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1.
  • Gidlöf, Olof, et al. (author)
  • A Common Missense Variant in the ATP Receptor P2X7 Is Associated with Reduced Risk of Cardiovascular Events
  • 2012
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
  • Journal article (peer-reviewed)abstract
    • Background and Purpose: Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies. Methods: Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model. Results: The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively). Conclusions: A common loss-of-function missense variant in the gene encoding the P2X7 receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.
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  • Li, Cairu, et al. (author)
  • Ability of physical activity measurements to assess health-related risks.
  • 2009
  • In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63, s. 1448-1451
  • Journal article (peer-reviewed)abstract
    • The aim of this study is to evaluate if two different physical activity (PA) questionnaires have similar ability to rank individuals, and to examine associations with cardiovascular-metabolic risk factors, compared to an objective measure. In a random sample (n=369, age: 65+/-6 years) from the population-based 'Malmö Diet and Cancer' (MDC) cohort, PA was measured by a leisure-time comprehensive questionnaire (MDC-score), a simple leisure-time questionnaire and by accelerometer-monitoring (CSA). Moderate correlations were observed between MDC-score and CSA in men and women (r=0.35 and 0.24, respectively). In men, both questionnaires and CSA were inversely associated with waist circumference, insulin resistance and metabolic syndrome. In women, the MDC-score was positively associated with high-density lipoprotein-cholesterol, and the simple questionnaire inversely associated with anthropometric indexes, but no association was seen between PA estimates and cardiovascular components. We conclude that both PA questionnaires distinguish health risks associated with anthropometric-metabolic risk factors, particularly in men.European Journal of Clinical Nutrition advance online publication, 29 July 2009; doi:10.1038/ejcn.2009.69.
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  • Merlo, Juan, et al. (author)
  • Self-administered questionnaire compared with a personal diary for assessment of current use of hormone therapy: an analysis of 16,060 women
  • 2000
  • In: American Journal of Epidemiology. - 0002-9262. ; 152:8, s. 788-792
  • Journal article (peer-reviewed)abstract
    • A personal diary may be more appropriate than a questionnaire for assessing self-reported current use of hormone therapy (estrogens, progestagens, or their combination); however, use of a questionnaire is more feasible and less expensive. The authors compared both methods for 16,060 Swedish women aged 45-73 years from the Malmo Diet and Cancer Study (baseline, 1991-1996). In a reliability analysis, the authors investigated the agreement (kappa value) between the questionnaire and the diary regarding current hormone therapy use (yes vs. no), studying the ability to replicate results whether or not they were correct. They also explored associations between discrepancy and individual characteristics. A validity analysis was conducted to determine whether use of the questionnaire achieved an outcome without systematic error (i.e., high specificity and sensitivity); the personal diary was considered the "gold standard." Agreement between both methods was high: 95.5% (kappa = 0.840). The sensitivity was 84.9% and the specificity 97.7%. Higher body mass index and being a widow were associated with agreement, whereas age (50-59 years), use of anxiolytics/hypnotics or opiates, high alcohol consumption, past smoking, and higher educational level were associated with discrepancy. Compared with a personal diary, a simple self-administered questionnaire is a valid method for assessing current use of hormone therapy.
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4.
  • Smith, Gustav, et al. (author)
  • Common Genetic Variants on Chromosome 9p21 Confers Risk of Ischemic Stroke A Large-Scale Genetic Association Study
  • 2009
  • In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 2:2, s. 159-164
  • Journal article (peer-reviewed)abstract
    • Background-Epidemiological studies indicate a genetic contribution to ischemic stroke risk, but specific genetic variants remain unknown, with the exception of a few rare variants. Recent genome-wide association studies identified and replicated common genetic variants on chromosome 9p21 to confer risk of coronary heart disease. We examined whether these variants are associated with ischemic stroke. Methods and Results-We genotyped 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n = 1837 cases, 947 controls) and the Malmo Diet and Cancer study (MDC; n = 888 cases, 893 controls). We examined association in each study and in the pooled dataset. Adjustments were made for cardiovascular risk factors and further for previous myocardial infarction in MDC. We found a modest increase in ischemic stroke risk for 2 common (minor allele frequencies 0.46 to 0.49) variants, rs2383207 (P = 0.04 in Lund Stroke Register, P = 0.01 in MDC) and rs10757274 (P = 0.03 in Lund Stroke Register, P = 0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an odds ratio of 1.15 (95% CI, 1.05 to 1.25; P = 0.002) for the strongest variant rs2383207. Results were similar after adjustment for clinical covariates. rs1333049 also showed significant association in MDC, which increased in the pooled sample (P = 0.004). Conclusions-In this large sample (n = 4565), we detected common genetic determinants for ischemic stroke on chromosome 9p21. Our findings indicate that ischemic stroke shares pathophysiological determinants with coronary heart disease and other arterial diseases and highlight the need for large sample sizes in stroke genetics. (Circ Cardiovasc Genet. 2009; 2: 159-164.)
