Circulating red cell volume and red cell survival can be accurately determined in sheep using the [14C]cyanate label

The sheep commonly serves as an animal model for investigation of human fetal and newborn erythropoiesis and red blood cell kinetics. Measurement of red cell volume (RCV) and survival (RCS) in sheep would be useful for studying mechanisms of neonatal anemia. Unfortunately 51Cr, the standard method for RCV, is not suitable for RCS in sheep because 51Cr leaves the red cell too rapidly. We developed and validated the permanent label [14C]cyanate as a method for measuring both RCV and RCS in sheep. In 19 sheep, RCV was determined simultaneously using [14C]cyanate and 51Cr. RCV determined by [14C]cyanate agreed almost perfectly with RCV by 51Cr; correlation coefficient = 0.990. The line of regression had a slope of 0.94 and an intercept of 40; these parameters are not significantly different from a line of identity. In nine sheep, RCS was determined using [14C]cyanate. Survival after d 1 accurately fit a model containing two components: 1) an early exponential loss likely related to damage caused by labeling and handling and 2) a linear decrease that reflected normal survival of undamaged red cells. Mean potential life span (MPL) determined from the linear phase was 114 +/- 12 d (mean +/- 1 SD). These results agree with reported MPL values determined either by 59Fe or differential hemolysis. Together, these observations establish [14C]cyanate-labeled red cells as a tool for measuring both RCV and RCS in sheep and enhance the value of the ovine model for investigating neonatal anemia.     

Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease

Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study we tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant 3-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD.