| 1. |
- Forsberg, Anna M., et al.
(författare)
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Prevalence of colonic neoplasia and advanced lesions in the normal population : a prospective population-based colonoscopy study
- 2012
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:2, s. 184-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.
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| 2. |
- Malmström, Johan, et al.
(författare)
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Streptococcus pyogenes in human plasma: adaptive mechanisms analyzed by mass spectrometry based proteomics.
- 2012
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 287:2, s. 1415-1425
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a major bacterial pathogen and a potent inducer of inflammation causing plasma leakage at the site of infection. A combination of label free quantitative mass spectrometry-based proteomics strategies were used to measure how the intracellular proteome homeostasis of S. pyogenes is influenced by the presence of human plasma, identifying and quantifying 842 proteins. In plasma the bacterium modifies its production of 213 proteins, and the most pronounced change was the complete down-regulation of proteins required for fatty acid biosynthesis (FAB). Fatty acids are transported by albumin (HSA) in plasma. S. pyogenes expresses HSA-binding surface proteins, and HSA carrying fatty acids reduced the amount of FAB proteins to the same extent as plasma. The results clarify the function of HSA-binding proteins in S. pyogenes and underline the power of the quantitative mass spectrometry strategy used here to investigate bacterial adaptation to a given environment.
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| 3. |
- Wisniewska, Magdalena, et al.
(författare)
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Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes.
- 2014
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 289:26, s. 18175-18188
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment enabling bacterial interactions with the host. In the present study we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice, with a non-virulent strain. Particularly one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP, suggest a role for the protein in S. pyogenes pathogenesis.
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| 4. |
- Björck, Lena, 1959, et al.
(författare)
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Medication in relation to ST-segment elevation myocardial infarction in patients with a first myocardial infarction: Swedish Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA)
- 2010
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 170:15, s. 1375-1381
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The extent and the severity of acute myocardial infarction (MI) is decreasing. Out-of-hospital medical management before the hospital admission could alter clinical presentation in acute MI. We used a large national patient register to investigate the relation between previous medication use (aspirin, beta-blockers, angiotensin-converting enzyme [ACE] inhibitors, and statins) and the risk of presenting with ST-segment elevation MI (STEMI) or non-STEMI. METHODS: We included 103 459 consecutive patients from the Swedish Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA) admitted between January 1, 1996, and December 31, 2006, with a first acute MI. RESULTS: The patients with STEMI (43.5% of the total) were younger, had less prior cardiovascular disease, and used fewer medications before hospitalization. Of the STEMI patients, 61.4% had used no medication vs 45.9% of the patients with non-STEMI. After multiple adjustments, use of aspirin, beta-blockers, ACE inhibitors, and statins before hospitalization were all associated with substantially lower odds of presenting with STEMI. Furthermore, the risk decreased with the number of previous medications, and the use of 3 or more medications was associated with a multiply adjusted odds ratio of presenting with STEMI of 0.48 (99% confidence interval, 0.44-0.52) compared with no medications at admission. CONCLUSIONS: Use of aspirin, beta-blockers, ACE inhibitors, or statins before hospital admission in patients with a first acute MI is associated with substantially less risk of presenting with STEMI. The risk decreases with the increasing number of these medications used before acute MI, underlining the benefit of preventive medication in high-risk patients.
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| 5. |
- Dudas, Kerstin, 1963, et al.
(författare)
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Differences between acute myocardial infarction and unstable angina: a longitudinal cohort study reporting findings from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA)
- 2013
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to compare risk factors and comorbidities in patients with a first episode of acute coronary syndrome (ACS), being either acute myocardial infarction (AMI) or unstable angina pectoris (UAP). DESIGN: Cross-sectional and prospective. SETTING: The Swedish population. PARTICIPANTS: A total of 145 346 consecutive patients aged 25-105 years included in the Swedish Register of Cardiac Intensive Care Admission (Register of Information and Knowledge about Swedish Heart Intensive Care) and admitted to hospital between 1 January 1996 and 30 June 2009 with a first episode of either AMI or UAP. PRIMARY AND SECONDARY OUTCOME MEASURES: Type of ACS and 1-year outcome. RESULTS: Compared with patients with UAP, AMI patients were more likely to be older; men; and former or current smokers; they were also more likely to have had diabetes and peripheral artery disease, but had lower rates of prior heart failure (HF) and fewer cardioprotective medications on admission. Among patients aged <65 years, 1.4% of men and 1.6% of women with UAP died within 1 year in 2003-2006 compared with 4.2% of men and 3.1% of women AMI patients (multiple-adjusted OR 3.54 (99% CI 2.29 to 5.48) in women and 2.65 (99% CI 2.11 to 3.34) in men). Corresponding proportions in patients aged >/=65 years was 7.5% in men and 7.6% in women with UAP and 21.5% in men and 17.8% in women with AMI. CONCLUSIONS: In patients with a first-time ACS episode, male sex, slightly older age, smoking, diabetes and peripheral arterial disease (PAD), but fewer cardioprotective medications, were major determinants for presenting with AMI. Despite increasingly active treatment in AMI and more inclusive diagnostic criteria in recent years, persistently worse prognosis was observed in AMI patients.
