Perinatal management of right aortic arch with aberrant left subclavian artery associated with critical stenosis of the subclavian artery in a newborn.

A right-sided aortic arch with an aberrant left subclavian artery is a congenital vascular anomaly that is easily detectable in utero at the level of the three vessels and trachea view, but which is rarely symptomatic in the neonate. We present a newborn with prenatally diagnosed right-sided aortic arch and aberrant subclavian artery who showed a clinically relevant stenosis of the subclavian artery during the first week of life. An intravascular stent was implanted into the stenosis of the aberrant left subclavian artery by catheterization. This case report demonstrates that a right-sided aortic arch with an aberrant subclavian artery can be diagnosed prenatally, that in these patients a stenosis of the subclavian artery can occur in early infancy and requires awareness of the neonatologist or pediatrician, and that stent implantation represents a minimally invasive therapeutic approach.

Interferon-alpha inhibits proliferation of Ba/F3 cells by interfering with interleukin-3 action.

Interferons (IFNs) are potent inhibitors of cell proliferation that are used for the treatment of several haematological malignancies. The mechanisms through which IFNs exert their antiproliferative effects on target cells, however, are largely unknown. Here we show that IFN-alpha, in murine Ba/F3 cells, directly interferes with the action of the essential mitogen interleukin (IL)-3. In transiently transfected Ba/F3 cells, IFN-alpha efficiently inhibited the IL-3-stimulated expression of a luciferase reporter construct, GAS-luc, that is activated through the JAK2/STAT5 pathway. Electrophoretic mobility shift assays and Northern blot experiments, however, revealed that neither the IL-3-induced DNA binding of STAT5 nor the transcription of the STAT5-dependent genes oncostatin-M, pim-1 and c-fos were suppressed by IFN-alpha, suggesting that the diminished expression of the luciferase protein was due to a direct inhibition of IL-3-stimulated protein synthesis. This hypothesis was supported by the observation that IFN-alpha, even though it had no effect on the transcription of the c-fos gene, efficiently suppressed the IL-3-dependent expression of the c-Fos protein. Furthermore, our results indicate that IFN-alpha induced an overexpression of the double-stranded RNA-activated protein kinase (PKR), an enzyme that inhibits protein synthesis through the phosphorylation and inactivation of the eukaryotic initiation factor-2. Therefore, we hypothesize that IFN-alpha, in Ba/F3 cells, interrupts IL-3-dependent mitogenic signals, at least in part, through the suppression of protein synthesis and that induction of PKR activity may play a pivotal role in this process.

Role of STAT5 in interferon-alpha signal transduction in Ba/F3 cells.

In interferon-alpha (IFN-alpha) signalling, the essential role of the transcription factors STAT1 and STAT2 is well established. In contrast, the involvement of other STAT proteins, including STAT5, is much less well understood. Here we show that, in IFN-alpha-responsive Ba/F3 cells, this cytokine stimulates the DNA-binding of STAT5A and B but that IL-3 is a much more potent activator of both STAT5 isoforms. A stably expressed dominant-negative mutant of JAK2 suppressed the IL-3- but not the IFN-alpha-dependent DNA binding of STAT5, suggesting independent mechanisms of its activation. Northern blots revealed that IL-3 strongly induced the expression of two STAT5-regulated genes, pim-1 and oncostatin-M, whereas IFN-alpha had a weak stimulatory effect on pim-1 expression only. In summary our results suggest that, despite the capability of IFN-alpha to stimulate DNA binding of STAT5, this transcription factor does not play a pivotal role in IFN-alpha signalling in Ba/F3 cells.