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1.
  • Arvidson, E., et al. (författare)
  • The effects of exercise training on hypothalamic-pituitary-adrenal axis reactivity and autonomic response to acute stress-a randomized controlled study
  • 2020
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExercise training is suggested to have a stress-buffering effect on physiological reactions to acute stress. The so-called cross-stressor adaptation hypothesis is one of many theories behind the plausible effects, proposing that the attenuated physiological reaction seen in trained individuals in response to acute exercise is also seen when the individual is exposed to acute psychosocial stress. However, few randomized controlled trials (RCT) are available in this field. Therefore, the aim of the present trial was to study the effects of a 6-month aerobic exercise intervention on the physiological response to acute laboratory stress.MethodsA two-armed RCT including untrained but healthy individuals aged 20-50years was conducted. Assessments included a peak oxygen uptake test and a psychosocial stress test (the Trier Social Stress Test). A total of 88 participants went through both baseline and follow-up measures (48 in the intervention group and 40 in the control group) with a similar proportion of women and men (20 women and 28 men in the intervention group and 18 women and 22 men in the control group). Outcome measures were adrenocorticotrophic hormone, cortisol, systolic and diastolic blood pressure, and heart rate responses to acute psychosocial stress.ResultsOxygen uptake and time-to-exhaustion increased significantly following the intervention, while a decrease was seen in the control group. The analyses showed attenuated responses to acute psychosocial stress for all variables in both groups at follow-up, with no differences between the groups. No correlation was seen between amount of exercise training and reactivity to the stress test. Despite the increased oxygen uptake in the intervention group, no differences were seen between the groups for any of the outcome variables at follow-up.ConclusionsIn this study, the cross-stressor adaptation hypothesis could not be confirmed. Both groups showed decreased reactions indicating a habituation to the stress test.Trial registrationClinicalTrials.gov NCT02051127. Registered on 31 January 2014-retrospectively registered.
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2.
  • Arvidsson, Elin, et al. (författare)
  • Exercise training and physiological responses to acute stress: study protocol and methodological considerations of a randomised controlled trial
  • 2018
  • Ingår i: BMJ Open Sport & Exercise Medicine. - : BMJ. - 2055-7647. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This paper describes the protocol and methodological prerequisites for a randomised controlled exercise intervention. Selected baseline data from the study are also presented, demonstrating some methodological challenges related to exercise intervention trials. The aim of the trial was to study the effects of exercise training on physiological responses to acute psychosocial stress in untrained individuals. Methods: Individuals with a low level of physical activity were invited to participate in an exercise intervention lasting for 6 months. A total of 119 participants were included and went through a peak oxygen uptake test and a psychosocial stress test at baseline. Adrenocorticotropic hormone (ACTH) and cortisol were measured in connection to the stress test to identify the physiological response. Results: Almost 90% of the participants reported themselves as untrained, but results from the objectively measured oxygen uptake did not seem to correspond to the reported sedentary lifestyle. The primary outcome measures at baseline varied between individuals. The mean change from pre-test to peak value was 214% for ACTH and 94% for cortisol. Of these, 13 individuals did not respond in ACTH and/or and cortisol. Discussion: Supposedly untrained individuals seeking participation in an exercise intervention might not be as untrained as they report, a methodological consideration of importance when evaluating the effects of training. Another important consideration is related to the primary outcome measure, which should be measurable and possible to affect. Absence of reaction at baseline means that changes can only be detected as an increased reaction.
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4.
  • Bengtsson, Anders, et al. (författare)
  • SLE serum induces classical caspase-dependent apoptosis independent of death receptors
  • 2008
  • Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 126:1, s. 57-66
  • Tidskriftsartikel (refereegranskat)abstract
    • The main source of autoantigens in systemic lupus erythematosus (SLE) is most likely apoptotic material. We have previously shown that sera from SLE patients can induce apoptosis in monocytes and lymphocytes, and here we characterized mechanisms of apoptosis induced by SLE serum. SLE serum seems to induce caspase-dependent classical apoptosis since cells exposed to SLE serum displayed morphology consistent with classical apoptosis as demonstrated by confocal microscopy, and pan-caspase inhibitor Z-VAD.fmk significantly reduced SLE serum-induced apoptosis. Death-receptor-independent pathways seemed to be involved since SLE serum induced apoptosis equally in FADD-mutant and wild-type Jurkat cell lines, and blocking of Fas and TNFR1 did not reduce apoptosis induction. Importantly, apoptosis was significantly reduced in a Bcl-2 overexpressing Jurkat cell line indicating involvement of mitochondrial pathways. Thus, based on morphology and caspase inhibition experiments, we have demonstrated that SLE serum induce classical caspase-dependent apoptosis, and this was independent of death receptor pathways.
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7.
  • Eriksson, Martin, et al. (författare)
  • Immediate effect of visual and auditory feedback to control the running mechanics of well-trained athletes
  • 2011
  • Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 29:3, s. 253-262
  • Tidskriftsartikel (refereegranskat)abstract
    • The correlation between mechanical factors of running and running economy as measured by metabolic cost is a subject of much interest in the study of locomotion. However, no change in running technique has been shown to result in an immediate improvement in running economy on an intra-individual basis. To evaluate the effect of a modified running technique, it is probably necessary that the individual trains with the new technique for a longer period using a feedback system to control the new kinematics. In this study, we examine the feasibility of using visual and auditory feedback to adapt running technique according to a simplistic model of the mechanical cost of running. The model considers only the mechanical work against gravity, which is the product of the magnitude of the vertical displacement of the runner's centre of mass and the step-frequency. In the experiments reported here, 18 trained runners, running at 16km center dot h-1 on a treadmill, were given feedback on these parameters together with indicated target levels. In almost all cases, the runners were able to adjust their technique accordingly.
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8.
  • Eriksson, Martin, et al. (författare)
  • Wireless Vertical Displacement Measurement during Running using an Accelerometer and a Mobile Phone
  • 2011
  • Konferensbidrag (refereegranskat)abstract
    • The purpose of this study was to investigate in the usability of a wireless accelerometer linked to a mobile phone via Bluetooth radio for measuring vertical displacement in running athletes. Five experienced runners were monitored during lactate threshold testing at three to five different velocities. Accelerometer data was received, processed and stored on the phone to be compared to simultaneous position transducer (ground truth) recordings after data collection. A paired t-test and statistical analysis show no significant differences in the reliability of the recordings. While further investigations are encouraged, the accelerometer and algorithm (running in J2ME on the mobile phone) proof as aflexible, easy-to-use tool for out-of-the-lab monitoring and to provide real-time feedback for running technique experiments.
