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Thorax 2004;59:252-256. doi: 10.1136/thorax.2003.012658 Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro [...]

Background & Aims: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. Methods: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. Results: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. Conclusions: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.

We have previously demonstrated that the ribozyme located 34 nucleotides downstream of the polyadenylation site on the antigenomic RNA of the hepatitis delta virus can stabilize the downstream transcript after polyadenylation. Here, we have reports on further investigations of the molecular mechanism of this stabilization effect and the potential role of the small and large delta antigens. We found that the downstream transcripts after polyadenylation were stabilized by the ribozyme independently of either the small or large delta antigen. The stabilization effect was abolished as the ribozyme activity was eliminated by mutations on either the enzyme domain or target site of the ribozyme. These findings suggested that it was the ribozyme activity rather than the RNA structure or the delta antigens that contributed to the stabilization effect.

By performing immunofluorescence staining assays in confluent COS-7 cells, hepatitis B virus core, small surface and large surface proteins were found to localize largely in the nucleus, diffusely in the cytoplasm, and accumulatively in a perinuclear area, respectively. When two proteins were co-expressed, the core protein was found co-localized with the large but not small surface protein in the cytoplasm. By performing subcellular fractionation experiments, the large surface protein was found to reduce the amount of the core protein in the nuclear fraction to an undetectable level. These results indicate that the large but not small surface protein can alter the subcellular localization of the core protein.

The nuclear localization signal of hepatitis B virus core protein contained three SPRRR motifs. Substitution of a single serine residue on the third SPRRR motif enhanced significantly the nuclear localization of core protein. By performing immunofluorescence staining assays and subcellular fractionation experiments, it was demonstrated that although nuclear transport of the wild type core protein was markedly suppressed by co-expression of hepatitis B virus surface proteins, nuclear transport of this serine mutant protein was not affected. These results indicated that the serine residue in the SPRRR motifs played an important role in regulating the nuclear transport of core protein and the interaction between core and surface proteins.Copyright 1995, 1999 Academic Press, Inc.

In this paper, the direct boundary element method based on a quadratic discontinuous element is used to investigate the edge crack propagation process for a linear elastic body with wavy surface. The load movement is assumed to be moving away from, moving toward to, and passing through the crack. The effect of waviness, friction and load magnitude are studied. For the cases of load moving away from the crack, if the ratio ϵ/α is smaller than 0.1 where ϵ is the amplitude of the wavy surface, then the effect of waviness may be ignored. For the cases of crack located at trough, the direction of crack propagation turns to a specific direction. This direction depends mainly on the wavy amplitude ϵ and friction force. The extension distance is larger for μ = 0.2 than μ = 0.0 as the load moves towards the crack. This trend is also true for a crack located at the trough of the wavy surface. However the patterns of crack growth are essentially the same. The load position of initial crack propagation may be influenced by friction. For the cases of load passing through the crack, the extension distance before the load passes through the crack is larger than that after the load passes through the crack in most cases studied in this paper.

Background: Patients with systemic lupus erythematosus (SLE) frequently suffer from infections, but the predisposing risk factors, as well as the exact frequency and nature of such infections, are not fully understood. Aim: To describe the frequency, types and risk factors for infections in a group of Chinese patients in the early stage of SLE in Hong Kong. Design: Retrospective record study. Methods: We reviewed the case records of 91 Chinese SLE patients, presenting <12 months after SLE diagnosis. Details of major infections (requiring intravenous antimicrobial therapy, or any confirmed mycobacterial infection) and minor infections were reviewed. Clinical and laboratory features, the systemic lupus erythematosus disease activity index (SLEDAI) at presentation and drug treatment were recorded and analysed. Results: There were 48 major infections and 62 minor infections during 260 patient-years of follow-up. A lymphocyte count 1.0 × 109/l at presentation was independently associated with an increased risk for major infection: hazard ratio 4.7 (95%CI 1.6–13.7), p = 0.005. SLEDAI, use of corticosteroids and immunosuppressive therapy were all not associated with increased risk of infection. Discussion: Lymphopenia was an important risk factor for major infections in this group of Chinese patients in the early stages of SLE. SLE patients with lymphopenia at presentation should be closely monitored for the development of infective complications.