LMP1 antagonizes WNT/β-catenin signalling through inhibition of WTX and promotes nasopharyngeal dysplasia but not tumourigenesis in LMP1(B95-8) transgenic mice

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) can induce cell transformation and tumourigenesis, but the mechanism is not understood. Previous studies have suggested that LMP1 acts through up-regulation of cellular proliferation pathways including the Wnt/β-catenin pathway, in which β-catenin is the central effector. Increased levels of β-catenin coupled with a decrease in E-cadherin lead to reduced cell adhesion. This pathway is antagonized by WTX (Wilms' tumour gene on the X chromosome), which can promote the ubiquitination and degradation of β-catenin. In the present study, we established L2/LMP1B(95 - 8) /EGFP transgenic mice to investigate the in vivo role of LMP1. Down-regulation of WTX and E-cadherin was accompanied by increased expression of β-catenin in these mice. Even though invasive tumours did not develop, dysplasia was seen in the nasopharynx and oropharynx epithelium of these transgenic mice. Analysis of LMP1(+) , WTX(+) , and LMP1 siRNA silenced HNE-1 cell lines demonstrated that WTX could exert a dominant role in LMP1-mediated WNT/β-catenin pathway regulation. This study indicates that LMP1 antagonizes the WNT/β-catenin pathway by inhibiting WTX, and this reduction in WTX is associated with epithelial dysplasia via regulation of the WNT/β-catenin pathway molecules E-cadherin and β-catenin. Further studies are required for a better understanding of the relationship between LMP1-mediated antagonization of the WNT/β-catenin pathway and tumourigenesis.     

Temporary tricuspid valve leaflet detachment for closure of perimembranous ventricular septal defect: Early experiences

Background  

Detachment of the Tricuspid Valve Leaflet (TVD) has been described for better access to repair Perimembranous Ventricular Septal Defects (pVSD). The present report is our early experience with which has been found to be safe and easy with reproducible results.     

Association of bilirubin and protein thiols in relation to copper and ceruloplasmin in hyperbilirubinemic patients

Objective： Bilirubin is a double edged sword in biological system, acting as a toxic molecule and cytoprotectant. Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo. In the current work we tried to know the relationship between both conjugated and uneonjugated bilirubin with copper and protein thiols in patients with hyperbilirubihernia. Methods： Study was conducted on 56 hyperbilirubinemie eases and 56 healthy controls. Serum copper, ceruloplasmin, protein thiols, total bilirubin, conjugated and unconjugated bilirubin, uneonjugated bilirubin/albumin ratio, total protein, albumin, AST, ALT and ALP were estimated. Results： There was significant increase in serum copper, total biliruhin, conjugated and uneonjugated bilirubin, uneonjugated bilirubin/albumin ratio, AST, ALT, and ALP, and decrease in serum ceruloplasmin, protein thiols, total protein, and albumin in hyperbilirubinemie cases when compared to healthy controls. Conjugated bilirubin correlated positively with liver enzymes AST and ALP, and negatively with protein thiols, total protein and albumin. Uneonjugated bilirubin correlated positively with ALT. Protein thiols correlated negatively with copper and positively with eeruloplasmin, and also correlated negatively with liver enzymes like AST, ALT and ALP, and positively with total protein and albumin. Conclusion： Combination of elevated levels of trace elements like copper and availability of reducing agent like bilirubin may prove deleterious by generating free radicals.     

Life-threatening megaloblastic pancytopenia with normal mean cell volume: Case series

The mean red blood cell volume (MCV) is usually increased in severe megaloblastic anemia due to pernicious anemia. However, during one year in a university hospital, three patients with life-threatening pancytopenia and normal MCV were proven to have severe vitamin B12 deficiency. The red blood cell distribution width was markedly increased (three times normal) and led to review of the blood smear and recognition of megaloblastosis as well as prominent red cell fragmentation. These three cases illustrate that vitamin B12 status should be evaluated in cases of pancytopenia, independent of the MCV value.     

Vertical fixation with fibrin glue-assisted secondary posterior chamber intraocular lens implantation in a case of surgical aphakia

We report the first case of vertical fixation by fibrin glue-assisted secondary posterior chamber intraocular lens implantation in a case of surgical aphakia. Advantages of vertical fixation are discussed.