| 1. |
- Alsmark, Cecilia M., et al.
(författare)
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The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae
- 2004
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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. ; 101:26, s. 9716-9721
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Tidskriftsartikel (refereegranskat)abstract
- We present the complete genomes of two human pathogens, Bartonella quintana (1,581,384 bp) and Bartonella henselae (1,931,047 bp). The two pathogens maintain several similarities in being transmitted by insect vectors, using mammalian reservoirs, infecting similar cell types (endothelial cells and erythrocytes) and causing vasculoproliferative changes in immunocompromised hosts. A primary difference between the two pathogens is their reservoir ecology. Whereas B. quintana is a specialist, using only the human as a reservoir, B. henselae is more promiscuous and is frequently isolated from both cats and humans. Genome comparison elucidated a high degree of overall similarity with major differences being B. henselae specific genomic islands coding for filamentous hemagglutinin, and evidence of extensive genome reduction in B. quintana, reminiscent of that found in Rickettsia prowazekii. Both genomes are reduced versions of chromosome I from the highly related pathogen Brucella melitensis. Flanked by two rRNA operons is a segment with similarity to genes located on chromosome II of B. melitensis, suggesting that it was acquired by integration of megareplicon DNA in a common ancestor of the two Bartonella species. Comparisons of the vector-host ecology of these organisms suggest that the utilization of host-restricted vectors is associated with accelerated rates of genome degradation and may explain why human pathogens transmitted by specialist vectors are outnumbered by zoonotic agents, which use vectors of broad host ranges.
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| 2. |
- Andelid, Kristina, 1953, et al.
(författare)
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Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis
- 2021
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Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods: In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results: We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air-liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNF alpha in this cross-talk. Conclusions: For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNF alpha-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.
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| 3. |
- Andersson, Maria L. E., et al.
(författare)
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Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease. Methods: In all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change <= 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by >= 5.8. Results: The group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels. The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression. Conclusion: Increasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.
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| 4. |
- Bonn, Stephanieb E. E., et al.
(författare)
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Effect of a Smartphone Application on Physical Activity and Weight Loss After Bariatric Surgery-Results from a Randomized Controlled Trial
- 2023
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Ingår i: Obesity Surgery. - : SPRINGER. - 0960-8923 .- 1708-0428. ; 33:9, s. 2841-2850
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Ways to motivate and support patients in being physically active after bariatric surgery are needed. This trial was aimed at evaluating the effect of using a smartphone application targeting physical activity during 12 weeks on moderate-to-vigorous physical activity (MVPA, primary outcome) and secondary outcomes of inactivity, light physical activity (LPA), body mass index (BMI), and percent total weight loss (%TWL) after bariatric surgery.Materials and Methods Data from a randomized controlled trial comprising 146 patients (79.5% women) undergoing bariatric surgery was analyzed. Mean age and BMI pre-surgery were 40.9 years and 40.5 kg/m(2), respectively. Participants were randomized 1:1 to an intervention or a control group. Physical activity and body weight were objectively measured at baseline pre-surgery and post-surgery follow-ups after 6 weeks (weight only), 18 weeks, 6 months, and 1 year. Linear mixed models were fitted to assess longitudinal differences in outcomes between the groups.Results A significant effect of the intervention (group-by-time interaction 16.2, 95% CI 3.5 to 28.9) was seen for MVPA at 18 weeks; the intervention group had increased their MVPA since baseline, while the control group had decreased their MVPA. The control group had lowered their BMI approximately 1 kg/m(2) more than the intervention group at follow-up after 18 weeks and 12 months, yet, mean BMI did not differ between the groups. No intervention effect was seen on inactivity, LPA, or %TWL.ConclusionOur results indicate that use of a smartphone application targeting physical activity may have the potential to promote short-term MVPA post bariatric surgery.
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| 5. |
- Olofsson, Peder S., et al.
