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Autologous haematopoietic stem-cell transplantation (AHSCT) has been experimented as a treatment in patients affected by severe forms of multiple sclerosis (MS) who failed to respond to standard immunotherapy. The rationale of AHSCT is to 'reboot' the immune system and reconstitute a new adaptive immunity. The aim of our study was to identify, through a robust and unbiased transcriptomic analysis, any changes of gene expression in T-cells potentially underlying the treatment effect in patients who underwent non-myeloablative AHSCT for treatment of MS. We evaluated by microarray DNA-chip technology the gene expression of peripheral CD4+ and CD8+ T-cell subsets sorted from patients with MS patients before AHSCT, at 6 months, 1 year and 2 years after AHSCT and from healthy control subjects. Hierarchical clustering analysis revealed that reconstituted CD8+ T-cells of MS patients at 2 years post-transplantation, aggregated together with healthy controls, suggesting a normalization of gene expression in CD8+ cells post-therapy. When we compared the gene expression in MS patients before and after therapy, we detected a large number of differentially expressed genes (DEG) in both CD8+ and CD4+ T-cell subsets at all time points after transplantation. We catalogued the biological function of DEG and we selected 27 genes known to be involved in immune function for accurate quantification of gene expression by real-time PCR. The analysis confirmed and extended with quantitative data, a number of significant changes in both the CD4+ and CD8+ T-cells subsets from MS post-transplant. Notably, CD8+ T-cells revealed more extensive changes in the expression of genes involved in effector immune responses. [ABSTRACT FROM AUTHOR]

Among Amazonian communities, exposure to methylmercury is associated mainly with fish consumption that may affect fetal development in pregnant women. Therefore a temporal assessment was performed to assess the exposure of reproductive aged women to mercury who reside in the riparian communities of São Luís do Tapajós and Barreiras located in the Tapajós basin of the Brazilian Amazon from 1999 to 2012. The total mercury concentration in the 519 hair samples was assessed by cold vapor atomic absorption spectrometry. Data analysis showed that the average total mercury concentration decreased from 1.066 to 0.743 μg/g in those years. In 1999 the proportion of volunteers with mercury levels ≥10 μg/g was approximately 68 %. In general, exposure to mercury decreased among women of reproductive age, but the potential risks to reproduction and human health is still an issue as 22 % of the woman continued showing high mercury levels (≥10 μg/g) in 2012. [ABSTRACT FROM AUTHOR]

TP73 encodes for two proteins: full-length TAp73 and ΔNp73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TA TP73 and ΔN TP73 expression in acute myeloid leukaemia (AML) samples and normal CD34+ progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TA TP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB- MYH11, whereas higher ΔN TP73 expression was detected in non-RGA cases. TP53 expression did not vary according to ΔN TP73/TA TP73 expression ratio. Leukaemic cells with higher ΔN TP73/TA TP73 ratios were significantly more resistant to cytarabine-induced apoptosis. [ABSTRACT FROM AUTHOR]

Introdução: Atualmente, a fibrolaringoscopia flexível é considerada um método de primeira escolha no exame otorrinolaringológico, principalmente na avaliação da funcionalidade laríngea. Objetivo: O objetivo do estudo é descrever a prevalência de alterações laríngeas, observadas no serviço de endoscopia respiratória alta da Universidade, correlacionado-as com a idade e sexo dos pacientes. Método: Realizamos um estudo retrospectivo abordando prontuários de duzentos e quatorze pacientes do Ambulatório de Endoscopia Respiratória Alta atendidos num período de 18 meses. Os resultados foram avaliados no programa SPSS, versão 10.0, sendo realizadas freqüências, medidas de tendência central e desvio-padrão e teste de associação (qui-quadrado). Resultados: Dos 214 pacientes analisados, 21% (n=45) sinais sugestivos de doença do refluxo gastroesofágico (DRGE) e 7,5% (n=16) sinais sugestivos de câncer de laringe (onde 7 foram confirmados), sendo os restantes 71,5 % (n=153) considerados normais. Dos 45 pacientes que apresentaram DRGE, a freqüência foi maior no sexo feminino, predominando na faixa etária superior a 43 anos. Dos sete pacientes que tiveram câncer de laringe confirmado, todos os casos foram no sexo masculino e na faixa etária superior a 43 anos. Conclusão: O câncer de laringe foi claramente mais prevalente em homens. Com relação aos pacientes com sinais sugestivos de DRGE, não se observou diferença significativa de prevalência entre os sexos.

Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. [ABSTRACT FROM AUTHOR]

Recent evidence has shown that deregulated expression of members of the microRNA-29 (miR-29) family may play a critical role in human cancer, including hematological malignancies. However, the roles of miR-29 in the molecular pathophysiology of T-cell acute lymphoblastic leukemia (T-ALL) has not been investigated. Here, we show that lower levels of miR-29a were significantly associated with higher blast counts in the bone marrow and with increased disease-free survival in T-ALL patients. Furthermore, miR-29a levels are extremely reduced in T-ALL cells compared to normal T cells. Microarray analysis following introduction of synthetic miR-29a mimics into Jurkat cells revealed the downregulation of several predicted targets (CDK6, PXDN, MCL1, PIK3R1, and CXXC6), including targets with roles in active and passive DNA demethylation (such as DNMT3a, DNMT3b, and members of the TET family and TDG). Restoring miR-29a levels in Jurkat and Molt-4 T-ALL cells led to the demethylation of many genes commonly methylated in T-ALL. Overall, our results suggest that reduced miR-29a levels may contribute to the altered epigenetic status of T-ALL, highlighting its relevance in the physiopathology of this disease., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

This study evaluated current levels of mercury exposure and sensory symptoms in adults from three riverine communities in Pará State, Brazil, two of which located in the Tapajós River basin and one in the Tocantins basin. Participants in this study included 78 residents in Barreiras (Tapajós), 30 in São Luiz do Tapajós (Tapajós), and 49 in Furo do Maracujá (Tocantins). Total hair mercury concentrations were quantified by atomic absorption spectrophotometry, and neurological evaluation was conducted by routine examination. Mercury concentrations in the Tapajós communities were higher than those in the Tocantins (p < 0.01). Evaluation of neurological changes showed no significant difference between the communities in exposed areas and control areas for the changes observed by conventional neurological examination, except for gait deviation (p < 0.05). The study concludes that despite the mercury exposure levels, there was a low frequency of sensory alterations according to conventional neurological testing.

TP73 encodes for two proteins: full-length TAp73 and DeltaNp73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and DeltaNTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TATP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11, whereas higher DeltaNTP73 expression was detected in non-RGA cases. TP53 expression did not vary according to DeltaNTP73/TATP73 expression ratio. Leukaemic cells with higher DeltaNTP73/TATP73 ratios were significantly more resistant to cytarabine-induced apoptosis.