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Sökning: WFRF:(Nilsson Bjorn)

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41.
  • Schmidt, Eva, et al. (författare)
  • Expression of the Hutchinson-Gilford progeria mutation during osteoblast development results in loss of osteocytes, irregular mineralization, and poor biomechanical properties.
  • 2012
  • Ingår i: The Journal of biological chemistry. - 1083-351X. ; 287:40, s. 33512-33522
  • Tidskriftsartikel (refereegranskat)abstract
    • Hutchinson-Gilford progeria syndrome (HGPS) is a very rare genetic disorder that is characterized by multiple features of premature aging and largely affects tissues of mesenchymal origin. In this study, we describe the development of a tissue-specific mouse model that overexpresses the most common HGPS mutation (LMNA, c.1824C>T, p.G608G) in osteoblasts. Already at the age of 5 weeks, HGPS mutant mice show growth retardation, imbalanced gait and spontaneous fractures. Histopathological examination revealed an irregular bone structure, characterized by widespread loss of osteocytes, defects in mineralization, and a hypocellular red bone marrow. Computerized tomography analysis demonstrated impaired skeletal geometry and altered bone structure. The skeletal defects, which resemble the clinical features reported for bone disease in HGPS patients, was associated with an abnormal osteoblast differentiation. The osteoblast-specific expression of the HGPS mutation increased DNA damage and affected Wnt signaling. In the teeth, irregular dentin formation, as was previously demonstrated in human progeria cases, caused severe dental abnormalities affecting the incisors. The observed phenotype also shows similarities to reported bone abnormalities in aging mice and may therefore help to uncover general principles of the aging process.
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44.
  • Stenstrom, Bjorn, et al. (författare)
  • Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice
  • 2007
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:9, s. 2041-2046
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish variant of moist oral smokeless tobacco (snus) is popular in Sweden and Norway, banned from sale within the European Union and is currently being introduced in USA. The aim of the present study was to determine if snus is carcinogenic to the stomach, particularly in Helicobacter pylori (H.P.)-infected hosts at increased risk for gastric cancer development. Snus (General (TM); Swedish Match, Sweden) was mixed with powdered standard mouse chow at a concentration of 5-9% (wt/wt) and given to wild-type (WT, FVB) and gastrin transgenic (INS-GAS, FVB) mice for 6 months with or without H.P. (strain 67:21, CagA(+), VacA(+)) infection. At necropsy, pathological evaluation of stomachs from uninfected snus-treated WT mice showed mild morphological changes, whereas 50% snus-treated INS-GAS mice developed carcinoma in situ (CIS), compared with 25% not exposed to snus. When snus was given to H.P.-infected mice, 9 of 17 WT mice developed CIS with intramucosal invasion, and the remaining 8 of 17 WT mice developed high-grade dysplasia (score > 1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12 H.P.-infected INS-GAS mice developed CIS with intramucosal invasion and submucosal herniation. We suggest that snus is a potential gastric carcinogen in mice. The development of CIS was associated with increased rates of the epithelial cell proliferation and apoptosis, common features of gastric carcinogenesis.
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45.
  • Ström, Daniel, 1971, et al. (författare)
  • A new device for coating single particles under controlled conditions
  • 2005
  • Ingår i: Chemical Engineering Science. - : Elsevier BV. - 0009-2509. ; 60, s. 4647-4653
  • Tidskriftsartikel (refereegranskat)abstract
    • A new device for coating a single levitated particle in a controllable environment is designed and tested. This enables fluidized bed processing to be simulated experimentally on a single-particle level. The device consists of a coating chamber, which contains a capillary tube for levitating the particle, a micro-dispenser for producing discrete drops of controlled size and velocity and a device for supplying gas with specified temperature and humidity. The coating chamber consists of two parts, a confined space where the particle is levitated and a droplet insertion cone where the coating solution is injected into the particle suspending gas flow. A capillary with a well-defined diameter connects the droplet insertion cone and the area where the particle is levitated. The device is equipped with a piezo-actuated flow-through micro-dispenser that has the ability to produce discrete droplets with high reproducibility in terms of droplet size and velocity. The gas required for the coating process is taken from a gas container where the water content is analysed and kept at a minimum. A liquid flow is then introduced into the gas flow at a well-defined flow rate, mixed and evaporated in a three-way mixing vault. The humidified gas flow is then split into two separate flows; a suspending gas flow and a protecting gas flow for the inside of the coating chamber. The device is equipped with a high-speed video camera for monitoring both droplet production and droplet impact. Temperatures and flow rates throughout the device are measured and logged. Preliminary results show the influence of solvent, gas quality and coating procedure on the quality of the coating.