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  • Wirfält, Elisabet, et al. (author)
  • Food patterns and components of the metabolic syndrome in men and women: a cross-sectional study within the Malmo Diet and Cancer cohort
  • 2001
  • In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 154:12, s. 1150-1159
  • Journal article (peer-reviewed)abstract
    • This study examined the relations between food patterns and five components of the metabolic syndrome in a sample of Swedish men (n = 2,040) and women (n = 2,959) aged 45-68 years who joined the Malmo Diet and Cancer study from November 1991 to February 1994. Baseline examinations included an interview-administered diet history, a self-administered questionnaire, blood pressure and anthropologic measurements, and blood samples donated after an overnight fast. Cluster analysis identified six food patterns for which 43 food group variables were used. Logistic regression analysis was used to examine the risk of each component (hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, and central obesity) and food patterns, controlling for potential confounders. The study demonstrated relations, independent of specific nutrients, between food patterns and hyperglycemia and central obesity in men and hyperinsulinemia in women. Food patterns dominated by fiber bread provided favorable effects, while food patterns high in refined bread or in cheese, cake, and alcoholic beverages contributed adverse effects. In women, food patterns dominated by milk-fat-based spread showed protective relations with hyperinsulinemia. Relations between risk factors and food patterns may partly depend on gender differences in metabolism or food consumption and on variations in confounders across food patterns.
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7.
  • Albert, J., et al. (author)
  • Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
  • 2014
  • In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:10, s. 673-677
  • Journal article (peer-reviewed)abstract
    • The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.
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10.
  • Berglund, Annika, et al. (author)
  • Higher prehospital priority level of stroke improves thrombolysis frequency and time to stroke unit : the Hyper Acute STroke Alarm (HASTA) study
  • 2012
  • In: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 43:10, s. 2666-2670
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences.METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel.RESULTS: During 2008, 942 patients were randomized of which 53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in the Emergency Medical Communication Center randomized intervention group reached the stroke unit 26 minutes earlier than the control group (P<0.001) after the emergency call. Thrombolysis was given to 24% of the patients in the intervention group compared with 10% of the control subjects (P<0.001). The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention.CONCLUSIONS: This randomized study shows negligible harm to other medical emergencies, a significant increase in thrombolysis frequency, and a shorter time to the stroke unit for patients with stroke upgraded to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care.
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  • Berglund, Carolina, et al. (author)
  • Genetic diversity of methicillin-resistant Staphylococcus aureus carrying type IV SCCmec in Orebro County and the western region of Sweden
  • 2009
  • In: Journal of Antimicrobial Chemotherapy. - Oxford : Oxford University Press. - 0305-7453 .- 1460-2091. ; 63:1, s. 32-41
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Recent studies have shown a predominance of type IV SCCmec among the methicillin-resistant Staphylococcus aureus (MRSA) isolated in the low endemic areas of Orebro County and the western region of Sweden. However, many of these isolates were not possible to classify as existing subtypes IVa, IVb, IVc or IVd. METHODS: We analysed 16 such MRSA isolates by multilocus sequence typing, spa typing, staphylocoagulase (SC) typing and detection of type IVg and IVh SCCmec. MRSA that remained as unknown type IV SCCmec were investigated by long-range PCR covering the J1 region; however, only two isolates were possible to amplify by PCR. The nucleotide sequences of the entire SCCmec of these two MRSA were determined. In addition, isolates that had unknown SC types were investigated by nucleotide sequencing of the coa genes. RESULTS: Five of 16 isolates were classified as type IVg SCCmec, and four isolates had type IVh SCCmec. Two subtypes of type IV SCCmec shared J1 regions previously identified in other types of SCCmec, types I.2 and II.2. The novel elements were designated as type IVi and IVj SCCmec. In addition, the genetic backgrounds of these Swedish MRSA were diverse and constituted at least nine sequence types and eight SC types, including four new types of SC. CONCLUSIONS: Type IV SCCmec is occurring in heterogeneous clones of MRSA in Sweden, and the majority of the type IV SCCmec were identified in community-acquired MRSA. We describe two novel subtypes of type IV SCCmec with common J1 regions shared by other types of SCCmec, which indicate that J1 regions occurred as primordial SCC.
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  • Berglund, Carolina, 1980- (author)
  • Molecular epidemiology of methicillin-resistant staphylococcus aureus : epidemiological aspects of MRSA and the dissemination in the community and in hospitals
  • 2008
  • Doctoral thesis (other academic/artistic)abstract
    • Methicillin-resistenta Staphylococcus aureus (MRSA) som bär på genen mecA, har förekommit och spridit sig över hela världen, främst i sjukhusmiljö, och orsakat utbrott av vårdrelaterade (så kallade nosokomiala) infektioner. Dessa infektioner kan inte behandlas med stafylokock-penicilliner och MRSA-bakterierna är ofta resistenta även mot flera andra grupper av antibiotika vilket medför att infektionerna ofta är påtagligt svårbehandlade. Under senare år har emellertid allt fler fall beskrivits av samhällsförvärvad MRSA infektion, det vill säga uppträdande av MRSA hos personer som tidigare ej har haft kontakt med sjukhusvård eller behandlats med antibiotika. Det har länge varit oklart om de samhällsförvärvade MRSA [community-acquired (CA-MRSA)] representerar spridning av bakterier från sjukhusmiljön ut till samhället eller om dessa MRSA är spontant uppträdande. Många av dessa stammar har dessutom visat sig bära på sjukdomsrelaterade gener som vanligen inte återfinns hos S. aureus, t.ex. Panton Valentine leukocidin (PVL) som associeras med hudinfektioner och allvarlig lunginflammation med hög dödlighet hos unga och annars friska individer. Denna avhandling beskriver den molekylära epidemiologin hos MRSA med fokus på samhällsförvärvade MRSA som utgjorde mer än hälften av samtliga fall av MRSA i Örebro län och som dessutom ofta producerade PVL toxinet, vars funktion vidare analyserades i detalj. Undersökning av ursprung och släktskap hos samtliga MRSA som isolerats i Örebro län, samt karaktärisering av det genetiskt element som kallas staphylococcal cassette chromosome mec (SCCmec) vilket innehåller genen mecA och ibland även andra resistensgener, visade att CA-MRSA inte är relaterade till de nosokomiala MRSA, och att dessa har uppstått oberoende av varandra. Flertalet MRSA visade sig dessutom bära på SCCmec, och resistensmekanismer, som tidigare inte beskrivits. Troligen har dessa MRSA uppstått genom ett genetiskt utbyte av SCCmec mellan methicillin-resistenta koagulas-negativa stafylokocker (MR-KNS), som utgör huvudparten av normalfloran på huden, och methicillin-känsliga S. aureus som därvid erhåller genen mecA och resistensmekanismer mot samtliga stafylokockantibiotika. I den här avhandlingen framläggs bevis för att ett sådant genetiskt utbyte har skett på Barnkliniken på Universitetssjukhuset i Örebro i slutet på 1990-talet, vilket resulterade i uppkomsten av en ny klon av MRSA som därefter orsakade ett allvarligt utbrott. Kartläggning av DNA-sekvensen hos flertalet unika SCCmec från svenska MRSA gav dessutom en bättre förståelse för hur resistens uppkommer och sprider sig, samt mekanismerna bakom detta. Dessa nya kunskaper kan bidra till en förbättrad diagnostik av MRSA. Detta är framför allt av stor betydelse eftersom nya effektiva kloner av MRSA verkar kunna uppstå ute i samhället med potential att orsaka svårbehandlade infektioner men även att sprida sig bland den friska befolkningen.
