Tomoko Arai

Toho University, Edo, Tokyo, Japan

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Publications (4)18.38 Total impact

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    ABSTRACT: To play its physiological role, 1,25(OH)2D3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group AA+Aa (19.7 +/- 7.2%). There were no significant differences between the two groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. The study results showed that the patients in group aa were more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+]e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.
    No preview · Article · Dec 2001 · Nephron
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    ABSTRACT: We investigated the detailed distribution of high-density lipoproteins (HDL) particle size in patients with cholesteryl ester transfer protein (CETP) deficiency. Serum samples pre-stained with Sudan black B were electrophoresed using 4-30% polyacrylamide gradient gels, and the Stokes diameter of HDL particles was determined in 23 patients with genetic CETP deficiency, nine patients with hyperalphalipoproteinemia and seven subjects with normal HDL cholesterol concentrations. The mean Stokes diameter of HDL particles in CETP deficient patients (11.2+/-0.6 nm) was significantly greater than hyperalphalipoproteinemia (10.7+/-0.3 nm, P<0.05) and normal subjects (9.5+/-0.4 nm, P<0.01). A significant relationship was found between mean HDL size and serum CETP mass concentrations (P<0.05). When the particle size of all detected HDL bands was investigated, extra-large HDL particles larger than 12 nm were found in 14 of the 23 patients with CETP deficiency, which were not found in any of the hyperalphalipoproteinemia patients or normal subjects. Serum low-density lipoproteins (LDL) cholesterol and total cholesterol concentrations were lower in CETP deficiencies with extra-large HDL particles than those in non-carriers (P<0.01). These results indicate that extra-large HDL may be an index to clarify the relationship between genetic CETP deficiency and atherosclerosis.
    Full-text · Article · Nov 2000 · Clinica Chimica Acta
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    ABSTRACT: Nitric oxide (NO) synthesized by the vascular endothelium regulates mammalian blood vessels and other systems in humans. Recently, an endothelial nitric oxide synthase (ecNOS) gene polymorphism, the 27-bp repeat in intron 4 (ecNOS4), was reported to be related to the pathogenesis of coronary heart disease and terminal renal failure. We analyzed this polymorphism in a group of 413 healthy subjects, and measured their plasma nitrite and nitrate (NOx) levels. The frequency of the b allele was 89.8% , and the frequency of the a allele was 10.2%. The frequency of ecNOS4 b/b, ecNOS4 b/a, and ecNOS4 a/a in the healthy subjects in this study was 0.814 (n=336), 0.169 (n=70) and 0.017 (n=7), respectively. Using this polymorphism as a DNA marker, we found a strong association between the alleles of the ecNOS gene polymorphism and the plasma NOx levels. The basal NO metabolite levels were 28.8 micromol/L in subjects with ecNOS4 a/a, 31.4 micromol/L in those with ecNOS4 b/a, and 35.5 micromol/L in those with ecNOS4 b/b. The mean plasma NOx level of the subjects who were homozygous for the a allele was nearly 20% lower than in the subjects with the b allele. The plasma NOx level of the subjects with the a allele was 31.2+/-2.00 micromol/L, and significantly lower than the 35.5+/-0.93 micromol/L in those without the a allele (P <0.05). The results of this study indicate that the ecNOS4 gene locus may be responsible for variations in the genetic control of plasma NOx and that analysis of ecNOS4 gene polymorphism may be a useful tool for studying the relation between NO and diseases.
    Preview · Article · Apr 1998 · Biochemical and Biophysical Research Communications
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Publication Stats

389 Citations
18.38 Total Impact Points


  • 2000
    • Toho University
      Edo, Tokyo, Japan
  • 1998
    • Toranomon Hospital
      Edo, Tōkyō, Japan