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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 361 records · Page 20Linked to original sources

Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states.

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Synaptosomal T3 binding sites in rat brain: their localization on synaptic membrane and regional distribution.

Previous studies have shown the existence of specific high affinity T3 binding sites in rat cerebrocortical synaptosomes. In this study, to define the localization of the binding sites, T3 binding to disrupted synaptic membrane fractions was compared with the binding to intact synaptosomes obtained from the rat cerebral cortex. Scatchard analysis revealed two orders of T3 binding sites with almost identical apparent dissociation constant (Kd) in synaptosomes and synaptic membrane fractions. However, the maximal binding capacity (MBC) of the higher affinity binding sites for synaptic membrane fractions was significantly greater than that for intact synaptosomes (4.2 +/- 0.2 vs 3.0 +/- 0.3 pg T3/mg protein). Regional distribution of the synaptosomal T3 binding sites in various areas of the rat brain was also studied. The Kd values were not significantly different in discrete brain regions. On the other hand, the MBCs of the higher affinity binding sites were greater in the cerebral cortex and hypothalamus (72.8 +/- 1.4 and 64.8 +/- 9.5 pg T3/g tissue) than in the cerebellum (22.1 +/- 1.6 pg T3/g tissue). Similar difference was also observed in the lower affinity sites. These results indicate that the specific T3 binding sites in brain synaptosomes are localized mainly on synaptic membranes and that the MBC is different in discrete brain regions.

Animals↗

Effects of aging on intracellular transport of vitamin B12 (B12) in rat enterocytes.

To elucidate the effect of aging on the vitamin B12 (B12) transport in enterocytes, young and old (3-4 months and over 1.5 years, respectively) female rats were studied. Two units of rat intrinsic factor (IF), saturated with 57Co-labeled cyanocobalamin were orally administered, and the amount of B12 absorbed into each subcellular fraction of enterocytes was assayed. Concentration of endogenous B12 in each subcellular fraction was also studied. Absorption of radioactive B12 in the lysosomal fraction was maximum between 2 and 4 hr in each age group. In the older rats, the amount absorbed was lower than in the young rats. The older rats showed a significantly lower value of endogenous B12 in the mitochondria. It has already been reported by us that there exist two B12 binders in enterocytes: lysosomal and microsomal binders. The concentrations of lysosomal and microsomal binders as well as B12 uptake in the mitochondria were significantly lower in the older rats than in the young rats. These data might help to explain the lower B12 absorption in the lysosomal fraction and lower B12 contents in the mitochondrial fraction.

Aging↗

[The prognosis of Graves' disease after antithyroid drug treatment: clinical significance of the T3 suppression test and abnormal thyroid stimulators].

The prognostic significance of both the triiodothyronine (T3) suppression test and the detectability of thyroid stimulating immunoglobulins in patients with Graves' disease who had been treated with antithyroid drugs was evaluated. Eighty-three patients underwent a T3 suppression test after having been euthyroid for at least 6 months. In 33 patients, the human thyroid stimulator (HTS) was assayed by measuring cyclic AMP increase in cultured thyroid adenoma cells, and TSH-binding inhibitor immunoglobulins (TBII) were measured by using the radioreceptor assay of TSH. Among 43 patients who had discontinued the drug treatment, 37 patients were under observation for 6-42 months. When a fall in 30-minute thyroid 99mTcO4- uptake of 50% or more after T3 administration was defined as positive suppression, the relapse rate was 30% in non-suppressive cases and 26% in suppressive cases. The relapse rate was lower in cases whose pre-suppression uptake was less than 3.0% (3 out of 17 patients) or in cases whose uptake after T3 administration was less than 0.8% (1 out of 9 patients). Of 15 patients with negative suppression, 5 (33.3%) were positive in HTS and 4 (26.7%) were positive in TBII. On the other hand, two (11.1%) each of 18 patients with positive suppression were positive in HTS and TBII respectively. Neither HTS nor TBII had been detected at the cessation of therapy in any of the 12 patients who remained euthyroid during the follow-up period. On the other hand, four (44.4%) out of 9 patients who relapsed had been positive in either HTS of TBII. Thus the Graves' disease specific immunoglobulins were found to be significantly associated with the relapse of the disease (p less than 0.05). The above data indicates that regardless of the suppressibility of 99mTcO4- uptake after T3 administration, the rate of recurrence is high when the uptake after T3 is more than 0.9% and/or when either HTS or TBII are positive.

Adult↗

Metal contents in duodenal aspirates of normal subjects during pancreozymin-secretin test.

The calcium, magnesium, zinc, copper and manganese concentrations in the duodenal aspirates obtained during pancreozymin-secretin tests were measured in 16 normal subjects. Total outputs of calcium, magnesium, zinc, copper and manganese during the 70 minute period (10 minutes after pancreozymin injection and 60 minutes after secretin injection) were 4.91 +/- 3.47 mg, 1.88 +/- 0.96 mg, 180 +/- 42 micrograms, 162 +/- 104 micrograms and 16.9 +/- 14.2 micrograms (mean +/- S.D.), respectively. The concentrations of metals were the highest in P fraction (during 10 minutes after pancreozymin injection) and the lowest is S3 fraction (during the 20-40 minute period after secretin injection). Although calcium, magnesium, copper and manganese concentrations varied widely from case to case especially in P fraction, zinc concentration exhibited comparatively small variation in every fraction. Magnesium, copper and manganese concentrations exhibited significant correlations with icterus indices of the aspirates. Zinc and magnesium concentrations correlated with amylase activity and magnesium concentration exhibited an inverse relation to bicarbonate concentration. Most metal concentrations correlated well each other, but there were no correlations between zinc and calcium and between zinc and manganese concentrations. Zinc seemed to be excreted mainly with pancreatic juice and copper and manganese mainly with bile.

