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Kouki Mori

Publications and source records attributed to Kouki Mori.

17 recordsLinked to original sources
PubMed2006

Development of subclinical hyperthyroidism due to Graves' disease in a hypothyroid woman who had undergone hemithyroidectomy for adenomatous goiter and radiotherapy for nasopharyngeal cancer.

A variety of thyroid disorders develop following external radiation to head and neck cancers. Hypothyroidism is the most common clinical consequence of the radiotherapy and lifelong thyroid hormone replacement is required in many cases. Patients who received both hemithyroidectomy and the external radiation to the neck are at especially high risk for permanent hypothyroidism. Here we report an unusual case with radiation-induced hypothyroidism who had undergone hemithyroidectomy for adenomatous goiter 8 years before the radiotherapy for nasopharyngeal cancer and subclinical hyperthyroidism due to Graves' disease developed during thyroxine replacement therapy. Thus subclinical hyperthyroidism due to Graves' disease can develop in patients with radiation-induced hypothyroidism even if they have undergone hemithyroidectomy for thyroid nodules. Therefore careful and periodic evaluation of thyroid function is required even on adequate thyroxine replacement therapy.

Adult↗
PubMed2006

Effects of perinatal exposure to low doses of cadmium or methylmercury on thyroid hormone metabolism in metallothionein-deficient mouse neonates.

Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain type 3 deiodinase (D3) activity in MT-I/II null and wild-type neonates. In contrast, exposure to Cd resulted in a decrease in serum T4 levels in MT-I/II null neonates. Consistently, brain D2 activity was increased in Cd-exposed MT-I/II null neonates. No significant changes in liver D1 and brain D3 activities were induced by Cd administration. Our study demonstrates that perinatal exposure to low doses of Cd or MeHg can induce changes in brain deiodinase activities in the neonates, suggesting that thyroid hormone metabolism in fetuses and neonates might be a potential target of Cd and MeHg.

Administration, Oral↗
PubMed2005

Methylmercury inhibits type II 5'-deiodinase activity in NB41A3 neuroblastoma cells.

Methylmercury (MeHg) is a well-known neurotoxicant and prenatal exposure to MeHg results in severe brain damage. Since MeHg has a high affinity for thiol groups, we sought to determine whether MeHg inhibited type II iodothyronine deiodinase (D2) activity, by which prohormone thyroxine (T4) is converted to active thyroid hormone, 3,5,3'-triiodothyronine (T3) in the brain, using NB41A3 mouse neuroblastoma cells. In MeHg-treated cells, D2 activity was inhibited in a dose- and time-dependent manner; relatively low concentrations of MeHg (30 nM) inhibited D2. Kinetic analysis using a double reciplocal plot of D2 activity revealed competitive inhibition by MeHg. DTT protected D2 from MeHg when cells were incubated with both MeHg and DTT or when MeHg was added to the assay buffer containing DTT and cell sonicates from untreated cells. Removal of MeHg from culture medium did not recover D2 activity. These results demonstrate that MeHg inhibited D2 activity in NB41A3 cells and the selenocysteine in the catalytic subunit of D2 may be involved in the inhibitory action of MeHg. Further our results suggest that T3 deficiency due to D2 inhibition in the brain may be involved in the neurotoxicity of MeHg.

Animals↗
PubMed2005

The effects of gestational arsenic exposure and dietary selenium deficiency on selenium and selenoenzymes in maternal and fetal tissues in mice.

Although toxicological and metabolic interactions of arsenic (As) and selenium (Se) have been suggested by epidemiolgical literatures, the past experimental studies mostly focused on acute, high-dose interaction, leaving the long-term, low-dose interaction unexplored. In the present study pregnant mice, fed either Se-deficient or adequate (0 or 5 micromol Se/kg diet, respectively) diet, were given oral gavage of sodium arsenite (0 or 58 micromol/kg per day; chosen as less than half of the fetotoxic dose in this protocol) from gestational day (GD) 7-16. The levels of As and Se as well as five selenoenzymes (glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and type-I, -II and -III iodothyronine deiodinases (DI-I, -II and -III) were examined on GD17 in the tissues of dams and of fetus. The Se-deficient mice showed significantly enhanced accumulation of As compared to the Se-adequate mice in maternal liver (increased by 48%) and fetal brain (by 31%). Although no direct evidence of the enhanced toxicity in the Se-deficient group was obtained, the As exposure affected the levels of Se and selenoenzymes, an effect which was more discernible in Se-deficient group. Although most of theses changes were mild or moderate, the DI-II activity in Se-deficient fetal brain showed a drastic four-fold increase by As exposure, suggesting a possible disturbance of thyroid hormone environment in the fetus. These data suggested that apparently non-toxic, in utero dose of As, showed enhanced accumulation when combined with Se-deficiency and could affect the metabolism/kinetics of Se in fetal brain, which might result in developmental toxicity in mice.

