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1.
  • Luis, Ana S., et al. (författare)
  • A single sulfatase is required to access colonic mucin by a gut bacterium
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 332-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a barrier that separates these microorganisms from the intestinal epithelium(1). Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate degradation of the complex O-glycans found in mucins. In the distal colon, these glycans are heavily sulfated, but specific sulfatases that are active on colonic mucins have not been identified. Here we show that sulfatases are essential to the utilization of distal colonic mucin O-glycans by the human gut symbiont Bacteroides thetaiotaomicron. We characterized the activity of 12 different sulfatases produced by this species, showing that they are collectively active on all known sulfate linkages in O-glycans. Crystal structures of three enzymes provide mechanistic insight into the molecular basis of substrate specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O-glycans in vitro and also has a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by a prominent group of gut bacteria, an important process for both normal microbial gut colonization(2) and diseases such as inflammatory bowel disease(3). A single sulfatase produced by a bacterium found in the human colon is essential for degradation of sulfated O-glycans in secreted mucus.
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4.
  • Bäckhed, Fredrik, 1973, et al. (författare)
  • Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications
  • 2003
  • Ingår i: Microbes Infect. - 1286-4579 .- 1769-714X. ; 5:12, s. 1057-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Cells of the mucosal lining are the first to encounter invading bacteria during infection, and as such, they have developed numerous ways of detecting microbial intruders. Recently, we showed that epithelial cells recognize lipopolysaccharide (LPS) through the CD14-Toll-like receptor (TLR)-4 complex. Here, we identify the substructures of LPS that are recognized by the TLR4 receptor complex. In contrast to lipid A, the O-antigen does not mediate an inflammatory response; rather it interferes with the lipid A recognition. An Escherichia coli strain genetically modified to express penta-acylated lipid A not only showed reduced immunogenicity, but was also found to inhibit pro-inflammatory signalling induced by wild-type E. coli (hexa-acylated lipid A) as well as LPS from other bacteria of the Enterobacteriaceae family. Furthermore, penta-acylated LPS from Pseudomonas aeruginosa acted as an antagonist to hexa-acylated E. coli LPS, as did E. coli, as shown by its inhibitory effect on IL-8 production in stimulated cells. Hypo-acylated lipid A, such as that of P. aeruginosa, is found in several species within the gut microflora as well as in several bacteria causing chronic infections. Thus, our results suggest that the composition of the microflora may be important in modulating pro-inflammatory signalling in epithelial cells under normal as well as pathologic conditions.
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  • Bensing, Sophie, et al. (författare)
  • Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1
  • 2007
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:3, s. 949-954
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.
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  • Bongo, A. K. S., et al. (författare)
  • Periodontal health in an indigenous Sami population in Northern Norway: a cross-sectional study
  • 2020
  • Ingår i: Bmc Oral Health. - : Springer Science and Business Media LLC. - 1472-6831. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim of the study was to describe prevalence, severity and distribution of periodontal disease as well as associated risk factors in an indigenous Sami population in Northern Norway, and to investigate differences between the indigenous Sami and the non-Sami population. Methods This cross-sectional study included data from the Dental Health in the North study (N = 2078; 18-75 years). Data on Ethnicity, household income, education, smoking habits, dental attendance, and tooth brushing habits were collected by a questionnaire. Periodontal conditions were assessed by clinical examination. A modified version of the new AAP/EFP classification system of periodontal disease was used to estimate the severity of periodontitis. Three stages were used: 'Non-severe periodontitis', 'Stage II', and stage 'III/IV'. Results Of the total study population 66.5% reported Sami affiliation. The total prevalence of periodontitis was 49.7%, with 20.1% in Stage III/IV, but no differences between Sami and non-Sami. When controlled for sex, age, education, smoking and dental attendance the Sami had higher probability of having more severe stages of periodontitis; Odds Ratio(Stage II) (OR) = 1.3; 95% CI: 1.1-1.7; and ORStage III/IV (OR) = 1.6; 95% CI: 1.1-2.2) compared to non-Sami. The Sami had higher prevalence of periodontal pocket depth (PD) >= 4 mm (t = 1.77; p < 0.001) and PD >= 6 mm (t = 1.08; p = 0.038) than the non-Sami. Conclusions The prevalence of periodontitis was high in communities in the core area of Sami settlement in Northern Norway, regardless of ethnicity. People with Sami ethnicity had more deep periodontal pockets and an increased odds of having severe stages of periodontitis. Future studies should address possible explaining factors behind the potential higher risk of having more severe periodontitis among indigenous people in Sami settlements.
