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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 379 records · Page 21Linked to original sources
PubMed1982

Characteristics of rT3 5'-monodeiodination in rat brain: comparison with T4 and T3 5-monodeiodinations.

The present study revealed the existence and some characteristics of rT3 5'-deiodinase in rat brain by measuring the production of 3,3'-T2 from rT3 by radioimmunoassay. The conversion of rT3 to 3,3'-T2 was dependent on the duration of the incubation, tissue amount, temperature and pH (the optimal pH was 8.0), suggesting its enzymatic nature. Apparent Km was estimated to be 0.16 microM and the Vmax was 139.3 fmol/mg protein/min. The converting activity was dependent on the concentration of dithiothreitol (DTT). In contrast to T4 or T3 5-deiodinase, rT3 5'-deiodinase activity in the rat brain was the highest in cerebellum and the activity was low in the neonatal rat brain. Moreover, the 5'-deiodinase activity was inhibited by propylthiouracil (PTU). These differences between rT3 5'-deiodinase and T4 or T3 5-deiodinase suggest that different deiodinases are present in rat brain, and the local conversion of thyroid hormone is important for its action in the central nervous system.

Age Factors↗
PubMed1982

Mechanism of uptake of cobalamin into enterocyte mitochondria.

To study the mechanism which cobalamin is taken up by the mitochondria, 57Co-cyanocobalamin-binder complex and freshly prepared mitochondria were prepared from the enterocytes of rats. Subsequently, the binder complex was incubated together with mitochondria in a calcium-containing medium in vitro. Uptake of cobalamin was determined by measuring the radioactivities bound to the mitochondria. Consequently, lysosomal and microsomal binders enhanced cobalamin uptake into the mitochondria, but intrinsic factor did not. It was found that the uptake into the mitochondria was inhibited by previous treatment with calcium-chelating agents. The uptake was completely restored after addition of calcium ions to the mitochondria.

Animals↗
PubMed1982

Brain content of cobalamin and its binders in elderly subjects.

The biological aspects of cobalamin were studied in autopsy brains of eight elderly subjects who had lacked marked neurologic symptoms. Separation of the gray and white matter of the frontal and temporal lobes, and subsequently, subcellular fractionation of each matter were attempted. The contents of cobalamin and its binders and cobalamin concentrations were measured in each subcellular fraction and whole homogenate. The contents of cobalamin were in the ranges of 50 to 60 ng/g wet tissue. No marked differences in contents were found between the frontal and temporal lobes. The mitochondria-rich fraction contained more cobalamin than did the microsomal fraction. Two binders were found; a large-sized and a small-sized. The molecular weight of the larger binder was ca. 120,000, coinciding with the elution region of transcobalamin I, and the molecular weight of the smaller binder was 40,000, coinciding with the elution region of transcobalamin II, in gel filtration respectively. More of the larger binder than the smaller was found in the mitochondria-rich and microsomal fractions. These data are useful for the study of various aspects of cobalamin in brains with various types of neurologic pathology or aging changes.

Aged↗
PubMed1982

[Evaluation of diastolic phase by left ventricular volume curve using S2-gated equilibrium method in radioisotope angiography].

S2-gated (the second heart sound) method was designed by authors. In 6 normal subjects and 16 patients (old myocardial infarction 12 cases, hypertension 2 cases and aortic regurgitation 2 cases), radioisotope (RI) angiography using S2-gated equilibrium method was performed. In RI angiography, 99mTc-human serum albumin (HSA) 555MBq (15 mCi) as tracer, PDP11/34 as minicomputer and PCG/ECG synchronizer (Metro Inst.) were used. Then left ventricular (LV) volume curve by S2-gated and electrocardiogram (ECG) R wave-gated method were obtained. Using LV volume curve, left ventricular ejection fraction (EF), mean ejection rate (mER, s-1), mean filling rate (mFR, s-1) and rapid filling fraction (RFF) were calculated. mFR indicated mean filling rate during rapid filling phase. RFF was defined as the filling fraction during rapid filling phase among stroke volume. S2-gated method was reliable in evaluation of early diastolic phase, compared with ECG-gated method. There was the difference between RFF in normal group and myocardial infarction (MI) group (p less than 0.005). RFF in 2 groups were correlated with EF (r = 0.82, p less than 0.01). RFF was useful in evaluating MI cases who had normal EF values. The comparison with mER by ECG-gated and mFR by S2-gated was useful in evaluating MI cases who had normal mER values. mFR was remarkably lower than mER in MI group, but was equal to mER in normal group approximately. In conclusion, the evaluation using RFF and mFR by S2-gated method was useful in MI cases who had normal systolic phase indices.

