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  • 1
    Online Resource
    Online Resource
    Increased proteolytic activity and matrix metalloprotease expression in lungs during infection by porcine reproductive and respiratory syndrome virus
    Microbiology Society ; 2001
    In:  Journal of General Virology Vol. 82, No. 6 ( 2001-06-01), p. 1253-1261
    Details
    In: Journal of General Virology, Microbiology Society, Vol. 82, No. 6 ( 2001-06-01), p. 1253-1261
    Abstract: The local increase in the secretion of extracellular proteases, allowing cleavage of the extracellular matrix and thereby facilitating the infiltration of T cells, monocytes and neutrophils, is a hallmark of chronic inflammation and autoimmunity. In pulmonary genetic diseases, such as emphysema and cystic fibrosis, proteases can also favour the development of local immunodeficiency by degrading key regulators of the immune response, such as CD4, CD8, IgG, ICAM-1 and C3b receptors. Since several infectious agents can give rise to severe pulmonary disorders associated with opportunistic infections, we sought to determine whether an increase in proteolytic activity occurred during infection with porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of a new disease in swine characterized by severe respiratory problems in young pigs. Piglets were infected with the virus and bronchoalveolar lavages were collected at various times post-infection to measure the net proteolytic activity. It was shown that PRRSV infection leads to a significant increase in proteolytic activity in pulmonary fluids. Maximal activity was found at 7 and 14 days post-infection, with a return towards normal levels at day 42. Zymographic analyses showed a significant increase in the secretion of matrix metalloproteases (MMPs) 2 and 9, two enzymes involved in tissue remodelling. Histological analyses showed a correlation between the increase in proteolytic activity and the appearance of lesions that were characterized by massive lymphomononuclear cell infiltration. These results suggest that virus infection of the lungs can lead to a transient increase in proteolytic activity that could favour opportunistic infection.
    Type of Medium: Online Resource
    ISSN: 0022-1317 , 1465-2099
    URL: Article
    DOI: 10.1099/0022-1317-82-6-1253
    RVK:
    XA 53770
    RVK:
    WA 15000
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2001
    detail.hit.zdb_id: 2007065-2
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease
    Proceedings of the National Academy of Sciences ; 2005
    In:  Proceedings of the National Academy of Sciences Vol. 102, No. 34 ( 2005-08-23), p. 12183-12188
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 34 ( 2005-08-23), p. 12183-12188
    Abstract: Relatively little is known about the human genetics of susceptibility to common diseases caused by bacterial pathogens. Tuberculosis, caused by Mycobacterium tuberculosis , is a major cause of morbidity and mortality worldwide. So far, genetic studies of tuberculosis susceptibility have largely been focused on adult patients despite the fact that tuberculosis is highly prevalent among children. To study the host genetic component of pediatric tuberculosis susceptibility, we enrolled 184 ethnically diverse families from the Greater Houston area with at least one child affected by pediatric tuberculosis disease. Using a family-based control design, we found allelic variants of the natural resistance-associated macrophage protein gene 1 ( NRAMP1 ) (alias SLC11A1 ) significantly associated with tuberculosis disease in this pediatric patient population [ P = 0.01; odds ratio = 1.75 (95% confidence interval, 1.10-2.77)]. The association of NRAMP1 with pediatric tuberculosis disease was significantly heterogeneous ( P = 0.01) between simplex [ P 〈 0.0008; odds ratio = 3.13 (1.54-6.25)] and multiplex families ( P = 1), suggesting an interplay between mechanisms of genetic control and exposure intensities. In striking contrast to previous studies in the adult population, we observed that the common alleles of NRAMP1 polymorphisms were risk factors for pediatric tuberculosis disease. To explain the different direction of allelic association between adult and pediatric disease, we hypothesize that NRAMP1 influences the speed of progression from infection to tuberculosis disease.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0503368102
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2005
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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