No abstract

Occult HBV infection may not have a significant impact on response to IFN therapy for chronic HCV and development of HCC after therapy. Occult HBV may be sensitive to IFN although HBV is not completely eradicated.

SummaryThe relationships between tissue plasminogen activator (tPA), its fast acting inhibitor (PAI-1) and euglobulin clot lysis time (ELT) were investigated with healthy volunteers’ plasma. Turbidimetric clot lysis assay by the microtiter plate reader was utilized for ELT with a slight modification. Both tPA and PAI-1 showed the significant correlation with ELT. tPA had a significantly positive, not negative, correlation with ELT (R = 0.387, p <0.001). Higher correlation coefficients (R = 0.580, p <0.001 and R = 0.599, p <0.001) were obtained between ELT and total PAI-1 or free PAI-1 than tPA or tPA-PAI-1 complex (R = 0.427, p <0.001). The positive correlation was also obtained between tPA and PAI-1. These data suggest that PAI-1 is a highly important factor for ELT, especially, the amounts of free PAI-1 being the key factor to determine the ELT, which can represent the potential activity of the fibrinolytic system.

Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling. In the present study, we examined the novel PKC isoform protein kinase C delta (PKC␦) and its role in vascular SMC apoptosis. In A10 SMCs, overexpression of PKC␦ was sufficient to induce apoptosis, whereas inhibition of PKC␦ diminished H 2 O 2 -induced apoptosis. Moreover, evidence is provided that the tumor suppressor p53 is an essential mediator of PKC␦-induced apoptosis in SMCs. Activation of PKC␦ led to accumulation as well as phosphorylation of p53 in SMCs; this induction correlated with apoptosis. Furthermore, blocking p53 induction with small interference RNA or targeted gene deletion prevented PKC␦-induced apoptosis, whereas restoring p53 expression rescued the ability of PKC␦ to induce apoptosis in p53 null SMCs. We also establish that PKC␦ regulates p53 at both transcriptional and post-translational levels. Specifically, the transcriptional regulation required p38 MAPK, whereas the post-translational modification, at least for serine 46, did not involve MAPK. Additionally, PKC␦, p38 MAPK, and p53 co-associate in cells under conditions favoring apoptosis. Together, our data suggest that SMC apoptosis proceeds through a pathway that involves PKC␦, the intermediary p38 MAPK, and the downstream target tumor suppressor p53. Apoptosis of vascular smooth muscle cells (SMCs)3 is a well established component of the remodeling that occurs during normal development of the circulatory system (1, 2) as well as during the course of neointimal formation after intervention for atherosclerosis (3-5). Because increased total cellularity is a prominent feature of an occluding neointima, the balance between proliferation and apoptosis during vessel healing appears central to this pathologic process (6, 7). Indeed, accumulating evidence suggests that abnormal SMC apoptosis leads to neointimal hyperplasia (8 -11). However, despite the importance of SMC apoptosis, the precise molecular mechanism underlying the regulation of apoptotic pathways in SMCs remains largely undetermined.Apoptosis is a multistage, genetically controlled process of selective cell deletion. Protein kinases regulate the early stages of apoptosis by phosphorylating key proteins (12, 13), whereas caspases, a family of cysteine proteases, are the main effectors whose activation results in the characteristic morphological changes associated with programmed cell death such as membrane blebbing, chromatin condensation, and DNA fragmentation (14,15).Members of the protein kinase C (PKC) family are activated by diverse stimuli and participate in multiple cellular processes such as growth, differentiation, and apoptosis (16). The novel PKC isoform, protein kinase C delta (PKC␦), has been shown to be associated with the response to DNA damage and other apoptotic stimuli in specific cell types (17)(18)(19)(20). The critical role of PKC␦ in vascular SMC apoptosis and pathogenesis of a neointimal lesion has been recently demonstrated using PKC␦ "knock-out" mice....