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Masaki Ikemoto

Publications and source records attributed to Masaki Ikemoto.

8 recordsLinked to original sources

Intrinsic function of S100A8/A9 complex as an anti-inflammatory protein in liver injury induced by lipopolysaccharide in rats.

BACKGROUND: We hypothesized that the S100A8/A9 complex is effective in the suppression of acute inflammatory changes. METHODS: To clarify such a functional role of the S100A8/A9 complex in acute inflammatory disorder, the complex purified from human leukocytes (approx. 1 mg) was intraperitoneally injected into rats 1.0 or 3.5 h after an injection of lipopolysaccharide (LPS). RESULTS: The serum concentrations of interleukin-6 (IL-6) and nitric oxide (NOx) were significantly decreased in the treated rats. Conversely, when anti-S100A8/A9 complex IgG was injected into the tail blood vessel of a rat 1.0 h after the injection of LPS, the serum concentration of IL-6 increased slightly, indicating that the antibody immunoregulatorily blocked the activity of the complex as an anti-inflammatory protein in vivo. In addition, the S100A8/A9 complex bound non-specifically with interleukin-1beta (IL-1beta), IL-6 and TNF-alpha in vitro, suggesting that the complex could bind with these cytokines in vivo. A large number of endogenous S100A8/A9 complex-positive cells that accumulated in the inflamed region in the liver 6 h after the injection of LPS were microscopically observed, while apparent inflammatory changes were not found microscopically in other organs, such as the kidney, lung and spleen. In rats treated with the S100A8/A9 complex, neither acute inflammatory changes nor S100A8/A9 complex-positive cells were also observed microscopically in the liver tissue. CONCLUSIONS: These findings suggest that the S100A8/A9 complex indirectly suppresses the overproduction of NOx from activated neutrophils and/or macrophages by neutralizing the activity of pro-inflammatory cytokines. Thus, the S100A8/A9 complex may play an important role in the suppression of acute inflammation by modulating the vital activity of pro-inflammatory cytokines in vivo.

Animals↗

Advantage of serum type-I arginase and ornithine carbamoyltransferase in the evaluation of acute and chronic liver damage induced by thioacetamide in rats.

BACKGROUND: We evaluated the usefulness of serum type-I arginase (ARG) and ornithine carbamoyltransferase (OCT) in thioacetamide (TAA)-induced acute and chronic liver injury in rats. METHODS: In an acute injury model, we measured the time-courses of serum concentrations of ARG and OCT using ELISA, together with AST and ALT using biochemical enzymatic assays after a single administration of TAA (200 mg/kg, i.p.). In the chronic model, TAA was repeatedly administered (20 mg/kg/day, p.o.) for 16 weeks and serum concentrations of the enzymes were evaluated. RESULTS: In the acute model, the concentrations of the enzymes were increased in a similar manner, peaking 24 h after the administration, and ARG showed the earliest and greatest increase among the enzymes tested. In the chronic model, the serum concentration of OCT was significantly increased only 1 week after oral treatment, while concentrations of the other enzymes were increased at 8 to 12 weeks. In the histological analysis, TAA treatment damaged hepatocytes in both the acute and chronic model. CONCLUSIONS: These results clearly show the usefulness of ARG and OCT for the evaluation of acute and chronic liver injury, respectively.

Alanine Transaminase↗

A sensitive ELISA for serum ornithine carbamoyltransferase utilizing the enhancement of immunoreactivity at alkaline pH.

BACKGROUND: We developed a new enzyme-linked immunosorbent assay (ELISA) for ornithine carbamoyltransferase (OCT) and evaluated its usefulness. METHODS: Recombinant human OCT expressed in E. coli was used as an antigen to obtain the monoclonal antibodies for this assay. RESULTS: The reactivity of the antibodies to native OCT as well as recombinant OCT was enhanced at alkaline pH (8.5-10), and the assay's sensitivity was markedly improved. The antibodies react identically with native and recombinant OCT at pH 9.4. The dilution test showed a good linearity between dilution ratios and the concentrations. Different concentrations of OCT added were recovered on average at 90.4%. There was a good correlation between OCT protein levels in the ELISA and OCT enzyme activities (r=0.987, p<0.0001). A significant difference in the serum level of OCT was observed between chronic hepatitis patients (110.7+/-80 ng/ml) and healthy subjects (34.4+/-20.7 ng/ml) (p<0.0001). The serum levels of OCT between sexes differed significantly in the healthy subjects (p<0.0001). CONCLUSIONS: Our newly established ELISA for OCT using monoclonal antibodies is sensitive enough for clinical application.

