| 1. |
- Frostfeldt, Gunnar, et al.
(författare)
-
Low molecular weight heparin (Dalteparin) as adjuvant treatment to thrombolysis in acute myocardial infarction-a pilot study : BIOchemical markers in acute coronary syndromes (BIOMACS II)
- 1999
-
Ingår i: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 33:3, s. 627-633
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study.
|
|
| 2. |
|
|
| 3. |
- Frostfeldt, Gunnar, et al.
(författare)
-
Possible reasons for the prognostic value of troponin-T on admission in patients with ST-elevation myocardial infarction
- 2001
-
Ingår i: Coronary Artery Disease. - 0954-6928 .- 1473-5830. ; 12:3, s. 227-237
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with acute myocardial infarction and ST-segment elevation, increased troponin-T (TnT) on admission implies an increased mortality. OBJECTIVE: To elucidate the underlying mechanisms of the prognostic value of TnT. METHODS AND RESULTS: One hundred and one patients were included and all received thrombolytic treatment. The patients were compared according to TnT level on admission (cut-off 0.1 microg/l). Elevation of TnT was associated with long-term mortality and also with longer delay, more episodes of chest pain during the last 24 h and fewer noninvasive signs of reperfusion at 90 min. In the group with elevated TnT, the coronary angiography at 24 h showed a strong trend towards lower patency in the infarct-related artery. TnT was also associated with increased infarct size if a higher cut-off level (0.43 microg/l) was used. In univariate analysis, elevated TnT, longer delay, repeated chest pain, Q-waves on admission and reduced left ventricular (LV) function were significantly associated with long-term mortality. In multivariate models, only reduced LV function and less than TIMI (thrombolysis in myocardial infarction) grade 3 flow turned out to be significant independent risk factors. CONCLUSIONS: The prognostic value of TnT level on admission regarding long-term mortality was confirmed and seems mainly to be explained by its association with longer delay and recent myocardial damage, but its association with reduced effect of thrombolytic treatment, larger infarct size and impaired LV function might also be of importance.
|
|
| 4. |
- Hedström, Brita, et al.
(författare)
-
Visby Innerstad : En användningsplan
- 1973
-
Rapport (populärvet., debatt m.m.)abstract
- Sedan lång tid föreligger i stort sett enighet om att bevara innerstadens bebyggelse och att anpassa eventuella nytillskott till det redan bestående. Med den inställningen har förändringsprocessen både dämpats och mildrats men ändå inte bragts att avstanna. Förändringar sker ständigt om det också huvudsakligen i smått: de många synbart så anspråkslösa byggnadsåtgärderna adderar efterhand ihop sig till något större och mer genomgripande. Långsamt, nästan omärkligt, ändrar innerstaden sitt ansikte.Ändå är det inte själva husen som förändrats mest utan användningen av dem. Ur funktionell synpunkt har 1950 - och 60-talen har varit något av en omstörtning i innerstadens historia: den har förlorat nästan hälften av de boende, en stor del av detaljhandeln och praktiskt taget helt sin gamla roll som skolcentrum. I gengäld har ytterstaden vuxit ut till ett sammanhängande kilometerbrett bälte. Till stor del av denna funktionella förändring en följd av beslutet att bevara innerstadens bebyggelse. Vad som inte fått plats inom den gamla ramen har etablerats utandör den.Föreliggande arbete vill ge en översiktlig bild av förändringsförloppen, sedda i ett långt tidsperspektiv men med tonvikt på dagsläget. Bebyggelsen tas upp till utförlig granskning men också användningen av den. Det är just samspelet mellan husen och de funtkioner, de fyller, som kan sägas utgöra bokens huvudtema. I de flesta fall är detta sammanhang hus-användning alldeles konfliktfritt och föranleder därför inte heller någon diskussion. Vad som behandlas är de relativt få problematiska fallen, hus som borde rustas upp för att fylla sin uppgift, hus som är olämpligt nyttjade eller inte använda alls. En serie sådana fall tas upp till systematisk genomgång; samtidigt berörs också de trafik - och miljömässiga konsekvenserna. Bokens syfte är alltså klart: den ger ett underlag av fakta för arbetet med att jämka samman byggnader och användningsformer. I den meningen kan skriften kallas en anvädningsplan för Visby innanför murarna.Arkitekturskolanas arbete har bedrivitis parallellt med den kommunala Innerstadskommitténs verksamhet. Något organiserat samarbete har inte förekommit med de informella kontakterna har varit både täta och goda. Att likheterna mellan Innerstadskommittén och Arkitekturskolans slutsatser blivit så pass stora, kan tillskrivas en gemensam helhetssyn.En av Arkitekturskolans elever, arkitekt Lars-Ingvar Larsson, har tidigare självständigt genomfört en undersökning av förändringar i innerstaden 1945-70- Denna studie publicerats separat och bör uppfattas som ett komplement till den hör föreliggande.Förutom de i innehållsförteckningen nämnda har ytterligare några aktivt medverkat i arbetet. Studiet av trafikfrågorna i innerstaden, i hamnen och öster om ringmuren leddes av Åke Claesson, I fältstudier och diskussioner medverkande Göran Månsson.Arkitekturskolan har fått god hjälp av ett antal initierade personer i Visby. Särskild tacksamhet är vi skyldiga byggnadsnämnden ordförande Henning Jacobson, kommunalrådet C B Stenström, stadsarkitekten Måns Hagbergm f. länsbostadsdorektören Åke Malmberg och landsantikvarien Gunnar Svahnström. I boken publiceringskostnaderna har ekonomiskt bidrag lämnats av Gotlands kommun och Riksantikvarieämbetet.Boken har redigerats av Sture Balgård och Ann Mari Westerlind med hjälp av Henrik O Andersson, Bo Ek, Göran Lindahl, Fredrik von Platen, John Sjöström Gunnar Westerlind och Hans Wetterfors.Skeppsholmen, Stockholm, sommaren 1973.Arkitekturskolans lärare och elever.
|
|
| 5. |
- Morfeldt, E, et al.
