We studied 40 MELAS patients (21 male and 19 female) to characterize the clinical features and biochemical and muscle biopsy findings related to the mtDNA mutation at the nucleotide position of 3,243, the most common genetic defect in MELAS. The most frequent symptom was episodic sudden headache with vomiting and convulsions, which commonly affected patients aged 5 to 15 years (80%). Biochemical defects in the muscle were variable; 13 patients had complex I, seven complex IV, and four complexes I + IV deficiencies. In four muscle biopsies without ragged-red fibers or any enzyme defect, we based the diagnosis on the identification of strongly SDH-reactive blood vessels, which occurred in 87.5% of the biopsies. The mtDNA mutation was present in 32 of 40 patients (80%). We conclude that there are no clinical and pathologic differences between the patients with and without this mtDNA mutation.

We have studied the roles of c-Jun N-terminal protein kinase (JNK) and extracellular signal-regulated protein kinase (ERK) cascade in both the cisplatin-resistant Caov-3 and the cisplatin-sensitive A2780 human ovarian cancer cell lines. Treatment of both cells with cisplatin but not transplatin isomer activates JNK and ERK. Activation of JNK by cisplatin occurred at 30 min, reached a plateau at 3 h, and declined thereafter, whereas activation of ERK by cisplatin showed a biphasic pattern, indicating the different time frame. Activation of JNK by cisplatin was maximal at 1000 M, whereas activation of ERK was maximal at 100 M and was less at higher concentrations, indicating the different dose dependence. Cisplatin-induced JNK activation was neither extracellular and intracellular Ca 2؉ -nor protein kinase C-dependent, whereas cisplatin-induced ERK activation was extracellular and intracellular Ca 2؉ -dependent and protein kinase C-dependent. A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor, PD98059, had no effect on the cisplatin-induced JNK activity, suggesting an absence of cross-talk between the ERK and JNK cascades. We further examined the effect of each cascade on the viability following cisplatin treatment. Either exogenous expression of dominant negative c-Jun or the treatment by PD98059 induced sensitivity to cisplatin in both cells. Our findings suggest that cisplatin-induced DNA damage differentially activates JNK and ERK cascades and that inhibition of either of these cascades sensitizes ovarian cancer cells to cisplatin.

In this Letter we report the discovery of TeV gamma-ray emission from a supernova remnant made with the CANGAROO 3.8 m telescope. TeV gamma rays were detected at the sky position and extension coincident with the northeast rim of shell-type supernova remnant (SNR) SN 1006 (Type Ia). SN 1006 has been a most likely candidate for an extended TeV gamma-ray source, since the clear synchrotron X-ray emission from the rims was recently observed by ASCA (Koyama et al.), which is strong evidence for the existence of very high energy (up to hundreds of TeV) electrons in the SNR. The observed TeV gamma-ray flux was (2.4 ‫ע‬ 0.0.7 [systematic]) # 10 3.0 ‫ע‬ 0.9 (4.6 ‫ע‬ 0.6 ‫ע‬ 1.4) # 10 1.7 ‫ע‬ 0.5 from the 1996 and 1997 observations, respectively. Also, we set an upper limit on the TeV gamma-ray emission from the southwest rim, which is estimated to be cm Ϫ2 s Ϫ1 (≥ TeV, 95% confidence level) Ϫ12

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Approximately 15-20% of patients with Kawasaki disease (KD) are not responsive to high-dose intravenous gammaglobulin (IVIG). We have previously reported a predictive method for identifying IVIG-non-responsive patients (high-risk KD patients). We determined the safety and effectiveness of pulse methylprednisolone with high-dose IVIG (mPSL+IVIG) as a primary treatment for high-risk KD patients. Sixty-two high-risk KD patients were treated with pulse methylprednisolone 30 mg/kg over 2 h, followed by IVIG 2 g/kg over 24 h (mPSL+IVIG group) and were compared with a historical control group of 32 high-risk patients treated with IVIG 2 g/kg alone at the participating hospitals before this study was opened (IVIG group). High-risk patients were identified with at least two of three predictors (C-reactive protein >or=7 mg/dL, total bilirubin >or=0.9 mg/dL or aspartate aminotransferase >or=200 IU/L). Sixty-six percent (95% confidence interval [CI] 54-78%) of patients had a prompt defervescence in the mPSL+IVIG group compared with 44% (95% CI 26-62%) for the IVIG group (p=0.048). Coronary artery lesions were observed in 24.2% (95% CI 13.2-35.2%) and 46.9% (95% CI 28.6-65.2%) of patients in the mPSL+IVIG and IVIG groups, respectively (p=0.025). This is the first report showing that mPSL+IVIG is effective and safe as a primary treatment for high-risk KD patients.