يعرض 1 - 10 نتائج من 22 نتيجة بحث عن '"James C. Vary"', وقت الاستعلام: 1.05s تنقيح النتائج
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    دورية أكاديمية

    المصدر: PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3263 (2014)

    الوصف: Leprosy is characterized by polar clinical, histologic and immunological presentations. Previous immunologic studies of leprosy polarity were limited by the repertoire of cytokines known at the time.We used a candidate gene approach to measure mRNA levels in skin biopsies from leprosy lesions. mRNA from 24 chemokines and cytokines, and 6 immune cell type markers were measured from 85 Nepalese leprosy subjects. Selected findings were confirmed with immunohistochemistry.Expression of three soluble mediators (CCL18, CCL17 and IL-10) and one macrophage cell type marker (CD14) was significantly elevated in lepromatous (CCL18, IL-10 and CD14) or tuberculoid (CCL17) lesions. Higher CCL18 protein expression by immunohistochemistry and a trend in increased serum CCL18 in lepromatous lesions was observed. No cytokines were associated with erythema nodosum leprosum or Type I reversal reaction following multiple comparison correction. Hierarchical clustering suggested that CCL18 was correlated with cell markers CD209 and CD14, while neither CCL17 nor CCL18 were highly correlated with classical TH1 and TH2 cytokines.Our findings suggest that CCL17 and CCL18 dermal expression is associated with leprosy polarity.

    وصف الملف: electronic resource

  2. 2
    دورية أكاديمية
  3. 3
    دورية أكاديمية

    المساهمون: The Pennsylvania State University CiteSeerX Archives

    الوصف: This article cites 17 articles, 9 of which can be accessed free at

    وصف الملف: application/pdf

  4. 4
    دورية أكاديمية

    المساهمون: The Pennsylvania State University CiteSeerX Archives

    الوصف: Role of the Escherichia coli O157:H7 O side chain in adherence and analysis of an rfb locus.

    وصف الملف: application/pdf

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    المصدر: The Journal of infectious diseases. 213(7)

    الوصف: Leprosy is a chronic disease characterized by skin and peripheral nerve pathology and immune responses that fail to control Mycobacterium leprae. Toll-interacting protein (TOLLIP) regulates Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) signaling against mycobacteria. We analyzed messenger RNA (mRNA) expression of candidate immune genes in skin biopsy specimens from 85 individuals with leprosy. TOLLIP mRNA was highly and specifically correlated with IL-1R antagonist (IL-1Ra). In a case-control gene-association study with 477 cases and 1021 controls in Nepal, TOLLIP single-nucleotide polymorphism rs3793964 TT genotype was associated with increased susceptibility to leprosy (recessive, P = 1.4 × 10(-3)) and with increased skin expression of TOLLIP and IL-1Ra. Stimulation of TOLLIP-deficient monocytes with M. leprae produced significantly less IL-1Ra (P < .001), compared with control. These data suggest that M. leprae upregulates IL-1Ra by a TOLLIP-dependent mechanism. Inhibition of TOLLIP may decrease an individual's susceptibility to leprosy and offer a novel therapeutic target for IL-1-dependent diseases.

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    المصدر: Microbiology and Molecular Biology Reviews. 74:589-620

    الوصف: SUMMARY Despite the availability of effective treatment for several decades, leprosy remains an important medical problem in many regions of the world. Infection with Mycobacterium leprae can produce paucibacillary disease, characterized by well-formed granulomas and a Th1 T-cell response, or multibacillary disease, characterized by poorly organized cellular infiltrates and Th2 cytokines. These diametric immune responses confer states of relative resistance or susceptibility to leprosy, respectively, and have well-defined clinical manifestations. As a result, leprosy provides a unique opportunity to dissect the genetic basis of human in vivo immunity. A series of studies over the past 40 years suggests that host genes influence the risk of leprosy acquisition and the predilection for different clinical forms of the disease. However, a comprehensive, cellular, and molecular view of the genes and variants involved is still being assembled. In this article, we review several decades of human genetic studies of leprosy, including a number of recent investigations. We emphasize genetic analyses that are validated by the replication of the same phenotype in independent studies or supported by functional experiments demonstrating biological mechanisms of action for specific polymorphisms. Identifying and functionally exploring the genetic and immunological factors that underlie human susceptibility to leprosy have yielded important insights into M. leprae pathogenesis and are likely to advance our understanding of the immune response to other pathogenic mycobacteria. This knowledge may inform new treatment or vaccine strategies for leprosy or tuberculosis.

