Vaccines based on adenovirus (Ad) vectors are currently in development against several pathogens. However, neutralizing antibodies (NAb) to human adenovirus type 5 (AdHu5), the best-studied vector, are highly prevalent in humans worldwide. Less-prevalent adenoviruses, including human and simian serotypes, provide alternative vaccine platforms. In this study, sera from 200 Brazilian human subjects and New-World monkeys were tested for NAb titers to human serotypes AdHu5 and AdHu26 and chimpanzee-origin Ad viruses of serotype 6 (AdC6) and serotype 68 (AdC68). Seroprevalence rates of NAb in humans were 69.5% for AdHu5, 44% for AdHu26, 21% for AdC6 and 23.5% for AdC68. In addition, NAb titers to human Ad were consistently higher than those found to simian serotypes. Surprisingly, sera from some New-World monkey species were able to neutralize AdC6 and/or AdC68. A possible explanation for these findings and the implications for the development of Ad-vector vaccines are discussed in detail.
During a survey of typical, dominant hereditary spherocytosis (HS) patients, we identified a frameshift mutation of the ankyrin gene in three unrelated probands. All three probands, who were from different ethnic backgrounds, suffered from severe HS requiring splenectomy. Analysis of both intragenic and flanking polymorphisms revealed that these probands did not share a common ankyrin allele, providing evidence that these mutations arose independently on separate chromosomal backgrounds. This frameshift mutation associated with severe HS, Ankyrin Florianópolis, is the first description of a recurrent mutation in the ankyrin gene.
Summary. During a survey of typical, dominant hereditary spherocytosis (HS) patients, we identified a frameshift mutation of the ankyrin gene in three unrelated probands. All three probands, who were from different ethnic backgrounds, suffered from severe HS requiring splenectomy. Analysis of both intragenic and flanking polymorphisms revealed that these probands did not share a common ankyrin allele, providing evidence that these mutations arose independently on separate chromosomal backgrounds. This frameshift mutation associated with severe HS, Ankyrin Floriano Âpolis, is the first description of a recurrent mutation in the ankyrin gene.
Introduction: Despite the great advances in serological testing for transfusion-transmitted infections, the selection of blood donors by blood bank operators remains the only way to avoid transmission within the testing window period. Part of this selection is the self-exclusion form, on which the donors can exclude their blood from donation without any explanation. This study assessed the clinical and epidemiological characteristics related to positivity for viral hepatitis and to the use of the confi dential self-exclusion (CSE) form. Methods: This transversal study analyzed the data collected from blood donors' fi les in a hospital in Southern Brazil. Univariate and multivariate analyses identifi ed the clinical and epidemiological variables related to positive serologies of viral hepatitis and to whether the donor was self-excluded. Results: Of the 3,180 donors included in this study, 0.1% tested positive for HBsAg, 2.1% for anti-HBc, and 0.9% for anti-HCV. When the 93 donors with positive serologies for viral hepatitis were compared with those who were negative, a greater proportion of the positive serology group was found to have had a history of blood transfusions (OR=4.908; 95%CI=1.628 -14.799; p<0.01), had repeatedly donated (OR=2.147; 95%CI=1.236 -3.729; p<0.01), and used the CSE form for self-exclusion (OR=7.139; 95%CI=2.045 -24.923; p<0.01). No variables were independently associated with self-exclusion. Conclusions: A history of blood transfusion, repeated donations, and self-exclusion are factors that should be considered during viral hepatitis screenings in blood banks.
Background: Hepcidin is the principal regulator of iron absorption and its tissue distribution. Its correlation with iron homeostasis in individuals infected with human immunodeficiency virus type-1 (HIV-1) treated with different regimens of highly active antiretroviral therapy (HAART) was investigated. Methods: Serum hepcidin levels were determined in 448 volunteers. Of these, 372 were HIV-1-infected individuals, and 93 did not receive HAART (ART-naïve) while 279 received HAART consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI-based) and protease inhibitors (PI-based); both were used in association with a nucleoside reverse transcriptase inhibitor (NRTI). Seventy-six additional HIV-1 seronegative individuals were enrolled in the study. The following parameters were quantified: hematological parameters, iron biomarkers and markers of infection (CD4 + and CD8 + T-cells), and HIV-1 RNA (viral load). Results: Serum hepcidin, iron and ferritin levels, as well as the marker of infection, CD4 + T-cells, were significantly lower in the ART-naïve group compared with other groups. Additionally, transferrin saturation, iron binding capacity, hemoglobin level and erythrocyte level were not significantly different, and anemia was not observed in the different groups. Conclusions: HIV-1 infection affected serum hepcidin, iron and ferritin levels in the ART-naïve group, and the different HAART regimens restored the levels of hepcidin and iron homeostasis in HIV-1-infected individuals who have unde
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