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Introduction Normal cellular proliferation is a complex process that requires the coordinated integration of both stimulatory and inhibitory growth factors. TGF-[beta], a 25-kDa homodimer prototypic of a family of proteins [...], TGF-[beta] is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventingthe nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-[beta] activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity. TGF-[beta] signaling mediated by pSMAD2, bone morphogenetic protein 4 (BMP4), EGF, or PDGF was unaffected bytheTAT-SNX9 peptide. Furthermore, while the TAT-SNX9 peptide prevented TGF-[beta]'s profibrotic activity in vitro as well as in 2 murine treatment models of pulmonary fibrosis, a 3-amino acid point mutant that was unable to bind pSMAD3 proved ineffective. These findings indicate that specifically targeting pSMAD3 can ameliorate both the direct and indirect fibroproliferative actions of TGF-[beta].

Objectives: The purpose of this study was to clarify the prognostic significance of visceral pleura invasion in T2 non-small cell lung cancer (NSCLC). Materials and methods: Between 1990 and 2001, 439 consecutive patients with T2 NSCLC underwent curative surgical resection. The subjects included 234 patients with stage IB, 95 with stage IIB, and 110 with stage IIIA and B disease. The patients were divided into two groups according to the existence of visceral pleura invasion (group I without, group II with). Both groups were compared with regard to tumor size, histology, associated mediastinal lymph node involvement, and survival rates. Results: Visceral pleura invasion (group II) was identified in 114 patients (26%), and was present in 22% of patients with NSCLC with a tumor size of 3 cm or less and in 27% of those with a tumor larger than 3 cm (P=0.37). Visceral pleura invasion was associated with a higher frequency of mediastinal lymph node involvement (group I=22%, group II=34%, P=0.009). Five- and 10-year survival rates were 50 and 45% in group I, and 36 and 22% in group II (P=0.0006). In stage IB, visceral pleura invasion was identified in 53 patients (23%), and 5- and 10-year survival rates were 63 and 60% in the visceral pleura non-invasion group, and 44 and 28% in visceral pleura invasion group (P=0.0018). By multivariate Cox model analysis, age at intervention (relative risk=1.03, P=0.0017), N status (relative risk=1.53, P<0.0001), tumor size (relative risk=1.83, P=0.0452) and visceral pleura invasion (relative risk=1.42, P=0.0291) were independent predictors of poor prognosis. Conclusions: We were able to demonstrate that visceral pleura invasion was a factor of poor prognosis in T2 NSCLC. It was found to correlate with more extensive mediastinal lymph node involvement and a decreased survival rates. Therefore, the patients with visceral pleura invasion should be closely followed up especially. [Copyright &y& Elsevier]

Objective: Hemifacial spasm (HFS) caused by vertebrobasilar dolichoectasia (VBD) is very rare, and in theses cases, it is difficult to decompress the nerve from its vascular compression. The objective of this study was to investigate the outcome of microvascular decompression (MVD) for HFS caused by VBD., Methods: There were 10 patients of HFS caused by VBD at our hospital between September 1978 and September 2008. We evaluated magnetic resonance angiography (MRA) and time of flight magnetic resonance imaginge (TOF MRI) findings using the criteria for VBD. We compared the clinical outcomes of MVD for the 10 patients with VBD with the overall outcomes of the total 2058 MVDs performed for HFS., Results: The results of MVD for HFS caused by VBD were successful in 90.9% of cases. The postoperative complication rate in VBD was 45.5%. Offending vessels in patients with VBD were identified visually during surgery. Adverse effects after MVD were found in 4 patients. We found that the diameter of VBD was significantly greater in patients with complications than in those with no complications (p=0.028)., Conclusion: Our data shows that MVD may be a good treatment modality for HFS caused by VBD but care must be taken to avoid adverse effects from the procedure. It is important to detach the dolichoectatic artery from its surrounding structures sufficiently to allow it to be easily movable. In addition, attempts should be made to lessen the retraction of the cerebellum during release of the dolichoectatic artery.

The extent of resection and release of the trachea is important for successful anastomosis. Bilateral bronchial dissection is one of the release techniques for resection of the lower trachea. We present the experience of cervical video-assisted mediastinoscopic bilateral bronchial release for long segmental resection and anastomosis of the lower trachea.

Objective: Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with Bispectral index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring., Methods: We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing., Results: The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were 0.63 +/- 0.26 in low dose group, and 1.31 +/- 0.48 in high dose group. The treatment durations were 4.89 +/- 1.68 days and 3.38 +/- 1.24 days in low dose BCT and high dose BCT, respectively., Conclusion: It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP.