National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Asthma & T cell. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Th2 response polarization during infection with the helminth parasite Schistosoma mansoni.

Abstract: Summary: T-helper 2 (Th2) cell responses play a critical role in protection against helminth infections. In the case of Schistosoma mansoni, an important helminth parasite of man, data from a mouse model of human disease have shown that Th2 responses are essential to allow host survival. In this infection, parasite eggs are the primary stimulus for Th2 response development. Recent work has shown that egg molecules exert multiple levels of control over the development of host interferon-γ-associated inflammatory responses. Soluble egg antigen inhibits the ability of dendritic cells to make interleukin-12 and induces Th2-polarized adaptive immune responses that in combination with regulatory T-cell responses effectively limit Th1 response development. In this article, we discuss the factors influencing Th2 response polarization during infection with S. mansoni.

Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis

Abstract: OBJECTIF: Evaluer l'activite bactericide precoce (EBA) des nouvelles fluoroquinolones (levofloxacine, gatifloxacine et moxifloxacine) chez les patients atteints de tuberculose pulmonaire (TBP). SCHEMA : Essai ouvert randomise. Quarante adultes atteints d'une TBP recemment diagnostiquee et a bacilloscopie positive ont ete attribues a raison de 10 par bras soit a l'isoniazide (INH) 300 mg, soit a la levofloxacine 1000 mg, a la gatifloxacine 400 mg ou a la moxifloxacine 400 mg par jour pendant 7 jours. On a recueilli des expectorations pour culture quantitative pendant 2 jours avant la mise en route de la monotherapie et chaque jour au cours des 7 jours de monotherapie. L'activite bactericide a ete estimee en mesurant la diminution du nombre de bacilles au cours des 2 premiers jours (EBA 0-2) et au cours des 5 derniers jours de la monotherapie (EBA prolongee, EBA 2-7). Le personnel du laboratoire ignorait le traitement attribue. RESULTATS: L'EBA 0-2 de l'INH (0.67 log 10 cfu/ml/ jour) est plus elevee que celle de la moxifloxacine (0.33 log 10 cfu/ml/jour) et de la gatifloxacine (0.35 log 10 cfu/ ml/jour), mais pas que celle de la levofloxacine a 1000 mg par jour (0.45 log 10 cfu/ml/jour) (P = 0.14). L'activite bactericide entre les jours 2 et 7 est similaire pour les trois fluoroquinolones. Dans une comparaison combinant les fluoroquinolones, l'EBA 2-7est superieure a celle de l'INH. CONCLUSION: La moxifloxacine, la gatifloxacine et les fortes doses de levofloxacine ont d'excellentes EBA qui ne sont que legerement inferieures a l'INH et elles ont une EBA prolongee plus importante. Ces medicaments meritent des etudes complementaires dans le traitement de la TB a germes sensibles.

Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity.

Abstract: Here, we disrupted the p70 S6 kinase (p70(s6k)) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70(s6k-/-) cells proliferated at a slower rate than parental cells, suggesting that p70(s6k) has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70(s6k-/-) cells, indicating that other events inhibited by the drug, independent of p70(s6k), also are important for both cell proliferation and the action of rapamycin. In p70(s6k-/-) cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70(s6k-/-) cells, indicating that these events proceed independently of p70(s6k) activity. This study localizes the function of p70(s6k) to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.

Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis

Abstract: Background Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disease with a median survival of only 3–5 years that is diagnosed using a combination of clinical, radiographic and pathologic criteria. Histologically, IPF is characterised by usual interstitial pneumonia (UIP), a fibrosing interstitial pneumonia with a pattern of heterogeneous, subpleural regions of fibrotic and remodelled lung. We hypothesised that gene expression profiles of lung tissue may identify molecular subtypes of disease that could classify subtypes of IPF/UIP that have clinical implications. Methods and findings We collected transcriptional profiles on lung tissue from 119 patients with IPF/UIP and 50 non-diseased controls. Differential expression of individual transcripts was identified using an analysis of covariance (ANCOVA) model incorporating the clinical diagnosis of each patient as well as age, gender and smoking status. Validation was performed in an independent cohort of 111 IPF/UIP and 39 non-diseased controls. Our analysis identified two subtypes of IPF/UIP based on a strong molecular signature associated with expression of genes previously associated with fibrosis (matrix metalloproteinases, osteopontin, keratins), cilium genes and genes with unknown function. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing and higher expression of both the airway mucin gene MUC5B and the metalloproteinase MMP7, a gene recently implicated in attenuating ciliated cell differentiation during wound repair. Conclusions Expression of cilium genes appears to identify two unique molecular phenotypes of IPF/UIP. The different molecular profiles may be relevant to therapeutic responsiveness in patients with IPF/UIP.

IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

Abstract: Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10−/−) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.