51 resultados para I-3-mediated Resistance


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Kirje 3.4.1973

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Koska panhuilu on vasta "aloitteleva" musiikkioppilaitossoitin, sille ei vielä ole valmiita tasokurssiohjelmistotaulukoita. Panhuilunsoiton opetuksen aloittamisen edellytyksenä on kurssivaatimusten ja ohjelmistoluetteloiden laatiminen myös perusasteelle ja musiikkiopistoasteelle (I/D). Työn tarkoituksena oli siis laatia panhuilulle peruskurssien 1-3 ja I-tason kurssivaatimukset ja tutkinto-ohjelmistoluettelot. Työ sisältää myös tasosuoritusten arviointiohjeet ja osion opettajalle, jossa esitellään tasosuoritukseen sopivia esimerkkisävellyksiä soitinkoulujen, etydivihkojen ja kokoelmavihkojen sisällöistä. Näin opettaja tai itsenäisesti opiskeleva harrastaja pystyy sijoittamaan muitakin teoksia eri suoritustasoille. Aineisto koostuu panhuilulle sävelletyn materiaalin lisäksi oboe-, poikkihuilu-, nokkahuilu-, ja viulukirjallisuudesta, joita olen kerännyt Sibelius-Akatemian, Helsingin Konservatorion sekä Helsingin kaupunginkirjastoista. Nimittäin varsinaisesti panhuilulle sävellettyjä kappaleita on erittäin vähän ja ne ovat vaihtelevan tasoisia. Tasosuoritusten arviointiohjeita käyttäen keräsin kirjastoista tai ostin sopivat nuottimateriaalit ja mapitin kaikki kokoelmavihkot, soitinkoulut ja säestykselliset sävellykset. Tämän jälkeen lajittelin materiaalit omiin kansioihinsa tasokurssien mukaan. Ohjelmistotaulukot ovat eriteltyinä kunkin tasokurssin mukaan. Ne sisältävät seuraavia osa-alueita: soitinkoulut, etydit, kokoelmat, säestykselliset sävellykset, sarjat, konsertot, sonaatit ja kamarimusiikki. Näiden lisäksi jokaiselle tasokurssille on mukana asteikkovaatimukset. Opinnäytetyö on samalla pieni ohjekirja panhuiluopettajalle tai itsenäisesti opiskelevalle oppilaalle: hän saa tietoa panhuilun hengitystekniikasta ja ansatsista verrattuna poikkihuiluun ja oboeen sekä siitä, mitä liikkeitä hänen tulisi varoa soittaessaan panhuilua. Tämän tyyppinen tieto on tärkeää, sillä panhuilu on hyvin fyysinen soitin ja jos sitä "väärinkäyttää", se saattaa aiheuttaa nuorelle oppilaalle pysyviä niskavammoja tms. Osaa aineistosta olen päässyt kokeilemaan eritasoisilla ja -ikäisillä oppilailla Raahessa kesällä 2006 pidetyllä panhuiluleirillä.

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Lyme borreliosis is a tick-transmitted infection caused by the spirochete bacterium Borrelia burgdorferi sensu lato. The tick injects bacteria into host skin, where a first line defence, mainly the complement system, neutrophils, dendritic cells and macrophages are ready to attack foreign intruders. However, in the case of Lyme borreliosis, the original immune response in the skin is untypically mild among bacterial infections. A further untypical feature is the ability of B. burgdorferi to disseminate to distant organs, where, in some patients, symptoms appear after years after the original infection. This study aimed at uncovering some of the immune evasion mechanisms utilized by B. burgdorferi against the complement system, neutrophils and dendritic cells. B. burgdorferi was shown to inhibit chemotaxis of human neutrophils towards nformyl- methyl-leucyl-phenylalanine (fMLP). Outer surface protein B (OspB) of B. burgdorferi was shown to promote resistance to the attack of the complement system and neutrophil phagocytosis at low complement concentrations. B. burgdorferi was shown to inhibit migration of dendritic cells in vitro towards CCL19 and CCL21 and also in an in vivo model. This effect was shown to be due to the absence of CD38 on the borrelia-stimulated dendritic cell surface. A defect in p38 mitogen-activated-protein-kinase (p38) signaling was linked to defective CD38 expression. A defect in CD38 expression on B. burgdorferi-stimulated neutrophils was also observed. In this study, a number of novel immune evasion strategies utilized by B burgdorferi were chracterized. However, further studies are needed as other immune evasion mechanisms await to be uncovered.

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The aim of this study was to characterize the cellular mechanisms leading to the beneficial effect of anti-oxidative gene therapy and pro-angiogenic stem cell therapy in acute peripheral ischemia. Post-ischemic events aim to re-establish tissue blood perfusion, to clear cellular debris, and to regenerate lost tissue by differentiation of satellite cells into myoblasts. Although leukocytes have an essential role in clearing cellular debris and promoting angiogenesis, they also contribute to tissue injury through excessive ROS production. First, we investigated the therapeutic properties of extracellular superoxide dismutase (SOD3) gene transfer. SOD3 was shown to reduce oxidative stress, to normalize glucose metabolism, and to enhance cell proliferation in the ischemic muscle. Analysis of the mitogenic Ras-Erk1/2 pathway showed SOD3 mediated induction offering a plausible explanation for enhanced cell proliferation. In addition, SOD3 reduced NF-κB activity by enhancing IκBα expression thus leading to reduced expression of inflammatory cytokines and adhesion molecules with consequent reduction in macrophage infiltration. Secondly, we sought to determine the fate and the effect of locally transplanted mesenchymal stem/stromal cells (MSCs) in acute ischemia. We showed that a vast majority of the transplanted cells are cleared from the injury site within 24 hours after local transplantation. Despite rapid clearance, transplantation was able to temporarily promote angiogenesis and cell proliferation in the muscle. Lack of graft-derived growth factor expression suggests other than secretory function to mediate this observed effect. In conclusion, both SOD3 and MSCs could be utilized to alleviate peripheral ischemia induced tissue injury. We have described a previously unidentified growth regulatory role for SOD3, and suggest a novel mechanism whereby transplanted MSCs enhance the reparative potential of the recipient tissue through physical contacts.

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Rapid identification and resistance determination of pathogens in clinical specimens is vital for accurate treatment and monitoring of infectious diseases. Antimicrobial drug resistance is increasing globally and healthcare settings are facing this cost-intensive and even life-threatening problem. The incidence of resistant pathogens in Finland has remained relatively steady and manageable at least for the time being. DNA sequencing is the gold standard method for genotyping, mutation analysis, and identification of bacteria. Due to significant cost decrease in recent years, this technique is available to many research and clinical laboratories. Pyrosequencing technique, a rapid real-time DNA sequencing method especially suitable for analyzing fairly short stretches of DNA, was used in this study. Due to its robustness and versatility, pyrosequencing was applied in this study for identification of streptococci and detection of certain mutations causing antimicrobial resistance in different bacteria. Certain streptococcal species such as S. pneumoniae and S. pyogenes are significantly important clinical pathogens. S. pneumoniae causes e.g. pneumonia and otitis media and is one of the most important community-acquired pathogens. S. pyogenes, also known as group A streptococcus, causes e.g. angina and erysipelas. In contrast, the socalled alpha-haemolytic streptococci, such as S. mitis and S. oralis, belong to the normal microbiota, which are regarded to be non-pathogenic and are nearly impossible to identify by phenotypic methods. In this thesis, a pyrosequencing method was developed for identification of streptococcal species based on the 16S rRNA sequences. Almost all streptococcal species could be differentiated from one another by the developed method, including S. pneumoniae from its close relatives S. mitis and S. oralis . New resistance genes and their variants are constantly discovered and reported. In this study, new methods for detecting certain mutations causing macrolide resistance or extended spectrum beta-lactamase (ESBL) phenotype were developed. These resistance detection approaches are not only suitable for surveillance of mechanisms causing antimicrobial resistance but also for routine analysis of clinical samples particularly in epidemic settings. In conclusion, pyrosequencing was found to be an accurate, versatile, cost-effective, and rapid DNA sequencing method that is especially suitable for mutation analysis of short DNA fragments and identification of certain bacteria.

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Artikel i konferensrapport.

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Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, insulin resistance, impaired glucose tolerance, hypertension and dyslipidemia. The prevalence of MetS is increasing worldwide in all age groups. MetS is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. Aims: The aim of the present study was to investigate the prevalence, secular trends and childhood predictors of MetS in young adults. Furthermore, the relations between MetS and subclinical atherosclerosis were studied and whether apolipoproteins (apo) B and A-I, C-reactive protein (CRP) and type II secretory phospholipase A2 (sPLA2) were associated with MetS, and to what extent the atherogenicity of MetS was explained by these factors. Participants and Methods: The present thesis is part of the large scale population-based, prospective study, the Cardiovascular Risk in Young Finns Study. The first cross-sectional study was conducted in 1980 and included 3,596 participants aged 3-18 years. Carotid and brachial ultrasound studies were performed for 2,283 of these participants in 2001 and 2,200 of these participants in 2007. Results: The overall prevalence of MetS in young adults aged 24-39 years in 2001 was 10-15 % and 6 years later in 30-45 year-old adults it was 15-23 % depending on the MetS definition used. Between the years 1986 and 2001, MetS prevalence increased from 1.0 % to 7.5 % (p<0.0001) in 24-year-old participants that was mostly driven by the increased central obesity. Participants with MetS had increased carotid intima-media thickness (cIMT) and decreased carotid elasticity compared to those without the syndrome. Impaired brachial flow-mediated dilatation (FMD) was not related to MetS but it modified the relationship between MetS and cIMT (P for interaction 0.023). High levels of apoB, CRP, sPLA2 and low levels of apoA-I associated with MetS in young adults. In prospective analysis both MetS and high apoB predicted (P<0.0001) incident high cIMT, defined as cIMT>90th percentile and/or plaque. The association between MetS and incident high cIMT was attenuated by ~40 % after adjustment with apoB. Conclusions: MetS is common in young adults and increases with age. Screening for risk factors, especially obesity, at an early life stage could help identify children and adolescents at increased risk of developing MetS and cardiovascular disease later in life. MetS identifies a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MetS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis. In addition, the atherogenicity of MetS in this population assessed by incident high cIMT appears to be substantially mediated by elevated apoB.