[Cardiac manifestations of idiopathic hypereosinophilic syndrome]. / Manifestations cardiaques du syndrome hyperéosinophilique essentiel.

BACKGROUND: The aim of our study is to describe the more common cardiac manifestations of idiopathic hypereosinophilic syndrome representing the major cause of mortality. MAIN POINTS: Current therapy consists of corticosteroid, hydroxyurea and interferon alpha. Recent publications confirm the activity of imatinib mesylate, a selective tyrosine kinase inhibitor, in patients with idiopathic hypereosinophilic syndrome. In cases with marked valvular compromise or with endomyocardial thrombosis or fibrosis, cardiac surgery can provide substantial benefits. PERSPECTIVES: A better understanding of the pathophysiology of this syndrome could lead to the development of new therapeutic agents.

The supercoiling sensitivity of a bacterial tRNA promoter parallels its responsiveness to stringent control.

In Salmonella typhimurium, expression of the hisR locus, a tRNA operon, decreases upon inhibiting DNA gyrase. Here, the hisR promoter dependence on negative DNA supercoiling was examined in vivo and in vitro. Mutant analysis showed the sequence determinants of this dependence to lie in the region between the -10 box and the transcription start site. As with most promoters subject to stringent control, this portion of the hisR promoter is C-G-rich. Replacing a C/G bp with T/A at position -7 partially relieves the supercoiling response while changing the sequence between -5 and + 1 (-CCCCCG-) for -GTTAA- abolishes the response in vitro and in vivo. The relief of the supercoiling dependence closely correlates with increased promoter susceptibility to melting in vivo and a lesser requirement for initiating nucleotides in the formation of stable initiation complexes in vitro. Studies in isoleucine-starved cells showed that such sequence changes mitigate and abolish the hisR promoter response to stringent control, respectively. The data presented suggest that the hisR promoter's sensitivity to stringent regulation arises from the same physical property that confers supercoiling sensitivity, i.e. resistance to melting. We propose that the stringent control mechanism acts by hampering the ability of RNA polymerase to melt the DNA helix.