We focused on determining the most accurate and convenient genotyping methods and most appropriate single nucleotide polymorphism (SNP) among four such polymorphisms associated with interleukin-28B (IL-28B) in order to design tailor-made therapy for patients with chronic hepatitis C virus (HCV) patients. 4%) patients, the four SNPs were not in LD. Eight of nine (88.9%) patients whose rs8099917 was homozygous for the major allele were virological responders, even though one or more of the other SNPs were heterozygous. The HP, TaqMan, and Invader methods were suitable to determine the SNPs associated with IL-28B. The rs8099917 polymorphism should be the best predictor for the response to the PEG-IFN/RBV treatment among Japanese chronic hepatitis C patients.

Summary Hepatitis B virus (HBV) is classified into several genotypes. Genotype G (HBV/G) is characterised by worldwide dispersion, low intragenotypic diversity and a peculiar sequence of the precore and core region (stop codon and 36‐nucleotide insertion). As a rule, HBV/G is detected in co‐infection with another genotype, most frequently HBV/A2. In a previous in vivo study, viral replication of HBV/G was significantly enhanced by co‐infection with HBV/A2. However, the mechanism by which co‐infection with HBV/A2 enhances HBV/G replication is not fully understood. In this study, we employed 1.24‐fold HBV/A2 clones that selectively expressed each viral protein and revealed that the core protein expressing construct significantly enhanced the replication of HBV/G in Huh7 cells. The introduction of the HBV/A2 core promoter or core protein or both genomic regions into the HBV/G genome showed that both the core promoter and core protein are required for efficient HBV/G replication. The effect of genotype on the interaction between foreign core protein and HBV/G showed that HBV/A2 was the strongest enhancer of HBV/G replication. Furthermore, Western blot analysis of Dane particles isolated from cultures of Huh7 cells co‐transfected by HBV/G and a cytomegalovirus (CMV) promoter–driven HBV/A2 core protein expression construct indicated that HBV/G employed HBV/A2 core protein during particle assembly. In conclusion, HBV/G could take advantage of core proteins from other genotypes during co‐infection to replicate efficiently and to effectively package HBV DNA into virions.

Summary.  Background and objectives: Analysis of dysfibrinogens has improved our understanding of molecular defects and their effects on the function of intact fibrinogen. To eliminate the influence of plasma heterozygous molecules, we synthesized and analyzed recombinant‐variant fibrinogens. Methods: We synthesized two recombinant‐variant fibrinogens with a single amino acid substitution at the 15Gly residue in the Bβ‐chain: namely, Bβ15Cys and Bβ15Ala. Results: Western blotting analysis of purified fibrinogen revealed the existence of a small amount of a dimeric form only for Bβ15Cys fibrinogen. For Bβ15Cys fibrinogen, functional analysis indicated (a) no thrombin‐catalyzed fibrinopeptide B (FPB) release and (b) markedly impaired lateral aggregation in thrombin‐ and reptilase‐catalyzed fibrin polymerizations. For Bβ15Ala fibrinogen, such analysis indicated slight impairments of both thrombin‐catalyzed FPB release and lateral aggregation in thrombin‐catalyzed fibrin polymerization, but nearly normal lateral aggregation in reptilase‐catalyzed fibrin polymerization. These impaired lateral aggregations were accompanied by thinner fibrin fiber diameters (determined by scanning electron microscopy of the corresponding fibrin clots). Conclusion: We conclude that a region adjacent to Bβ15Gly plays important roles in lateral aggregation not only in desA fibrin polymerization, but also in desAB fibrin polymerization, and we speculate that the marked functional differences between Bβ15A and Bβ15C fibrinogens in FPB release and fibrin polymerization might not only be due to the presence of a substituted cysteine residue in Bβ15C fibrinogen, but also to the existence of disulfide‐bonded forms. Finally, our data indicate that the Bβ15Gly residue plays important roles in FPB release and lateral aggregation of protofibrils.

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Introduction: We have reported a heterozygous dysfibrinogenemia, fibrinogen Otsu I, caused by the deletion of γAsn319 and γAsp320, which was originally identified in the dysfibrinogen Vlissingen/Frankfurt IV (V/FIV) associated with thrombosis. Unlike the V/FIV family, the Otsu propositus showed no thrombotic tendencies. To analyze the relationship between thrombosis and the heterozygous plasma variant fibrinogen, we used purified plasma fibrinogen from the Otsu patient and compared it with a normal control. Materials and Methods:Thrombin-induced fibrin clot formation and clot structure were observed by fibrin polymerization and scanning electron microscopy, respectively. For in vitro observation of fibrinolysis, plasmin generation and clot lysis assays were performed by the addition of tissue type plasminogen activation (tPA) and plasminogen. Results and Conclusions:Polymerization of Otsu was markedly impaired, while fibrin fibers were much thicker and the density of the bundles of fibrin fibers was less and porous compared with normal. Lysis of the Otsu clot was not significantly different from normal when a tPA and plasminogen mixture was overlaid onto the clots. For Otsu, the penetration of the tPA/plasminogen mixture into the clot was much faster than normal and the protection against plasmin cleavage was impaired, however, tPA-induced plasmin activation of the Otsu fibrin was slower than that of normal fibrin, resulting in a clot lysis of Otsu similar to normal.