Adult↗
PubMed1982

Cobalamin contents of the brains in some clinical and pathologic states.

To study the cobalamin content of the brains in various clinico-pathologic states in the elderly, the patho-histology and cobalamin content were examined in autopsy brains with special attention to the temporal and frontal lobes. Consequently, a decrease of cobalamin contents and its binding protein (binder) was found in brains with dementia, severe neuronal loss, myelin degeneration, brain atrophy, ventricular dilatation, and vascular lesions in comparison with those in the controls.

Aged↗
PubMed1981

Inner ring monodeiodination of thyroxine and 3,5,3'-L-triiodothyronine in rat brain.

To elucidate the metabolism of thyroid hormone in the central nervous system (CNS), 5-monodeiodinating activities were studied by incubating T4 or T3 with an aliquot of the P2 fraction of the rat brain in the presence of dithiothreitol and measuring the amounts of rT3 or 3,3'-L-diiodothyronine (3,3'-T2) produced by RIA. The production of rT3 or 3,3'-T2 was dependent upon duration of the incubation, amount of tissue used, temperature, and pH (the optimal pH was 8.0). These findings show that these reactions are enzymic in nature. For the conversion of T4 to rT3, the Km was estimated to be 1.33 microM, and the Vmax was 173 fmol/mg protein . min. For the conversion of T3 to 3,3'-T2, the Km was estimated to be 2.31 microM, and the Vmax was 94 fmol/mg protein . min. Both the conversion of T4 to rT3 and that of T3 to 3,3'-T2 were dependent on the concentration of dithiothreitol, but were not inhibited by propylthiouracil, the well known inhibitor of 5'-deiodinating activity. Both activities were mainly found in the synaptosomal fractions. The P2 fraction from fetal and neonatal rat brains had significantly higher activity than that from the adult brain. These findings demonstrate the presence of 5-monodeiodinating activities in the rat brain.

Aging↗
PubMed1981

Reversible changes of the histological abnormalities of the thyroid in patients with painless thyroiditis.

The histological abnormalities on percutaneous needle biopsy of the thyroid were investigated in two patients (cases 1 and 2) with transient thyrotoxicosis and low radioactive iodine uptake by the thyroid and in a patient (case 3) with transient hypothyroidism which might be the consequence of transient thyrotoxicosis. The most characteristic findings of lymphocytic thyroiditis, such as extensive lymphocyte infiltration with collapsed follicles and degeneration of follicular cells of the thyroid, were found in case 1, in whom the thyroid biopsy was performed in the thyrotoxic phase. Ashkanazy cells were not present and fibrosis was not observed in this specimen. Histological examination of the thyroid biopsy specimen, which was obtained in the recovery phase in case 1, revealed well preserved thyroid follicles and slight lymphocytic infiltration. In addition, papillary infoldings of cuboidal epithelium were found in cases 2 and 3, in whom the thyroid biopsy was done in the hypothyroid phase. The follow-up biopsy of the thyroid was performed in the recovery phase in case 3. The biopsy specimen showed focal lymphocytic infiltration and the follicles lined by low cuboidal cells without papillary infoldings. In all biopsy specimens, there was no evidence of subacute thyroiditis, as characterized by granulomatous changes and breakdown of colloid follicles with foreign body giant cell reaction. The present findings revealed that the histological abnormalities, such as lymphocytic infiltration and follicular epithelial changes of the thyroid, observed in the patients with painless thyroiditis, can improve spontaneously during the course of several months.

Adult↗
PubMed1981

Age-related changes of serum 3,3'-diiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine concentrations in man.

