SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Bengtsson Caroline) "

Sökning: WFRF:(Bengtsson Caroline)

  • Resultat 1-50 av 55
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Klarström-Engström, Kristin, 1986-, et al. (författare)
  • Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation
  • 2014
  • Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 9:4, s. 041003-
  • Tidskriftsartikel (refereegranskat)abstract
    • Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam(3)CSK(4) (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and Fc gamma RII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam(3)CSK(4) and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam(3)CSK(4)- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam(3)CSK(4) activated platelets utilize the same pathway as Fc gamma RII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam(3)CSK(4). These results clarify the importance of TLR2/1 and Fc gamma RII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections.
  •  
2.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
  •  
3.
  • Abrikossova, Natalia, et al. (författare)
  • Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes
  • 2012
  • Ingår i: Nanotechnology. - Bristol, United Kingdom : IOP Publishing Ltd.. - 0957-4484 .- 1361-6528. ; 23:27
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.
  •  
4.
  • Ahrén, Maria, et al. (författare)
  • Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
  • 2010
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
  •  
5.
  • Bengtsson, Anna, et al. (författare)
  • Outdoor Environments at Three Nursing Homes: Semantic Environmental Descriptions
  • 2015
  • Ingår i: Journal of Housing for the Elderly. - : Informa UK Limited. - 0276-3893 .- 1540-353X. ; 29, s. 53-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Research suggests that the outdoor environment is an important source of variety and change as well as health and well-being for nursing home residents. However, not every outdoor environment has the potential to be a positive resource in the life of older persons at nursing homes, and in this respect we need to study the particular design and content of the outdoor environment. The semantic environmental description (SMB) is a quantitatively based standardized tool intended to systematically describe an environment through assessments of 8 dimensions, namely: pleasantness, complexity, unity, enclosedness, potency, social status, affection, and originality. In this study the SMB was used to compare the outdoor environment of an imagined ideal nursing home and the outdoor environments of 3 existing nursing homes. Furthermore, assessments of an imagined ideal nursing home by pensioners and by nursing home staff were compared. The environment that was the closest to the ideal environment according to the assessments was a park-like environment that was larger and had more variation in vegetation than the other environments. The article concludes by discussing the SMB dimensions in relation to important environmental qualities in nursing home gardens.
  •  
6.
  • Bengtsson, Caroline, et al. (författare)
  • Chronic rhinosinusitis impairs sleep quality : results of the GA(2)LEN study
  • 2017
  • Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 40:1
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY OBJECTIVES: To analyse the prevalence of sleep problems in subjects with CRS and to determine whether the disease severity of CRS affects sleep quality.METHODS: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria. The disease severity of CRS was defined by the number of reported CRS symptoms. Sleep quality was assessed using the Basic Nordic Sleep Questionnaire.RESULTS: Of the 26 647 subjects, 2249 (8.4%) had CRS. Reported sleep problems were 50-90% more common among subjects with CRS compared with those without or the total population. The prevalence of reported sleep problems increased in conjunction with the severity of CRS. After adjusting for gender, BMI, age, tobacco use, asthma, somatic diseases, physical activity level and educational level, participants with four symptoms of CRS (compared with subjects without CRS symptoms) displayed a higher risk of snoring (adj. OR (95% CI): 3.13 (2.22-4.41)), difficulties inducing sleep (3.98 (2.94-5.40)), difficulties maintaining sleep (3.44 (2.55-4.64)), early morning awakening (4.71 (3.47-6.38)) and excessive daytime sleepiness (4.56 (3.36-6.18)). The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems.CONCLUSIONS: Sleep problems are highly prevalent among subjects with CRS. The disease severity of CRS negatively affects sleep quality.
  •  
7.
  •  
8.
  • Bengtsson, Caroline, et al. (författare)
  • Impact of nasal obstruction on sleep quality : a community-based study of women
  • 2015
  • Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 272:1, s. 97-103
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to analyse the impact of self-reported nasal obstruction on sleep quality in women. A community-based sample of 400 women underwent a full night of polysomnography. Airway diseases, allergies and sleep-related symptoms were assessed by questionnaires. Women with subjective nasal obstruction were subdivided into three groups: persistent nasal obstruction (PNO, n = 46), hay fever (n = 88) and nasal obstruction at night (NON, n = 30). Sleep problems and related daytime symptoms were most prevalent among women with NON. After adjusting for age, BMI, smoking and asthma, NON was an independent predictor of 'Difficulties inducing sleep due to nasal obstruction' [adjusted odds ratio (95 % CI): 89.5 (27.0-296.7)], 'Snoring' [4.2 (1.7-10.2)], 'Sweating at night' [2.6 (1.1-6.1)], 'Difficulties maintaining sleep' [2.7 (1.2-6.2)], and 'Waking up hastily gasping for breath' [32.2 (8.7-119.1)]. 'Dry mouth on awakening' [7.7 (3.2-18.4)], 'Waking up unrefreshed' [2.7 (1.2-6.0)], 'Excessive daytime sleepiness' [2.6 (1.1-6.0)], and 'Daytime nasal obstruction' [12.2 (4.8-31.2)] were also associated with NON. Persistent nasal obstruction and hay fever were both associated with some reported sleep problems due to an overlap with NON. When women with NON were excluded, only 'Daytime nasal obstruction' was still significantly associated with PNO, while hay fever was associated with 'Daytime nasal obstruction' and 'Waking up hastily gasping for breath'. There were no significant differences in objectively measured sleep variables between any of the three subgroups and the study cohort. Self-reported nasal obstruction at night in women has a significant effect on several subjective day- and nighttime symptoms, but it does not appear to affect objectively measured sleep quality.
  •  
9.
  •  
10.
  • Bengtsson, Caroline, et al. (författare)
  • Incident chronic rhinosinusitis is associated with impaired sleep quality: Results of the RhiNE study
  • 2019
  • Ingår i: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:6, s. 899-905
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nasal cavity and paranasal sinuses. Associations between CRS and poor sleep quality have been reported. This 10-year follow-up study investigates possible associations between incident CRS and sleep quality. Methods: A questionnaire was sent to 16,500 individuals in Sweden, Norway, Denmark, Iceland and Estonia in 2000. It included questions on airway diseases, age, sex, body mass index, smoking habits, comorbidities, education and sleep quality. In 2010, a second questionnaire was sent to the same individuals, with a response rate of 53%. A subgroup of 5,145 individuals without nasal symptoms in 2000 was studied. Multiple logistic regression was performed to examine associations between CRS (defined according to the European position paper on rhinosinusitis and nasal polyps epidemiological criteria) at follow-up and sleep quality, with adjustment for potential confounders. Individuals with the respective sleep problem at baseline were excluded. Results: Over 10 years, 141 (2.7%) of the individuals without nasal symptoms in 2000 had developed CRS. CRS was associated with difficulties inducing sleep (adjusted odds ratio 2.81 [95% CI 1.67–4.70]), difficulties maintaining sleep (2.07 [1.35–3.18]), early morning awakening (3.03 [1.91–4.81]), insomnia (2.21 [1.46–3.35]), excessive daytime sleepiness (2.85 [1.79–4.55]), and snoring (3.31 [2.07–5.31]). Three insomnia symptoms at baseline increased the risk of CRS at follow-up by 5.00 (1.93–12.99). Conclusions: Incident CRS is associated with impaired sleep quality and excessive daytime sleepiness. Insomnia symptoms may be a risk factor for the development of CRS. © 2019 American Academy of Sleep Medicine. All rights reserved.
  •  
11.
  • Bengtsson, Caroline, 1975- (författare)
  • Nasal obstruction – impact on insomnia symptoms and sleep-disordered breathing
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Nasal obstruction is very common in the general population, but the role of nasal obstruction in sleep quality is not clear. Nasal obstruction is also prevalent in patients with obstructive sleep apnoea (OSA) and may contribute to poor adherence to continuous positive airway pressure (CPAP) treatment.Aims: To investigate the impact of subjective nasal obstruction, as a single symptom or as part of chronic rhinosinusitis (CRS), in both objective and subjective sleep quality, in three different population based cohorts. Another aim was to investigate the usefulness of the Sinonasal Outcome Test-22 (SNOT-22) and peak nasal inspiratory flow (PNIF) in the treatment of OSA patients.Methods and results: In paper I (the SHE-study), a community-based sample of 400 women were investigated with polysomnography and questions on sleep quality, daytime- and nasal symptoms. Women with nasal obstruction at night (n=30) had significantly higher prevalence of several night time symptoms and excessive daytime sleepiness (EDS), but the polysomnography was normal.In paper II (the GA2LEN study, n= 26, 647) and paper III (RHINE II and RHINE III studies, n= 5, 145) questionnaires on sleep quality, daytime- and nasal symptoms were used, and CRS was defined according to the epidemiological diagnostic criteria of the European Position Paper of Rhinosinusitis and Nasal Polyps (EPOS). In paper II, sleep problems were highly prevalent in CRS, and there was a dose-response relationship between the disease severity of CRS and sleep problems. The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems.In paper III, 2.7% of individuals without nasal symptoms at baseline had developed CRS at follow-up 10 years later. Strong associations between incident CRS and impaired sleep quality and EDS were found. Three insomnia symptoms at baseline increased the risk for CRS at follow-up.In paper IV, 197 OSA patients initiating CPAP treatment were investigated before starting CPAP and at the follow-up 3-4 weeks later. SNOT-22 scores were generally high among all OSA patients indicating a large sinonasal disease burden, and improved among those with CPAP adherence ≥ 4 hours/night. A low PNIF value increased the risk for poor CPAP adherence.Conclusions: Subjective nasal obstruction at night impairs subjective sleep quality in women, but does not affect objective sleep quality. CRS impairs subjective sleep quality, and insomnia symptoms may be a risk factor for CRS. SNOT-22 and PNIF may be useful tools in the treatment of OSA patients.
  •  
12.
  • Bengtsson, Caroline, et al. (författare)
  • Nasal polyposis is a risk factor for nonadherence to CPAP treatment in sleep apnea: the population-based DISCOVERY study
  • 2023
  • Ingår i: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 19:3, s. 573-579
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: The aim was to evaluate nasal polyposis as a risk factor for nonadherence to continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). Methods: This was a population-based, longitudinal analysis of patients starting CPAP treatment for OSA in the Swedish quality registry Swedevox between 2010 and 2018. Data were cross-linked with national registries. The impact of nasal polyposis on CPAP adherence was analyzed using uni-and multivariable logistic and linear regression models. Relevant confounders (age, sex, usage of nasal and oral steroids) were identified using a direct acyclic graph. Results: Of 20,521 patients with OSA on CPAP treatment (29.5% females), 331 (1.6%) had a diagnosis of nasal polyposis at baseline. At the 1-year follow-up, nasal polyposis was associated with an increased risk of CPAP usage < 4 hours/night (unadjusted odds ratio [OR] 1.21; 95% confidence interval [CI] 0.95-1.55); adjusted OR 1.38; 95% CI 1.08-1.77). In this group, unadjusted nocturnal mean CPAP usage was 15.4 minutes (95% CI-31.62 to 0.83) shorter and was an adjusted 24.1 minutes (95% CI-40.6 to-7.7) shorter compared with patients with OSA without nasal polyposis. Conclusions: Nasal polyposis is associated with reduced CPAP usage per night. These results highlight the importance of diagnosing nasal polyposis in patients with OSA before the start of CPAP treatment. Treatment of the condition may improve adherence, efficacy, and patient outcomes.
  •  
13.
  • Bengtsson, Caroline, et al. (författare)
  • Sinonasal outcome test-22 and peak nasal inspiratory flow : valuable tools in obstructive sleep apnoea
  • 2020
  • Ingår i: Rhinology. - 0300-0729 .- 1996-8604. ; 58:4, s. 341-348
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sinonasal complaints contribute to low adherence to continuous positive airway pressure (CPAP) treatment. We aimed to investigate sinonasal health in obstructive sleep apnoea (OSA) patients, using the sinonasal outcome test-22 (SNOT-22), and to analyse whether SNOT-22 is affected by CPAP adherence. We also aimed to investigate whether peak nasal inspiratory flow (PNIF) was able to predict adherence to CPAP. Methods:The study population comprised 197 OSA patients (60 females) initiating CPAP treatment The SNOT-22, PNIF and the Epworth Sleepiness Scale were assessed at baseline and follow-up. One-night polygraphy, the Hospital Anxiety and Depression Scale, peak expiratory flow and health-related issues were assessed at baseline. At follow-up, the patients were categorised into adherent (>4 hours/night) and non-adherent (<4 hours/night) to CPAP treatment. Results: The average time for following up CPAP treatment was (mean +/- SD) 24.0 +/- 23.9 days and it did not differ significantly between the groups.The SNOT-22 score was elevated among all OSA patients, 36.1 +/- 19.4.There was a larger improvement in the SNOT-22 score at follow-up among adherent CPAP users compared with non-adherent users (-10.4 +/- 13.9 vs. -3.2 +/- 15.4). A PNIF value of < 100 litres/min increased the risk of non-adherence to CPAP with an adjusted odds ratio (OR) of 2.40 ((95% CI 1.16-5.00)). Conclusions: The SNOT-22 was elevated in patients with OSA, indicating a considerable sinonasal disease burden.The SNOT-22 improved with good CPAP adherence. A low PNIF value was able to predict poor CPAP adherence. Both the SNOT-22 and PNIF can be valuable tools in the evaluation of OSA patients and in the management of CPAP treatment.
  •  
14.
  • Bengtsson, Hanna, et al. (författare)
  • Heat-treated and homogenised potato pulp suspensions as additives in low-fat sausages
  • 2011
  • Ingår i: Meat Science. - : Elsevier BV. - 1873-4138 .- 0309-1740. ; 88:1, s. 75-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Differently homogenised and heat treated potato pulp, used as a dietary fibre additive in low-fat sausages, gave rise to an enhanced instrumentally and sensory measured firmness and compactness, respectively. This is believed to be due to the high content of insoluble fibre, which creates a fibrous network that enhances the texture of the sausage, while not interfering with the meat protein network. The process and frying losses of the sausages, using potato pulp as an additive, were not significantly different compared to the reference. Comparing the different potato pulp sausages using various kinds of heat treatment of the potato pulp significantly lowered the frying loss and increased the firmness. An explanation to these observations could be that the potato pulp exposed to shorter heat treatment compared with longer gave rise to a lower amount of amylase-leakage from the swelling starch granules caught in the potato pulp matrix. (C) 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.
  •  
15.
  • Bengtsson, Johan (författare)
  • Negative symptoms, repetitive transcranial magnetic stimulation and heart rate variability in schizophrenia and depression
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Negative symptoms comprise anhedonia, avolition, and blunted affect. Although first described in schizophrenia, these symptoms share phenomenology with the depressive state. Pharmacological treatment has not been successful in reducing negative symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment option for moderate to severe depression. There have also been attempts to treat negative symptoms in both schizophrenia and depression with rTMS.Cardiovascular disease is common in schizophrenia and depression. Heart rate variability (HRV) is an established proxy for cardiac autonomic functioning and numerous studies have found lower HRV in patients with schizophrenia and depression. The impact of psychopharmacological treatment on HRV has been extensively studied and anticholinergic compounds have been found to decrease HRV.Lastly, since the most commonly used rTMS depression targets are also the brain regions involved in central autonomic regulation, there is reason to consider a potential effect of rTMS on HRV.The overall aim of this thesis was to investigate negative symptoms, rTMS, and HRV in schizophrenia and depression.Study I was a validation study of a Swedish translation of the Clinical Assessment Interview for Negative Symptoms (CAINS). Thirty-four patients with schizophrenia were interviewed and it was concluded that the Swedish version of the CAINS exhibited acceptable psychometric properties.Study II was a double-blind randomized controlled trial of rTMS for negative symptoms in schizophrenia and depression. There was a significant decrease of negative symptoms in the depression group, but not in the schizophrenia group. There were no effects on overall depressive symptoms in either group.Study III assessed determinants of HRV in schizophrenia, depression, and healthy controls. The results indicated lower HRV in both patient groups, even after controlling for several factors, and also that anticholinergic burden impacted HRV.In Study IV, the relationship between HRV and the functional and structural connectivity of the anterior cingulate cortex was investigated in patients with schizophrenia and compared with that in healthy controls. It was found that connectivity with the cerebellum might play a role in the autonomic modulation network in patients with schizophrenia.Lastly, in Study V, the effect of a treatment course with rTMS on HRV was investigated in patients with depression, as well as HRV’s relationship to symptom change. No effects on HRV were detected, nor any correlations between HRV and symptom change. Further, baseline HRV could not predict treatment response.
  •  
16.
  • Bengtsson, Johan, et al. (författare)
  • Theta burst transcranial magnetic stimulation of the dorsomedial prefrontal cortex in schizophrenia and depression
  • 2015
  • Ingår i: Brain Stimulation. - : Elsevier BV. - 1935-861X.
  • Konferensbidrag (refereegranskat)abstract
    • Negative symptoms in schizophrenia and core depressive symptoms share phenomenology and repetitive transcranial magnetic stimulation (rTMS) is a treatment modality for both conditions. The most common treatment site has been the dorsolateral prefrontal cortex (DLPFC) but there might be more optimal targets. Furthermore, the implementation of the currently approved protocols is hampered by the long duration. More intense stimulation protocols such as the theta burst stimulation (TBS) are significantly shorter and may be as effective and safe.The overall aim of this project is to evaluate the treatment effect of TBS on poor motivation and anhedonia in schizophrenia and depression and to explore the neurobiological correlates of these deficits.The dorsomedial prefrontal cortex (dmPFC) is a key cortical area in networks associated with motivation and anhedonia and it is affected in both schizophrenia and depression. The dmPFC has recently been identified as a possible site of stimulation and is now within reach by new angled coils that have deeper tissue penetration.Our study will enroll 38 patients with schizophrenia, 38 patients with depression and 38 healthy volunteers. Patients will be given daily TBS (totally 2400 pulses, 1200 on each hemisphere) over the dmPFC during 10 days. Target symptoms will be assessed with the Clinical Assessment Interview for Negative Symptoms (CAINS). We will also assess cortical excitability with paired-pulse stimulation and the pre-attentive memory function with mismatch negativity (MMN), spontaneous motor activity (assessed with 24 hours accelerometer) as well as autonomic nervous system tone (assessed by skin conductance, heart rate variability and breathing pattern). In addition, we will evaluate cognitive function (speed of processing, verbal fluency, auditory and working memory, visuospatial ability) during rest and stress.
  •  
17.
  • Bengtsson, Kenneth, et al. (författare)
  • Så kan Sverige bli ledande nation i resurseffektivitet
  • 2016
  • Ingår i: Dagens Nyheter. - 1101-2447. ; :2016-04-30
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Ny rapport. Det svenska näringslivet kan bli mer hållbart, resurssmart och därmed internationellt konkurrenskraftigt. Men för det behövs en tydlig politisk avsiktsförklaring och riktlinjer. Vi har listat sex områden där policyutveckling brådskar, skriver företrädare för näringsliv, forskning och myndigheter i en gemensam uppmaning.
  •  
18.
  • Bengtsson, Linus, et al. (författare)
  • Commentary: containing the Ebola outbreak-the potential and challenge of mobile network data
  • 2014
  • Ingår i: Plos Currents. - : Public Library of Science. - 2157-3999. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The ongoing Ebola outbreak is taking place in one of the most highly connected and densely populated regions of Africa (Figure 1A). Accurate information on population movements is valuable for monitoring the progression of the outbreak and predicting its future spread, facilitating the prioritization of interventions and designing surveillance and containment strategies. Vital questions include how the affected regions are connected by population flows, which areas are major mobility hubs, what types of movement typologies exist in the region, and how all of these factors are changing as people react to the outbreak and movement restrictions are put in place. Just a decade ago, obtaining detailed and comprehensive data to answer such questions over this huge region would have been impossible. Today, such valuable data exist and are collected in real-time, but largely remain unused for public health purposes - stored on the servers of mobile phone operators. In this commentary, we outline the utility of CDRs for understanding human mobility in the context of the Ebola, and highlight the need to develop protocols for rapid sharing of operator data in response to public health emergencies.
  •  
19.
  • Bengtsson, Mattias, 1978, et al. (författare)
  • Labour Market Policy under Conditions of Permanent Austerity: Any Sign of Social Investment?
  • 2017
  • Ingår i: Social Policy & Administration. - : Wiley. - 0144-5596 .- 1467-9515. ; 51:2, s. 367-388
  • Tidskriftsartikel (refereegranskat)abstract
    • Social investment (SI) is part of a strategy to modernize the European welfare states by focusing on human resource development throughout the life-course, while ensuring financial sustainability. Recognizing that this strategy was only partially implemented by the EU member states prior to the financial and Eurozone crises, this article investigates whether reforms and expenditure patterns in labour market policy (LMP) have moved more towards or away from SI following the 2008 financial crisis. We use quantitative and qualitative data to investigate the degree to which there have been shifts in the SI aspects of LMPs in eight countries across four welfare state regimes. We also investigate which aspects of LMPs have been strengthened and which have been weakened, enabling us to make a nuanced assessment of labour market SIs across the EU in a period of permanent austerity. We find that although the eight countries under examination have different starting points, there is little evidence of increased SI-orientation of LMPs. Upskilling, which is at the heart of SI, did not increase from 2004–08 to 2009–13, while incentive reinforcement and employment assistance – more about labour market entry and marketing of skills – grew in importance. If this trend continues across Europe, there is a risk that SI will become lost in translation and end up as a clearer neo-liberal version of workfarism.
  •  
20.
  • Bengtsson, Stefan, et al. (författare)
  • Mind the gap! Moving from awareness to action : Showcasing emergent research from the Swedish Graduate School in Education for Sustainable Development (GRESD)
  • 2015
  • Ingår i: Abstract list of WEEC 2015. - : WEEC.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: The main purpose of the symposium is to showcase some recent research findings produced by PhD students accepted by or affiliated with the Swedish Graduate School in Education for Sustainable development (GRESD). Objectives: GRESD started as a state sponsored one-time research capacity development project that accepted 9 post-graduate student and included additional 9 post-graduate students all focusing on ESD in their PhD projects. With the project coming to an end and having produced a number of dissertations targeting an international research audience, it is the intention to showcase some of the central contributions made and to receive feedback on from practitioners and researchers on how existent research projects can tie into and contribute to existent demands in environmental education (EE) practice and practice. The presentations of research results are aimed to cover a wide range of issues, including topics such as evaluation of classroom practices, students qualifications, globalization and teachers’ ethical reflections the role of place-specific artifacts in learning. As GRESD is a collaboration between eight universities with their specific traditions and approaches to educational research, approaches show a creative variety of theoretical backgrounds. This variation is also reflected in the presentations that are putting into play Lacanian psychoanalysis, discourse theory, pragmatist theory and phenomenography in order to shed new light on critical areas of environmental education. Methods: The symposium will consist of an introduction (10 minutes) brief presentations (10-15 minutes each) of central research findings in the context of their overarching research projects, followed by a synthesis and suggestions by a selected commentator (20 minutes) and general discussions with the audience (20 minutes). The dialogue following the presentations is intended to outline possible future research projects as well as emerging areas topics in the portrayed GRESD research that could feed into existing demands in EE practice and research.
