Peter Påhlsson
Linköping University
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Featured researches published by Peter Påhlsson.
Nephrology Dialysis Transplantation | 2011
Hilde Kloster Smerud; Peter Bárány; Karin Lindström; Anders Fernström; Anna Sandell; Peter Påhlsson; Bengt Fellström
BACKGROUND Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon®), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. METHODS Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased ∼8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. CONCLUSIONS In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.
Clinica Chimica Acta | 2002
Ingvar Rydén; Peter Påhlsson; Arne Lundblad; Thomas Skogh
Abstract Background : Fucosylation of α1-acid glycoprotein (AGP, orosomucoid) has previously been found to be increased in patients with rheumatoid arthritis. Furthermore, the degree of fucosylation has been suggested to reflect disease activity. Therefore, we investigated the fucosylation of AGP in 131 patients (96 women and 35 men) with recent onset rheumatoid arthritis (RA). We compared the results with traditional biochemical markers of inflammation, i.e. plasma concentrations of AGP (P-AGP), and C-reactive protein (P-CRP). Methods : AGP fucosylation measured with a novel lectin enzyme-linked immunosorbent assay (ELISA) was compared with a disease activity score (DAS28) and its components, and with P-AGP, and P-CRP at the time of diagnosis, and at a follow-up visit 1 year later. Results : Both men and women with RA had increased AGP fucosylation compared to healthy individuals. We found a weak correlation between AGP fucosylation and DAS28 only in men. In men with initially increased AGP fucosylation, the level of fucosylation correlated with the change in DAS28 during the first year following diagnosis. Conclusion : We conclude that AGP fucosylation is not superior to traditional markers of disease activity in RA. However, AGP fucosylation may give some additional information to traditional biochemical markers on the disease progression in men.
Journal of Chromatography A | 1997
Sten Ohlson; Maria Bergström; Peter Påhlsson; Arne Lundblad
Weak monoclonal antibodies were used as ligands in a high-performance liquid affinity chromatography system. Isocratic weak affinity chromatography was achieved when similar carbohydrate antigens were separated according to their weak binding to the immobilized monoclonal antibody. These chromatographic systems were studied in detail in terms of affinity, specificity and efficiency. The influence of the physico-chemical factors of temperature, pH, ionic strength and organic solvents was also evaluated. The issue of specificity was specially considered, as non-specific interactions are prevalent and usually of a weak affinity nature. This study clearly demonstrates the potential to use weak affinity biological interactions as the basis of chromatographic analysis and separation.
Scandinavian Journal of Immunology | 1996
U. Srinivas; Peter Påhlsson; Arne Lundblad
Recent studies have demonstrated that selectins, a new family of cell‐adhesion molecules with similar domain structures, mediate the adhesion of peripheral blood cells to interleukin‐1 (IL‐1)‐activated endothelium. In the present study the authors evaluated the role of E‐selectin‐Sialyl Lewis x (SLex)/Sialyl Lewis a (SLea) interaction in mediating in vitro adhesion of two colon cancer cell lines, HT‐29 and COLO 201, to human umbilical cord endothelial cells (HUVEC). Colon cancer cell lines had a strong expression of blood group‐related carbohydrate epitopes as evaluated by fluorescence‐activated cell sorter (FACS) analysis. It was established that adhesion of HT‐29 and COLO 201 cells to IL‐1 stimulated HUVEC was calcium dependent and could be inhibited by a monoclonal antibody directed against E‐selectin. Prior incubation of cells with two different antibodies directed against SLex and antibodies directed against related Lewis epitopes, Lex and Lea, had no significant effect on adhesion. Three antibodies directed against SLea differed in their capacity to inhibit the adhesion of HT‐29 and COLO 201 cells to HUVEC. Only one antibody directed against the SLea structure was effective in inhibiting adhesion of both COLO 201 and HT‐29 cells. The difference could not be attributed to titre, the type or number of glycoproteins, or to a difference in the amount of SLea present on individual proteins, suggesting that presence and right presentation of SLea epitope might be important for adhesion of colon cancer cells. Finally, in the in vitro system used, adhesion of HT‐29 and COLO 201 cells to activated HUVEC is mediated predominantly by E‐selectin/SLea interaction. SLex and related epitopes, Lex and Lea, seem to have limited relevance for colon cancer cell recognition of E‐selectin.