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9.
  • Gulez, N., et al. (författare)
  • Homozygosity For a Novel Mutation in the C1q C Chain Gene in a Turkish Family With Hereditary C1q Deficiency
  • 2010
  • Ingår i: Journal of Investigational Allergology & Clinical Immunology. - 1698-0808. ; 20:3, s. 255-258
  • Tidskriftsartikel (refereegranskat)abstract
    • Hereditary complete deficiency of complement component C1q is associated with a high prevalence of systemic lupus erythematosus and increased susceptibility to severe recurrent infections. An 11-year-old girl was screened for immunodeficiency due to a history of recurrent meningitis and pneumonia. Immunologic studies revealed absence of classic pathway hemolytic activity and undetectable levels of C1q. Exon-specific amplification of genomic DNA by polymerase chain reaction followed by direct sequence analysis revealed a novel homozygous missense mutation at codon 48 in the C1q C gene causing a glycine-to-arginine substitution affecting the collagen-like region of C1q. No changes were seen in the exons of the A and B chains. The mutation affected both the formation and the secretion of C1q variant molecules. We describe a novel mutation in the C1q C chain gene that leads to an interchange in amino acids resulting in absence of C1q in serum.
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10.
  • Gullstrand, Birgitta, et al. (författare)
  • Combination of Autoantibodies Against Different Histone Proteins Influences Complement-dependent Phagocytosis of Necrotic Cell Material by Polymorphonuclear Leukocytes in Systemic Lupus Erythematosus.
  • 2012
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:8, s. 1619-1627
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as well as association to disease activity and clinical phenotype in SLE. METHODS: ELISA and immunoblot were used to measure antibodies to different histone proteins in sera from patients with SLE and complement-deficient individuals. Phagocytosis of NC by PMN and oxidative burst activity was assessed by flow cytometry. RESULTS: A clearly increased phagocytosis of NC was seen in patients with active SLE, which was associated with high levels of anti-H ab concentrations and oxidative burst activity. The complement system contributed to efficient phagocytosis of NC by PMN through activation of the classical pathway, and the phagocytosis was mediated by FcγRIIA, FcγRIIIB, and CR1 in combination. A pattern of high phagocytosis, consumption of classical pathway components, and a broad anti-H ab repertoire was seen particularly in patients with nephritis and serositis. The combination of antibodies to several different histone proteins, often with anti-DNA antibodies, promoted an efficient uptake of NC, whereas antibodies against only histone H1 or a few histones seemed to be of less importance. CONCLUSION: The distributions of specificities among anti-H ab are of great importance in the complement-dependent phagocytosis of debris from NC in SLE. Measurement of anti-H ab could be useful in monitoring of this disease and contribute to improved understanding of the autoimmune process.
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  • Gullstrand, Birgitta, et al. (författare)
  • Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells.
  • 2009
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 156, s. 303-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary Inherited deficiencies in components of the classical complement pathway are strong disease susceptibility factors for the development of systemic lupus erythematosus (SLE) and there is a hierarchy among deficiency states, the strongest association being with C1q deficiency. We investigated the relative importance of the different complement pathways regarding clearance of apoptotic cells. Phagocytosis of labelled apoptotic Jurkat cells by monocyte-derived macrophages in the presence of sera from individuals with complement deficiencies was studied, as well as C3 deposition on apoptotic cells using flow cytometry. Sera from individuals deficient in C1q, C4, C2 or C3 all showed decreased phagocytosis. Mannose binding lectin (MBL) and the alternative pathway did not influence phagocytosis. Notably, the components of the complement classical pathway, including C1q, were equally important in clearance of apoptotic cells. This indicates that deposition of C3 fragments is of major significance; we therefore studied C3 deposition on apoptotic cells. Experiments with MBL-deficient serum depleted of C1q or factor D confirmed the predominance of the classical pathway. At low dilution, sera deficient of C1q, C4 or C2 supported C3 fragment deposition demonstrating alternative pathway activation. In conclusion, we have found that complement-mediated opsonization and phagocytosis of apoptotic cells, particularly those undergoing secondary necrosis, are dependent mainly upon an intact classical pathway. The alternative pathway is less important, but may play a role in some conditions. C1q was not more important than other classical pathway components, suggesting a role in additional pathogenetic processes in SLE other than clearance of apoptotic cells.
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12.
  • Gullstrand, Lennart, et al. (författare)
  • A new method for recording the temporal pattern of stride during treadmill running
  • 2009
  • Ingår i: Sports Engineering. - : Springer Science and Business Media LLC. - 1369-7072 .- 1460-2687. ; :11, s. 195-200
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the reliability of a new infrared light based method (IR40) for recording temporal stride patterns during treadmill running. The IR40 device, emitting a tight web of 40 infrared light beams 10 mm above the treadmill running surface, was compared to a previously validated electro-pneumatic contact shoe (CS) method while nine well-trained athletes ran at 2.8, 3.3, 3.9, 4.4, 5.0, and 5.6 m s−1. Disconnection and reconnection of the IR beams marked the stance phase. The sampling rate was 500 Hz for both methods. The stance phase duration was on average 11.5 (±8.4) ms longer with the IR40 than with the CS depending on earlier touch down (8.3 ± 6.2 ms) and delayed toe off (3.2 ± 5.3 ms) registrations. Significantly different stance phases were recorded between all velocities and for both methods. Thus, despite the fact that the IR40 systematically measured a somewhat longer stance phase duration than CS, the IR40 is nonetheless useful for temporal stride analysis during treadmill running.      
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13.
