Kouki Mori
Tohoku University
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Environmental Health Perspectives | 2008
Minoru Yoshida; Natsuki Shimizu; Megumi Suzuki; Chiho Watanabe; Masahiko Satoh; Kouki Mori; Akira Yasutake
Background Although a long latency period of toxicity after exposure to methylmercury (MeHg) is known to exist in humans, few animal studies have addressed this issue. Substantiation of delayed MeHg toxicity in animals would affect the risk evaluation of MeHg. Objectives Our goal in this study was to demonstrate the existence of a latency period in a rodent model in which the toxicity of perinatal MeHg exposure becomes apparent only later in life. Our study included metallothionein (MT) knockout mice because studies have suggested the potential susceptibility of this strain to the neurodevelopmental toxicity of MeHg. Methods Pregnant MT-null and wild-type C57Bl/6J mice were exposed to MeHg through their diet containing 5 μg Hg/g during gestation and early lactation. We examined behavioral functions of the offspring using frequently used paradigms, including open field behavior (OPF), passive avoidance (PA), and the Morris water maze (MM), at ages of 12–13 and 52–53 weeks. Results At 12 weeks of age, behavioral effects of MeHg were not detected, except for OPF performance in MeHg-exposed MT-null females. At 52 weeks of age, the MeHg-exposed groups showed poorer performance both in PA and MM, and their OPF activity differed from controls. These effects of MeHg appeared exaggerated in the MT-null strain. The brain Hg concentration had leveled off by 13 weeks of age. Conclusions The results suggest the existence of a long latency period after perinatal exposure to low-level MeHg, in which the behavioral effects emerged long after the leveling-off of brain Hg levels. Hence, the initial toxicologic event responsible for the late effects should have occurred before this leveling-off of brain Hg.
Current Opinion in Endocrinology, Diabetes and Obesity | 2010
Kouki Mori; Katsumi Yoshida
PURPOSE OF REVIEW Viral infection activates both the innate and adaptive immunity and is implicated as a trigger of autoimmune diseases including Hashimotos thyroiditis. This review summarizes our knowledge respecting the role of viral infection in the cause of Hashimotos thyroiditis. RECENT FINDINGS Components of several viruses such as hepatitis C virus, human parvovirus B19, coxsackie virus and herpes virus are detected in the thyroid of Hashimotos thyroiditis patients. Bystander activation of autoreactive T cells may be involved in triggering intrathyroidal inflammation. Signaling molecules associated with antiviral responses including Toll-like receptors may participate in Hashimotos thyroiditis induction. However, studies have provided insufficient direct evidence for the viral hypothesis in Hashimotos thyroiditis. SUMMARY Despite interesting circumstantial evidence, whether viral infection is responsible for Hashimotos thyroiditis remains unclear. Studies addressing this issue are required to substantiate a contribution from viral infection to Hashimotos thyroiditis and, consequently, the prospect for developing preventive modalities for Hashimotos thyroiditis.
Clinical Endocrinology | 2002
Yoshinori Nakagawa; Kouki Mori; Saeko Hoshikawa; Makiko Yamamoto; Sadayoshi Ito; Katsumi Yoshida
objective Previous studies recommend the discontinuation of antithyroid drug (ATD) therapy during pregnancy in women with well‐controlled Graves’ hyperthyroidism (GH). In this study, we investigated whether this termination of ATD therapy during pregnancy is beneficial in terms of postpartum GH recurrence.
Journal of Endocrinological Investigation | 1996
Katsumi Yoshida; Yoshihiko Aizawa; Nobuko Kaise; Hiroshi Fukazawa; Yoshinori Kiso; Noriyo Sayama; Kouki Mori; Hironobu Hori; Keishi Abe
Thyroid-stimulating antibody (TSAb) activity and the TSH-binding inhibitory immunoglobulin (TBII) index were assessed in 158 patients with Graves’ disease who had been treated with 131I 6–14 years earlier. Twenty-one patients (13%) were still hyperthyroid, 45 (28%) were euthyroid, 44 (28%) were subclinically hypothyroid, and 48 (30%) were overtly hypothyroid. Positive results were obtained in 10 (48%) of the 21 patients with hyperthyroidism for both TSAb and TBII assays, and in 3 patients (14%) in one of the assays. In contrast, only two (5%) patients with subclinical hypothyroidism and 1 (2%) patient with overt hypothyroidism tested positive in both assays, and 11 (25%) subclinically hypothyroid patients and 15 (31%) overtly hypothyroid patients tested positive in one of the assays. The correlation coefficients between TSAb and TBII were 0.88 (p<0.01) in hyperthyroid patients, 0.49 (p<0.01) in euthyroid patients, 0.34 (p<0.05) in subclinically hypothyroid patients, and 0.12 (p>0.05) in patients with overt hypothyroidism. Findings indicate the presence of long-term changes in the population of TSH receptor antibodies years after 131I treatment, which may influence thyroid function.
Thyroid | 2004
Saeko Hoshikawa; Kouki Mori; Nobuko Kaise; Yoshinori Nakagawa; Sadayoshi Ito; Katsumi Yoshida
Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including equilibrium dialysis followed by radioimmunoassay (RIA) but not when determined by RIA after ultrafiltration of sera. These results indicate an increased T4 binding to TBG during pregnancy in the patients with FDH. Furthermore, our results suggest that normal serum FT4 determined by equilibrium dialysis is not an ultimate standard for the diagnosis of FDH in the patients with the mutant albumin R218P.
