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We have previously shown that the expression of periostin is significantly downregulated in human bladder cancer tissues and that periostin suppresses cell invasiveness and metastasis of cancer cells. To clarify the molecular mechanism of this suppression by periostin, we searched for periostin-binding proteins and identified TAB1, which interacts with and activates TAK1, by mass analysis of proteins co-precipitated with periostin in 293T cells expressing periostin. The association between periostin and TAB1 was confirmed by a pulldown assay in 293T cells co-tranfected with expression plasmids of periostin, TAB1 and TAK1. TAK1 was also co-precipitated with periostin in this assay. Co-transfection experiments in 293T also showed that periostin could activate TAK1. Introduction of siRNA for TAB1 suppressed TAK1 activation by periostin. Analyses with deletion mutants of periostin revealed that the C-terminal region of periostin was necessary and sufficient for the association with TAB1 and the TAK1 activation. The suppression of invasiveness by periostin was attenuated by siRNA targeting TAK1 or TAB1 in 293T (human embryonic kidney) and T24 (human bladder carcinoma) cell lines. These findings indicate that periostin is involved in the suppression of cell invasiveness via the TAB1/TAK1 signaling pathway.

We examined the usefulness of Magnetic Resonance Imaging (MRI) test in the acute phase of carbon monoxide intoxication for forecasting delayed encephalopathy (DE). [Case 1] 26-year-old female. COHb 12%. Takotsubo (Ampulla) cardiomyopathy was supervened. Pallidal disorder was recognized in MRI test in the early stage. Although Prophylactic HBO was performed, DE began. 36 days later, disorder was recognized in large area, such as, in cerebral white matter and callosum, and abnormality was found in WMS-R and MMSE. Since HBO was performed, DE subsided. In MRI test, on the other hand, high signal range in cerebral white matter and callosum were gradually decreased and WMS-R and MMSE were improved. [Case 2] 19-year-old female. COHb 9.4%. The state was considered to be mild but pallidal disorder was found in MRI test at the beginning. DE did not start, then the part of pallidal disorder was narrowed. WMS-R and MMSE showed slightly low level. [Case 3] 19-year-old female. COHb 7.3%. The state was considered to be mild and there was no abnormal findings in MRI test in the early stage. DE did not start. [Case 4] 48-year-old male. COHb 48.9%. Rhabdomylosis was supervened, then ischemic change in a left radiate crown was recognized in the early MRI test. Since the third day, disorientation and restlessness had been developed, so that the patient was transferred to psychiatric department, though it was still difficult to distinguish the case from DE. Although the case is relatively mild, pallidal disorder is recognized in the early MRI test. Pallidal disorder alone can cause memory disorder and cognitive impairment. Even if pallidal disorder alone is recognized in the early MRI test, white matter disorder is developed with time, and then DE begins. If there are no typical carbon monoxide intoxication findings, some cases can be suspected as DE. It is useful to perform serial MRI test in order to prepare for delayed encephalopathy in carbon monoxide intoxication.