The FASEB Journal | 2007
Peter Gunnarsson; Louise Levander; Peter Påhlsson; Magnus Grenegård
We studied whether the acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in [Ca2+]i in neutrophils and sought to identify the corresponding AGP receptor (or receptors). We found that AGP elicited a minimal rise in [Ca2+]i in Fura‐2‐loaded neutrophils, and this response was markedly enhanced by pretreatment with anti‐L‐selectin antibodies. (The EC50 value of the AGP‐induced Ca2+ response was 9 μg/ml.) Activation of phospholipase‐C, Src tyrosine kinases, and PI3 kinases proved to be essential for the AGP‐mediated increase in [Ca2+]i, whereas the p38 MAPK and SYK signaling pathways were not involved. Furthermore, antibodies against sialic acid binding, immunoglobulin‐like lectin 5 (Siglec‐5) and oligosac‐charide 3′‐sialyl‐lactose both antagonized the AGP‐in‐duced response and caused an immediate increase in [Ca2+]i in anti‐L‐selectin‐treated neutrophils, which indicates a signaling capacity of Siglec‐5. We used modified forms of AGP (treated with mild periodate or neuraminidase) to establish the importance of sialic acid residues. The modified forms of AGP caused a much smaller rise in [Ca2+]i than did unaltered AGP. Affinity chromatography confirmed that unchanged AGP, but not neuraminidase‐treated AGP, bound to Siglec‐5. Our report provides the first evidence for a signaling capacity by AGP through a defined receptor. Pre‐engagement of L‐selectin significantly enhanced this signaling capacity.— Gunnarsson, P., Levander, L., Påhlsson, P., Grenegård, M. The acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin‐like lectins (Siglecs). FASEB J. 21, 4059–4069 (2007)
Journal of Immunology | 2002
Per Bengtson; Arne Lundblad; Göran Larson; Peter Påhlsson
We recently identified several individuals carrying a missense mutation (G329A; Arg110-Gln) in the FUT7 gene encoding fucosyltransferase VII. This enzyme is involved in the biosynthesis of the sialyl Lewis x (Lex) epitope on human leukocytes, which has been identified as an important component of leukocyte ligands for E- and P-selectin. No enzyme activity was measurable in expression studies in COS-7 cells using the mutated FUT7 construct. One of the identified individuals carried this mutation homozygously. Flow cytometry analysis of polymorphonuclear leukocytes (PMN) from this individual showed a nearly complete absence of staining with mAbs directed against sialyl Lex and a diminished staining with an E-selectin IgG chimera. However, staining with P-selectin IgG chimera and Abs directed against P-selectin glycoprotein ligand-1 was not affected by the mutation. PMN from the homozygously mutated individual was further analyzed in an in vitro flow chamber assay. The number of rolling PMN and the rolling velocities on both E- and P-selectin were in the range of PMN from nonmutated individuals. FUT4 and FUT7 mRNA was quantified in PMN isolated from individuals carrying the FUT7 mutation. It was found that PMN from both FUT7 homozygously and heterozygously mutated individuals exhibited an elevated expression of FUT4 mRNA compared with PMN from FUT7 nonmutated individuals. The elevated expression of fucosyltransferase IV was reflected as an increased expression of the Lex and CD65s Ags on PMN from these individuals. The significance of the mutation was supported by transfection of BJAB cells.
Glycoconjugate Journal | 2008
Johan Olausson; Lena Tibell; Bengt-Harald Jonsson; Peter Påhlsson
Lectins are carbohydrate binding proteins that are involved in many recognition events at molecular and cellular levels. Lectin-oligosaccharide interactions are generally considered to be of weak affinity, however some mushroom lectins have unusually high binding affinity towards oligosaccharides with Kd values in the micromolar range. This would make mushroom lectins ideal candidates to study protein–carbohydrate interactions. In the present study we investigated the properties of a recombinant form of the mushroom lectin Aleuria aurantia (AAL). AAL is a fucose-binding lectin composed of two identical 312-amino acid subunits. Each subunit contains five binding sites for fucose. We found that one of the binding sites in rAAL had unusually high affinities towards fucose and fucose-containing oligosaccharides with Kd values in the nanomolar range. This site could bind to oligosaccharides with fucose linked α1-2, α1-3 or α1-4, but in contrast to the other binding sites in AAL it could not bind oligosaccharides with α1-6 linked fucose. This binding site is not detected in native AAL (nAAL) one possible explanation may be that this site is blocked with free fucose in nAAL. Recombinant AAL was produced in E. coli as a His-tagged protein, and purified in a one-step procedure. The resulting protein was analyzed by electrophoresis, enzyme-linked lectin assay and circular dichroism spectroscopy, and compared to nAAL. Binding properties were measured using tryptophan fluorescence and surface plasmon resonance. Removal of the His-tag did not alter the binding properties of recombinant AAL in the enzyme-linked lectin assay. Our study forms a basis for understanding the AAL-oligosaccharide interaction and for using molecular techniques to design lectins with novel specificities and high binding affinities towards oligosaccharides.
