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  • 1.
    Andersson, David
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Boyacioglu, Anders
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Bilateral deficit vid excentrisk och koncentrisk muskelaktion: En jämförande studie mellan den summerade unilaterala och bilaterala kraftutvecklingen hos roddare visavi sprinters2006Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Aim

    The main aim of the study was to investigate the difference in bilateral deficit between rowers and sprinters during maximal eccentric/concentric muscle actions.

    • Are there any significant differences in bilateral deficit between rowers and sprinters?

    • Do the amount of years in practice effect the bilateral deficit?

    Method

    Fourteen male subject participants divided in 2 equal sized groups (7 individuals in each group; rowers and sprinters) performed maximal unilateral/bilateral eccentric and concentric muscle actions in a leg press machine at a velocity of 0.2m/s. The range of motion in the knee joint was 70° – 140°. Dependent t-tests have been performed within each group pre and post test. P was set to 0,05 to prevent type I faults (false positive) a Bonferroni test was made for two comparisons and set to 0,0253.

    Results

    Average bilateral deficit for rowers were: 11% concentric and 33% eccentric. Number of years in practice and bilateral deficit: practiced >8years concentric 7% and eccentric 24%. Practiced <8 years concentric 21% and eccentric 55%.

    Average bilateral deficit for sprinters were: 5% concentric and 24% eccentric. Number of years in practice and bilateral deficit: practiced >8years concentric 4% and eccentric 26%. Practiced <8years concentric 16% and eccentric 11%.

    Conclusions

    The main explanation for the larger differences in bilateral deficit for rowers in eccentric muscle action compared to sprinters may be related for the fact that the rowers have an almost non - eccentric phase during rowing. When comparing the amount of years in practice and bilateral deficit we saw that it decreased with the number of practiced years for booth rowers and sprinters. The reason to this pattern is probably on a neural base.

  • 2.
    Apró, William
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Tannerstedt, Jörgen
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Nutrition och muskeluppbyggnad2007Oppgave
    Abstract [sv]

    Senare års studier har gett oss en klarare bild av hur muskeluppbyggnaden stimuleras och regleras av styrketräning och nutrition. Mycket forskning kvarstår dock innan fullständiga rekommendationer kan ges. Vad som dock är klart är att de allmänna rekommendationerna som idag uppgår till 0.8 g protein • kg-1 kroppsvikt • dag-1 i de flesta länder (Lemon, 2000) inte räcker till för fysiskt aktiva individer. Atletens ökade proteinbehov kan dock enkelt tillgodoses via ökat matintag varvid supplementering ur den aspekten inte är nödvändig.

    Vidare vet man att tillgängligheten och tillförseln av aminosyror runt träningen är avgörande för maximal stimulering av proteinsyntesen. Muskeln behöver tillgång till essentiella aminosyror när träningen påbörjas för maximal stimulering av proteinsyntesen. Huruvida aminosyrorna behöver tas i form av en dryck i kosttillskottsform eller kan intas i form av vanlig mat för att tillräckligt fort kunna förse muskeln med EAA är inte utrett.

  • 3.
    Arama, Charles
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Sciences Techniques and Technologies of Bamako, Mali.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    The path of malaria vaccine development: challenges and perspectives2014Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 5, 456-466 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Malaria is a life-threatening disease caused by parasites of the Plasmodium genus. In many parts of the world, the parasites have developed resistance to a number of antimalarial agents. Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies, use of insecticidal nets by individuals at risk and active research into malaria vaccines. Protection against malaria through vaccination was demonstrated more than 30years ago when individuals were vaccinated via repeated bites by Plasmodium falciparum-infected and irradiated but still metabolically active mosquitoes. However, vaccination with high doses of irradiated sporozoites injected into humans has long been considered impractical. Yet, following recent success using whole-organism vaccines, the approach has received renewed interest; it was recently reported that repeated injections of irradiated sporozoites increased protection in 80 vaccinated individuals. Other approaches include subunit malaria vaccines, such as the current leading candidate RTS,S (consisting of fusion between a portion of the P.falciparum-derived circumsporozoite protein and the hepatitis B surface antigen), which has been demonstrated to induce reasonably good protection. Although results have been encouraging, the level of protection is generally considered to be too low to achieve eradication of malaria. There is great interest in developing new and better formulations and stable delivery systems to improve immunogenicity. In this review, we will discuss recent strategies to develop efficient malaria vaccines.

  • 4.
    Arneson, Sofia
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för biologi och miljö (BOM).
    Att motverka dehydrering hos äldre i teori och praktik2015Independent thesis Basic level (degree of Bachelor), 180 hpOppgave
    Abstract [sv]

    Syfte: Att kartlägga likheter och skillnader i åtgärder och hjälpmedel mot dehydrering hos äldre i teori och praktik.

    Metod: Initialt utfördes litteraturstudier via universitetsbibliotekets söktjänst OneSearch. Tre intervjuer utfördes på undersköterskor på gruppboende, demensboende och hemtjänst. Dessa erbjuder en inblick i den praktiska verksamheten.

    Resultat: Följande faktorer av betydelse för att förebygga eller motverka dehydrering identifierades samstämmigt i litteratur och vid intervjuer: (1) kunskap om den äldre via dokumentation, (2) anpassning av tillvägagångssätt vid servering av dryck efter den äldres preferenser och tillstånd, (3) hemtrevlig miljö med sociala interaktioner, (4) bedömning av vätskeintag, väskebalans och riskfaktorer via uppmärksamhet, vätskeregistrering och med hjälp av flera andra yrkesgrupper samt med hänsyn till den äldres historik, (5) påminnelser (särskilt vid demens) och en stor mängd lättabsorberade drycker som intas succesivt vid diarré och kräkningar, (6) lättanvända och specialutformade hjälpmedel. Följande metoder särskilde sig: (1) utbildning för vårdare; begränsad på de undersökta platserna, (2) tekniska hjälpmedel och sväljterapi (kostmodifieringar, anpassade huvudpositioner, sväljträning) vid dysfagi; kostmodifieringar används på de undersökta platserna, (3) färgsättning av koppar och kannor, vilket visats kunna ha betydelse för intag.

    Slutsats: Skillnader fanns gällande utbildning och användning av sväljterapi, tekniska hjälpmedel och infusioner. Utbildning av personalen, mer frekvent vätskeregistrering och fullständig sväljterapi utgör förbättringsmöjligheter. Vissa av dessa åtgärder kräver ökade resurser och/eller tydliga riktlinjer. Acceptans för tekniska hjälpmedel är inte en självklarhet. Undersökningar gällande möjligheterna i att med färgval och design av dryckeskärl stimulera de äldre att dricka mer kan vara värt att undersöka vidare. Intervjuerna syftade främst till att ge en inblick i den praktiska verksamheten och generaliserbarheten av erhållna resultat är begränsad. De flesta åtgärder som har identifierats är ”mjuka” till sin karaktär. Det är svårt att få en klar bild av olika metoders effektivitet. Några av metoderna som har utvärderats med goda resultat vid dysfagi och som därför kan förbättra vätskeintaget är sväljterapi och stimulering av sväljmuskulatur. 

