Transgenic Expression of Entire Hepatitis B Virus in Mice Induces Hepatocarcinogenesis Independent of Chronic Liver Injury

Hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide, is most commonly caused by chronic hepatitis B virus (HBV) infection. However, whether HBV plays any direct role in carcinogenesis, other than indirectly causing chronic liver injury by inciting the host immune response, remains unclear. We have established two independent transgenic mouse lines expressing the complete genome of a mutant HBV (“preS2 mutant”) that is found at much higher frequencies in people with HCC than those without. The transgenic mice show evidence of stress in the endoplasmic reticulum (ER) and overexpression of cyclin D1 in hepatocytes. These mice do not show any evidence of chronic liver injury, but by 2 years of age a majority of the male mice develop hepatocellular neoplasms, including HCC. Unexpectedly, we also found a significant increase in hepatocarcinogenesis independent of necroinflammation in a transgenic line expressing the entire wildtype HBV. As in the mutant HBV mice, HCC was found only in aged—2-year-old—mice of the wildtype HBV line. The karyotype in all the three transgenic lines appears normal and none of the integration sites of the HBV transgene in the mice is near an oncogene or tumor suppressor gene. The significant increase of HCC incidence in all the three transgenic lines—expressing either mutant or wildtype HBV—therefore argues strongly that in absence of chronic necroinflammation, HBV can contribute directly to the development of HCC

Family relations and behavioral-emotional problems in adolescents - an analysis with the adolescent version of the Family Relations Test for Children and Adolescents

Objectives: So far hardly any instruments are available for the German-speaking countries, covering family relations from the perspective of young people reliably. Moreover, the relationship between family relations from the perspective of young people and behavioral problems has been rarely investigated. Method: Based on the Family Relations Test, which has been developed originally for children, the Family Relations Test for Children and Adolescents was developed in order to assess the family relations from the perspective of adolescents (94 items, 44 % newly developed). A clinical sample (n = 152) and a fi eld sample (n = 132) was tested with this instrument and additionally behavioural problems of the adolescents were rated by the parents and the adolescents. Results: The two-factor solution of the principal component analysis resulted in a clear distinction between two factors describing positive and negative family relations. The internal consistencies (Cronbach's Alpha) of the scales describing positive and negative relations are between.91 and.93. On these total scores young people from the clinic sample describe overall stronger negative relations in their families compared to young people in the fi eld sample. Within the clinic sample moderate correlations between the extent of mental problems of young people rated by themselves and their parents could be found. Conclusions: Positive and negative relationships of young people to the individual family members and to all members of the family as a whole can be assessed reliably and factorially valid. As expected, signifi cant correlations between negative family relations and mental problems could be found. The adolescent version of the Family Relations Test for Children and Adolescents proves to be a useful tool, to assess family relationships from the perspective of young people and thus to identify possible factors maintaining mental disorders of young people