We report a case of hyperpyrexia presumed due to topical salicylate toxicity occurring immediately following general anaesthesia for appendicectomy in an eleven year old boy. Some of the features strongly suggested the diagnosis of malignant hyperpyrexia.
No abstract
Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native three-dimensional conformation with high fidelity whilst eliminating misfolded, aggregation-prone species. While protein aggregates can contribute to pathologies exemplified by Alzheimer's and Parkinson's diseases, their abundance is normally minimised by molecular chaperones such as HSP70/90, which promote native folding and drive the recycling of aberrantly folded species. Cytoplasmic chaperones (e.g. HSP70/40) can resolve insoluble protein aggregates should the preventive mechanisms falter. However, it is unknown whether an analogous disaggregation system is needed and exists in the Endoplasmic Reticulum (ER), where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates that accumulate upon expression of metastable proteins. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observed steady-state aggregate accumulation in the ER. Strikingly, pharmacological induction of ER stress did not augment aggregates but rather stimulated their clearance within hours. We found that this disaggregation activity was catalysed by the stress-responsive ER molecular chaperone - BiP. Its elimination abolished the disaggregation activity in cells. Further, we reconstructed the disaggregation reaction in-vitro by a minimal system of ATP-fuelled BiP and its J-protein cofactor. These data reveal a hitherto unknown, non-redundant function of the ER stress response. Thus, our findings may facilitate the identification of aggregation-antagonising strategies and rationalising the age-dependent protein misfolding pathology.
JIerr P a t o nCintanr C l b r e a warde dnrch das Friedensgericbt den reranlasst die Tade~nrsrclie dcs ciucm Picbtrr snfieltorigen Gtfliigals zu uutersuchen, und in der Annrlime, drss die Vergiffung durch arseuigc Satir.?Statt Refunden babr , untwsuchte er die in clerii M q c n
D a s Kirschlorbeerwasser gehiirt bekanntlich zii den Arzneimitteln von ungewisser Wirkung. Einige Aerste verordnen es in sehr grohen Dosen, andere betracliten es schon in kleinen Mengen als giftig. Unter den Ursachen dieser Verschiedenheit kommen in Betraclit besonders die Verandernngen in der Stiirke des Wassers; in der ersten Zeit seiner Anwendung liefs man von 2Pfd. Blattern 1 Pfd. Wavser destilliren, wEhrend man jetzt 2 Pfd. Wasser davon zu destilliren vorschreibt. Die Natur des Bodens und der Einflufs der Sonne aul'sern ebenfalls bedeutende Wirkung anf die Beschaffenheit der Blatter, die man aber unmiiglich genau vorher hestimmen kann.Um wenigstens zu sehen, ob die verschiedenen Epochen der Vegetation auE den Gehalt der Kirschlorbeerblatter an Blausaure influirten, liers ich Blatter, die zu verschiedenen Zeiten von demselben Baume genoninien waren, destilliren und fing damit den 15. Juni an und hijrte den 30. August aufj das W e t t e r w a r in dieser Zeit i m Allgemeinen schiin. Der Blausauregehalt dieser verschiedenen W I s s e r w a r nicht merklich abweichend; indessen gaben die Blatter g e p n Ende Juli gesammelt einen etwas reichern Gelialt an Blausaure zu erkennen. 500 Grm. eines 1838 bereiteten Wassers gaben mit salpeters. Silber einen Niedarschlag yon Cyansilber, der 8 Decigrm. wasserleerer Blausiiure anceigte, oder auf die Unce 5 Centigrm. Von den verschiedenen Darstellungsmethoden diirfte die uber freiem Peuer die beste sein. Die Dampfdestillation giebt in diesein Falle weniger gute Producte. Die allgemeine Meinung, dafs das Kirschlorbeerwasser bald sich cersetze, m u h verworfen werden. Von zehn
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