Brain Research Bulletin | 2007
Koreaki Sugimoto; Kouki Mori; Katsuya Uchida; Daisuke Kobayashi; Keiichi Itoi
Thyroid-stimulating hormone (TSH) stimulates the synthesis and release of thyroid hormones including triiodothyronine (T3) and thyroxine (T4). Semiquantitative analyses using northern blot and in situ hybridization suggested that TSH gene transcription is upregulated under conditions of hypothyroidism. However, no quantitative analysis of TSH gene expression using real-time polymerase chain reaction (PCR) has been reported. In this study, we quantitated the TSHbeta messenger ribonucleic acid (mRNA) level as well as the TSHbeta heterogeneous nuclear ribonucleic acid (hnRNA) level in the anterior pituitary of hypothyroid rats, by real-time PCR using the LightCycler system. The hnRNA is the primary deoxyribonucleic acid (DNA) transcript, which reflects the transcription rate more reliably than the mRNA because of its short half-life. In the anterior pituitary of rats with methimazol-induced chronic hypothyroidism, both mRNA and hnRNA expression of TSHbeta were upregulated fourfold relative to normal rats (n=4). Our method provides a rapid and accurate measure of gene transcription. In the present report, we described a technique for accurate measurement of TSHbeta hnRNA level.
Molecular and Cellular Endocrinology | 2001
Kouki Mori; Katsumi Yoshida; Jun-ichi Tani; Yoshinori Nakagawa; Saeko Hoshikawa; Sadayoshi Ito
Double-stranded RNA (dsRNA) plays a role in the regulation of cell growth and apoptosis as well as in the cellular antiviral responses. However, it remains unknown if dsRNA-activated signaling systems are functional in the thyroid. Here we report the presence of the dsRNA-dependent protein kinase (PKR) in FRTL-5 rat thyroid cells. In poly(I)-poly(C) (pIC)-stimulated cells, activation of nuclear factor-kappa B (NF kappa B) binding was clearly induced. Incubation of FRTL-5 cells with pIC resulted in a marked increase in interferon regulatory factor-1 (IRF-1) mRNA and phosphorylated signal transducer and activator of transcription-1 (STAT1) levels. Addition of pIC to cells led to type I interferon (IFN) gene expression, especially IFN beta, which can induce STAT1 phosphorylation, suggesting that dsRNA indirectly induced STAT1 phosphorylation through expression of type I IFN. Thus, our results suggest that the dsRNA-activated signaling pathway may be involved in the regulation of IFN-inducible genes in the thyroid.
Autoimmunity | 2011
Kazuki Morohoshi; Michiko Osone; Katsumi Yoshida; Yoshinori Nakagawa; Saeko Hoshikawa; Hiroshi Ozaki; Yurie Takahashi; Sadayoshi Ito; Kouki Mori
FTY720 is an immunomodulator that alters migration and homing of lymphocytes via sphingosine 1-phosphate receptors. This compound has been shown to be effective in suppressing autoimmune diseases in experimental and clinical settings. In the present study, we tested whether FTY720 prevented autoimmune thyroiditis in iodide-treated non-obese diabetic (NOD) mice, a model of Hashimotos thyroiditis (HT) in humans. Mice were given 0.05% iodide water for 8 weeks, and this treatment effectively induced thyroiditis. Iodide-treated mice were injected intraperitoneally with either saline or FTY720 during the iodide treatment. FTY720 clearly suppressed the development of thyroiditis and reduced serum anti-thyroglobulin antibody levels. The number of circulating lymphocytes and spleen cells including CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T cells was decreased in FTY720-treated mice. Our results indicate that FTY720 has immunomodulatory effects on iodide-induced autoimmune thyroiditis in NOD mice and may be a potential candidate for use in the prevention of HT.
Autoimmunity | 2009
Kouki Mori; Katsumi Yoshida; Masahiko Mihara; Yoshiyuki Ohsugi; Yoshinori Nakagawa; Saeko Hoshikawa; Hiroshi Ozaki; Sadayoshi Ito
We explored the role of interleukin-6 (IL-6) in the development of autoimmune thyroiditis in nonobese diabetic (NOD) mice, an animal model of Hashimotos thyroiditis, using anti-mouse IL-6 receptor antibody (MR16-1). Thyroiditis was induced by iodide ingestion or mouse thyroglobulin (Tg) immunization. Mice were injected intraperitoneally with saline, control rat IgG, or MR16-1 (2 or 8 mg). Iodide ingestion did not increase serum IL-6 levels and MR16-1 (2 mg) failed to prevent the development of thyroiditis. In contrast, Tg immunization induced a rapid and significant increase in serum IL-6 levels. While MR16-1 (2 mg) had no effect on Tg-induced thyroiditis, the severity, but not incidence, of thyroiditis was reduced in 8 mg MR16-1-treated mice compared with saline-injected mice. However, thyroiditis development in the 8 mg MR16-1-treated mice was indistinguishable from that in the control IgG-treated mice. MR16-1 (8 mg) did not affect serum anti-Tg antibody levels. These results suggest that IL-6 may play only a minor role in the development of autoimmune thyroiditis in NOD mice.
Cellular Immunology | 2011
Kazuki Morohoshi; Katsumi Yoshida; Yoshinori Nakagawa; Saeko Hoshikawa; Hiroshi Ozaki; Yurie Takahashi; Sadayoshi Ito; Kouki Mori
We examined whether a synthetic retinoid Am80 prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic mice, an animal model of Hashimotos thyroiditis (HT). Am80 (0, 0.1 or 1 mg/kg/day) was orally administered in feed during the 8-week iodide treatment. While iodide ingestion effectively induced thyroiditis, Am80 administration failed to interfere with thyroiditis development and serum anti-thyroglobulin antibody levels regardless of the dose of the retinoid. Splenic T cell numbers, splenocyte proliferation and interferon-γ production were decreased in the Am80-treated mice. Our data suggest that Am80 is not a candidate for use in the prevention of HT.