Treatment of hepatitis C in potential lung transplant candidates.

International guidelines list hepatitis C virus (HCV) as a contraindication to lung transplant (LTx). Since the development of these guidelines, the natural history of HCV after nonhepatic transplant has been clarified, and more effective antiviral therapy is available. In renal transplant candidates, HCV treatment before transplantation improves posttransplant outcome.

Insulin increases the expression of contractile phenotypic markers in airway smooth muscle.

We have previously demonstrated that long-term exposure of bovine tracheal smooth muscle (BTSM) strips to insulin induces a functional hypercontractile phenotype. To elucidate molecular mechanisms by which insulin might induce maturation of contractile phenotype airway smooth muscle (ASM) cells, we investigated effects of insulin stimulation in serum-free primary BTSM cell cultures on protein accumulation of specific contractile phenotypic markers and on the abundance and stability of mRNA encoding these markers. In addition, we used microscopy to assess insulin effects on ASM cell morphology, phenotype, and induction of phosphatidylinositol (PI) 3-kinase signaling.

Nuclear factor-kappaB-mediated cell survival involves transcriptional silencing of the mitochondrial death gene BNIP3 in ventricular myocytes.

Background: A survival role for the transcription factor nuclear factor-kappaB (NF-kappaB) in ventricular myocytes has been reported; however, the underlying mechanism is undefined. In this report we provide new mechanistic evidence that survival signals conferred by NF-kappaB impinge on the hypoxia-inducible death factor BNIP3.

Methods And Results: Activation of the NF-kappaB signaling pathway by IKKbeta in ventricular myocytes suppressed mitochondrial permeability transition pore (PTP) opening and cell death provoked by BNIP3.

BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF.

Hypoxic regions within solid tumors are often resistant to chemotherapy and radiation. BNIP3 (Bcl-2/E1B 19 kDa interacting protein) is a proapoptotic member of the Bcl-2 family that is expressed in hypoxic regions of tumors. During hypoxia, BNIP3 expression is increased in many cell types and upon forced overexpression BNIP3 induces cell death.

Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes.

In this study, we provide evidence for the operation of BNIP3 as a key regulator of mitochondrial function and cell death of ventricular myocytes during hypoxia. In contrast to normoxic cells, a 5.6-fold increase (P<0.

IKK beta is required for Bcl-2-mediated NF-kappa B activation in ventricular myocytes.

The transcription factor nuclear factor kappa B (NF-kappa B) is regulated by cytoplasmic inhibitor I kappa B alpha. An integral step in the activation of NF-kappa B involves the phosphorylation and degradation of I kappa B alpha. We have previously reported that I kappa B alpha activity is diminished in ventricular myocytes expressing Bcl-2 (de Moissac, D.