| 1. |
- Gunnarsson, Iva, et al.
(författare)
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Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis
- 2007
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Ingår i: Arthritis and Rheumatism. - : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 56:4, s. 1263-1272
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Rituximab is a monoclonal antibody directed against the CD20 marker of B cells. Because of its ability to deplete B lymphocytes, it has been suggested that the drug could be of benefit in B cell-dependent diseases, including systemic lupus erythematosus (SLE). The purpose of this study was to investigate the histopathologic and clinical effects of combination treatment with rituximab and cyclophosphamide (CYC) in patients with CYC-resistant proliferative lupus nephritis.METHODS: Seven female patients with proliferative lupus nephritis were treated with rituximab in combination with CYC. Renal biopsies were performed before treatment and during followup. SLE activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group index. In 6 of the 7 patients, immunostaining of lymphocyte subpopulations in the renal tissue was performed before treatment and during followup.RESULTS: At 6 months of followup, significant clinical improvement was noted, with a reduction in SLEDAI scores (from a mean of 15 to 3), anti-double-stranded DNA antibody levels (from a mean of 174 IU/ml to 56 IU/ml), and anti-C1q antibody levels (from a mean of 35 units/ml to 22 units/ml). On repeat renal biopsy, improvement in the histopathologic class of nephritis occurred in a majority of patients, and a decrease in the renal activity index was noted (from 6 to 3). A reduction in the number of CD3, CD4, and CD20 cells in the renal interstitium was noted in 50% of the patients on repeat biopsy.CONCLUSION: At 6 months of followup, all patients had responded both clinically and histopathologically to combination therapy. For patients with proliferative lupus nephritis who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option.
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| 2. |
- Jonasson, Mats, et al.
(författare)
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Utilisation of actuators to improve vehicle stability at the limit: from hydraulic brakes towards electric propulsion
- 2009
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Ingår i: Proceedings of the 21st International Symposium on Dynamics of Vehicles on Roads and Tracks (IAVSD’09), KTH Stockholm, 17-21 August 2009.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The capability of over-actuated vehicles to maintain stability during limit handling is studied in this paper. A number of important differently actuated vehicles, equipped with hydraulic brakes towards more advanced chassis solutions, are presented. A virtual evaluation environment has specifically been developed to cover the complex interaction between the driver and the vehicle undercontrol. In order to fully exploit the different actuators set-up, and the hard non-convex constraints they possess, the principle of control allocation by nonlinear optimisation is successfully employed. The final evaluation is made by exposing the driver and the over-actuated vehicles to a safety-critical manoeuvre. Thereby, the differently actuated vehicles are ranked by a quantitativeindicator of stability.
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| 3. |
- Lindberg, Jenny, et al.
(författare)
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Monocyte and Neutrophil Chemotactic Activity at the Site of Interstitial Inflammation in Patients on High-Flux Hemodialysis or Hemodiafiltration
- 2009
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Ingår i: Blood Purification. - : S. Karger AG. - 0253-5068 .- 1421-9735. ; 28:1, s. 47-52
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: We have observed a difference between patients on low-flux hemodialysis (HD) or peritoneal dialysis and patients on hemodiafiltration (HDF) or high-flux HD in the capacity of transmigrated leukocytes to mobilize CD11b in response to inflammatory stimuli compared with healthy subjects. This could be due to different interstitial chemokine concentrations. Methods: We measured concentrations of circulating and interstitial macrophage inflammatory protein-1 alpha (MIP-1 alpha), matrix metalloproteinase-9 (MMP-9)/neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in 10 patients on HDF or high-flux HD and 11 healthy subjects by using immunoassay. Results: The interstitial concentrations of MIP-1 alpha, MMP-9/NGAL and IL-8 were similar in patients and healthy subjects, while the corresponding concentration of MCP-1 was significantly higher in patients on HDF or high-flux HD as compared with healthy subjects (p < 0.01). Conclusion: We suggest that an equal or higher concentration of chemokines in the interstitium in patients with HDF or high-flux HD might be one mechanism responsible for the preserved function of transmigrated leukocytes. Copyright (C) 2009 S. Karger AG, Basel
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| 4. |
- Paulsson, Josefin, et al.
