甲状腺機能亢進症の病態生理
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I. TSH secretion in patients with Graves' disease<BR>1. In hyperthyroid patients, serum TSH levels determined by radioimmunoassay were undetectable (<1.0 μU/ml).<BR>2. Three euthyroid patients with Graves' disease were treated with 1-methyl-2- mercaptoimidazole followed by thyroxine. Reciprocal changes in TSH and thyroxine levels were observed, but LATS did not change.<BR>II. LATS in Graves' disease<BR>1. Concentration and identification of LATS : LATS cantaining IgG which was separated from serum by DEAE-Sephadex column chromatography was passed through a CM-C column, and LATS fractions with high specific activity were obtained. The protein in these fractions with LATS was identified by immunoelectrophoresis as IgG.<BR>There was no correlation between LATS activity and the concentrations of IgG, IgA and IgM which were measured by immunodiffusion technique.<BR>2. LATS production by lymphocyte culture : Peripheral lymphocytes obtained from patients with Graves' disease were cultured with phytohemagglutinin, and LATS like activity was detected in the cultured medium. The LATS like activity was identified as LATS, by the time- and dose-response curves, association with IgG fraction of DEAE-Sephadex column chromatography, and neutralization with anti-IgG serum. Neither LATS nor TSH like activity was detected in the control cultured media.<BR>3. The nature of LATS inhibitor in thyroid gland : LATS inhibitor was investigated in an attempt to find a specific antigen to LATS.<BR>1) Incubation of LATS-IgG with human thyroid homogenates resulted in inhibition of LATS activity. When the subcellular fractions were used, LATS-inhibitory activity was demonstrated in microsomal fraction and cell sap, and dose-response relationship was obtained.<BR>2) Following treatment with acidic buffer (pH 3.0) or 2M NaSCN where dissociation of antigen antibody complexes is known to occur, some of the LATS activity was recovered from microsomes which were previously incubated with LATS-IgG. Similar results were obtained when the mixture of the LATS-IgG and thyroid cell sap was treated with acidic buffer.<BR>3) By incubation with thyroid cell sap, LATS activity was inhibited but TSH was not.<BR>4) The LATS inhibitory activity of the cell sap was markedly reduced when the cell sap was pretreated with acidic buffer (pH 2.5, 3.0), 2M NaSCN or 6M urea.<BR>5) The thyroid cell sap was fractionated by means of gel filtration using Sepharose 4B, but the LATS inhibitory activity was distributed to each fraction. When the cell sap was applied to a column of DEAE-cellulose, the LATS inhibitory activity was concentrated in the fractions which were eluted by the buffer with high ionic strength.<BR>4. Relationship between LATS and antithyroid antibodies : <BR>1) No correlation was observed between LATS activity and titer of antithyroid antibodies which were determined by TRC for thyroglobulin, CFT and cytotoxic factor assay with thyroid microsomes.<BR>2) A case of "Graves' disease without hyperthyroidism" was presented. The patient has exophthalmos, goiter, LATS and antithyroid antibodies. Histological examination of thyroid gland revealed the findings of chronic thyroiditis.<BR>5. No effect of LATS was found on adenyl cyclase activity which was determined by the method of Pastan but the further experiments are necessary to confirm the finding.
- 日本内分泌学会の論文