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    المصدر: Infection and Immunity. 68:3040-3047

    الوصف: Two novel putative Escherichia coli virulence genes, iha and iroN from E. coli ( iroN E. coli ), were detected in 55 and 39%, respectively, of 67 E. coli isolates from patients with urosepsis. iha and iroN E. coli exhibited divergent associations with other putative virulence genes, phylogenetic markers, host characteristics, and antimicrobial resistance.

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    المصدر: Infection and Immunity. 64:4795-4801

    الوصف: Shiga-toxigenic Escherichia coli strains belonging to serotype O157 are important human pathogens, but the genetic basis of expression of the O157 antigen and the role played by the lipopolysaccharide O side chain in the adherence of this organism to epithelial cells are not understood. We performed TnphoA mutagenesis on E. coli O157:H7 strain 86-24 to identify a mutant (strain F12) deficient in O-antigen expression. Nucleotide sequence analysis demonstrated that the transposon inserted within an open reading frame with significant homology to rfbE of Vibrio cholerae O1 (U. H. Stroeher, L. E. Karageorgos, R. Morona, and P. A. Manning, Proc. Natl. Acad. Sci. USA 89:2566-2570, 1992), which is postulated to encode perosamine synthetase. This open reading frame was designated rfbE(EcO157:H7). The guanine-plus-cytosine fraction (0.35) suggests that rfbE(EcO157:H7) may have originated in a species other than E. coli. rfbE(EcO157:H7) is conserved in nontoxigenic E. coli O157 strains expressing a variety of other flagellar antigens but is not found in E. coli O55:H7 strains, which are more closely related to E. coli O157:H7. Strain F12 was significantly more adherent to HeLa cells in a quantitative adherence assay than was its E. coli O157:H7 parent, but they did not differ in other phenotypes. Restoration of the expression of the O side chain by complementation of the TnphoA mutation in strain F12 by a plasmid expressing intact rfbE(EcO157:H7) reduced the adherence of the hyperadherent strain F12. We conclude that rfbE(EcO157:H7) is necessary for the expression of the O157 antigen, that acquisition of E. coli rfb genes occurred independently in E. coli O157:H7 and unrelated O157 strains, and that the O side chain of E. coli O157:H7 lipopolysaccharide interferes with the adherence of E. coli O157:H7 to epithelial cells.

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    المصدر: PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3263 (2014)
    PLoS Neglected Tropical Diseases, 8(11)
    PLoS Neglected Tropical Diseases

    الوصف: Background Leprosy is characterized by polar clinical, histologic and immunological presentations. Previous immunologic studies of leprosy polarity were limited by the repertoire of cytokines known at the time. Methodology We used a candidate gene approach to measure mRNA levels in skin biopsies from leprosy lesions. mRNA from 24 chemokines and cytokines, and 6 immune cell type markers were measured from 85 Nepalese leprosy subjects. Selected findings were confirmed with immunohistochemistry. Principal Results Expression of three soluble mediators (CCL18, CCL17 and IL-10) and one macrophage cell type marker (CD14) was significantly elevated in lepromatous (CCL18, IL-10 and CD14) or tuberculoid (CCL17) lesions. Higher CCL18 protein expression by immunohistochemistry and a trend in increased serum CCL18 in lepromatous lesions was observed. No cytokines were associated with erythema nodosum leprosum or Type I reversal reaction following multiple comparison correction. Hierarchical clustering suggested that CCL18 was correlated with cell markers CD209 and CD14, while neither CCL17 nor CCL18 were highly correlated with classical TH1 and TH2 cytokines. Conclusions Our findings suggest that CCL17 and CCL18 dermal expression is associated with leprosy polarity.
    Author Summary Leprosy presents with a polarized spectrum, with lepromatous leprosy having high bacillary numbers and TH2 dermal cytokines, versus tuberculoid leprosy showing very few bacilli and TH1 cytokines. The mechanism underlying this polarized presentation is largely unknown. In the following study, we isolated mRNA from skin biopsies from 85 individuals with leprosy and measured the expression of a panel of 24 cytokines and 6 cell markers. We found that three soluble mediators (CCL17, CCL18 and IL10) and one cell marker (CD14) were differentially expressed in leprosy dermal lesions. CCL18 and IL10 were more highly expressed within lepromatous lesions, and CCL17 and CD14 were more highly expressed within tuberculoid lesions. In addition, CCL18 protein expression was confirmed by immunostaining. CCL17 and CCL18, were more strongly associated with leprosy polarity than traditional TH1 and TH2 cytokines. These data suggest that newer soluble chemokines may be important in leprosy pathogenesis and uncover a molecular signature of the two polar phenotypes of leprosy, which may be useful in future diagnostics.