Annual Research Meeting for Graduate Students

Histiocytic necrotizing lymphadenitis (HNL) usually affects cervical lymph nodes of young individuals and has a self-limited clinical course. Viral infection is ascribed as its cause, but its pathogenesis still remains unknown. A real-time PCR assay is useful for not only sensitive detection but also quantitation of virus DNA with a wide linear range. Using this technology, we estimated the load of herpesvirus: Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV) type 6, 7, and 8. The mean EBV-DNA copy number was 10 2.1 copies/ microg of DNA in lymph nodes from patients with HNL (6/20, 30%), 10 2.4 in RL (12/19, 63%). By in situ hybridization, EBV-encoded RNA was also detected in the cases with more than 10 1.2 copies/microg of EBV-DNA. HHV6-DNA was detected in 3/20 (15%) HNL cases, 1/ 19 (5.3%) RL. HHV7-DNA in 2/20 (10%) HNL and 4/19 (21%) RL, with no distinct difference. Neither CMV nor HHV8 was detected in any case by the real-time PCR assay. In this study we could not identify a definitely causative herpesvirus for HNL. However one HNL case had a significantly larger copy number of HHV6-DNA and positive immunostains for HHV6 early/late antigen in necrotic foci, suggesting that HHV6 infection might be associated with some cases of HNL. Aurora-B is a protein kinase required for chromosome condensation/segregation and for the progression of cytokinesis during the cell cycle. We report here that Aurora-B phosphorylates type III intermediate filaments (IFs), glial fibrillary acidic protein (GFAP) and desmin, and that this phosphorylation regulates their filament organization during cytokinesis. In vitro, Aurora-B phosphorylates GFAP and desmin, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by Aurora-B; Thr-7/Ser-13/Ser-38 of GFAP and Thr-16 of desmin are common with those related to Rho-associated kinase (Rho-kinase) which has been reported to phosphorylate GFAP and desmin at cleavage furrow during cytokinesis. We indentified Ser-11 and Ser-59 of desmin to be specific sites phosphorylated by Aurora-B. Use of antibodies that specifically recognized desmin phosphorylated at Ser-11 and Ser-59 led to the finding that these sites are also phosphorylated specifically at the cleavage furrow during cyto-48 kinesis in Saos-2 cells. Desmin mutants, in which phosphorylation sites by Aurora-B and/or Rho-kinase are changed to Ala or Gly, cause dramatic defects in filament separation between daughter cells in cytokinesis. Therefore, one function of Aurora-B is the regulation of cleavage furrow-specific phosphorylation and segregation of type III IFs …