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Påhlsson, Peter
Publikationer (10 of 43) Visa alla publikationer
Tengdelius, M., Gurav, D., Konradsson, P., Påhlsson, P., Griffith, M. & Oommen, O. P. (2015). Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles. Chemical Communications, 51(40), 8532-8535
Öppna denna publikation i ny flik eller fönster >>Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles
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2015 (Engelska)Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 51, nr 40, s. 8532-8535Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Gold nanoparticles coated with fucoidan-mimetic glycopolymers were synthesized that displayed good colloidal stability and promising anti-cancer properties. Fucoidan mimetic glycopolymers on their own were nontoxic, while glycopolymer coated gold nanoparticles displayed selective cytotoxicity to human colon cancer cell lines (HCT116) while it was non-toxic to mouse fibroblast cells (NIH3T3).

Ort, förlag, år, upplaga, sidor
ROYAL SOC CHEMISTRY, 2015
Nationell ämneskategori
Kemi Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-119269 (URN)10.1039/c5cc02387d (DOI)000354043200034 ()25892661 (PubMedID)
Anmärkning

Funding Agencies|Swedish Strategic Research StemTherapy

Tillgänglig från: 2015-06-12 Skapad: 2015-06-12 Senast uppdaterad: 2017-12-04
Tengdelius, M., Lee, C.-J., Grenegård, M., Griffith, M., Påhlsson, P. & Konradsson, P. (2014). Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization. Biomacromolecules, 15(7), 2359-2368
Öppna denna publikation i ny flik eller fönster >>Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization
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2014 (Engelska)Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, nr 7, s. 2359-2368Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The sulfated marine polysaccharide fucoidan has been reported to have health benefits ranging from antivirus and anticancer properties to modulation of high blood pressure. Hence, they could enhance the biological function of materials for biomedical applications. However, the incorporation of fucoidan into biomaterials has been difficult, possibly due to its complex structure and lack of suitable functional groups for covalent anchoring to biomaterials. We have developed an approach for a rapid synthesis of fucoidanmimetic glycopolymer chains through cyanoxyl-mediated free-radical polymerization, a method suitable for chain-end functionalizing and subsequent linkage to biomaterials. The resulting sulfated and nonsulfated methacrylamido alpha-L-fucoside glycopolymers fucoidan-mimetic properties were studied in HSV-1 infection and platelet activation assays. The sulfated glycopolymer showed similar properties to natural fucoidan in inducing platelet activation and inhibiting HSV-1 binding and entry to cells, thus indicating successful syntheses of fucoidan-mimetic glycopolymers.

Ort, förlag, år, upplaga, sidor
American Chemical Society (ACS), 2014
Nationell ämneskategori
Kemi Klinisk medicin Fysik
Identifikatorer
urn:nbn:se:liu:diva-109382 (URN)10.1021/bm5002312 (DOI)000339090500003 ()24813544 (PubMedID)
Tillgänglig från: 2014-08-15 Skapad: 2014-08-15 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
Landberg, E., Åström, E., Kågedal, B. & Påhlsson, P. (2012). Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety. Clinica Chimica Acta, 414, 58-64
Öppna denna publikation i ny flik eller fönster >>Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety
2012 (Engelska)Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 414, s. 58-64Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background

Carbohydrate deficient transferrin (CDT) is used for detection of alcohol abuse and follow-up. High performance liquid chromatography (HPLC) of transferrin glycoforms is highly specific for identification of alcohol abuse, but unresolved disialo- and trisialotransferrin glycoforms sometimes makes interpretation difficult. The cause of this phenomenon is unknown, cannot be explained by genetic variants of transferrin, but seems to be associated with liver disease.

Methods

Nineteen serum samples showing di–tri bridging when analyzed by HPLC were collected. Transferrin was purified by affinity chromatography, and N-linked oligosaccharides were released enzymatically. The N-glycans were further analyzed by high performance anion-exchange chromatography with pulsed amperometric detection and MALDI-TOF mass spectrometry.

