GEX1A is a microbial product with antitumor activity. HeLa cells cultured with GEX1A accumulated p27(Kip) and its C-terminally truncated form p27*. GEX1A inhibited the pre-mRNA splicing of p27, producing p27* from the unspliced mRNA containing the first intron. p27* lacked the site required for E3 ligase-mediated proteolysis of p27, leading to its accumulation in GEX1A-treated cells. The accumulated p27* was able to bind to and inhibit the cyclin E-Cdk2 complex that causes E3 ligase-mediated degradation of p27, which probably triggers the accumulation of p27. By using a series of photoaffinity-labeling derivatives of GEX1A, we found that GEX1A targeted SAP155 protein, a subunit of SF3b responsible for pre-mRNA splicing. The linker length between the GEX1A pharmacophore and the photoreactive group was critical for detection of the GEX1A-binding protein. GEX1A serves as a novel splicing inhibitor that specifically impairs the SF3b function by binding to SAP155.

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[Purpose] To clarify the influence of nonspecific low back pain (NSLBP) on force fluctuation and the myoelectric data of back muscles during isometric trunk extension at low to high force levels. [Subjects] Fourteen male subjects with NSLBP and 14 healthy male control subjects participated in this study. [Methods] All participants extended their trunk isometrically maintaining 10 levels of target force [2, 5, 10, 15, 20, 30, 50, 70, 80 and 90% of maximal voluntary contraction (MVC) in a random order] for about 4 seconds with visual feedback. A force transducer and tri-axis force sensor were positioned at the 7th thoracic vertebra to measure force output and the direction of force. Myoelectric activities of the back muscles (longissimus thoracis, L2 level; multifidus, S1 level) were recorded by surface electromyography. [Results] Force output of NSLBP subjects fluctuated more than that of healthy subjects at 30% and 50%MVC. Higher median power frequency in the multifidus was observed in NSLBP subjects at moderate to high force levels. [Conclusion] These results show that the properties of force output in NSLBP subjects differ from those in healthy subjects, suggesting that the assessment of force fluctuation of back muscles at moderate force levels is a useful index for evaluating and discriminating NSLBP.

Abstract.[Purpose] To clarify the relationship between spinal alignment and trunk muscle activities in upright sitting without manual intervention.[Subjects] Twenty-three healthy male volunteers with no history of lumbar disorders participated in this study.[Methods] Trunk alignment and surface electromyographic activities of 6 trunk muscles were measured synchronously during the motion from slump to upright sitting position. The amplitude of the muscle activities were normalized to maximal voluntary contraction. Subjects were classified into 3 spinal alignment groups: long lordosis (LL), short lordosis (SL), and kyphosis (K).[Results] The LL group consisted of 9 subjects (39%), the SL group of 9 subjects (39%), and the K group of 5 subjects (22%). The K group had significantly lower muscle activity of the back and abdominal muscles. The SL group had significantly greater muscle activity of the lumbar paraspinals than the LL group, and greater activity of the lumbar multifidus was observed in the SL group than in the other groups. The LL group showed significantly greater muscle activity of the internal oblique muscle than the other groups.[Conclusion] Upright sitting without manual correction leads to various kinds of spinal alignment. Judging from trunk muscle activities, we suggest that the desirable spinal alignment in upright sitting is a neutral lumbar position with no thoracolumbar kyphosis.