  • 5.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Roca, Jordi
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Rubér, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Vicente Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Atikuzzaman, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Measurement of Activity and Concentration of Paraoxonase 1 (PON-1) in Seminal Plasma and Identification of PON-2 in the Sperm of Boar Ejaculates2015Inngår i: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 82, nr 1, 58-65 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON-1, extracellular) and type 2 (PON-2, intracellular) in boar semen. To evaluate PON-1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON-1 and total cholesterol levels. Seminal-plasma PON-1 concentration ranged from 0.961 to 1.670ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal-plasma PON-1 concentration and enzymatic activity were negatively correlated (r=-0.763; Pless than0.01). The activity of seminal-plasma PON-1 negatively correlated with ejaculate volume (r=-0.726, Pless than0.05), but positively correlated with sperm concentration (r=0.654, Pless than0.05). Total seminal-plasma cholesterol concentration positively correlated with PON-1 activity (r=0.773; Pless than0.01), but negatively correlated with PON-1 concentration (r=-0.709; Pless than0.05). The presence of intracellular PON-2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON-2 localised to the post-acrosomal area of the sperm head and principal piece of the tail in membrane-intact spermatozoa. In summary, PON is present in boar semen, with PON-1 at low levels in seminal plasma and PON-2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal-plasma parameters. Mol. Reprod. Dev. 82: 58-65, 2015. (c) 2014 Wiley Periodicals, Inc.

  • 6.
    Beniamin, Armanos
    Högskolan i Skövde, Institutionen för vård och natur.
    Establishment of an Expression and Purification System for Plasmodium falciparum Multi Drug Resistance (pfmdr) Transporter2007Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Malaria is a life threatening parasite disease caused and transmitted by infected female anopheles mosquito. However, the parasite, Plasmodium falciparum, has become resistant to most anti malarial drugs, such as chloroquine, which contributes to fever and anaemia because of its ability to digest the haemoglobin in the red blood cells. The aims of this project were to establish whether “Bac to Bac” Baculoviral Expression System is suitable for expression of pfmdr 1 gene and for purification of the pgh 1 protein. The pfmdr 1 gene encodes an ABC transporter protein, pgh 1, fixed in the cell membrane of the Plasmodium falciparuum gut, which assist in elimination of drug compounds. Furthermore, “Bac to Bac” Baculoviral Expression System uses vectors with histidine tags to clone the pfmdr 1 gene and subsequently transform these into DH10Bac cells to produce the recombinant bacmid DNA. Since pfmdr 1 gene is an AT-rich sequence, PCR was optimized, by lowering the annealing and extension temperature to 47Co and 66Co respectively. The results show that “Bac to Bac” Baculoviral Expression System can be used to express the pfmdr 1 gene, though further experiments has to be performed.

  • 7.
    Berg, Monica
    Karlstads universitet, Estetisk-filosofiska fakulteten.
    God hälsa som mål: En textanalys av olika rekommendationer2007Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Syftet med denna uppsats är undersöka om det finns skillnader och likheter i rekommendationer inom tre olika fält där kostsammansättning och fysisk aktivitet behandlas.

    Frågor som besvaras är vilka skillnader och likheter i rekommendationer angående intag av protein, kolhydrater och fett och motion som ges. För att få svar på dessa frågor har en textanalys som baseras på Holliday’s tredimensionella modell för diskursanalys använts. Resultatet visar att de främsta skillnaderna i rekommendationer rör hur man ska fördela det totala energiintaget mellan de energigivande näringsämnena. Likheter som visar sig är att andelen snabba kolhydrater i kosten bör minskas samt att daglig motion påverkar vår hälsa positivt.

  • 8. Berggren, D. Moreno
    et al.
    Folkvaljon, Y.
    Engvall, M.
    Sundberg, J.
    Lehman, S.
    Lambe, M.
    Antunovic, P.
    Garelius, H.
    Hellstrom-Lindberg, E.
    Jadersten, M.
    Lorenz, Fryderyk
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Nilsson, L.
    Ejerblad, E.
    VALIDATION OF PROGNOSTIC SCORING SYSTEMS FOR MYELODYSPLASTIC SYNDROMES IN THE SWEDISH MDS-REGISTER2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, 243-243 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 9.
    Bergh, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zetterström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Graffmo, Karin Sixtensdotter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Jonsson, P. Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lang, Lisa
    Stockholm, Sweden.
    Danielsson, Jens
    Stockholm, Sweden.
    Oliveberg, Mikael
    Stockholm, Sweden.
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping2015Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 14, 4489-4494 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.

  • 10.
    Bergman, Ingrid-Maria
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edman, Kjell
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Rosengren, K. Johan
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Edfors, Inger
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR)1, TLR2, TLR6, and TLR10 genes.2010Inngår i: International Symposium on Animal Genomics for Animal Health Paris, France, 31 May – 2 June 2010: The AGAH 2010 Abstract Book, 2010, 35- s.Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    The Toll-like receptors (TLR) are vitally important pattern recognition receptors linking innate and adaptive immunity. Several single nucleotide polymorphisms (SNP) in human TLR genes have been associated with disease. There are few studies on associations between polymorphisms in TLR genes and disease in pigs, but the TLR2/TLR6 heterodimer is activated by Mycoplasma hyopneumoniae, and the expression of TLR2, TLR4, and TLR9 is modulated in the presence of different Salmonella serovars. Porcine TLR1, TLR6, and TLR10 are located in a cluster on the p arm of chromosome 8, while TLR2 resides on the q arm. Previously, we identified quantitative trait loci (QTL) for immune-related traits on pig chromosome 8, close to the KIT gene and the microsatellite S0225, respectively. In order to explore polymorphism in some TLR genes in European wild boars and domestic pigs, TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 domestic pigs of Hampshire, Landrace, and Large White origin. Similarly, TLR10 was sequenced in 15 wild boars and 15 domestic pigs. In TLR1 and TLR2, more SNP were present in the domestic pigs than in the wild boars. In TLR6, SNP numbers were similar in both animal groups, but the level of heterozygosity was higher in the domestic pigs than in the wild boars. In TLR10, again, more SNP were present in the domestic pigs, and a higher number of nonsynonymous SNP were detected in TLR10 compared to the other genes. This may suggest redundancy for TLR10 in pigs. 

  • 11.
    Betsholtz, Christer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    Keller, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    PDGF, Pericytes and the Pathogenesis of Idiopathic Basal Ganglia Calcification (IBGC)2014Inngår i: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 24, nr 4, 387-395 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Platelet-derived growth factors (PDGFs) are important mitogens for various types of mesenchymal cells, and as such, they exert critical functions during organogenesis in mammalian embryonic and early postnatal development. Increased or ectopic PDGF activity may also cause or contribute to diseases such as cancer and tissue fibrosis. Until recently, no loss-of-function (LOF) mutations in PDGF or PDGF receptor genes were reported as causally linked to a human disease. This changed in 2013 when reports appeared on presumed LOF mutations in the genes encoding PDGF-B and its receptor PDGF receptor-beta (PDGF-R) in familial idiopathic basal ganglia calcification (IBGC), a brain disease characterized by anatomically localized calcifications in or near the blood microvessels. Here, we review PDGF-B and PDGF-R biology with special reference to their functions in brain-blood vessel development, pericyte recruitment and the regulation of the blood-brain barrier. We also discuss various scenarios for IBGC pathogenesis suggested by observations in patients and genetically engineered animal models of the disease.

  • 12.
    Borssén, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Nordlund, J
    Haider, Z
    Landfors, M
    Larsson, P
    Forestier, E
    Heyman, M
    Hultdin, M
    Lönnerholm, G
    Syvänen, AC
    Degerman, S
    DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemiaManuskript (preprint) (Annet vitenskapelig)
  • 13.
    Cancar, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Serbia’s way to accession with the European Union and the European Medicines Agency: a comparison of regulatory activity in the field of pharmaceuticals in Serbia and Sweden2014Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Introduction:  On 24 January, 2014 Serbia was approved opening negotiations on accession into the European Union (EU). The European Commission is responsible for launching assistance programmes to support preparatory procedures for the candidate countries; one of those programmes is the Instrument for pre-accession Assistance (IPA) programme. The aim of the IPA programme is to build contacts and relationships between the European Medicines Agency (EMA) and Serbia’s Medicines and Medical Devices Agency (ALIMS), for future collaboration in the EMA activities and its relationship with the Member States of EU.

