甲状腺機能亢進症における眼球突出に関する実験:眼球突出因子に関する実験
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概要
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In order to obtain some information about endocrine exophthalmos, the author attempted to determine the exophthalmos producing activity of desiccated thyroid (thyradine), thyroxine (T<SUB>4</SUB>) and triiodothyronine (T<SUB>3</SUB>), to separate exopthalmos producing substance (EPS) from thyroid stimulating hormone (TSH) with column chromatography using pig thyrotropin preparation (pretiron) as the starting material and finally to test the effect of the thyroid hormone preparations on the exophthalmos producing response in gold fish, induced by pretiron.<BR>The bioassay of EPS was performed by the determination of the percent increase in intercorneal distance (ICD) in gold fish after the intracloacal injection of the materials. The bioassay of TSH was performed with Bakke-Ogura's in vitro method using the suppressive effect of TSH on the release of <SUP>131</SUP>I from bovine thyroid slice. Column chromatography was performed on CM-C and DEAE-C.<BR>The following results were obtained : <BR>1) No marked diurnal variation was observed in ICD in gold fish, and ICD was not affected by the operative procedure of cutting off the fins or intracloacal puncture.<BR>2) As the increase in ICD after the injection of 0.9% saline was under 5%, the author defined that an increase over 5% was significant. Macroscopic exophthalmos was observed at 3 hrs. after the injection of 5 Junkmann-Schoeller Units (JSU) of pretiron, and the peak of percent increase was reached at about 5 hrs.. The exophthalmic response of gold fish was decreased in summer when water temperature showed above 30°C.<BR>3) At 5 hrs. after the injection of pretiron a linear responsiveness of percent increase in ICD to graded doses of TSH was observed to be between 1.25 JSU and 10.0 JSU of pretiron, but on the other hand, at 10 hrs it was observed to be between 1.25 JSU and 5.0 JSU.<BR>4) Chromatographing pretiron on CM-C using 0.01M phosphate buffer solution for the first elution, and 1.0 M NaCl for the second, the second fraction had biologically highly thyroid stimulating and exophthalmos producing activity. Changing the elute beffer gradiently from the phosphate buffer to 1.0 M NaCl, the latter half of the second fraction also showed both thyroid stimulating and exophthalmos producing activity.<BR>5) DEAE-C, 0.005 M glycine-NaOH, 0.1 M glycine-NaOH, 0.2 M NaH<SUB>2</SUB>PO<SUB>4</SUB> and 1.0 M NaCl were used as the elute buffer. The fractions eluted by the 1st, 2nd, 3rd and 4th buffer were named Fraction I, II, III and IV, respectively. Fraction III showed marked thyroid stimulating activity, and Fraction II, III and IV showed exophthalmos producing activity equally.<BR>6) An exophthalmic response was observed on the 4th day following the administration of a large quantity (20 mg) of thyradine, but it was not observed following the administration of T<SUB>3</SUB> or T<SUB>4</SUB>.<BR>7) The pretreatment with T<SUB>3</SUB> showed a marked, inhibiting effect on exophthalmos production by pretiron, compared with that of thyradine or T<SUB>4</SUB>.<BR>From the results above mentioned, it is suggested that EPS is distinct from TSH and that T<SUB>3</SUB> may be used as one of the therapeutic drugs for proptosis in patients with hyperthyroidism.
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