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15.
  • Berglund, Carolina, et al. (author)
  • Multilocus sequence typing of methicillin-resistant Staphylococcus aureus from an area of low endemicity by real-time PCR
  • 2005
  • In: Journal of clinical microbiology. ; 43:9, s. 4448-4454
  • Journal article (peer-reviewed)abstract
    • A protocol for multilocus sequence typing (MLST) of methicillin-resistant Staphylococcus aureus (MRSA) was adapted to real-time LightCycler System PCR for efficient and rapid amplification of seven housekeeping genes in the same PCR run and real-time detection of the products. The method was evaluated on a representative and well-characterized collection of clinical MRSA isolates (n = 57) obtained from an area of low endemicity. Twenty sequence types (STs) and nine clonal complexes were identified. Combining STs and the staphylococcal cassette chromosome mec (SCCmec) type identified 27 different genotypes, and type IV SCCmec was present in 11 different STs. The presence of the Panton Valentine leukocidin (PVL) genes was found in isolates of four different STs. Eleven different STs were found among the community-acquired as well as among the hospital-acquired MRSA. The genetic heterogeneity was also denoted by pulsed-field gel electrophoresis analysis that showed 24 different pulsotypes among the 57 MRSA isolates. The presence of more than one different type of SCCmec in the same ST indicates that the MRSA clones have arisen at several occasions in the same genetic background by independent acquisition of SCCmec into methicillin-sensitive strains. This circumstance shows the importance of combining MLST data with SCCmec-typing results when investigating the origins of MRSA.
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16.
  • Berglund, Carolina, et al. (author)
  • Novel type of staphylococcal cassette chromosome mec in a methicillin-resistant Staphylococcus aureus strain isolated in Sweden
  • 2008
  • In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:10, s. 3512-3516
  • Journal article (peer-reviewed)abstract
    • We identified a novel type of staphylococcal cassette chromosome mec (SCCmec) element carried by methicillin-resistant Staphylococcus aureus (MRSA) strain JCSC6082 isolated in Sweden. The SCCmec element was demarcated by characteristic nucleotide sequences at both ends and was integrated at the 3' end of orfX. The element carried a novel combination of a type 5 ccr gene complex and class C1 mec gene complex. The J regions of the element were homologous to those of the SCCmercury element of S. aureus strain 85/2082, with nucleotide identity greater than 99%. However, the novel SCCmec element from JCSC6082 did not carry the mer operon nor Tn554, suggesting that evolution to SCCmec could have been from a common ancestor by acquisition of the class C1 mec gene complex. The novel SCCmec element from JCSC6082 was flanked by a novel SCC-like chromosome cassette (CC6082), which was demarcated by two direct repeats and could be excised from the chromosome independently of the SCCmec element. Our data suggest that novel SCCmec elements can be generated on the staphylococcal chromosome through the recombination between extant SCC elements and mec gene complexes.
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  • Berglund, Carolina, et al. (author)
  • The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus
  • 2008
  • In: Microbes and infection. - Paris : Elsevier. - 1286-4579 .- 1769-714X. ; 10:8, s. 878-884
  • Journal article (other academic/artistic)abstract
    • Methicillin-resistant Staphylococcus aureus isolated in the community (CA-MRSA) have been reported to carry the loci for Panton Valentine leukocidin (PVL) in high frequency. CA-MRSA in Orebro County, Sweden, constitutes at least 50% of MRSA and the PVL locus is detected in as many as 66% of these CA-MRSA isolates. The aim of this study was to characterize PVL-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus by molecular methods, to determine the nucleotide sequence of lukS-PV and lukF-PV in S. aureus isolates of different origins, and to investigate the biological consequence of variations occurring in the genes. The PVL-positive MRSA investigated were composed of six different STs (ST8, 36, 80, 152, 154, and 256). Six additional STs (ST5, 22, 25, 30, 88, and 567) were detected when investigating PVL-positive methicillin-susceptible S. aureus with MLST. Despite the different genetic origins of the isolates analyzed, the PVL genes were well conserved and only one mutation was non-synonymous. Evaluation of the consequence of this mutation showed that the mutated toxin and wild-type toxin had comparable biological activity on human polymorphonuclear cells.
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19.
  • Berglund, Carolina, et al. (author)
  • The origin of a methicillin-resistant Staphylococcus aureus isolate at a neonatal ward in Sweden : possible horizontal transfer of a staphylococcal cassette chromosome mec between methicillin-resistant Staphylococcus haemolyticus and Staphylococcus aureus
  • 2008
  • In: Clinical Microbiology and Infection. - Oxford : Blackwell. - 1198-743X .- 1469-0691. ; 14:11, s. 1048-1056
  • Journal article (peer-reviewed)abstract
    • The first methicillin-resistant Staphylococcus aureus (MRSA) strain originated when a staphylococcal cassette chromosome mec (SCCmec) with the gene mecA was integrated into the chromosome of a susceptible S. aureus cell. The SCCmec elements are common among the coagulase-negative staphylococci, e.g. Staphylococcus haemolyticus, and these are considered to be potential SCCmec donors when new clones of MRSA arise. An outbreak of MRSA occurred at a neonatal intensive-care unit, and the isolates were all of sequence type (ST) 45, as characterized by multilocus sequence typing, but were not typeable with respect to SCCmec types I, II, III or IV. During the same time period, methicillin-resistant S. haemolyticus (MRSH) isolates identified in blood cultures at the same ward were found to be genotypically homogenous by pulsed-field gel electrophoresis, and did not carry a type I, II, III or IV SCCmec either. Thus, the hypothesis was raised that an SCCmec of MRSH had been transferred to a methicillin-susceptible S. aureus strain and thereby created a new clone of MRSA that caused the outbreak. This study showed that MRSA from the outbreak carried a ccrC and a class C mec complex that was also found among MRSH isolates. Partial sequencing of the mec complexes showed more than 99% homology, indicative of a common type V SCCmec. This finding may provide evidence for a recent horizontal transfer of an SCCmec from MRSH to an identified potential recipient, an ST45 methicillin-susceptible S. aureus strain, thereby creating a new clone of MRSA that caused the outbreak.
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  • Berglund, Eva, et al. (author)
  • Medicinsk fysik
  • 2007
  • Book (pop. science, debate, etc.)abstract
    • Medicinsk fysik är ett ämnesövergripande läromedel, som ger en inblick i modern medicinsk diagnostik och terapi med strålning, områden i ständig utveckling. Boken beskriver och förklarar olika strålningsfysikaliska tillämpningar och hur fysiken gör det möjligt att framställa medicinska bilder.
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  • Berglund, Marika, et al. (author)
  • Nationell kartläggning av arsenikhalter i brunnsvatten samt hälsoriskbedömning
  • 2005
  • Reports (other academic/artistic)abstract
    • Arsenik (As) är ett grundämne som förekommer naturligt i berggrunden. I områdenmed sulfidrika bergarter som vissa skiffrar och andra äldre sedimentbergarter kanarsenikhalten i vattnet vara över eller mycket över gränsvärdet för dricksvatten (10 μgAs/l). Dricksvattnet från framför allt bergborrade brunnar kan därför utgöra enbetydande källa till arsenikexponering. Drygt en miljon permanentboende och ungefärlika många fritidsboende har sin dricksvattenförsörjning från egen brunn. Antaletborrade brunnar ökar. Tidigare undersökningar har visat förhöjda till högaarsenikhalter i brunnsvatten, framför allt i bergborrade brunnar, i Skelleftefältet iVästerbotten, i ett stråk mellan Västerås och Enköping och kring Sollefteå. I flera länsaknas i dagsläget helt information om arsenikhalter i grundvatten.Gränsvärdet för arsenik i dricksvatten baseras på livstidsrisken för cancer. Arsenikkan ge tumörer i hud, lunga och urinblåsa, möjligen även i lever och njure. Detidigaste symptomen på kronisk arsenikförgiftning är pigmenteringsförändringar ihuden och förtjockning av hudens hornlager framför allt på handflator och fotsulor.Risken för negativa hälsoeffekter minskar om exponeringen minskar eller upphör. Detär således önskvärt att begränsa intaget av arsenik så långt det är möjligt. Detta gällerspeciellt för barn, eftersom experimentella studier tyder på att foster och små barn kanvara känsligare än vuxna.Inom ramen för den nationella hälsorelaterade miljöövervakningen analyseradesunder 2004 arsenik i 199 brunnsvattenprover tagna före eventuella filter. I dennarapport redovisas även resultaten från arsenikanalyser utförda vid SGU 2001-2003(totalt 178 brunnsvatten). Sammantaget redovisas arsenikanalyser för 377brunnsvatten från 14 län och 97 kommuner. I några län har endast ett fåtal prov tagits.Syftet med undersökningen var att kartlägga arsenikhalter i enskilda brunnar samt attsätta uppmätta halter i relation till kända risknivåer och göra en hälsoriskbedömning.Arsenikhalterna var låga i del flesta län. I 4,8% av brunnarna var arsenikhalten högreän 10 μg/l (range 11-297 g/l) och i 1,9% av brunnarna var halten högre än 100 μg/l(range 108-297 g/l). De högsta halterna uppmättes i Västerbotten (297 μg/l),Stockholm (max-halt 231μg/l) och Västmanlands län (25 μg/l). Arsenikhalter straxunder gränsvärdesnivån 10 μg/l uppmättes i Jämtland, Norrbotten ochVästernorrlands län samt på Öland. I övriga län låg alla uppmätta arsenikhalter under10 μg/l.SyfteAtt kartlägga arsenikhalter i enskilda brunnar samt att sätta uppmätta halter i relationtill kända risknivåer och göra en hälsoriskbedömning.
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  • Berglund, Pontus, et al. (author)
  • Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern
  • 2008
  • In: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 61:2, s. 184-191
  • Journal article (peer-reviewed)abstract
    • Aims: To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours. Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels. Conclusion: The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.
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  • Berglund, Staffan, 1975-, et al. (author)
  • Effects of iron supplementation on serum hepcidin and serum erythropoietin in low-birth-weight infants
  • 2011
  • In: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 94:6, s. 1553-1561
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status. OBJECTIVE: The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and iron-deficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID). DESIGN: We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed. RESULTS: Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (±SD) concentration of 19.2 ± 2.5 ng/mL in the 2-mg/kg group compared with 13.0 ± 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between iron-deficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status. CONCLUSIONS: Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials.gov as NCT00558454.
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24.
  • Bjurhager, Ingela, et al. (author)
  • Ultrastructure and Mechanical Properties of Populus Wood with Reduced Lignin Content Caused by Transgenic Down-Regulation of Cinnamate 4-Hydroxylase
  • 2010
  • In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 11:9, s. 2359-2365
  • Journal article (peer-reviewed)abstract
    • Several key enzymes in lignin biosynthesis of Populus have been down-regulated by transgenie approaches to investigate their role in wood lignification and to explore their potential for lignin modification. Cinnamate 4-hydroxylase is an enzyme in the early phenylpropanoid pathway that has not yet been functionally analyzed in Populus. This study shows that down-regulation of cinnamate 4-hydroxylase reduced Klason lignin content by 30% with no significant change in syringyl to guaiacyl ratio. The lignin reduction resulted in ultrastructural differences of the wood and a 10% decrease in wood density. Mechanical properties investigated by tensile tests and dynamic mechanical analysis showed a decrease in stiffness, which could be explained by the lower density. The study demonstrates that a large modification in lignin content only has minor influences on tensile properties of wood in its axial direction and highlights the usefulness of wood modified beyond its natural variation by transgene technology in exploring the impact of wood biopolymer composition and ultrastructure on its material properties.
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25.
  • Björmsjö, Maria, et al. (author)
  • Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula : A Randomized Controlled Trial
  • 2022
  • In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Wolters Kluwer. - 0277-2116 .- 1536-4801. ; 74:3, s. e65-e72
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Compared to formula-fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti-infective and anti-inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.METHODS: In a double-blind controlled trial, term formula-fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low-iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low-iron formula with no added lactoferrin (Lf-; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.RESULTS: No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF-β)1, TGF-β2, tumor necrosis factor alfa (TNF-α) or interleukin2 (IL-2) at 4, 6, or 12 months, except of higher TGF-β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.CONCLUSIONS: Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well-nourished and healthy population.
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26.
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27.
  • Björmsjö, Maria, et al. (author)
  • Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age : A Randomized Controlled Trial
  • 2021
  • In: Nutrients. - : MDPI. - 2072-6643. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Many infant formulas are fortified with iron at 8-14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf-) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 mu g/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.
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28.
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29.
  • Björmsjö, Maria, et al. (author)
  • Vaccine response was higher in formula-fed infants compared to breastfed but not affected by lactoferrin or iron in a randomised controlled trial
  • 2024
  • In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227.
  • Journal article (peer-reviewed)abstract
    • Aim: To examine how reduced iron content and added bovine lactoferrin in infant formula affect the antibody response following routine immunisation.Methods: In this randomised controlled trial, 180 Swedish formula-fed infants received, from 6 weeks to 6 months of age, a 2 mg/L iron formula with (n = 72) or without (n = 72) bovine lactoferrin, or a control formula with 8 mg/L iron and no lactoferrin (n = 36). Another 72 infants were recruited as a breastfed reference. Serum immunoglobulin G (IgG) levels against Haemophilus influenzae type b (Hib), diphtheria and tetanus were assessed at four, six and 12 months of age.Results: With an equal gender distribution, 180 + 72 term infants were included with a mean age of 7.0 ± 0.7 weeks. At 12 months, infants fed low iron formula showed a significantly higher geometric mean Hib IgG (1.40 μg/mL [1.07–1.83]) compared to the control formula infants (0.67 μg/mL [0.42–1.07]). For all three vaccines, breastfed infants had significantly lower IgG levels at six and 12 months of age.Conclusion: Except for higher Hib IgG levels at 12 months in infants fed low iron formula, the interventions did not affect vaccine IgG response. Unexpectedly, breastfed infants had significantly lower vaccine IgG levels compared to formula-fed infants.
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30.
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31.
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32.
  • Borgquist, Signe, et al. (author)
  • Diet and body constitution in relation to sub-groups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators.
  • 2007
  • In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 9:1, s. 11-11
  • Journal article (peer-reviewed)abstract
    • Background The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases. Method A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmo Diet and Cancer study ( Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance. Results A large hip circumference and high body mass index were associated with high grade tumours ( P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation ( P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation ( P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D-1 overexpression ( P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution. Conclusion Low energy and low total fat ( polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D1 and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results.
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33.
  • Calling, Susanna, et al. (author)
  • Effects of body fatness and physical activity on cardiovascular risk: risk prediction using the bioelectrical impedance method.