(författare)
-
Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein : implications for antigenic variation.
- 2001
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 167:7, s. 3870-7
-
Tidskriftsartikel (refereegranskat)abstract
- Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the approximately 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HVRs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.
|
|
| 6. |
- van Sorge, Nina M., et al.
(författare)
-
Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors
- 2021
-
Ingår i: EMBO Journal. - : Wiley-VCH Verlagsgesellschaft. - 0261-4189 .- 1460-2075. ; 40
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface-expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.
|
|
| 7. |
- André, Ingemar, et al.
(författare)
-
Streptococcal M protein: Structural studies of the hypervariable region, free and bound to human C4BP
- 2006
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 45:14, s. 4559-4568
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases, including acute tonsillitis and toxic shock syndrome. The surface-localized M protein, which is the most extensively studied virulence factor of S. pyogenes, has an similar to 50-residue N-terminal hypervariable region (HVR) that plays a key role in the escape of the host immunity. Despite the extensive sequence variability in this region, many HVRs specifically bind human C4b-binding protein (C4BP), a plasma protein that inhibits complement activation. Although the more conserved parts of M protein are known to have dimeric coiled-coil structure, it is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic resonance (NMR) to study the conformational properties of HVRs from M4 and M22 proteins in isolation and in complex with the M protein binding portion of C4BP. We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the folded nucleus of the M4 HVR has a length of similar to 27 residues. Moreover, we demonstrate that the C4BP binding surface of M4-N is found within a region of four heptad repeats. Using molecular modeling, we propose a model for the structure of the M4 HVR that is consistent with our experimental information from NMR spectroscopy.
|
|
| 8. |
- Areschoug, Thomas, et al.
(författare)
-
A Proline-Rich Region with a Highly Periodic Sequence in Streptococcal beta Protein Adopts the Polyproline II Structure and Is Exposed on the Bacterial Surface.
- 2002
-
Ingår i: Journal of Bacteriology. - 0021-9193. ; 184:22, s. 6376-6383
-
Tidskriftsartikel (refereegranskat)abstract
- Proline-rich regions have been identified in many surface proteins of pathogenic streptococci and staphylococci. These regions have been suggested to be located in cell wall-spanning domains and/or to be required for surface expression of the protein. Because little is known about these regions, which are found in extensively studied and biologically important surface proteins, we characterized the proline-rich region in one such protein, the beta protein of group B streptococci. The proline-rich region in beta, designated the XPZ region, has a proline at every third position, and the sequence is highly periodic in other respects. Immunochemical analysis showed that the XPZ region was not associated with the cell wall but was exposed on the bacterial surface. Moreover, characterization of a beta mutant lacking the XPZ region demonstrated that this region was not required for surface expression of the beta protein. Comparison of the XPZ region in different beta proteins showed that it varied in size but always retained the typical sequence periodicity. Circular dichroism spectroscopy indicated that the XPZ region had the structure of a polyproline II helix, an extended and solvent-exposed structure with exactly three residues per turn. Because of the three-residue sequence periodicity in the XPZ region, it is expected to be amphipathic and to have distinct nonpolar and polar surfaces. This study identified a proline-rich structure with unique properties that is exposed on the surface of an important human pathogen.
|
|
| 9. |
- Areschoug, Thomas, et al.
(författare)
-
Host-pathogen interactions in Streptococcus pyogenes infections, with special reference to puerperal fever and a comment on vaccine development.
- 2004
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 22 Suppl 1:Suppl 1, s. 9-14
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes (group A streptococcus) causes a variety of diseases, including acute pharyngitis, impetigo, rheumatic fever and the streptococcal toxic shock syndrome. Moreover, S. pyogenes was responsible for the classical example of a nosocomial infection, the epidemics of puerperal fever (childbed fever) that caused the death of numerous women in earlier centuries. The most extensively studied virulence factor of S. pyogenes is the surface M protein, which inhibits phagocytosis and shows antigenic variation. Recent data indicate that many M proteins confer phagocytosis resistance because the variable N-terminal region has non-overlapping sites that specifically bind two components of the human immune system, the complement inhibitor C4b-binding protein (C4BP) and IgA-Fc. Concerning puerperal fever, molecular and epidemiological analysis suggests that the S. pyogenes surface protein R28 may have played a pathogenetic role in these epidemics. This article summarizes the properties of M protein and the R28 protein and considers a potential problem encountered in connection with the use of animal models for vaccine development.
|
|
| 10. |
- Areschoug, Thomas, et al.
(författare)
-
Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc.
- 2002
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:15, s. 12642-12648
-
Tidskriftsartikel (refereegranskat)abstract
- The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the beta protein, is known to bind human IgA-Fc. Here, we show that the beta protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing beta protein, but not to an isogenic beta-negative mutant. This binding was due to a direct interaction between beta and FH, as shown by experiments with purified proteins. Inhibition tests and studies with beta fragments demonstrated that FH and IgA-Fc bind to separate and non-overlapping regions in beta. Heparin, a known ligand for FH, specifically inhibited the binding between beta and FH, suggesting that FH has overlapping binding sites for beta and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that beta-expressing GBS may use bound FH to evade complement attack. The finding that beta protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis.
|
|
| 11. |
- Bengtsson, Gunnar, et al.
