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1.
Immunol Invest ; 42(3): 235-46, 2013.
Article in English | MEDLINE | ID: mdl-23461615

ABSTRACT

Because green tea polyphenols (GTPs) possess anti-inflammatory properties and are effective in inhibiting autoimmune diseases in experimental settings, we examined whether GTPs prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis (HT). Mice were given 0.05% iodide water or iodide water supplemented with 0.2% GTPs for 8 weeks. GTPs administration led to an enhanced production of interleukin-10 by concanavalin A-stimulated splenocytes but did not interfere with thyroiditis development. Serum thyroxine levels were not influenced by GTPs. Our data suggest that administration of GTPs may not be an effective strategy for the prevention of HT.


Subject(s)
Disease Models, Animal , Hashimoto Disease/prevention & control , Polyphenols/administration & dosage , Tea/chemistry , Animals , Female , Hashimoto Disease/chemically induced , Hashimoto Disease/immunology , Humans , Iodides/administration & dosage , Male , Mice , Mice, Inbred NOD , Thyroiditis, Autoimmune/chemically induced , Thyroiditis, Autoimmune/immunology , Thyroiditis, Autoimmune/prevention & control
2.
Cell Immunol ; 270(1): 1-4, 2011.
Article in English | MEDLINE | ID: mdl-21601836

ABSTRACT

We examined whether a synthetic retinoid Am80 prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic mice, an animal model of Hashimoto's 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.


Subject(s)
Benzoates/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/immunology , Tetrahydronaphthalenes/metabolism , Thyroiditis, Autoimmune , Administration, Oral , Animals , Autoantibodies/blood , Autoantibodies/immunology , Benzoates/administration & dosage , Diabetes Mellitus, Type 1/metabolism , Drug Interactions , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Lymphocyte Count , Mice , Mice, Inbred NOD , Retinoids/administration & dosage , Retinoids/metabolism , Spleen/immunology , T-Lymphocytes/immunology , Tetrahydronaphthalenes/administration & dosage , Thyroiditis, Autoimmune/chemically induced , Thyroiditis, Autoimmune/metabolism , Thyroiditis, Autoimmune/prevention & control
3.
Autoimmunity ; 44(6): 490-5, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21457062

ABSTRACT

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 Hashimoto's 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.


Subject(s)
Propylene Glycols/therapeutic use , Receptors, Lysosphingolipid/antagonists & inhibitors , Sphingosine/analogs & derivatives , Thyroiditis, Autoimmune/prevention & control , Animals , Autoantibodies/blood , Autoantibodies/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cytokines/blood , Female , Fingolimod Hydrochloride , Flow Cytometry , Forkhead Transcription Factors/biosynthesis , Forkhead Transcription Factors/blood , Iodides , Lymphocyte Count , Male , Mice , Mice, Inbred NOD , Sphingosine/therapeutic use , Thyroiditis, Autoimmune/chemically induced
4.
Autoimmunity ; 44(6): 483-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21332425

ABSTRACT

Viral infection is implicated as a cause of autoimmune diseases. Whereas its role in Hashimoto's thyroiditis (HT) remains undefined, recent studies suggested a link between human parvovirus B19 (B19) infection and HT. We tested such possibility by using B19 nonstructural protein 1 (NS1) transgenic C57BL/6 mice, which harbor nonpermissive genetic background (H-2(b)). Mice were immunized with either thyroglobulin (Tg) or saline. No thyroiditis developed in saline-treated mice and Tg-immunized males regardless of the presence or absence of NS1. In contrast, thyroiditis was induced by Tg immunization in 25% of transgenic females, but not in wild-type females. However, the thyroiditis incidence in the former did not differ significantly from that of the latter. In addition, intrathyroidal T-cell receptor gene expression was not augmented in Tg-immunized transgenic females. Immunization with Tg led to a comparable increase in serum anti-Tg antibody levels in the wild-type and transgenic mice. Our results indicate that the introduction of B19 NS1 gene into C57BL/6 mice is insufficient to promote the development of autoimmune thyroiditis. Further studies are required, however, before concluding that B19 infection is not involved in HT induction.


Subject(s)
Autoimmune Diseases/immunology , Hashimoto Disease/immunology , Parvovirus B19, Human/genetics , Parvovirus B19, Human/immunology , Viral Nonstructural Proteins/genetics , Animals , Autoimmune Diseases/genetics , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cytokines/blood , Female , Flow Cytometry , Hashimoto Disease/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Th1-Th2 Balance , Thyroglobulin/administration & dosage
5.
Endocr J ; 58(1): 59-63, 2011.
Article in English | MEDLINE | ID: mdl-20962436

ABSTRACT

Red blood cell (RBC) zinc (Zn) concentration reflects a patient's mean thyroid hormone level over the preceding several months. The aim of this study was to examine whether RBC Zn level can be used as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism (TH) from permanent hypothyroidism (PH). RBC Zn level was measured in 30 untreated PH patients with Hashimoto's thyroiditis and 7 untreated TH patients with painless thyroiditis in whom preceding transient thyrotoxicosis had been confirmed. RBC Zn concentration was significantly lower in TH patients than that in PH patients. There was a positive correlation between RBC Zn and serum TSH, and the latter was clearly lower in TH patients than that in PH patients. However, RBC Zn level was again significantly lower in TH patients than PH patients despite of the comparable serum TSH levels in both groups when RBC Zn was evaluated in patients with serum TSH levels of less than 50 mU/L. Thus TH patients could be identified with RBC Zn measurement, allowing us avoidance of unnecessarily prolonged T4 administration to them.


Subject(s)
Biomarkers/blood , Erythrocytes/chemistry , Hypothyroidism/diagnosis , Zinc/blood , Female , Humans , Male , Thyroiditis/complications , Thyrotropin/blood
7.
Autoimmunity ; 42(3): 228-34, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19301205

ABSTRACT

We explored the role of interleukin-6 (IL-6) in the development of autoimmune thyroiditis in nonobese diabetic (NOD) mice, an animal model of Hashimoto's 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.


Subject(s)
Interleukin-6/physiology , Thyroiditis, Autoimmune/etiology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Autoantibodies/blood , Autoantibodies/immunology , Concanavalin A/pharmacology , Disease Models, Animal , Hashimoto Disease/etiology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin Isotypes/blood , Immunoglobulin Isotypes/immunology , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Iodine/administration & dosage , Iodine/pharmacology , Mice , Mice, Inbred NOD , Receptors, Interleukin-6/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Thyroglobulin/immunology , Thyroiditis, Autoimmune/immunology , Thyroiditis, Autoimmune/pathology , Thyroiditis, Autoimmune/prevention & control , Vaccination
9.
Endocr J ; 55(1): 113-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18202530

ABSTRACT

Thyrotoxic periodic paralysis (TPP) is mainly associated with Graves' disease but rarely with autonomously functioning thyroid nodule (AFTN). We herein report a case of AFTN associated with TPP in which the latter resolved after (131) I therapy for the former. We analyzed the genes encoding thyrotropin receptor (TSHR), the alpha-subunit of the stimulatory G protein (Gsalpha), calcium channel CACNA1S and potassium channel KCNE3, and found that the patient does not carry the known mutations in these genes. Whereas the pathogenesis of TPP and AFTN remains to be understood, the present case suggests that ion channel defects responsible for familial hypokalemic periodic paralysis may not be associated with TPP, and that mutations in TSHR and Gs alpha genes may be less frequent in AFTN patients in the Japanese population.