  •  
21.
  • Bengtsson, Sara, 1978- (författare)
  • Stress steroids as accelerators of Alzheimer's disease. : Effects of chronically elevated levels of allopregnanolone in transgenic AD models.
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background Alzheimer’s disease (AD) and dementia are devastating con­ditions not only for the affected patients but also for their families.  The economical costs for the society are tremendous. Mid-life psychological stress, psychosocial stress and post-traumatic stress disorder cause cognitive dysfunction and lead to increased risk for dementia. However, the mecha­nisms behind stress-induced AD and dementia are not known. AD is char­acterized by solid amyloid plaques in the CNS. However, over the last decade it has been concluded that the levels of soluble beta-amyloid (Aβ) correlate to cognitive performance while plaques often do not. The soluble Aβ accu­mulate intracellularly and disturb the synaptic function. Interestingly, the levels of intracellular Aβ depend on neuronal activity. Previous studies have shown that decreased neuronal activity cause increased intracellular levels of Aβ and cognitive decline. Stress steroids produced in the brain, e.g. allopreg­nanolone, enhance the activity of the GABAergic system, i.e. the main in­hibitory system of the brain. Consequently, allopregnanolone affects neu­ronal activity. Therefore, it is possible that elevated levels of allopreg­nanolone (due to e.g. stress) cause increased intracellular levels of Aβ. This could be a mechanism behind stress-induced AD. The purpose of this thesis was to investigate if elevation of allopregnanolone is a possible link in the mechanism behind stress-induced AD by investigating the effects of chroni­cally elevated levels of allopregnanolone in transgenic mouse models for AD.Methods Swe/PS1 and Swe/Arc mice (transgenic models for AD) were treated chronically with elevated allopregnanolone levels, comparable to those at mild stress. After an interval of no treatment, the mice were tested for learning and memory performance in the Morris water maze. The brain tissue of the mice was then analyzed for disease markers, i.e. soluble and insoluble Aβ40 and Aβ42 using enzyme-linked immunosorbent assay, and amyloid plaques using immunohistochemistry and Congo red staining tech­nique. The brain tissue was also analyzed for a marker of synaptic function, i.e. synaptophysin.Results Chronic treatment of allopregnanolone caused impaired learning performance in both the Swe/PS1 and the Swe/Arc mouse models. The Swe/PS1 mice had increased levels of soluble Aβ in both hippocampus and cortex. Interestingly, the levels of soluble Aβ were unchanged in the Swe/Arc mice. Three months of allopregnanolone treatment in the Swe/PS1 mouse model caused decreased plaque size, predominantly in hippocampus. It may be concluded that chronic allopregnanolone elevation caused smaller but more abundant congophilic plaques as both total plaque area and number of plaques were increased in mice with poor learning ability. Additional spots for accumulation of Aβ, predominantly the more toxic Aβ42, and thus addi­tional starting points for plaque production could be a part of the mechanism behind stress-induced Alzheimer’s disease.Conclusions The conclusion of this thesis is that chronic elevation of allo­pregnanolon accelerated the development of Alzheimer’s disease in the Swe/PS1 and the Swe/Arc transgenic mouse models. Allopregnanolone may be an important link in the mechanism behind stress-induced AD. However, further studies are required to grasp the extent of its pathological influence.
  •  
22.
  • Bengtsson Sonesson, Ludwig, et al. (författare)
  • Carbon Ruins : An exhibition of the fossil age
  • 2019
  • Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
    • It is 2053. The Swedish government has just opened its landmark museum FOSSIL with its first exhibition Carbon Ruins. The exhibition and its grand opening is a celebration of the fact that global net-zero emissions of carbon dioxide were reached in 2050. Sweden, in line with its 2017 targets, reached net-zero emissions of greenhouse gases already in 2045, being the first country in the world to step out of the fossil age, which globally lasted between 1849 and 2049.‘Carbon Ruins’ aims to transport the visitor into a future where transitions to post-fossil society has already happened. By focusing on recognisable objects the exhibition bridges the gap between the daily lives of humans and the abstract impacts of climate change. The choice of the objects and the associated stories are based on climate models and expertise from the Narrating Climate Futures network. The characters and events which construct the story have been generated through participatory workshops with researchers and practitioners in food, transport, steel, energy and plastic
  •  
23.
  • Bengtsson, Torbjörn, et al. (författare)
  • The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation
  • 2008
  • Ingår i: Journal of Internal Medicine. - : Institutionen för medicin och hälsa. - 0954-6820 .- 1365-2796. ; 263:5, s. 558-571
  • 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.
  •  
24.
  • Brooks, Christopher, et al. (författare)
  • Rapid and near real-time assessments of population displacement using mobile phone data following disasters: the 2015 Nepal Earthquake
  • 2016
  • Ingår i: Plos Currents. - : Public Library of Science. - 2157-3999. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Sudden impact disasters often result in the displacement of large numbers of people. These movements can occur prior to events, due to early warning messages, or take place post-event due to damages to shelters and livelihoods as well as a result of long-term reconstruction efforts. Displaced populations are especially vulnerable and often in need of support. However, timely and accurate data on the numbers and destinations of displaced populations are extremely challenging to collect across temporal and spatial scales, especially in the aftermath of disasters. Mobile phone call detail records were shown to be a valid data source for estimates of population movements after the 2010 Haiti earthquake, but their potential to provide near real-time ongoing measurements of population displacements immediately after a natural disaster has not been demonstrated.Methods: A computational architecture and analytical capacity were rapidly deployed within nine days of the Nepal earthquake of 25th April 2015, to provide spatiotemporally detailed estimates of population displacements from call detail records based on movements of 12 million de-identified mobile phones users.Results: Analysis shows the evolution of population mobility patterns after the earthquake and the patterns of return to affected areas, at a high level of detail. Particularly notable is the movement of an estimated 390,000 people above normal from the Kathmandu valley after the earthquake, with most people moving to surrounding areas and the highly-populated areas in the central southern area of Nepal.Discussion: This analysis provides an unprecedented level of information about human movement after a natural disaster, provided within a very short timeframe after the earthquake occurred. The patterns revealed using this method are almost impossible to find through other methods, and are of great interest to humanitarian agencies.
  •  
25.
  • Covaciu, Lucian, 1964-, et al. (författare)
  • Brain temperature in healthy volunteers subjected to intranasal cooling
  • 2011
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:8, s. 1277-1284
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods.Methods: Intranasal balloons catheters circulated with saline at 20 °C were applied for 60 min in 10 healthy, unsedated volunteers. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects personal experience were filled after the experiment.Results: Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C. The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent at MMSE test. Postcooling nasal examination detected increased nasal secretion in 9 of the 10 volunteers. Volunteer’s acceptance of the method was good.   Conclusion: Both MR techniques revealed brain temperature reductions after 60 min intranasal cooling with balloons circulated with saline at 20 °C in healthy and unsedated volunteers.
  •  
26.
  • Covaciu, Lucian, et al. (författare)
  • Brain temperature in volunteers subjected to intranasal cooling
  • 2011
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:8, s. 1277-1284
  • Tidskriftsartikel (refereegranskat)abstract
    • Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20A degrees C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 +/- A 0.8A degrees C and by phase-mapping -1.8 +/- A 0.9A degrees C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 +/- A 0.3A degrees C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20A degrees C in awake, unsedated volunteers.
  •  
27.
  • De Marinis, Yang, et al. (författare)
  • GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.
