RESUMO
We describe two serious Trametes polyzona pulmonary infections, which occurred in Réunion Island, in critically ill patients. The identification was performed using sequencing of the internal transcribed spacer region of ribosomal DNA and D1/D2 region of 28S rDNA. In one case, the significance of T. polyzona in the pathological process was certain, proven by histopathological evidence of fungal lung infection. T. polyzona, an emerging filamentous basidiomycete, prevalent in tropical areas, has not been described so far in human infections.
Assuntos
Pneumopatias Fúngicas/diagnóstico , Micoses/diagnóstico , Trametes/isolamento & purificação , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Pré-Escolar , DNA Fúngico/genética , Feminino , Humanos , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , RNA Ribossômico 28S/genética , Reunião/epidemiologia , Análise de Sequência de DNARESUMO
Neuroblastoma (NB) is a frequent embryonal tumor of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harboring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes.
Assuntos
Tronco Encefálico/anormalidades , Mutação em Linhagem Germinativa , Neuroblastoma/genética , Neuroblastoma/patologia , Receptores Proteína Tirosina Quinases/genética , Adulto , Quinase do Linfoma Anaplásico , Sistema Nervoso Central/embriologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Mutação de Sentido Incorreto , Neuroblastoma/congênito , Oncogenes , SíndromeRESUMO
Steroid-sensitive nephrotic syndrome (SSNS) is classically thought to be a T-cell disorder. The aim of this study was to examine whether or not thymus homeostasis was affected in SSNS. Mature and naive T cell recent thymic emigrants were quantified in the peripheral blood of nephrotic patients and controls. Because the generation of new T cells by the thymus ultimately depends on hematopoietic stem cells, CD34+ cells were also included in the study. Nineteen patients with SSNS during relapse, 13 with SSNS during proteinuria remission, and 18 controls were studied. Cell-surface markers (CD3, CD4, CD8, CD19, CD16, CD56, CD45RA, CD62L, CD34, and CD38) were analyzed by flow cytometric analysis. T-cell rearrangement excision circles (TRECs) were quantified in CD2+ cells by real-time polymerase chain reaction. Stroma cell-derived factor-1 (SDF-1) genotype and metalloproteinase-9 (MMP-9) plasma levels were also determined. Mature T cells (CD4+ and CD8+), circulating naive T cells (CD62L+ and CD3+ CD62L+), and recent thymic emigrants (CD45RA+) as well as TRECs, that measure thymus production, had a similar level in the three groups of patients. Conversely, CD34+ hematopoietic stem cells displayed a two-fold increase in SSNS patients during relapse either compared with controls or SSNS patients at remission. In addition, compared with controls, SSNS patients at remission displayed (1) a decrease in CD19+ cells (B cells) and (2) an increase in CD16CD56+ cells [natural killer (NK) cells]. In conclusion, thymus homeostasis is not significantly affected in nephrotic patients. Hematopoietic stem-cell mobilization at proteinuria relapse, as well as changes in B and NK cells during remission, suggest that SSNS might be due to a general disturbance of hematopoietic and immune cell trafficking.