Results

The HPLC-analysis showed three different types of glycoform patterns. The N-glycans from fifteen samples showed patterns with increased number of triantennary structures containing one or two fucose residues. One sample contained an increased amount of triantennary glycans without fucose. Three samples showed a glycosylation pattern similar to normal transferrin.

Conclusions

The di–tri bridging phenomenon was associated with alterations in transferrin glycosylation in the majority of cases. Transferrin contained a higher extent of triantennary and often fucosylated N-linked oligosaccharides. These results may be important in future diagnostic approaches to liver diseases.

Ort, förlag, år, upplaga, sidor
Elsevier, 2012
Nyckelord
Transferrin, CDT, Di-tri bridging, Glycosylation, Liver disease
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-88368 (URN)10.1016/j.cca.2012.07.026 (DOI)000312685400014 ()
Anmärkning

Funding Agencies|Medical Research Council of Southeast Sweden||

Tillgänglig från: 2013-04-03 Skapad: 2013-02-04 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
Preechaburana, P., Erlandsson, P., Åström, E., Påhlsson, P., Filippini, D. & Robinson, N. D. (2012). Disposable total internal reflection fluorescence lab-on-a-chip for medical diagnosis.
Öppna denna publikation i ny flik eller fönster >>Disposable total internal reflection fluorescence lab-on-a-chip for medical diagnosis
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2012 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

Lab-on-a-chip detection of fluorescence transduced chemical stimuli is demonstrated using fluidics and optical coupling disposable elements in a configuration compatible with distributed diagnosis.

Disposable optical elements are designed to separate excitation by total internal reflection using regular glass slides as optical light guide and fluidics support, while high dynamic range image acquisition with consumer cameras complement the platform to support a broad range of responses with a same configuration. Complementary tone mapping procedures are introduced to systematically double the sensitivity for selected range intervals.

Chemical sensitization to free fucose, a diagnostic marker for liver cirrhosis and several cancer forms, illustrates the platform capabilities for diagnosis targets.

Nationell ämneskategori
Naturvetenskap
Identifikatorer
urn:nbn:se:liu:diva-86181 (URN)
Tillgänglig från: 2012-12-10 Skapad: 2012-12-10 Senast uppdaterad: 2015-06-01Bibliografiskt granskad
Bergstrom, M., Åström, E., Påhlsson, P. & Ohlson, S. (2012). Elucidating the selectivity of recombinant forms of Aleuria aurantia lectin using weak affinity chromatography. Journal of chromatography. B, 885, 66-72
Öppna denna publikation i ny flik eller fönster >>Elucidating the selectivity of recombinant forms of Aleuria aurantia lectin using weak affinity chromatography
2012 (Engelska)Ingår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 885, s. 66-72Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Aberrant glycosylation is connected to several pathological conditions and lectins are useful tools to characterize glycosylated biomarkers. The Aleuria aurantia lectin (AAL) is of special interest since it interacts with all types of fucosylated saccharides. AAL has been expressed in Escherichia coil as a fully functional recombinant protein. Engineered variants of AAL have been developed with the aim of creating monovalent lectins with more homogenous binding characteristics. Four different forms of AAL were studied in the present work: native AAL purified from A. aurantia mushrooms, recombinant AAL dimer, recombinant AAL monomer and recombinant AAL site 2 (S2-AAL). The affinities of these AAL forms toward a number of saccharides were determined with weak affinity chromatography (WAC). Disaccharides with fucose linked alpha 1-3 to GIcNAc interacted with higher affinity compared to fucose linked alpha 1-6 or alpha 1-4 and the obtained dissociation constants (K-d) were in the range of 10 mu M for all AAL forms. Tetra- and pentasaccharides with fucose in alpha 1-2, alpha 1-3 or alpha 1-4 had K-d values ranging from 0.1 to 7 mM while a large alpha 1-6 fucosylated oligosaccharide had a K-d of about 20 mu M. The recombinant multivalent AAL forms and native AAL exhibited similar affinities toward all saccharides, but S2-AAL had a lower affinity especially regarding a sialic acid containing fucosylated saccharide. It was demonstrated that WAC is a valuable technique in determining the detailed binding profile of the lectins. Specific advantages with WAC include a low consumption of non-labeled saccharides, possibility to analyze mixtures and a simple procedure using standard HPLC equipment.

