| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
A new type of albumin with increased affinity for 3,3',5-triiodothyronine (T_3) and a somewhat increased affinity for thyroxine (T_4) was characterized. The association constant for T_3 of the variant albumin was 5.1x10^6/M (control albumin; 6.2x10^5/M), and that for T_4 was 5.2x10^6/M (control albumin; 2.1x10^6/M), respectively. The increased binding of the patient's albumin to T_3 and T_4 was markedly inhibited by barbitone, 8-anilino-1-naphthalenesulfonic acid and Cl ions.
Isoelectrofocusing (IEF) studies revealed eitht T_3-binding bands, B(T_3)_<1-8>, with identical pls in both patient's and normal albumins. However, the most of the ^<125>I-T_3 was associated with bnads corresponding to B(T_3)_<4-5> with low pls in the patient's albumin, while in normal albumin, it was alwaya associated with two bands corresponding to B(T_3)^<2-3>. Six T_4-binding bands were also seen on IEF slabs. The intensities of these two bands, B(T_3)_<4-5>, were enhanced by stripping the serum of endogenous i
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odothyronines. These two bands were displaced by unlabelen T_3, T_4 and T_3 analog, and those in normal albumin were completely saturated by smaller amounts of respective ligands. These results indicate that albumin moieties corresponding to B(T_3)_4 and B(T_3)_5 have higher affinities for T_3, and the patient's albumin contains abnormally higher concentrations of these two isoforms. Studies on samples treated with dithiothreitol (DTT) showed that DTT (0.1-5 mM) effectively abolished T_3-binding by B(T_3)_<4-5> and T_4-binding by B(T_4)_<5-6>, particularly in the patient's albumin. This results indicate that like FDH-albumin, the increased binding of T_3 and T_4 by the new variant albumin involves disufide bond(s). From these observations, we conclude that the abnormality in T_3-binding of albumin in the patient with dysalbuminemic hypertriiodothyroninemia is mainly due to increased amount of the isoforms of albumin present in normal albumin, that have higher affinities for T_3. Quantitive abnormality may be a common finding in various dysalbuminemic syndromes. Less
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