Mimosine, a non-protein amino acid, is mainly known for its action as a reversible inhibitor of DNA replication and, therefore, has been widely used as a cell cycle synchronizing agent. Recently, it has been shown that mimosine also induces apoptosis, as mainly reflected in its ability to elicit characteristic nuclear changes. The present study elucidates the mechanism underlying mimosine's apoptotic effects, using the U-937 leukemia cell line. We now demonstrate that in isolated rat liver mitochondria, mimosine induces mitochondrial swelling that can be inhibited by cyclosporine A, indicative of permeability transition (PT) mega-channel opening. Mimosine-induced apoptosis was accompanied by formation of hydrogen peroxide and a decrease in reduced glutathione levels. The apoptotic process was partially inhibited by cyclosporine A and substantially blocked by the antioxidant N-acetylcysteine, suggesting an essential role for reactive oxygen species formation during the apoptotic processes. The apoptosis induced by mimosine was also accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase 3 and 9 activation. Our results thus imply that mimosine activates apoptosis through mitochondrial activation and formation of H2O2, both of which play functional roles in the induction of cell death.

We report on three patients who were treated with corticosteroids only prior to the diagnosis of splenic lymphoma. Corticosteroids were administered for different conditions, at different doses, and for various periods of time. The primary diagnosis was splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma in the three cases, and it was reached with variable difficulty. We suggest that the corticosteroid treatment was one of the causes for the complications in reaching a diagnosis. The morphologic appearance of the microscopic splenic nodules was the most variable feature and may possibly reflect the dose and duration of the corticosteroid therapy. However, the histopathologic changes are probably not related with Epstein-Barr virus-induced immunosuppression.

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