Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels.

Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on-treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty-two patients with HBeAg-positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on-treatment factors, on-treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log(10) IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940-1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On-treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut-off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log(10) PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on-treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg-positive CHB patients with entecavir treatment.

Infection by a symbiotic polydnavirus induces wasting and inhibits metamorphosis of the moth Pseudoplusia includens.

Insect pathogens and parasites often affect the growth and development of their hosts, but understanding of these processes is fragmentary. Among the most species-rich and important mortality agents of insects are parasitoid wasps that carry symbiotic polydnaviruses (PDVs). Like many PDV-carrying wasps, Microplitis demolitor inhibits growth and pupation of its lepidopteran host, Pseudoplusia includens, by causing host hemolymph juvenile hormone (JH) titers to remain elevated and preventing ecdysteroid titers from rising. Here we report these alterations only occurred if P. includens was parasitized prior to achieving critical weight, and were fully mimicked by infection with only M. demolitor bracovirus (MdBV). Metabolic assays revealed that MdBV infection of pre-critical weight larvae caused a rapid and persistent state of hyperglycemia and reduced nutrient stores. In vitro ecdysteroid assays further indicated that prothoracic glands from larvae infected prior to achieving critical weight remained in a refractory state of ecdysteroid release, whereas infection of post-critical weight larvae had little or no effect on ecdysteroid release by prothoracic glands. Taken together, our results suggest MdBV causes alterations in metabolic physiology, which prevent the host from achieving critical weight. This in turn inhibits the endocrine events that normally trigger metamorphosis.

The role of inverted repeat (IR) sequence of the virE gene expression in Agrobacterium tumefaciens pTiA6.

Agrobacterium tumefaciens pTiA6 virE promoter has a vir box, an inverted repeat (IR) sequence, a putative -35 region and a consensus -10 region. To study how the IR sequence of the virE promoter plays a role in virE gene expression, various mutants were constructed by base substitution and deletion in the virE promoter region. Substitution of the 3'-end region of the IR sequence, 5'-TCCGTTTCAA-3' to 5'-GCGGCCGCTC-3' displayed 2.6% of the native virE promoter activity. A deletion mutant of 5'-CGTTTCAA-3' on the 3'-end region of the IR sequence expressed 6% of the native virE promoter activity. These mutational analyses demonstrated that the IR sequence of the virE promoter plays a role as a cis-acting element in virE expression.

No evidence of hSNF5/INI1 point mutations in choroid plexus papilloma.

Choroid plexus carcinomas (CPC) have been shown to carry mutations in the hSNF5/INI1 gene on chromosomal arm 22q11.2. A recent study on choroid plexus papillomas (CPP) and CPC revealed frequent losses of chromosomal portions on the long arm of chromosome 22 (-22q). The region harbouring hSNF5/INI1 was affected in 47% of the CPP and 73% of the CPC, respectively. -22q occurred more frequently in adult than in infantile CPP suggesting different pathogenetic pathways for these tumours. These findings may indicate a potential tumour suppressor gene function of hSNF5/INI1 in a subset of choroid plexus tumours. In order to examine its potential role in the pathogenesis of choroid plexus tumours, we analysed exons 1-9 of hSNF5/INI1 by SSCP analysis in a series of 21 formalin-fixed and paraffin-embedded CPP. No alterations in migratory patterns were detected. These data indicate that somatic point mutations of hSNF5/INI1 do not play a role in the pathogenesis of CPP and that CPP and CPC may arise by two different molecular pathways.