Animals↗
PubMed2005

Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact.

When human blood monocytes were cocultured with stromal cells derived from human giant cell tumor of bone (GCTSC) and a Millipore filter (0.4 microm) was interposed between monocytes and GCTSC, multinucleated giant cell formation of monocytes was induced. The multinucleated giant cells have characters as osteoclast-like cells, indicating that a soluble osteoclast-inducing factor(s) is secreted from GCTSC expressing RANK, RANKL/ODF/OPGL and TACE mRNA. Furthermore, OCIF/OPG inhibited GCTSC-induced osteoclastogenesis, showing that the RANK-RANKL system is involved in GCTSC-induced osteoclastogenesis and that soluble form of ODF/RANKL induces osteoclasts from monocytes. GCTSC expressed the cytokine mRNAs such as M-CSF, GM-CSF, IL-3, IL-4, IL-6, and IFN-gamma mRNAs. None of IL-1ralpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10, IL-18, TNF-alpha, G-CSF and IFN-gamma could be detected in all culture media. A significant amount of IL-6 could be detected in the culture media of all GCTSC. IL-8 was found in the culture media of two GCTSC and two osteosarcoma-derived cells. M-CSF was detected in all culture media. GCTSC express CaSR, and stimulation of GCTSC with either extracellular Ca(2+) or neomycin, agonist of CaSR, augmented the expression of RANKL. Some lines of GCTSC expressed alkaline phosphatase, osteocalcin and Cbfa1, suggesting that GCTSC are intimately related to osteoblastic lineage.

Alkaline Phosphatase↗
PubMed2005

Visceral pleural perforation in two cases of ultrathin bronchoscopy.

Recently, ultrathin bronchoscopes with a thinner external diameter, greater visual range, improved visibility, and a larger working channel have been developed. The utility of a 2.8-mm diameter ultrathin bronchoscope in diagnosing peripheral pulmonary nodules has been reported by some authors. While the feasibility of approaching peripheral pulmonary lesions is attractive, peculiar complications that have not been experienced with standard bronchoscopy may occur. We report two cases in which pneumothoraces occurred because their visceral pleuras were perforated with an ultrathin bronchoscope during the procedure. The peculiar mechanism of pneumothorax in relation to ultrathin bronchoscopy is discussed.

Aged↗
PubMed2005

Autoinduction of tumor necrosis factor-alpha in FRTL-5 rat thyroid cells.

Tumor necrosis factor-alpha (TNFalpha) may play a role in the development of autoimmune thyroiditis such as Hashimoto's thyroiditis. In the present study, we examined whether TNFalpha induced its own expression in FRTL-5 rat thyroid cells. Lipopolysaccharide (LPS) markedly increased TNFalpha mRNA levels in FRTL-5 cells as assessed by semiquantitative RT-PCR. In addition, LPS-stimulated cells released TNFalpha protein into the culture medium. Similarly, TNFalpha induced its own gene and protein expression in FRTL-5 cells as assessed by RT-PCR and metabolic labeling and immunoprecipitation of TNFalpha. The autoinduction of TNFalpha gene was also observed in TNFalpha-stimulated human thyroid epithelial cells. TNFalpha induction was specific to LPS and TNFalpha since interferon-alpha or amiodarone failed to increase TNFalpha mRNA levels in FRTL-5 cells. Human TNFalpha induced rat TNFalpha gene expression, indicating that type 1 TNF receptor (TNF-R) is involved in the autoinduction. TNFalpha did not increase either type 1 or type 2 TNF-R mRNA levels, suggesting that upregulation of TNF receptors is not involved in the autoinduction of TNFalpha. Although the biological significance of autoinduction of TNFalpha remains unclear, our results suggest that thyroid epithelial cells may participate in the development of autoimmune thyroiditis through production of TNFalpha. Furthermore, inhibition of TNFalpha production in the thyroid may represent a novel approach to mitigating inflammation in autoimmune thyroiditis.

Actins↗
PubMed2004

Experimental autoimmune thyroiditis in nonobese diabetic mice lacking interferon regulatory factor-1.

