The subtilisin-like proprotein convertases PC1͞3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway. They are expressed together or separately in neuroendocrine cells throughout the brain and dispersed endocrine system in both vertebrates and invertebrates. Disruption of the gene-encoding mouse PC1͞3 has now been accomplished and results in a syndrome of severe postnatal growth impairment and multiple defects in processing many hormone precursors, including hypothalamic growth hormone-releasing hormone (GHRH), pituitary proopiomelanocortin to adrenocorticotropic hormone, islet proinsulin to insulin and intestinal proglucagon to glucagon-like peptide-1 and -2. Mice lacking PC1͞3 are normal at birth, but fail to grow normally and are about 60% of normal size at 10 weeks. . The PC1͞3-null mice differ from a human subject reported with compound heterozygosity for defects in this gene, who was of normal stature but markedly obese from early life. The PC1͞3-null mice are not obese. The basis for these phenotypic differences is an interesting topic for further study. These findings prove the importance of PC1͞3 as a key neuroendocrine convertase.
In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).
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