Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts.

Angiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Candesartan, a member of this group, also acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, a key regulator shown to be important for placental development.

Maternal platelets pass interstices of trophoblast columns and are not activated by HLA-G in early human pregnancy.

In early human gestation, maternal arterial blood flow into the intervillous space of the developing placenta is obstructed by invaded trophoblasts, which form cellular plugs in uterine spiral arteries. These trophoblast plugs have recently been described to be loosely cohesive with clear capillary-sized channels into the intervillous space by 7 weeks of gestation. Here, we analysed localisation of maternal platelets at the maternal-foetal interface of human first trimester pregnancy, and tested the hypothesis whether HLA-G, which is primarily expressed by extravillous trophoblasts, affects aggregation and adhesion of isolated platelets.

Novel phenotypes observed in patients with -linked leukaemia/familial thrombocytopenia syndrome and a biallelic risk allele as leukaemogenic cofactor.

The phenotypes of patients with the recently discovered, dominant, -linked leukaemia predisposition and familial thrombocytopenia syndrome are variable, and the exact mechanism of leukaemogenesis remains unclear. Here, we present novel clinical and laboratory phenotypes of seven individuals from three families with germline mutations and a refined genetic analysis of one child with additional high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL), aiming to elucidate second oncogenic hits. Four individuals from two pedigrees harboured one novel or one previously described variant in the central domain of (c.