    Aim: The aim is to describe regulatory activities of ALIMS on human medicines, since the country is not yet a Member State of the EU and to put this into relation with Sweden, a Member State of the EU, which may promote new activities to be introduced in ALIMS’s regulatory work.

    Method: This is a descriptive comparative literature report of institutions working with pharmaceutical regulatory activities.

    Findings: The Serbian Law on Medicines and Medical Devices, established in 2010 suggests that the activities of ALIMS are generally in accordance with the EU standards and guidelines. Since Serbia is not yet a member of the EU, the pharmaceutical regulatory system for granting centralized authorization or marketing authorization based on mutual recognition is not yet possible. However, the Law of Medicines and Medical Devices states that exceptions can be made and ALIMS can issue authorization of centrally authorized medicines if it has reasons related to protection of public health.

    Conclusions: ALIMS has a well developed regulatory authority thanks to international collaboration and a desire to become an EU Member State. 

  • 14.
    Cederquist, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Palmqvist, Richard
    Emanuelsson, Monica
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Grönberg, Henrik
    Retained immunohistochemical staining in a large Swedish HNPCC family with a pathogenic MLH1 missense mutationManuskript (preprint) (Annet vitenskapelig)
  • 15. Cif, Laura
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, University College London-Institute of Neurology, Queen Square, London, UK.
    Seventy Years of Pallidotomy for Movement Disorders2017Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, nr 7, 972-982 s.Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid-1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa-induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience.

  • 16.
    Dantoft, Widad
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Davis, Monica M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lindvall, Jessica M.
    Tang, Xiongzhuo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Uvell, Hanna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Junell, Anna
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Beskow, Anne
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Engström, Ylva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    The Oct1 homolog Nubbin is a repressor of NF-kappa B-dependent immune gene expression that increases the tolerance to gut microbiota2013Inngår i: BMC Biology, ISSN 1741-7007, Vol. 11, 99- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Innate immune responses are evolutionarily conserved processes that provide crucial protection against invading organisms. Gene activation by potent NF-kappa B transcription factors is essential both in mammals and Drosophila during infection and stress challenges. If not strictly controlled, this potent defense system can activate autoimmune and inflammatory stress reactions, with deleterious consequences for the organism. Negative regulation to prevent gene activation in healthy organisms, in the presence of the commensal gut flora, is however not well understood. Results: We show that the Drosophila homolog of mammalian Oct1/POU2F1 transcription factor, called Nubbin (Nub), is a repressor of NF-kappa B/Relish-driven antimicrobial peptide gene expression in flies. In nub(1) mutants, which lack Nub-PD protein, excessive expression of antimicrobial peptide genes occurs in the absence of infection, leading to a significant reduction of the numbers of cultivatable gut commensal bacteria. This aberrant immune gene expression was effectively blocked by expression of Nub from a transgene. We have identified an upstream regulatory region, containing a cluster of octamer sites, which is required for repression of antimicrobial peptide gene expression in healthy flies. Chromatin immunoprecipitation experiments demonstrated that Nub binds to octamer-containing promoter fragments of several immune genes. Gene expression profiling revealed that Drosophila Nub negatively regulates many genes that are involved in immune and stress responses, while it is a positive regulator of genes involved in differentiation and metabolism. Conclusions: This study demonstrates that a large number of genes that are activated by NF-kappa B/Relish in response to infection are normally repressed by the evolutionarily conserved Oct/POU transcription factor Nub. This prevents uncontrolled gene activation and supports the existence of a normal gut flora. We suggest that Nub protein plays an ancient role, shared with mammalian Oct/POU transcription factors, to moderate responses to immune challenge, thereby increasing the tolerance to biotic stress.

  • 17. Davies, Brandon S J
    et al.
    Beigneux, Anne P
    Barnes, Richard H
    Tu, Yiping
    Gin, Peter
    Weinstein, Michael M
    Nobumori, Chika
    Nyrén, Rakel
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Goldberg, Ira
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bensadoun, André
    Young, Stephen G
    Fong, Loren G
    GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries.2010Inngår i: Cell metabolism, ISSN 1932-7420, Vol. 12, nr 1, 42-52 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries.

  • 18. de Veer, Simon J.
    et al.
    Swedberg, Joakim E.
    Akcan, Muharrem
    Rosengren, K. Johan
    Brattsand, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Craik, David J.
    Harris, Jonathan M.
    Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition2015Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 469, nr 2, 243-253 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Laskowski inhibitors regulate serine proteases by an intriguing mode of action that involves deceiving the protease into synthesizing a peptide bond. Studies exploring naturally occurring Laskowski inhibitors have uncovered several structural features that convey the inhibitor's resistance to hydrolysis and exceptional binding affinity. However, in the context of Laskowski inhibitor engineering, the way that various modifications intended to fine-tune an inhibitor's potency and selectivity impact on its association and dissociation rates remains unclear. This information is important as Laskowski inhibitors are becoming increasingly used as design templates to develop new protease inhibitors for pharmaceutical applications. In this study, we used the cyclic peptide, sunflower trypsin inhibitor-1 (SFTI-1), as a model system to explore how the inhibitor's sequence and structure relate to its binding kinetics and function. Using enzyme assays, MD simulations and NMR spectroscopy to study SFTI variants with diverse sequence and backbone modifications, we show that the geometry of the binding loop mainly influences the inhibitor's potency by modulating the association rate, such that variants lacking a favourable conformation show dramatic losses in activity. Additionally, we show that the inhibitor's sequence (including both the binding loop and its scaffolding) influences its potency and selectivity by modulating both the association and the dissociation rates. These findings provide new insights into protease inhibitor function and design that we apply by engineering novel inhibitors for classical serine proteases, trypsin and chymotrypsin and two kallikrein-related peptidases (KLK5 and KLK14) that are implicated in various cancers and skin diseases.

  • 19.
    Degerman, Sofie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Siwicki, Jan Konrad
    Revie, John
    Borssen, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Evelönn, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Chrzanowska, Krystyna H.
    Ryden, Patrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Keith, W. Nicol
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias2014Inngår i: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, nr 7, 606-615 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

  • 20.
    Devad, Martin
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Wallin, Peter
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Kosttillskott åt folket?!: en kvantitativ studie om användandet av och åsikter om kosttillskott2007Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Syfte & frågeställningar

    Syftet var att undersöka användandet av och uppfattningar om kosttillskott bland människor som tränar på gym. Frågeställningarna löd enligt följande:

    - Vilka kategorier av människor som tränar på gym använder kosttillskott?

    - Skiljer sig åsikterna om kosttillskott beroende på om man använder det eller inte?

    - Har användandet av kosttillskott någon inverkan på attityden till dopning?

    Metod

    Studien baseras på en kvantitativ enkätundersökning vilken utfördes på fyra olika gym inom Storstockholm. Tre utav gymmen representeras av två stora kedjor och det fjärde av ett mindre gym, vilket inte ingick i någon kedja. Gymmen selekterades genom att ta fram de två stora gymkedjornas samtliga anläggningar inom stor Stockholm och sedan numrera dessa varpå lottdragning utfördes. Samma procedur genomfördes gällande det mindre gymmet. Individerna som kom att delta i studien blev 169st varav 105 män och 64 kvinnor. Dessa selekterades genom ett frivilligt urval i samband med att de utvalda gymmen besöktes. Datan analyserades i SPSS där vi använt ett chi-2- samt Man Whitney U- test.

