113 research outputs found

    Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases

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    Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients

    Biomarkers in Natural Fish Populations Indicate Adverse Biological Effects of Offshore Oil Production

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    Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills.Samples from natural populations of haddock (Melanogrammus aeglefinus) and Atlantic cod (Gadus morhua) in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs) were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea.It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production

    Brukarens roll i välfärdsforskning och utvecklingsarbete

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    Tekstene er fra forelesninger samt fra doktorantkurset "Brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg". Kurset ble avholdt våren 2009.Fra omslag: På 1980-talet blev ”brukare” ett modeord i offentlig förvaltning och förvaltningsforskning. Termen betecknar den som använder sig av välfärdsservice (jfr. engelskans service user), eller ”slutmottagare” av offentlig nyttighet eller åtgärd. Brukare av välfärdstjänster vet hur hjälp och service fungerar i praktiken och kan därför ge synnerligen viktig återkoppling enligt devisen: ”Den som har skorna på fötterna vet var de skaver”. Välfärdsorganisationer har all anledning att involvera brukare i planering och policyarbete i syfte att utveckla förmågan att göra rätt saker. Det finns inte mycket dokumentation och forskning kring brukarmedverkan i utvecklingsarbete och forskning på välfärdsområdet. I synnerhet saknas kunskap om hur välfärdstjänster tas emot och realiseras i brukarens livssammanhang. En ambition i doktorandkursen ”brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg” var att samla och presentera kunskaper på området. Kursen genomfördes våren 2009 i ett unikt samarbete mellan Karlstads Universitet, Sheffield University i England, Högskolan i Hedmark i Norge, Hälsohögskolan i Jönköping och Högskolan i Borås/FoU Sjuhärad Välfärd. Texterna i denna bok härrör från kursens föreläsningar och paperarbeten. De ger många exempel på hur brukare kan involveras i forskning och utvecklingsarbete, och presenterar en rad praktiska metoder för brukarsamverkan. Boken rekommenderas till välfärdens politiker och yrkespersoner, till studenter som förbereder sig för välfärdens yrken liksom till forskare och utvecklingsarbetare som vill utveckla samarbete med brukare och brukarorganisationer. Den vänder sig givetvis även till brukare och brukarorganisationer som vill engagera sig i forskning och utvecklingsarbete

    Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

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    Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

    Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

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    We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease
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