| 1. |
- Morfeldt, E, et al.
(författare)
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Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein : implications for antigenic variation.
- 2001
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 167:7, s. 3870-7
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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.
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| 2. |
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| 3. |
- Andersson, Jonas, 1977-, et al.
(författare)
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Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity : results from a randomized controlled trial with 5-year follow-up
- 2008
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Ingår i: Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals. - : Informa UK Limited. - 1366-5804. ; 13:7, s. 671-679
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Tidskriftsartikel (refereegranskat)abstract
- C-reactive protein (CRP) is a marker of metabolic and cardiovascular disease. To study the effects of lifestyle on CRP in a high-risk population we conducted a randomized controlled trial on 200 obese subjects (BMI > 27 kg m(-2)) with impaired glucose tolerance recruited from primary care settings. They were randomized to either a 1-month stay at a wellness centre focusing on diet, exercise and stress management (intervention group) or 30-60 min of oral and written information on lifestyle intervention (control group). A significant reduction of CRP was observed after 1 month and 1 year in the intervention group. They reduced their CRP levels more than the control group 1 year after intervention (p=0.004). In conclusion lifestyle intervention can decrease CRP in obese individuals with impaired glucose tolerance for up to 1 year. Further research is needed to evaluate whether the CRP level reduction translates into a decreased risk for cardiovascular morbidity.
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| 4. |
- André, Ingemar, et al.
(författare)
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Streptococcal M protein: Structural studies of the hypervariable region, free and bound to human C4BP
- 2006
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 45:14, s. 4559-4568
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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.
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| 5. |
- Bengtsson, Torbjörn, et al.
(författare)
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The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation
- 2008
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Ingår i: Journal of Internal Medicine. - : Institutionen för medicin och hälsa. - 0954-6820 .- 1365-2796. ; 263:5, s. 558-571
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation.Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay.Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS-production, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.
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| 6. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 7. |
- Bergman, Torbjörn, 1957-, et al.
(författare)
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Appendix : On definition and measurement
- 2021
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Ingår i: Coalition governance in Western Europe. - Oxford : Oxford University Press. - 9780198868484 ; , s. 727-748
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Bokkapitel (refereegranskat)abstract
- The appendix introduces our empirical study of the coalition life cycle. The structure of each country chapter is based on six core tables, each one capturing a major stage in the coalition life cycle. In the book chapters, the tables help structure the analysis and provide wealth of information and details of the coalition cycle. Nevertheless, the book chapters and this appendix only present a sample of the data and information that we have collected for this research project. For reasons of space, we have had to limit the presentation in the book chapters in terms of time-periods and variables. This appendix presents many more details that are important for readers who are not familiar with the definitions used in coalition research or interested in how particular variables where measured. In addition to the definitions and measurements presented in this appendix, all the data and all the variables are presented in an on-line data appendix at www.erdda.org.
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| 8. |
- Fälker, Knut, 1971-, et al.
(författare)
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The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLC gamma 2 signalling cascade
- 2014
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Ingår i: Cellular Signalling. - New York, USA : Elsevier. - 0898-6568 .- 1873-3913. ; 26:2, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- The specific TLR2/1 complex activator Pam3CSK4 has been shown to provoke prominent activation and aggregation of human non-nucleated platelets. As Pam3CSK4-evoked platelet activation does not employ the major signalling pathway established in nucleated immune cells, we investigated if the TLR2/1 complex on platelets may initiate signalling pathways known to be induced by physiological agonists such as collagen via GPVI or thrombin via PARs. We found that triggering TLR2/1 complex-signalling with Pam3CSK4, in common with that induced via GPVI, and in contrast to that provoked by PARS, involves tyrosine phosphorylation of the adaptor protein LAT as well as of PLC gamma 2 in a src- and Syk-dependent manner. In this respect, we provide evidence that Pam3CSK4 does not cross-activate GPVI. Further, by the use of platelets from a Glanzmann's thrombasthenia patient lacking beta(3), in contrast to findings in nucleated immune cells, we show that the initiation of platelet activation by Pam3CSK4 does not involve integrin beta(3) signalling; whereas the latter, subsequent to intermediate TXA2 synthesis and signalling, was found to be indispensable for proper dense granule secretion and full platelet aggregation. Together, our findings reveal that triggering the TLR2/1 complex with Pam3CSK4 initiates human platelet activation by engaging tyrosine kinases of the src family and Syk, the adaptor protein LAT, as well as the key mediator PLC gamma 2. (C) 2013 Elsevier Inc. All rights reserved.
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| 9. |
- Johansson, Torbjörn, et al.
(författare)
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Biologisk mångfald i skogslandskapet.
- 1994
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I skogslandskapet är mångfalden av arter och framför allt hotade sådana, koncentrerade till sumpskogar, gammal skog, död ved, och lövträd.Förekomsten av nyckelbiotoper i länet har uppskattats utifrån de ca 5% av skogsmarksarealen som idag är inventerade.Ingenting tyder på att situationen skulle vara väsentligt annorlunda i övriga delar av länet.Endast 2-3% av skogsmarksarealen i länet, inkl reservaten, bedöms utgöra biotoper med så höga naturvärden att de uppfyller kraven för nyckelbiotop.Detta ger en bild av hur mycket av skogen som idag har naturskogskaraktär och därmed också hur omfattande omdaningen av skogslandskapet har varit. Arterna i skogslandskapet påverkas i olika utsträckning av det moderna skogsbruket.
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| 10. |
- Katus, Hugo, et al.
(författare)
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Early diagnosis of acute coronary syndrome
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:41, s. 3049-3055
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Forskningsöversikt (refereegranskat)abstract
- The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research.
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