  • Gullstrand, Lennart (författare)
  • Measurements for improvement of running capacity : physiological and biomechanical evaluations
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Running is included in a large number of sports and one of the most well investigated modes of locomotion in both physiology and biomechanics. This thesis focuses on how some new methods from both areas may be used to capture running capacity in mid-distance and distance running from laboratory and field recordings. Measurement of running economy is included and defined as oxygen uptake at a given submaximal velocity in a steady-state condition. Running economy is mostly recorded on motor driven, level treadmills and consequently does not include the frontal air resistance effect. However, running economy is the sum from of a number of sub-factors. Stride characteristics and vertical displacement (Vdisp) of the centre of mass (CoM) are two of them and here novel measuring methods are described and validated to get a wider spectrum of factors that influence running economy. Aims: The aim of the work presented in this thesis was to describe and validate novel and easy-to-handle methods for improved capture of running economy with some of its subfactors. The intention is later to integrate and refine the methods mentioned for regular use when analyzing and monitoring runners capacity. Methods: The outcome of an incremental lactate-threshold test (4x4 min) was compared with and without 30 s stops for blood sampling on a treadmill (n=10). A lightweight, portable, metabolic device was validated against the Douglas bag method (DBM) in a wide range of VO2 during ergometer cycling, and thereafter used for comparison of running economy and lactate threshold measurements during treadmill and indoor track running. Further, the device was compared to the DBM during treadmill running (n=14). An infrared radiation device emitting a dense web of 40 IR beams over the running surface was validated with respect to stance-phase duration against force plate in overground running and a contact shoe during treadmill running (n=14). The Vdisp of the CoM was measured with a position transducer and an accelerometer and compared to the output of an optoelectronic motion capture system during treadmill running (n=13). Results: Lactate-threshold running-velocity results were equal during continuous running and running with 30 s intervals. During ergometer cycling the portable device was valid and reliable in a wide range of measurements and during track running the device showed a VO2 cost approximately 6% higher than during treadmill running, most probably expressing the air resistance. The IR device demonstrated systematically an 11.5 ±8.4ms longer stance duration than the contact shoe over a wide range of velocities. Vdisp measured with a one-point position transducer somewhat overestimated (7 mm) the Vdisp CoM from the optoelectronic system, but can be compensated for. Conclusions: Blood sampling may, preferably be performed with 30 s interruptions of running during lactate threshold testing on treadmill as no difference from sampling during continuous running was detected. Running economy measurements with the portable metabolic device were reliable for running on treadmill and track, but overestimated VO2 with 5-6% compared to DBM on the treadmill. The convenient IR mat and position transducer may well be used to capture stride characteristics and CoM Vdisp during treadmill running.
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14.
  • Gullstrand, Lennart, et al. (författare)
  • Measurements of vertical displacement in running, a methodological comparison
  • 2009
  • Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362 .- 1879-2219. ; 30:1, s. 71-75
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was (1) to evaluate measurements of vertical displacements (V-disp) of a single point on sacrum as an estimate of the whole body centre of mass (CoM) V-disp during treadmill running and (2) to compare three methods for measuring this single point. These methods were based on a position transducer(PT), accelerometers (AMs) and an optoelectronic motion capture system. Criterion method was V-disp of the whole body CoM measured with the motion capture system. Thirteen subjects ran at 10, 12, 14, 16. 18, 20 and 22 km h(-1) with synchronous recordings with the three methods. Four measurements of the (V-disp) were derived: (1) V-disp of CoM calculated from a segment model consisting of 13 segments tracked with 36 reflective markets, (2) V-disp of the sacrum recorded with the PT, (3) V-disp of the sacrum Calculated from the AM, and (4) V-disp of the sacrum calculated as the mid point of two reflective markets (sacrum marker, SM) attached at the level of the sacral bone. The systematic discrepancy between the Measurements of sacrum V-disp and CoM V-disp varied between 0 and 1.5 mm and decreased with increasing running velocity and decreasing step duration. PT and SM measurements showed strong correlation, whereas the AM showed a variability increasing with velocity. The random discrepancy within each Subject was 7 mm for all three methods. In conclusion single-point recordings of the sacrum V-disp may be used to monitor changes in V-disp of CoM during treadmill running.
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15.
  • Gullstrand, Lennart, et al. (författare)
  • Validation of a kayak ergometer power output
  • 2013
  • Konferensbidrag (refereegranskat)abstract
    • IntroductionIt is of a significant interest that ergometers used for evaluating elite athletes are valid and reliable. In this study the aim was to investigate how well displayed power output on a widely used kayak ergometer, DS, (Dansprint ApS, DK) related to a validation setup. Previously Gore et al. (2013) described the accuracy of 12 of the same ergometer using a motor driven calibration rig simulating power between 50 up to 450 W. They found that the ergometers underestimated true mean power with 21-23%. The reference rig simulated a 1 dimensional (1D) movement; this study however, is based on 3D analysis, which was hypothesized to better describe real paddling movement’s and allow more precise power calculations.MethodsTwo male national team kayakers took part in the study performing workloads from 70 up to 500 W (+30 W/stage) two times with 3 days between the measurement sessions. They were instructed to target the desired workloads displayed during 35 s bouts. The reference method included a ProReflex optoelectronic system (Qualisys AB, Gothenburg, Sweden) and force transducers (LCM 200, Futek Inc, Ca, US). The force transducers were connected with the rope from ergometer flywheel close to each end of the ergometer paddle to continuously measure force during the bouts of work. The kinematic set-up included eight cameras placed around the ergometer and two reflective markers were attached close to each force transducer.ResultsThe reference method used here showed that the validated ergometer underestimated power with 37.7 % over the whole measured range compared to the reference method. The difference was systematic (r2=0.989) and the linear regression model could be applied (DS power = -2.362+0.628*x). When applying a 1D analysis of the collected data, it coincided with the results from Gore et al. (2013).DiscussionThe data suggest that 1. The measurement solution and/or calculation for describing power output in the DS have limitations. 2. The testing rig referred to in the Introduction (Gore et al. 2013) do not fully estimate true power and 3. The reference method used here is suggested to more exactly represent true paddling power as it includes a 3D movement analysis and close to original paddling simulation set-up. Both reference methods (1D and 3D analysis) show linear differences vs. the DS ergometer, giving an option to adjust the displayed power to a true power produced by elite-athletes.
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16.
  • Halvorsen, Kjartan, et al. (författare)
  • Acute Effects Of Reducing Vertical Displacement And Step Frequency On Running Economy
  • 2012
  • Ingår i: Journal of Strength and Conditioning Research. - 1064-8011 .- 1533-4287. ; 26:8, s. 2065-2070
  • Tidskriftsartikel (refereegranskat)abstract
    • This work studies the immediate effects of altering the vertical displacement of CoM (VD) and step frequency (SF) on the metabolic cost of level treadmill running at 16 km·h on sixteen male runners. Alterations of VD, SF and the product VD SF was induced using a novel feedback system which presents target and current values to the runner by visual or auditory display. Target values were set to 5 and 10% reductions from individual baseline values. Results were expressed as relative changes from baseline values.Alterations led to an increase in metabolic cost in most cases, measured as VO2 uptake per minute and kg body mass. Correlations were weak. Still, linear multiple regression revealed a positive coefficient (0.28) for the relationship between VD SF and VO2. Separate rank correlation tests showed negative correlation (τ = -0.19) between SF and VO2 and positive correlation (τ = -0.16) between VD and VO2. There is a coupling between VD and SF caused by the mechanics of running, hence isolated reduction of either factor was hard to achieve. The linear model also showed a negative coefficient for the relationship between the height of center of mass above ground (CoMh) and VO2.The effect size was small (multiple R-squared 0.07 and 0.12). Still the results indicate that reducing VD SF by reducing vertical displacement can have a positive effect on running economy, but a concurrent reduction in CoMh may reduce or diminish the positive effect. Mid- and long-term effects of altering the technique should also be studied.
