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Biomedical subjects

Shinichi Okamura

Publications and source records attributed to Shinichi Okamura.

6 recordsLinked to original sources

Zinc ions suppress mitogen-activated interleukin-2 production in Jurkat cells.

Calcineurin (CN) is thought to play an important role in the immune system by regulating cytokine production, for example, interleukin-2 (IL-2) in T-lymphocytes. We have previously shown that physiological concentrations of Zn2+ inhibit CN activity in vitro [K. Takahashi, E. Akaishi, Y. Abe, R. Ishikawa, S. Tanaka, K. Hosaka, Y. Kubohara, Zinc inhibits calcineurin activity in vitro by competing with nickel, Biochem. Biophys. Res. Commun. 307 (2003) 64-68], in spite of the fact that Zn2+ is an essential element of the CN catalytic domain. In this study, in order to assess whether Zn2+ regulates (suppresses) CN activity in vivo and whether Zn2+ can be used as an anti-inflammatory and/or immunosuppressive drug, we examined the effects of Zn2+ on IL-2 production induced by the mitogen, concanavalin A (ConA), in Jurkat T-cells. Zn2+ at 0.2 mM suppressed ConA-induced IL-2 accumulation in the medium of an in vitro culture of Jurkat cells. Zn2+ at 0.03-0.3 mM dose-dependently suppressed ConA-induced IL-2 mRNA expression in Jurkat cells. Zn2+ also suppressed IL-2 mRNA expression induced by phorbol ester (PMA) and ionomycin. Furthermore, Zn2+ and the immunosuppressant FK506 showed an additive inhibitory effect on ConA-induced IL-2 mRNA expression. These results suggest that exogenously added Zn2+ may disturb (increase) the intracellular Zn2+ concentration and inhibit CN activity, thereby suppressing IL-2 production in Jurkat cells. The present study further indicates that Zn2+ may have therapeutic potential in the treatment of T-cell related inflammation and also that Zn2+ may be utilized as a supplemental drug with FK506.

Cations, Divalent↗

Case-mix payment in Japanese medical care.

The Japanese medical care system, highly rated internationally, has recently experienced a crisis that has placed a burden on all of its citizens, providers, and payers, due to the expansion of medical expenditures in rapidly aging society with the stagnant economy. To address this, in April 2003, Japan implemented a case-mix payment system, instead of conventional fee-for-service payment, based on an original case classification with 2552 groups (Diagnosis Procedure Combination: DPC), with inpatients from 82 special functioning hospitals. This system contains two parts: per diem prospective payment for hospital's fee with a three-level step down according to average length of stay for each diagnosis group, which is adjusted to secure the previous year's remuneration in each hospital; fee-for-service payment for doctor's fee based on national fee schedule. The payment system reduced average length of stay, but did not change inpatient expenditures and increased outpatient expenditures. The in-hospital mortality rate, although un-adjusted, did not changed, but the readmission rate increased mainly through an increase in planned, not accidental, readmissions. For the expansion of this system, ongoing program refinement, reflecting the results of data analysis, is indispensable.

Diagnosis-Related Groups↗

Diagnostic value of the serum platelet-activating factor acetylhydrolase activity in inflammatory bowel disease.

Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme hydrolyzing platelet-activating factor (PAF), a potent inflammatory mediator, but the relationship between this enzyme and inflammatory bowel disease (IBD) is not fully elucidated. The aim of the present study was to examine the usefulness of the serum PAF-AH activity in order to differentiate ulcerative colitis (UC) from Crohn's disease (CD). The serum PAF-AH activity was measured in 57 patients with IBD (39 UC and 18 CD patients) and 13 control subjects by a spectrophotometric method. The serum PAF-AH activity was thus found to be significantly lower in patients with CD (median 265.5 U/l) than in those with UC (355 U/l) or control subjects (374 U/l). This marker at a cutoff level of 386 U/l demonstrated a sensitivity of 46%, a specificity of 100%, and a positive predictive value of 100% regarding its ability to distinguish UC from CD. Moreover, the marker responded inversely to the changes in the disease activity of IBD. These results suggest that measuring the serum PAF-AH activity is a useful diagnostic modality for making a differential diagnosis between UC and CD.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Metronidazole plus ciprofloxacin therapy for active Crohn's disease.

OBJECTIVE: The aim of this study was to investigate the efficacy of metronidazole plus ciprofloxacin for the treatment of Japanese patients with active Crohn's disease. METHODS AND PATIENTS: Seven patients (counting one patient twice with 2 enrollments at a 5-month interval) with a flare-up of Crohn's disease were enrolled. While continuing the baseline treatment under which the patients relapsed, they received metronidazole 250 mg twice (4 patients) or three times (3 patients) daily plus ciprofloxacin 200 mg three times daily for 4 weeks. The efficacy was evaluated by the changes in the assessment score of IOIBD, the International Organization for the Study of Inflammatory Bowel Disease, and the inflammation markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count. RESULTS: Metronidazole plus ciprofloxacin decreased the CRP in seven patients and the IOIBD score in six patients. Significant differences were detected in these parameters at weeks 2 and 4 compared with baseline. Five of the patients achieved normalization of CRP and a reduction of the IOIBD score to zero or one. Although one patient complained of taste disturbance, no other adverse events occurred and all patients completed the 4 weeks of study medication. CONCLUSION: The addition of metronidazole plus ciprofloxacin could be a useful intervention for the treatment of Japanese patients with active Crohn's disease.

Adult↗

Increased activity and expression of phospholipase D2 in human colorectal cancer.

Phospholipase D (PLD) has been reported as relevant to some types of human cancer, but its role in human colorectal cancer still remains to be elucidated. Thus, this study was conducted to determine the activity and the expression of PLD2 in human colorectal cancer. A significant elevation of PLD2 activity and higher expression of PLD2 protein were detected in human colorectal cancer in comparison with corresponding normal mucosa. The tendency of higher expression of PLD2 mRNA was also observed. The ratio of PLD2 activity in cancer to that in corresponding normal mucosa was greater in colorectal cancer with nodal involvement and deeper tumor invasion. Our results indicate that PLD2 has a possible implication in carcinogenesis and progression and would be a new therapeutic target and a potential tumor marker for colorectal cancer.

Aged↗