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- Abdo, A. A., et al.
(författare)
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DISCOVERY OF HIGH-ENERGY GAMMA-RAY EMISSION FROM THE BINARY SYSTEM PSR B1259-63/LS 2883 AROUND PERIASTRON WITH FERMI
- 2011
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Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 736:1, s. L11-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of >= 100 MeV gamma-rays from the binary system PSR B1259-63/LS 2883 using the Large Area Telescope (LAT) on board Fermi. The system comprises a radio pulsar in orbit around a Be star. We report on LAT observations from near apastron to similar to 128 days after the time of periastron, t(p), on 2010 December 15. No gamma-ray emission was detected from this source when it was far from periastron. Faint gamma-ray emission appeared as the pulsar approached periastron. At similar to t(p) + 30 days, the >= 100 MeV gamma-ray flux increased over a period of a few days to a peak flux 20-30 times that seen during the pre-periastron period, but with a softer spectrum. For the following month, it was seen to be variable on daily timescales, but remained at similar to(1-4) x 10(-6) cm(-2) s(-1) before starting to fade at similar to t(p) + 57 days. The total gamma-ray luminosity observed during this period is comparable to the spin-down power of the pulsar. Simultaneous radio and X-ray observations of the source showed no corresponding dramatic changes in radio and X-ray flux between the pre-periastron and post-periastron flares. We discuss possible explanations for the observed gamma-ray-only flaring of the source.
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- Hamsten, C., et al.
(författare)
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Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma
- 2016
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Blackwell Publishing. - 0105-4538 .- 1398-9995. ; 71:9, s. 1357-1361
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.
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- Gafvelin, G, et al.
(författare)
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Selective COX-2 Inhibition Exerts No Negative Effects on Peripheral Blood Lymphocytes in Allergic Asthmatics
- 2016
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 170:1, s. 57-61
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Selective inhibition of cyclooxygenase-2 (COX-2) reduces the production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), which can have both pro- and anti-inflammatory effects on allergic inflammation. Moreover, in vitro PGE<sub>2</sub> has been shown to affect inflammation through the modulation of lymphocyte responses. <b><i>Methods:</i></b> Sixteen subjects with mild allergic asthma were recruited to a two-period cross-over study: one treatment period with the selective COX-2 inhibitor etoricoxib and one without. Each treatment period ended with an airway challenge with the patient's relevant allergen. Antigen-specific proliferation with the major cat allergen, Fel d 1, was analysed in PBMCs. CD4+ T cells were phenotyped using flow cytometry, and mRNA expression of FOXP3 in anti-CD3-stimulated CD4+ cells were analysed. <b><i>Results:</i></b> No significant impact of in vivo inhibition of COX-2 was detected on the proportion of Th1, Th2, or Treg cells in peripheral blood. Likewise, the treatment had minor effects on the stimulated expression of FOXP3 mRNA in CD4+ T cells. Proliferation of PBMCs to the major cat allergen Fel d 1 was slightly reduced by etoricoxib treatment in cat-allergic patients. <b><i>Conclusions:</i></b> Short-term treatment with the COX-2 inhibitor etoricoxib had a minor impact on T-cell responses, supporting its safe use also in subjects exposed to triggers of lymphocyte activation.
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| 14. |
- Grote, Ludger, 1964, et al.
(författare)
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National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach
- 2023
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Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. Methods: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. Results: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. Conclusions: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).
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- Grundstrom, J, et al.
(författare)
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Covalent coupling of vitamin D3 to the major cat allergen Fel d 1 improves the effects of allergen-specific immunotherapy in a mouse model for cat allergy
- 2012
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 157:2, s. 136-146
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Allergen-specific immunotherapy (SIT) is currently the only curative treatment for allergy but the treatment needs to be improved. We hypothesize that covalent coupling of immunomodulating vitamin D3 to the major cat allergen Fel d 1 can enhance the beneficial effects of SIT to cat allergy. <i>Methods:</i> We treated mice sensitized to Fel d 1 with subcutaneous injections of two doses of recombinant Fel d 1 coupled to 1α,25-dihydroxyvitamin D3 (rFel d 1:VD3) and compared to treatment with the same doses of rFel d 1 in a mouse model for cat allergy. Airway hyperresponsiveness (AHR), cytokines and cells in bronchoalveolar lavage (BAL), in vitro activation of splenocytes to rFel d 1, and Fel d 1-specific immunoglobulins were evaluated. <i>Results:</i> Treatment with both doses of rFel d 1:VD3 decreased AHR, cellular influx and Th2 cytokines in BAL compared to untreated mice. High- and low-dose rFel d 1 treatment also decreased AHR and BAL Th2 cytokines, with less decrease for the low-dose treatment. Importantly, the total number of cells and eosinophils in BAL was markedly reduced at both high- and low-dose rFel d 1:VD3 compared to treatment with rFel d 1 alone. Finally, treatment with both rFel d 1 and rFel d 1:VD3 induced Fel d 1-specific serum IgG. <i>Conclusion:</i> Our results indicate a beneficial therapeutic effect of rFel d 1:VD3 on airway inflammation, AHR and rFel d 1-specific immune responses and thus suggest that this novel immunomodulatory candidate may improve both the efficacy and safety of SIT.
