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Biomedical subjects

Takafumi Ohmura

Publications and source records attributed to Takafumi Ohmura.

4 recordsLinked to original sources

Daily expression of clock genes in whole blood cells in healthy subjects and a patient with circadian rhythm sleep disorder.

In recent years, circadian rhythm sleep disorders in humans have been increasing. Clinical features characteristic of this disorder are well known, but the specific causes remain unknown. However, various derangements of circadian expression of the clock gene are a probable cause of this disease. We have attempted to elucidate the relationship between the expression of the clock genes in whole blood cells and the clinical features characteristic of this disorder. In this study, we indicate the daily expression of clock genes period (Per) 1, 2, 3, Bmal1, and Clock in whole blood cells in 12 healthy male subjects. The peak phase of Per1, Per2, and Per3 appeared in the early morning, whereas that of Bmal1 and Clock appeared in the midnight hours. Furthermore, in one patient case with circadian rhythm sleep disorder, we observed variations of the peak phase in clock genes by treatments such as light therapy, exercise therapy, and medicinal therapy. This study suggested that the monitoring of human clock genes in whole blood cells, which may be functionally important for the molecular control of the circadian pacemaker as well as in suprachiasmatic nucleus, might be useful to evaluate internal synchronization.

ARNTL Transcription Factors↗

Case study: differences in human Per2 gene expression, body temperature, cortisol, and melatonin parameters in remission and hypersomnia in a patient with recurrent hypersomnia.

Recurrent hypersomnia is characterized by recurring episodes of hypersomnia of 18 h or more per day lasting from several days to several weeks. We report the case of a 17-year-old male subject with recurrent hypersomnia who displayed change in the 24 h expression of the hPer2 gene in whole red and white blood cells as well as markers [deep body temperature (DBT) and cortisol] of the circadian time structure during an episode of hypersomnia compared to remission. The patient was studied for the temporal characteristics of hPer2 gene, DBT, cortisol, and melatonin expression during a single 24 h span during an episode of hypersomnia and again during a single 24 h span in the following remission. The approximation of a 24 h cosine curve to the time series data revealed circadian rhythmicity (P < 0.05) only in DBT in the two stages of the disease with differences in amplitude and acrophase. Cortisol circadian rhythmicity was detected during remission, but not during hypersomnia. Statistically significant differences were detected by ANOVA between the remission and active disease stages in the 24 h mean level of hPer2 gene expression (P < 0.05), cortisol (P < 0.05), and DBT (P < 0.05). The findings of this case study suggest the expression of hPer2 gene and alterations in circadian time structure might play an important role in the pathogenesis of recurrent hypersomnia, although additional study is required.

Adolescent↗

Bromocriptine reverses P-glycoprotein-mediated multidrug resistance in tumor cells.

One of the most important causes of anticancer treatment failure is the development of multidrug resistance (MDR). The main characteristics of tumor cells displaying the MDR phenomena are cross-resistance to structurally unrelated cytotoxic drugs having different mechanisms of action and the overexpression of the MDR1 gene, which encodes a transmembrane glycoprotein named P-glycoprotein (P-gp). This study evaluated whether bromocriptine, a D2 dopaminergic receptor agonist, influenced anticancer drug cytotoxicity and P-gp activity in a P-gp-expressing cell line compared to a non-expressing subline. The K(i) values for P-gp of cyclosporine and verapamil were 1.09 and 540 microM, respectively, and that of bromocriptine was 6.52 microM in a calcein-AM efflux assay using porcine kidney epithelial LLC-PK1 and L-MDR1 cells, overexpressing human P-gp. Bromocriptine at 10 microM reduced the IC50 of doxorubicin (DXR) in K562-DXR from 9000 to 270 ng/ml and that of vincristine (VCR) in K562-VCR from 700 to 0.30 ng/ml, whereas the IC50 values of DXR and VCR in the K562 subline were only marginally affected by these drugs. Bromocriptine restored the anticancer effect of DXR, VCR, vinblastine, vinorelbine and etoposide on MDR-tumor cells overexpressing P-gp. These observations suggest that bromocriptine has the potential to reverse tumor MDR involving the efflux protein P-gp in the clinical situation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