JOURNAL OF THE KYORIN MEDICAL SOCIETY

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The changes in the activity of a protein kinase, which is found in liver cell nuclei, during the process of chemical carcinogenesis was investigated to clarify the biological role of the enzyme. Thirteen-week old Wistar male rats were administered with 0.04 % thioacetamide (TAA) in the drinking water for 24 weeks. Liver was removed from the rats at different intervals and cell nuclei were isolated. A hypotonic extracts of the nuclei, extractable nucleic protein (ENP) fraction, was further separated into fractions by an anion exchange column chromatography. The protein kinase activity in those fractions was measured with casein and [^<32>P] ATP as the substrates. The kinase activity in normal rat liver found mainly in the fraction eluted from the column with 0.15 and 0.3M NaCl containing eluates. The activity was slightly decreased during the first 4 weeks but maintained a certain level thereafter. On the other hand, the kinase activity in TAA-administered rat liver was increased first 2 weeks, then slightly decreased after 4 weeks, and extremely decreased 12-24 weeks after the administration. While, DNA synthetic activity in normal rat liver was slightly decreased during the first 4 weeks and maintaining a certain levels thereafter. In the TAA-administered rat liver the DNA synthetic activity was increased 1 or 4 weeks after TAA administration, extremely decreased at 12 weeks, but again increased at 24 weeks. The result indicates the enzyme would regulate the DNA repair synthesis or DNA replication in the regenerating liver, but the effect would be diminished during the chemical carcinogenesis in the rat liver.

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In order to clarify a pathophysiological role of protein kinases (PKase) existed in a hypotonic nuclear extract, effects of anticarcinogenic agents on the PKase activity, were investigated in combination with DNA synthetic activity in the liver and tumor tissues, from normal and tumor transplanted (Meth A fibrosarcoma) BALB/c mice. Extractable nuclear protein (ENP) fraction prepared from nuclei with 10 mM Tris-HCl buffer (pH 7.5) was applied to a DEAE-Sepharose column and proteins were eluted with 50 mM Tris-HCl buffer (pH 7.5) containing 0.15, 0.3 and 2.0M Nad, successively. PKase activities, measured with casein and [^<32>P] ATP as substrates, were detected in 0.15M and 0.3M NaCl-eluted fractions. The PKase and DNA synthetic activities in the normal mouse liver, were increased 24 hours after administration of either bleomycin, 5-fluorouracil, cisplatin or cyclophosphamide. On the other hand, in liver and tumor tissues of the tumor-bearing mice, the enzyme activities were extremely increased in comparison with those found in normal mouse liver. The PKase activities, however, were remarkably decreased by the administration of all the agents mentioned above. DNA synthetic activity was also decreased by the administration of cisplatin and cyclophosphamide, but not decreased by bleomycin and 5-fluorouracil. These results suggest that nuclear protein kinase activity seems to be an additional sensitive indicator together with DNA synthetic activity, for evaluating effects of anticarcinogenic agents.

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A 52-year-old woman developed a burning pain in the right upper extremity after a distal radius fracture. She was diagnosed as having reflex sym-pathetic dystrophy (RSD). Treatment with stellate ganglion block was initiated. However, this proved to be ineffective. Previous case reports suggested that total analgesia induced by blocking of sensory and motor fibers, in addition to sympathetic fibers, might influence emotional status and the pain threshold. Then, a series of brachial plexus blocks with 5ml of 1 % mepivacaine and 4 mg of dexamethasone were applied to this case and proved to be sufficiently effective. Subsequent active exercise therapy improved the range of motion, and reinforced the muscle power by interrupting the vicious circle of pain. Therefore, we recommend that brachial plexus block and rehabilitation should be started immediately for treatment of reflex sympathetic dystrophy in the upper extremity.

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