  • 2006
  • In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 34:6, s. 568-575
  • Journal article (peer-reviewed)abstract
    • Aims: To explore the effects of body fat percentage (BF%) on incidence of and mortality from cardiovascular disease (CVD) and to study the cardio-protective effect of physical activity in relation to BF%. Methods: A total of 26,942 men and women, aged 45-73 years, without history of CVD were followed up for incidence of coronary events (CE), ischaemic stroke, and CVD mortality over seven years in relation to sex-specific quartiles (Q1-Q4) of BF%. The cardio-protective effect of leisure-time physical activity was studied in relation to BF%. Results: In men, the relative risk (RR) for CE and CVD mortality increased progressively with BF%. RR for CE in Q4 was 1.37 (95% confidence interval: 1.07-1.74), adjusted for age, height, smoking, high alcohol intake, and physical activity, compared with Q1. In women, BF% was significantly associated with incidence of CE and stroke. BF% was more strongly correlated to body mass index (BMI) (r=50.83) and waist circumference (r=0.76) in women than in men (r=0.59 and r=50.66, respectively). BF% was a stronger risk factor than BMI in women, and equally strong as waist circumference. A significant interaction (p=0.013 for incidence of CE, p=0.026 for ischaemic stroke) was found between BF% and sex. The raised cardiovascular risk was reduced by physical activity in subjects with high BF%. Conclusions: BF% is a risk factor for CE, ischaemic stroke, and CVD mortality. An interaction between BF% and sex suggests that BF% is a stronger CVD risk factor in women. The raised cardiovascular risk associated with high BF% is reduced by physical activity.
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34.
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35.
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36.
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37.
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38.
  • Carlsson, Lars, et al. (author)
  • Enhanced systolic myocardial function in elite endurance athletes during combined arm-and-leg exercise
  • 2011
  • In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 111:6, s. 905-913
  • Journal article (peer-reviewed)abstract
    • The aim here was to employ color tissue velocity imaging (TVI), to test the hypothesis that highly trained endurance athletes exhibit enhanced systolic function of the left ventricular (LV) myocardium both at rest and during combined arm-and-leg exercise in comparison with untrained subjects. For each of the ten elite male (EG) and ten matched control participants (CG), LV dimensions and systolic function were assessed at rest using echocardiography. Subsequently, these subjects exercised continuously on a combined arm-and-leg cycle ergometer for 3 min each at 50, 60, 70, 80, 90 and 100% of VO2max. Oxygen uptake, heart rate, systolic blood pressure (SBP) and peak contraction systolic velocities of the LV myocardium (PSV) were recorded in the end of each level. At rest, the trained and untrained groups differed with respect to LV dimensions, but not systolic function. At 60–100% VO2max, the EG group demonstrated both higher PSV and SBP. The observation that the EG athletes had higher PSV than CG during exercise at 60–100% VO2max, but not at rest or at 50% of VO2max, suggested an enhanced systolic capacity. This improvement is likely to be due to an enhanced inotropic contractility, which only becomes apparent during exercise.
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39.
  • Constantinescu, Radu, 1966, et al. (author)
  • Key clinical milestones 15 years and onwards after DBS-STN surgery-A retrospective analysis of patients that underwent surgery between 1993 and 2001
  • 2017
  • In: Clinical Neurology and Neurosurgery. - : Elsevier BV. - 0303-8467. ; 154, s. 43-48
  • Journal article (peer-reviewed)abstract
    • Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for motor fluctuations in Parkinson's disease (PD), but does not halt disease progression. The long-term deterioration of key functions such as cognition, speech, ability to swallow, gait, urinary bladder control, orientation and reality perception is decisive for patients' independency in daily life. In this paper we investigated patients with advanced PD operated at our center with STN-DBS for at least 15 years ago, in respect to key clinical milestones reflecting their overall function in daily living. Patients and methods: Retrospective analysis of clinical data concerning key clinical milestones including death in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska Hospital before January 1, 2001, were regularly assessed until death, dropout, or January 11, 2016. Results: Sixteen men and seven women with a median (range) disease duration of 18 (10-28) years were operated with STN-DBS. The median (range) follow-up time post-surgery was 12 (2-18) years and 692 person-years of disease duration were observed. In January 2016, nine PD-patients (39%) were still alive (eight with active STN-DBS). Initially, motor symptoms improved in all patients. Sustained benefit (implying active stimulation at the last follow up) was maintained in 19 of them (83%) but STN-DBS was inactivated in four (17%) due to inefficacy. Over time, all patients deteriorated slowly, and a majority developed severe non-motor and axial symptoms such as dementia, inability to talk, swallow and walk, urinary incontinence, psychosis, and need for nursing home care. At the last follow up, 16/23 (70%) patients were treated with antidepressants. Conclusion: A majority of PD-patients experience sustained motor benefit with continuous STN-DBS. However, over time, non-motor and axial symptoms slowly and severely restrict PD-patients' function in their daily living. (C) 2017 Elsevier B.V. All rights reserved.
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40.
  • Covaci, Adrian, et al. (author)
  • Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.
  • 2015
  • In: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 141:Oct 13, s. 77-85
  • Journal article (peer-reviewed)abstract
    • For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300mg/L or above 3000mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.
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41.
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42.
