Kaoru Arii

Kochi University, Kōchi-shi, Kochi-ken, Japan

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Publications (47)140.38 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A 31-year-old woman developed polyarthralgia and extension disorder of the right elbow of 2 months' duration without abdominal symptom. Laboratory findings revealed C-reactive protein 2.7 mg/dL. Anti-nuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibody were negative. F-18 FDG PET/CT showed elevated pinpoint uptakes of FDG in the entheses. In contrast, MRI revealed no specific findings. Four months after PET/CT, she developed right lower abdominal pain. Colonoscopy showed abscess in ascending colon, which the initial PET/CT finding might mean early image of infective colitis. A diagnosis of early reactive arthritis was made. Treatment with antibiotics improved colitis, colonic abscess, and enthesitis after 2 months. Moreover, F-18 FDG PET/CT showed no accumulation in colon and entheses. These findings suggest that F-18 FDG PET/CT scanning allows enthesitis in the early stage of reactive arthritis, before the possible detection by the other procedures.
    Clinical nuclear medicine 02/2011; 36(2):121-3. DOI:10.1097/RLU.0b013e318203bb97 · 3.93 Impact Factor
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    ABSTRACT: We have demonstrated that pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, enhanced human serum paraoxonase (PON1) gene promoter activity and that protein kinase C (PKC) activated PON1 expression through Sp1 in cultured HepG2 cells. We investigated whether PKC was involved in pitavastatin-induced PON1 expression. PON1 gene promoter activity was assessed by a reporter gene assay using cultured Huh7 cells. PON1 protein expression and PKC activation were measured by Western blotting. The binding activity of Sp1 to the PON1 gene upstream was analyzed by electrophoretic mobility shift assay. Both PON1 gene promoter activity and PON1 protein expression were elevated by pitavastatin stimulation. The effects of pitavastatin on PON1 promoter activity and PON1 protein expression were attenuated by both bisindolylmaleimide IX (Ro-31-8220) and bisindolylmaleimide I. Electrophoretic mobility shift assay showed that pitavastatin increased the Sp1-PON1 DNA binding, and this effect was attenuated by Ro-31-8220. Pitavastatin activated atypical PKC, but never conventional or novel PKC. Myristoylated pseudosubstrate peptide inhibitor of PKCzeta abolished the pitavastatin-increased PON1 promoter activity; however, calphostin C and Gö6976 (PKC inhibitors except for PKCzeta) did not influence the promoter activity. In addition, an overexpression of dominant negative form of PKCzeta expression vector obviously decreased pitavastatin-induced PON1 promoter activation. These observations suggest that pitavastatin activates PKC, especially PKCzeta isoform, which increases the binding intensity of Sp1 to PON1 DNA promoter responsible for enhanced transcription of PON1 gene and increased PON1 protein expression in Huh7 cells.
    Metabolism: clinical and experimental 09/2010; 59(9):1287-93. DOI:10.1016/j.metabol.2009.12.003 · 3.89 Impact Factor

