Reappraisal of the importance of mutations in the NS5A-PKR-binding domain of hepatitis C-1b virus in the era of optimally individualized therapy.

Past studies have reported that mutations in the protein kinase R-binding domain (PKRBD) sequences of hepatitis C virus (HCV) NS5A proteins are correlated with response to fixed-duration interferon (IFN)-based therapy in patients infected with HCV-1b. In this study, we investigated whether the substitutions in PKRBD, including the IFN sensitivity-determining region (ISDR) and 26 additional downstream amino acids from ISDR, will have effects upon patients infected with chronic HCV-1b in the era of individualized therapy with peginterferon and ribavirin. Thirty-seven patients were treated with optimally tailored therapy guided by baseline viral load combined with rapid and early virological responses while 23 patients were treated without guidance and/or assigned suboptimal treatment duration. The amino acid sequences of the PKRBD were determined by PCR and sequencing. The overall sustained virological response (SVR) rate of patients who received optimally individualized therapy was 78.4%, which was better than the SVR rate of patients who received suboptimal therapy (47.8%, P = 0.015). Multivariate analysis showed that optimally individualized therapy (P = 0.019) and 80/80/80 adherence (P = 0.006) were independent favourable predictors of SVR in the entire cohort. Further sub-analysis of the predictive factors of SVR in patients treated with optimally individualized therapy showed that mutations in the 26-amino acid downstream from the ISDR (P = 0.024) were the only independent predictor of SVR. We concluded that mutations in 26-amino acid downstream portion from the ISDR remained a prognosticator of SVR in the era of optimally tailored therapy.

Distribution of lysosome-associated membrane proteins-1 and -2, and cathepsin D in eosinophilic granular bodies: possible relationship to cyst development in pilocytic astrocytomas.

Pilocytic astrocytomas are usually cystic; cyst formation within these tumours may result in increased intracranial pressure, due to the effect of their mass, and contribute to cerebral damage. Eosinophilic granular bodies (EGBs) are produced abundantly in pilocytic astrocytomas but their role in disease progression remains unknown. Immunohistochemistry studies showed EGBs to exhibit pronounced reactivity to antibodies against lysosome-associated membrane proteins (LAMP)-1 and LAMP-2, and the lysosomal enzyme cathepsin D. Both LAMP-1 and LAMP-2 showed peripheral rim and granular staining patterns. The EGBs were scattered widely across cysts and, where EGBs aggregated in clusters, were usually close to areas of fluid in the cysts. Most EGBs had nuclei either attached or close by, indicating that the EGBs may be derived from anucleated astrocytes. The results suggest that EGBs, together with other factors, may play a role in the development of cysts in pilocytic astrocytomas.

[Thymoma with pure red cell aplasia and hemophagocytic syndrome--one case report].

Erythropoietic hypoplasia occurring in the absence of abnormalities in the leukopoietic and thrombocytopoietic series is often defined as "pure red cell aplasia" (PRCA). This condition may appear as an acquired defect of either acute or chronic type, and a congenital form as well. The chronic form of acquired PRCA occurred mostly in adults. It has been reported that a demonstrable thymoma occurred in more than 50% of patients with PRCA. Recent studies suggested that it may contribute to several immune mechanisms. Here we report a case of thymoma with PRCA whose clinical presentations include severe anemia, shock with severe metabolic acidosis, high levels of several organ enzymes (SGOT, SGPT, LDH, CPK, Amylase) and acute renal shutdown with similar manifestations to septic shock. Our explanation to his condition is multi-organ tissue hypoxia caused by severe anemia. Hemophagocytic syndrome was found by the repeated bone marrow smear before death. The clinical course of this patient was so impressive as to be presented here for discussion.