(författare)
-
A design scheme for incomplete state or output feedback with applications to boiler and power system control
- 1974
-
Ingår i: Automatica. - : Elsevier BV. - 0005-1098. ; 10:1, s. 15-30
-
Tidskriftsartikel (refereegranskat)abstract
- The problem of designing a linear feedback when all state variables are not available is discussed. The design scheme is based on computation of a complete state feedback and a reduction to a specified structure. The reduction is made by approximation of the eigenspace corresponding to a set of dominant eigenvalues. The method consists of successive choices of weightings on this space. The method is applied to the control of a boiler and a three-machine power system. In the power system case the complete state feedback can be replaced by local output feedback without significant decrease in performance.The examples indicate that the proposed method is a realistic design method for multivariable systems.
|
|
| 12. |
- Berggård, Karin, et al.
(författare)
-
Bordetella pertussis binds to human C4b-binding protein (C4BP) at a site similar to that used by the natural ligand C4b
- 2001
-
Ingår i: European Journal of Immunology. - 1521-4141. ; 31:9, s. 2771-2780
-
Tidskriftsartikel (refereegranskat)abstract
- Human complement regulators are important targets for pathogenic microorganisms. In one such interaction, Bordetella pertussis binds human C4b-binding protein (C4BP), a high-molecular-weight plasma protein that acts as inhibitor of the classical pathway of complement activation. At least two different B. pertussis surface components, one of which is the virulence factor filamentous hemagglutinin (FHA), contribute to the binding. We used a set of C4BP mutants and monoclonal antibodies to characterize the region in C4BP that binds B. pertussis and analyzed the salt sensitivity of the interaction. These studies indicated that positively charged residues at the interface between complement control protein modules 1-2 in the C4BP alpha-chain are important for binding, and that the site in C4BP that binds B. pertussis is very similar, but not identical, to the C4b-binding site. Bacteria-bound C4BP retained its complement regulatory function and B. pertussis selectively bound C4BP in human plasma, indicating that binding occurs also in vivo. Together, these findings indicate that B. pertussis exploits a site in C4BP, resembling that used by the natural ligand C4b.
|
|
| 13. |
- Bergman Bruhn, Åsa, et al.
(författare)
-
Motivational factors for occupational safety and health improvements : A mixed-method study within the Swedish equine sector
- 2023
-
Ingår i: Safety Science. - : Elsevier. - 0925-7535 .- 1879-1042. ; 159
-
Tidskriftsartikel (refereegranskat)abstract
- A well-functioning systematic occupational safety and health management is beneficial for both individuals and organizations, and employee motivation seems to be crucial for positive outcomes. Occupational safety and health issues are a major concern for the Swedish equine sector since the work environment in horse stables is known to be characterized by low mechanization, high physical workloads, and high injury risks. The purpose of this study was to gain an increased understanding of how systematic occupational safety and health management is performed and which factors that influence motivation for occupational safety and health improvements in the Swedish equine sector. An explanatory sequential mixed-methods study, based on quantitative data from questionnaires and qualitative data from semi-structured interviews, was conducted. Various statistical analyses were performed to obtain quantitative data and an abductive applied thematic analysis was applied for the qualitative data. The results indicate that both intrinsic motivators, i.e. attitudes, values, and influence, as well as contextual factors such as motivational management, occupational culture, and workplace resources, influence compliance in systematic occupational safety and health management and participation in occupational safety and health improvements, which in turn affect workplace outcomes regarding safety and health. The positive relationship found between an implemented and functioning systematic occupational safety and health management and employee motivation for occupational safety and health improvements indicate the importance of employee involvement and participation. Understanding the motivational factors for occupational safety and health improvements from an employee perspective is an important step to creating healthy and sustainable workplaces.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Bernsel, Andreas, et al.
(författare)
-
Prediction of membrane-protein topology from first principles
- 2008
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:20, s. 7177-7181
-
Tidskriftsartikel (refereegranskat)abstract
- The current best membrane-protein topology-prediction methods are typically based on sequence statistics and contain hundreds of parameters that are optimized on known topologies of membrane proteins. However, because the insertion of transmembrane helices into the membrane is the outcome of molecular interactions among protein, lipids and water, it should be possible to predict topology by methods based directly on physical data, as proposed >20 years ago by Kyte and Doolittle. Here, we present two simple topology-prediction methods using a recently published experimental scale of position-specific amino acid contributions to the free energy of membrane insertion that perform on a par with the current best statistics-based topology predictors. This result suggests that prediction of membrane-protein topology and structure directly from first principles is an attainable goal, given the recently improved understanding of peptide recognition by the translocon.
|
|
| 17. |
- Bilén, Anna-Karin, et al.
(författare)
-
Miljökvalitetsmålen 2016 : Årlig uppföljning av miljökvalitetsmålen
- 2016
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Blekinge bedöms inte något miljökvalitetsmål vara möjligt att nå till år 2020. För att kunna lämna över ett hållbart samhälle till nästa generation krävs förebyggande arbete, ef?????????????????r. Ambitionerna måste öka och miljöfrågorna prioriteras högre på den politiska agendan.De mål som rör biologisk mångfald och bevarande av kulturmiljö följer enneutral eller negativ trend. I odlingslandskapet leder färre lantbrukare ochbrist på betesdjur till igenväxning av hagmarker. Livsmiljöer försvinner och????????????????????????????????????????,främst möte insekter.För att god ekologisk status ska uppnås i vattendragen behövs ny vattenlagstiftning och mer resurser för tillsyn. I Blekinges kustvatten är övergödning ett stort miljöproblem och det krävs kraftfulla åtgärder för att minska näringsläckaget. Arbetet med vattenförsörjningsplaner behöver fortsätta för att trygga framtida dricksvattenförsörjning. De senaste årens fynd av PFAS i dricksvatten visar på vikten av att skydda vattentäkter, genomföra riskbedömningar och undersöka förekomst av föroreningar.Obalans mellan den tätbefolkade kusten och den glesbyggda landsbygden är en utmaning i länet. Byggandet vid kusten ställer krav på en hänsynsfull bebyggelseutveckling som tydligt beaktar miljökvalitetsmålen.Internationella överenskommelser om kemikalier och minskade utsläpp till luft och vatten är nödvändigt för att uppnå uppsatta mål. Dessutom behövs en omställning till ett samhälle som baseras på förnybar energi. För att skapa en hållbar framtid måste vi förändra vår livsstil och vår attityd till konsumtion. Lokala och regionala åtgärder såsom arbete för en giftfri förskola och minskade utsläpp av mikroplaster är steg i rätt riktning.Minskad biologisk mångfald påverkar tillsammans med klimatförändringar, övergödning och miljögifter många av de ekosystemtjänster som vi är beroende av för mänsklig välfärd och en hållbar samhällsutveckling. Det pågår insatser som förbättrar tillståndet i miljön, men det går för långsamt. Det krävs mer resurser och modiga politiska beslut för att möjliggöra en hållbar framtid, den framtid som vi är skyldiga våra barn!
