| 1. |
- Chen, X., et al.
(författare)
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A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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| 3. |
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| 4. |
- Ekström, Per, et al.
(författare)
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The immune modulator Linomide prevents neuronal death in injured peripheral nerves of the mouse
- 1998
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Ingår i: NeuroReport. - 0959-4965. ; 9:7, s. 1337-1341
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal death after injury or disease could result from imbalanced cytokine expression. Linomide (LS-2616, quinoline-3-carboxamide), a synthetic immunomodulator with effects on cytokine production, suppresses autoimmune diseases of the nervous system. Here adult mice were pre-treated with 200 mg/kg/day of Linomide for 9 days, after which the sciatic nerves were crushed. After another 10 days of Linomide treatment the dorsal root ganglia were dissected out and stained for apoptosis, either immediately or after 2 days in culture, which increases cell death. Superior cervical ganglia were also cultured for 2 days. The Linomide pretreatment profoundly reduced (~60- 80%) the injury-induced apoptotic death of neurons and satellite cells in both systems. The results suggest that modulation of the inflammatory cytokine cascade is a promising road to nerve cell rescue.
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| 6. |
- Karlsson, Anders, et al.
(författare)
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Surface-Shaving of Staphylococcus aureus Strains and Quantitative Proteomic Analysis Reveal Differences in Protein Abundance of the Surfaceome.
- 2024
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Ingår i: Microorganisms. - 2076-2607. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a pathogen known to cause a wide range of infections. To find new targets for identification and to understand host-pathogen interactions, many studies have focused on surface proteins. We performed bacterial-cell surface-shaving, followed by tandem mass tag for quantitative mass spectrometry proteomics, to examine the surfaceome of S. aureus. Two steps were performed, the first step including surface protein-deficient mutants of S. aureus Newman strain lacking important virulence genes (clfA and spa, important for adhesion and immune evasion and srtAsrtB, linking surface-associated virulence factors to the surface) and the second step including isolates of different clinical origin. All strains were compared to the Newman strain. In Step 1, altogether, 7880 peptides were identified, corresponding to 1290 proteins. In Step 2, 4949 peptides were identified, corresponding to 919 proteins and for each strain, approximately 20 proteins showed differential expression compared to the Newman strain. The identified surface proteins were related to host-cell-adherence and immune-system-evasion, biofilm formation, and survival under harsh conditions. The results indicate that surface-shaving of intact S. aureus bacterial strains in combination with quantitative proteomics is a useful tool to distinguish differences in protein abundance of the surfaceome, including the expression of virulence factors.
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| 7. |
- Karlsson, Johan, et al.
(författare)
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Data warehousing as a basis for web-based documentation of data mining and analysis
- 1999
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Ingår i: Studies in Health Technology and Informatics. - : IOS Press. - 0926-9630 .- 1879-8365. ; 68, s. 423-427
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we present a case study for data warehousing intended to support data mining and analysis. We also describe a prototype for data retrieval. Further we discuss some technical issues related to a particular choice of a patient record environment.
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| 8. |
- Karlsson, Niclas G., 1966, et al.
(författare)
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Glycosylation differences between pig gastric mucin populations: a comparative study of the neutral oligosaccharides using mass spectrometry.
- 1997
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Ingår i: The Biochemical journal. - 0264-6021. ; 326 ( Pt 3), s. 911-7
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Tidskriftsartikel (refereegranskat)abstract
- Five mucin populations were isolated from the cardiac region,corpus and antrum of pig gastric mucosa. The released neutral oligosaccharides were permethylated and analysed using high-temperature gas chromatography-mass spectrometry (GC-MS) as well as matrix-assisted laser-desorption mass spectrometry (MALDI-MS). Thirty different oligosaccharides with up to six monosaccharide residues were characterized using both techniques, but the presence of an additional 49 structures was suggested on the basis of their molecular mass by MALDI-MS. Oligosaccharides based on core-1 (Galbeta1-3GalNAcalpha1-) and core-2 [Galbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-] structures were widely distributed, whereas core-3 structures (GlcNAcbeta1-3GalNAcalpha1-) were present only in mucins from the cardiac region and corpus, and core-4 structures [GlcNAcbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-] were present exclusively in mucins from the cardiac region. Furthermore the oligosaccharides from one of the mucins from the corpus were significantly longer than those from the other populations. The results illustrate vast structural diversity, but the relative abundances show only a few dominating structures, suggesting that many oligosaccharides may be quite rare in pig gastric mucins. Well-defined mucin populations with distinctly different glycosylation can thus be identified in pig stomach, suggesting that glycosylation of the large secreted mucins from this tissue is not a random event.