To evaluate the effects of aging on T4 metabolism, serum 3,3'diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,5-diiodothyronine (3,5-T2) as well as T4, T3, and rT3 concentrations were determined by RIAs in 81 normal subjects, aged 24-81 yr. 3,3'-T2, 3',5'-T2, and 3,5-T2 antisera were prepared by immunizing rabbits with the protein conjugate of each diiodothyronine. Since the 3',5'-T2 antiserum cross-reacted with rT3 to the extent of 1.8%, correction was made by subtracting 1.8% of the rT3 value from the measured 3',5'-T2 value. The other 2 antisera had no noticeable cross-reactivity with various thyroid hormone derivatives. Although no significant relation existed between T4 levels and age (r = -0.14; P greater than 0.1) serum T3 showed a significant correlation with age (r = -0.28; P less than 0.05). In contrast, no significant correlation was observed between rT3 and age (r = 0.12; P greater than 0.1). Serum 3,3'-T2, 3',5'-Tw, and 3,5-T2 values (nanograms per dl) all had significant inverse correlations with age, the coefficients of correlation being -0.38 for 3,3'-T2 (P less than 0.01), -0.58 for 3',5'-Tw (P less than 0.01), and -0.47 for 3,5-T2 (P less than 0.01). These findings suggest that sequential monodeiodinating activities in T4 metabolism decrease with increasing age.

Adult↗
PubMed1981

Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue.

Conversion of T4 to T3 was studied in normal, Graves', and neoplastic thyroid tissues obtained at surgery. Homogenates of human thyroid follicular adenoma and carcinomas were incubated with [125I]T4 and dithiothreitol (DTT) at 37 C for 60 min under N2 gas. T3 formation was assessed by measuring [125I]T3 formed, using paper chromatography. In the second series of experiments, the suspensions of the 100,000 X g pellet of normal thyroid tissues adjacent to the tumor and Graves' thyroid tissues were incubated with unlabeled T4 and DTT at 37 C for 60 min under N2 gas. T3 generated was measured by RIA. T3 generation in the thyroid tissue was dependent on incubation time, amount of the tissue used, concentration of DTT, temperature, and pH. Propylthioracil inhibited T3 formation, while methimazole had no effect. A kinetic study with the homogenate of a thyroid adenoma and 100,000 X g pellet suspensions of two normal and three Graves' thyroids gave apparent Km values of 2.7, 4.9, and 4.1 microM for T4, respectively, and Vmax values of 0.8, 3.0, and 10.9 pmol T3/mg protein.min, respectively. Conversion of T4 to T3 was observed in two of three tumor tissues studied and was markedly enhanced in Graves' thyroid tissues (mean +/- SE, 11.9 +/- 2.0 pmol/mg protein.min) compared to that of normal thyroid tissues (3.2 +/- 0.6 pmol/mg protein.min; P less than 0.01). It is concluded that T4 is enzymatically converted to T3 in normal and Graves' thyroids and differentiated thyroid neoplasms. Moreover, enhanced conversion of T4 to T3 was found in Graves' thyroid tissue.

Adenoma↗
PubMed1981

3,3',5'-triiodothyronine (reverse T3) in human cerebrospinal fluid.

To examine the metabolic products of thyroid hormones in the central nervous system, total and free rT3 as well as T4 in human cerebrospinal fluid (CSF) were determined in 41 patients. Total T4, T3, and rT3 concentrations in CSF were determined by RIA, and free T4, T3, and rT3 fractions were analyzed by the magnesium precipitation method. The mean (+/- SE) total T4 and T3 concentrations in CSF were 166 +/- 24 and 2.6 +/- 1.5 ng/dl, respectively; the values were approximatey 2% of those in normal control pooled sera. Total rT3 concentrations in CSF from 29 clinically euthyroid patients who were apparently in a normal nutritional state ranged from 5.2-23 ng/dl (mean +/- SE, 11.2 +/- 0.9 ng/dl); the value was approximately 40% of that in sera. A patient with primary hypothyroidism had a markedly diminished CSF rT3 concentration (1.1 ng/dl), and the remaining 11 patients, suffering from severe diseases such as meningitis and cerebrovascular accident, had significantly higher CSF rT3 concentrations (37.5 +/- 6.6 ng/dl) than the clinically euthyroid patients. Although free T4 and T3 concentrations in CSF (5.9 +/- 1.1 and 0.16 +/- 0.05 ng/dl, respectively) were similar to those in serum (2.1 +/- 0.2 and 0.22 +/- 0.01 ng/dl, respectively), the free rT3 concentration in CSF (0.70 +/- 0.12 ng/dl) was approximately 20 times higher than that (0.044 +/- 0.016 ng/dl) in serum. Furthermore, the reciprocal relationship was observed between CSF total rT3 concentrations and free rT3 percentages in CSF. These data suggest the possibility that rT3 may be produced from T4 in human brain and that there may be a transport mechanism regulating free rT3 in CSF.

