In this study we provide further evidence associating activated cells of the monocyte lineage with the lesions of multiple sclerosis (MS). Using a combination of immunohistochemistry and reverse transcriptase-dependent in situ polymerase chain reaction analysis, we have identified monocytes expressing inducible nitric oxide synthase (iNOS) to be prevalent in the plaque areas of post mortem brain tissue from patients with MS. In addition, we have obtained evidence of the nitration of tyrosine residues in brain areas local to accumulations of iNOS-positive cells. In parallel studies we have assessed the effects of inhibitors of iNOS induction, as well as scavengers of nitric oxide and peroxynitrite in the experimental allergic encephalomyelitis model. Significant therapeutic effects were seen with the inhibitor of iNOS induction, tricyclodecan-9-xyl-xanthogenate, a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and a peroxynitrite scavenger, uric acid. In particular, treatment with high doses of uric acid virtually prevented clinical symptoms of the disease. Together with our demonstration of the presence of activated macrophages expressing high levels of iNOS and evidence of peroxynitrite formation in brain tissue from patients with MS, these findings are of importance in the development of approaches to treat this disease.
Two cases of spindle cell hemangioendothelioma (SCH) are reported. One of the patients was a 16 year old Japanese female, who had been suffering from Ollier's disease (multiple enchondrornatosis) since 3 years of age and had developed multiple SCH in the right leg at the age of 11 years. Spindle cell hemangioendothelioma lesions coincided with the site of enchondromatosis and increased in number thereafter. This is the first report of Ollier's disease complicated with multiple SCH. Another patient, a 33 year old Japanese female, who was a carrier of hepatitis B virus (HBV), developed solitary SCH in the lateral aspect of the right ankle where a lipoma was extirpated 10 years previously. Tumor cells of both cases were composed of four cell types: (i) spindle cells; (ii) epithelioid cells; (iii) vacuolated endothelial cells; and (iv) usual endothelial cells. Endothelia in the cavernous area and vacuolated cells reacted to Ulex europaeus agglutin 1 (UEA‐I), factor VIII‐related antigen and vimentin. Spindle cells and epithelioid cells reacted only to vimentin.
Accumulation of the p53 protein has been found in several types of lymphomas. However, p53 gene mutations have been infrequently demonstrated in some specific types of lymphomas. In the present study, a correlation between p53 immunoreactivity and p53 gene mutations in a large panel of non-Hodgkin's lymphoma (NHL) cases is attempted. A panel of 202 cases of NHL was evaluated by immunohistochemical staining for p53 protein. All cases that were immunohistochemically positive for p53 protein were analyzed by the polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) method to identify mutations within the p53 gene. In order to confirm the mutation, sequencing of PCR-amplified p53 gene segments was performed. Overexpression of p53 protein was found in 59 of the 202 cases of NHL, but only four of these 59 cases showed a shift on SSCP analysis, and point mutations were detected in three of them by the subsequent sequencing. p53 immunoreactivity was generally greater in high-grade lymphoma. The results of this study suggest that immunohistochemical reactivity for p53 protein is not a reliable indicator of the presence of their structural alterations of p53 gene exons 4-9 in NHL.
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