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Wyświetlanie 1-10 z 17
Tytuł:
IL-17high asthma with features of a psoriasis immunophenotype
Autorzy:
Pandis, Ioannis
Sousa, Ana R.
Sanak, Marek
Howarth, Peter
Horvath, Ildiko
Krug, Norbert
Montuschi, Paolo
Sandstrom, Thomas
Bakke, Per S.
Djukanovic, Ratko
Bigler, Jeanette
Auffray, Charles
Östling, Jörgen
Sterk, Peter J.
Guo, Yike
Schofield, James P. R.
Fowler, Stephen J.
Shaw, Dominick E.
Jevnikar, Zala
Sun, Kai
Dahlen, Sven-Erik
Caruso, Massimo
Vaarala, Outi
Lutter, Rene
Ward, Jonathan
van Geest, Marleen
Wilson, Susan
Skipp, Paul J.
Chung, Kian Fan
Adcock, Ian M.
Opis:
Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n 5 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and b-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
Autorzy:
Bates, Stewart
Maitland-van der Zee, Anke-Hilse
Dahlén, Sven-Erik
Yasinska, Valentyna
Gómez, Cristina
Kolmert, Johan
Behndig, Annelie
Geiser, Thomas
James, Anna
Djukanovic, Ratko
Bakke, Per S.
Knowles, Richard G.
Riley, John H.
Sousa, Ana R.
Montuschi, Paolo
Chanez, Pascal
Sanak, Marek
Chung, Kian Fan
Krug, Norbert
Kermani, Nazanin Zounemat
Caruso, Massimo
Shaw, Dominick E.
Sparreman-Mikus, Maria
Adcock, Ian M.
Dahlén, Barbro
Andersson, Lars I.
Sterk, Peter J.
Pohanka, Anton
Ericsson, Magnus
Wikström Jonsson, Eva
Horváth, Ildikó
Wheelock, Craig E.
Howarth, Peter H.
Fowler, Stephen J.
Opis:
Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Tytuł:
Stratification of asthma phenotypes by airway proteomic signatures
Autorzy:
Nicholas, Ben
Lefaudeux, Diane
Horvath, Ildiko
Riley, John
Dahlen, Sven-Erik
Sun, Kai
Sandstrom, Thomas
Bakke, Per S.
Bansal, Aruna T.
Djukanovic, Ratko
Sousa, Ana R.
Montuschi, Paolo
Sanak, Marek
Chung, Kian Fan
Lutter, Rene
Krug, Norbert
Auffray, Charles
Caruso, Massimo
Xian, Yang
Staykova, Doroteya
Shaw, Dominick E.
Pandis, Ioannis
Corfield, Julie
De Meulder, Bertrand
Folisi, Caterina
Howarth, Peter
Adcock, Ian M.
Rowe, Anthony
Sterk, Peter J.
Wilson, Susan
Guo, Yike
Burg, Dominic
Skipp, Paul J.
Strazzeri, Fabio
Ward, Jonathan
Brandsma, Joost
Schofield, James P.R.
Fowler, Stephen J.
Opis:
neutrophils
proteomics
biomarkers
asthma
Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
eosinophils
Dostawca treści:
Repozytorium Uniwersytetu Jagiellońskiego
Artykuł
Wyświetlanie 1-10 z 17

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