Efficacy of glimepiride for the treatment of diabetes occurring during glucocorticoid therapy.
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Aged↗
Biomedical subjects
Toshio Tanaka
Publications and source records attributed to Toshio Tanaka.
[Pharmacogenomics and pharmainformatics].
Pharmacogenomics is defined to identify the genes which are involved in determining the responsiveness and to distinguish responders and non-responders to a given drug. Genome sequencing, transcriptome and proteome analysis are of particular significance in pharmacogenomics. Sequencing is used to locate polymorphisms, and monitoring of gene expression can provide clue about the genomic response to disease and treatment. The transcriptome analysis can be done by methods of random cDNA sequencing (expressed sequence tag project, body map project, serial analysis of gene expression, et al), mRNA display (differential display, fluorescent differential display, RNA arbitraly primed PCR, molecular indexing, gene expression fingerprinting, et al) and differential hybridization(cDNA high density filter, cDNA microarray, oligomicrochip, et al). We used transcriptome analysis to identify therapeutic target genes by studying change of gene expression in animal models of cerebral vasospasm (1) and of hypoxia/ischemia and found novel drug target candidates through this pharmacogenomic strategy (2). We found remarkable up-regulation of heme oxygenase-1(HO-1) mRNA in the basilar artery and it might be closely related to the occurrence of delayed vasospasm after subarachnoid hemorrhage. In this report, we clearly demonstrate that intrathecal administration of antisense HO-1 oligodeoxynucleotide aggravates vasospasm, suggesting HO-1 gene induction has spasmolytic effects. Furthermore, we found the protective effects of HO-1 gene induction by endogenous or clinical compounds in cerebral vasospasm. Therapeutic gene induction of HO-1 could be a novel strategy for the prevention and treatment of Hb-induced pathologic conditions including delayed cerebral vasospasm. Our results suggest that the pharmacogenomic transcriptome analysis and pharmainformatics has the potential for strategy to define novel drug targets in various diseases (3). (1) J Clin Invest 104: 59-66, 1999. (2) J Biol Chem 276: 19921-19928, 2001. (3) J Cardiovasc Pharm 36: S1-S4, 2000.
Animals↗
[Production of recombinant human CRP and its application on clinical testing].
Recently, changes in the serum CRP level 1/10 the concentration range ordinarily used as a marker of acute inflammation has received attention in relation to cardiovascular injury at the AACC/CDC joint forum at Atlanta held on March 13, 2001. We have succeeded in the development of recombinant human CRP(rCRP) by inserting the cloned CRP gene into expression vector pTRP, followed by transformation of E. coli. Genes encoding the signal peptide of E. coli alkaline phosphatase and kil gene were additionally inserted, so that rCRP can be secreted into the culture supernatant. Five grams of rCRP was purified from 180 L culture supernatant by affinity chromatography. The purified rCRP was indistinguishable from native rCRP with respect to Ca(2+)-dependent binding activity to phosphorylcholine, electrophoretic behavior in the presence or absence of SDS, N-terminal amino acid, and immunochemical properties. rCRP was found to have a potential as a reference material and/or calibrator for hsCRP assay.
C-Reactive Protein↗
[Evaluation of an exercise program for obese males].
PURPOSE: We developed a one-year exercise program based on evaluation of life style and physical fitness and investigated its efficacy. SUBJECTS AND METHODS: Sixty one Japanese males (30 < or = age < 59, body mass index: BMI > or = 26.4 kg/m2) were enrolled in the stady. The exercise program consisted of four sections: (1) Preparation for preventing injury; (2) Increase of daily activity; (3) Enjoying exercise; (4) Preparation and practice of individual-based on a exercise program. The subjects visited Okayama Southern Institute of Health and were being monitored weekly for one-year. They were instructed to check daily steps every day and increase daily walking to at least 1000 steps more than the daily walk at baseline. Before and after one-year follow up study, we evaluated life style and physical fitness in terms of body composition, aerobic exercise level, muscle strength and flexibility. RESULTS: The continuation rate for the program was 66%. Body weight (pre 81.5 +/- 7.4 kg vs post 78.6 +/- 7.3 kg), body fat percentage (pre 30.3 +/- 4.1% vs post 28.4 +/- 5.0%) and waist hip ratio (pre 0.95 +/- 0.04 vs post 0.92 +/- 0.04) were significantly reduced. Aerobic exercise level and muscle strength were increased. Regarding volition for exercise, execution, continuation and steps per day were also improved. CONCLUSION: Regular exercise at an institution (once a week) and change in daily life style may play critical role in reducing body weight. This new program proved quite useful for Japanese obese males.
Adult↗
Long-chain alkyl ester of AMP acts as an antagonist of glucose-induced signal transduction that mediates activation of plasma membrane proton pump in Saccharomyces cerevisiae.
One of the long-chain alkyl esters of AMP, adenosine 5'-hexadecylphosphate (AMPC16), exhibited a cytotoxic growth inhibitory effect on cells of various yeast strains. The growth inhibitory effect of AMPC16 on Saccharomyces cerevisiae cells was observed only in medium containing Mg2+, which accelerated cellular uptake of the nucleotide analogue. In the presence of Mg2+, AMPC16 completely inhibited glucose-induced extracellular acidification by the intact cells and also interfered with activation of the plasma membrane ATPase, but did not directly inhibit the ATPase activity itself. AMPC16 treatment prevented cells from increasing their intracellular sn-1,2-diacylglycerol (DAG) level in response to glucose, whereas the inhibition of proton extrusion by the cells could be largely reversed by the coaddition of a membrane-permeable DAG analogue. The DAG analogue, a physiological activator of protein kinase C (PKC), was not protective against the inhibition of glucose-induced proton extrusion by staurosporine, which is capable of directly interfering with the action of PKC. These results implied that AMPC16 caused a Mg(2+)-dependent cytotoxic effect on Sac. cerevisiae cells by interfering with a phosphatidylinositol type of signal that mediates activation of the plasma membrane proton pump.
Adenosine Monophosphate↗
Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism.
The growth of budding yeast, Saccharomyces cerevisiae, was inhibited in medium containing 25 microM farnesol (FOH). The FOH-treated cells were still viable, and were characterized by a transition from budded to unbudded phase as well as a significant loss of intracellular diacylglycerol (DAG). FOH-induced growth inhibition could be effectively prevented by the coaddition of a membrane-permeable DAG analogue which can activate yeast protein kinase C (PKC). However, yeast cell growth was not initiated upon addition of the PKC activator when the cells had been pretreated with FOH for 20 min. The failure in cell growth recovery was believed to be due to a signalling-mediated cell cycle arrest in FOH-pretreated cells. Differential display analysis demonstrated that the expression of cell cycle genes encoding DNA ligase (CDC9) and histone acetyltransferase (HAT2) was strongly repressed in FOH-treated cells. Repression of the expression of these genes was effectively cancelled when cells were grown in medium supplemented with DAG. The authors propose an interference with a phosphatidylinositol-type signalling which is involved in cell cycle progression as a cause of FOH-induced growth inhibition in yeast cells.
Acetyltransferases↗