    Resultat

    Resultaten visade att användandet av kosttillskott var störst bland styrketränande män vilkas huvudmål med träningen var att förbättra hälsan samt bygga muskler. Åsikterna om kosttillskott skilde sig åt beroende på om respondenterna använde det eller inte. Detta framkom då de respondenter som nyttjade kosttillskott såg fler fördelar och hade en positivare inställning till användandet. I studien framkom det att majoriteten (85.1 %, n = 168) av respondenterna var emot användandet av dopning. Bland användarna var det 26.7 % (n = 75) som ansåg att det var upp till individen att bestämma om denne ville nyttja dopning.

    Slutsats

    Användandet av kosttillskott var förhållandevis stort då 44,9 % av respondenterna använde det mer eller mindre regelbundet. Majoriteten (59,6 %) av respondenterna uppgav att det var upp till individen att bestämma om denne ville nyttja kosttillskott. Tron på att kosttillskott ger effekt på träningen men att det kan bli skadligt vid överdosering delades också av majoriteten (54,8 %) av respondenterna.

  • 21. Drager, Luciano F.
    et al.
    Li, Jianguo
    Shin, Mi-Kyung
    Reinke, Christian
    Aggarwal, Neil R.
    Jun, Jonathan C.
    Bevans-Fonti, Shannon
    Sztalryd, Carole
    OByrne, Sheila M.
    Kroupa, Olessia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Blaner, William S.
    Polotsky, Vsevolod Y.
    Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea2012Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, nr 6, 783-U33 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5 once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a 5-fold decrease in LpL activity (P 0.01) and an 80 increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.

  • 22.
    Edfors, Inger
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Torremorrel, M
    Univ Minnesota.
    Escherichia coli and Salmonella in pigs2010Inngår i: Breeding for Disease Resistance in Farm Animals / [ed] RFA Axford, S Bishop, F Nicholas, JB Owen, Walllingford, UK: CABI Publishing, 2010, 3rd, 232-250 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Diarrhoea due to bacterial infections is a problem mainly in the young growing animal, including the pig. Among the bacteria that cause diarrhoea in pigs are various strains of Escherichia coli and Salmonella. Considerable genetic variation in resistance/susceptibility has been found for both neonatal and post-weaning diarrhoea caused by E. coli carrying F4 fimbriae and post-weaning diarrhoea and oedema disease due to E. coli strains with F18 fimbriae. The loci for the receptors of both types of fimbriae have been mapped: the F4 receptor(s) to chromosome 13 (SSC13) and the F18 receptor to chromosome 6 (SSC6). Several candidate genes have been suggested for the F4 receptor, among them different mucine genes (MUC4, MUC13), and a very close association between a single-nucleotide polymorphism (SNP) in an alpha (1, 2) fucosyltransferase gene (FUT1) and the F18 receptor has been identified.Resistance to Salmonella infections in mice is associated with the antimicrobial activity of macrophages, and some studies have suggested that it is linked with polymorphism in the Nramp1 gene. The gene has been identified in several species including the pig, but data are so far lacking concerning association between polymorphism in the porcine gene and resistance-susceptibility to Salmonella infection. Using transcriptome profiles, several porcine genes that are differentially up or downregulated during Salmonella infection have been identified. Further studies of associations between polymorphisms in these genes and the outcome of Salmonella infection may facilitate the development of tools to identify carrier pigs, and lead towards identification of markers that can be used to select for resistant pigs.Breeding for increased disease resistance can be potentially performed in several ways; excluding susceptible breeding of animals after exposure, marker-assisted selection (MAS) based on closely linked loci or direct selection based on polymorphism in the causative gene. The rapid development in molecular genetics has provided dense genome maps and the tools to identify and study individual genes, both at the deoxyribonuclease acid (DNA) and the expression level. Overall use of genetic markers influencing disease traits is expected to increase significantly in the coming years. This number will grow as large-scale accurate disease phenotypes are collected in pedigreed populations. It is likely that many disease markers will contribute additively to the selection criteria and will be used as part of complex selection indices that will balance other economically significant traits.

  • 23.
    Ekhtiari Bidhendi, Elaheh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Bergh, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Zetterström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease2016Inngår i: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, nr 6, 2249-2253 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is an adult-onset degeneration of motor neurons that is commonly caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Both patients and Tg mice expressing mutant human SOD1 (hSOD1) develop aggregates of unknown importance. In Tg mice, 2 different strains of hSOD1 aggregates (denoted A and B) can arise; however, the role of these aggregates in disease pathogenesis has not been fully characterized. Here, minute amounts of strain A and B hSOD1 aggregate seeds that were prepared by centrifugation through a density cushion were inoculated into lumbar spinal cords of 100-day-old mice carrying a human SOD1 Tg. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill after approximately 100 days, which is 200 days earlier than for mice that had not been inoculated or were given a control preparation. Concomitantly, exponentially growing strain A and B hSOD1 aggregations propagated rostrally throughout the spinal cord and brainstem. The phenotypes provoked by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. Together, our data indicate that the aggregate strains are prions that transmit a templated, spreading aggregation of hSOD1, resulting in a fatal ALS-like disease.

  • 24.
    Ekorn, Bonnie
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Holmgren, Maria
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Frulle = full rulle?: en kvantitativ studie om frukostens inverkan på elevers fysiska prestation i ämnet idrott och hälsa2007Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Sammanfattning

    Syfte och frågeställningar

    Syftet var att undersöka om frukosten har någon inverkan på den fysiska prestationen i ämnet idrott och hälsa. Frågeställningarna var:

    • Finns det något samband mellan fysisk prestation och frukost hos elever som äter respektive inte äter frukost?

    • Är det någon skillnad i den fysiska prestationen mellan könen, bland de elever som äter respektive inte äter frukost?

    • Finns det något samband mellan fysisk prestation, tidpunkt för frukostintag och idrott och hälsa bland elever som äter respektive inte äter frukost?

    Metod

    Undersökningen är kvantitativ och har genomförts bland 89 elever i skolår 7 och 8. Det externa bortfallet var 28,8 procent. Studien genomfördes i idrott och hälsa där eleverna deltog och sedan svarade på en enkät. I statistikprogrammet SPSS fastställdes resultatet.

    Resultat

    Frukosten har en inverkan på prestationen i form av svett. De elever som äter frukost svettas mer. Det finns ingen skillnad i prestation mellan flickor och pojkar som har ätit respektive inte ätit frukost. Tidpunkten för frukostintaget har en inverkan på prestationen i form av svett. Ju kortare tid mellan frukostintag och aktivitetsutövande, desto mer svettas eleven.

    Slutsats

    Som slutsats kan vi se att frukosten har en inverkan på prestationen i form av svett. De elever som äter frukost svettas mer.

  • 25.
    Elmahalawy, Safaa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Single Nucleotide Polymorphism (SNP) in dyf7- 141 of Haemonchus contortus as potential marker for ivermectin resistance2017Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Fulltekst tilgjengelig fra 2018-12-26 11:28
  • 26.
    Gallwitz, Maike
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär immunologi. Molekylär immunologi.
    Rapid species-specific diversification of the mast cell chymase locus during mammalian evolution.2006Inngår i: Immunogenetics, Vol. 58, 641-654 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Ghareh Baghi, Ghareh Baghi
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Assessment of Valvular Aortic Stenosis by Signal Analysis of the Phonocardiogram2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Aortic stenosis (AS) is one of the most prevalent valvular heart diseases in elderly people. According to the recommendations of both the American Heart Association and the European Society of Cardiology, severity assessment of AS is primarily based on echocardiographic findings. The experience of the investigator here play important roles in the accuracy of the assessment, and therefore in the disease management. However, access to the expert physicians could be limited, especially in rural health care centers of developing countries.

    This thesis aims to develop processing algorithms tailored for phonocardiographic signal with the intension to obtain a noninvasive diagnostic tool for AS assessment and severity grading. The algorithms employ a phonocardiogram as input signal and perform analysis for screening and diagnostics. Such a decision support system, which we call “the intelligent phonocardiography”, can be widely used in primary healthcare centers.

    The main contribution of the thesis is to present innovative models for the phonocardiographic analysis by taking the segmental characteristics of the signal into consideration. Three novel methodologies are described, based on the presented models, to perform robust classification. In the first attempt, a novel pattern recognition framework is presented for screening of AS-related murmurs. The framework offers a hybrid model for classifying cyclic time series in general, but is tailored to detect the murmurs as a special case study. The time growing neural network is another method that we use to classify short time signals with abrupt frequency transition. The idea of the growing frames is extended to the cyclic signals with stochastic properties for the screening purposes. Finally, a combined statistical and artificial intelligent classifier is proposed for grading the severity of AS.

    The study suggests comprehensive statistical validations not only for the evaluation and representation of systolic murmurs but also for setting the methodology design parameters, which can be considered as one of the significant features of the study. The resulting methodologies can be implemented by using web and mobile technologies to be utilized in distributed healthcare system.

  • 28.
    Ghebresus, Awet Ambesaghir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Division for Clinical Pharmacology,Department of Laboratory Medicine, Karolinska Institutet .
    Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Studies of Nandrolone Decanoate2015Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Introduction: Nandrolone is one of the most abused androgenic anabolic steroid. Nandrolone is, inside the body, primarily metabolized into 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Nandrolone abuse has been shown to cause alterations in the lipid- and endocrine profile, also to induce endothelial dysfunction. The mechanisms behind the alterations in these endogenous substances are not known, but one might speculate that alteration in gene expression may partly play a role.

    Aim: To analyze how a single dose of nandrolone affect the oxidative stress, the cholesterol and endocrine profile in healthy volunteers, and to analyze the androgenic effect as determined by testosterone and LH/FS levels in relation to genetic variations, in order to increase the knowledge on nandrolone side effects in humans.

    Materials and Methods: Elevenhealthy subjects were included. Genotyping was done using TaqMan allelic discrimination method and quantitative PCR. Real-time PCR was conducted to quantify the gene expression of HMGCR and the SOD’s. The cholesterol profile and hormone levels were analyzed at the Division of Clinical Chemistry and the hematocrit profile were measured at the Anti-Doping Laboratory according to WADA’s technical document TD2014 BAR.

    Results: Several correlations between lipoproteins and hormones were found. The gene expression of HMGCR was induced but showed no correlation with other results. Significant alterations were found on the serum levels of LH, FSH, testosterone, total cholesterol, LDL, ApoB and SHBG. Association between UGT2B17 ins/del polymorphism and a slower decrease of serum testosterone showed significance. The hematocrit profile was not altered whereas an increase in lymphocyte count was noted.

    Conclusions: One single dose of nandrolone causes a perturbation in the blood lipid- and endocrine profile. Genetic polymorphism may partly affect the serum levels of testosterone post nandrolone administration.

  • 29.
    Halin Bergström, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rudolfsson, Stina H.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype2016Inngår i: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 18, nr 3, 152-161 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prostate cancer generally metastasizes to bone, and most patients have tumor cells in their bone marrow already at diagnosis. Tumor cells at the metastatic site may therefore progress in parallel with those in the primary tumor. Androgen deprivation therapy is often the first-line treatment for clinically detectable prostate cancer bone metastases. Although the treatment is effective, most metastases progress to a castration-resistant and lethal state. To examine metastatic progression in the bone microenvironment, we implanted androgen-sensitive, androgen receptor-positive, and relatively slow-growing Dunning G (G) rat prostate tumor cells into the tibial bone marrow of fully immune-competent Copenhagen rats. We show that tumor establishment in the bone marrow was reduced compared with the prostate, and whereas androgen deprivation did not affect tumor establishment or growth in the bone, this was markedly reduced in the prostate. Moreover, we found that, with time, G tumor cells in the bone microenvironment progress to a more aggressive phenotype with increased growth rate, reduced androgen sensitivity, and increased metastatic capacity. Tumor cells in the bone marrow encounter lower androgen levels and a higher degree of hypoxia than at the primary site, which may cause high selective pressures and eventually contribute to the development of a new and highly aggressive tumor cell phenotype. It is therefore important to specifically study progression in bone metastases. This tumor model could be used to increase our understanding of how tumor cells adapt in the bone microenvironment and may subsequently improve therapy strategies for prostate metastases in bone.

  • 30.
    Hedberg, Carina
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Kyhlstedt, Madeleine
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Samvarierar frukostfrekvens och betyg?: En kvantitativ studie om sambandet mellan frukostfrekvens och betyg hos gymnasieelever på samhälls- och naturvetenskapliga programmen2008Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Sammanfattning

    Syfte och frågeställningar

    Syftet med denna studie var att undersöka om det hos gymnasieelever på samhälls- och naturvetenskapliga programmen finns ett samband mellan frukostfrekvens och prestation mätt i betyg. För att kunna uppnå syftet användes följande frågeställningar:

    • Finns det en korrelation mellan frukostfrekvens och betyg (betyg mäts i medelpoäng för svenska, engelska, matematik och samhällskunskap)?

    • Kan potentiella confounders förklara detta eventuella samband?

    Metod

    Den undersökta populationen bestod av 238 gymnasieelever i åldrarna 15-19 år. 122 av dessa var flickor och 116 var pojkar. På tre valda gymnasieskolor i Stockholms län gjordes ett riktat slumpmässigt urval bland eleverna. Studien byggde på självrapporterad data som inhämtades genom en enkät. Vi ställde frågor om exempelvis kroppsstorlek, frukostfrekvens, betyg, föräldrarnas postgymnasiala studienivå, studietid utanför lektionstid och boendeform.

    Resultat

    Könsfördelningen var jämn – 51,3 % var flickor och 48,7 % var pojkar. För båda könen gällde att drygt två tredjedelar åt frukost samtliga veckans skoldagar. Anmärkningsvärt är att en av tio flickor aldrig åt frukost under en skolvecka. En stor andel elever hade betyget MVG och särskilt utmärkande var flickornas betyg i engelska där hela tre fjärdedelar hade det högsta betyget. Gällande programmen var både antalet elever och kön relativt jämnt fördelade. Medianmedelpoängen utifrån de fyra betygen i matematik, svenska, engelska och samhällskunskap var för flickor 17,5 (sd 2,5) och för pojkar 16,8 (sd 2,7). Det fanns en positiv korrelation (Spearman’s) mellan frukostfrekvens och medianmedelpoäng. För att ta hänsyn till möjliga confounders gjordes en logistisk regression. Av de oberoende variablerna visade sig endast frukostfrekvens och vilket program eleven gick vara signifikanta prediktorer för medelpoängen. Således hade de som åt frukost bättre betyg än de som inte gjorde det och de som gick naturvetenskapliga programmet hade bättre betyg än de som gick samhälls-vetenskapliga programmet. 20 % av variationen i medelpoäng förklaras alltså av de två variablerna frukostfrekvens och gymnasieprogram.

    Slutsats

    Slutsatsen är att det finns ett positivt samband mellan frukostfrekvens och prestation mätt i betyg. Även efter kontroll för confounders var denna korrelation signifikant. Även vilket gymnasieprogram eleven studerade korrelerade med medelpoäng.