(författare)
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Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease
- 2007
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 192:2, s. 328-334
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence support a role of neutrophils in coronary artery disease (CAD). However little is known about the action of neutrophils at a local inflammatory site represented by an atherosclerotic plaque. To gain insight into these issues, we applied a skin blister model that permits analyses of in vivo transmigrated neutrophils. We hypothesised that the chronic inflammation in stable CAD mediates priming of neutrophils that impacts the out-come of neutrophil action at an inflammatory site. Thirteen patients with angiographically verified CAD were eligible for study entry together with 13 age and sex matched controls. Markers of inflammation (IL-6 and CRP), neutrophil activation (IL-8 and MMP-9/NGAL), and functional aspects (CD11b up-regulation and intracellular H(2)O(2) production) of peripheral and in vivo transmigrated neutrophils were studied. Systemic IL-8 and MMP-9/NGAL concentrations were significantly increased in patients indicating a primed state in circulating neutrophils. In vivo transmigrated neutrophils in stable CAD patients had an increased propensity to release MMP-9/NGAL and a reduced capacity to up-regulate CD11b and to produce hydrogen peroxide. These aberrations at the inflammatory site may be a consequence of a primed state of circulating neutrophils and point towards potential mechanisms whereby neutrophils at a local inflammatory site may contribute to the pathogenesis of CAD.
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| 5. |
- Schepis, Danika, et al.
(författare)
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Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus
- 2009
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 126:1, s. 140-6
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.
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| 6. |
- Szummer, Karolina, et al.
(författare)
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Influence of Renal Function on the Effects of Early Revascularization in Non-ST-Elevation Myocardial Infarction Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)
- 2009
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Ingår i: CIRCULATION. - 0009-7322 .- 1524-4539. ; 120:10, s. 851-U55
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Tidskriftsartikel (refereegranskat)abstract
- Background-It is unknown whether patients with non-ST-elevation myocardial infarction derive a similar benefit from an early invasive therapy at different levels of renal function. Methods and Results-A total of 23 262 consecutive non-ST-elevation myocardial infarction patients andlt;= 80 years old were included in a nationwide coronary care unit register between 2003 and 2006. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease Study formula. Patients were divided into medically or invasively treated groups if revascularized within 14 days of admission. A propensity score for the likelihood of invasive therapy was calculated. A Cox regression model with adjustment for propensity score and discharge medication was used to assess the association between early revascularization and 1-year mortality across renal function stages. There was a gradient, with significantly fewer patients treated invasively with declining renal function: eGFR andgt;= 90 mL . min(-1) . 1.73 m(-2), 62%; eGFR 60 to 89 mL . min(-1) . 1.73 m(-2), 55%; eGFR 30 to 59 mL . min(-1) . 1.73 m(-2), 36%; eGFR 15 to 29 mL . min(-1) . 1.73 m(-2), 14%; and eGFR andlt; 15 mL . min(-1) . 1.73 m(-2)/ dialysis, 15% (P andlt; 0.001). After adjustment, the overall 1-year mortality was 36% lower (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P andlt; 0.001) with an invasive strategy. The magnitude of survival difference was similar in normal-to-moderate renal function groups. The lower mortality observed with invasive therapy declined with lower renal function, with no difference in mortality in patients with kidney failure (eGFR andlt; 15 mL . min(-1) . 1.73 m(-2)) or in those receiving dialysis (hazard ratio 1.61, 95% confidence interval 0.84 to 3.09, P=0.15). Conclusions-Early invasive therapy is associated with greater 1-year survival in patients with non-ST-elevation myocardial infarction and mild-to-moderate renal insufficiency, but the benefit declines with lower renal function, and is less certain in those with renal failure or on dialysis.
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| 7. |
- Vuong, Mai Tuyet, et al.
(författare)
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Genetic variation in the transforming growth factor-beta1 gene is associated with susceptibility to IgA nephropathy
- 2009
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 24:10, s. 3061-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis. METHODS: We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden. RESULTS: Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P
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