Alanine Transaminase↗

[Differential diagnosis of hepatitis: development of new laboratory tests for autoimmune hepatitis and progress in pathophysiology].

Liver dysfunction has been found in 8.1% of postpartum women in the general population. This dysfunction was speculated to be developed by postpartum aggravation of subclinical autoimmune hepatitis. Therefore, we developed two methods for detection of autoantibodies to liver-specific antigens: an ELISA for anti-liver-specific arginase antibodies, and a highly sensitive radioligand assay for anti-CYP2D6 antibodies. Basic examinations of dilution curve, inhibition study and reproducibility were satisfactory for clinical application in both assays. Anti-arginase antibodies and anti-CYP2D6 antibodies were found in 28.6% and 42.6% of patients with autoimmune hepatitis, respectively. There was no correlation between the two autoantibodies and thus, combined use of these antibodies detects 55.3% of autoimmune hepatitis. Autoimmune hepatitis exists frequently when we include mild cases.

Arginase↗

[Arginase].

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Arginase↗

New ELISA system for myeloid-related protein complex (MRP8/14) and its clinical significance as a sensitive marker for inflammatory responses associated with transplant rejection.

BACKGROUND: C-reactive protein (CRP), a useful marker for inflammatory diseases, is not always sensitive to inflammatory reaction in the liver or other tissues. The aim of this study was to develop a sensitive and specific method for detecting inflammatory responses associated with transplant rejection. METHODS: We developed a new, highly sensitive ELISA system for the measurement of serum human myeloid-related protein complex (MRP8/14), using monoclonal antibodies against MRP8/14, and applied it to specimens obtained from patients undergoing small intestine or liver transplantation. RESULTS: This assay could detect MRP8/14 concentrations as low as 2 micro g/L. Within-run CVs were 3.7-6.1% and between-day CVs were 5.6-8.7% for MRP8/14 concentrations of 117-3300 micro g/L. Mean recovery was 104% (range, 80-128%). We observed a marked increase in serum MRP8/14 postoperatively in most recipients of transplants, followed by an increase in CRP 1-7 days after the increase in the complex. The increase in serum MRP8/14 occurred simultaneously with permeation of lymphocytes into the transplanted tissues as a result of rejection of the graft tissues. CONCLUSIONS: Accurate measurement of serum MRP8/14 provides a useful clinical diagnostic method tool for detecting inflammation associated with rejection of transplanted tissues.

Acute Disease↗

Anti-CYP2D6 antibodies detected by quantitative radioligand assay and relation to antibodies to liver-specific arginase in patients with autoimmune hepatitis.

BACKGROUND: Antibodies to cytochrome P4502D6 (CYP2D6) were measured and their prevalence compared with that of antibodies to liver-specific arginase in patients with autoimmune hepatitis (AIH). METHODS: Anti-CYP2D6 antibodies were measured by sensitive radioligand assay and enzyme-linked immunosorbent assay (ELISA), and anti-arginase antibodies were measured by ELISA in 132 patients (definite AIH 11, probable AIH 36, hepatitis C 20, hepatitis B 23, other autoimmune diseases 42) and 50 healthy controls. RESULTS: CYP2D6 index (radioligand assay) was significantly higher in all groups of patients than those in healthy controls. A higher index than the cut-off value (mean+3 S.D. in healthy controls) was found in 36.4%, 44.4%, 25.0%, 17.4% and 28.6% of patients with definite AIH, probable AIH, hepatitis C, hepatitis B and other autoimmune diseases, respectively. CYP2D6 index was not related to serum IgG, anti-nuclear antibody or AIH scores, and was weakly correlated with anti-arginase antibody activity. When CYP2D6 index and anti-arginase antibodies were combined, 55.3% of AIH patients were positive for either one or both antibodies. CONCLUSIONS: Anti-CYP2D6 antibodies by radioligand assay were frequently present in patients with AIH. Combined tests for anti-CYP2D6 radioligand assay and anti-arginase antibodies resulted in detection of 55% of AIH patients.

Antibody Specificity↗