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| 6. |
- Egesten, Arne, et al.
(författare)
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Binding of albumin promotes bacterial survival at the epithelial surface.
- 2011
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; Dec, s. 2469-2476
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Tidskriftsartikel (refereegranskat)abstract
- Albumin (HSA) is the dominating protein in human plasma. Many bacterial species, especially streptococci, express surface proteins that bind HSA with high specificity and affinity, but the biological consequences of these protein-protein interactions are poorly understood. Group G streptococci (GGS), carrying the HSA-binding protein G, colonize the skin and the mucosa of the upper respiratory tract, mostly without causing disease. In case of bacterial invasion, pro-inflammatory cytokines are released that activate the epithelium to produce antibacterial peptides, in particular the chemokine MIG/CXCL9. In addition, the inflammation causes capillary leakage and extravasation of HSA and other plasma proteins; environmental changes at the epithelial surface to which the bacteria need to respond. In this study, we find that GGS adsorb HSA from both saliva and plasma via binding to protein G, and that HSA bound to protein G binds and inactivates the antibacterial MIG/CXCL9 peptide. Another surface protein of GGS, FOG, was found to mediate adherence of the bacteria to pharyngeal epithelial cells through interaction with glycosaminoglycans. This adherence was not affected by the activation of the epithelium with a combination of IFN-γ and TNF-α, leading to the production of MIG/CXCL9. However, at the activated epithelial surface, adherent GGS were protected against killing by MIG/CXCL9 through protein G dependent HSA-coating. The findings identify a previously unknown bacterial survival strategy that help to explain the evolution of HSA-binding proteins among bacterial species of the normal human microbiota.
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| 7. |
- Ermert, David, et al.
(författare)
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Binding of complement inhibitor C4b-binding protein to a highly virulent S. pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.
- 2013
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 288:45, s. 32172-32183
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes AP1, a strain of the highly virulent M1 serotype, uses exclusively protein H to bind the complement inhibitor C4b-binding protein (C4BP). We found a strong correlation between the ability of AP1 and its isogenic mutants lacking protein H to inhibit opsonisation with complement C3b and binding of C4BP. C4BP bound to immobilized protein H or AP1 bacteria retained its cofactor activity for degradation of 125I-C4b. Further, C4b deposited from serum onto AP1 bacterial surfaces was processed into C4c/C4d fragments, which did not occur on strains unable to bind C4BP. Recombinant C4BP mutants, which (i) lack certain CCP domains, or (ii) have mutations in single aa as well as (iii) mutants with additional aa between different CCP domains were used to determine that the binding is mainly mediated by a patch of positively charged amino acid residues at the interface of domains CCP1 and CCP2. Using recombinant protein H fragments, we narrowed down the binding site to the N-terminal domain A. With a peptide microarray, we identified one single 18 amino acid long peptide comprising residues 92-109, which specifically bound C4BP. Biacore was used to determine KD = 6x10-7 M between protein H and a single subunit of C4BP. C4BP binding also correlated with elevated levels of adhesion and invasion to endothelial cells. Taken together, we identified the molecular basis of C4BP-protein H interaction and found that it is not only important for decreased opsonisation but also for invasion of endothelial cells by Streptococcus pyogenes.
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| 8. |
- Frick, Inga-Maria, et al.
(författare)
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Antibacterial activity of the contact and complement systems is blocked by SIC, a protein secreted by Streptococcus pyogenes.