  • 31.
    Henriksson, Richard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Backman, Cristina M
    Harvey, Brandon K
    Kadyrova, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Bazov, Igor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Shippenberg, Toni S
    Bakalkin, Georgy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain2014Inngår i: Biochimica et Biophysica Acta, ISSN 0006-3002, Vol. 1839, nr 11, 1226-1232 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dynorphin kappa-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.

  • 32.
    Hysing, Tommy
    Örebro universitet, Institutionen för klinisk medicin.
    Uppföljning av TSH`s beslutsgränser för analys av TPO-antikroppar2006Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Mätning av autoantikroppar mot tyreoperoxidas (TPO) är en

    viktig del för att diagnostisera autoimmun tyreoideafunktions rubbning. Hos det stora flertalet som har en autoimmun tyreoidea sjukdom hittar man TPO-antikroppar. Vid hypotyreos är det av betydelse att se om det finns TPO-antikroppar för att påvisa eller utesluta autoimmunitet som orsak till hypotyreosen.

    Ett problem är att det inte finns något allmänt accepterat referensintervall för TPO-antikroppar. I Sverige varierar det mellan 2 och 60 kIU/l beroende på vilken mätmetod som används.

    Syftet med denna undersökning är att se hur vanligt det är med förhöjda värden för tyreoidea stimulerande hormon (TSH) och hur fördelningen av antikroppar för tyreoidea peroxidas (TPO-antikroppar) ser ut vid normala och subnormala TSH-värden.

    De serumprover som ingick i undersökningen analyserades med en fluoroimmunoassay teknik på instrumentet AutoDELFIAÔ , Perkin-Elmer. Proverna valdes slumpmässigt från de rutinprover som kommer till laboratoriet.

    Mellan 8 – 13 % av de undersökta patientproverna har en lätt förhöjning (4,3 – 6,0 mIU/l) av TSH-värdena. Totalt för alla värden mer än 4,3 mIU/l är 15 %.

    Kvinnor har en högre andel av TPO-antikroppar jämfört med män vilket andra undersökningar också visat.

    Referensintervallet, < 35 kIU/l, för TPO-antikroppar är relevant gentemot frågeställningen. I den undersökta populationen är det ett prov som hamnar utanför detta intervall.

    44 % hade förhöjda värden på TPO-antikroppar vid måttligt förhöjda TSH värden, detta indikerar att analys av TPO-antikroppar bör göras när TSH visar värden > 4,3 mIU/l.

    Den metodjämförelse som gjordes mellan fluoroimmunoassay och kemiluminiscens visar på dålig korrelation.

    Denna undersökning är en pilotstudie för att kunna gå vidare med frågeställningar som

    - kan man korrigera på något sätt för de olikheter som uppenbarligen finns mellan de olika mätmetoderna

    - kan man ta bort spädningssteget i fluoroimmunoassay-metoden för att därigenom kunna sänka referensgränsen

  • 33.
    Isoz, Isabelle
    Umeå universitet, Medicinsk fakultet, Medicinsk kemi och biofysik.
    Role of yeast DNA polymerase epsilon during DNA replication2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Each cell division, the nuclear DNA must be replicated efficiently and with high accuracy to avoid mutations which can have an effect on cell function. There are three replicative DNA polymerases essential for the synthesis of DNA during replication in eukaryotic cells. DNA polymerase α (Pol α) synthesize short primers required for DNA polymerase δ (Pol δ) and DNA polymerase ε (Pol ε) to carry out the bulk synthesis. The role of Pol δ and Pol ε at the replication fork has been unclear. The aim of this thesis was to examine what role Pol ε has at the replication fork, compare the biochemical properties of Pol δ and Pol ε, and to study the function of the second largest and essential subunit of Pol ε, Dpb2.

    To identify where Pol ε replicates DNA in vivo, a strategy was taken where the active site of Pol ε was altered to create a mutator polymerase leaving a unique error-signature. A series of mutant pol ε proteins were purified and analyzed for enzyme activity and fidelity of DNA synthesis. Two mutants, M644F and M644G, exhibited an increased mutation rate and close to normal polymerase activity. One of these, the M644G gave rise to a specific increase of mismatch mutations resulting from T-dTMP mis-pairing during DNA synthesis in vitro. The M644G mutant was introduced in yeast strains carrying a reporter gene, URA3, on either side of an origin in different orientations. Mutations which inactivated the URA3 gene in the M644G mutant strains were analyzed. A strand specific signature was found demonstrating that Pol ε participates in the synthesis of the leading strand.

    Pol δ and Pol ε are both stimulated by the processivity clamp, PCNA, in in vitro replication assays. To clarify any differences they were challenged side by side in biochemical assays. Pol ε was found to require that single-stranded template (ssDNA) was entirely coated with RPA, whereas Pol δ was much less sensitive to uncoated ssDNA. The processivity of Pol δ was stimulated to a much higher degree by PCNA than of Pol ε. In presence of PCNA the processivity of Pol δ and Pol ε was comparable. In contrast, Pol ε was approximately four times slower than Pol δ when replicating a single-primed circular template in the presence of all accessory proteins and an excess of polymerase. The biochemical characterization of the system suggests that Pol ε and Pol δ are loaded onto the PCNA-primer-ternary complex by separate mechanisms. A model is proposed where the loading of Pol ε onto the leading strand is independent of the PCNA interaction motif which is required by enzymes acting on the lagging strand.

    The essential gene DPB2 encodes for the second largest subunit of Pol ε. We carried out a genetic screen in S.cerevisiae and isolated a lethal mutant allele of dpb2 (dpb2-200). When over-expressed together with the remaining three subunits of Polε, Pol2, Dpb3 and Dpb4, the dpb2-201 did not copurify. The biochemical property of Pol2/Dpb3/Dpb4 complex was compared with wild-type four-subunit Pol ε (Pol2/Dpb2/Dpb3/Dpb4) and a Pol2/Dpb2 complex in replication assays. The absence of Dpb2 in the complex did not significantly affect the specific activity or the processivity, but gave a slightly reduced efficiency in holoenzyme assays when compared to wild-type four-subunit Pol ε. We propose that Dpb2 is not essential for the enzyme activity of Pol ε.

  • 34. Jacobsen, M
    et al.
    Kracht, SS
    Esteso, G
    Cirera, S
    Edfors, Inger
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Archibald, AL
    Bendixen, C
    Anderson, L
    Fredholm, M
    Jorgensen, CB
    Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs.2010Inngår i: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 41, 21-25 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    P>Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13. Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4, to be associated with F4ab/ac susceptibility.

  • 35.
    Jegefalk, Annelie
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Csiffary, Thomas
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap.
    Ökat kreatinintag = Ökad kraft: en träningsstudie om kreatinets prestationshöjande effekt och korrelationen mellan styrkeökning och kreatinupptag.2007Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Sammanfattning

    Syfte och frågeställningar

    Syftet med studien var att undersöka kreatinets prestationshöjande effekt på styrka efter en sex dagars kreatinuppladdning samt undersöka om en korrelation mellan kreatinupptag och styrkeförändring förelåg. Frågeställningar var:

    Hur skiljer sig den statiska styrkan i biceps efter en sex dagar lång kreatinuppladdning?

    Hur skiljer sig den dynamiska styrkan i bänkpress efter en sex dagar lång kreatinuppladdning?

    Finns det någon korrelation mellan förändring av styrka och upptag av kreatin?