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11.
  • Brustad, M., et al. (författare)
  • Oral health in the indigenous Sami population in Norway - the dental health in the North study
  • 2020
  • Ingår i: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 78:2, s. 98-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This study aims at presenting the feasibility of using the public oral health clinics in indigenous Sami communities, as arena for a comprehensive data collection for population-based epidemiological oral health research among adults (age, 18-75 years) in a multi-ethnic setting. Material and methods: The study design was cross-sectional. The data collection was incorporated into the clinical procedure at six public dental clinics situated in the Administrative Area for the Sami Language in Finnmark County, Northern Norway, during 2013-2014. Both clinical- and questionnaire-data were collected. The quality of clinical data was thoroughly calibrated and validated. Results: Altogether, 2235 people participated in the study gave a crude response rate at 88.7%. In the final data sample (n = 2034), 56.9% were female. We constructed three ethnic groups (Sami, Mixed Sami/Norwegian and Norwegian). Altogether, 67.7% reported Sami or mixed Sami ethnicity. The internal validity of the clinical data was found to be satisfactory when assessed by comprehensive quality procedure, calibration and reliability assessments. Conclusion: This study design and method assessments provide solid documentation that public dental clinics are suitable as arenas for data collection in epidemiological oral health studies in the Sami population in this region.
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  • Bugaytsova, Jeanna, et al. (författare)
  • pH regulated H. pylori adherence : implications for persistent infection and disease
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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  • Buskas, T., et al. (författare)
  • Efficient synthesis of polylactosamine structures through regioselective glycosylations
  • 2001
  • Ingår i: Journal of carbohydrate chemistry. - 0732-8303 .- 1532-2327. ; 20:7-8, s. 569-583
  • Tidskriftsartikel (refereegranskat)abstract
    • Di-, tri-and tetramers of ß-(1?3)-linked N-acetyllactosamine residues have been synthesised as their methyl glycosides, to be used in ITC binding studies to various galectins. The synthetic strategy involves two types of regioselective glycosylations: couplings of a galactosyl donor to 3,4-diol N-tetrachlorophthalimido glucose acceptors to give the lactosamine monomer building blocks, and subsequent formation of the oligomers through consecutive couplings of lactosamine donors to 2',3',4'-lactosamine acceptors, with high selectivity for the desired products.
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15.
  • Buts, L, et al. (författare)
  • Solving the phase problem for carbohydrate-binding proteins using selenium derivatives of their ligands : a case study involving the bacterial F17-G adhesin
  • 2003
  • Ingår i: Acta Crystallographica Section D. - : International Union of Crystallography (IUCr). - 2059-7983. ; 59:6, s. 1012-1015
  • Tidskriftsartikel (refereegranskat)abstract
    • The Escherichia coli adhesin F17-G is a carbohydrate-binding protein that allows the bacterium to attach to the intestinal epithelium of young ruminants. The structure of the 17 kDa lectin domain of F17-G was determined using the anomalous dispersion signal of a selenium-containing analogue of the monosaccharide ligand N-acetyl-D-glucosamine in which the anomeric oxygen was replaced by an Se atom. A three-wavelength MAD data set yielded good experimental phases to 2.6 Angstrom resolution. The structure was refined to 1.75 Angstrom resolution and was used to solve the structures of the ligand-free protein and the F17-G-N-acetyl-D-glucosamine complex. This selenium-carbohydrate phasing method could be of general use for determining the structures of carbohydrate-binding proteins.
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16.
  • Buts, L, et al. (författare)
  • The fimbrial adhesin F17-G of enterotoxigenic Escherichia coli has an immunoglobulin-like lectin domain that binds N-acetylglucosamine
  • 2003
  • Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 49:3, s. 705-715
  • Tidskriftsartikel (refereegranskat)abstract
    • The F17-G adhesin at the tip of flexible F17 fimbriae of enterotoxigenic Escherichia coli mediates binding to N-acetyl-beta-D-glucosamine-presenting receptors on the microvilli of the intestinal epithelium of ruminants. We report the 1.7 Angstrom resolution crystal structure of the lectin domain of F17-G, both free and in complex with N-acetylglucosamine. The monosaccharide is bound on the side of the ellipsoid-shaped protein in a conserved site around which all natural variations of F17-G are clustered. A model is proposed for the interaction between F17-fimbriated E. coli and microvilli with enhanced affinity compared with the binding constant we determined for F17-G binding to N-acetylglucosamine (0.85 mM(-1)). Unexpectedly, the F17-G structure reveals that the lectin domains of the F17-G, PapGII and FimH fimbrial adhesins all share the immunoglobulin-like fold of the structural components (pilins) of their fimbriae, despite lack of any sequence identity. Fold comparisons with pilin and chaperone structures of the chaperone/usher pathway highlight the central role of the C-terminal beta-strand G of the immunoglobulin-like fold and provides new insights into pilus assembly, function and adhesion.
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  • Ingelman-Sundberg, M, et al. (författare)
  • Human cytochrome P-450 (CYP) genes: a web page for the nomenclature of alleles
  • 2001
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 10:12, s. 1307-1308
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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21.
  • Lahmann, Martina, Docent i kemi, 1963-, et al. (författare)
  • A facile approach to diosgenin and furostan type saponins bearing a 3 beta-chacotriose moiety
  • 2002
  • Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 337:21-23, s. 2153-2159
  • Tidskriftsartikel (refereegranskat)abstract
    • Combination of a one-pot coupling technique and the use of benzyl ethers as permanent protecting groups offered a short and simple route to dioscin-type saponins. This strategy in combination with a mild reductive opening procedure of the spiroketal function in diosgenin also offered a convenient approach to bidesmosidic furostan type saponins. (Me3NBH3)-B-./AlCl3 promoted acetal opening of 3-O-TBDMS-protected diosgenin gave the 26-OH acceptor 9 into which a benzylated beta-glucose moiety was introduced by a S(N)2-type imidate coupling. After cleavage of the silyl ether, the 3beta-O-glucose and the 4-O-linked rhamnose of the chacotriose unit were introduced by a NIS/AgOTf-promoted one-pot coupling sequence utilising thioglycoside donors and their different reactivity in different solvents. After removal of a benzoyl group, the same coupling conditions were also used for the coupling of the second 2-O-linked rhamnose unit. The target substance was obtained after cleavage of the protecting benzyl ethers under Birch-type conditions, which did not affect the double bond in the steroid skeleton.
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  • Lahmann, Martina, Docent i kemi, 1963-, et al. (författare)
  • Investigation of the reactivity difference between thioglycoside donors with variant aglycon parts
  • 2002
  • Ingår i: Canadian journal of chemistry (Print). - Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 80:8, s. 889-893
  • Tidskriftsartikel (refereegranskat)abstract
    • The reactivity of perbenzoylated thioglycosides with various thiol aglycons has been compared and quantified using competitive glycosylation experiments. Methyl 2,3,4-tri-O-benzyl-alpha-D-glucopyranoside was employed as acceptor and DMTST as a promoter. The reactivity was found, as expected, to depend on the electron donating properties of the aglycon. Hence, the most reactive donor, the cyclohexyl thioglycoside, was found to be about three times as reactive as the thioethyl glycoside, which in turn was twice as reactive as the thiomethyl donor. The thiophenyl donor was even less reactive, whereas p-halophenyl donors were inert under the glycosylation conditions used - but could be activated using NIS-TfOH as promoter. Furthermore, it was found that galactosyl donors were three to four times more reactive than the corresponding glucosyl derivative. These results allowed the design of an orthogonal coupling between thioglycosides with the same protecting groups (benzoyls) but with different thiol aglycons.
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  • Lahmann, Martina, Docent i kemi, 1963-, et al. (författare)
  • One-pot oligosaccharide synthesis exploiting solvent reactivity effects
  • 2000
  • Ingår i: Organic Letters. - Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 2:24, s. 3881-3882
  • Tidskriftsartikel (refereegranskat)abstract
    • One-pot syntheses of trisaccharides have been accomplished simply by changing the solvent system between the two subsequent glycosylation reactions and utilizing the difference in glycosylation rate between different solvents. By tuning the reactivity of accepters and donors and performing the first glycosylation in Et2O (low glycosylation rate) and the second in CH2Cl2/Et2O (higher glycosylation rate), trisaccharides were synthesized in high yields (76-84%).
