Tomoji Watanabe

Altered expression of CUG binding protein 1 mRNA in myotonic dystrophy 1: possible RNA-RNA interaction.

The triplet repeats mutation, which causes myotonic dystrophy 1 (DM1), is thought to have a dominant negative effect on RNA levels. In light of previous results using differential display analysis, the present study focused on the expression of CUG binding protein 1 (CUGBP1) mRNA. Northern blot analysis demonstrated that the quantity of CUGBP1 mRNA in three DM1 patients was approximately 70% of that observed in three normal controls (P < 0.05). In addition, a semi-quantitative RT-PCR assay showed that the relative amount of CUGBP1 mRNA was reduced in muscle biopsy samples from 10 DM1 patients compared to that from five normal individuals (P < 0.01) and 10 myopathic disease controls (P < 0.01). The amount of CUGBP1 mRNA was negatively correlated with the size of the CTG expansion (r = -0.85, P < 0.05). In vitro RNA-RNA binding experiments demonstrated that the incubation of expanded CUG repeats with CUGBP1 RNA generated a higher molecular weight band, which was digested by RNase III. The CUGBP1 mRNA was found to contain several CAG repeat sequences. These results suggest that the CUG expansion may bind to complementary sequences within the CUGBP1 mRNA and that this molecular interaction may affect CUGBP1 mRNA expression in DM1.

Caffeine Contracture of the Skinned Muscle Fiber in Malignant Hyperthermia and Neuromuscular Diseases

Caffeine contracture of skinned muscle fiber was analyzed in subjects who had recovered from malignant hyperthermia (MH) and in patients with other neuromuscular diseases. In several muscle specimens, the calcium-induced (Ca-induced) Ca release (CICR) was also studied and compared to the caffeine contracture. The caffeine contracture test was very sensitive in detecting abnormalities, but it seemed less specific for diagnosis of true MH.