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Vergara C.,Johns Hopkins University | Murray T.,Johns Hopkins University | Rafaels N.,Johns Hopkins University | Lewis R.,Johns Hopkins University | And 18 more authors.
Genetic Epidemiology | Year: 2013

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels. © 2013 Wiley Periodicals, Inc. Source

Cruz A.O.,Hospital Universitario Professor Edgard Santos | Santana A.L.S.,Federal University of Bahia | Santos A.C.,Federal University of Bahia | Athanazio D.A.,Federal University of Bahia
Jornal Brasileiro de Patologia e Medicina Laboratorial | Year: 2016

Introduction and objectives: We evaluated the sensitivity and specificity of morphological criteria for the diagnosis of prostate adenocarcinoma in consecutive, prostate needle biopsies specimens with emphasis on the location and number of nucleoli. Methods: The morphological features of 387 consecutive prostate needle biopsies specimens, in 2013, were systematically examined and stratified according to the final diagnosis of benign, suspicious and malignant lesions. We also tested how well each criterion predicted the final diagnosis after the immunohistochemical evaluation for expression of the basal cell markers (p63 and high molecular weight cytokeratin) and racemase. Results: A prominent nucleoli is the most common feature of carcinoma; however it is also relatively common in benign cases. The frequencies of prominent central nucleoli in malignant, suspicious and benign cases were 99%, 89% and 27%, respectively. Marginated nucleoli (85%, 60% and 7%), double nucleoli (86%, 53% and 10%), and multiple nucleoli (47%, 14% and 2%) were less common in benign cases, with significant difference among the groups. From the 36 cases initially diagnosed as suspicious, the presence of marginated nucleoli and mitoses were associated with the final diagnosis of malignancy. Prominent central nucleoli were more associated with cases which the final diagnosis after immunohistochemistry was benign. Conclusion: The location and number of nucleoli may be valuable morphological markers to identify suspicious lesions, since these features are more specific for malignancy than nucleolar prominence. The presence of prominent nucleoli commonly leads to the initial diagnosis of suspicious lesion that, subsequently, will be resulted in benignity confirmed by immunohistochemistry. © 2016, Sociedade Brasileira de Pneumologia e Tisiologia. All rights reserved. Source

Bastos M.D.L.,Federal University of Bahia | Santos S.B.,Federal University of Bahia | Souza A.,Federal University of Bahia | Finkmoore B.,University of California at Berkeley | And 10 more authors.
BMC Infectious Diseases | Year: 2012

Background: HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis.Methods: The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups.Results: There were no differences in the demographic, clinical and TST response between the two study groups. IFN-γ and TNF-α production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-γ production in PPD stimulated cultures, TNF-α levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients.Conclusion: While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-α production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth. © 2012 Bastos et al.; licensee BioMed Central Ltd. Source

Pitanga T.N.,Federal University of Bahia | Nascimento V.M.L.,Fundacao de Hematologia e Hemoterapia da Bahia HEMOBA | Carvalho M.O.S.,Hospital Universitario Professor Edgard Santos | Goncalves M.S.,Federal University of Bahia
Cytokine | Year: 2016

This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll-like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3 (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC). TLR and NLRP3 inflammasome could contribute to the maintenance of the inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as danger signals activating these pathways. In this study, first, we evaluated TLR (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 expression in PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from healthy individuals (AA-PBMC). In the second moment, we investigated whether SS-RBC could interfere with the expression of these molecules in PBMC from healthy donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3 inflammasome expression were investigated by qPCR. IL-1β, Leukotriene-B4 (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1β were highly expressed in SS-PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase-1, IL-1β and IL-18 expression and induced IL-1β, LTB4 and nitrite production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome expression, but increased TLR2 and IL-18 expression and reduced nitrite production. In conclusion, our data suggest that TLR and inflammasome complexes may be key inducers of inflammation in SCA patients, probably through SS-RBC; also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation, indicating the need to develop new therapeutic strategies to SCA patients that act with different mechanisms of those observed for HU. © 2016 Elsevier Ltd. Source

Grant A.V.,Johns Hopkins University | Araujo M.I.,Hospital Universitario Professor Edgard Santos | Ponte E.V.,Federal University of Bahia | Oliveira R.R.,Hospital Universitario Professor Edgard Santos | And 5 more authors.
PLoS ONE | Year: 2012

Background: IL-13 is a signature cytokine of the helper T cell type 2 (TH2) pathway which underlies host defense to helminthic infection and activates production of IgE in both parasitized populations and in urban settings after allergen exposure. Methodology/Principal Findings: Two functional polymorphisms in IL13, rs1800925 (or c.1-1111C>T) and rs20541 (or R130Q) were previously found to be associated with Schistosoma hematobium infection intensity. They have not been thoroughly explored in S. mansoni-endemic populations, however, and were selected along with 5 tagging SNPs for genotyping in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area of Conde, Bahia, in Brazil. Regression models using GEE to account for family membership and family-based quantitative transmission disequilibrium tests (QTDT) were used to evaluate associations with total serum IgE (tIgE) levels and S. mansoni fecal egg counts adjusted for non-genetic covariates. We identified a protective effect for the T allele at rs20541 (P = 0.005) against high S. mansoni egg counts, corroborated by QTDT (P = 0.014). Our findings also suggested evidence for protective effects for the T allele at rs1800925 and A allele at rs2066960 after GEE analysis only (P = 0.050, 0.0002). Conclusions/Significance: The two functional variants in IL13 are protective against high S. mansoni egg counts. These markers showed no evidence of association with tIgE levels, unlike tIgE levels previously studied in non-parasitized or atopic study populations. © 2012 Grant et al. Source

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