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Streptococcus mutans, a major etiological agent of dental caries, frequently causes systemic disease, such as subacute bacterial endocarditis, if it enters the bloodstream. In this study, the production pathways of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induced by S. mutans in mouse macrophage were examined using a quantitative real-time polymerase chain reaction and an enzyme-linked immunosorbent assay. The S. mutans stimulated the expression of TNF-α and IL-1β mRNA at a multiplicity of infection of 1 : 100, which increased at 2 and 4 h, respectively, to 24 h. It also induced the production of high levels of the TNF-α and IL-1β proteins, which increased at 2 h and reached a peak at 4 and 24 h, respectively. Nuclear factor-κB (NF-κB) was activated and reached a maximum level 30 min after the S. mutans treatment. The expression of TNF-α and IL-1β mRNA and protein was suppressed by the treatment with pyrrolidine dithiocarbamate, an NF-κB inhibitor. The S. mutans-induced TNF-α expression was suppressed by the presence of SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, or SP600125, a Jun N-terminal kinase (JNK) MAP kinase inhibitor. On the other hand, IL-1β expression was inhibited by extracellular signal-regulated kinase (ERK)/p38/JNK MAP kinase inhibitor pretreatment. In addition, TNF-α production was suppressed more in the Toll-like receptor 2(-/-) (TLR2(-/-)) macrophages than in the TLR4(-/-) macrophages, whereas IL-1β production was suppressed more in the TLR4(-/-) macrophages than in the TLR2(-/-) macrophages. These results show that S. mutans stimulates the production of TNF-α and IL-1β in the mouse macrophage cell line, RAW 264.7, by activating ERK/p38/JNK, and NF-κB through TLR2 and TLR4, respectively. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: Controversy has ensued about the prognostic relevance of the new World Health Organization (WHO) schema for the classification of thymoma. In this study, we present the clinical and histologic features of 108 thymomas and evaluate the usefulness of this histologic schema in view of the prognosis. DESIGN: Retrospective, clinicopathologic analysis of our experience and a review of recent literature. SETTING: Department of Thoracic and Cardiovascular Surgery of a university hospital. METHODS: A series of 108 thymomas were reviewed and classified by the new WHO schema. The clinical characteristics and the survival outcome were investigated in reference to the WHO subtypes. The Cox proportional hazards model was applied to determine the factors affecting the tumor-related survival. Recent literature on the prognostic relevance of the WHO schema was reviewed. RESULTS: There were 7 type A tumors, 25 type AB tumors, 12 type B1 tumors, 32 type B2 tumors, 20 type B3 tumors, and 12 type C tumors. The histologic subtype closely correlated with the Masaoka stage (p = 0.00). The tumor-related survivals at 5 years and 10 years were 88.0% and 77.9%, respectively. Stage III and IV tumors had a significantly worse prognosis than stage I or II tumors (p < 0.05). Type B3 tumors had an intermediate prognostic ranking in comparison with the carcinomas and with the other groups. On multivariate analysis, the WHO subtype (A-B2 vs B3 vs C) could predict the tumor-related survival, but the Masaoka stage was the most important prognostic factor affecting the postoperative survival (p = 0.026). CONCLUSION: The Masaoka stage is the most important determinant of survival in surgically resected cases of thymoma. To clarify the prognostic relevance and clinical usefulness of the WHO schema, consistent parameters reflecting the surgical outcome and development of the diagnostic tools that could improve the interobserver agreement within type B are needed. [ABSTRACT FROM AUTHOR]