor beta Type I Receptor, and CD44 Protein Modulate Each Other's Signaling and Stability
- 2014
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:28, s. 19747-19757
-
Tidskriftsartikel (refereegranskat)abstract
- Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta(TGF beta), are key regulators of cellular functions, including proliferation, migration, and differentiation. Growth factor signaling is modulated by context-dependent cross-talk between different signaling pathways. We demonstrate in this study that PDGF-BB induces phosphorylation of Smad2, a downstream mediator of the canonical TGF beta pathway, in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was dependent on the kinase activities of both TGF beta type I receptor (T beta RI) and PDGF beta-receptor (PDGFR beta), and it was prevented by inhibitory antibodies against TGF beta. Inhibition of the activity of the T beta RI kinase greatly reduced the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate that the receptors for PDGF-BB and TGF beta interact physically in primary dermal fibroblasts and that stimulation with PDGF-BB induces internalization not only of PDGFR beta but also of T beta RI. In addition, silencing of PDGFR beta by siRNA decreased the stability of T beta RI and delayed TGF beta-induced signaling. We further show that the hyaluronan receptor CD44 interacts with both PDGFR beta and T beta RI. Depletion of CD44 by siRNA increased signaling via PDGFR beta and T beta RI by stabilizing the receptor proteins. Our data suggest that cross-talk between PDGFR beta and T beta RI occurs in dermal fibroblasts and that CD44 negatively modulates signaling via these receptors.
|
|
| 8. |
|
|
| 9. |
- Izadi, Arman, et al.
(författare)
-
The hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15, s. 1-22
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25. Despite having reduced binding, the IgG3 version promotes stronger phagocytosis of bacteria. Using atomic simulations, we show that IgG3’s Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions with immune cells. We replaced the hinge of IgG1 with four different IgG3-hinge segment subclasses, IgGhxx. Hinge-engineering does not diminish binding as with IgG3 but enhances opsonic function, where a 47 amino acid hinge is comparable to IgG3 in function. IgGh47 shows improved protection against S. pyogenes in a systemic infection mouse model, suggesting that IgGh47 has promise as a preclinical therapeutic candidate. Importantly, the enhanced opsonic function of IgGh47 is generalizable to diverse S. pyogenes strains from clinical isolates. We generated IgGh47 versions of anti-SARS-CoV-2 mAbs to broaden the biological applicability, and these also exhibit strongly enhanced opsonic function compared to the IgG1 subclass. The improved function of the IgGh47 subclass in two distant biological systems provides new insights into antibody function.
|
|
| 10. |
|
|
