RESUMEN
Mycobacterium abscessus complex has been characterized in the last decade as part of a cluster of mycobacteria that evolved from an opportunistic to true human pathogen; however, the factors responsible for pathogenicity are still undefined. It appears that the success of mycobacterial infection is intrinsically related with the capacity of the bacteria to regulate intracellular iron levels, mostly using iron storage proteins. This study evaluated two potential M. abscessus subsp. massiliense genes involved in iron storage. Unlike other opportunist or pathogenic mycobacteria studied, M. abscessus complex has two genes similar to ferritins from M. tuberculosis (Rv3841), and in M. abscessus subsp. massiliense, those genes are annotated as mycma_0076 and mycma_0077. Molecular dynamic analysis of the predicted expressed proteins showed that they have a ferroxidase center. The expressions of mycma_0076 and mycma_0077 genes were modulated by the iron levels in both in vitro cultures as well as infected macrophages. Structural studies using size-exclusion chromatography, circular dichroism spectroscopy and dynamic light scattering showed that r0076 protein has a structure similar to those observed in the ferritin family. The r0076 forms oligomers in solution most likely composed of 24 subunits. Functional studies with recombinant proteins, obtained from heterologous expression of mycma_0076 and mycma_0077 genes in Escherichia coli, showed that both proteins were capable of oxidizing Fe2+ into Fe3+, demonstrating that these proteins have a functional ferroxidase center. In conclusion, two ferritins proteins were shown, for the first time, to be involved in iron storage in M. abscessus subsp. massiliense and their expressions were modulated by the iron levels.
RESUMEN
Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guérin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc(2)-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17-specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine.
RESUMEN
Although biological similarities have been described among monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukaemia (CLL), the relationships between these two conditions are not fully understood, and new epidemiological studies in different populations and different countries continue to be reported. Here, we investigated 167 first-degree relatives from 42 families of patients with non-familial (sporadic) CLL, using four-colour flow cytometry. MBL was found in seven of 167 subjects (4.1%). Monoclonality was detected in all cases either by light-chain restriction or by polymerase chain reaction. Fluorescence in situ hybridization did not show any chromosomal abnormality. The prevalence of MBL according to age was 0 (0/54) in individuals aged less than 40 years, 2.5% (2/81) between 40 and 60 years, and 15.6% (5/32) in individuals over 60 years. The prevalence of MBL cases in individuals over 60 years was similar to that found in familial CLL relatives at the same age group. This suggests that in older first-degree relatives of patients with sporadic CLL, the risk of MBL detection is as high as in older first-degree relatives from CLL families, which could render these individuals belonging to 'sporadic CLL families' as susceptible as individuals from 'familial CLL' to the development of clinical CLL.
Asunto(s)
Linfocitos B , Leucemia Linfocítica Crónica de Células B/genética , Linfocitosis/genética , Adulto , Distribución por Edad , Anciano , Brasil/epidemiología , Aberraciones Cromosómicas , Femenino , Citometría de Flujo , Estudios de Seguimiento , Reordenamiento Génico de Linfocito B , Humanos , Separación Inmunomagnética/métodos , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/epidemiología , Linfocitosis/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por SexoRESUMEN
Myelodysplastic syndrome (MDS) is a rare hematological malignancy in children. It was performed FISH analysis in 19 pediatric MDS patients to investigate deletions involving the PPARgamma and TP53 genes. Significant losses in the PPARgamma gene and deletions in the tumor suppressor gene TP53 were observed in 17 and 18 cases, respectively. Using quantitative RT-PCR, it was detected PPARgamma transcript downexpression in a subset of these cases. G-banding analysis revealed 17p deletions in a small number of these cases. One MDS therapy-related patient had neither a loss of PPARgamma nor TP53. These data suggest that the PPARgamma and TP53 genes may be candidates for molecular markers in pediatric MDS, and that these potentially recurrent deletions could contribute to the identification of therapeutic approaches in primary pediatric MDS.
Asunto(s)
Eliminación de Gen , Síndromes Mielodisplásicos/genética , PPAR gamma/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Niño , Preescolar , Bandeo Cromosómico , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Cromosomas Humanos Par 2 , Cromosomas Humanos Par 8 , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/genética , Translocación Genética , Adulto , Aberraciones Cromosómicas , Bandeo Cromosómico , Citogenética , Humanos , Cariotipificación , Linfocitosis/diagnóstico , Linfocitosis/genética , Masculino , Modelos GenéticosRESUMEN
Foram operados, pelo Grupo de Ombro e Cotovelo do Departamento de Ortopedia e Traumatologia da Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo, 12 pacientes portadores de lesões extensas e irreparáveis do manguito rotador, apresentando como queixa principal a dor. Estes foram submetidos à tenotomia da cabeça longa do músculo bíceps do braço associada ao desbridamento da lesão extensa e irreparável do manguito rotador por via artroscópica. A média de idade era de 64 anos e o lado dominante foi acometido em 11 pacientes. O tempo de seguimento médio foi de 26 meses. Do total, 11 pacientes referiram-se satisfeitos com o tratamento realizado. Foi observada média de 28,2 pontos da escala UCLA na avaliação do período pós-operatório. Em relação à mobilidade ativa, houve acréscimo médio de 300 na elevação, 1,70 na rotação lateral e dois níveis vertebrais na rotação medial. Esta técnica proporciona alívio da dor em pacientes com lesões irreparáveis do manguito rotador.