- 2011
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 286, s. 1331-1340
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that activation of the complement and contact systems results in the generation of antibacterial peptides. Streptococcus pyogenes, a major bacterial pathogen in humans, exists in more than one hundred different serotypes due to sequence variation in the surface-associated M protein. Cases of invasive and life-threatening S. pyogenes infections are commonly associated with isolates of the M1 serotype, and in contrast to the large majority of M serotypes, M1 isolates all secrete the SIC protein. Here we show that SIC interferes with the activation of the contact system, and blocks the activity of antibacterial peptides generated through complement and contact activation. This effect promotes the growth of S. pyogenes in human plasma, and in a mouse model of S. pyogenes sepsis, SIC enhances bacterial dissemination, results which help to explain the high frequency of severe S. pyogenes infections caused by isolates of the M1 serotype.
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| 9. |
- Giang, Kok Wai, 1984, et al.
(författare)
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Stroke and coronary heart disease: predictive power of standard risk factors into old age-long-term cumulative risk study among men in Gothenburg, Sweden
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:14, s. 1068-1074
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to examine the short-term and long-term cumulative risk of coronary heart disease (CHD) and stroke separately based on age, sex, smoking status, systolic blood pressure, and total serum cholesterol. Methods and results The Primary Prevention Study comprising 7174 men aged between 47 and 55 free from a previous history of CHD, stroke, and diabetes at baseline examination (1970–73) was followed up for 35 years. To estimate the cumulative effect of CHD and stroke, all participants were stratified into one of five risk groups, defined by their number of risk factors. The estimated 10-year risk for high-risk individuals when adjusted for age and competing risk was 18.1% for CHD and 3.2% for stroke which increased to 47.8 and 19.6%, respectively, after 35 years. The estimates based on risk factors performed well throughout the period for CHD but less well for stroke. Conclusion The prediction of traditional risk factors (systolic blood pressure, total serum cholesterol, and smoking status) on short-term risk (0–10 years) and long-term risk (0–35 years) of CHD of stroke differs substantially. This indicates that the cumulative risk in middle-aged men based on these traditional risk factors can effectively be used to predict CHD but not stroke to the same extent.
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| 10. |
- Hedén Ståhl, Christina, 1972, et al.
(författare)
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High-normal blood pressure and long-term risk of type 2 diabetes: 35-year prospective population based cohort study of men
- 2012
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Ingår i: BMC cardiovascular disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: The link between type 2 diabetes and hypertension is well established and the conditions often coexist. High normal blood pressure, defined by WHO-ISH as systolic blood pressure (SBP) 130--139 mm Hg or diastolic blood pressure (DBP) 85--89 mm Hg, has been found to be an independent predictor for type 2 diabetes in studies, although with relatively limited follow-up periods of approximately 10 years. The aim of this study was to investigate whether hypertension, including mildly elevated blood pressure within the normal range, predicted subsequent development of type 2 diabetes in men over an extended follow-up of 35 years. METHODS: Data were derived from the Gothenburg Primary Prevention Study where a random sample of 7 494 men aged 47--55 years underwent a baseline screening investigation in the period 1970--1973. A total of 7 333 men were free from previous history of diabetes at baseline. During a 35-year follow-up diabetes was identified through the Swedish hospital discharge and death registries. The cumulative risk of diabetes adjusted for age and competing risk of death was calculated. Using Cox proportional hazard models we calculated the multiple adjusted hazard ratios (HR) (95% confidence interval (CI)) for diabetes at different blood pressure levels. RESULTS: During a 35-year follow-up, 956 men (13%) were identified with diabetes. The 35-year cumulative risk of diabetes after adjusting for age and competing risk of death in men with SBP levels <130 mm Hg, 130--139 mm Hg, 140--159 mm Hg and >=160 mm Hg were 19%, 30%, 31% and 49%, respectively. The HR for diabetes adjusted for age, body mass index (BMI), cholesterol, antihypertensive treatment, smoking, physical activity and occupation were 1.43 (95% CI 1.12-1.84), 1.43 (95% CI 1.14-1.79) and 1.95 (95% CI 1.55-2.46) for men with SBP 130--139 mm Hg, 140--159 mm Hg, and >= 160 mm Hg, respectively (reference; SBP<130 mm Hg). CONCLUSION: In this population, at mid-life, even high-normal SBP levels were shown to be a significant predictor of type 2 diabetes, independently of BMI and other conventional type 2 diabetes risk factors over an extended follow-up.
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