  • Rheumatology (Oxford, England) 04/2010; 49(4):829. DOI:10.1093/rheumatology/kep466 · 4.48 Impact Factor
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    ABSTRACT: To evaluate the accuracy of PET/CT using [(18)F]fluorodeoxyglucose (FDG) in determining the presence of enthesitis in patients with SpAs. Results of PET/CT scans of eight patients with SpA and seven patients with RA were retrospectively examined, with specific focus on five joints and three entheses. Volume fixation values are expressed as standardized uptake values (SUVs). Data from 20 patients with non-rheumatic (NR) diseases and 20 healthy subjects were also examined if non-specific, false positive findings were possible. We evaluated the clinical utility of PET/CT examinations in SpA, compared with MRI and Ga scintigraphy. Images of PET/CT scans of the shoulder, hip and knee joints revealed that FDG accumulated at the entheses in SpA and in the synovium in RA patients. The maximum SUVs [mean (s.d.)] were statistically higher in SpA patients compared with RA patients at the entheses of lumbar spinous process [4.83 (1.15) vs 1.42 (0.34); P < 0.05, respectively], pubic symphysis [3.93 (0.87) vs 1.35 (0.31); P < 0.05, respectively] and ischial tuberosity [4.76 (1.5) vs 1.35 (0.42); P < 0.05, respectively]. The positive frequencies of lumbar spinous processes and ischial tuberosity evaluated by PET/CT scan in the SpA group were significantly higher than that evaluated by MRI. MRI is now widely used to detect bone marrow oedema and enthesitis in patients with SpA. PET/CT scans offer an alternative method to identify enthesitis, and will likely contribute to the early diagnosis of SpA.
    Rheumatology (Oxford, England) 12/2009; 49(2):348-54. DOI:10.1093/rheumatology/kep379 · 4.48 Impact Factor
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    ABSTRACT: Human serum paraoxonase 1 (PON1) is associated with high-density lipoprotein and inhibits oxidative modification of low-density lipoprotein in vitro. Therefore, PON1 is expected to protect against atherosclerosis in vivo. We and other investigators have shown that PON1 enzymatic activity is decreased in diabetic patients; however, an alteration in hepatic PON1 synthesis under hyperglycemic conditions remains unclear. We previously demonstrated that Sp1 is a positive regulator of PON1 transcription and that an interaction between Sp1 and protein kinase C (PKC) is a crucial mechanism for the effect of Sp1 on PON1 transcription in cultured HepG2 cells. Because several PKC isoforms are activated under hyperglycemic conditions, we examined the effect of d-glucose, which can activate the diacylglycerol-PKC pathway, on the transcription and expression of PON1. For a reporter gene assay, Huh7 human hepatocyte cell line incorporated with PON1 (-1232/-6)-luciferase expression vector was established using a cationic lipid method. d-Glucose dose dependently enhanced PON1 promoter activity. d-Glucose also enhanced both messenger RNA and protein expression of PON1. Increased PON1 expression was also detected in primary human hepatocytes treated with high d-glucose concentrations. Bisindolylmaleimide, a PKC inhibitor, significantly inhibited d-glucose-induced transactivation of PON1; and mithramycin, an inhibitor of Sp1, completely abrogated the transactivation. Our data suggest that high glucose concentrations transactivate the PON1 gene through Sp1 activation by PKC in cultured hepatocytes. Up-regulated hepatic PON1 expression under high glucose conditions may be a compensatory mechanism in diabetes in which antioxidant capacity, including PON1 enzymatic activity, is attenuated.
    Metabolism: clinical and experimental 01/2009; 57(12):1725-32. DOI:10.1016/j.metabol.2008.07.032 · 3.89 Impact Factor
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    ABSTRACT: Human serum paraoxonase (PON1) is associated with HDL and inhibits oxidative modification of LDL. PON1 enzymatic activity has been shown to decrease in diabetic patients; however, the effect of PON1 status on long-term outcome has not been reported. In this study, we examined the association between baseline PON1 status and the development of cardiovascular disease (CVD) during 10 years of follow-up in 88 type 2 diabetic patients whose enzymatic activities, concentrations, and genetic polymorphisms of PON1 had been determined. A total of 20 CVD events were recorded during the follow-up period. Using Kaplan-Meier survival curves, we found a significantly increased incidence of CVD in patients with a lower concentration or paraoxonase activity of PON1 than each median value (log-rank 7.460; P < 0.01, and log-rank 4.187; P < 0.05, respectively). By Cox regression analysis, both concentration and paraoxonase activity were significantly associated with the development of CVD, even after correction for gender, age, and preexisting CVD (P < 0.05). Low concentration and enzymatic activity of PON1 may be an independent predictor of cardiovascular events in diabetic patients.
    Acta Diabetologica 10/2008; 46(3):239-42. DOI:10.1007/s00592-008-0066-3 · 2.40 Impact Factor
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    ABSTRACT: A 44-year-old man with intermittent asymmetric migratory oligoarthritis lasting the recent decade was admitted to our hospital. Considerable specific biomarkers for rheumatoid arthritis such as anti-agalactosyl IgG antibody are all negative. He was diagnosed as palindromic rheumatism (PR). Although hand X-rays showed no remarkable findings, hand magnetic resonance imaging (MRI) detected pannus and bone erosion. PR is defined as the disease characterized by short-lasting attacks of acute oligoarthritis, without radiographic changes. To our knowledge, the findings of MRI for PR have not been previously described. We propose that MRI findings in patients with PR is useful tool to distinguish PR from rheumatoid arthritis (RA) or other RA related diseases.
    Rheumatology International 08/2008; 29(1):87-9. DOI:10.1007/s00296-008-0654-0 · 1.52 Impact Factor
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    ABSTRACT: It has been shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have pleiotropic effects and that human serum paraoxonase (PON1) inhibits the oxidative modification of low-density lipoprotein. We investigated the effects of pitavastatin on PON1 gene promoter activity and PON1 protein expression through the activation of mitogen-activated protein (MAP) kinase signaling cascades in cultured Huh7 cells. Both PON1 gene promoter activity and PON1 protein expression were elevated by pitavastatin stimulation. Pitavastatin phosphorylated p44/42 MAP kinase. The effects of pitavastatin on PON1 promoter activity and PON1 protein expression were attenuated by PD98059. The cotransfection of Sp1 expression vector increased PON1 promoter activity, and mithramycin suppressed pitavastatin-enhanced PON1 promoter activity. The latter activity was attenuated by cotransfection with the expression vector of sterol regulatory element-binding protein-2 (SREBP-2) with mutated p44/42 MAP kinase specific phosphorylation sites. Pitavastatin increased the Sp1-PON1 DNA complex and this effect was attenuated by PD98059. These observations suggest that pitavastatin phosphorylates p44/42 MAP kinase and then activates the transcription of PON1 gene and increases the PON1 protein expression in Huh7 cells. Furthermore, we speculate that pitavastatin affects both the phosphorylation of SREBP-2 and the Sp1 binding to PON1 DNA through the activation of p44/42 MAP kinase signaling cascade.
    Atherosclerosis 06/2008; 202(2):439-45. DOI:10.1016/j.atherosclerosis.2008.05.013 · 3.99 Impact Factor