Ort, förlag, år, upplaga, sidor
Elsevier, 2012
Nyckelord
Affinity, Aleuria aurantia lectin, Glycan interaction, Recombinant protein, Weak affinity chromatography
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-76625 (URN)10.1016/j.jchromb.2011.12.015 (DOI)000301563400010 ()
Anmärkning
Funding Agencies|Linnaeus University||Linkoping University||Medical council of Southeast Sweden||Tillgänglig från: 2012-04-13 Skapad: 2012-04-13 Senast uppdaterad: 2017-12-07
Kloster Smerud, H., Barany, P., Lindström, K., Fernström, A., Sandell, A., Påhlsson, P. & Fellström, B. (2011). New treatment for IgA nephropathy:  enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrology, Dialysis and Transplantation, 26(10), 3237-3241
Öppna denna publikation i ny flik eller fönster >>New treatment for IgA nephropathy:  enteric budesonide targeted to the ileocecal region ameliorates proteinuria
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2011 (Engelska)Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, nr 10, s. 3237-3241Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 (R)), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. less thanbrgreater than less thanbrgreater thanMethods. 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). less thanbrgreater than less thanbrgreater thanResults. 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 similar to 8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. less thanbrgreater than less thanbrgreater thanConclusions. 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.

Ort, förlag, år, upplaga, sidor
Oxford University Press (OUP): Policy B, 2011
Nyckelord
budesonide, clinical trial, corticosteroid, IgA nephropathy, prospective
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-72664 (URN)10.1093/ndt/gfr052 (DOI)000296349200030 ()
Anmärkning
Funding Agencies|Pharmalink AB||Tillgänglig från: 2011-12-02 Skapad: 2011-12-02 Senast uppdaterad: 2017-12-08
Olausson, J., Jonsson, B.-H., Tibell, L. & Påhlsson, P. (2011). Production and characterization of a monomeric form and a single-site form of Aleuria aurantia lectin. Glycobiology, 21(1), 34-44
Öppna denna publikation i ny flik eller fönster >>Production and characterization of a monomeric form and a single-site form of Aleuria aurantia lectin
2011 (Engelska)Ingår i: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 21, nr 1, s. 34-44Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Lectins have been widely used in structural and functional studies of complex carbohydrates. Lectins usually bind carbohydrates with relatively low affinity but compensate for this by multivalency. When using lectins in different biological and analytical assays the multivalent nature of lectins can sometimes produce unwanted reactions such as agglutination or precipitation of target glycoproteins. The mushroom lectin Aleuria aurantia binds to fucose-containing oligosaccharides. It is composed of two identical subunits where each subunit contains five binding sites for fucose. In the present study two forms of recombinant AAL were produced using site-directed mutagenesis. A monomeric form of AAL was produced by exchange of Tyr6 to Arg6, and a monovalent fragment of AAL was produced by insertion of a NdeI restriction enzyme cleavage site and a stop codon in the coding sequence. The AAL forms were expressed