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46.
  • Tesfa, Daniel, et al. (författare)
  • The role of BAFF and G-CSF for rituximab-induced late-onset neutropenia (LON) in lymphomas
  • 2021
  • Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 38:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Mechanisms for late-onset neutropenia (LON) after rituximab treatment are poorly defined both for non-Hodgkin lymphoma (NHL) and for autoimmune disorders. We performed a case-control analysis of a prospective cohort of 169 evaluable consecutive rituximab-treated NHL patients to assess cytokines involved in neutro- and lymphopoiesis (G-CSF, SDF1, BAFF, APRIL) and inflammation (CRP) as possible LON mechanisms. Fifteen patients (9%) developed LON (peripheral blood /PB/ absolute neutrophil counts /ANC/<0.5 G/L, all with marked depletion of CD20(+) B-lymphocytes in bone marrows); they were compared with 20 matched NHL controls without LON. At start of LON, significantly higher PB G-CSF and BAFF levels (P=0.0004 and 0.006, respectively), as well as CRP rises were noted compared to controls; these G-CSF and BAFF and most CRP values returned to levels of the controls in post-LON samples. G-CSF (but not BAFF) changes correlated to CRP rises (but not to ANC levels). BAFF levels correlated significantly to absolute monocyte counts and PB large granular lymphocyte counts (but not to ANC, C-CSF or CRP values). No changes of SDF1 or APRIL levels were noted. Neither LON cases nor controls displayed anti-neutrophil autoantibodies. Collectively, LON in NHL patients was timewise related to transient bursts of blood G-CSF and BAFF concentrations, suggesting that these neutro- and lymphopoiesis growth factors play a role in emergence of rituximab-induced LON, and that inflammation may be a trigger for G-CSF production during LON.
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47.
  • van de Ven, Johannes P. H., et al. (författare)
  • A functional variant in the CFI gene confers a high risk of age-related macular degeneration
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:7, s. 813-813
  • Tidskriftsartikel (refereegranskat)abstract
    • Up to half of the heritability of age-related macular degeneration (AMD) is explained by common variants(1-5). Here, we report the identification of a rare, highly penetrant missense mutation in CFI encoding a p.Gly119Arg substitution that confers high risk of AMD (P = 3.79 x 10(-6); odds ratio (OR) = 22.20, 95% confidence interval (CI) = 2.98-164.49). Plasma and sera from cases carrying the p.Gly119Arg substitution mediated the degradation of C3b, both in the fluid phase and on the cell surface, to a lesser extent than those from controls. Recombinant protein studies showed that the Gly119Arg mutant protein is both expressed and secreted at lower levels than wild-type protein. Consistent with these findings, human CFI mRNA encoding Arg119 had reduced activity compared to wild-type mRNA encoding Gly119 in regulating vessel thickness and branching in the zebrafish retina. Taken together, these findings demonstrate that rare, highly penetrant mutations contribute to the genetic burden of AMD.
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48.
  • Weissmann, Mikael, Docent, 1977-, et al. (författare)
  • Hybrid Threats and Hybrid Warfare : Time for a Comprehensive Approach?
  • 2021
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Hybrid warfare strategies blend conventional warfare, irregular warfare and cyber-attacks with other influencing methods, such as disinformation, diplomacy and foreign political inteference. There is a need for novel comprehensive approaches to counter them.
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