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17.
  • Halvorsen, Kjartan, et al. (författare)
  • Minimal marker set for center of mass estimation in running
  • 2009
  • Ingår i: Gait & Posture. - : Elsevier BV. - 0966-6362 .- 1879-2219. ; 30:4, s. 552-555
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose was to study the validity of a recently proposed method [Forsell C, Halvorsen K. A method for determining minimal sets of markers for the estimation of center of mass, linear and angular momentum. journal of Biomechanics 2009;42(3):361-5] for estimating the trajectory of the whole-body center of mass (CoM) in the case of running at: velocities ranging from 10 to 22 km h(-1). The method gives an approximation to the CoM using the position of fewer markers on the body than the standard method of tracking each segment of the body. Fourteen male athletes participated. A standard method for determining the CoM from a model of 13 segments and using the position of 36 markers was used as reference method. Leave-one-out cross-validation revealed errors that decreased with increasing number of markers used in the approximative method. Starting from four markers, the error in absolute position of the CoM decreased from 15 mm to 3 mm in each direction. For the velocity of the CoM the estimation bias was neglectable, and the random error decreased from 0.15 to 0.05 m s(-1). The inter-subject and intra-subject variability in the estimated model parameters increased with increasing number of markers. The method worked well also when applied to running at velocities outside the range of velocities in the data used to determine the model parameters. The results indicate that a model using 10 markers represents a good trade-off between simplicity and accuracy, but users must take into account requirements of their specific applications.
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19.
  • Jönsen, Andreas, et al. (författare)
  • Association between SLE nephritis and polymorphic variants of the CRP and Fc gamma RIIIa genes
  • 2007
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 46:9, s. 1417-1421
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding Fc gamma RIIa, Fc gamma RIIIa, Fc gamma RIIIb, CRP and IL-1Ra. Methods. Genetic polymorphisms were analysed in 323 unrelated SLE patients and 200 healthy blood donors. The genotype frequencies were compared between clinical subsets of SLE patients, as well as with healthy controls. Clinical manifestations included the ACR classification criteria. Nephritis was further classified according to WHO class on renal biopsy. Results. Presence of a CRP4 A-allele was associated with SLE nephritis (P< 0.01) and inversely correlated with arthritis (P < 0.01), when comparing within the SLE group. The Fc gamma RIIIa F/F genotype was also associated with nephritis (WHO class III and IV, P=0.04 for the SLE group) and in combination with the CRP4 A-allele a stronger association was noted (P<0.001). Furthermore, the Fc gamma RIIIb NA2/NA2 genotype was associated with butterfly rash (P< 0.01). An association was found between seizures and the presence of both the Fc gamma RIIa R/R and the Fc gamma RIIIa F/F genotypes (P< 0.01) and an inverse correlation between serositis and the CRP4 A-allele when present together with the IL-1Ra 2-allele (P=0.01). Furthermore, a combination of the Fc gamma RIIa R/R genotype and CRP4 A-allele was associated with lymphopenia (P= 0.02) and a similar result was found for the combination of Fc gamma RIIIa F/F and Fc gamma RIIIb NA2/NA2 (P= 0.04). Conclusions. Polymorphic variants of the CRP and Fc gamma-receptor genes are associated with the clinical phenotype in SLE. Our findings suggest an immune complex-mediated pathogenesis in nephritis and seizures, while development of arthritis may depend on other pathogenetic pathways.
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20.
  • Jönsen, Andreas, et al. (författare)
  • Genetically determined mannan-binding lectin deficiency is of minor importance in determining susceptibility to severe infections and vascular organ damage in systemic lupus erythematosus.
  • 2007
  • Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 16:4, s. 245-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Deficiency of mannan-binding lectin (MBL) has been reported to impact susceptibility to severe nfections and atherosclerosis in systemic lupus erythematosus (SLE). In this study, MBL gene polymorphisms were analysed in 143 SLE patients and the frequency of severe infections and organ damage according to SLICC/ACR Damage Index regarding cerebrovascular accidents, angina pectoris, coronary by-pass surgery, myocardial infarction and peripheral arterial disease leading to significant tissue loss, were recorded during a mean follow-up time of 15 years from diagnosis. In a multiple logistic regression model, smoking (P = 0.001), hypertension (P = 0.030), alcohol intake (P = 0.027) and higher triglyceride concentration (P = 0.026) were associated with cerebrovascular, cardiovascular and peripheral arterial organ damage (CPAD), while the association with MBL deficiency did not reach significance (P = 0.098). Alcohol intake (> 15 g/month) was inversely correlated with CPAD (OR = 0.29, 95%Cl 0.096-0.87). MBL deficiency was not significantly more common in SLE patients with severe infections in a multivariate analysis (P > 0.3). In conclusion, classical risk factors such as smoking, hypertension, low alcohol intake and elevated triglyceride concentration were relatively more important for development of CPAD than MBL deficiency in SLE. Furthermore, MBL deficiency did not contribute to development of major infections in SLE.
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21.
  • Jönsson, Göran, et al. (författare)
  • Vaccination against encapsulated bacteria in hereditary C2 deficiency results in antibody response and opsonization due to antibody-dependent complement activation.
  • 2012
  • Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 144:3, s. 214-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Hereditary C2 deficiency (C2D) is an important susceptibility factor for invasive infections caused by encapsulated bacteria such as pneumococci and Haemophilus influenzae type b. The infections are mostly seen in childhood indicating that antibody-mediated acquired immunity is affected. C2D persons and healthy controls were vaccinated with ActHIB® and Pneumo23®. Analysis of specific antibodies to pneumococci serotype 6B, 7F, and 23F, and Hib was performed. Post-vaccination IgG antibodies against pneumococci serotype 6B and 23F at a concentration ≥1.0mg/L was found in similar frequency in C2D persons and controls. Post-vaccination sera from C2D persons showed poor complement-mediated opsonization and phagocytosis of pneumococci by granulocytes when depending on classical and lectin pathway activation only, but increased (p=0.007) and equaled that of the normal controls when also alternative pathway activation was allowed due to antibody-dependent C2 bypass activation. In conclusion, the C2D persons benefited from the vaccination and achieve an increased phagocytic capacity.