  • Atherosclerosis Supplements 05/2008; 9(1):41-41. DOI:10.1016/S1567-5688(08)70157-0 · 2.29 Impact Factor

  • Atherosclerosis Supplements 05/2008; 9(1):122-122. DOI:10.1016/S1567-5688(08)70489-6 · 2.29 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease which is induced by proinflammatory cytokines or oxidative stress. The activation of nuclear factor-kappa B (NF-kappaB) that contributed to imbalance between apoptosis and proliferation of rheumatoid synovial cells (SC). Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of stroke. We aimed to investigate the suppressive effect of edaravone on collagen-induced arthritis (CIA) mice and on the activated molecules in SC stimulated by interleukin-1beta (IL-1beta). Edaravone was administrated intravenously at a dose of 3mg/kg of body weight to CIA mice. The progression of CIA was evaluated by the macroscopic arthritis scoring system of paws. Interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3) concentrations in culture medium of human SC were measured by enzyme linked immunosorbent assays. Caspase-3/7 activity and nuclear factor-kappa B (NF-kappaB) protein level of cultured human SC were estimated by fluorometric assay and Western blot analysis, respectively. Edaravone significantly decreased macroscopic arthritis score in CIA mice. Acceleration of IL-6 and MMP-3 productions and attenuation of caspase-3/7 activity in IL-1beta-stimulated SC were abated by edaravone. Activated NF-kappaB in IL-1beta-stimulated SC was suppressed by edaravone. Edaravone, antioxidants available for clinical use, appears to have therapeutic effect on RA. We suggest that the inhibitory effect of edaravone on RA might be exerted, at least in part, through suppression of activated NF-kappaB. Therefore, we expect therapeutical use of edaravone as an anti-rheumatic agent.
    Molecular Immunology 02/2008; 45(2):463-9. DOI:10.1016/j.molimm.2007.05.020 · 2.97 Impact Factor
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    ABSTRACT: alpha2-Heremans Schmid glycoprotein (AHSG), also designated fetuin-A, is an abundant plasma protein that is expressed in hepatocytes. AHSG/fetuin-A has diverse biological functions including regulation of calcium homeostasis and inhibition of insulin receptor tyrosine kinase activity. The aim of this study was to detect single nucleotide polymorphisms (SNPs) of the AHSG gene that can be involved in regulation of AHSG/fetuin-A expression. By a cycle sequencing method, two common SNPs in the promoter region of AHSG gene, -799A/T (rs2248690, dbSNP ID) and -425G/T (rs2077119), were identified. A reporter gene assay using HepG2 cells showed that the -799A allele had significantly higher promoter activity compared with the -799T allele. The overexpression of c-Fos/c-Jun significantly repressed transcriptional activity and a gel shift assay showed that the -799T DNA fragment had a greater affinity for transcription factor AP-1 than the -799A. In 40 unrelated healthy subjects, serum AHSG/fetuin-A levels increased with the following order of genotypes: -799TT<-799AT<-799AA (mean+/-S.E.M.; 222.1+/-11.0, 291.8+/-8.1, and 349.0+/-13.0 microg/ml, respectively, P<0.001). In conclusion, SNP rs2248690 in the promoter region of the AHSG gene affects the AHSG gene transcription, possibly by producing different association with AP-1.
    Diabetes research and clinical practice 01/2008; 79(1):164-70. DOI:10.1016/j.diabres.2007.08.005 · 2.54 Impact Factor
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    ABSTRACT: Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin receptor signal transduction pathway. We investigated the effects of glucose on PTP1B transcription in the human hepatocyte cell line Huh7. Using a reporter gene assay, we found that D-glucose dose-dependently enhanced the PTP1B promoter activity. Real-time PCR demonstrated that D-glucose also increased PTP1B mRNA expression. Protein kinase C (PKC) inhibitors partially but significantly inhibited the transactivation by D-glucose. Mithramycin, a Sp1 inhibitor, completely abrogated this transactivation. The deletion of three possible Sp1 sites in the promoter region of PTP1B significantly reduced the basal promoter activity and transactivation by D-glucose. Sp1 activation by PKC is one of the key mechanisms in the regulation of several gene expressions. Our data suggested that glucose enhanced PTP1B transcription through Sp1 activation by PKC. Increased hepatic PTP1B expression may partly explain glucose toxicity in diabetes.
    Molecular and Cellular Endocrinology 07/2007; 271(1-2):64-70. DOI:10.1016/j.mce.2007.04.005 · 4.41 Impact Factor
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    ABSTRACT: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.
    Clinical nephrology 07/2007; 67(6):358-65. DOI:10.5414/CNP67358 · 1.13 Impact Factor
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    ABSTRACT: The oxidative modification of low-density lipoproteins (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Iron plays a part in the formation of highly toxic free radicals such as hydroxide and superoxide anions, which can induce lipid peroxidation. We investigated whether serum iron status was associated with circulating oxidized LDL (oxLDL) levels in type 2 diabetic patients, in whom oxidative stress and susceptibility to lipid oxidation were supposedly increased. Serum ferritin levels were significantly correlated with plasma oxLDL concentrations in both male and female patients (p<0.02 and p<0.05, respectively). No correlation was detected between ferritin and LDL-cholesterol (LDL-C) concentrations despite the close correlation between LDL-C and oxLDL concentrations (p<0.0001). Stepwise regression analysis showed that ferritin concentration was an independent positive determinant of oxLDL level, in addition to triglyceride concentration, body mass index and sex. This is the first report to show that serum ferritin is associated with circulating oxLDL levels in patients with type 2 diabetes. Further work is required to establish a causative link between iron excess and the development of diabetic vascular complications.
    Endocrine Journal 11/2006; 53(5):665-70. DOI:10.1507/endocrj.K06-010 · 2.00 Impact Factor