  • Daskoulidou, Nikoleta, et al. (author)
  • High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling
  • 2015
  • In: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 93:5, s. 511-521
  • Journal article (peer-reviewed)abstract
    • ORAI and stromal interaction molecule (STIM) are storeoperated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca2+ store to Ca2+ influx. However, the roles of ORAI and STIMin vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucose or hyperglycaemia using in vitro cell models, in vivo diabetic mice and tissues from patients. We found that ORAI1-3 and STIM1-2 were ubiquitously expressed in human vasculatures. Their expression was upregulated by chronic treatment with high glucose (HG, 25 mM D-glucose), which was accompanied by enhanced store-operated Ca2+ influx in vascular endothelial cells. The increased expression was also observed in the aortae from genetically modified Akita diabetic mice (C57BL/6-Ins2(Akita)/J) and streptozocin-induced diabetic mice, and aortae from diabetic patients. HG-induced upregulation of ORAI and STIM genes was prevented by the calcineurin inhibitor cyclosporin A and NFATc3 siRNA. Additionally, in vivo treatment with the nuclear factor of activated T cells (NFAT) inhibitor A-285222 prevented the gene upregulation in Akita mice. However, HG had no direct effects on ORAI1-3 currents and the channel activation process through cytosolic STIM1 movement in the cells coexpressing STIM1-EYFP/ORAIs. We concluded that upregulation of STIM/ORAI through Ca2+-calcineurin-NFAT pathway is a novel mechanism causing abnormal Ca2+ homeostasis and endothelial dysfunction under hyperglycaemia.
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43.
  • Dunér, Pontus, et al. (author)
  • Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease.
  • 2009
  • In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; Feb 14., s. 593-603
  • Journal article (peer-reviewed)abstract
    • Abstract. Dunér P, To F, Alm R, Gonçalves I, Fredrikson GN, Hedblad B, Berglund G, Nilsson J, Bengtsson E (Malmö University Hospital, Lund University, Lund, Sweden). Immune responses against fibronectin modified by lipoprotein oxidation and their association with cardiovascular disease. J Intern Med 2009; doi: 10.1111/j.1365-2796.2008.02067.xObjectives. Accumulation and subsequent oxidation of LDL in the arterial wall are considered as key events in the development of atherosclerosis. We have investigated the possibility that LDL oxidation results in release of aldehydes that modify surrounding matrix proteins and that this may target immune responses against the plaque extracellular matrix and modulate the disease progression. Results. Using custom-made ELISAs we demonstrate that human plasma contains autoantibodies against aldehyde-modified fibronectin (FN) and to a lesser extent also other extracellular matrix proteins including collagen type I, type III, and tenascin-C. Immunohistochemistry and western blot analysis showed that aldehyde-modified FN is present in human atherosclerotic plaques and that aldehydes generated by oxidation of LDL formed adducts with FN in vitro. We also demonstrate that aldehyde-modification of FN results in a loss of its ability to promote basal secretion of cytokines and growth factors from cultured macrophages without affecting the ability of the cells to respond to stimulation with LPS. A prospective clinical study demonstrated that subjects that subsequently developed acute myocardial infarction or sudden cardiac death had lower baseline levels of autoantibodies against aldehyde-modified FN than matched controls. Conclusions. These observations demonstrate that oxidation of LDL in the arterial wall may lead to aldehyde-modification of surrounding extracellular matrix proteins and that these modifications may affect macrophage function and activate autoimmune responses of pathophysiological importance for the development of atherosclerosis.
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44.
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45.
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46.
  • Engström, Gunnar, et al. (author)
  • Blood pressure increase and incidence of hypertension in relation to inflammation-sensitive plasma proteins.
  • 2002
  • In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 22:12, s. 2054-2058
  • Journal article (peer-reviewed)abstract
    • Objective— The reasons for the relationship between inflammation-sensitive plasma proteins (ISPs) and incidence of cardiovascular diseases are poorly understood. This study explored the hypothesis that ISPs are associated with future hypertension and age-related blood pressure increase. Method and Results— Blood pressure and plasma levels of fibrinogen, {alpha}1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid were determined in 2262 healthy men aged 35 to 50 years, initially without treatment for hypertension. The cohort was re-examined after 15.7 (±2.2) years. Incidence of hypertension and blood pressure increase was studied in relation to number of elevated proteins (ie, in the top quartile) at baseline. Among men without treatment for hypertension at follow-up, mean (±SD) increase in systolic blood pressure was 18.8±17, 19.2±17, 19.3±17, and 22.1±18 mm Hg, respectively, for men with 0, 1, 2, and >=3 elevated proteins (P for trend=0.02, adjusted for confounders). The corresponding values for pulse pressure increase was 15.5±14, 15.8±14, 17.4±14, and 17.8±15 mm Hg, respectively (P=0.02). Incidence of hypertension (>=160/95 mm Hg or treatment) and future blood pressure treatment showed similar associations with ISPs. Increase in diastolic blood pressure showed no association with ISPs. Conclusions— Plasma levels of ISPs are associated with a future increase in blood pressure. This could contribute to the relationship between ISP levels and cardiovascular disease.
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47.