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22.
  • Klint, Cecilia, et al. (författare)
  • Binding of immune complexes to erythrocyte CR1 (CD35): difference in requirement of classical pathway components and indication of alternative pathway-mediated binding in C2-deficiency
  • 2000
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 52:1, s. 103-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Deficiency of complement components within the classical pathway is associated with increased risk for immune complex disease. However, C2-deficient individuals often have a mild disease and about 50% are healthy. To study the importance of the different components for immune complex clearance, bovine serum albumin (BSA)/anti-BSA complexes were opsonized in human serum and the binding to erythrocyte complement receptor type 1 (CR1, CD35) was measured in vitro. In C2-depleted serum the complexes were opsonized and bound to CR1 but the reaction needed a longer opsonization time than in normal human serum (NHS). In contrast, serum reagent lacking C1q, C4 or C3 did not promote binding in this assay system. We also demonstrated that elevated levels of factor B could restore binding of complexes to erythrocytes in C2-depleted serum via alternative pathway activation. These results indicate that in spite of lack of a complete classical pathway, C2-deficient individuals could retain some immune complex opsonizing activity via the alternative pathway. This finding could contribute to the understanding of differences in association between complement deficiency and immune-complex disease.
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23.
  • Leffler, Jonatan, et al. (författare)
  • Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease.
  • 2012
  • Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 188:7, s. 3522-3531
  • Tidskriftsartikel (refereegranskat)abstract
    • Ongoing inflammation including activation of the complement system is a hallmark of systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. We found that sera from a subset of patients with active SLE had a reduced ability to degrade in vitro-generated NETs, which was mostly restored when these patients were in remission. Patients that failed to degrade NETs had a more active disease and they also displayed lower levels of complement proteins C4 and C3 in blood. We discovered that NETs activated complement in vitro and that deposited C1q inhibited NET degradation including a direct inhibition of DNase-I by C1q. Complement deposition on NETs may facilitate autoantibody production, and indeed, Abs against NETs and NET epitopes were more pronounced in patients with impaired ability to degrade NETs. NET-bound autoantibodies inhibited degradation but also further increased C1q deposition, potentially exacerbating the disease. Thus, NETs are a potent complement activator, and this interaction may play an important role in SLE. Targeting complement with inhibitors or by removing complement activators such as NETs could be beneficial for patients with SLE.
  •  
24.
  • Lindh, Jacob, 1971, et al. (författare)
  • Blended learning through global network and interdisciplinary live distance experiments at human performance laboratories.
  • 2009
  • Ingår i: Learning in the Synergy of Multiple Disciplines, 4th European Conference on Technology Enhanced Learning, EC-TEL 2009, Nice, France, September 29 - October 2, 2009.. - : Springer. - 9783642046353 ; 5794 Springer 2009
  • Tidskriftsartikel (refereegranskat)abstract
    • Under a previous grant (2005-2008) we designed an interdisciplinary inquiry-based laboratory course in sports kinesiology, taught simultaneously over the Internet for undergraduate students at the University of Gothenburg and at Stanford University. Student groups developed their own research questions, conducted online distance experiments, processed their unique data with support from an interdisciplinary global network of expert consultants, and presented original scientific results. We will demonstrate one virtual experiment that is central to the course to conference attendees and present a unique set of interactive learning tools for the scientific process. This student-conducted experiment was first tested in a laboratory in Stockholm in 2007, and broadcasted live to three universities, with experts and students actively taking part via Polycom and Marratech. Real-time communication was possible in all directions through a moderator in Stockholm. Our course model seems to improve student learning outcomes while advancing the field of sports science.
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25.
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26.
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27.
  • Lood, Christian, et al. (författare)
  • C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells : a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis
  • 2009
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:10, s. 3081-3090
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: C1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll-like receptor-induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon-alpha (IFNalpha). METHODS: Peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFNalpha production was determined by an immunoassay. RESULTS: C1q significantly inhibited PBMC IFNalpha production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFNalpha production induced by ICs and CpG DNA but increased PDC IFNalpha production induced by HSV. The regulatory role of C1q was not specific for IFNalpha but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins. CONCLUSION: Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients.
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28.
  • Lood, Christian, et al. (författare)
  • IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?
  • 2012
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:8, s. 2698-2706
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) that stimulate leukocytes through Fc? receptors (Fc?R) with subsequent inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycanhydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. This study was undertaken to investigate whether EndoS affects the proinflammatory properties of ICs and has the potential to be developed as a therapy for SLE. Methods ICs purified from SLE patients or RNA-containing ICs formed in vitro were treated with EndoS and used in several assays reflecting different important features of SLE pathogenesis, such as phagocytosis by polymorphonuclear cells (PMNs) and plasmacytoid dendritic cells (PDCs), complement activation, and interferon-a (IFNa) production by PDCs. Results EndoS treatment abolished all proinflammatory properties of the ICs investigated. This included Fc?R-mediated phagocytosis by PDCs (P = 0.001) and subsequent production of IFNa (P = 0.002), IC-induced classical pathway of complement activation (P = 0.008), chemotaxis, and oxidative burst activity of PMNs (P = 0.002). EndoS treatment also had a direct effect on the molecular structure of ICs, causing decreased IC size and glycosylation. Conclusion Our findings indicate that EndoS treatment has prominent effects on several pathogenetically important IC-mediated events, and suggest that EndoS has the potential to be developed as a novel therapy for SLE.
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29.
  • Lood, Christian, et al. (författare)
  • IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE : a possible new treatment?