  • Atherosclerosis Supplements 06/2006; 7(3):254-254. DOI:10.1016/S1567-5688(06)81017-2 · 2.29 Impact Factor

  • Atherosclerosis Supplements 06/2006; 7(3):354-354. DOI:10.1016/S1567-5688(06)81393-0 · 2.29 Impact Factor

  • Atherosclerosis Supplements 06/2006; 7(3):294-295. DOI:10.1016/S1567-5688(06)81199-2 · 2.29 Impact Factor

  • Atherosclerosis Supplements 06/2006; 7(3):210-210. DOI:10.1016/S1567-5688(06)80821-4 · 2.29 Impact Factor
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    ABSTRACT: A male patient with rheumatoid arthritis (RA) developed acute stroke and was treated with the free radical scavenger, edaravone. Polyarthralgia improved with a reduction in serum C-reactive protein concentration soon after the start of edaravone administration. The disease activity score 28 (DAS28) also decreased. Edaravone appears to be effective for the control of RA. The usefulness of this potentially novel therapeutic agent should be tested in a well designed randomized controlled trial.
    Journal of Clinical Pharmacy and Therapeutics 05/2006; 31(2):197-9. DOI:10.1111/j.1365-2710.2006.00722.x · 1.67 Impact Factor

Publication Stats

804 Citations
140.38 Total Impact Points


  • 2004-2011
    • Kochi University
      • Department of Endocrinology, Metabolism and Nephrology
      Kōchi-shi, Kochi-ken, Japan
  • 2009
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 1996-2008
    • Kochi Medical School
      Kôti, Kōchi, Japan