|
|
| 18. |
- Blom, Anna M., et al.
(författare)
-
A novel interaction between type IV pili of Neisseria gonorrhoeae and the human complement regulator C4B-binding protein
- 2001
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 166:11, s. 6764-6770
-
Tidskriftsartikel (refereegranskat)abstract
- C4b-binding protein (C4BP) is an important plasma inhibitor of the classical pathway of complement activation. Several bacterial pathogens bind C4BP, which may contribute to their virulence. In the present report we demonstrate that isolated type IV pili from Neisseria gonorrhoeae bind human C4BP in a dose-dependent and saturable manner. C4BP consists of seven identical alpha-chains and one beta-chain linked together with disulfide bridges. We found that pili bind to the alpha-chain of C4BP, which is composed of eight homologous complement control protein (CCP) domains. From the results of an inhibition assay with C4b and a competition assay in which we tested mutants of C4BP lacking individual CCPs, we concluded that the binding area for pili is localized to CCP1 and CCP2 of the alpha-chain. The binding between pili and C4BP was abolished at 0.25 M NaCl, implying that it is based mostly on ionic interactions, similarly to what have been observed for C4b-C4BP binding. Furthermore, the N-terminal part of PilC, a structural component of pili, appeared to be responsible for binding of C4BP. Membrane cofactor protein, previously shown to be a receptor for pathogenic N. gonorrhoeae on the surface of epithelial cells, competed with C4BP for binding to pili only at high concentrations, suggesting that different parts of pili are involved in these two interactions. Accordingly, high concentrations of C4BP were required to inhibit binding of N. gonorrhoeae to Chang conjunctiva cells, and no inhibition of binding was observed with cervical epithelial cells.
|
|
| 19. |
|
|
| 20. |
- Brandén, Gunnar
(författare)
-
Understanding Intergenerational Mobility : Inequality, Student Aid and Nature-Nurture Interactions
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay I: A body of evidence has emerged in the literature on intergenerational mobility documenting that unequal countries experience less social mobility: a relationship known as the Great Gatsby Curve. In this paper I estimate the Great Gatsby Curve within Sweden across 125 commuting zones and 20 cohorts, exploiting both cross-sectional and longitudinal variation. I find that children who were exposed to higher levels of inequality during childhood experienced less social mobility as adults, thereby confirming the existence of a Great Gatsby Curve in Sweden. I also present new evidence on the underlying mechanisms of the Great Gatsby Curve. By decomposing intergenerational mobility into separate transmission channels, I find that the Great Gatsby Curve is exclusively driven by the mediating effect that children's educational attainment and development of cognitive and non-cognitive skills has on the persistence of income across generations. Hence, the results suggest that adverse effects of inequality on mobility can be alleviated by policies that target children's educational attainment and development of cognitive and non-cognitive skills.
|
|
| 21. |
- Carlin, Aaron F., et al.
(författare)
-
Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5
- 2009
-
Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 206:8, s. 1691-1699
-
Tidskriftsartikel (refereegranskat)abstract
- Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall-anchored beta protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS. protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.
|
|
| 22. |
- Carlsson, Fredric, et al.
(författare)
-
Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein.
- 2003
-
Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 198:7, s. 1057-1068
-
Tidskriftsartikel (refereegranskat)abstract
- The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S. pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis. Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies. These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system.
|
|
| 23. |
|
|
| 24. |
- Carlsson, Fredric, et al.
(författare)
-
Signal sequence directs localized secretion of bacterial surface proteins.
- 2006
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 442:7105, s. 943-946
-
Tidskriftsartikel (refereegranskat)abstract
- All living cells require specific mechanisms that target proteins to the cell surface. In eukaryotes, the first part of this process involves recognition in the endoplasmic reticulum of amino-terminal signal sequences and translocation through Sec translocons, whereas subsequent targeting to different surface locations is promoted by internal sorting signals(1). In bacteria, N-terminal signal sequences promote translocation across the cytoplasmic membrane, which surrounds the entire cell, but some proteins are nevertheless secreted in one part of the cell by poorly understood mechanisms(2,3). Here we analyse localized secretion in the Gram-positive pathogen Streptococcus pyogenes, and show that the signal sequences of two surface proteins, M protein and protein F ( PrtF), direct secretion to different subcellular regions. The signal sequence of M protein promotes secretion at the division septum, whereas that of PrtF preferentially promotes secretion at the old pole. Our work therefore shows that a signal sequence may contain information that directs the secretion of a protein to one subcellular region, in addition to its classical role in promoting secretion. This finding identifies a new level of complexity in protein translocation and emphasizes the potential of bacterial systems for the analysis of fundamental cell-biological problems(4).
|
|
| 25. |
- Catton, Erin A., et al.
