Interleukin-6 mRNA is unstable and degraded with a half-life of 30 min. Instability determinants can entirely be attributed to the 3 untranslated region. By grafting segments of this region to stable green fluorescent protein mRNA and subsequent scanning mutagenesis, we have identified two conserved elements, which together account for most of the instability. The first corresponds to a short noncanonical AU-rich element. The other, 80 nucleotides further 5, comprises a sequence predicted to form a stem-loop structure. Neither element alone was sufficient to confer full instability, suggesting that they might cooperate. Overexpression of myc-tagged AUF1 p37 and p42 isoforms as well as suppression of endogenous AUF1 by RNA interference stabilized interleukin-6 mRNA. Both effects required the AU-rich instability element. Similarly, the proteasome inhibitor MG132 stabilized interleukin-6 mRNA probably through an increase of AUF1 levels. The mRNA coimmunoprecipitated specifically with myc-tagged AUF1 p37 and p42 in cell extracts but only when the AU-rich instability element was present. These results indicate that AUF1 binds to the AU-rich element in vivo and promotes IL-6 mRNA degradation.

Risk factors for PGD in the UNOS/ISHLT registry are consistent with prior smaller studies. Recipient, donor, and therapy variables are independently associated with PGD, as defined in a large registry.

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IntroductionFirst described in Japan, takotsubo cardiomyopathy is increasingly becoming recognized worldwide as a cause of sudden and reversible diminished left ventricular function characterized by left apical ballooning and hyperkinesis of the basal segments, often with symptoms mimicking a myocardial infarction. Associated with physical or emotional stress, its exact pathogenesis has not been established, though evidence supports a neurohumoral etiology. Additionally, recurrence of this condition is rare. In this report, we present a rare case of recurrent takotsubo cardiomyopathy in a post-menopausal woman who presented with transient neurological complaints on both occasions.Case presentationWe present a rare case of a 76-year-old Caucasian woman with no history of congestive heart failure who presented to our emergency department twice with transient neurological complaints. On the first occasion, she was found to have transient aphasia which resolved within 24 hours, yet during that period she also developed symptoms of congestive heart failure and was noted to have a new, significantly depressed ejection fraction with apical akinesis and possible apical thrombus. One month after her presentation a repeat echocardiogram revealed complete resolution of all wall motion abnormalities and a return to baseline status. Seven months later she presented with ataxia, was diagnosed with vertebrobasilar insufficiency, and again developed symptoms and echocardiography findings similar to those of her first presentation. Once again, at her one-month follow-up examination, all wall motion abnormalities had completely resolved and her ejection fraction had returned to normal.ConclusionThough the exact etiology of takotsubo cardiomyopathy is unclear, a neurohumoral mechanism has been proposed. Recurrence of this disorder is rare, though it has been reported in patients with structural brain abnormalities. This report is the first to describe recurrent takotsubo cardiomyopathy in a patient with transient neurological symptoms. In our patient, as expected in patients with this condition, complete resolution of all left ventricular abnormalities occurred within a short period of time. It is important for clinicians to be aware of this increasingly recognized syndrome, including its association with recurrence, especially in the clinical setting of neurologic dysfunction.