Interferon regulatory factor-1 (IRF-1) is pivotal in the regulation of interferon (IFN)-mediated immune reactions, and studies suggest that IRF-1 is involved in the development of autoimmune diseases. IRF-1+/+, +/-, and -/- nonobese diabetic (NOD) mice were immunized with mouse thyroglobulin (mTg) to determine whether IRF-1 is required in experimental autoimmune thyroiditis (EAT), a murine model for Hashimoto's thyroiditis (HT). IRF-1-deficient mice developed EAT and anti-mTg antibodies comparable to IRF-1+/+ and +/- mice. Whereas both CD4+ and CD8+ T cells were found in thyroids of IRF-1+/+ mice, the latter was not in IRF-1-/- mice. Major histocompatibility complex class II antigen was comparably expressed in thyroids of IRF-1+/+ and -/- mice. Lack of IRF-1 resulted in decreased CD8+ T cell number in the spleen and reduced IFNgamma production by splenocytes. Our results suggest that IRF-1 is not pivotal in EAT in NOD mice.

Animals↗
PubMed2004

Artifactually elevated serum-free thyroxine levels measured by equilibrium dialysis in a pregnant woman with familial dysalbuminemic hyperthyroxinemia.

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.

Adult↗
PubMed2003

The functional interaction between CD98 and CD147 in regulation of virus-induced cell fusion and osteoclast formation.

Membrane fusion is an important event in the functioning of a living organism. Life starts as a sperm fuses with the membrane of an egg, leading to its fertilization. Membrane fusion is also required for myogenesis, osteogenesis and placenta formation. Multinucleated giant cells originating from monocytes-macrophages are associated with granulomatous lesions formed in response to foreign bodies, viruses, and bacteria. The CD4 molecule acts as a receptor for HIV. The major virus envelope glycoprotein, gp120, attaches to CD4 molecules expressed on the host cell surface. After binding to CD4 on the target cells, HIV is internalized via direct, pH-independent fusion of the viral and cell membranes. However, attachment of HIV to CD4 on the target cells is not sufficient for fusion. Interaction of gp160-expressing cells with neighboring cells bearing surface CD4 molecules is also required for syncytium formation. Syncytium formation and subsequent generalized cell fusion have been reported as potentially important mechanisms of virus-induced cytotoxic effects. Some antibodies against CD98/FRP-1 suppressed virus-induced cell fusion and CD98-mediated cell fusion of monocytes, indicating that CD98/FRP-1 molecules are able to regulate cell fusion. In this study, the functional interaction between CD98 and CD147 was investigated. Three kinds (Ab1, 2, and 3) of anti-CD147 and three kinds of anti-CD98 antibodies were used. Ab1 suppressed CD98-mediated cell fusion, but showed no effect on cell aggregation of Cd(+)U2ME-7 cells, U937-2 cells expressing HIV gp160. On the other hand, Ab2 enhanced the CD98-mediated cell fusion. Ab1 showed suppressive effect at early stage and Ab2 showed enhancing effect at later stage. Ab2 and 3 suppressed the spontaneous cell agglutination and cell fusion of Cd(+)JME-2 cells, Jurkat cells expressing HIV gp160. Ab2 suppressed CD98-mediated cell fusion, but showed no effect on cell aggregation of Cd(+)JME-2 cells. Ab2 cancelled suppression of cell fusion induced by suppressive antibody against CD98. Ab2 and 3 also suppressed CD98-mediated cell fusion of monocytes. This study indicates the functional interaction between CD98 and CD147 in the regulation of cell fusion.

Antibodies, Monoclonal↗
PubMed2003

Relapse of Graves' disease in a patient with pheochromocytoma.

We describe a patient with right adrenal tumor detected incidentally. The tumor was diagnosed as pheochromocytoma by endocrinological and radiological studies, and was removed surgically. Graves' disease, which had been in remission for more than two decades after discontinuation of antithyroid drug treatment, relapsed during preoperative evaluation of pheochromocytoma when the patient was treated with alpha- and beta1-adrenergic antagonists. Administration of methimazole resulted in a rapid improvement of thyroid function and the patient remained euthyroid on small doses of methimazole. This case may suggest possible involvement of excessive catecholamine secretion and beta2-adrenergic receptor activation by pheochromocytoma in the relapse of Graves' disease.

Adrenal Gland Neoplasms↗
PubMed2002

Human osteosarcoma-derived cell lines produce soluble factor(s) that induces differentiation of blood monocytes to osteoclast-like cells.