  • 2010
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 11:6, s. 543-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 muM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in alpha cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose independent, and does not involve paracrine effects mediated by insulin or somatostatin. GLP-1 is without much effect on alpha cell electrical activity but selectively inhibits N-type Ca(2+) channels and exocytosis. Adrenaline stimulates alpha cell electrical activity, increases [Ca(2+)](i), enhances L-type Ca(2+) channel activity, and accelerates exocytosis. The stimulatory effect is partially PKA independent and reduced in Epac2-deficient islets. We propose that GLP-1 inhibits glucagon secretion by PKA-dependent inhibition of the N-type Ca(2+) channels via a small increase in intracellular cAMP ([cAMP](i)). Adrenaline stimulates L-type Ca(2+) channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP](i).
  •  
28.
  • Dehvari, Nodi, et al. (författare)
  • Amyloid precursor protein accumulates in aggresomes in response to proteasome inhibitor
  • 2012
  • Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 60:5, s. 533-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Aggresomes are cytoplasmic inclusions which are localized at the microtubule organizing center (MTOC) as a result of induced proteasome inhibition, stress or over-expression of certain proteins. Aggresomes are linked to the pathogenesis of many neurodegenerative diseases. Here we studied whether amyloid precursor protein (APP), a type-I transmembrane glycoprotein, is localized in aggresomes after exposure to stress condition. Using confocal microscopy we found that APP is located in aggresomes and co-localized with vimentin, gamma-tubulin, 20S and ubiquitin at the MTOC in response to proteasome dysfunction. An interaction between vimentin and APP was found after proteasome inhibition suggesting that APP is an additional protein constituent of aggresomes. Suppression of the proteasome system in APP-HEK293 cells overexpressing APP or transfected with APP Swedish mutation caused an accumulation of stable, detergent-insoluble forms of APP containing poly-ubiquitinated proteins. In addition, brain homogenates from transgenic mice expressing human APP with the Arctic mutation demonstrated an interaction between APP and the aggresomal-marker vimentin. These data suggest that malfunctioning of the proteasome system caused by mutation or overexpression of pathological or non-pathological proteins may lead to the accumulation of stable aggresomes, perhaps contributing to the neurodegeneration.
  •  
29.
  • Eberhardson, Michael, et al. (författare)
  • Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
  • 2022
  • Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
  •  
30.
  • Franck, Marina Christina Mikaela, et al. (författare)
  • Urocortin3-expressing neurons in sensory transmission
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Urocortin 3 (UCN3) is a neuropeptide involved in mechanosensation and stress regulation, and Ucn3-Cre neurons have been assigned a role in mechanical itch. Here, we show that Ucn3 marks a population of excitatory neurons in the mouse dorsal horn, divided into two non-overlapping subpopulations expressing protein kinase C g or calretinin/calbindin 2. Chemogenetic activation of spinal Ucn3-Cre neurons evoked a targeted biting/licking behavior towards the corresponding dermatome. Genetic deletion of vesicular glutamate transporter 2 (VGLUT2) in Ucn3-Cre neurons removed the phenotype, showing that the biting/licking behavior is VGLUT2-dependent. Conditional deletion of VGLUT2 did not affect acute thermal or mechanical withdrawal responses, nor thermal withdrawal responses after nerve growth factor-induced hypersensitivity or the prurifensive response to 48/80 or von Frey stimuli applied in nape. Instead, we found that a group of spinal Ucn3 neurons were activated in response to artificial scratching or 48/80-induced itch. Electrophysiological experiments showed that spinal Ucn3 neurons received both glycinergic and GABAergic tonic inhibition, and monosynaptic inputs from both Aβ and C fibers, which could be confirmed by rabies tracing. Spinal Ucn3/Ucn3-Cre neurons thus represent a mechanically sensitive population with several roles in the itch-scratch cycle. 
  •  
31.
  • Grdic Eliasson, Dubravka, et al. (författare)
  • A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.
  • 2011
  • Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 29:23, s. 3951-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation.
  •  
32.
  •  
33.
  • Kälvegren, Hanna, et al. (författare)
  • Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X(1)-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y(1) and P2Y(12) receptor activation
  • 2010
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 103:2, s. 398-407
  • Tidskriftsartikel (refereegranskat)abstract
    • Toll-like receptor 2 (TLR2), which recognise and respond to conserved microbial pathogen-associated molecular patterns, is expressed on the platelet surface. Furthermore, it has recently been shown that the TLR2/1 agonist Pam(3)CSK(4) stimulates platelet activation. The aim of the present study was to clarify important signalling events in Pam(3)CSK(4)-induced platelet aggregation and secretion. Platelet interaction with Pam(3)CSK(4) and the TLR2/6 agonist MALP-2 was studied by analysing aggregation, ATP-secretion, [Ca2+](i) mobilisation and thromboxane B2 (TxB(2)) production. The results show that Pam(3)CSK(4) but not MALP-2 induces [Ca2+](i) increase, TxB(2) production, dense granule secretion and platelet aggregation. Preincubation of platelets with MALP-2 inhibited the Pam(3)CSK(4)-induced responses. The ATP-secretion and aggregation in Pam(3)CSK(4)-stimulated platelets was impeded by the purinergic P2X(1) inhibitor MRS 2159, the purinergic P2Y(1) and P2Y(12) antagonists MRS 2179 and cangrelor, the phospholipase C inhibitor U73122, the calcium chelator BAPT-AM and aspirin. The calcium mobilisation was lowered by MRS 2159, aspirin and U73122 whereas the TxB(2) production was antagonised by MRS 2159, aspirin and BAPT-AM. When investigating the involvement of the myeloid differentiation factor-88 (MyD88) -dependent pathway, we found that platelets express MyD88 and interleukin 1 receptor-associated kinase (IRAK-1), which are proteins important in TLR signalling. However, Pam(3)CSK(4) did not stimulate a rapid (within 10 minutes) phosphorylation of IRAK-1 in platelets. In conclusion, the results show that Pam(3)CSK(4)-induced platelet aggregation and secretion depends on a P2X(1)-mediated Ca2+ mobilisation, production of TxA(2) and ADP receptor activation. The findings in this study further support a role for platelets in sensing bacterial components.
  •  
34.
  • Ludvigsson, Jonas F., 1969-, et al. (författare)
  • Swedish Inflammatory Bowel Disease Register (SWIBREG) : a nationwide quality register
  • 2019
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 54:9, s. 1089-1101
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory relapsing disease with increasing incidence. IBD research and long-term follow-up of patients have, however, been hampered by lack of detailed data on disease phenotype, patient-reported outcome measures, Physician Global Assessment, disease activity, and hospital-administered drugs.Aim: To review the Swedish IBD quality register (SWIBREG).Methods: Review of SWIBREG including questionnaire data from users and patients.Results: SWIBREG was launched in 2005, and as of April 2019, contains 46,400 patients with IBD (Crohn's disease: n = 15,705, ulcerative colitis: n = 21,540, IBD unclassified and other colitis (including e.g., microscopic colitis): n = 9155). Of these IBD patients, 7778 had been diagnosed in childhood (16.8%). Earlier research has shown that combining SWIBREG and the Swedish National Patient Register (NPR) yields a positive predictive value of 100% (95%CI = 95-100%) for having a diagnosis of IBD. Moreover, out of all patients in the NPR with a diagnosis of IBD plus either IBD-related surgery or immunomodulatory/biological treatment during the past 18 months, SWIBREG covers 59.0%. SWIBREG records not only information on conventional therapies but also on biological treatment, surgery, smoking, disease activity, patient-reported outcome measures (PROMs), and patient-experienced measures (PREMs). Data are presented through a graphical decision support system.Conclusion: SWIBREG benefits patients with IBD, and offers an ideal opportunity for healthcare personnel and researchers to examine disease phenotype and activity, PROMs/PREMs, and hospital-administered drugs in patients with IBD.
  •  
35.
  • Lyon, Helen N., et al. (författare)
  • The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts
  • 2007
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 3:4
  • Tidskriftsartikel (refereegranskat)abstract
    • A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples.
  •  
36.
  • Lönn, Johanna, 1982-, et al. (författare)
  • Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition
  • 2012
  • Ingår i: Results in Immunology. - : Elsevier BV. - 2211-2839. ; 2, s. 7-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.
  •  
37.
  • Mårild, Karl, 1982, et al. (författare)
  • Histologic activity in inflammatory bowel disease and risk of serious infections : A nationwide study
  • 2024
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 22:4, s. 831-846
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear.METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses.RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61).CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD.
  •  
38.
  • Petersdorf, Effie W., et al. (författare)
  • HLA-B leader and survivorship after HLA-mismatched unrelated donor transplantation
  • 2020
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:3, s. 362-369
  • Tidskriftsartikel (refereegranskat)abstract
    • Hematopoietic cell transplantation (HCT) from HLA-mismatched unrelated donors can cure life-threatening blood disorders, but its success is limited by graft-versus-host disease (GVHD). HLA-B leaders encode methionine (M) or threonine (T) at position 2 and give rise to TT, MT, or MM genotypes. The dimorphic HLA-B leader informs GVHD risk in HLA-B-mismatched HCT. If the leader influences outcome in other HLA-mismatched transplant settings, the success of HCT could be improved for future patients. We determined leader genotypes for 10 415 patients receiving a transplant between 1988 and 2016 from unrelated donors with one HLA-A, HLA-B, HLA-C, HLA-DRB1, or HLA-DQB1 mismatch. Multivariate regression methods were used to evaluate risks associated with patient leader genotype according to the mismatched HLA locus and with HLA-A, HLA-B, HLA-C, HLA-DRB1, or HLA-DQB1 mismatching according to patient leader genotype. The impact of the patient leader genotype on acute GVHD and mortality varied across different mismatched HLA loci. Nonrelapse mortality was higher among HLA-DQB1-mismatched MM patients compared with HLA-DQB1-mismatched TT patients (hazard ratio, 1.35; P = .01). Grades III to IV GVHD risk was higher among HLA-DRB1-mismatched MM or MT patients compared with HLA-DRB1-mismatched TT patients (odds ratio, 2.52 and 1.51, respectively). Patients tolerated a single HLA-DQB1 mismatch better than mismatches at other loci. Outcome after HLA-mismatched transplantation depends on the HLA-B leader dimorphism and the mismatched HLA locus. The patient's leader variant provides new information on the limits of HLA mismatching. The success of HLA-mismatched unrelated transplantation might be enhanced through the judicious selection of mismatched donors for a patient's leader genotype.
  •  
39.
  • Petersdorf, Effie W., et al. (författare)
  • HLA-DQ heterodimers in hematopoietic cell transplantation
  • 2022
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 139:20, s. 3009-3017
  • Tidskriftsartikel (refereegranskat)abstract
    • HLA-DQ heterodimers increase the susceptibility to autoimmune diseases, but their role in hematopoietic cell transplantation is unknown. We tested the hypothesis that outcome after HLA-matched and HLA-DQ-mismatched hematopoietic cell transplantation is influenced by HLA-DQ heterodimers. Heterodimers were defined in 5164 HLA-matched and 520 HLA-DQ-mismatched patients and their transplant donors according to well-established crystallographic criteria. Group 1 (G1) heterodimers are any DQA1*02/03/04/05/06a paired with any DQB1*02/03/040. Group 2 (G2) heterodimers are DQA1*01a paired with any DQB1*05/060. Multivariable models identified significantly higher relapse risk in G1G2 and G2G2 compared with G1G1 HLA-matched patients with malignant disease; risk increased with an increasing number of G2 molecules. In HLA-DQ-mismatched transplantation for malignant diseases, matching or mismatching for G2 increased relapse risk. G2 lowered disease-free survival after both HLA-matched and HLA-DQ-mismatched transplantation. A paradigm based on HLA-DQ heterodimers provides a functional definition of the hematopoietic cell transplantation barrier and a means to lower risks for future patients.
  •  
40.
  • Petersdorf, Effie W., et al. (författare)
  • Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation : a retrospective cohort study
  • 2020
  • Ingår i: The Lancet Haematology. - : ELSEVIER SCI LTD. - 2352-3026. ; 7:1, s. E50-E60
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which differentially influence natural killer and T-cell alloresponses. The main aim of the study was to evaluate the role of the leader dimorphism in GVHD after HLA-B-mismatched unrelated HCT.Methods: We did a retrospective cohort study of 33 982 patients who received an unrelated HCT done in Australia, Europe, japan, North America, and the UK between jan 1, 1988, and Dec 31, 2016. Data were contributed by participants of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation. All cases were included and there were no exclusion criteria. Multivariate regression models were used to assess risks associated with HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 mismatching. Among the 33 982 transplantations, the risks of GVHD associated with HLA-B M and T leaders were established in 17 100 (50.3%) HLA-matched and 1457 (4.3%) single HLA-B-mismatched transplantations using multivariate regression models. Leader frequencies were defined in 2 004 742 BeTheMatch US registry donors.Findings: Between jan 20, 2017, and March 11, 2019, we assessed 33 982 HCTs using multivariate regression models for the role of HLA mismatching on outcome. Median follow-up was 1841 days (IQR 909-2963). Mortality and GVHD increased with increasing numbers of HLA mismatches. A single HLA-B mismatch increased grade 3-4 acute GVHD (odds ratio [OR] 1.89, 95% CI 1. 53-2.33; p<0.0001). Among the single HLA-B-mismatched transplantations, acute GVHD risk was higher with leader mismatching than with leader matching (OR 1.73, 1.02-2.94; p=0 .042 for grade 2-4) and with an M leader shared allotype compared with a T leader shared allotype (OR 1.98, 1.39-2.81; p=0.0001 for grade 3-4). The preferred HLA-B-mismatched donor is leader-matched and shares a T leader allotype. The majority (1836 939 [91.6%]) of the 2004742 US registry donors have the TT or MT genotype.Interpretation: The HLA-B leader informs GVHD risk after HLA-B-mismatched unrelated HCT and differentiates high-risk HLA-B mismatches from those with lower risk. The leader of the matched allotype could be considered to be as important as the leader of the mismatched allotype for GVHD. Prospective identification of leader-matched donors is feasible for most patients in need of a HCT, and could lower GVHD and increase availability of HCT therapy. These findings are being independently validated and warrant further research in prospective trials. 
  •  
41.
  • Petersdorf, Effie W., et al. (författare)
  • Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation
  • 2020
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:24, s. 2712-2718
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1-matched and -mismatched unrelated donors. PATIENTS AND METHODS Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1-matched or -mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient's mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients. RESULTS In HLA-A, -B, -C, -DRB1,-DQB1-matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor's mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient's mismatched HLA-DPB1 allotype. CONCLUSION The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1-matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.
  •  
42.
  • Power, Daniel, et al. (författare)
  • Population mobility reductions associated with travel restrictions during the Ebola epidemic in Sierra Leone : Use of mobile phone data
  • 2018
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP): Policy B - Oxford Open Option D. - 1464-3685 .- 0300-5771. ; 47:5, s. 1562-1570
  • Tidskriftsartikel (refereegranskat)abstract
    • Travel restrictions were implementeded on an unprecedented scale in 2015 in Sierra Leone to contain and eliminate Ebola virus disease. However, the impact of epidemic travel restrictions on mobility itself remains difficult to measure with traditional methods. New ‘big data’ approaches using mobile phone data can provide, in near real-time, the type of information needed to guide and evaluate control measures.We analysed anonymous mobile phone call detail records (CDRs) from a leading operator in Sierra Leone between 20 March and 1 July in 2015. We used an anomaly detection algorithm to assess changes in travel during a national ‘stay at home’ lockdown from 27 to 29 March. To measure the magnitude of these changes and to assess effect modification by region and historical Ebola burden, we performed a time series analysis and a crossover analysis.Routinely collected mobile phone data revealed a dramatic reduction in human mobility during a 3-day lockdown in Sierra Leone. The number of individuals relocating between chiefdoms decreased by 31% within 15 km, by 46% for 15–30 km and by 76% for distances greater than 30 km. This effect was highly heterogeneous in space, with higher impact in regions with higher Ebola incidence. Travel quickly returned to normal patterns after the restrictions were lifted.The effects of travel restrictions on mobility can be large, targeted and measurable in near real-time. With appropriate anonymization protocols, mobile phone data should play a central role in guiding and monitoring interventions for epidemic containment.
  •  
43.
  •  
44.
  • Skoglund, Caroline, 1981-, et al. (författare)
  • C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin.
  • 2008
  • Ingår i: Immunology and cell biology. - : Wiley. - 0818-9641 .- 1440-1711. ; 86:5, s. 466-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood platelets and C-reactive protein (CRP) are both used clinically as markers of ongoing inflammation, and both participate actively in inflammatory responses, although the biological effects are still incompletely understood. Rapidly adhering platelets express receptors for complement factor 1q (C1q) and the Fc part of immunoglobulin G (IgG), and CRP is known to activate/regulate complement via C1q binding, and to ligate FcgammaRs. In the present study, we used normal human IgG pre-adsorbed to a well-characterized methylated surface as a model solid-phase immune complex when investigating the effects of CRP and C1q on platelet adhesion and activation. Protein adsorption was characterized using ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non-coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q (markedly) decreased the spreading of adhering platelets. The combination of C1q and CRP was slightly more potent in reducing cell adhesion to IgG, and also impaired the adhesion to HSA and non-coated surfaces. Platelet production of thromboxane B2 (TXB(2)) was also reduced by C1q both in the presence and absence of CRP, whereas CRP alone had no effect on TXB(2) production. We conclude that CRP and C1q regulate the behaviour of platelets, and that this may be an important immunoregulatory mechanism during inflammatory conditions.
  •  
45.
  • Skoglund, Caroline, 1981-, et al. (författare)
  • C-reactive protein inhibit complement-mediated platelet activation suggesting a protective role in atherogenesis
  • 2006
  • Ingår i: Atherosclerosis Supplements. - Clare, Ireland : Elsevier. - 1567-5688 .- 1878-5050. ; 7:3, s. 284-284
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    •   Objective: C-reactive protein (CRP) represents a powerful predictor of coro- nary artery disease. However, its physiological role is not fully understood. The binding of CRP to its ligand phosphorylcholine (PC) activates the com- plement system via the classical pathway, although limited to the initial stages, i.e. no membrane attack complex is formed. The aim of this study was to chaxacterize CRP-induced complement activation on PC-coated surfaces, and to investigate the regulatory effects of PC-bound crp on complement induced platelet activation.Methods: PC conjugated to keyhole limpet hemocyanin was immobilized to cross-linked fibrinogen on silica particles. Ellipsometry and polyclonal anti- bodies were used to quantify deposition of serum proteins, complement factors and CRP on the surfaces. Washed platelets as well as serum were prepared according to standard protocols. CRP concentrations were measured with a high sensitivity assay. Lumi-aggregometry was used to evaluate the effects of PC-coated particles and CRP on complement-induced platelet aggregation and secretion.Results: Serum (5%) induced platelet aggregation and secretion through complement-dependent mechanisms. PC-coated particles antagonized the complement-mediated platelet activation but only if CRP was present. Inter- estingly, we found that a minor elevation of CRR below 5 rag/1 was sufficient to inhibit platelet activation.Conclusions: We suggest that CRP bound to PC-expressing ligands, e.g. bacteria or modified low-density lipoproteins in an atherosclerotic lesion, modulate complement activation and thereby prevent a harmful platelet activation.
  •  
46.
  • Skoglund, Caroline, et al. (författare)
  • C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets
  • 2010
  • Ingår i: Immunobiology. - Jena, Germany : Elsevier. - 0171-2985 .- 1878-3279. ; 215:12, s. 987-995
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood platelets are emerging as important immunomodulatory cells, but complement interaction with platelets is not well understood. Several platelet structures have been described as complement protein 1q (C1q) binding receptors, such as C1qRp/CD93 and gC1qR. However, there are conflicting results whether these receptors are C1q binding structures, or even at all expressed on the cell surface. Recently, the collagen-binding integrin alpha II beta I was reported to bind C1q on mast cells, and this receptor is also present on platelets. The aim of this study was to further characterize the effects of C1q on platelets, by quantifying the platelet surface expression of P-selectin (CD62P) and monitoring the formation of platelet-neutrophil aggregates. Using flow cytometry, we found that C1q dose-dependently triggered a rapid but moderate and transient up-regulation of P-selectin already within 5s of C1q exposure. Pre-incubation with an antibody directed against gC1qR significantly inhibited (with 57% compared to control) the up-regulation, whereas an antibody towards the alpha II beta I-integrin showed no effect. Stimulation with C1q did not change the cytosolic calcium-levels, as measured with the fluorescent ratiometric probe Fura-2, however, a protein kinase C inhibitor (GF109203x) blocked the C1q-induced P-selectin expression. Furthermore, pre-incubation of platelets with C1q diminished both the collagen as well as the collagen-related peptide-induced up-regulation of P-selectin, most evident after 90 s of stimulation. This indicates that C1q may regulate platelet activation via the GPVI receptor, which is a novel finding. Moreover, C1q antagonized the collagen-induced formation of platelet-neutrophil aggregates, indicating a reduced interaction between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1(PSGL-1/CD162). In summary, C1q induces a moderate rapid platelet P-selectin expression, modulates subsequent collagen and collagen-related peptide stimulation of platelets, and inhibits the formation of platelet-neutrophil aggregates. These immuno-regulatory effects of C1q may have a crucial role in innate immunity and inflammation. (C) 2009 Elsevier GmbH. All rights reserved.
  •  
47.
  • Skoglund, Caroline, et al. (författare)
  • C1q regulates collagen-dependent production of reactive oxygen species, aggregation and levels of soluble P-selectin in whole blood
  • 2012
  • Ingår i: Immunology Letters. - Amsterdam, Netherlands : Elsevier. - 0165-2478 .- 1879-0542. ; 142:1-2, s. 28-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood platelets express several receptors involved in immunity (e.g. complement-, toll-like- and Fc gamma-receptors) and release inflammatory mediators. Furthermore, formation of platelet-leukocyte aggregates has an important role during inflammatory conditions such as coronary artery disease. Thus, apart from their well-known role in haemostasis, platelets are today also recognized as cells with immunomodulatory properties. We have previously reported regulatory effects of complement protein 1q (C1q) on platelet activation in experimental setups using isolated cells. In the present study we have proceeded by investigating effects of C1q on collagen-induced aggregation, production of reactive oxygen species (ROS), formation of platelet-leukocyte aggregates and levels of soluble P-selectin in whole blood. Impedance measurements showed that C1q inhibited collagen-induced aggregation whereas it potentiated the collagen-provoked production of ROS in a luminol-dependent chemiluminescence assay. The effects of C1q on aggregation and ROS-production were dependent upon platelets, as they were no longer observed in presence of the platelet (GpIIb/IIIa) inhibitor Reopro. Furthermore, the levels of soluble P-selectin were found to be lowered upon treatment with C1q prior to addition of collagen. There was also a trend towards a decreased formation of large platelet-leukocyte aggregates in collagen-stimulated whole blood following C1q treatment. In conclusion, our data indicate that C1q could have a role in regulating platelet activation and associated leukocyte recruitment during vessel wall injury. This has implications for inflammatory disorders such as coronary artery disease.