(författare)
-
Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
- 2023
-
Ingår i: Nature Communications. - 2041-1723. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.
|
|
| 26. |
- Claesson Lingehall, Helena, 1965-
(författare)
-
Delirium in older people after cardiac surgery : risk factors, dementia, patients’ experiences and assessments
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background:Delirium is common in older people undergoing cardiac surgery. Delirium is an acute or subacute neuro-psychiatric syndrome, characterized by a change in cognition, disturbances in consciousness; it fluctuates, develops over a short period of time and always has an underlying cause. It is associated with a disturbance in psychomotor activity, and is classified according to different clinical profiles such as hypoactive, hyperactive and mixed delirium. Delirium after cardiac surgery is not harmless, it increases the risk of complications such as prolonged stay in hospital, falls, reduced quality of life, reduced cognitive function and increased mortality.Aim:The overall aim of this thesis was to investigate postoperative delirium in older people undergoing cardiac surgery with Cardiopulmonary Bypass (CPB), focusing on risk factors, dementia and patients’ experiences; and to evaluate an assessment for screening delirium.Methods:This thesis compromises four studies. All participants (n=142) were scheduled for cardiac surgery with use of CPB at the Cardiothoracic Surgery Department, Heart Centre, Umeå University Hospital, Sweden, between February and October 2009. Six structured interviews were conducted preoperatively, day one and day four postoperatively, and in home visits, one, three and five years after surgery (2010, 2012 and 2014). The assessment scales used in Studies I, II and IV were: the Mini-Mental State Examination (MMSE) for cognition, the Organic Brain Syndrome Scale (OBS) for delirium, Geriatric Depression Scale 15 (GDS-15) for depression, Katz staircase with Activities of Daily Living (ADL) for participants’ functional status and the Numerical Rating Scale (NRS) for pain. During the hospital stay, nursing staff used the Swedish version of the Nursing Delirium Screening Scale (Nu-DESC) to assess delirium. Semi-structured interviews were also carried out (III) in the one-year follow up. Delirium, dementia and depression were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR).Results: Out of 142 participants 54.9% (78/142) developed delirium after cardiac surgery (I). Independent risk factors, predisposing and precipitating, associated with delirium were: age, diabetes, gastritis/peptic ulcer, volume load during operation, longer time on ventilator in intensive care, increased temperature and plasma sodium concentration in the intensive care unit. Out of 114 participants thirty (26.3%) developed dementia within the five years of follow-up. It was shown that a lower preoperative MMSE score and postoperative delirium were factors independently associated with development of dementia (II). One year after cardiac surgery, participants diagnosed with postoperative delirium described in detail feelings of extreme vulnerability and frailty. Despite this, the participants were grateful for the care they had received (III). Hypoactive was the most common symptom profile for delirium. The Swedish version of Nu-DESC showed high sensitivity in detecting hyperactive delirium, but low sensitivity in detecting hypoactive delirium (IV).Conclusion:Delirium was common among older patients undergoing cardiac surgery. Both predisposing and precipitating factors contributed to postoperative delirium. Preventive strategies should be considered in future randomized studies. It might also be suggested that cognitive function should be screened for preoperatively and patients who develop delirium should be followed up to enable early detection of symptoms of dementia. Whether prevention of postoperative delirium can reduce the risk of future dementia remains to be studied. To minimise unnecessary suffering, patients and next of kin should be informed about and prepared for the risk of delirium developing during hospitalization. The Swedish version of Nu-DESC should be combined with cognitive testing to improve detection of hypoactive delirium, but further research is needed. Healthcare professionals need knowledge concerning postoperative delirium in order to prevent, detect and treat delirium so as to avoid and relieve the suffering it might cause.
|
|
| 27. |
|
|
| 28. |
- Claesson Lingehall, Helena, et al.
(författare)
-
Preoperative Cognitive Performance and Postoperative Delirium Are independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery : A Longitudinal Cohort Study
- 2017
-
Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:8, s. 1295-1303
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery.Design: Longitudinal cohort study.Setting: Cardiothoracic Division, Umeå University Hospital, Sweden.Patients: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009.Intervention: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively.Measurements and Main Results: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic regression model showed a lower preoperative Mini-Mental State Examination score (p < 0.001; odds ratio, 0.68; 95% CI, 0.54–0.84) and the occurrence of postoperative delirium (p = 0.002; odds ratio, 7.57; 95% CI, 2.15–26.65) were associated with dementia occurrence.Conclusions: Our findings suggest that older patients with reduced preoperative cognitive functions or who develop postoperative delirium are at risk of developing dementia within 5 years after cardiac surgery. Cognitive functions should be screened for preoperatively, those who develop postoperative delirium should be followed up to enable early detection of dementia symptoms, and management should be implemented.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Contreras, F.-Xabier, et al.
(författare)
-
Molecular recognition of a single sphingolipid species by a protein's transmembrane domain
- 2012
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 481:7382, s. 525-529
-
Tidskriftsartikel (refereegranskat)abstract
- Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.
|
|
| 32. |
- Damber, Jan-Erik, et al.
