Mutations of the transcription factor PU.1 are not associated with acute lymphoblastic leukaemia

The transcription factor PU.1 plays a crucial role during normal haematopoiesis in both myeloid cells and B-lymphocytes. Mice with a disruption in both alleles of the PU.1 locus were found to lack macrophages and B cells and had delayed appearance of neutrophils. In addition, critical decrease of PU.1 expression is sufficient to cause acute myeloid leukaemia (AML) and lymphomas in mice. Recently, we reported that heterozygous mutations in the PU.1 gene are present in some patients with AML. Thus, we hypothesised that PU.1 mutations might also contribute to the development of acute leukaemias of the B-cell lineage. Here, we screened 62 patients with B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis for genomic mutations by direct sequencing of all five exons of the PU.1 gene. We found no genomic alteration of the PU.1 gene suggesting that PU.1 mutations are not likely to be common in B-ALL

Altering a Histone H3K4 Methylation Pathway in Glomerular Podocytes Promotes a Chronic Disease Phenotype

Methylation of specific lysine residues in core histone proteins is essential for embryonic development and can impart active and inactive epigenetic marks on chromatin domains. The ubiquitous nuclear protein PTIP is encoded by the Paxip1 gene and is an essential component of a histone H3 lysine 4 (H3K4) methyltransferase complex conserved in metazoans. In order to determine if PTIP and its associated complexes are necessary for maintaining stable gene expression patterns in a terminally differentiated, non-dividing cell, we conditionally deleted PTIP in glomerular podocytes in mice. Renal development and function were not impaired in young mice. However, older animals progressively exhibited proteinuria and podocyte ultra structural defects similar to chronic glomerular disease. Loss of PTIP resulted in subtle changes in gene expression patterns prior to the onset of a renal disease phenotype. Chromatin immunoprecipitation showed a loss of PTIP binding and lower H3K4 methylation at the Ntrk3 (neurotrophic tyrosine kinase receptor, type 3) locus, whose expression was significantly reduced and whose function may be essential for podocyte foot process patterning. These data demonstrate that alterations or mutations in an epigenetic regulatory pathway can alter the phenotypes of differentiated cells and lead to a chronic disease state

Coledocoduodenostomia laparoscópica

OBJETIVO: Estudar, a curto e médio prazos, o resultado e complicações da coledocoduodenostomia (CDD) realizada por via laparoscópica. MÉTODO: Estudo prospectivo de 20 pacientes com indicação de coledocoduodenostomia vídeo-laparoscópica operados na DIGEST no período de 1991 a 2003. RESULTADOS: Dos 20 pacientes com indicação para CDD laparoscópica, quatro tinham coledocolitíase associada à litíase vesicular, oito litíase residual de colédoco, dois estenose benigna e seis tumor periampolar. Houve duas conversões para ressecção de colédoco. Dentre as 18 CDD, todos tinham via biliar acima de 1,5 cm de diâmetro. Foi observado vazamento biliar pelo dreno cavitário em quatro casos (duração máxima de quatro dias) resolvidos espontaneamente, uma infecção de ferida e uma morte súbita no 2º. dia de pós-operatório. Os seis portadores de tumor periampolar tiveram sobrevida média de 7,2 meses evoluindo sem prurido ou icterícia até o óbito. CONCLUSÕES: Além da demonstração da viabilidade do método laparoscópico na realização da CDD, evidenciou-se que o posicionamento de trocarte adicional facilita a confecção da anastomose. Acredita-se que, a ocorrência de vazamento da anastomose possa diminuir com a experiência e que a CDD seja alternativa interessante na paliação dos tumores periampolares