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- Löfdahl, Anna, et al.
(författare)
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5-HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo
- 2016
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 4:15
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary fibrosis is characterized by excessive accumulation of connective tissue, along with activated extracellular matrix (ECM)-producing cells, myofibroblasts. The pathological mechanisms are not well known, however serotonin (5-HT) and 5-HT class 2 (5-HT2) receptors have been associated with fibrosis. The aim of the present study was to investigate the role of 5-HT2B receptors in fibrosis, using small molecular 5-HT2B receptor antagonists EXT5 and EXT9, with slightly different receptor affinity. Myofibroblast differentiation [production of alpha-smooth muscle actin (α-SMA)] and ECM synthesis were quantified in vitro, and the effects of the receptor antagonists were evaluated. Pulmonary fibrosis was also modeled in mice by subcutaneous bleomycin administrations (under light isoflurane anesthesia), and the effects of receptor antagonists on tissue density, collagen-producing cells, myofibroblasts and decorin expression were investigated. In addition, cytokine expression was analyzed in serum. Lung fibroblasts displayed an increased α-SMA (P < 0.05) and total proteoglycan production (P < 0.01) when cultured with TGF-β1 together with 5-HT, which were significantly reduced with both receptor antagonists. Following treatment with EXT5 or EXT9, tissue density, expression of decorin, number of collagen-producing cells, and myofibroblasts were significantly decreased in vivo compared to bleomycin-treated mice. Receptor antagonization also significantly reduced systemic levels of TNF-α and IL-1β, indicating a role in systemic inflammation. In conclusion, 5-HT2B receptor antagonists have potential to prevent myofibroblast differentiation, in vitro and in vivo, with subsequent effect on matrix deposition. The attenuating effects of 5-HT2B receptor antagonists on fibrotic tissue remodeling suggest these receptors as novel targets for the treatment of pulmonary fibrosis.
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| 2. |
- Ekström, Kenneth, 1956-, et al.
(författare)
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How to organise transitions between units in preschool : does it matter
- 2010
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Ingår i: International Journal of Transitions in Childhood. - Melbourne : The University of Melbourne, Australia. - 1833-2390. ; 4:1, s. 4-12
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is, to deepen our understanding of what transitions within a preschool institution mean from the perspective of those involved. The issue is important to focus on, since an overview of research shows, that there are hardly any studies made on transitions within preschools. In the study presented nine preschool teachers were interviewed, representing two preschools differing in approach regarding how the transitions between different units were organised. One of the preschools had “marked” transitions between four units for groups of children strictly based on age. The transitions were perceived as a matter of course, as something natural. The other preschool with only two groups, one for younger children and one for older children, had “smoother” transitions based on individual considerations. Here, the maturity of the individual child was taken into account. In the interpretation of the results, in order to gain a deeper understanding of the meaning of the transitions for the people involved, using the concept of rites of passage, two approaches were revealed. The first regarded transitions to be a part of the pedagogy, supporting the natural development of the child, as a rite of passage, leaving one social stage in their life and move over to another. The second saw transitions as necessary due to external factors, trying to attain a pedagogical environment, where transitions were as smooth as possible, with no marked rites of passage, not for the individual, not for the collective.
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| 4. |
- Eloranta, Sandra, et al.
(författare)
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Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000-2013
- 2018
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Ingår i: European Journal of Haematology. - : WILEY. - 0902-4441 .- 1600-0609. ; 100:1, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden.Methods: Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100000 person-years and 95% confidence intervals (CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison.Results: With 359 identified PCNSL cases (median age 66years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% (P=.002). The increasing trend was primarily observed among elderly individuals (70+years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6years after diagnosis.Conclusion: The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging.
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| 5. |
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En båge genom tiden - ritualer kring en göteborgshistoria. Om Flickläroverket i Artisten
- 2024
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- 1929 bildades Göteborgs första Högre allmänna läroverk för Flickor – Flickläroverket som fick en byggnad 1935 i det kulturella centrumet, Götaplatsen. Efter några år som Kjellbergska gymnasiet, sedan Komvux, blev byggnaden del av Artisten, Högskolan för scen och musik, HSM 1992. Byggnaden har burit kvinnors utbildning, konst och kultur över många generationer, en minneskedja som nu är bruten. Boken - En båge genom tiden – ritualer kring en göteborgshistoria – en konst- och forskningsantologi – är resultatet av de offentliga minnesdagar där de deltagande drygt 200 kvinnorna (70– 97 år) som varit elever på Flickläroverket, studenter vid Artisten, konstnärer och forskare – bidrog till och deltog i gestaltande ritualer, minnesrum, dans, utställningar och samtal som gav liv åt en utbildningskultur och konst som berört samhället i generationer. I boken bidrar ett 20-tal Göteborgsbaserade konstnärer och forskare med olika perspektiv på byggnadens poetiska, sociala och konstnärliga dimensioner. Bland annat beskrivs återskapandet av Bågdansen, som dansades varje år vid Lucia mellan 1934-1972. Här beskrivs även den medie-debatt som ledde till räddningen av målningen Dansen av Nils Nilsson från 1935 och hur nedtagningen gick till. Tillsammans med ett rikt foto- och bildmaterial, filmdokumentationer och ett ljudarkiv utgör boken ett tidsdokument där konst fungerar som minnesbärare över tid och rum.
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| 9. |
- Glimelius, Ingrid, 1975-, et al.
(författare)
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Predictors of histology, tissue eosinophilia and mast cell infiltration in Hodgkin's Lymphoma : a population-based study
- 2011
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 87:3, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Classical Hodgkin’s lymphoma (HL) lesions comprise few tumour cells, surrounded by numerous inflammatory cells. Like in other malignancies, the microenvironment is presumed to be clinically important in HL; however, microenvironment predictors remain poorly characterised. The aim of this study was to investigate how selected patient characteristics and genetic factors affect HL phenotype, in particular tissue eosinophilia, mast cell counts and HL histological subtype.Methods: In a population-based study, patients with HL were interviewed about potential HL risk factors. Available tumours, n = 448, were classified histologically; the number of eosinophils and mast cells were estimated, and eosinophil cationic protein (ECP) and eosinophil protein-x (EPX) gene polymorphisms were determined. Associations were assessed in regression models.Results: Self-reported history of asthma was predictive of having tumour eosinophilia [≥200 eosinophils/10 high power fields, univariate odds ratio (OR) = 2.22, 95% CI 1.06–4.64, P = 0.03]. High numbers of eosinophils were predominantly seen in patients carrying the genotype ECP434GG [multivariate relative levels (RLs) = 1.84, 95% CI 1.02–3.30, P = 0.04]. Lower number of eosinophils was seen in Epstein–Barr virus (EBV)-positive tumours (univariate RL = 0.52, 95% CI 0.3–0.9, P = 0.02) and in older patients (univariate RL = 0.85, 95% CI 0.73–0.99, P = 0.03). Well-known factors such as young age, female sex and EBV-negative status predicted nodular sclerosis histology.Conclusion: The number of eosinophils in HL tumours is influenced by patient traits such as asthma, ECP genotype and EBV status. EBV status was predictive of histology.
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| 10. |
- Hollander, Peter, et al.
(författare)
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An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome
- 2018
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 100:1, s. 88-97
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows anongoing inflammatory response consisting of varying degrees of infiltrating eosinophils,mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.Methods: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.Results: The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barrvirus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.Conclusions: Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.
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