(författare)
-
Rhythmical oscillations in rat testicular microcirculation as recorded by laser Doppler flowmetry
- 1983
-
Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 118:2, s. 117-123
-
Tidskriftsartikel (refereegranskat)abstract
- We have earlier reported that local testicular blood flow, recorded by laser Doppler flowmetry, shows large oscillations with a frequency of 5-10 min-1. In the present study it is proposed that the recorded oscillations represent mainly local microvascular blood flow variations rather than variations in total testicular blood flow or tissue movements. The reasons for this are: (a) Blood flow simultaneously measured at two separate sites showed oscillations with different frequencies. (b) A local subcapsular injection of room-tempered saline under one probe site eradicated oscillations under that probe but not under another adjacent probe. (c) When the testicular capsule was split open, recordings of blood flow continued to show oscillations. (d) The amplitude of the oscillations was rather large (peak to peak value about 50% of mean flow value). No movements of the testicular surface were seen. A 20 min continuous infusion of 0.4 microgram/min noradrenaline did induce a decrease in plasma testosterone concentration, but did not change the mean blood flow. However, the oscillations nearly completely disappeared during the infusion period. The present study also shows that laser Doppler flowmetry is a versatile method and the rat testis provides a suitable organ in the study of the origin and functional importance of these oscillations
|
|
| 33. |
- Damber, Jan-Erik, et al.
(författare)
-
Testicular blood flow measured with a laser Doppler flowmeter : acute effects of catecholamines.
- 1982
-
Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 115:2, s. 209-215
-
Tidskriftsartikel (refereegranskat)abstract
- Laser Doppler flowmetry was used to continuously measure testicular blood flow in rats. The method was found applicable on surgically exposed testes. Regular oscillations in blood flow, with a periodicity of 8.6 +/- 0.7 cycles per minute (mean +/- SD), were observed in recordings from 22 to 23 rats. Clamping of the testicular artery reduced the blood flow signal to background values. Effects of catecholamines administered into the tail artery on testicular blood flow together with systemic effects on mean arterial blood pressure and heart rate were measured. It was found that noradrenaline as well as adrenaline caused a significant decrease in blood flow when 10 micrograms was injected. Only noradrenaline decreased the blood flow when 1 microgram was given. The large oscillations detected in the blood flow recordings disappeared quickly when 10 or 1 micrograms of both hormones was administered. It was concluded that catecholamines can exert rapid effects on testicular blood flow
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Diderholm, Erik, et al.
(författare)
-
The prognostic and therapeutic implications of increased troponin T levels and ST depression in unstable coronary artery disease : the FRISC II invasive troponin T electrocardiogram substudy
- 2002
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 143:5, s. 760-767
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In unstable coronary artery disease, both increased troponin T level and occurrence of ST-segment depression are associated with a worse prognosis. In the Fast Revascularisation in InStability in Coronary disease trial II invasive study, we evaluated whether the troponin T level, alone and combined with ST depression, identified more severe coronary artery disease or a greater efficacy of an early invasive strategy. METHODS: In the study, 2457 patients with unstable coronary artery disease were randomized to early invasive or noninvasive strategy. Troponin T value and admission electrocardiogram results were available in 2286 patients. RESULTS: In the noninvasive cohort, death or myocardial infarction occurred in 16.6% with troponin T level > or =0.03 microg/L versus 8.5% with troponin T level < 0.03 microg/L (P <.001). In the invasive group, 49% of patients with both ST depression and troponin T level > or =0.03 microg/L had 3-vessel or left main disease compared with 17% if neither finding was present (P <.001). The invasive strategy reduced death/myocardial infarction at 12 months in the cohort with both ST depression and troponin T level > or =0.03 microg/L from 22.1% to 13.2% (risk ratio, 0.60; 95% confidence interval, 0.43 to 0.82; P =.001). In the cohort with either ST depression or troponin T level > or =0.03 microg/L or neither of these findings, the absolute gain of the invasive strategy was smaller and more uncertain. CONCLUSION: Patients with unstable coronary artery disease with the combination of troponin T level > or =0.03 microg/L and ST depression have a poor prognosis and, in half of the cases, 3-vessel or left main disease. In these patients, an early invasive strategy will substantially reduce death/myocardial infarction.
|
|
| 37. |
- Engberg, Anna E., 1982-, et al.
(författare)
-
Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides
- 2009
-
Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 30:13, s. 2653-2659
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 mu g/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma. (C) 2009 Elsevier Ltd. All rights reserved.
|
|
| 38. |
- Feyzi, Emadoldin, et al.
(författare)
-
Characterization of heparin and heparan sulfate domains binding to the long splice variant of platelet-derived growth factor A chain
- 1997
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 272:9, s. 5518-5524
-
Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factors (PDGFs) are homo- or heterodimers of two related polypeptides, known as A and B chains. The A chain exists as two splice variants due to the alternative usage of exons 6 (PDGF-AL, longer) and 7 (PDGF-AS, shorter). Exon 6 encodes an 18-amino acid sequence rich in basic amino acid residues, which has been implicated as a cell retention signal. Several lines of evidence indicate that the retention is due to binding of PDGF-AL to glycosaminoglycans, especially to heparan sulfate. We have analyzed the saccharide domains of smooth muscle cell-derived heparan sulfate involved in this interaction. Furthermore, we have employed selectively modified heparin oligosaccharides to elucidate the dependence of the binding on different sulfate groups and on fragment length. The shortest PDGF-AL binding domain consists of 6-8 monosaccharide units. Studies using selectively desulfated heparins and heparin fragments suggest that N-, 2-O-, and 6-O-sulfate groups all contribute to the interaction. Structural comparison of heparan sulfate oligosaccharides separated by affinity chromatography on immobilized PDGF-AL showed that the bound pool was enriched in -IdceA(2-OSO3)-GlcNSO3(6-OSO3)- disaccharide units. Furthermore, analogous separation of a partially O-desulfated heparin decamer preparation, using a highly selective nitrocellulose filter-trapping system, yielded a PDGF-AL-bound fraction in which more than half of the disaccharide units had the structure -IdceA(2-OSO3)-GlcNSO3(6-OSO3)-. Our results suggest that the interaction between PDGF-AL and heparin/heparan sulfate is mediated via N-sulfated saccharide domains containing both 2-O- and 6-O-sulfate groups.
|
|
| 39. |
- Frostfeldt, Gunnar, et al.