When monocytes were cocultured with human osteosarcoma-derived cells (HOS cells), multinucleated giant cell formation of monocytes was induced. Intriguingly, even when a filter was interposed between monocytes and HOS cells, polykaryocytes also appeared. The multinucleated giant cells have characters similar to osteoclast-like cells. These findings indicate that soluble factor(s) secreted from HOS cells play an important role in polykaryocyte formation from monocytes. Twelve cloned cells were established from HSOS-1 cells and their capacities of inducing osteoclasts were investigated. Three cloned cells inducing nos. 4 and 9 had an ability of inducing osteoclasts (multinucleated giant cells, TRAP, calcitonin receptor and c-src mRNAs, osteoresorbing activity), and three cells, including nos. 1 and 5, did not show the ability. HOS cells and the cloned cells expressed several cytokine mRNAs. M-CSF was detected in the culture fluids of HOS cells, which also expressed RANK and RANK/ODF/OPGL mRNAs. Intriguingly, HOS cells secreting a soluble osteoclast inducing factors(s) expressed TNF-alpha converting enzyme mRNA. Furthermore, OCIF/OPG inhibited HOS cell-induced osteoclastogenesis and soluble RANKL could be detected in the culture fluids of HOS cells expressing TACE, suggesting that one of soluble osteoclast-inducing factor(s) is soluble RANKL. When blood monocytes were indirectly cocultured with HSOS-1 cells or cloned no. 9 cells in the presence of OCIF for 14 days, HOS cell-mediated osteoclastogenesis was suppressed, indicating that RANK-RANKL system is involved in the HOS cell-mediated osteoclastogenesis.

Acid Phosphatase↗
PubMed2002

Postpartum recurrence of Graves' hyperthyroidism can be prevented by the continuation of antithyroid drugs during pregnancy.

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. DESIGN: A nonrandomized, retrospective study. PATIENTS: Sixty-five pregnant GH patients treated with maintenance doses of ATDs were assigned into two groups: ATD therapy was discontinued before delivery in Group 1, but continued during pregnancy and after delivery in Group 2. MEASUREMENTS: The prevalence of postpartum recurrence or exacerbation of GH within 1 year after delivery was examined. Serum T4, T3 TSH, and TSH receptor antibody levels were measured. RESULTS: In Group 1, 70.8% (17/24) of patients suffered a recurrence of GH within 1 year after delivery. In contrast, a postpartum exacerbation of GH was observed in only 29% (12/41) of patients in Group 2 (P < 0.01). Both exacerbations and recurrences of GH appeared primarily within 4-6 months after delivery. Apparent neonatal hypothyroidism and malformations were not observed in the offspring of either group. CONCLUSION: Continuing antithyroid drug therapy throughout pregnancy prevents postpartum recurrence of Graves' hyperthyroidism without resulting in neonatal hypothyroidism or malformations.

Adult↗
PubMed2002

Prevention of lymphocytic thyroiditis in iodide-treated non-obese diabetic mice lacking interferon regulatory factor-1.

OBJECTIVE: Interferon regulatory factor-1 (IRF-1) is a critical regulator of interferon-gamma(IFNgamma)-mediated immune responses. To determine whether IRF-1 is involved in the pathogenesis of thyroiditis in animal models, we evaluated the incidence of iodide-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice lacking IRF-1 as well as IRF-1 +/+ and +/- mice. DESIGN: IRF-1 +/+, +/- and -/- NOD mice at 6 weeks of age were fed water (group 1) or iodide water (group 2) for 8 weeks. METHODS: Thyroids were examined histopathologically and intrathyroidal lymphocytic infiltration was arbitrarily graded. Serum thyroxine (T(4)) and anti-mouse thyroglobulin antibody (anti-mTgAb) levels were measured. Spleen cell population was analyzed by flow cytometry, and IFNgamma and interleukin-10 produced by splenocytes were measured by enzyme-linked immunosorbent assay. RESULTS: In group 1, only 4.3% of NOD mice developed LT. In contrast, 67.6% of mice in group 2 developed the disease. Iodide treatment induced LT in more than 80% of IRF-1 +/+ and +/- mice. However, no IRF-1 -/- mice in group 2 developed LT. There was no difference in both serum anti-mTgAb and T(4) levels among the three IRF-1 genotypes of NOD mice. Numbers of splenic CD8(+) T cells and IFNgamma production by Concanavalin A-stimulated splenocytes were markedly decreased in IRF-1-deficient NOD mice. CONCLUSIONS: IRF-1 is involved in the development of iodide-induced LT in NOD mice.

Animals↗