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  • Lahmann, Martina, Docent i kemi, 1963-, et al. (författare)
  • Synthesis of a polyphosphorylated GPI-anchor core structure
  • 2002
  • Ingår i: Canadian journal of chemistry (Print). - : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 80:8, s. 1105-1111
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a linear assembly approach a highly differentially protected derivative of the common GPI-anchor core structure (alpha-D-Man-(1-->6)-alpha-D-Man-(1-->2)-alpha-D-Man-(1-->4)-alpha-D-GlcNH(2)-(1-->6)-D-myo-inositol) has been synthesized. All mannose donors were prepared from a common thioglycoside precursor (1), and coupled to GlcN(3)-myo-inositol acceptor 5 in a linear five-step glycosylation-deprotection sequence in 49% overall yield, to give the key intermediate 10, with orthogonal temporary protecting groups at the 6", 2", 6', and 2 positions of the trimannoside motif and at the 1 and 2 positions of the inositol part. Consecutive removal of the temporary protecting groups in the trimannoside moiety followed by phosphorylation, gave a tetraphosphosphate derivative in 60% overall yield. Removal of a camphor acetal afforded a 1,2-inositol diol, which was converted to a 1,2-cyclic phosphate using commercial methyl dichlorophosphate (-->17, 95%). One-step deprotection using sodium in liquid ammonia afforded the target polyphosphorylated core structure 18 (60%), which will be tested for metabolic insulin action.
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  • Mthembu, Yolanda H., et al. (författare)
  • Recombinant mucin-type proteins carrying LacdiNAc on differentO-glycan core chains fail to supportH. pyloribinding
  • 2020
  • Ingår i: Molecular Omics. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051 .- 2515-4184. ; 16:3, s. 243-257
  • Tidskriftsartikel (refereegranskat)abstract
    • The beta 4-N-acetylgalactosaminyltransferase 3 (B4GALNT3) transfers GalNAc in a beta 1,4-linkage to GlcNAc forming the LacdiNAc (LDN) determinant on oligosaccharides. The LacdiNAc-binding adhesin (LabA) has been suggested to mediate attachment ofHelicobacter pylorito the gastric mucosaviabinding to the LDN determinant. TheO-glycan core chain specificity of B4GALNT3 is poorly defined. We investigated the specificity of B4GALNT3 on GlcNAc residues carried byO-glycan core 2, core 3 and extended core 1 precursors using transient transfection of CHO-K1 cells and a mucin-type immunoglobulin fusion protein as reporter protein. Binding of the LabA-positiveH. pyloriJ99 and 26695 strains to mucin fusion proteins carrying the LDN determinant on differentO-glycan core chains and human gastric mucins with and without LDN was assessed in a microtiter well-based binding assay, while the binding of(125)I-LDN-BSA to various clinicalH. pyloriisolates was assessed in solution. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and western blotting confirmed the requirement of a terminal GlcNAc for B4GALNT3 activity. B4GALNT3 added a beta 1,4-linked GalNAc to GlcNAc irrespective of whether the latter was carried by a core 2, core 3 or extended core 1 chain. No LDN-mediated adhesion ofH. pyloristrains 26 695 and J99 to LDN determinants on gastric mucins or a mucin-type fusion protein carrying core 2, 3 and extended core 1O-glycans were detected in a microtiter well-based adhesion assay and no binding of a(125)I-labelled LDN-BSA neoglycoconjugate to clinicalH. pyloriisolates was identified.
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28.
  • Ruda, K., et al. (författare)
  • Synthesis of an inositol phosphoglycan fragment found in Leishmania parasites
  • 2000
  • Ingår i: Tetrahedron. - 0040-4020 .- 1464-5416. ; 56:24, s. 3969-3975
  • Tidskriftsartikel (refereegranskat)abstract
    • Synthesis of 1 and 2a is described using a block synthetic strategy. Compound 4 was used as precursor for the two mannose derivatives which, coupled together, forms the dimannoside building block. Thioglycoside 7 was coupled to 8 yielding inositol phosphoglycan 9a, which was selectively deprotected and reacted with 2,3,4,6-tetra-O-benzyl-a-D-glucopyranos-1-yl H- phosphonate to form the protected target molecule 12. Deprotection of 12 by acidic deacetalisation/desilylation and subsequent catalytic hydrogenolysis resulted in cleavage of the anomeric phosphodiester to produce 1. Debenzylation with sodium in liquid ammonia followed by acidic deacetalisation/desilylation gave the target compound 2a. (C) 2000 Published by Elsevier Science Ltd.
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29.