(författare)
-
Development of myocardial microcirculation and metabolism in acute ST-elevation myocardial infarction evaluated with positron emission tomography
- 2005
-
Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 12:1, s. 43-54
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early reperfusion is an established therapeutic objective in acute myocardial infarction (MI). The relationship of regional myocardial microcirculation and metabolism toward outcome in acute human MI is not well known.METHODS AND RESULTS: In 8 patients, positron emission tomography (PET) was performed with oxygen 15-labeled water at 3 hours, 24 hours, and 3 weeks after the start of fibrinolytic treatment, with carbon 11 acetate at 3 hours and with fluorine 18 fluorodeoxyglucose at 24 hours and 3 weeks. Absolute quantification of perfusion and water-perfusable tissue fraction (PTF), metabolic activity, and substrate extraction in 4 regions of interest was performed. Coronary angiography was performed at 24 hours. Short-term outcome at 3 weeks was evaluated by contractile reserve with dobutamine stress echocardiography and lung water measurements with PET. Early regional perfusion, PTF, and extraction and utilization of oxygen and glucose decreased closer to the infarct region ( P < .001 for all). Infarct-related oxygen utilization and extraction of oxygen and glucose were closely related to outcome ( P < .01 for all). PTF improved significantly in the infarct-related regions over time in proportion to early oxygen extraction and utilization.CONCLUSIONS: This pilot study indicates that PET might be useful in the evaluation of treatment efficacy and that restoration of oxidative metabolism is more closely related to myocardial damage recovery than perfusion in the early phase after MI.
|
|
| 40. |
- Ghumra, Ashfaq, et al.
(författare)
-
Structural requirements for the interaction of human IgM and IgA with the human Fc alpha/mu receptor
- 2009
-
Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 39:4, s. 1147-1156
-
Tidskriftsartikel (refereegranskat)abstract
- Here we unravel the structural features of human IgM and IgA that govern their interaction with the human Fc alpha/mu receptor (hFc alpha/mu R). Ligand polymerization status was crucial for the interaction, because hFc alpha/mu R binding did not occur with monomeric Ab of either class. hFc alpha/mu R bound IgM with an affinity in the nanomolar range, whereas the affinity for dimeric IgA (dIgA) was tenfold lower. Panels of mutant IgM and dIgA were used to identify regions critical for hFc alpha/mu R binding. IgM binding required contributions from both C mu 3 and C mu 4 Fc domains, whereas for dIgA, an exposed loop in the C alpha 3 domain was crucial. This loop, comprising residues Pro440-Phe443, lies at the Fc domain interface and has been implicated in the binding of host receptors Fc alpha RI and polymeric Ig receptor (pIgR), as well as IgA-binding proteins produced by certain pathogenic bacteria. Substitutions within the Pro440-Phe443 loop resulted in loss of hFc alpha/mu R binding. Furthermore, secretory component (SC, the extracellular portion of pIgR) and bacterial IgA-binding proteins were shown to inhibit the dIgA-hFc alpha/mu R interaction. Therefore, we have identified a motif in the IgA-Fc inter-domain region critical for hFc alpha/mu R interaction, and highlighted the multi-functional nature of a key site for protein-protein interaction at the IgA Fc domain interface.
|
|
| 41. |
- Gustafsson, Mattias C U, et al.
(författare)
-
Factor H Binds to the Hypervariable Region of Many Streptococcus pyogenes M Proteins but Does Not Promote Phagocytosis Resistance or Acute Virulence.
- 2013
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 9:4
-
Tidskriftsartikel (refereegranskat)abstract
- Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.
|
|
| 42. |
- Hammarlund, Karl Gunnar, 1954-, et al.
(författare)
-
Att lära historia – inte bara lära om historia
- 2009
-
Konferensbidrag (refereegranskat)abstract
- Den kunskap som eleverna förväntas erövra i den svenska skolan är, enligt de nu gällande läroplanerna för grundskola och gymnasium, ett mångtydigt begrepp: ”Kunskap kommer till uttryck i olika former – såsom fakta, förståelse, färdighet och förtrogenhet – som förutsätter och samspelar med varandra. Skolans arbete måste inriktas på att ge utrymme för olika kunskapsformer och att skapa ett lärande där dessa former balanseras och blir till en helhet.” I den ämnesspecifika kursplanen för grundskolan uttrycks historieämnets syfte analogt som ”att utveckla ett kritiskt tänkande och ett analytiskt betraktelsesätt som redskap för att förstå och förklara samhället och dess kultur.” Det är dock osäkert i vilken utsträckning den svenska skolan faktiskt uppfyller sin målsättning. Utvärderingar, senast den nationella utvärdering av grundskolan 2003 (NU03), antyder att undervisningen fortfarande – åtminstone till en del – präglas av traditionell allmänbildning som avspeglar läroböckernas innehåll. Undersökningar av läromedel och läromedelsanvändning pekar också i riktning mot att elever i den svenska skolan främst möter historien i form av fakta som ska läras in, inte ifrågasättas, prövas eller vidareutvecklas. Historieundervisningen kan alltså fortfarande ofta utformas så att eleverna förväntas ”lära att” snarare än ”lära hur”. Eller med andra ord att eleverna lär om historien snarare än att de tillägnar sig en förståelse av den egna livsvärlden betraktad i ett perspektiv av förflutet-nutid-framtid. En bidragande orsak till detta kan vara att de svenska styrdokumenten visserligen formulerar mål för undervisningen men inte lämnar några föreskrifter eller rekommendationer om form och innehåll. Detta ger stor frihet för den enskilde läraren, men ställer också krav på lärarens förmåga till innovativ planering, kunskap om och tillgång till läromedel och läranderesurser samt tillgång till tid för planering och genomförande. Under läsåret 2008/09 har lärare från Högskolan i Halmstad (lärarutbildningen) och Eketånga Montessoriskola arbetat med att utveckla dels en översiktsplanering för historia i årskurs 7-9, dels en detaljplanerad modul för fem veckors undervisning i svensk 1500- och 1600-talshistoria (genomförd under november-december 2008). En utgångspunkt för översiktsplaneringen har varit den struktur som prövats i det brittiska Schools History Project vilket innebär utrymme för historia som utvecklingslinjer, temastudier, djupstudier och lokalhistoria. I den detaljplanerade modulen har tonvikten lagts vid lokalhistoria, dels eftersom 1600-talet satt tydliga spår i Halmstads historia, dels eftersom lokalhistoria gör det möjligt för eleverna att knyta samman det förflutna med den konkreta livsvärld som omger dem. Läroboken har kompletterats med historiska kartor och annat källmaterial. Klassrumsarbetet har kompletterats med exkursioner och museibesök. I detta paper presenteras dels undervisningsplaneringen och de historiedidaktiska överväganden som legat till grund för dess utformning, dels elevers och undervisande lärares synpunkter på den genomförda undervisningsmodulen.