  •  
48.
  • Skoglund, Caroline, 1981-, et al. (författare)
  • C1q regulates collagendependentproduction of reactive oxygen species, formation of plateletleukocyteaggregates and levels of soluble Pselectinin whole blood
  • 2010
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Blood platelets are nowadays recognized as cells with immuno‐modulatory properties as they express receptors involved in immunity (e.g. complement‐, toll‐like‐ and Fcγ‐receptors) and release inflammatory mediators. Furthermore, formation of plateletleukocyte aggregates has an important role during inflammatory conditions, e.g. coronary artery disease. We have previously reported regulatory effects of complement protein 1q (C1q) on platelet activation in experimental setups using isolated cells. In the present study we have continued by investigating the effect of C1q on collagen‐induced aggregation and production of reactive oxygen species (ROS), formation of plateletleukocyte aggregates and levels of soluble P‐selectin in whole blood. Impedance measurements showed that C1q, at physiological concentrations, inhibited collageninduced aggregation in whole blood, whereas it potentiated the collagen‐provoked production of ROS in a luminal‐dependent chemiluminescence assay. The potentiation was dependent on platelets, as the effect was not seen when the platelet fibrinogen binding receptor GpIIb/IIIa was blocked by Reopro. Moreover, the formation of large platelet‐leukocyte aggregates in collagen‐stimulated whole blood was inhibited by C1q. This may be explained by the finding that C1q antagonized the collagen‐induced activation, revealed by lowered levels of soluble P‐selectin. In conclusion, C1q may have an important role in regulating platelet activation and associated leukocyte recruitment during vessel wall injury and thus be involved in inflammatory disorders such as coronary artery disease.
  •  
49.
  • Skoglund, Caroline, 1981- (författare)
  • Platelets in inflammation : Role of complement protein C1q, C-reactive proteinand toll-like receptors
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Platelets are proven essential in haemostasis, however, they are now also increasingly recognized as cells with important immunomodulatory properties, e.g. through interaction with leukocytes and several species of bacteria and by release inflammatory mediators upon activation. Moreover, platelets express receptors involved in immunity and inflammation such as Fcγ‐receptor IIa, complement protein C1q‐receptors (gC1qR, cC1qR, CD93 and α2β1) and toll‐like receptors (TLR‐1, ‐2, ‐4, ‐6 and ‐9). C1q, C‐reactive protein (CRP) and TLRs are all pattern recognition molecules able to recognize non‐self structures and initiate an immune response. Uncontrolled or misdirected activation of platelets and the immune response is involved in the onset and progress of several conditions with an inflammatory component, such as coronary artery disease and autoimmune diseases.Hence, the aims of the present thesis were to investigate the effects and q mechanisms of C1and CRP on platelet activation, and to clarify the intracellular signaling events provoked by TLR‐2 stimulation of platelets. Platelet interaction with immune complexes is poorly understood, however by utilizing well‐characterized model surfaces with adsorbed IgG and microscopy, we show that both C1q and CRP are able to inhibit FcγR‐mediated platelet adhesion and spreading. Using isolated platelets in suspension and flow cytometry, we also found that C1q triggers a rapid, moderate and transient up‐regulation of P‐selectin that is sensitive to blockade of gC1qR and protein kinase C (PKC), but not blockade of α2β1. Additionally, subsequent platelet activation by collagen or collagen‐related peptide (GPVI specific) is inhibited by C1q, suggesting a role for GPVI in C1q‐mediated regulation of collagen‐induced platelet activation. Whole blood studies revealed that C1q inhibits total cell aggregation, formation of platelet‐leukocyte aggregates, and potentiates the production of reactive oxygen species (ROS), all in a platelet‐dependent manner. Furthermore, using the TLR‐2/1 agonist Pam3CSK4 we found that TLR‐2/1‐activation of platelets is mediated via a P2X1‐dependent increase in intracellular free Ca2+, P2Y1 and P2Y12 –receptor ligation, and activation of cyclooxygenase. We also found that platelets express IRAK‐1, however, without being rapidly phosphorylated upon Pam3CSK4 stimulation and thus probably not involved in the early aggregation/secretion response. Furthermore, TLR‐2/6 stimulation does not lead to platelet activation but instead inhibits TLR‐2/1‐provoked activation. Taken together, these findings further strengthen the role of platelets as key players in inflammatory processes.
  •  
50.
  • Stenseke, Marie, et al. (författare)
  • Kris i naturen – vår existens har blivit sårbar
  • 2019
  • Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Fler arter än någonsin i mänsklighetens historia hotas av utrotning och den biologiska mångfalden lokalt har förändrats kraftigt i en stor del av världens ekosystem. Grundläggande förändringar behövs både i samhället och för individer, för att bromsa den negativa trenden, skriver en rad debattörer.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 55
Typ av publikation
tidskriftsartikel (44)
doktorsavhandling (5)
annan publikation (2)
konferensbidrag (2)
konstnärligt arbete (1)
forskningsöversikt (1)
visa fler...
visa färre...
Typ av innehåll
refereegranskat (39)
övrigt vetenskapligt/konstnärligt (12)
populärvet., debatt m.m. (4)
Författare/redaktör
Bengtsson, Caroline (10)
Skoglund, Caroline (7)
Lindberg, Eva (7)
Bengtsson, Torbjörn, ... (6)
Janson, Christer (5)
Skoglund, Caroline, ... (5)
visa fler...
Bengtsson, Torbjörn (5)
Ludvigsson, Jonas F. ... (4)
Bengtsson, Mats (4)
Theorell-Haglöw, Jen ... (4)
Spellman, Stephen R (4)
Olén, Ola (4)
Horowitz, Mary (4)
Nordenvall, Caroline (4)
Jonsson, Lars, 1952- (4)
Petersdorf, Effie W. (4)
Olsson, Malin (3)
Myrelid, Pär (3)
Tuomi, Tiinamaija (3)
Groop, Leif (3)
Carrington, Mary (3)
Holmström, Mats (3)
Isomaa, Bo (3)
Thorleifsson, Gudmar (3)
Thorsteinsdottir, Un ... (3)
Stefansson, Kari (3)
Karling, Pontus (3)
Wichmann, H. Erich (3)
Meitinger, Thomas (3)
Kong, Augustine (3)
Grip, Olof (3)
Bengtsson, Jonas (3)
Wetterö, Jonas (3)
Eberhardson, Michael (3)
Wetter, Erik (3)
Bengtsson, Linus (3)
Buckee, Caroline (3)
Lu, Xin (3)
Tatem, Andrew J. (3)
Fox, Caroline S. (3)
Rejler, Martin (3)
Fagerberg, Ulrika L. (3)
Strid, Hans (3)
Jäghult, Susanna (3)
Kälvegren, Hanna (3)
Walters, G. Bragi (3)
De Santis, Dianne (3)
Dubois, Valerie (3)
Gooley, Ted (3)
Madrigal, J. Alejand ... (3)
visa färre...
Lärosäte
Uppsala universitet (22)
Linköpings universitet (16)
Karolinska Institutet (15)
Örebro universitet (14)
Göteborgs universitet (12)
Lunds universitet (11)
visa fler...
Umeå universitet (6)
Stockholms universitet (3)
Handelshögskolan i Stockholm (3)
Jönköping University (2)
Högskolan i Halmstad (1)
Malmö universitet (1)
Chalmers tekniska högskola (1)
Sveriges Lantbruksuniversitet (1)
visa färre...
Språk
Engelska (52)
Svenska (3)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (37)
Naturvetenskap (8)
Samhällsvetenskap (3)
Teknik (2)
Lantbruksvetenskap (2)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy