The human polyomavirus BK (BKV)-associated hemorrhagic cystitis (HC) has been a frequent and, seldom life-threatening complication after bone marrow transplantation (BMT). The authors report a male with melodysplastic syndrome, who developed BKV-associated late-onset HC 12 days after HLA-matched unrelated BMT. His urine contained epithelial cells with intranuclear inclusion bodies suggestive of BKV infection and was positive for BKV in polymerase chain reaction. He did not respond to any treatment for HC. In addition, he developed BKV-associated acute renal failure on day 26, followed by hepatic veno-occlusive disease on day 42. This is the first case in which BKV may be associated with fatal progressive renal failure.
Purpose: We examined the activity of gemcitabine against neuroblastoma in vitro and in vivo. In addition, we investigated the cellular mechanisms of high sensitivity to the agent in neuroblastoma cells. Experimental Design: We examined 11 neuroblastoma cell lines for sensitivity to gemcitabine and other chemotherapeutic agents used clinically for neuroblastoma. The in vivo sensitivity of neuroblastoma to gemcitabine was determined in xenograft models. Furthermore, the major metabolic enzymes of gemcitabine were assessed and compared in leukemia and carcinoma cells. Apoptosis and mitochondrial membrane potentials were also evaluated. Results: The IC 50 s for gemcitabine in 11 neuroblastoma lines ranged between 3 nmol/L and 4 Amol/L.The high activity of gemcitabine against neuroblastoma was confirmedin animal models. Interestingly, enzymes in neuroblastoma cells involved in the metabolism of deoxycytidine analogue have unique characteristics among solid tumors.The median of deoxycytidine kinase activity in neuroblastoma lines was similar to that in leukemia lines, which have low IC 50 s for cytarabine. Cytidine deaminase (CDA) activity in neuroblastoma was hardly detectable and significantly lower than that in carcinoma. The defect of CDA activity was associated with negative expression of mRNA. Furthermore, gemcitabine-induced apoptosis was observed irrespective of the caspase-8 status of neuroblastoma cells, which indicates that apoptosis depends on the mitochondrial pathway. Conclusions: Neuroblastoma is highly sensitive to gemcitabine. Although the cellular mechanism involved in sensitivity to gemcitabine is multifactorial, low CDA activity may contribute high sensitivity in neuroblastoma cells.These results suggest that clinical application of gemcitabine to the treatment of neuroblastoma is warranted.
Acute myositis with transient decrease of albumin, immunoglobulin, and complement following rotavirus gastroenteritis MOTOKI BONNO.' MASAMUNE HIGASHIGAWA.' TAKASHI NAKANO,' MASAZUMI MIYAHARA.' EIICHI AZUMA,'.' YOSHIHIRO KOMADA.' MASAHIRO ITO' AND MINORU SAKURAI' iDqxirtiiieiit of' Prclirrtr?cs. 'Depnrti?ierrt cf Cliriicnl iiwrnunology, Mie University Sclzool of Medicine, a r i d .'Abstract A 2-year-old boy developed acute myositis associated with rotavirus gastroenteritis. He had remarkableshelling and subcutaneous edema. mostly i n the legs, 4 days after the onset of gastroenteritis. Marked ele\ ation of creatine kinase was observed while serum albumin, immunoglobulin, and complement were decreaaed.
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