| 31. |
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| 32. |
- Dweik, Raed A, et al.
(author)
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An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.
- 2011
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In: American journal of respiratory and critical care medicine. - 1535-4970. ; 184:5, s. 602-15
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Journal article (peer-reviewed)abstract
- Measurement of fractional nitric oxide (NO) concentration in exhaled breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While Fe(NO) measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of Fe(NO) in clinical practice.
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| 33. |
- Flowers, Sarah A., et al.
(author)
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Selected Reaction Monitoring to Differentiate and Relatively Quantitate Isomers of Sulfated and Unsulfated Core 1 O-Glycans from Salivary MUC7 Protein in Rheumatoid Arthritis
- 2013
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In: Molecular & Cellular Proteomics. - 1535-9476. ; 12:4, s. 921-931
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis is a common and debilitating systemic inflammatory condition affecting up to 1% of the world's population. This study aimed to investigate the immunological significance of O-glycans in chronic arthritis at a local and systemic level. O-Glycans released from synovial glycoproteins during acute and chronic arthritic conditions were compared and immune-reactive glycans identified. The sulfated core 1 O-glycan (Galβ1–3GalNAcol) was immune reactive, showing a different isomeric profile in the two conditions. From acute reactive arthritis, three isomers could be sequenced, but in patients with chronic rheumatoid arthritis, only a single 3-Gal sulfate-linked isomer could be identified. The systemic significance of this glycan epitope was investigated using the salivary mucin MUC7 in patients with rheumatoid arthritis and normal controls. To analyze this low abundance glycan, a selected reaction monitoring (SRM) method was developed to differentiate and relatively quantitate the core 1 O-glycan and the sulfated core 1 O-glycan Gal- and GalNAc-linked isomers. The acquisition of highly sensitive full scan linear ion trap MS/MS spectra in addition to quantitative SRM data allowed the 3- and 6-linked Gal isomers to be differentiated. The method was used to relatively quantitate the core 1 glycans from MUC7 to identify any systemic changes in this carbohydrate epitope. A statistically significant increase in sulfation was identified in salivary MUC7 from rheumatoid arthritis patients. This suggests a potential role for this epitope in chronic inflammation. This study was able to develop an SRM approach to specifically identify and relatively quantitate sulfated core 1 isomers and the unsulfated structure. The expansion of this method may afford an avenue for the high throughput investigation of O-glycans.
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| 34. |
- Lood, Christian, et al.
(author)
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IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE : a possible new treatment?
- 2012
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:8, s. 2698-2706
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Journal article (peer-reviewed)abstract
- OBJECTIVESystemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) which stimulate leukocytes through FcγRs with subsequent inflammation. Treatment with EndoS, an IgG glycan hydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. In the present study we asked if EndoS could affect pro-inflammatory properties of ICs and have the potential to be developed as a therapy in SLE.METHODSICs, purified from SLE patients or RNA-containing ICs formed in vitro, were treated with EndoS and used in several assays reflecting different important parts of SLE pathogenesis such as phagocytosis by polymorphonuclear neutrophils (PMNs) and plasmacytoid dendritic cells (pDCs), complement activation and IFNα production by pDCs.RESULTSOur results demonstrate that EndoS treatment could abolish all pro-inflammatory properties of ICs investigated. This includes FcγR-mediated phagocytosis by pDCs (p<0.0001) and subsequent production of IFNα (p<0.0001), IC-induced classical complement pathway activation (p<0.0001), chemotaxis and oxidative burst activity of PMNs (p=0.002). We could also demonstrate direct effects on the molecular structure of ICs after EndoS treatment with decreased size and glycosylation patterns.CONCLUSIONSProminent effects of EndoS treatment were seen in several pathogenetically important IC-mediated events and our data suggest that EndoS have the potential to be developed as a novel therapy in SLE.
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| 38. |
- Repapi, Emmanouela, et al.
(author)
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Genome-wide association study identifies five loci associated with lung function.
- 2010
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
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Journal article (peer-reviewed)abstract
- Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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