Adult↗

Major factors limiting sensitivity of sandwich enzyme immunoassay for ferritin, immunoglobulin E, and thyroid-stimulating hormone.

By using IgG-coated polystyrene balls and beta-D-galactosidase-labelled Fab', sandwich enzyme immunoassays for human ferritin, immunoglobulin E (IgE), and thyroid-stimulating hormone (TSH) were developed, and their sensitivities were shown to be largely limited by the purity, binding efficiency, and amount of beta-D-galactosidase-labelled Fab' used. (1) Their sensitivities were enhanced 10 to 50-fold by using affinity-purified Fab' labelled with beta-D-galactosidase. (2) Their sensitivities depended upon the efficiency of specific binding of the labelled Fab' to antigens adsorbed on antibody IgG-coated polystyrene balls. (3) Their sensitivities were improved by using the minimal amount of labelled Fab' that gave a reliable calibration curve. Under optimal conditions the sensitivities obtained for ferritin, IgE, and TSH were 0.09 pg (0.2 amol), 0.48 pg (2.4 amol, 0.2 mIU), and 3.2 millimicronU (5.7 amol) per tube, respectively.

Ferritins↗

High affinity 3,5,3'-L-triiodothyronine binding to synaptosomes in rat cerebral cortex.

Studies were undertaken to define the existence of specific T3-binding sites in the synaptosomal fraction of rat cerebral cortex. Development-related changes of the synaptosomal T3-binding sites were compared with those of nuclear T3 receptors in rat cerebral cortex. Scatchard analysis was compatible with the existence of two sets of high affinity T3-binding sites: K1, with a mean (+/- SE) apparent dissociation constant (Kd) of 3.22 +/- 0.63 x 10(-11) M and a mean (+/- SE) maximum binding capacity (MBC) of 3.2 +/- 0.3 pg T3/mg protein, and K2, with a K4 of 2.64 +/- 0.15 x 10(-9) M and a MBC of 218.3 +/0 15.0 pg T3/mg protein. When compared to T3, 27-, 135-, 500-, and 1000-fold higher concentrations of T4, 3,5-diiodothyronine (3,5-T2), triiodothyroacetic acid, and rT3, respectively, were needed to obtain 50% depression of the synaptosomal T3 binding. Tetraiodothyroacetic acid, 3,3'-T2, 3'5'-T2, 3-monoiodothyronine (3-T1), 3'-T1, and thyronine had little effect. The MBC of T3 nuclear receptors was the highest at 2 days of age and significantly decreased thereafter, although an almost constant K4 was observed in all age groups studied. On the contrary, the MBC of the higher affinity synaptosomal T3-binding sites was low in 2-day-old rats (20.3 +/- 1.2 pg T3/g tissue) and increased thereafter to the level in young adult ras (50.4 +/- 2.2 pg T3/g tissue). However, the Kd of synaptosomal T3-binding sites was also unchanged in all age groups studied. These findings clearly indicate that there exist specific T3-binding sites in synaptosomes from rat cerebral cortex.

Aging↗

Sequential deiodination of thyroxine in human thyroid gland.

The inner ring monodeiodination [T4 to rT3, T3 to 3,3'-diiodothyronine(3,3'-T2)] as well as the outer ring monodeiodination (T4 to T3, rT3 to 3,3'-T2) was demonstrated with thyroid tissues obtained from patients with Graves' disease by measuring the products by RIAs. Sequential deiodination of T4 to 3,3'-T2 was also recognized in normal human thyroid glands. These iodothyronine deiodinations were dependent on incubation time, tissue volume, temperature, pH, and concentration of dithiothreitol. The monodeiodination of rT3 to 3,3'-T2 proceeded very rapidly and the maximal production of 3,3'-T2 was obtained at about 5 min. In the other reactions, the products accumulated in an almost linear fashion during the period of 60 min. The optimal pH for 5-monodeiodination was 9.0, while that for 5-monodeiodination was 5.5-6.5. In the absence of dithiothreitol, all of these reactions were abolished. Propylthiouracil and iopanoic acid inhibited the reactions, whereas methimazole and potassium iodide had no effect. Kinetic study revealed that the apparent Km and maximum velocity of the conversion of T3 to 3,3'-T2 were 10.9 microM and 19 pmol 3,3'-T2/mg protein.min, respectively, and that those of rT3 to 3,3'-T2 were 0.37 microM and 80 pmol 3,3'-T2/mg protein.min, respectively. There was a significant difference in the conversion of T4 to rT3 between normal [0.56 +/- 0.04 pmol/mg protein.min (mean +/- SE)] and Graves' thyroids 0.88 +/- 0.06 pmol/mg protein min). Moreover, a significant difference was found between 3,3'-T2 production rate from T3 or rT3 in the Graves' thyroids and that in the normal thyroids. The overall reaction from T4 to 3,3'-T2 in the Graves' thyroids (4.04 +/- 0.70 pmol/mg protein.min) was significantly higher than that in the normal thyroids (0.63 +/- 0.11 pmol/mg protein.min; P less than 0.001). The results indicate the existence of 5-deiodinase that produces rT3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from rT3 in human thyroids. Accelerated conversion of T4 to 3,3'-T2 via either T3 or rT3 was observed in Graves' thyroid glands.

Diiodothyronines↗