Hepatic STAT1-Nuclear Translocation and Interleukin 28B Polymorphisms Predict Treatment Outcomes in Hepatitis C Virus Genotype 1-Infected Patients

We investigated associations between signal transducer and activator of transcription (STAT) 1 in pretreated liver tissues, interleukin (IL) 28B polymorphism and treatment response in hepatitis C virus (HCV)-infected patients treated with peginterferon and ribavirin.We performed immunostaining analysis of STAT1 in liver tissues and determined IL28B polymorphism at rs8099917. We then compared the results with treatment outcomes in HCV genotype 1 patients with high viral load who were receiving peginterferon plus ribavirin. In univariate analysis, younger age, white blood cell counts, virological responder, early virological responder (EVR), mild activity (A1) of liver inflammation grading, and lower STAT1 nuclear-stain of hepatocytes in zone 1, zone 2 and total zones of liver were associated with sustained virological responder (SVR). Multivariate analysis showed that EVR, age and hepatic STAT1 nuclear-stain in zone 2 of liver were independent predictors of SVR. It was also revealed that IL28B and STAT1-nuclear translocation in hepatocytes are independent predictors of response to treatment with peginterferon and ribavirin in chronic hepatitis C patients.Concomitant assessment of lower STAT1 nuclear-stain of hepatocytes and IL28B polymorphism is useful for prediction of SVR in HCV genotype 1 patients

The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions

Follicular Dendritic Cell-Specific Prion Protein (PrPc) Expression Alone Is Sufficient to Sustain Prion Infection in the Spleen

Prion diseases are characterised by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. Following peripheral exposure high levels of prion-specific PrPSc accumulate first upon follicular dendritic cells (FDC) in lymphoid tissues before spreading to the CNS. Expression of PrPC is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrPC expression was specifically “switched on” or “off” only on FDC. We show that PrPC-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrPC-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrPC expression on FDC

New monoclonal antibodies directed against mouse follicular dendritic cells.

The follicular dendritic cells (FDC) in B-lymphoid follicles are unique reticular cells that retain immune complexes on their surfaces. We developed new monoclonal antibodies (MAb), SKY01, 28, 41, and 49, against mouse FDC without useful cell markers. Immunohistochemical study of spleen and lymph node tissues from Balb/c, C3H, and C57BL/6 mice revealed that SKY01 and 49 were highly specific for FDC, whereas SKY28 and 41 reacted with other stromal components as well as FDC. On immunoelectron microscopy (IEM), reaction products for all MAb were localized on the surfaces of FDC. In ontogenetic study of Balb/c spleen, FDC precursors were not immunodetected with any of the MAb at 1 week after birth. The FDC that first appeared as immune complex-retaining cells at 2 weeks were a subpopulation of SKY01-, 49-, 28+, and 41+ reticular cells. At 3 weeks, FDC were positive for all MAb, like adult spleen. These results indicate that our MAb recognize differentiation antigens of FDC. Comparative immunohistochemical studies of spleen from athymic nude and severe combined immunodeficiency mice suggested that B-cells may be required for the differentiation of FDC. Consequently, these MAb are considered useful tools for research on FDC. </jats:p