NF-κB suppresses ROS levels in BCR-ABL(+) cells to prevent activation of JNK and cell death.

Elevated levels of reactive oxygen species (ROS) are found in most oncogenically transformed cells and are proposed to promote cellular transformation through mechanisms such as inhibition of phosphatases. BCR-ABL, the oncoprotein associated with the majority of chronic myeloid leukemias (CMLs), induces accumulation of intracellular ROS, causing enhanced signaling downstream of PI3K. Previously we have shown that the transcription factor nuclear factor-kappa B (NF-κB) is activated by BCR-ABL expression and is required for BCR-ABL-mediated cellular transformation. Inhibition of IκB kinase (IKKß) and NF-κB leads to cell death through an unknown mechanism. Here, we analyze the potential involvement of NF-κB in moderating BCR-ABL-induced ROS levels to protect from death. The data confirm that BCR-ABL promotes ROS and demonstrate that NF-κB prevents excessive levels. Inhibition of NF-κB leads to an increase in ROS levels and to cell death, which is at least partially controlled through ROS-induced c-Jun N-terminal kinase activity. The data demonstrate that one function for NF-κB in oncogenesis is the suppression of oncoprotein-induced ROS levels and that inhibition of NF-κB in some cancers, including CML, will increase ROS levels and promote cell death.

Rubeola during pregnancy.

We report three cases of rubeola during pregnancy complicated by pneumonia. All had bacterial superinfection of the lungs and a clinically mild hepatitis. One woman delivered at term and two underwent successful tocolysis, one of whom had an unexplained stillbirth 7 weeks later. Rubeola virus is not a teratogen, although it has been associated with increased spontaneous abortion and perinatal mortality.

The changing nature of diagnosis in an inpatient service over 20 years.

This study examined factors related to mental illness in children and adolescents. A survey of all 362 files of child and adolescent patients discharged from a single residential treatment facility in 1961-1962, 1971-1972, and 1978 revealed several major diagnostic trends. The proportion of cases diagnosed as schizophrenic decreased by one-third, those diagnosed as neurotic increased over ten-fold, and significant increases occurred in the proportion of children diagnosed as autistic, personality disorder, and behavior disorder of childhood and adolescence. There was a decrease in cases between 6 and 12 years of age and a significant increase in 13- to 18-year-olds. The relative importance of symptoms appeared to be interpreted differently at various times. Significant changes were also found In treatment length, in medications used, and in a number of factors related to the characteristics of the family.

Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro.

Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies from normal subjects heterozygous as the G-6-PD locus show type-A G-6-PD and 50% type B, only two of the 1308 colonies from the CML patients had type-A G-6-PD. These data provide little evidence for persistence of normal committed stem cells in CML, a finding in contrast to that made previously in polycythemia vera, another clonal stem cell myeloproliferative disorder.