Brachial plexopathy as a complication of induced hypothermia following cardiac arrest.

Induced hypothermia following cardiac arrest is a common treatment in the critical care unit. Topical cooling measures are easy to initiate and widely utilised. We report a case of brachial plexopathy occurring in association with topical cooling measures and discuss the diagnosis, management and avoidance of such complications.

Clinical experience with a pumpless extracorporeal lung assist device.

We present three patients with respiratory failure in whom conventional mechanical lung ventilation resulted in unacceptably high levels of carbon dioxide, severe acidosis and high vasopressor requirements. A pumpless arteriovenous extracorporeal carbon dioxide removal device (Novalung) was inserted. Arterial carbon dioxide levels were reduced rapidly with a corresponding increase in pH, reduction in vasopressor requirements and reduction in inspiratory pressures. One patient required the additional use of high frequency oscillatory ventilation. There were no complications associated with use of the device. We conclude that use of extracorporeal carbon dioxide removal devices should be considered at an early stage in the management of respiratory failure refractory to conventional ventilatory techniques.

Coupling of termination, 3' processing, and mRNA export.

In a screen to identify genes required for mRNA export in Saccharomyces cerevisiae, we isolated an allele of poly(A) polymerase (PAP1) and novel alleles encoding several other 3' processing factors. Many newly isolated and some previously described mutants (rna14-48, rna14-49, rna14-64, rna15-58, and pcf11-1 strains) are defective in polymerase II (Pol II) termination but, interestingly, retain the ability to polyadenylate these improperly processed transcripts at the nonpermissive temperature. Deletion of the cis-acting sequences required to couple 3' processing and termination also produces transcripts that fail to exit the nucleus, suggesting that all of these processes (cleavage, termination, and export) are coupled. We also find that several but not all mRNA export mutants produce improperly 3' processed transcripts at the nonpermissive temperature. 3' maturation defects in mRNA export mutants include improper Pol II termination and/or the previously characterized hyperpolyadenylation of transcripts. Importantly, not all mRNA export mutants have defects in 3' processing. The similarity of the phenotypes of some mRNA export mutants and 3' processing mutants indicates that some factors from each process may mechanistically interact to couple mRNA processing and export. Consistent with this assumption, we present evidence that Xpo1p interacts in vivo with several 3' processing factors and that the addition of recombinant Xpo1p to in vitro processing reaction mixtures stimulates 3' maturation. Of the core 3' processing factors tested (Rna14p, Rna15p, Pcf11p, Hrp1p, Fip1p, and Cft1p), only Hrp1p shuttles. Overexpression of Rat8p/Dbp5p suppresses both 3' processing and mRNA export defects found in xpo1-1 cells.

Nucleocytoplasmic transport: driving and directing transport.

Nucleocytoplasmic transport involves assembly and movement across the nuclear envelope of cargo-receptor complexes that interact with the small GTPase Ran. The asymmetric distribution of Ran regulator proteins, RanGAP1 and RCC1, provides the driving force and directionality for nuclear transport.

Yeast heat shock mRNAs are exported through a distinct pathway defined by Rip1p.

We reported previously that heat or ethanol shock in Saccharomyces cerevisiae leads to nuclear retention of most poly(A)+ RNA but heat shock mRNAs (encoding Hsp70 proteins Ssa1p and Ssa4p) are efficiently exported in a process that is independent of the small GTPase Ran/Gsp1p, which is essential for most nucleocytoplasmic transport. To gain further insights into proteins essential or nonessential for export of heat shock mRNAs, in situ hybridization analyses to detect mRNA and pulse-labeling of proteins were used to examine several yeast mutant strains for their ability to export heat shock mRNAs following stress. Rip1p is a 42-kD protein associated with nuclear pore complexes and contains nucleoporin-like repeat sequences. It is dispensable for growth of yeast cells under normal conditions, but we report that it is essential for the export of heat shock mRNAs following stress. When SSA4 mRNA was induced from a GAL promoter in the absence of stress, it was efficiently exported in a strain lacking RIP1, indicating that Rip1p is required for export of heat shock mRNAs only following stress. Npl3p, a key mediator of export of poly(A)+ RNA, was not required for heat shock mRNA export, whereas Rss1p/Gle1p, a NES-containing factor essential for poly(A)+ RNA export, was also required for export of heat shock mRNAs after stress. High-level expression of the HIV-1 Rev protein, but not of Rev mutants, led to a partial block in export of heat shock mRNAs following stress. The data suggest a model wherein the requirement for Npl3p defines the mRNA export pathway, the requirement for Rip1p defines a pathway used for export of heat shock mRNAs after stress, and additional factors, including Rss1p/Gle1p and several nucleoporins (Rat7p/Nup159p, Rat2p/Nup120p, and Nup145p/Rat10p), are required in both pathways.