Subject(s)
Paralysis/etiology , Thyroid Nodule/complications , Thyrotoxicosis/etiology , Adult , Calcium Channels/genetics , Calcium Channels, L-Type , DNA Mutational Analysis , Humans , Male , Paralysis/genetics , Periodicity , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/physiopathology , Thyrotoxicosis/genetics , Ultrasonography
10.
Clin Immunol ; 126(1): 97-103, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17919982

ABSTRACT

We evaluated the effects of angiotensin II (Ang II) blockers, losartan, an Ang II receptor blocker, and enalapril, an angiotensin converting enzyme inhibitor, on the development of autoimmune thyroiditis in nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis (HT). Mice were assigned into three groups, untreated, losartan-treated (30 mg/kg/day), and enalapril-treated (10 mg/kg/day) groups. Thyroiditis was induced by iodide ingestion (experiment 1) or mouse thyroglobulin (Tg) immunization (experiment 2). Both procedures effectively induced thyroiditis. While iodide ingestion failed to induce anti-mouse Tg antibody (TgAb) production, Tg immunization resulted in a significant increase in serum TgAb levels. In both experiments, neither losartan nor enalapril interfered with the development of thyroiditis and TgAb production. These results suggest that Ang II may not be associated with the development of autoimmune thyroiditis in NOD mice. Thus, the Ang II blockade may not have therapeutic potential in HT.


Subject(s)
Angiotensin II/physiology , Hashimoto Disease/physiopathology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Disease Models, Animal , Enalapril/administration & dosage , Enalapril/pharmacology , Losartan/administration & dosage , Losartan/pharmacology , Mice , Mice, Inbred NOD , Sodium Iodide/pharmacology , Thyroglobulin/immunology
11.
Toxicology ; 237(1-3): 203-209, 2007 Jul 31.
Article in English | MEDLINE | ID: mdl-17582671

ABSTRACT

We have recently reported that methylmercury (MeHg) inhibits type II iodothyronine 5'-deiodinase (D2) activity in mouse neuroblastoma NB41A3 cells. In the present study, we determined the biological significance of D2 inhibition by MeHg. GH3 rat pituitary tumor cells were treated with MeHg and D2 activity and production of a thyroid hormone-responsive gene product, growth hormone (GH) were analyzed. MeHg inhibited D2 activity and decreased thyroxine (T4)-induced, but not 3,3',5-triiodothyronine (T3)-induced GH secretion in GH3 cells. Our results suggest that MeHg inhibition of D2 activity might be involved in the inhibition of GH production in GH3 cells. Thus, D2 inhibition could be a novel mechanism involved in MeHg toxicity.


Subject(s)
Enzyme Inhibitors/toxicity , Growth Hormone/biosynthesis , Iodide Peroxidase/antagonists & inhibitors , Methylmercury Compounds/toxicity , Animals , Cell Culture Techniques , Cell Line, Tumor , Culture Media , Rats , Thyroxine/pharmacology , Triiodothyronine/pharmacology , Iodothyronine Deiodinase Type II
12.
J Infect ; 55(2): e29-31, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17582502

ABSTRACT

Previous studies suggest a role of viral infection in the development of Hashimoto's thyroiditis (HT). Here we report a patient with HT in whom human parvovirus B19 (B19) DNA has been persistently detected in the thyroid regardless of the presence or absence of B19 DNA in peripheral blood mononuclear cells. In contrast to the DNA persistence, however, VP1 capsid protein was not detected in the thyroid by immunohistochemical studies. Thyroid specimens obtained by fine needle aspiration biopsy from two patients with HT and two with Graves' disease were negative for B19 DNA. Thus, whereas a causal link between B19 infection and HT remains to be determined, B19 DNA may persist in the thyroid and B19 infection may facilitate the intrathyroidal inflammatory process in HT patients.


Subject(s)
DNA, Viral/isolation & purification , Hashimoto Disease/virology , Parvovirus B19, Human/isolation & purification , Adult , Female , Humans
13.
Endocr J ; 54(1): 35-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17053292

ABSTRACT

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.


Subject(s)
Carcinoma/radiotherapy , Goiter, Nodular/surgery , Graves Disease/drug therapy , Hyperthyroidism/etiology , Hypothyroidism/etiology , Nasopharyngeal Neoplasms/radiotherapy , Thyroidectomy/adverse effects , Adult , Female , Graves Disease/complications , Graves Disease/surgery , Hormone Replacement Therapy/adverse effects , Humans , Hyperthyroidism/pathology , Hypothyroidism/drug therapy , Radiation Injuries , Thyroxine/adverse effects , Thyroxine/therapeutic use
14.
Toxicology ; 228(1): 77-84, 2006 Nov 10.
Article in English | MEDLINE | ID: mdl-16982123

ABSTRACT

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.