    Metod

    Studien genomfördes på 22 fysiskt aktiva friska svenska män och kvinnor (13 män, 9 kvinnor) som delades in i antingen en kreatingrupp (n=12) eller en kontrollgrupp (n=10). Båda grupperna genomförde tre testtillfällen (T1, T2, T3) där T1 syftades till att mäta upp deras 1RM. Vid T2 och T3 mättes deltagarnas statiska styrka i biceps (höger och vänster) samt deras dynamiska styrka i bänkpress. Mellan T2 och T3 gavs kreatingruppen 20 gram kreatin om dagen uppdelat vid 4 olika tillfällen i 6 dagar. En 24-timmars urininsamling genomfördes på samtliga deltagare i kreatingruppen under den andra dagen på kreatinuppladdningen för att mäta deras kreatinupptag.

    Resultat

    Kreatingruppens medelökning i bicepsövningen motsvarade som lägst 2,08 sekunder och som högst 9,33 sekunder där den största ökningen skedde under set 1 för höger arm. I den dynamiska bänkpressen visade kreatingruppen en ökning motsvarande 3,41 repetitioner. Inga signifikanta höjningar sågs för kontrollgruppen under något av seten. Inga korrelationer mellan kreatinupptag och styrkeförändring kunde påvisas i studien.

    Slutsats

    Resultaten från föreliggande studie indikerar på att ett oralt kreatinintag på 20 (4 tillfällen á 5 gram) gram kreatin om dagen i 6 dagar ger en förhöjd isometrisk prestation i biceps under tre set med 60 sekunders vila (p<0,05 under fem av sex set). Intaget tycks även resultera i en medelökning på 3,41 utförda repetitioner under det första setet i en dynamisk bänkpress (67 % av 1RM som belastning). Dessa resultat bör emellertid beskådas kritiskt sedan studien inte använde sig av något placebopreparat, vilket kan ha inneburit att en placeboeffekt förelåg.

  • 36.
    Jonsson, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Byström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Davidson, Alice E.
    UCL Institute of Ophthalmology, London, UK.
    Backman, Ludvig J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kellgren, Therese
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Tuft, Stephen J.
    UCL Institute of Ophthalmology, London, UK; Moorfields Eye Hospital, London, UK.
    Koskela, Timo
    Koskelas Eye Clinic, Umeå, Sweden.
    Ryden, Patrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Sandgren, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Hardcastle, Alison J.
    UCL Institute of Ophthalmology, London, UK.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)2015Inngår i: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, nr 4, 463-473 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.

  • 37.
    Klütsch, Cornelya
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Seppälä, E. H.
    Fall, T.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Hedhammar, Å.
    Lohi, H.
    Savolainen, Peter
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia2011Inngår i: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 42, nr 1, 100-103 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    P>The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.

  • 38. Kyro, Cecilie
    et al.
    Olsen, Anja
    Bueno-de-Mesquita, H. B(as).
    Skeie, Guri
    Loft, Steffen
    Aman, Per
    Leenders, Max
    Dik, Vincent K.
    Siersema, Peter D.
    Pischon, Tobias
    Christensen, Jane
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Cottet, Vanessa
    Kuehn, Tilman
    Chang-Claude, Jenny
    Boeing, Heiner
    Trichopoulou, Antonia
    Naska, Androniki
    Oikonomidou, Despoina
    Masala, Giovanna
    Pala, Valeria
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Peeters, Petra H.
    Bakken, Toril
    Weiderpass, Elisabete
    Asli, Lene Angell
    Sanchez, Soledad
    Jakszyn, Paula
    Sanchez, Maria-Jose
    Amiano, Pilar
    Maria Huerta, Jose
    Barricarte, Aurelio
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J.
    Travis, Ruth C.
    Slimani, Nadia
    Freisling, Heinz
    Ferrari, Pietro
    Gunter, Marc J.
    Murphy, Neil
    Riboli, Elio
    Tjonneland, Anne
    Landberg, Rikard
    Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2014Inngår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, nr 10, 1881-1890 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.

  • 39.
    Källebring, Tina
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    THE EXPRESSION OF THROMBOMODULIN, TISSUE FACTOR, TISSUE FACTOR PATHWAY INHIBITOR AND ENDOTHELIAL PROTEIN C RECEPTOR IN NORMAL AND IUGR PLACENTA2005Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    The aim of this study was to examine the expression of Thrombomodulin, Tissue Factor, Tissue Factor Pathway Inhibitor and Endothelial Protein C Receptor in placenta throughout the three phases of the third trimester in the normal placenta and in IUGR placenta from full term.

    Twenty-five normal placenta samples and twenty-five IUGR placenta samples were obtained and each sample was stained by immunohistochemistry using monoclonal antibodies. Each antibody was optimised for antigen retrieval method and for optimal dilution, before been applied to the test tissue.

    The results showed that each of the antibodies mentioned was expressed in normal placenta and in IUGR placenta.

    No significant difference could be established concerning the expression of each antibody mentioned between normal and IUGR placenta.

  • 40.
    Lee, Francis
    Linköpings universitet, Institutionen för tema, Tema teknik och social förändring. Linköpings universitet, Filosofiska fakulteten.
    Purity and interest: on relational work and epistemic value in the biomedical sciences2015Inngår i: Value practice in the life sciences and medicine / [ed] Isabelle Dussauge, Claes-Fredrik Helgesson, Francis Lee, oxford: Oxford University Press, 2015, 207-223 s.Kapittel i bok, del av antologi (Fagfellevurdert)
  • 41. Lindqvist, Breezy M.
    et al.
    Wingren, Sten
    Motlagh, Parviz Behnam
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Whole genome DNA methylation signature of HER2-positive breast cancer2014Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 9, nr 8, 1149-1162 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In order to obtain a comprehensive DNA methylation signature of HER2-positive breast cancer (HER2+ breast cancer), we performed a genome-wide methylation analysis on 17 HER2+ breast cancer and compared with ten normal breast tissue samples using the Illumina Infinium HumanMethylation450 BeadChip (450K). In HER2+ breast cancer, we found altered DNA methylation in genes involved in multicellular development, differentiation and transcription. Within these genes, we observed an overrepresentation of homeobox family genes, including several genes that have not been previously reported in relation to cancer (DBX1, NKX2-6, SIX6). Other affected genes included several belonging to the PI3K and Wnt signaling pathways. Notably, HER2, AKT3, HK1, and PFKP, genes for which altered methylation has not been previously reported, were also identified in this analysis. In total, we report 69 candidate biomarker genes with maximum differential methylation in HER2+ breast cancer. External validation of gene expression in a selected group of these genes (n = 13) revealed lowered mean gene expression in HER2+ breast cancer. We analyzed DNA methylation in six top candidate genes (AKR1B1, INA, FOXC2, NEUROD1, CDKL2, IRF4) using EpiTect Methyl II Custom PCR Array and confirmed the 450K array findings. Future clinical studies focusing on these genes, as well as on homeobox-containing genes and HER2, AKT3, HK1, and PFKP, are warranted which could provide further insights into the biology of HER2+ breast cancer.