(författare)
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Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase
- 2016
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Ingår i: Nature Biotechnology. - : Nature Publishing Group. - 1087-0156 .- 1546-1696. ; 34:10, s. 1066-1071
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4(+) T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals(1). Here we show that these CD4(+)CD44(hi)CD62L(Io) T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T-ChAT). Mice lacking ChAT expression in CD4(+) cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT(ChAT)) decreased blood pressure when infused into mice. Co-incubation of JT(ChAT) and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 T-ChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.
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| 6. |
- Andersson, Kristina E
(författare)
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Cholesterol-lowering and anti-atherogenic effects of oats in mice
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cholesterol-lowering effect of oats is well established, but the crucial properties eliciting this effect need to be further investigated to optimize the use of oats as functional foods. Furthermore, there are almost no reports investigating the effect of oats on atherosclerosis development. This thesis describes our work with finding suitable mouse models to study cholesterol-lowering and anti-atherogenic effects of oats, the mechanism behind, and how processing of oat foods might interfere with these beneficial effects. We found that supplementation of oat bran to an atherogenic diet significantly reduced plasma cholesterol and LDL+VLDL concentrations in C57BL/6 mice. The responsiveness to oats did however differ between two substrain of mice. Oat intake resulted in reduced plasma cholesterol, increased faecal excretion of bile acids and cholesterol, and increased expression of the bile acid producing enzyme CYP7A1 in the C57BL/6NCrl substrain. None of these parameters were altered in the C57BL/6JBomTac mice. The different expression of CYP7A1 in the two substrains of C57BL/6 strongly supports the importance of increased bile acid excretion, together with increase of bile acid synthesis from cholesterol, for oats to reduce levels of cholesterol in plasma. To address how processing of oats might interfere with its cholesterol-lowering properties, oat beta-glucans were enzymatically digested to different molecular weights and then fed to C57BL/6NCrl mice. Reducing the molecular weight of the beta-glucans affected its viscous properties in vitro. It also affected the production of short chain fatty acids in caecal contents of the mice, but did not influence the cholesterol-lowering properties. Thus molecular weight and viscous properties of beta-glucans do not seem to be crucial parameters for the cholesterol-lowering properties of oats in the C57BL/6 mice. When studying effects of oats on atherogenesis and inflammation we used a mouse model developing more pronounced hypercholesterolaemia, the LDL-receptor deficient mice. Oats reduced plasma cholesterol and levels of LDL+VLDL in this model too, and also reduced plasma concentrations of the inflammation markers fibrinogen and soluble vascular adhesion molecule-1 (sVCAM-1). Most importantly oat bran in the diet reduced incidence of atherosclerotic lesions in both the aortic root and the descending aorta. These findings demonstrate that oats have anti-atherogenic properties, and support health claims that oats can reduce risk of cardiovascular disease.
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| 7. |
- Andersson, Kristina E, et al.
(författare)
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Dietary oats and modulation of atherogenic pathways.
- 2012
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Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4133 .- 1613-4125. ; 56:7, s. 1003-1013
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Forskningsöversikt (refereegranskat)abstract
- Consumption of oats has long been known to lower plasma total and low-density lipoprotein (LDL) cholesterol levels, an effect usually attributed to the soluble fibers β-glucans. On the basis of this cholesterol-lowering effect, oats are ascribed cardiovascular health-promoting properties. However, besides cholesterol levels, effects of oats on parameters relating to atherosclerosis development have not been extensively investigated. Since oxidation of lipoproteins and inflammation are characteristics of atherosclerosis in addition to lipid accumulation in the vessel wall, micronutrients in oats (phytochemicals) with antioxidative and anti-inflammatory properties may contribute to an atheroprotective action. Here, we summarize evidence on antiatherogenic properties of oats obtained from in vitro assays, animal experiments, and human studies. Possible effects involving anti-inflammatory and antioxidative actions, as well as preservation of endothelial function, are considered in addition to those related to reduction of plasma cholesterol. Since results of in vitro assays with isolated oat components are difficult to compare with effects of whole oats in humans and experimental animals, more observational studies with isolated oat components or fractions of oats are warranted. Also, there is a lack of epidemiological studies focusing on effects of oat intake on the cardiovascular disease panorama.