  • Ruda, K., et al. (författare)
  • Synthesis of the Leishmania LPG core heptasaccharyl myo-inositol
  • 2000
  • Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 122:45, s. 11067-11072
  • Tidskriftsartikel (refereegranskat)abstract
    • Total synthesis of the core heptasaccharyl myo-inositol, Galp(a1-6)Galp(a1-3)Galf(ß1-3)[Glcp(a1-PO4-6)Manp](a1-3)Manp(a1-4)GlcN p(a1-6)Ins-1-PO4, and the corresponding hexasaccharyl myo-inositol, Galp(a1-6)Galp(a1-3)Galf(ß1-3)Manp(a1-3)Manp(a1-4)GlcNp(a1-6)Ins-1-PO4 , found in the lipophosphoglycans of Leishmania parasites are described. The target molecules contain synthetic challenges such as an unusual internal galactofuranosyl residue and an anomeric phosphodiester. The synthesis was accomplished using a convergent block synthetic strategy. Four building blocks, a trigalactoside, a dimannoside, a glucosyl inositolphosphate, and a glucosyl-a-1-H-phosphonate, all appropriately protected, were used. The trigalactoside was linked to the dimannoside followed by glycosylation with the glucosyl inositolphosphate to produce the fully protected hexasaccharyl myo-inositol. Subsequent oxidative coupling of the glucosyl-H-phosphonate formed the anomeric phosphodiester linkage to produce the protected heptasaccharyl myo-inositol. Both the assembly order of the subunits and sequence of deprotection were essential for the successful synthesis of these complex molecules. The deprotection was accomplished by deacetylation and clevage of benzyl ethers with sodium in liquid ammonia, followed by acidic deacetalization/desilylation to produce the target molecules.
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31.
  • Smith-Anttila, Casey J. A., et al. (författare)
  • Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1
  • 2017
  • Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 50:4, s. 223-231
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.
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32.
  • Smith, C. J. A., et al. (författare)
  • TSGA10-A Target for Autoantibodies in Autoimmune Polyendocrine Syndrome Type 1 and Systemic Lupus Erythematosus
  • 2011
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 73:2, s. 147-153
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High-titre autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in approximately 7% of APS1 patients, with immunoreactivity to pituitary tissue frequently described. Using APS1 patient serum to immunoscreen a pituitary cDNA expression library, testis specific, 10 (TSGA10) was isolated. Immunoreactivity against TSGA10 was detected in 5/99 (5.05%) patients with APS1, but also in 5/135 (3.70%) systemic lupus erythematosus (SLE) patients and 1/188 (0.53%) healthy controls. TSGA10 autoantibodies were not detected in the serum from patients with any other autoimmune disease. Autoantibodies against TSGA10 were detectable from a young age in 4/5 positive APS1 patients with autoantibody titres remaining relatively constant over time. Furthermore, real-time PCR confirmed TSGA10 mRNA to be most abundantly expressed in the testis and also showed moderate and low expression levels throughout the entire body. TSGA10 should be considered as an autoantigen in a subset of APS1 patients and also in a minority of SLE patients. No recognizable clinical phenotype could be found to correlate with positive autoantibody reactivity.
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33.
  • Soderberg, E, et al. (författare)
  • Rapid carbohydrate protecting group manipulations assisted by microwave dielectric heating
  • 2001
  • Ingår i: JOURNAL OF CARBOHYDRATE CHEMISTRY. - : MARCEL DEKKER INC. - 0732-8303. ; 20:5, s. 397-410
  • Tidskriftsartikel (refereegranskat)abstract
    • The protocols for oligosaccharide synthesis are often tedious due to extended synthetic routes and reaction times. We herein describe methods assisted by microwave dielectric heating, which enable very short reaction times and high yields for the introduc
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34.
  • Suhr, R, et al. (författare)
  • Synthesis of dihydrodiosgenin glycosides as mimetics of bidesmosidic steroidal saponins
  • 2003
  • Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2003:20, s. 4003-4011
  • Tidskriftsartikel (refereegranskat)abstract
    • The focus of this work is the synthesis of bidesmosidic saponin mimetics. Therefore, dihydrodiosgenin derivatives, which differ from the natural compounds by reduction of the 22-(hemi) acetal were used as glycosyl acceptors. In preliminary studies, the dihydrodiosgenin glycosides 16, 17 and 19, as well as trisaccharide 22, were synthesized. The acceptors 10 and 14 were subjected to DMTST-mediated glucosylation for the synthesis of these-substituted compound 3. For a selective 2,4-di-rhamnosylation of the dihydrodiosgenin glucopyranoside, differentiation of the glucose OH groups was achieved by selective benzoylation with 1-(benzoyloxy)benzotriazole. Reaction of the 3,6-di-O-benzoate 32 with the perbenzoylated ethyl thiorhamnopyranoside donor 15 gave the 2,4-di-rhamnosylated compound 33, together with the mono-rhamnosylated derivative. (
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