  • 42.
    Lundholm, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hägglöf, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikberg, Maria L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. anders.bergh@umu.se.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Edin, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Secreted Factors from Colorectal and Prostate Cancer Cells Skew the Immune Response in Opposite Directions2015Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 15651Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Macrophage infiltration has been associated with an improved prognosis in patients with colorectal cancer (CRC), but a poor prognosis in prostate cancer (PC) patients. In this study, the distribution and prognostic value of proinflammatory M1 macrophages (NOS2(+)) and immunosuppressive M2 macrophages (CD163(+)) was evaluated in a cohort of 234 PC patients. We found that macrophages infiltrating PC were mainly of an M2 type and correlated with a more aggressive tumor and poor patient prognosis. Furthermore, the M1/M2 ratio was significantly decreased in PC compared to CRC. Using in vitro cell culture experiments, we could show that factors secreted from CRC and PC cells induced macrophages of a proinflammatory or immunosuppressive phenotype, respectively. These macrophages differentially affected autologous T lymphocyte proliferation and activation. Consistent with this, CRC specimens were found to have higher degrees of infiltrating T-helper 1 cells and active cytotoxic T lymphocytes, while PC specimens displayed functionally inactive T cells. In conclusion, our results imply that tumour-secreted factors from cancers of different origin can drive macrophage differentiation in opposite directions and thereby regulate the organization of the anti-tumour immune response. Our findings suggest that reprogramming of macrophages could be an important tool in the development of new immunotherapeutic strategies.

  • 43.
    Lundin, Desiré
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Do the new signal transduction modulators have activity in vitro in tumor cells from ovarian carcinoma and lymphoma?2005Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    During the last decades, chemotherapy with cytotoxic drugs has played a significant role in cancer therapy. It’s important to develop new anticancer drugs, and drug sensitivity testing in vitro can be used to find the right diagnosis for the newly developed substances.

    The aim of this study was to investigate the cytotoxic activity of the new signal transduction modulators bortezomib, gefitinib and PKC412. The well-established substances cisplatin, cytarabine, doxorubicin and vincristin were investigated for comparison.

    The activity of the cytotoxic drugs was analysed in human tumor samples from patients with ovarian carcinoma (n=16) and lymphoma (n=15) by using the Fluorometric Microculture Cytotoxicity Assay (FMCA). The testing of cellular drug resistance by FMCA was accomplished successfully in 33 out of the 34 samples (97%).

    The results of this study indicated that the activity of cytotoxic drugs in tumor cells obtained from patients with ovarian carcinoma and lymphoma may be detected by the FMCA. It also suggested that bortezomib and gefitinib could represent promising agents for treatment of ovarian carcinoma and that PKC412 might be of less use for patients with this diagnose.

  • 44.
    Lönn, Johanna
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. PEAS Institute, Linköping, Sweden.
    Shahzad, Faisal
    PEAS Institute, Linköping, Sweden.
    Uhlin, Fredrik
    Department of Nephrology UHL, County Council of Östergötland, Sweden; Department of Medicine and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för läkarutbildning. Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Almroth, Gabriel
    Department of Nephrology UHL, County Council of Östergötland, Department of Medicine and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden.
    Nayeri, Fariba
    PEAS Institute, Linköping, Sweden; Department of Molecular and Clinical Medicine, Division of Infectious Diseases, University Hospital, Linköping, Sweden.
    High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure2012Inngår i: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 3, nr 4, 516-523 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased affinity to HSPG (P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

  • 45. Marincevic-Zuniga, Yanara
    et al.
    Zachariadis, Vasilios
    Cavelier, Lucia
    Castor, Anders
    Barbany, Gisela
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Fogelstrand, Linda
    Heyman, Mats
    Abrahamsson, Jonas
    Lonnerholm, Gudmar
    Nordgren, Ann
    Syvanen, Ann-Christine
    Nordlund, Jessica
    PAX5-ESRRB is a recurrent fusion gene in B-cell precursor pediatric acute lymphoblastic leukemia2016Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, nr 1, E20-E23 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 46.
    Mascher, Henrik
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Tannerstedt, Jörgen
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Blomstrand, Eva
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Nya aspekter på aminosyrors roll i den muskulära anpassningen till träning2006Inngår i: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 15, nr 3, 56-60 s.Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [sv]

    Sammanfattningsvis kan sägas att tillgängligheten av protein/aminosyror är nödvändig för den muskulära anpassningen till träning vid både styrke- och uthållighetsträning. Betydligt fler studier har undersökt effekterna på styrketräning, men vid båda typer av träning är dock kunskaperna om de bakomliggande mekanismerna ännu så länge små. Genom den omfattande forskning som pågår inom området kommer med all säkerhet de molekylära och cellulära förändringar som sker i samband med träning att kartläggas inom en relativt snar framtid. Därmed öppnas nya möjligheter att förbättra och optimera träningen, t.ex. genom kombination av olika typer av aktiviteter (uthållighet och styrketräning). Denna kunskap är också avgörande för att förstå och eventuellt kunna påverka träningseffekten genom förändringar i nutritionens sammansättning.

  • 47.
    Morrell, J. M.
    et al.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Nongbua, T.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Valeanu, S.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Lundstedt-Enkel, Katrin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Edman, A.
    Viking Genet, Ornsro, Skara, Sweden..
    Johannisson, A.
    Swedish Univ Agr Sci, Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Bull breed affects which parameters of sperm quality are indicative of fertility2016Inngår i: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 169, 112-113 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 48.
    Nilsson, Anders S.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Phage therapy-constraints and possibilities2014Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, nr 2, 192-198 s.Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The rise of antibiotic-resistant bacterial strains, causing intractable infections, has resulted in an increased interest in phage therapy. Phage therapy preceded antibiotic treatment against bacterial infections and involves the use of bacteriophages, bacterial viruses, to fight bacteria. Virulent phages are abundant and have proven to be very effective in vitro, where they in most cases lyse any bacteria within the hour. Clinical trials on animals and humans show promising results but also that the treatments are not completely effective. This is partly due to the studies being carried out with few phages, and with limited experimental groups, but also the fact that phage therapy has limitations in vivo. Phages are large compared with small antibiotic molecules, and each phage can only infect one or a few bacterial strains. A very large number of different phages are needed to treat infections as these are caused by genetically different strains of bacteria. Phages are effective only if enough of them can reach the bacteria and increase in number in situ. Taken together, this entails high demands on resources for the construction of phage libraries and the testing of individual phages. The effectiveness and host range must be characterized, and immunological risks must be assessed for every single phage.

  • 49.
    Nilsson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adamo, Hanibal
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Halin Bergström, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 19608Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.

  • 50.
    Nilsson, Torbjörn K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Böttiger, Anna K.
    Henriquez, Patricia
    Serra Majem, Lluis
    MTHFR polymorphisms and serum cobalamin affect plasma homocysteine concentrations differentially in females and males2014Inngår i: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 10, nr 5, 2706-2712 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A total of 523 subjects (297 females and 226 males) from the Canary Islands Nutrition Study (ENCA) were studied in order to examine the effect of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms, adjusted for age, serum (5)-folate and S-cobalamin levels, on total plasma homocysteine concentrations (tHcy). Genotyping was performed with Pyrosequencing(R) technology. The MTHFR 677T-allele was associated with increased tHcy concentrations only in males (P=0.005). The MTHFR 1298C-allele was found to be associated with higher tHcy levels but similarly, only in males (P=0.025). The MTHFR 1793A-allele was associated with decreased tHcy concentrations in the younger males (P=0.042). A haplotype-based approach was marginally superior in explaining the genetic interaction of the MTHFR polymorphisms on tHcy plasma levels (R-2 0.352 vs. 0.342 for a simple genotype-based approach). A nutrigenetic interaction between the MTHFR 677C>T genotype and S-cobalamin on tHcy levels was demonstrated in both genders. The increase in tHcy was more pronounced with decreasing S-cobalamin quintiles in 677TT homozygotes (P=0.005 for males and P=0.015 for females) than with decreasing S-folate quintiles (P for trend not significant). It was concluded that gene-nutrient interactions may differ depending on the sex and age of the subjects. The transferability of gene-nutrient interactions from one community to others may therefore be limited not only by different food patterns but also by different ages, genders and genotype distributions.

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