Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B

BACKGROUND: After perinatal transmission of hepatitis B virus, infants of anti-HBe positive HBsAg carrier mothers may develop fulminant hepatitis B. Previously it has been suggested, that fulminant hepatitis B in adults was associated with specific mutations in the HBV-genome. The aim of this study was to investigate, whether specific viral variants are associated with fulminant hepatitis B in young infants. METHODS: The complete HBV-genomes of five mothers and their infants with fulminant hepatitis were isolated from the sera, amplified and directly sequenced. RESULTS: Between 6 and 43 base pair exchanges between the HBV genomes of the infants and their mothers were identified. The mutations spread over the entire virus genome. Nucleotide exchanges in the basic core promotor and precore region were identified in all cases. A heterogeneous virus population was detected in four mothers. CONCLUSIONS: Many new mutations were proved to emerge during fulminant hepatitis B in infants, who had been perinatally infected. HBeAg negative variants were the predominant population in all children, whereas these mutants could only be detected as subpopulations in four mothers. The data suggest that the selection of a specific HBeAg negative viral strain may be associated with the development of fulminant hepatitis B in children

Genetische Analyse der Kandidatengene NFKB1 und UCHL1 bei deutschen Patienten mit Morbus Parkinson

In der vorliegenden Arbeit wurden die Kandidatengene NFKB1 und UCHL1 einer Mutationsanalyse unterzogen. Methode: Als Screening wurde die SSCP-Methode angewandt. Ggf. schlossen sich direkte Sequenzierung und Allelassoziationsuntersuchungen an. Ergebnis: Bei 96 sporadischen Patienten wurden keine Proteinstruktur verändernden Basenaustausche im NFKB1-Gen gefunden. Im UCHL1-Gen wurde ein S18Y-Polymorphismus im Exon 3 in der untersuchten deutschen Population gefunden. Für Träger des Y-Allels ergab sich ein geringeres Erkrankungsrisiko für sporadischen MP. Diskussion: Eine genetische Veränderung des NFKB1-Gens kommt allenfalls äußerst selten als ursächlicher Faktor in der Pathogenese des MP in Frage. Für den sporadischen MP ergab die Assoziationsstudie deutliche Hinweise für eine pathophysiologische Relevanz des UCHL1-Gens im Rahmen der multifaktoriellen Entstehung

Generation of Immune Responses against Hepatitis C Virus by Dendritic Cells Containing NS5 Protein-Coated Microparticles ▿

Dendritic cells (DCs) internalize and process antigens as well as activate cellular immune responses. The aim of this study was to determine the capacity of DCs that contain antigen-coated magnetic beads to induce immunity against the nonstructural hepatitis C virus (HCV) antigen 5 (NS5). Splenocytes derived from Fms-like tyrosine kinase receptor 3 (Flt3) ligand-pretreated BALB/c mice were incubated with magnetic beads coated with HCV NS5, lipopolysaccharide (LPS), and/or anti-CD40; purified; and used for immunization. Cellular immunity was measured using cytotoxic T-lymphocyte (CTL) and T-cell proliferation assays, intracellular cytokine staining, and a syngeneic tumor challenge using NS5-expressing SP2/0 myeloma cells in vivo. Splenocytes isolated from animals vaccinated with DCs containing beads coated with NS5, LPS, and anti-CD40 secreted elevated levels of interleukin-2 (IL-2) and gamma interferon in the presence of NS5. The numbers of CD4+, IL-2-producing cells were increased >5-fold in the group immunized with DCs containing beads coated with NS5, LPS, and anti-CD40, paralleled by an enhanced splenocyte proliferative response. Immunization promoted antigen-specific CTL activity threefold compared to the level for control mice and significantly reduced the growth of NS5-expressing tumor cells in vivo. Thus, strategies that employ NS5-coated beads induce cellular immune responses in mice, which correlate well with the natural immune responses that occur in individuals who resolve HCV

S2k Leitlinie Cholestase im Neugeborenenalter, AWMF-Register Nr. 068/015

Diese Leitlinie wurde unter Federführung der GPGE und mit Beteiligung der DGKJ, der GNPI und der DGKCH erstellt und soll als praktische Hilfe für die Diagnostik und Therapie der Cholestase im Neugeborenen- und jungen Säuglingsalter dienen. Sie soll den aktuellen Stand der Wissenschaft darstellen, das Erkennen der Erkrankung fördern und die Behandlung der Patienten verbessern