  • Engström, Gunnar, et al. (author)
  • Distribution and determinants of ischaemic heart disease in an urban population. A study from the myocardial infarction register in Malmo, Sweden
  • 2000
  • In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 247:5, s. 588-596
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Age adjusted incidence of myocardial infarction has been found to vary substantially between the residential areas of the city of Malmo. The objective of this study was to assess the extent to which major biological risk factors and socio-economic circumstances account for the differences in incidence of and mortality from myocardial infarction. DESIGN: Ecological study of risk factor prevalence and incidence and mortality from myocardial infarction. SETTING: Seventeen administrative areas in Malmo, Sweden. SUBJECTS: Assessment of risk factor prevalence was based on 28 466 men and women, ranging from 45 to 73 years old, who were recruited as participants in the Malmo Diet and Cancer study. Information on serum lipids was available in a random subsample of 5362 subjects. Information about socio-economic level of the residential area was based on statistics from the Malmo City Council and Statistics Sweden. MAIN OUTCOME MEASURES: Weighted least square regressions between prevalence of risk factors (i.e. smoking, hypertension, obesity, diabetes, hypercholesterolemia and hypertriglyceridemia), a myocardial infarction risk score, a socio-economic score and incidence and mortality from myocardial infarction. RESULTS: The risk factor prevalence and myocardial infarction incidence was highest in areas with low socio-economic level. Prevalence of smoking, obesity and hypertension was significantly associated with myocardial infarction incidence and mortality rates amongst men (all r > 0.60). Prevalence of smoking was significantly associated with incidence and mortality from myocardial infarction amongst women (r = 0.66 and r = 0.61, respectively). A myocardial infarction risk score based on four biological risk factors explained 40-60% of the intra-urban geographical variation in myocardial infarction incidence and mortality. The socio-economic score added a further 2-16% to the explained variance. CONCLUSION: In an urban population with similar access to medical care, well-known biological cardiovascular risk factors account for a substantial proportion of the intra-urban geographical variation of incidence of and mortality from myocardial infarction. The socio-economic circumstances further contribute to the intra-urban variation in disease.
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48.
  • Engström, Gunnar, et al. (author)
  • Incidence of myocardial infarction in women. A cohort study of risk factors and modifiers of effect
  • 2000
  • In: Journal of Epidemiology and Community Health. - 1470-2738. ; 54:2, s. 104-107
  • Journal article (peer-reviewed)abstract
    • STUDY OBJECTIVE: To assess whether the increased incidence of myocardial infarction and death associated with smoking, hypertension, hyperlipidaemia and diabetes varies significantly between groups defined in terms of occupation, education and marital status. SETTING: Malmo, Sweden. PARTICIPANTS: 9351 women, aged 28-55, with a mean follow up of 10.7 years. MAIN RESULTS: Smoking, hypertension (> or = 160/95 mm Hg or treatment), hyperlipidaemia (cholesterol > or = 6.5 mmol/l or triglycerides > or = 2.3 mmol/l), diabetes, low occupation and education levels were significantly more common among women who experienced a fatal or nonfatal myocardial infarction during the follow up (n = 104) than in other women (n = 9247). Exposure to smoking, hypertension and hyperlipidaemia showed substantial differences between groups defined in terms of education, occupation and marital status. The association between low occupation and myocardial infarction remained statistically significant after adjustments for several potential confounders (RR = 2.6, 95% CI 1.1, 6.0). Single women had similarly higher adjusted mortality rates than married women (RR = 1.4, 95% CI 1.1, 1.8). When other major risk factors were taken into account, the relative risk for mortality and myocardial infarction associated with smoking was 2.6 (95% CI 2.0, 3.4) and 7.8 (95% CI 4.4, 13.9), respectively. CONCLUSION: In this urban female population, short education and low occupation level were both associated with an increased prevalence of smoking, hypertension, hyperlipidaemia and diabetes. Low occupation level increases the rate of cardiac events caused by exposure to these four risk factors.
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49.
  • Engström, Gunnar, et al. (author)
  • Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study.
  • 2003
  • In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 253:5, s. 574-581
  • Journal article (peer-reviewed)abstract
    • Objectives. To explore whether a reduced lung function is a risk factor for developing diabetes and insulin resistance (IR), and whether such relationship contributes to the largely unexplained association between lung function and incidence of cardiovascular disease (CVD). Design. Forced vital capacity (FVC) was assessed at baseline. Incidence of diabetes and IR [according to the homeostasis model assessment (HOMA) model] was assessed in a follow-up examination after 13.9 ± 2.6 and 9.4 ± 3.6 years for men and women, respectively. After the follow-up examination, incidence of CVD (stroke, myocardial infarction or cardiovascular death) was monitored over 7 years. Setting. Populations-based cohort study. Subjects. Initially nondiabetic men (n = 1436, mean age 44.6 years) and women (n = 896, mean age 49.8 years). Results. Prevalence of IR at the follow-up examination was 34, 26, 21 and 21%, respectively, for men in the first (lowest), second, third and fourth quartile of baseline FVC (P for trend <0.0001). The corresponding values for women were 30, 29, 25 and 17%, respectively (P for trend <0.001). Adjusted for potential confounders, the odds ratio (OR) for IR (per 10% increase in FVC) was 0.91 (CI: 0.84-0.99) for men and 0.89 (CI: 0.80-0.98) for women. FVC was similarly significantly associated with the incidence of diabetes (OR = 0.90, CI: 0.81-1.00), adjusted for sex and other confounders. The incidence of CVD after the follow-up examination was significantly increased only amongst subjects with low FVC who had developed IR (RR = 1.7, CI: 1.02-2.7). Conclusion. Subjects with a moderately reduced FVC have an increased risk of developing IR and diabetes. This relationship seems to contribute to the largely unexplained association between reduced lung function and incidence of CVD.
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50.
  • Engström, Gunnar, et al. (author)
  • Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study.
  • 2007
  • In: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 21, s. 276-282
  • Journal article (peer-reviewed)abstract
    • Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This population-based longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (+/- 2.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (<160/95 mm Hg), incidence of hypertension (>= 160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P = 0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean + standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5 + 0.8, 19.6 + 0.9, 19.8 + 0.8 and 20.8 + 0.8 mm Hg, respectively, in the C3 quartiles (trend: P = 0.004). C3 was not associated diastolic blood pressure at follow-up. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.
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