| 1. |
- Brown, Kelly, 1973, et al.
(författare)
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Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome.
- 2010
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Ingår i: BMC pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: This study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease. METHODS: A cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA. RESULTS: Oscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods. CONCLUSIONS: Identification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.
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| 2. |
- Salomonsson, Emma, et al.
(författare)
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Mutational tuning of galectin-3 specificity and biological function.
- 2010
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 285, s. 35079-35091
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are defined by a conserved beta-galactoside binding site, which has been linked to many of their important functions in e.g. cell adhesion, signaling and intracellular trafficking. Weak adjacent sites may enhance or decrease affinity for natural beta-galactoside containing glycoconjugates, but little is known about the biological role of this modulation of affinity (fine specificity). We have now produced 10 mutants of human galectin-3, with changes in these adjacent sites, which have altered carbohydrate-binding fine specificity but which retain the basic beta-galactoside binding activity as show by glycan-array binding and a solution-based fluorescence anisotropy assay. Each mutant was also tested in two biological assays to provide a correlation between fine specificity and function. Galectin-3 R186S, which has selectively lost affinity for LacNAc, a disaccharide moiety commonly found on glycoprotein glycans, has lost the ability to activate neutrophil leukocytes and intracellular targeting into vesicles. K176L has increased affinity for beta-galactosides substituted with GlcNAcbeta1-3 as found in poly-N-acetyllactosaminoglycans, and increased potency to activate neutrophil leukocytes, even though it has lost other aspects of galectin-3 fine specificity. G182A has altered carbohydrate-binding fine specificity and altered intracellular targeting into vesicles, a possible link to the intracellular galectin-3-mediated anti-apoptotic effect known to be lost by this mutant. Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse and human galectin-3 and as such, evidence for adaptive change during evolution.
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