|
|
| 43. |
- Hellstrom-Lindahl, Ewa, et al.
(författare)
-
In vitro binding of [H-3]PIB to human amyloid deposits of different types
- 2014
-
Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 21:1, s. 21-27
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar proteins arranged in beta-pleated sheets. [C-11] PIB has been used in PET studies to assess A beta deposition in brain of patients with Alzheimer's disease (AD). The possibility to visualize other types of amyloid deposits with [C-11] PIB would be of potential clinical importance in early diagnosis and for following therapeutic effects. In the present study, we evaluated in vitro binding of [3 H] PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain (AL), amyloid protein A (AA) and Ab amyloid. We found significantly higher binding of [H-3] PIB in tissue from systemic amyloidoses than in control tissue, i.e. 4.7 times higher (p<0.05). [H-3] PIB showed the highest affinity to cortex of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and AL type of amyloidosis and large variations in affinity were observed even within tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which disrupts the beta-sheet structure, decreased the protein levels and, concomitantly, the binding of [H-3] PIB in all four types of amyloidoses.
|
|
| 44. |
- Hillarp, Andreas, et al.
(författare)
-
Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation
- 2004
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 91:2, s. 300-307
-
Tidskriftsartikel (refereegranskat)abstract
- In 1999, a simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced by a working group of the organisation for national quality assurance in laboratory medicine in Sweden. The new protocol allowed local calibration by means of only two lyophilised national plasma calibrators and expression of results as an international normalized ratio (INR). This is our report of a three-year follow-up involving the analysis of data from all laboratories, in hospitals (n=88 in 2002) and primary health care units (n=246 in 2002) that perform the Owren PT assay in Sweden. The interlaboratory variation was significantly improved after the introduction of the new calibration procedure. For the larger hospital-based laboratories, the mean coefficient of variation (CV) was reduced from 7.9% to 5.2% (p<0.0001) when analysing test materials with INR range 2-4. In the higher INR range (>4), the CV was reduced even further, from 10.4% to 6.8% (p<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.2% to 5.7% in the INR range 2-4 (p<0.0001). At the INR range >4, the CV was reduced from 9.5% to 7.8%. The intralaboratory variation was also improved for both types of laboratory categories. This study shows an improved precision, with CV less than 6% at the therapeutic INR range, for both hospital-based laboratories and smaller laboratories in the primary health care system. The results indicate that the Owren PT assay is well suited for local INR calibration employing only two calibrant plasmas in a simplified procedure.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Hillarp, Andreas, et al.
(författare)
-
Mer samstämmiga laboratorieresultat efter övergången till INR. Skillnaderna mellan sjukhus- och primärvårdslaboratorier utjämnade
- 2002
-
Ingår i: Läkartidningen. - 0023-7205. ; 99:50, s. 70-5073
-
Tidskriftsartikel (refereegranskat)abstract
- In 1999 a new and simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced in Sweden by the national external quality assessment scheme (Equalis). The new protocol allowed local calibration by means of lyophilised national plasma calibrators and expression of results as an international normalised ratio (INR). A two-year follow-up involving analysis of data from all laboratories that have returned results to Equalis is reported. There was a significant reduction in both between-laboratory and within-laboratory variation after the introduction of the new calibration procedure. For the larger hospital laboratories analysing external controls with INR>2, the mean coefficient of variation (CV) was reduced from 9.1% to 5.6% (P<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.8% to 6.3% (P<0.0001). This study shows that the Owren PT assay is well suited for INR calibration employing calibrant plasmas.
|
|
| 48. |
- Husmann, Linda K, et al.
(författare)
-
Expression of the Arp protein, a member of the M protein family, is not sufficient to inhibit phagocytosis of Streptococcus pyogenes
- 1995
-
Ingår i: Infection and Immunity. - 1098-5522. ; 63:1, s. 345-348
-
Tidskriftsartikel (refereegranskat)abstract
- Many Streptococcus pyogenes immunoglobulin-binding proteins have structural similarities to the antiphagocytic M protein, including the well-known C repeats. One of these molecules is the immunoglobulin A-binding protein Arp, which is expressed by a serotype 4 strain for which no antiphagocytic M protein has yet been described. We expressed Arp4 in an S. pyogenes strain from which the structural gene for the M protein has been deleted and found that Arp4 is not sufficient to inhibit phagocytosis.
|
|
| 49. |
- Jenkins, HT, et al.
(författare)
-
Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor
- 2006
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 281:6, s. 3690-3697
-
Tidskriftsartikel (refereegranskat)abstract
- Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement.
|
|
| 50. |
|
|
