Impact of pulmonary hypertension on long-term outcome in patients with severe aortic stenosis.

Aims: Pulmonary hypertension (PH) is common in severe symptomatic left-sided valvular disease, particularly in aging populations. Inconsistent results have been reported concerning the association between PH and adverse outcomes after aortic valve replacement for aortic stenosis (AS). We therefore retrospectively investigated the prognostic significance of PH using peak tricuspid regurgitation velocity (TRV), as defined by the current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines, in a large cohort of patients with severe AS.

MDA-9/syntenin is essential for factor VIIa-induced signaling, migration, and metastasis in melanoma cells.

Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, is a novel gene that positively regulates cancer cell motility, invasion, and metastasis through distinct biochemical and signaling pathways, but how MDA-9/syntenin is regulated in response to signals with the extracellular environment and promotes tumor progression is unclear. We now demonstrate that MDA-9/syntenin is dramatically up-regulated by a combination of rFVIIa and factor F(X) in malignant melanoma. Induction of MDA-9/syntenin in melanoma was found to occur in a thrombin-independent signaling pathway and involves the PAR-1/c-Src/Rho GTPases Rac1 and Cdc42/c-Jun N-terminal kinase axis resulting in the activation of paxillin, NF-κB, and matrix metalloproteinase-2 (MMP-2).

Prope tolerance to heart allografts in mice associated with persistence of donor interleukin-10-transduced stem cells.

Background: We previously reported that transduction of the human interleukin (IL)-10 gene into the total fetal liver stem cells (hIL-10-TFLs) of mice protects against their rejection in an allogeneic host. In this study, we explored the effects of these cells in two different models of organ transplantation.

Methods: Balb/c mice were sublethally irradiated before receiving skin or vascularized heterotopic heart grafts from C57Bl/6 mice.

Transplantation tolerance induced in humans at the fetal or the neonatal stage.

Patients transplanted with HLA-mismatched stem cells from fetal livers develop transplantation tolerance to donor antigens. Engraftment needs no conditioning regimen prior to transplantation in neonates with severe combined immunodeficiency disease or in human fetal patients having not yet developed any immune maturity, especially T-cell differentiation. The chimeric patients have donor-derived T lymphocytes which progressively demonstrate positive interactions with other host cells.