as His-tagged proteins in E.coli and purified by affinity chromatography. Binding properties of the two AAL forms were performed using hemagglutination assay, surface plasmon resonance and enzyme-linked lectin assay analyses. Both the monomeric AAL form (mAAL) and the monovalent AAL form (S2-AAL) retained their capacity to bind fucosylated oligosaccharides. However, both constructs exhibited properties that differed from the intact recombinant AAL (rAAL). Monomeric AAL showed similar binding affinities to fucosylated oligosaccharides compared to rAAL but had less hemagglutinating capacity. S2-AAL showed a lower binding affinity to fucosylated oligosaccharides and, in contrast to rAAL and mAAL, S2-AAL did not bind to sialylated fuco-oligosaccharides such as sialyl-Lex. The study shows that molecular engineering techniques may be a tool for producing lectins with more defined properties such as decreased valency and defined specificities and affinities. This may be very valuable for development of reliable diagnostic and biological assays for carbohydrate analysis.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2011
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:liu:diva-20310 (URN)10.1093/glycob/cwq129 (DOI)000285193100005 ()
Tillgänglig från: 2009-09-03 Skapad: 2009-09-03 Senast uppdaterad: 2017-12-13
Gunnarsson, P., Fornander, L., Påhlsson, P. & Grenegård, M. (2010). Sialic acid residues play a pivotal role in alpha(1)-acid glycoprotein (AGP)-induced generation of reactive oxygen species in chemotactic peptide pre-activated neutrophil granulocytes. INFLAMMATION RESEARCH, 59(2), 89-95
Öppna denna publikation i ny flik eller fönster >>Sialic acid residues play a pivotal role in alpha(1)-acid glycoprotein (AGP)-induced generation of reactive oxygen species in chemotactic peptide pre-activated neutrophil granulocytes
2010 (Engelska)Ingår i: INFLAMMATION RESEARCH, ISSN 1023-3830, Vol. 59, nr 2, s. 89-95Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We have recently shown that terminal sialic acid residues are essential for alpha(1)-acid glycoprotein (AGP)-induced Ca2+ mobilization in neutrophils. The aim of the present study was to establish the importance of sialic acid residues on AGP in modulating human neutrophil functions, with emphasis on the generation of reactive oxygen species (ROS). ROS were measured by luminol-enhanced chemiluminescence in isolated human neutrophils. We found that AGP did not provoke ROS generation in resting or L-selectin presensitized neutrophils. Moreover, AGP did not affect the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced ROS generation, but it slightly suppressed opsonized zymosan-induced responses. However, when the neutrophils were prestimulated with fMLP, the subsequent addition of AGP provoked a marked ROS response. Dose-response studies and time studies revealed that the ROS generating capacity of AGP was highest at a concentration of 0.05 mg/ml and when given 3-10 min after addition of fMLP. A desialylated form of AGP or pretreatment of neutrophils with 3- and 6-sialyllactose caused a substantially lower ROS response in neutrophils prestimulated with fMLP. Our data show that AGP can stimulate a second ROS response in fMLP preactivated neutrophils and that terminal sialic acid residues on AGP play a crucial role in this regard.

Nyckelord
alpha(1)-Acid glycoprotein, Neutrophils, Reactive oxygen species, Sialic acid
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-53823 (URN)10.1007/s00011-009-0071-1 (DOI)000273787200001 ()19669698 (PubMedID)
Tillgänglig från: 2010-02-05 Skapad: 2010-02-05 Senast uppdaterad: 2014-08-27
Levander, L., Grenegård, M., Ryden, I. & Påhlsson, P. (2009). Effects of alpha 1-acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils. Scandinavian Journal of Immunology, 69(5), 412-420
Öppna denna publikation i ny flik eller fönster >>Effects of alpha 1-acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils
2009 (Engelska)Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, nr 5, s. 412-420Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We recently showed that the acute-phase protein alpha(1)-acid glycoprotein (AGP) induces rises in cytosolic calcium concentration, [Ca2+](i,) in neutrophils through sialic acid dependent interactions with the neutrophil receptors siglec-5 and/or siglec-14. Whereas both siglec-5 and siglec-14 have a relatively broad specificity for sialylated oligosaccharide structures, including both structures with terminal alpha 2-3 or alpha 2-6 linked sialic acid, there is a markedly reduced affinity to the fucosylated epitope sialyl Lewis x (SLe(x)). Increased fucosylation, leading to increased expression of SLe(x) on AGP is commonly associated with inflammatory conditions. In the present study, we investigated whether an increased SLe(x) expression would affect the Ca2+-mobilizing effect of AGP. AGP with elevated fucose content isolated from patients with untreated chronic joint inflammation showed a decreased [Ca2+](i) modulatory effect on neutrophils compared to normally fucosylated AGP. Furthermore a hyperfucosylated AGP form produced by in vitro fucosylation, that consequently had an elevated expression of SLe(x), could not elicit a [Ca2+](i) increase in neutrophils. The role of the carbohydrate portion of AGP in modulating neutrophil responses was further strengthened by showing that synthetic glycoconjugates carrying oligosaccharides with terminal alpha 2-3 or alpha 2-6 linked sialic acid were able to mimic the Ca2+-mobilizing effect of AGP whereas a synthetic glycoconjugate carrying SLe(x) was not. Based on these data, we conclude that increased fucosylation can alter the ability of AGP to induce neutrophil signalling and further supports an important role of the oligosaccharide chains of AGP in the modulation of leukocyte functions during an inflammatory process.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-18019 (URN)10.1111/j.1365-3083.2009.02240.x (DOI)
Anmärkning

On the day of the defence day the title of this article was "Increased fucosylation of α1‐acid glycoprotein decreases its Ca2+ mobilizing capacity in neutrophils".

Tillgänglig från: 2009-05-04 Skapad: 2009-05-04 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Gunnarsson, P., Levander, L., Påhlsson, P. & Grenegård, M. (2009). α1-acid glycoprotein (AGP)-induced platelet shape change involvesthe Rho/Rho kinase signalling pathway. Thrombosis and Haemostasis, 102(4), 694-703
Öppna denna publikation i ny flik eller fönster >>α1-acid glycoprotein (AGP)-induced platelet shape change involvesthe Rho/Rho kinase signalling pathway
2009 (Engelska)Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 102, nr 4, s. 694-703Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

α1-acid glycoprotein (AGP) is an acute-phase protein that contributes to inflammation processes. The role of AGP in platelet activation and thrombosis is, however, largely unknown. Therefore, we thoroughly investigated the effects of AGP on human platelets. Platelets were isolated from healthy volunteers and subsequently exposed to AGP. Platelet responses were monitored as change in light transmission, intracellular calcium concentration, light microscopy and protein phosphorylation by Western blot. We found that AGP induced platelet shape change independently of a second release of adenine nucleotides or thromboxane A2, and that effect was abolished by endotheliumderived platelet inhibitors such as nitric oxide (NO) and adenosine. Furthermore, AGP triggered a minor calcium response and a pronounced Rho/Rho-kinase-dependent increase in Thr696 phosphorylation of myosin phosphatase target subunit 1 (MYPT1). Moreover, the Rho/Rho-kinase inhibitor Y-27632 significantly decreased the AGP-induced shape change. The results also showed that the AGP-elicited shape change was antagonised by pretreatment with low doses of collagen and thrombospondin- 1. Our results describe a novel mechanism by which AGP stimulates platelet shape change via activation of the Rho/Rhokinase signalling pathway. Physiological important platelet inhibitors, such as NO, completely counterbalance the effect of AGP. Hence, the present study indicates that AGP directly contributes to platelet activation, which in turn might have an impact in physiological haemostasis and/or pathological thrombosis.

Ort, förlag, år, upplaga, sidor
Stuttgart, Germany: Schattauer Gmbh, 2009
Nyckelord
shape change, Rho-kinase, Platelets, α1-acid glycoprotein
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-20474 (URN)10.1160/TH09-03-0156 (DOI)000271039400013 ()
Tillgänglig från: 2009-09-09 Skapad: 2009-09-09 Senast uppdaterad: 2018-10-02Bibliografiskt granskad
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