Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of "collateral damage" of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology.

Chromosome 9, which is often partially or fully reduced to homozygosity in bladder cancer cells, harbors several tumor suppressor loci including deleted in bladder cancer chromosome region 1 (DBCCR1) at 9q32-33. To study DBCCR1 function, stable cell lines, inducible for DBCCR1 expression by tetracycline, were made, but the DBCCR1 protein was not expressed at detectable levels. To understand the fate of DBCCR1-expressing cells, human bladder tumor cells were transiently transfected with an expression vector containing DBCCR1 fused to enhanced green fluorescent protein (EGFP). Initially, DBCCR1-EGFP-expressing cells demonstrated diffuse cytoplasmic green fluorescence with nuclear exclusion patterns. After time, the intensity level of green fluorescence increased and a granular distribution of protein became visible in the cells. At this point, cells rounded up and detached from the tissue culture dish. Cells transfected with a control vector, containing only EGFP, and partial DBCCR1-EGFP fusion constructs did not demonstrate this behavior. DBCCR1-mediated cell death in cultured tumor cells was independent of caspase-3 activation and did not result in detectable DNA strand breaks by TUNEL staining that are hallmarks of the classical apoptotic pathway.

It appears that DBCCR1 and ASML3a are involved in the process of bladder tumorigenesis. Their interaction may provide clues to discern their functions.

While progression from low to high grade occurred in less than 15% of patients, grade regression was observed in almost 50%. The loss of p53 positivity in regressing tumors indicates that these recurrences are molecularly distinct from the corresponding initial tumor.

Background: Transgenic TCR mice are often used experimentally as a source of T cells of a defined specificity. One of the most widely used transgenic TCR models is the OT-1 transgenic mouse in which the CD8+ T cells express a TCR specific for the SIINFEKL peptide of ovalbumin presented on k b . Although OT-1 CD8+ can be used in a variety of different experimental settings, we principally employ adoptive transfer and peptide-driven expansion of OT-1 cells in order to explore the distribution and fate of these antigen-specific OT-1 T cells. We set out to develop a quantitative PCR assay for OT-1 cells in order to assess the distribution of OT-1 CD8+ T cells in tissues that are either intrinsically difficult to dissociate for flow cytometric analysis or rendered incompatible with flow cytometric analysis through freezing or fixation.