79 research outputs found

    Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses.

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    Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-α was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre-conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence

    Haemophilus influenzae Protein F Mediates Binding to Laminin and Human Pulmonary Epithelial Cells.

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    The mucosal pathogen non-typeable Haemophilus influenzae (NTHi) adheres to the respiratory epithelium, or in the case of epithelial damage, to the underlying basement membrane and extracellular matrix that amongst other proteins consists of laminin. We have recently identified Protein F, an ABC-transporter involved in NTHi immune evasion. Homology modeling of the Protein F tertiary structure revealed a strong resemblance to the streptococcal laminin-binding proteins Lbp and Lmb. Here, we show that Protein F promotes binding of NTHi to laminin and primary bronchial epithelial cells. Analyses with recombinant proteins and synthetic peptides revealed that the N-terminal part of Protein F contains the host-interacting region. Moreover, Protein F exists in all clinical isolates, and isogenic NTHi Δhpf mutants display significantly reduced binding to laminin and epithelial cells. We thus suggest Protein F as an important and ubiquitous NTHi adhesin

    Combining information from surveys of several species to estimate the probability of freedom from Echinococcus multilocularis in Sweden, Finland and mainland Norway

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    <p>Abstract</p> <p>Background</p> <p>The fox tapeworm <it>Echinococcus multilocularis </it>has foxes and other canids as definitive host and rodents as intermediate hosts. However, most mammals can be accidental intermediate hosts and the larval stage may cause serious disease in humans. The parasite has never been detected in Sweden, Finland and mainland Norway. All three countries require currently an anthelminthic treatment for dogs and cats prior to entry in order to prevent introduction of the parasite. Documentation of freedom from <it>E. multilocularis </it>is necessary for justification of the present import requirements.</p> <p>Methods</p> <p>The probability that Sweden, Finland and mainland Norway were free from <it>E. multilocularis </it>and the sensitivity of the surveillance systems were estimated using scenario trees. Surveillance data from five animal species were included in the study: red fox (<it>Vulpes vulpes</it>), raccoon dog (<it>Nyctereutes procyonoides</it>), domestic pig, wild boar (<it>Sus scrofa</it>) and voles and lemmings (Arvicolinae).</p> <p>Results</p> <p>The cumulative probability of freedom from EM in December 2009 was high in all three countries, 0.98 (95% CI 0.96-0.99) in Finland and 0.99 (0.97-0.995) in Sweden and 0.98 (0.95-0.99) in Norway.</p> <p>Conclusions</p> <p>Results from the model confirm that there is a high probability that in 2009 the countries were free from <it>E. multilocularis</it>. The sensitivity analyses showed that the choice of the design prevalences in different infected populations was influential. Therefore more knowledge on expected prevalences for <it>E. multilocularis </it>in infected populations of different species is desirable to reduce residual uncertainty of the results.</p

    Versican in inflammation and tissue remodelling: the impact on lung disorders.

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    Versican is a proteoglycan that has many different roles in tissue homeostasis and inflammation. The biochemical structure is comprised of four different types of the core protein with attached glycosaminoglycans that can be sulphated to various extents and has the capacity to regulate differentiation of different cell types, migration, cell adhesion, proliferation, tissue stabilization and inflammation. Versican's regulatory properties are of importance during both homeostasis and changes that lead to disease progression. The glycosaminoglycans that are attached to the core protein are of the chondroitin sulfate/dermatan sulfate type and are known to be important in inflammation through interactions with cytokines and growth factors. For a more complex understanding of versican it is of importance to study the tissue niche, where the wound healing process in both healthy and diseased conditions take place. In previous studies our group has identified changes in the amount of the multifaceted versican in chronic lung disorders such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome, which could be a result of pathologic, transforming growth factor ÎČ driven, on-going remodelling processes. Reversely, the context of versican in its niche is of great importance since versican has been reported to have a beneficial role in other contexts e.g. emphysema. Here we explore the vast mechanisms of versican in healthy lung and in lung disorders

    Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients

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    Background: During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Methods: Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. Results: The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients. Conclusions: Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD

    The first case of Brucella canis in Sweden: background, case report and recommendations from a northern European perspective

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    Infection with Brucella canis has been diagnosed in Sweden for the first time. It was diagnosed in a three-year-old breeding bitch with reproductive disturbances. Fifteen in-contact dogs were tested repeatedly and all of them were negative for B. canis. The source of infection could not be defined. The present article describes the case and the measures undertaken and gives a short review over B. canis. Recommendations on how to avoid the infection in non-endemic countries are given

    Kan man levandegöra grammatiken i svenskundervisningen? - eller blir det konstigt med konst?

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    I detta examensarbete undersöks om man med relativt otraditionella metoder kan skapa sprÄkutvecklande lÀrandesituationer. Vi hade en idé om att anvÀnda bilden och musiken i svenskundervisningen och med utgÄngspunkt i dessa uttrycksmedel försöka skapa sprÄkutvecklande lÀrandesituationer. Vi lÀt eleverna skriva till bild och musik och dÀrefter analysera sin egen text. Vi undersökte sedan om eleverna ansÄg att de hade hjÀlp av övningarna för sin sprÄkutveckling.Grammar studies, Linguistic developmen

    Extracellular Matrix Remodelling In COPD

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    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that involves major remodelling of cells and tissue in the lung. There has been much focus on the inflammatory response, while less attention has been paid to structural changes and alterations of the extracellular matrix (ECM). In this review we revisit some of the latest findings on what is currently known about ECM alterations in COPD. We also discuss mechanisms involved in tissue repair and pay extra attention to the potential role of glycosaminoglycans in the disease

    MarknĂ€ra ozon i Örebro lĂ€n oktober 2002 - september 2003

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    IVL har pĂ„ uppdrag av Örebro lĂ€ns luftvĂ„rdsförbund sammanstĂ€llt resultat frĂ„n ozonmĂ€tningar som pĂ„gick under oktober 2002 till och med september 2003 i Örebro lĂ€n. I rapporten redovisas Ă€ven en kunskapssammanstĂ€llning av marknĂ€ra ozons skadliga inverkan pĂ„ mĂ€nniskors hĂ€lsa samt effekter pĂ„ vĂ€xtligheten. Rapporten innehĂ„ller Ă€ven en redovisning av de existerande nationella och internationella miljömĂ„len / grĂ€nsvĂ€rden som rör marknĂ€ra ozon. I föreliggande rapport har mĂ€tningarna sammanstĂ€llts och olika medelvĂ€rden samt ozonindex har berĂ€knats. Dessa har jĂ€mförts med kringliggande lĂ€ns ozonmĂ€tningar. Vidare redovisas ozonhalterna i relation till nationella och internationella mĂ„l vĂ€rden / grĂ€nsvĂ€rden.IVL har pĂ„ uppdrag av Örebro lĂ€ns luftvĂ„rdsförbund sammanstĂ€llt resultat frĂ„n ozonmĂ€tningar som pĂ„gick under oktober 2002 till och med september 2003 i Örebro lĂ€n. I rapporten redovisas Ă€ven en kunskapssammanstĂ€llning av marknĂ€ra ozons skadliga inverkan pĂ„ mĂ€nniskors hĂ€lsa samt effekter pĂ„ vĂ€xtligheten. Rapporten innehĂ„ller Ă€ven en redovisning av de existerande nationella och internationella miljömĂ„len / grĂ€nsvĂ€rden som rör marknĂ€ra ozon. I föreliggande rapport har mĂ€tningarna sammanstĂ€llts och olika medelvĂ€rden samt ozonindex har berĂ€knats. Dessa har jĂ€mförts med kringliggande lĂ€ns ozonmĂ€tningar. Vidare redovisas ozonhalterna i relation till nationella och internationella mĂ„l vĂ€rden / grĂ€nsvĂ€rden
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