Subject(s)
Cadmium/toxicity , Environmental Pollutants/toxicity , Maternal Exposure , Metallothionein/deficiency , Thyroid Gland/drug effects , Thyroid Hormones/metabolism , Administration, Oral , Animals , Animals, Newborn , Brain/drug effects , Brain/enzymology , Cadmium/pharmacokinetics , Dose-Response Relationship, Drug , Environmental Pollutants/pharmacokinetics , Female , Iodide Peroxidase/metabolism , Liver/drug effects , Liver/enzymology , Male , Metallothionein/genetics , Methylmercury Compounds/toxicity , Mice , Mice, Inbred C57BL , Mice, Knockout , Pregnancy , Thyroid Gland/metabolism
15.
Toxicol Lett ; 161(2): 96-101, 2006 Feb 20.
Article in English | MEDLINE | ID: mdl-16140479

ABSTRACT

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.


Subject(s)
Iodide Peroxidase/antagonists & inhibitors , Methylmercury Compounds/pharmacology , Neuroblastoma/enzymology , Animals , Cell Line, Tumor , Iodide Peroxidase/metabolism , Kinetics , Methylmercury Compounds/toxicity , Mice , Iodothyronine Deiodinase Type II
16.
J Endocrinol ; 187(1): 17-24, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16214937

ABSTRACT

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.


Subject(s)
Epithelial Cells/immunology , Gene Expression Regulation , Thyroid Gland/immunology , Thyroiditis, Autoimmune/immunology , Tumor Necrosis Factor-alpha/metabolism , Actins/analysis , Animals , Cell Line , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Glyceraldehyde-3-Phosphate Dehydrogenases/analysis , Immunoprecipitation , Rats , Receptors, Tumor Necrosis Factor, Type I/analysis , Receptors, Tumor Necrosis Factor, Type II/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/genetics
18.
Clin Immunol ; 113(2): 187-92, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15451476

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , DNA-Binding Proteins/deficiency , Phosphoproteins/deficiency , Thyroiditis, Autoimmune/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Cell Differentiation/immunology , Disease Models, Animal , Flow Cytometry , Immunohistochemistry , Interferon Regulatory Factor-1 , Mice , Mice, Inbred NOD , Spleen/immunology , Thyroglobulin/immunology , Thyroid Gland/immunology , Thyroid Gland/pathology , Thyroiditis, Autoimmune/pathology
19.
Thyroid ; 14(2): 155-60, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15068631

ABSTRACT

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.


Subject(s)
Artifacts , Hyperthyroxinemia/blood , Pregnancy Complications/blood , Serum Albumin/deficiency , Thyroxine/blood , Adult , Amino Acid Substitution , Arginine , Cytosine , Dialysis/methods , Female , Genes, Dominant , Guanine , Hemofiltration , Humans , Hyperthyroxinemia/complications , Hyperthyroxinemia/diagnosis , Hyperthyroxinemia/metabolism , Metabolism, Inborn Errors/complications , Mutation , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/metabolism , Proline , Radioimmunoassay , Serum Albumin/genetics , Thyroxine/metabolism , Thyroxine-Binding Proteins/metabolism
20.
Eur J Endocrinol ; 147(6): 809-14, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12457457

ABSTRACT

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.


Subject(s)
DNA-Binding Proteins/deficiency , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Iodides/adverse effects , Mice, Inbred NOD/physiology , Phosphoproteins/deficiency , Thyroiditis, Autoimmune/prevention & control , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Incidence , Interferon Regulatory Factor-1 , Iodides/therapeutic use , Mice , Mice, Knockout/genetics , Phosphoproteins/genetics , Phosphoproteins/metabolism , Thyroiditis, Autoimmune/chemically induced , Thyroiditis, Autoimmune/epidemiology , Thyroiditis, Autoimmune/pathology
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