Is high water evaporation rate associated with low blood pressure in chronic peritoneal dialysis patients?
CAPD patients had lower BP and BW in the high WER stage. These decreases were associated with higher ambient temperature and WER. We hypothesize that increased insensible salt and fluid loss secondary to high WER during hot seasons, especially in subtropical areas, ameliorates the hypervolemia and hypertension in CAPD patients.
Mutations were found exclusively in the kinase domain of JAK2. The panel of mutations conferred resistance to high concentrations of inhibitor accompanied by sustained activation of the Stat5, Erk1/2, and Akt pathways. Using a JAK2 substrate, enhanced catalytic activity of the mutant JAK2 kinase was observed in inhibitor concentrations 200-fold higher than is inhibitory to the wild-type protein. When testing the panel of mutations in the context of the Jak2 V617F allele, we observed that a subset of mutations conferred resistance to inhibitor, validating the use of TEL-JAK2 in the initial screen. These results demonstrate that small-molecule inhibitors select for JAK2 inhibitor-resistant alleles, and the design of next-generation JAK2 inhibitors should consider the location of mutations arising in inhibitor-resistant screens.