p53 Prevents Immature Escaping from Cell Cycle G2 Checkpoint Arrest through Inhibiting cdk2-dependent NF-Y Phosphorylation / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and this function is required for the maintenance of genomic integrity. In this study, we addressed a role of p53 in escaping from cell cycle G2 arrest following DNA damage. MATERIALS AND METHODS: Cell cycle checkpoint arrest in the human colon cancer cell line HCT116 and its derivatives carry p53 or p21 deletions, were examined by FACS analysis, immunoprecipitation, Western blot and IP-kinase assay. RESULTS: While the cells with functional p53 were arrested at both the G1 and G2 checkpoints, the p53-deficient cells failed to arrest at G1, but they were arrested at G2. However, the p53-deficient cells failed to sustain G2 checkpoint arrest and they entered mitosis earlier than did the p53-positive cells and so this resulted in extensive cell death. Cdc2 kinase becomes reactivated in p53-deficient cells in association with entry into mitosis, but not in the p53-positive cells. Upon DNA damage, the p21-deficient cells, like the p53-negative cells, not only failed to repress cdk2- dependent NF-Y phosphorylation, but they also failed to repress the expression of such cell cycle G2-regulatory genes as cdc2, cyclin B, RNR-R2 and cdc25C, which have all been previously reported as targets of NF-Y transcription factor. CONCLUSION: p53 is essential to prevent immature escaping from cell cycle G2 checkpoint arrest through p21-mediated cdk2 inactivation, and this leads to inhibition of cdk2-dependent NF-Y phosphorylation and NF-Y dependent transcription of the cell cycle G2-rgulatory genes, including cdc2 and cyclin B.

A Quantitative Assessment of Knee Extensor Spasticity Using Isokinetic Dynamometer

OBJECTIVE: To find useful parameters in biomechanical assessment of spasticity. METHOD: Knee extensor muscles of 60 limbs of 47 patients which showed clinical spasticity were stretched by isokinetic dynamometer. Stretch was done with the velocities of 60o/sec, 120o/sec, 180o/sec, 240o/sec. Four parameters [torque onset angle (TOA), peak torque angle (PTA), peak eccentric torque (PET), peak eccentric torque area (PETA)] were measured at each stretch velocity. Then, regression analysis was performed in relationship between each parameter and strech velocity. We analysed the correlation between the slope of each parameter in regression equation and clinical Modified Ashworth Scale (MAS) RESULTS: The slope of TOA and PTA had negative value so that they showed the decreasing trend of their value according to increasing velocity. On the other hand the slope of PET and PETA had positive value which meant that those parameters increased according to increasing velocity. The slope of PET and PETA were correlated statistically. The higher the MAS score was, the larger value of slope of PET, PTEA were noted. CONCLUSION: Peak eccentric torque and Peak eccentric torque area are thought to be useful parameters in biomecha nical assessment of spasticity.

The Effects of Botulinum Toxin A on Upper Limb Function in Children with Cerebral Palsy

OBJECTIVE: To evaluate the efficacy of botulinum toxin type A in the treatment of spasticitc and dystonic upper limbs in a group of cerebral palsy children METHOD: Eighteen children with cerebral palsy who did not have fixed contractures in the wrist and hand were enrolled (mean age 9.0 years; range 6~15). Measurements were obtained before and at 1 and 3 months after botulinum toxin A injections. Assessments included spasticity (modified Ashworth scale), range of motion of thumb and functional assessments including Melbourne assessment of unilateral upper limb function and Jebsen Taylor hand function test. Hand and forearm muscles were injected with 1~3 u/kg botulinum toxin. RESULTS: Spasticity measured by modified Ashworth scale decreased by 1 month and diminished spasticity continued for 3 months. Range of motion of thumb increased by 1 and 3 months. In Jebsen hand function test, patients showed functional improvements in item 6 (lifting light weight object) and item 7 (lifting heavy object). Melbourne assessment of unilateral upper limb function scores improved from a mean value of 92 at baseline to a mean value of 101 at 1 month and a mean value of 105 at 3 months. CONCLUSION: Botulinum toxin A would be helpful in some selected cerebral palsy patients with upper limb dysfunction. But further research including randomized controlled study is needed on the use of botulinum toxin A to improve function.