To determine if megakaryocytes are targeted by immune thrombocytopenic purpura (ITP) autoantibodies, as are platelets, we have studied the effects of ITP plasma on in vitro megakaryocytopoiesis. Umbilical cord blood mononuclear cells were incubated in the presence of thrombopoietin and 10% plasma from either ITP patients (n ؍ 53) or healthy donors. The yield of megakaryocytic cells, as determined by flow cytometry, was significantly reduced in the presence of ITP plasma containing antiplatelet glycoprotein Ib (GPIb) autoantibodies (P < .001) as compared with both the control and patient plasma with no detectable antiGPIIb/IIIa or anti-GPIb autoantibodies. Platelet absorption of anti-GPIb autoantibodies in ITP plasmas resulted in double the megakaryocyte production of the same plasmas without absorption, whereas platelet absorption of control plasma had no effect on megakaryocyte yield. Furthermore, 2 human monoclonal autoantibodies isolated from ITP patients, 2E7, specific for human platelet glycoprotein IIb heavy chain, and 5E5, specific for a neoantigen on glycoprotein IIIa expressed on activated platelets, had significant inhibitory effects on in vitro megakaryocytopoiesis (P < .001). Taken together, these data indicate that autoantibodies against either platelet GPIb or platelet GPIIb/IIIa in ITP plasma not only are involved in platelet destruction, but may also contribute to the inhibition of platelet production. (Blood. 2003;102: 887-895)
A 16-year study of wild, unprovisioned sifaka Propithecus verreauxi verreauxi at Beza Mahafaly in southwest Madagascar provides estimates of age-speci®c fertility, mortality, and dispersal in a population of 426 marked animals, and longitudinal records of individual life histories. Sifaka females give birth for the ®rst time later and live longer, for their size, than mammals in other orders; they also give birth later and continue reproducing longer, for their size, than other primates. Theory postulates that these features, commonly referred to as bet-hedging, evolve in unpredictable environments in association with widely varying infant survival and a trade-off between reproductive effort and adult survival. The climate of south-west Madagascar is highly unpredictable compared to almost all other regions in the tropics with similar average rainfall, and we argue that sifaka females are bet-hedgers par excellence. Male sifaka, in contrast, become reproductively active at an earlier age than females, and are less likely to have long lives than females. The atypical direction of this asymmetry between males and females re¯ects a`slowing down' of female life histories rather than a`speeding up' of male life histories. Two other unusual features of sifaka biology and behaviour may be linked to the unpredictability of Madagascar's climate: intense local competition between females, and a sex ratio at birth strongly biased in favour of males in most years. In drought years, reproductive females must cope with suddenly intensi®ed resource constraints. This, in turn, may strongly limit the number of`breeding slots' available over the long-term for females.
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