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| 9. |
- Karlsson, Niclas G., 1966, et al.
(författare)
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Molecular characterization of the large heavily glycosylated domain glycopeptide from the rat small intestinal Muc2 mucin.
- 1996
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Ingår i: Glycoconjugate journal. - 0282-0080. ; 13:5, s. 823-31
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Tidskriftsartikel (refereegranskat)abstract
- The largest high-glycosylated domain, glycopeptide A, of the "insoluble' mucin complex of the rat small intestine has earlier been purified and characterized (Carlstedt et al., 1993, J Biol Chem 268: 18771-81). A rabbit antiserum raised against deglycosylated glycopeptide A was used to clone part of a mucin showing homology to the human MUC2 mucin (Hansson et al., 1994, Biochem Biophys Res Commun 198. 181-90). This serum specifically stained goblet cells (paranuclear) in the mouse small intestine. The size of the coding sequence of glycopeptide A was estimated by using reversed transcriptase PCR of mRNA from an inbred rat strain (GOT-W) using primers in the unique central and C-terminal parts of the proposed rat Muc2 sequences. The PCR and Southern blot of the PCR products showed a fragment of about 5.5 kb corresponding to about 1700 amino acids when the known Cys-rich sequences used for the primers were subtracted. This is slightly larger than the size estimated earlier by biochemical studies. The mRNA encoding the rat Muc2 was slightly smaller than the mRNA encoding the human MUC2 in a colorectal cell line. Although the size of glycopeptide A estimated from biochemical results and by PCR is not identical, the results obtained here further support that the "insoluble' mucin of the rat small intestine is encoded by the Muc2 gene. Most of the oligosaccharides in glycopeptide A were either neutral (40%) or sialylated (40%). The remaining ones were sulfated with the sulfate group attached to C-6 of N-acetylglucosamine linked to C-6 of the N-acetylgalactosaminitol as revealed by tandem mass spectrometry of the perdeuteroacetylated oligosaccharides. Eighteen oligosaccharides were found of which fourteen were characterized and found to be mostly novel. Our findings thus expand the current knowledge of the core peptide of the rat intestinal goblet cell mucin and provide a relatively complete picture of the glycosylation of a defined mucin domain.
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| 10. |
- Karlsson, Niclas G., 1966, et al.
(författare)
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Strategy for the investigation of O-linked oligosaccharides from mucins based on the separation into neutral, sialic acid- and sulfate-containing species.
- 1995
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Ingår i: Glycoconjugate journal. - 0282-0080. ; 12:1, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- A method for the separation of O-linked oligosaccharides into neutral, sialic acid-containing and sulfated species was applied to oligosaccharides released by alkaline borohydride from mucin glycopeptides from porcine small intestine. The released mixture of reduced oligosaccharides was applied to an anion exchange column, and the neutral oligosaccharides were collected as the unretarded fraction. A mixture of dimethyl sulfoxide and iodomethane was passed through the column to convert the sialic acid-containing oligosaccharides into methyl esters that were eluted and converted to methyl amides by methyl amine. Finally the sulfated oligosaccharide fraction was eluted with salt. The neutral and the derivatized sialic acid-containing oligosaccharides were analysed by gas chromatography-mass spectrometry after permethylation and the sulfated oligosaccharide fraction was analysed by high performance anion exchange chromatography.
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