  • 2012
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:8, s. 2698-2706
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVESystemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) which stimulate leukocytes through FcγRs with subsequent inflammation. Treatment with EndoS, an IgG glycan hydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. In the present study we asked if EndoS could affect pro-inflammatory properties of ICs and have the potential to be developed as a therapy in SLE.METHODSICs, purified from SLE patients or RNA-containing ICs formed in vitro, were treated with EndoS and used in several assays reflecting different important parts of SLE pathogenesis such as phagocytosis by polymorphonuclear neutrophils (PMNs) and plasmacytoid dendritic cells (pDCs), complement activation and IFNα production by pDCs.RESULTSOur results demonstrate that EndoS treatment could abolish all pro-inflammatory properties of ICs investigated. This includes FcγR-mediated phagocytosis by pDCs (p<0.0001) and subsequent production of IFNα (p<0.0001), IC-induced classical complement pathway activation (p<0.0001), chemotaxis and oxidative burst activity of PMNs (p=0.002). We could also demonstrate direct effects on the molecular structure of ICs after EndoS treatment with decreased size and glycosylation patterns.CONCLUSIONSProminent effects of EndoS treatment were seen in several pathogenetically important IC-mediated events and our data suggest that EndoS have the potential to be developed as a novel therapy in SLE.
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30.
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31.
  • Lood, Christian, et al. (författare)
  • Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus erythematosus - a possible link to venous thrombosis?
  • 2012
  • Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 21:13, s. 1423-1432
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing vascular diseases (VD) such as myocardial infarction, stroke and venous thrombosis, which can only partly be explained by traditional risk factors. The role of platelets in this process has not been extensively studied. Platelet activation supports complement binding to the platelet surface, and increased C4d has been seen on platelets in SLE patients as well as in non-rheumatic patients with stroke. In this study we investigated in vivo platelet deposition of the classical complement pathway components C1q, C4d and C3d in relation to VD in SLE patients. Furthermore, the ability of serum to support in vitro complement deposition on fixed heterologous platelets was analyzed. Methods: Blood from 69 SLE patients and age- and sex-matched healthy individuals was collected in sodium-citrate tubes and platelets isolated by centrifugation. Complement deposition on platelets was detected by flow cytometry. Results: We could demonstrate that SLE patients had increased C1q, C3d and C4d deposition on platelets as compared to healthy controls (p < 0.0001). SLE patients with a history of venous thrombosis had increased complement deposition on platelets as compared to SLE patients without this manifestation (p < 0.05). In vitro studies demonstrated that serum from patients with lupus anticoagulant, venous thrombosis or antiphospholipid antibody syndrome supported increased platelet C4d deposition in vitro as compared to SLE patients without these manifestations (p < 0.05). Our data support the hypothesis that platelet activation and the subsequent complement deposition on platelets are central in the development of venous thrombosis in SLE. Conclusions: Altogether we suggest that complement deposition on platelets could reflect important pathogenetic events related to the development of venous thrombosis in SLE and might be used as a marker for venous thrombosis in SLE.
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32.
  • Lood, Christian, et al. (författare)
  • Platelet activation and anti-phospholipid antibodies collaborate in the activation of the complement system on platelets in systemic lupus erythematosus.
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis.
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33.
  • Lood, Christian, et al. (författare)
  • Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.
  • 2010
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; Jul 1, s. 1951-1957
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (p<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFNalpha which up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
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34.
  • Lood, Christian, et al. (författare)
  • Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus
  • 2011
  • Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in many different organ systems, activation of leukocytes and production of pro-inflammatory cytokines. The heterodimer of the cytosolic calcium-binding proteins S100A8 and S100A9 (S100A8/A9) is secreted by activated polymorphonuclear neutrophils (PMNs) and monocytes and serves as a serum marker for several inflammatory diseases. Furthermore, S100A8 and S100A9 have many pro-inflammatory properties such as binding to Toll-like receptor 4 (TLR4). In this study we investigated if aberrant cell surface S100A8/A9 could be seen in SLE and if plasmacytoid dendritic cells (pDCs) could synthesize S100A8/A9. Methods: Flow cytometry, confocal microscopy and real-time PCR of flow cytometry-sorted cells were used to measure cell surface S100A8/A9, intracellular S100A8/A9 and mRNA levels of S100A8 and S100A9, respectively. Results: Cell surface S100A8/A9 was detected on all leukocyte subpopulations investigated except for T cells. By confocal microscopy, real-time PCR and stimulation assays, we could demonstrate that pDCs, monocytes and PMNs could synthesize S100A8/A9. Furthermore, pDC cell surface S100A8/A9 was higher in patients with active disease as compared to patients with inactive disease. Upon immune complex stimulation, pDCs up-regulated the cell surface S100A8/A9. SLE patients had also increased serum levels of S100A8/A9. Conclusions: Patients with SLE had increased cell surface S100A8/A9, which could be important in amplification and persistence of inflammation. Importantly, pDCs were able to synthesize S100A8/A9 proteins and up-regulate the cell surface expression upon immune complex-stimulation. Thus, S100A8/A9 may be a potent target for treatment of inflammatory diseases such as SLE.
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35.
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36.
  • Martini, Paolo G. V., et al. (författare)
  • Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases
  • 2010
  • Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients.
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37.
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38.
  • Melander Skattum, Lillemor, et al. (författare)
  • Serum bactericidal activity against Neisseria meningitidis in patients with C3 nephritic factors is dependent on IgG allotypes.
  • 2008
  • Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 129, s. 123-131
  • Tidskriftsartikel (refereegranskat)abstract
    • The main mechanisms of immune defense against Neisseria meningitidis are serum bactericidal activity (SBA) and opsonophagocytosis. Many complement deficiencies, among them acquired partial C3 deficiency due to stabilizing autoantibodies against the alternative pathway C3 convertase (C3 nephritic factors, C3 NeF); increase the risk of meningococcal infection. SBA against meningococci in patients with C3 NeF was determined along with allelic variants (GM alleles) of the immunoglobulin constant heavy G chain (IGHG) genes. In patients with C3 NeF and in control children, individuals homozygous for G1Mf and G3Mb showed higher SBA against meningococci than heterozygous individuals. Partial complement deficiency in early childhood might explain the influence of GM variants on SBA in control children. These novel findings imply that the IGHG genotype is important in defense against meningococci in individuals with low complement function and possibly in combination with other immunodeficiencies.
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39.
  • Nielsen, Christoffer T, et al. (författare)
  • Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation.
  • 2012
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:4, s. 1227-1236
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE.: To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in systemic lupus erythematosus (SLE) and to correlate this with clinical and serological parameters. METHODS.: Sixty-eight clinically well-characterized SLE patients, 38 healthy controls (HC), 6 systemic sclerosis (SSc), and 6 rheumatoid arthritis (RA) patients were included. The numbers of annexin V-binding MPs displaying IgG, IgM or C1q were enumerated by flow cytometry. MP protein levels were determined by mass spectrometry in clinically defined subsets of SLE patients and controls. The MP-IgG load was determined by flow cytometry of all SLE and HC samples. RESULTS.: SLE patients had significantly increased total and relative numbers of IgG-positive MPs (p = 0.0004) with a much higher average IgG-load/MP (p < 0.0001) than HCs. Quantitative mass spectrometry of purified MPs verified significantly increased IgG, IgM, and C1q in SLE. In RA and SSc the average IgG/MP was significantly lower than in SLE (p = 0.006 and 0.05, respectively). Also, IgM/MP and C1q/MP were higher in SLE than in controls (p < 0.05) except for IgM in the RA-group. IgG-positive MPs were significantly associated with the presence of anti-dsDNA, anti-ENA, and anti-histone antibodies, with total IgG, and with decreased leukocyte counts. Average IgG/MP was associated with lower concentrations of MPs, the presence of anti-C1q antibodies, and with complement consumption. CONCLUSIONS.: Circulating cell-derived MPs in SLE carry increased loads of IgG, IgM, and C1q and IgG-MPs are associated with autoantibodies and complement activation. The findings link immunological reactions on MPs with the etiopathology of SLE. © 2012 American College of Rheumatology.
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40.
  • Nilsson, Johnny, et al. (författare)
  • Work-time profile, blood lactate concentration and rating of perceived exertion in the 1998 Greco-Roman Wrestling World Championship.
  • 2002
  • Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 20:11, s. 939-45
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to examine work-time profiles, blood lactate concentrations and perceived exertion among Greco-Roman wrestlers in the 1998 World Championship. Forty-two senior wrestlers from nine nations were studied in 94 matches. Each match was recorded with a video camera (Panasonic AG 455, film rate: 25 Hz) and analysed for duration of work (wrestling) and rest (interrupt) periods. Blood lactate concentration was determined with an electrochemical device (Analox P-LM5) and a rating of perceived exertion scale (Borg) was used to estimate general exertion and exertion in the extremity and trunk muscles. The mean duration of the matches was 427 s (range 324-535 s), with mean durations of work and rest of 317 and 110 s, respectively. The mean periods of work and rest were 37.2 and 13.8 s, respectively. Mean blood lactate concentration was 14.8 mmol x 1(-1) (range 6.9-20.6). The difference in mean blood lactate concentration between the first- and final-round matches was not significant (P > 0.05). Blood lactate concentration was significantly higher (P < 0.04) in matches of long duration than in those of short duration. The mean general rating of perceived exertion for all matches was 13.8 according to the scale used. Most of the wrestlers (53.3%) perceived exertion to be highest in the flexors of the forearm, followed by the deltoids (17.4%) and the biceps brachii muscles (12.0%). In addition to a relatively high rating of perceived exertion in the arm muscles, this indicates a high specific load on the flexor muscles of the forearm.
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41.
  • Nordin Fredrikson, Gunilla, et al. (författare)
  • Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop codon
  • 1998
  • Ingår i: Human Immunology. - 0198-8859. ; 59:11, s. 713-719
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency.
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42.
  • Nordin Fredrikson, Gunilla, et al. (författare)
  • Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations
  • 1998
  • Ingår i: Journal of Clinical Immunology. - 0271-9142. ; 18:4, s. 272-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316-->Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the properdin-deficient individuals produced properdin mRNA in a normal fashion. In type I deficiency no intracellular or secreted properdin was found, indicating rapid intracellular degradation. Monocytes from the males with type II deficiency expressed and secreted properdin normally. Properdin in sera with type II deficiency showed abnormal oligomerization with a relative decrease in properdin trimers and tetramers. Our findings suggest that the low concentration of circulating properdin in type II deficiency is caused by increased extracellular catabolism. Analysis of properdin expression by monocytes in a female carrier in the family with properdin deficiency type I provided direct evidence of lyonization at the cellular level.
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43.
  • Papp, Marian E., et al. (författare)
  • A randomized controlled pilot study of the effects of 6-week high intensity hatha yoga protocol on health-related outcomes among students
  • 2019
  • Ingår i: Journal of Bodywork & Movement Therapies. - : Elsevier BV. - 1360-8592 .- 1532-9283. ; 23:4, s. 766-772
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Modern hatha yoga exercises (YE) provide an alternative form of physical activity which may reduce stress, facilitate recovery and improve health. This study investigated the short-term effects of high intensity hatha yoga exercises (HIY) on health-related outcomes.Methods: A 6-week randomized controlled study was performed to compare HIY with a control group not changing their exercise behavior. Healthy students (N = 44; median age: 25 years, range 20–39 years; HIY: n = 21, including 3 men; control group: n = 23, including 3 men) novice to yoga participated in the intervention which included one weekly class and recommended home training. Participants provided self-reports in questionnaires before and after the intervention. Self-reports included anxiety and depression (Hospital Anxiety and Depression Scale), stress (Perceived Stress Scale), sleep quality (Pittsburgh Sleep Quality Index), insomnia (Insomnia Severity Index), subjective health complaints (Common Symptoms in General Practice Index) and self-rated health (single-item).Results: After the 6-week intervention, there were no between-group differences in anxiety, depression, stress, sleep or self-rated health. However, when investigating associations within the HIY-group, a higher HIY-dose was related to less depression (r = 0.47; p = 0.03), improved sleep quality (r = 0.55; p = 0.01), and less insomnia (r = 0.49; p = 0.02).Conclusions: There were no short-term between-group effects of HIY on mental distress, sleep or self-rated health. However, within the HIY-group, a higher dose was associated with improved mental health in terms of depression and with improved sleep. Although future studies with larger samples are needed, these preliminary findings suggest short-term positive effects of HIY on health-related outcomes among students.Trial registration number NCT01305096.
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44.