Humans↗
PubMed1981

Cushing's syndrome associated with corticogenic hypothyroidism: a case study.

Described here is a 27-year-old female, who had centripetal obesity, broad reddish-purple striae on the lower abdomen and hypertension. Serum cortisol levels, the results of a dexamethasone suppression test and an adrenal scintigram with 131I-19-iodocholesterol were all compatible with Cushing's syndrome due to an adrenal adenoma that secretes cortisol autonomously. This was confirmed by gross and microscopic examination of the removed adrenal tumor. In addition, the patient had markedly diminished T4 and T3 concentrations in serum. Basal TSH levels were not elevated and did not rise significantly after TRH injection. Serum T4 and T3 concentrations were elevated to the normal range when the hyperadrenocorticism was corrected. The results indicate that the patient had "'corticogenic hypothyroidism."

Adenoma↗
PubMed1981

Reciprocal relation between serum thyrotropin levels and intrapituitary 3,5,3'L-triiodothyronine generating activity from thyroxine in perinatal rats.

Thyroxine (T4) 5'-monodeiodinating activity in rat pituitary was studied, using paper chromatography. Rat anterior pituitary homogenates were incubated with 125I-T4, dithiothreitol and unlabeled L-T4 at 37 degrees C. The incubation mixture was extracted by ethanol and the extracts were subjected to descending paper chromatography. The conversion ratio of T4 to 3, 5, 3'L-triodothyronine (T3) was calculated from the radioactivity of T3 spot to total radioactivity on the paper strip. The T3 amount generated was estimated from the T4 concentration in the incubation mixture and the conversion ratio. The T3 generating activity from T4 increased as the amount of tissue increased. It was temperature-and pH-dependent, and thiol sensitive. These results suggest the enzymatic nature of T4 5'-monodeiodinating activity of the anterior pituitary. A kinetic study revealed low Km for T4 (7.9 +/- 1.6 nM, Mean +/- SE), with Vmax of 68.0 +/- 12.7 fmoles T3/mg protein/min. T4 monodeiodinating activity was consistently, though minimally, detected in fetal rat pituitaries and increased after birth, reaching the maximum at 22 days. It declined thereafter to the young adult level. Serum TSH levels were markedly elevated in fetus. They decreased after birth, reaching the nadir at 22 days, and then increased to young adult levels. Serum T4 and T3 levels were markedly diminished in fetus and gradually increased after birth, reaching the young adult levels at 17 days. Thus, a reciprocal relationship was observed between intrapituitary T3 generating activity from T4 and serum TSH levels in developing rats. It suggests that the conversion of T4 to T3 in the pituitary plays a role in regulating TSH secretion.

Animals↗
PubMed1981

Sex- and age-related changes of exophthalmos in graves' disease.

In order to evaluate the effect of sex and age on the protrusion of the eyes in patients with Graves' disease, exophalmometry was performed on 95 patients, aged 16-73. The mean (+/- SE) protrusion in the 190 eyes was 17.5 +/- 0.2 mm, being significantly higher than those in normal subjects (14.9 +/- 0.2 mm) and patients with Hashimoto's disease (14.3 +/- 0.2 mm). No significant difference existed in the degree of protrusion between thyrotoxic Graves' disease patients and those maintained in an euthyroid state during treatment with antithyroid drugs. When compared in terms of the duration of the treatment, the protrusion became prominent with the increased duration of the treatment, especially in male patients, although statistically not significant. The protrusion in male patients tended to increase, though not significantly, with increasing age, whereas it decreased significantly with increasing age in female patients.

Adolescent↗
PubMed1981

Primary aldosteronism associated with a primary double cancer of the thyroid and rectum: report of a case.

A variety of complications are encountered in primary aldosteronism. Among them, less well known is the association of functioning adrenocortical adenoma with neoplasia of other organs. Described here is a patient with primary aldosteronism who had undergone a surgical operation for thyroid cancer and died of meningoencephalitis due to Listeria monocytogenes. Moreover, the autopsy revealed that he had an adenocarcinoma of the rectum. To our knowledge, this is the first documented case of a patient who had both primary aldosteronism and a primary double cancer of the thyroid and rectum.

Adenocarcinoma↗