Glycoconjugate Journal | 1997
Ingvar Rydén; Gunnar Skude; Arne Lundblad; Peter Påhlsson
High-pH anion-exchange chromatography with pulsed amperometric detection is a highly sensitive technique that can be used for detecting changes in sialylation and fucosylation, as well as different branching patterns of N-linked oligosaccharides in glycoproteins. We examined the N-glycans of α1-acid glycoprotein obtained from twelve patients with various inflammatory conditions with this technique, as well as traditional concanavalin A crossed affinity immunoelectrophoresis. We found the chromatographic profiles of N-glycans in all patients with rheumatoid arthritis to be very similar, but significantly different from normal controls. N-glycans from patients with ulcerative colitis also showed specific alterations in their chromatographic profiles. However, some heterogeneity was found between these patients, perhaps reflecting changes in glycosylation secondary to certain states of the disease, or to medical treatment. We conclude that this technique is useful for detailed mapping of glycosylation changes in α1-acid glycoprotein in clinical samples, and that it may be used to further increase our knowledge about glycosylation changes in response to inflammatory disease. Abbreviations: AC, acute cholangitis; AGP, α1-acid glycoprotein; CAIE, crossed affinity immunoelectrophoresis; Con A, concanavalin A; HPAEC-PAD, high-pH anion-exchange chromatography with pulsed amperometric detection; IEC, ion exchange chromatography; RA, rheumatoid arthritis; SLex, sialyl Lex; UC, ulcerative colitis
Biosensors and Bioelectronics | 2002
Mathias Liljeblad; Arne Lundblad; Peter Påhlsson
A method based on a surface plasmon resonance technique for detection of changes in concentration and glycosylation of proteins in cell culture supernatant is described. The method was used to analyze alpha(1)-acid glycoprotein (AGP) produced by a human hepatoma cell line (HepG2). Cell culture supernatant was injected to a BIACORE 2000 instrument and AGP was captured on the sensor chip by immobilized antibodies. The captured glycoprotein was then analyzed for content of carbohydrate epitopes using three different lectins, Aleuria aurantia lectin (AAL), Sambucus nigra agglutinin (SNA), and Triticum vulgaris agglutinin (wheat germ agglutinin, WGA). The method was used to analyze changes in concentration and glycosylation of AGP produced by HepG2 cells grown with or without three different cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and transforming growth factor beta-1 (TGF beta(1)). Using the described method it was shown that when HepG2 cells were grown in the presence of IL-6 both AGP concentration and fucosylation increased. When HepG2 cells instead were grown in the presence of TGF beta(1) AGP fucosylation increased whereas AGP concentration decreased.
Glycoconjugate Journal | 2000
Mathias Liljeblad; Arne Lundblad; Peter Påhlsson
It is well established that IgG from rheumatoid arthritis (RA) patients are less galactosylated than IgG from normal individuals. Determination of agalacto-IgG may therefore aid in diagnosis and treatment of RA. The decrease in galactosylation of IgG leads to an increase in terminal N-acetylglucosamine residues, which can be detected using a specific lectin from Psathyrella velutina. In the present study IgG from RA and control serum was purified using affinity chromatography. The samples were then, after reduction, analyzed on a BIOCORE® 2000 system with immobilized Psathyrella velutina lectin. Using this technique it was possible to discriminate between IgG from RA patients and IgG from control individuals with respect to its content of IgG with terminal N-acetylglucosamine. The affinity biosensor technique makes it possible to detect binding without labeling or using secondary antibodies.