  • Papp, Marian E., et al. (författare)
  • Effects of high-intensity hatha yoga on cardiovascular fitness, adipocytokines, and apolipoproteins in healthy students : a randomized controlled study
  • 2016
  • Ingår i: Journal of Alternative and Complementary Medicine. - : Mary Ann Liebert Inc. - 1075-5535 .- 1557-7708. ; 22:1, s. 81-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Yoga exercises are often used as a form of body and mind exercise to increase performance. However, knowledge about the physiologic effects of performing high-intensity Hatha yoga exercises over a longer time period remains limited.Objective: To investigate the effects of high-intensity yoga (HIY) on cardiovascular fitness (maximal oxygen consumption, estimated from the Cooper running test), ratings of perceived exertion (RPE), heart rate (HR), heart rate recovery (HRR), blood pressure (BP), adipocytokines, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and glycosylated hemoglobin (HbA1c) in healthy students.Methods: The 44 participants (38 women and 6 men; median age, 25 years [range, 20–39 years]) were randomly assigned to an HIY or a control group. The HIY program was held for 6 weeks (60 minutes once a week). Cardiovascular fitness, RPE, HR, HRR, BP, adipocytokines, HbA1c, ApoA1, and ApoB were measured at baseline and after 6 weeks in both groups.Results: HIY had no significant effects on cardiovascular fitness (mean dose: 390 minutes [range, 210–800 minutes]), HR, HRR, BP, or any of the blood parameters. However, ApoA1 (1.47 ± 0.17 to 1.55 ± 0.16 g/L; p = 0.03) and adiponectin (8.32 ± 3.32 to 9.68 ± 3.83 mg/L; p = 0.003) levels increased significantly in the HIY group after 6 weeks.Conclusions: Six weeks of HIY did not significantly improve cardiovascular fitness. However, ApoA1 and adiponectin levels increased significantly in the HIY group. This finding suggests that HIY may have positive effects on blood lipids and an anti-inflammatory effect.
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45.
  • Persson, Ulf, et al. (författare)
  • A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fc gamma-RIIa Genes
  • 2013
  • Ingår i: Kidney and Blood Pressure Research. - : Karger: Open Access Journals / S. Karger AG. - 1420-4096 .- 1423-0143. ; 37:6, s. 641-648
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fc gamma-RIIa and IL1-Ra. Patients and Methods: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegeners granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. Results: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fc gamma-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. Conclusion: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.
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46.
  • Petersson, Lennart, et al. (författare)
  • The EU and South Africa: Trade and Diversification
  • 2007
  • Ingår i: The European Union and Developing Countries. Trade, Aid and Growth in an Integrating World. ; , s. 97-119
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
47.
  • Rosdahl, Hans, et al. (författare)
  • Evaluation of the Oxycon Mobile metabolic system against the Douglas bag method
  • 2010
  • Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 109:2, s. 159-171
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate two versions of the Oxycon Mobile portable metabolic system, (OMPS1 and OMPS2) in a wide range of oxygen uptake, using the Douglas bag method (DBM) as criterion method. The metabolic variables VO2, VCO2, respiratory exchange ratio and VE were measured during submaximal and maximal cycle ergometer exercise with sedentary, moderately trained individuals and athletes as participants. Test-retest reliability was investigated using the OMPS1. The coefficients of variation varied between 2% and 7% for the metabolic parameters measured at different work rates, and resembled those obtained with the DBM. With the OMPS1, systematic errors were found in the determination of VO2 and VCO2. At submaximal work rates VO2 was 6-14% and VCO2 5-9% higher than with the DBM. At VO2max both VO2 and VCO2 were slightly lower as compared to DBM (-4.1% and -2.8% respectively). With OMPS2, VO2 was determined accurately within a wide measurement range (about 1-5.5 L*min-1), while VCO2 was overestimated (3-7%). VE was accurate at submaximal work rates with both OMPS1 and OMPS2, whereas underestimations (4-8%) were noted at VO2max. The present study is the first to demonstrate that a wide range of VO2 can be measured accurately with the Oxycon Mobile portable metabolic system (second generation). Future investigations are suggested to clarify reasons for the small errors noted for VE and VCO2 versus the Douglas bag measurements, and also to gain knowledge of the performance of the device under applied and non-laboratory conditions.
  •  
48.
  • Truedsson, Lennart, et al. (författare)
  • Serum concentrations of C4 isotypes and factor B in type I C2 deficiency suggest haplotype-dependent quantitative expression of MHC class III complement genes
  • 1995
  • Ingår i: Experimental and Clinical Immunogenetics. - 0254-9670. ; 12:2, s. 66-73
  • Tidskriftsartikel (refereegranskat)abstract
    • The complement protein C4 exists as two isotypes, C4A and C4B, encoded by genes in the major histocompatibility complex (MHC) class III region. The serum concentrations of C4A4 were lower than those of C4B2 in serum from 19 individuals homozygous for type I C2 deficiency (p < 0.0002). These individuals all had the S042 complotype and most of them were homozygous for the haplotype HLA-B18,S042,DR2. In 14 individuals heterozygous for the C2Q0 gene and with the C4A4, C4B2 phenotype and in 51 individuals with the C4A3, C4B1 phenotype, the isotype concentrations were equal. Factor B concentrations in the C2-deficient individuals were lower than those in individuals with the C4A3, C4B1 phenotype (p < 0.0001). The findings strongly suggest that the quantitative expression of C4 isotypes and factor B is MHC haplotype dependent. C4 null alleles cannot be accurately determined by measuring relative C4 isotype serum concentrations.
  •  
49.
  • Tydén, Helena, et al. (författare)
  • Increased serum levels of S100A8/A9 and S100A12 are associated with cardiovascular disease in patients with inactive systemic lupus erythematosus.
  • 2013
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 52:11, s. 2048-2055
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. Patients with SLE have an increased morbidity and mortality from cardiovascular disease (CVD). The reason for this is not entirely understood, but is believed to be partly related to the long-lasting inflammatory process seen in SLE. The aim of the present study was to investigate whether there is an association between CVD and serum levels of the proinflammatory proteins S100A8/A9 and S100A12 in SLE.Methods. Serum levels of S100A8/A9 and S100A12 were measured with ELISA in 237 SLE patients with clinically inactive disease and without infections, as well as in 100 healthy individuals. Cardiovascular manifestations were defined according to the SLICC/ACR Damage Index (SLICC/ACR-DI).Results. Serum levels of S100A8/A9 were elevated in our inactive SLE patients as compared with healthy individuals (P < 0.0001), which was not seen for S100A12 (P = 0.12). SLE patients with a history of CVD had increased serum levels of both S100A8/A9 and S100A12 compared with patients with no CVD or venous thromboembolism (P = 0.003 and P = 0.006, respectively). The presence of organ damage according to SLICC/ACR-DI was associated with an increase in both S100A8/A9 and S100A12 serum levels (P = 0.001 and P = 0.006, respectively).Conclusion. Elevated serum levels of S100A8/A9 and S100A12 may be used as an indicator of severe disease and CVD in SLE, suggesting that SLE patients with elevated serum S100A8/A9 and S100A12 concentrations may benefit from more intense cardiovascular primary preventive strategies and possibly also from more intense and early immunosuppressive treatment.
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