IL-12 and IL-18 synergistically enhance IFN-γ mRNA transcription by activating STAT4 and AP-1, respectively. However, it is still unknown how STAT4/AP-1 elicit IFN-γ promoter activation. Using an IL-12/IL-18-responsive T cell clone, we investigated the mechanisms underlying synergistic enhancement of IFN-γ mRNA expression induced by these two cytokines. Synergy was observed in a reporter gene assay using an IFN-γ promoter fragment that binds AP-1, but not STAT4. An increase in c-Jun, a component of AP-1, in the nuclear compartment was elicited by stimulation with either IL-12 or IL-18, but accumulation of serine-phosphorylated c-Jun was induced only by IL-18 capable of activating c-Jun N-terminal kinase. The binding of AP-1 to the relevant promoter sequence depended on the presence of STAT4. STAT4 bound with c-Jun, and a phosphorylated c-Jun-STAT4 complex most efficiently interacted with the AP-1-relevant promoter sequence. Enhanced cobinding of STAT4 and c-Jun to the AP-1 sequence was also observed when activated lymph node T cells were exposed to IL-12 plus IL-18. These results show that STAT4 up-regulates AP-1-mediated IFN-γ promoter activation without directly binding to the promoter sequence, providing a mechanistic explanation for IL-12/IL-18-induced synergistic enhancement of IFN-γ gene expression.

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The mean platelet volume (MPV) is a laboratory marker associated with platelet function and activity. Increased MPV in thromboembolic disease is considered an important risk factor. The aim of this study was to compare the MPV and MPV/platelet count (MPV/P) ratio between deep vein thrombosis (DVT) and control subjects. We retrospectively reviewed the medical records of patients (n = 91) admitted due to newly diagnosed DVT from December 2010 to March 2012. The control group (n = 311) underwent health screening at our Hospital. Median MPV was higher in DVT patients compared to controls (8.6 fl vs. 7.9 fl, p < 0.0001). The DVT patients also had a higher MPV/P ratio compared to the control group (0.0388 fl/(10(9)/l) vs. 0.0308 fl/(10(9)/l), p < 0.0001). MPV was inversely correlated with platelet count in DVT patients (correlation coefficient = -0.33, p = 0.001). Receiver operator characteristic analysis revealed that an MPV cutoff value of 8.2 fl provided 70.3% sensitivity and 72.7% specificity. An MPV/P cutoff value of 0.0363 fl/(10(9)/l) showed 60% sensitivity and 73% specificity. MPV and MPV/P ratio could be considered meaningful laboratory markers for the risk of DVT.

The clinical outcomes of 2,054 renal recipients were examined retrospectively based on pre-transplant hepatitis B surface antigen (HBsAg) status to investigate the efficacy of lamivudine treatment in HBsAg positive recipients. Pre-transplant HBsAg positivity was documented in 66 recipients. The 10-year patient and graft survival rates in Ag positive group were significantly lower than those of Ag negative group (64.4/36.6% vs. 88.2/70.5%, respectively, P < 0.0001). Since 1997, lamivudine was used when hepatitis B virus polymerase chain reaction (HBV PCR) was positive or when the level of post-transplant viral load rose. Lamivudine given to 27 recipients markedly improved both 10-year patient and graft survivals compared to Ag positive renal recipients who did not take lamivudine (85.3/59.2% vs. 49.9/22.7%, respectively, P < 0.0001). Overall, 13 viral breakthroughs among 24 lamivudine-responsive patients were observed. The cumulative incidence of viral breakthrough at 60 months was 53.3%. Adefovir rescue in three viral breakthroughs patients induces virological response and restoration of liver function. In 10 patients who did not changed to adefovir, 6 patients are alive with elevated liver enzymes. In conclusion, in the era of lamivudine and adefovir, renal transplantation in HBsAg positive end-stage renal disease patients should not be abandoned.

The present study shows the expression profile and function of the homeobox gene, satb2 during zebrafish embryonic development. Satb2 was ubiquitously expressed from the 1 cell stage to the 10-somite stage in zebrafish embryos. Satb2 showed stage-specific expression profiles such as in the pronephric duct at 24 hpf, the branchial arches at 36 hpf, and the ganglion cell layer of the retina and fins at 48 hpf. Additionally, satb2 knockdown embryos were arrested at 50-60% epiboly, and transplantation experiments with satb2 knockdown cells showed migration defects. Interestingly, satb2 knockdown cells also exhibited down-regulation of dynamin II and VAMP4, which are involved in exocytosis and endocytosis, respectively. Furthermore, satb2 knockdown cells have a disorganized actin distribution and an underdeveloped external yolk syncytial layer, both of which are involved in epiboly. These results suggest that satb2 has a functional role in epiboly. This role may potentially be the regulation of endo-exocytic vesicle transport-dependent cell migration and/or the regulation of the development of the yolk syncytial layer.