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| 18. |
- Grundstrom, J, et al.
(författare)
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Development of a mouse model for chronic cat allergen-induced asthma
- 2014
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 165:3, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Allergic asthma is a chronic inflammatory airway disease caused by exposure to airborne allergens. In order to develop novel therapies for allergic asthma, models that are relevant to human disease are needed. <b><i>Methods:</i></b> Female BALB/c mice were presensitised subcutaneously with alum-adsorbed recombinant cat allergen Fel d 1, followed by intranasal challenges with cat dander extract spiked with recombinant Fel d 1 for 7 weeks. For reference, mice were presensitised and challenged with ovalbumin following the same protocol. Airway hyperresponsiveness, serum antibodies, airway inflammation and cell infiltration, and cytokines in lung tissue and bronchoalveolar lavage were measured. <b><i>Results:</i></b> Mice presensitised with recombinant Fel d 1 and challenged with cat dander extract or presensitised and challenged with ovalbumin showed airway hyperresponsiveness in response to metacholine. Mice of the cat allergen model showed influx of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage, combined with increased levels of IL-17a and increased IL-4 mRNA expression in lung tissue. In contrast, mice sensitised and challenged with ovalbumin showed a predominant influx of eosinophils in bronchoalveolar lavage and had an increased expression of IL-5 in lung tissue. Both protocols induced features of lung tissue remodelling and allergen-specific antibody responses. <b><i>Conclusions:</i></b> The presented mouse model for cat allergen-induced asthma exhibits hallmarks of chronic allergic asthma, like airway hyperresponsiveness, a mixed neutrophilic/eosinophilic infiltration in bronchoalveolar lavage, expression of IL-17a and signs of remodelling in lung tissue. The model will provide a relevant platform for the development of novel treatment strategies.
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| 31. |
- Ristivojevic, MK, et al.
(författare)
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Alpha-Gal on the Protein Surface Hampers Transcytosis through the Caco-2 Monolayer
- 2020
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:16
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Tidskriftsartikel (refereegranskat)abstract
- Transepithelial transport of proteins is an important step in the immune response to food allergens. Mammalian meat allergy is characterized by an IgE response against the carbohydrate moiety galactosyl-α-1,3-galactose (α-Gal) present on mammalian glycoproteins and glycolipids, which causes severe allergic reactions several hours after red meat consumption. The delayed reaction may be related to the processing of α-Gal carrying proteins in the gastrointestinal tract. The aim of this study was to investigate how protein glycosylation by α-Gal affects the susceptibility to gastric digestion and transport through the Caco-2 cell monolayer. We found that α-Gal glycosylation altered protein susceptibility to gastric digestion, where large protein fragments bearing the α-Gal epitope remained for up to 2 h of digestion. Furthermore, α-Gal glycosylation of the protein hampered transcytosis of the protein through the Caco-2 monolayer. α-Gal epitope on the intact protein could be detected in the endosomal fraction obtained by differential centrifugation of Caco-2 cell lysates. Furthermore, the level of galectin-3 in Caco-2 cells was not affected by the presence of α-Gal glycosylated BSA (bovine serum albumin) (BSA-α-Gal). Taken together, our data add new knowledge and shed light on the digestion and transport of α-Gal glycosylated proteins.
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| 32. |
- Ristivojevic, MK, et al.
(författare)
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α-Gal on the protein surface affects uptake and degradation in immature monocyte derived dendritic cells
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 12684-
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Tidskriftsartikel (refereegranskat)abstract
- Red meat allergy is characterized by an IgE response against the carbohydrate galactose-α-1,3-galactose (α-Gal), which is abundantly expressed on glycoproteins from non-primate mammals. The mechanisms of how α-Gal is processed and presented to the immune system to initiate an allergic reaction are still unknown. The aim of this study was to reveal whether the presence of α-Gal epitopes on the protein surface influence antigen uptake and processing in immature monocyte-derived dendritic cells (iMDDCs). Immature MDDCs were prepared from healthy blood donors and red meat allergic patients. We found an increased internalization of α-Gal carrying proteins over time in iMDDCs by flow cytometric analysis, which was independent of the donor allergic status. The uptake of α-Gal carrying proteins was significantly higher than the uptake of non-α-Gal carrying proteins. Confocal microscopy revealed α-Gal carrying proteins scattered around the cytoplasm in most iMDDCs while detection of proteins not carrying α-Gal was negligible. Fluorescent detection of protein on SDS-PAGE showed that degradation of α-Gal carrying proteins was slower than degradation of non-α-Gal carrying proteins. Thus, the presence of α-Gal on the protein surface affects both uptake and degradation of the protein, and the results add new knowledge of α-Gal as a clinically relevant food allergen.
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