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| 8. |
- Andersson, Kristina E, et al.
(författare)
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Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes.
- 2013
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 52:7, s. 1755-1769
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect. METHODS: Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks. RESULTS: C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % (P < 0.001) lower plasma cholesterol, 40 ± 5 % (P < 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl. CONCLUSIONS: Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.
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| 9. |
- Andersson, Kristina E, et al.
(författare)
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Effects of oats on plasma cholesterol and lipoproteins in C57BL/6 mice are substrain specific.
- 2010
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 103, s. 513-521
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Tidskriftsartikel (refereegranskat)abstract
- Cholesterol-lowering effects of oats have been demonstrated in both animals and human subjects. However, the crucial properties of oat-containing diets that determine their health effects need to be further investigated to optimise their use. A mouse model would be a valuable tool, but few such studies have been published to date. We investigated the effects of oat bran on plasma cholesterol and lipoproteins in two substrains of C57BL/6 mice. Western diet was made atherogenic by the addition of 0.8 % cholesterol and 0.1 % cholic acid. After 4 weeks on atherogenic diet, total plasma cholesterol had increased from 1.86-2.53 to 3.77-4.40 mmol/l. In C57BL/6NCrl mice, inclusion of 27 and 40 % oat bran reduced total plasma cholesterol by 19 and 24 %, respectively, reduced the shift from HDL to LDL+VLDL and caused increased faecal cholesterol excretion. There was no effect of oat bran on plasma levels of the inflammatory markers fibrinogen, serum amyloid A or TNF-alpha. Contrary to findings in C57BL/6NCrl mice, there was no sustained effect of oat bran (27 or 40 %) on plasma cholesterol in C57BL/6JBomTac mice after 4 weeks of feeding. Thus, C57BL/6NCrl mice fed an atherogenic diet are a good model for studies of physiological effects of oats, whereas a substrain derived from C57BL/6J, raised in a different breeding environment and likely possessing functional genetic differences from C57BL/6N, is considerably less responsive to oats. The present finding that two substrains of mice respond differently to oats is of practical value, but can also help to elucidate mechanisms of the cholesterol-lowering effect of oats.
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| 10. |
- Andersson, Kristina E, et al.
(författare)
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Oats (Avena sativa) reduce atherogenesis in LDL-receptor-deficient mice.
- 2010
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; Jul 1, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The cholesterol-lowering properties of oats, largely ascribed to its contents of soluble fibers, beta-glucans, are well established, whereas effects on atherogenesis are less well elucidated. Oats also contains components with reported antioxidant and anti-inflammatory effects that may affect atherogenesis. In this work we examined effects of oat bran on plasma cholesterol, markers of inflammation, eNOS expression and development of atherosclerosis in LDL-receptor-deficient (LDLr(-/-)) mice. METHODS AND RESULTS: Female LDLr(-/-) mice were fed Western diet+/-oat bran. Two concentrations of oat bran (40 and 27%) were compared regarding effects on plasma lipids. There was a dose-dependent reduction of plasma cholesterol by 42 and 20% with 40 and 27% oat bran, respectively. Both concentrations also lowered plasma triglycerides (by 45 and 33%) and relative levels of plasma LDL+VLDL. The reduction of plasma lipids was accompanied by increased faecal excretion of cholesterol and bile acids. Oat bran (40%) efficiently reduced atherosclerotic lesion area in the descending aorta (-77%) and aortic root (-33%). Plasma levels of fibrinogen and soluble vascular cell adhesion molecule-1 (VCAM-1) were significantly lower, and immunofluorescence of aortic sections revealed a 75% lower expression of VCAM-1 in oat-fed mice. The expression of eNOS protein in the aortic wall was increased in mice fed oat bran. CONCLUSIONS: Oat bran supplemented to a Western diet lowers plasma cholesterol, reduces levels of some inflammatory markers, increases eNOS expression and inhibits atherosclerotic lesion development in LDLr(-/-) mice. It remains to be investigated which components in oats contribute to these effects.
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