Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease

Among secreted phospholipases A2 (sPLA2s), human group X sPLA2 (hGX sPLA2) is emerging as a novel attractive therapeutic target due to its implication in inflammatory diseases. To elucidate whether hGX sPLA2 plays a causative role in coronary artery disease (CAD), we screened the human PLA2G10 gene to identify polymorphisms and possible associations with CAD end-points in a prospective study, AtheroGene. We identified eight polymorphisms, among which, one non-synonymous polymorphism R38C in the propeptide region of the sPLA2. The T-512C polymorphism located in the 5′ untranslated region was associated with a decreased risk of recurrent cardiovascular events during follow-up. The functional analysis of the R38C polymorphism showed that it leads to a profound change in expression and activity of hGX sPLA2, although there was no detectable impact on CAD risk. Due to the potential role of hGX sPLA2 in inflammatory processes, these polymorphisms should be investigated in other inflammatory diseases

Recriticality in a BWR (boiling water reactor) following a core damage event

This report describes the results of a study conducted by Pacific Northwest Laboratory to assist the US Nuclear Regulatory Commission in evaluating the potential for recriticality in boiling water reactors (BWRs) during certain low probability severe accidents. Based on a conservative bounding analysis, this report concludes that there is a potential for recriticality in BWRs if core reflood occurs after control blade melting has begun but prior to significant fuel rod melting. However, a recriticality event will most likely not generate a pressure pulse significant enough to fail the vessel. Instead, a quasi-steady power level would result and the containment pressure and temperature would increase until the containment failure pressure is reached, unless actions are taken to terminate the event. Two strategies are identified that would aid in regaining control of the reactor and terminate the recriticality event before containment failure pressures are reached. The first strategy involves initiating boration injection at or before the time of core reflood if the potential for control blade melting exists. The second strategy involves initiating residual heat removal suppression pool cooling to remove the heat load generated by the recriticality event and thus extend the time available for boration. 31 figs., 17 tabs

Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel in insulin-secreting cells

The action of polymyxin B (0.1 μM) on ATP-sensitive K+ (K+ ATP) channels in RINm5F insulin-secreting cells was investigated by patch-clamp techniques. Using inside-out patches, open-cells and outside-out patches, polymyxin B was found to block K+ ATP channels by, on average, approximately 90-95 of the initial control level of channel activity. The effects were rapid in onset, sustained and readily reversible. Similar effects were found in patches excised from cells pretreated overnight with 1 μM of the phorbol ester phorbol myristate acetate (PMA). External block of channels was associated with a marked decrease in single-channel current amplitude, whereas these effects were not seen when polymyxin B was added to the inside face of the membrane. In patches bathed with internally applied ATP (0.5 mM) and ADP (0.5 mM), polymyxin B inhibited channels but its actions were not reversible upon removal of the compound. However, when the same protocol was undertaken upon cells pre-treated with PMA, the effects of polymyxin B were readily reversed. Our data suggests that polymyxin B is a novel modulator of K+ ATP channels, exhibiting multiple blocking actions that may possibly involve a direct effect upon the channel and indirect effects mediated through the inhibition of endogenous protein kinase(s). © 1994 Springer-Verlag