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Biomedical subjects

T Sakurada

Publications and source records attributed to T Sakurada.

At least 325 records · Page 18Linked to original sources
PubMed1978

Mitochondrial thyroid hormone receptor: localization and physiological significance.

Binding studies of thyroid hormone to submitochondrial fractions from rat liver suggest that the component responsible for high-affinity, low-capacity (saturable) binding of hormones arises from the inner mitochondrial membrane. The partially purified component, approximately 150,000 daltons, appears to be half protein and half lipid, largely phospholipids, tentatively identified as lecithin, phosphatidyl ethanolamine, and cardiolipin. A similar hormone-binding macromolecule was found in mitochondria from rabbit kidney, from human liver and kidney, and from rat kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from mitochondria of adult rat brain, spleen, and testis, organs calorigenically unresponsive to thyroid hormones injected in vivo, but was present in mitochondria from brains of rats 12 days old and younger. The organ distribution of the hormone-binding protein and its presence in neonatal brain mitochondria supports the biological relevance of the mitochondrial component as a thyroid hormone receptor.

Animals↗
PubMed1978

Evidence that triiodothyronine and reverse triiodothyronine are sequentially deiodinated in man.

We have demonstrated that in patients given a single iv injection of T3, rT3, or, to a lesser extent, T4, all labeled with 125I in the outer or phenolic ring, chromatography of serum on columns of Sephadex G-25 superfine revealed the presence of a labeled material, separate from the administered hormone and from both iodide and iodoprotein. This peak has been termed pre-T3 because it elutes just before the T3 peak. Identification of the various compounds in pre-T3 was carried out by cation exchange chromatography. Pre-T3 generated from [125I]T3 consistently contained labeled compounds with the chromatographic behavior of 3,3'-diiodothyronine and 3'-monoiodothyronine, while pre-T3 generated from [125I]rT3 contained labeled products with the chromatographic mobility of 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine. In addition, pre-T3 also contained the glucuro- and sulfoconjugates of these several labeled products. These studies demonstrate that T3 and rT3 undergo progressive and probably sequential deiodination in the peripheral tissues, resulting in the formation of a variety of diiodothyronines and monoiodothyronine, as well as their glucuro- and sulfoconjugates.

Animals↗
PubMed1978

Appearance of labeled metabolites in the serum of man after the administration of labeled thyroxine, triiodothyronine (T3), and reverse triiodothyronine (rT3).

Chromatography of serum on columns of Sephadex G-25 superfine after the iv administration of 125I-labeled T4 consistently yielded labeled iodide, iodoprotein, T3, and a labeled peak that eluted from the column before the T3, termed "pre-T3." Much larger quantities of pre-T3 were generated after the iv administration of 125I-labeled T3 and rT3. The ratio of [125I]pre T3:[125I]T3 and [125I]pre T3:[125I]rT3 plateaued at approximately 10 h and 2 h, respectively, after the iv administration of the labeled hormone, and averaged approximately 15% in euthyroid subjects. As pre-T3 behaves like its precursors in the TCA precipitation-ethanol extraction or anion exchange chromatographic procedures used to separate labeled iodide and iodoprotein from administered labeled T3 and rT3, concentrations of labeled hormone measured by these techniques will be in error, because pre-T3 will be included. Thus, the MCR of labeled T3 and rT3 measured by Sephadex chromatography will always be higher than values obtained by the other two separative techniques and the magnitude of change will be similar to the ratio of pre-T3 to precursor T3 or rT3. The Sephadex chromatographic technique is laborious, but appears to be the method of choice where greatest accuracy of measurement is required. As the generation of pre-T3 from labeled T4 is sufficiently slow, the present chromatographic technique is not necessary in studying peripheral T4 turnover.

Chromatography, Gel↗
PubMed1978

Effects of intraventricularly administered polyamines spermidine and spermine on sleep-wakefulness cycles in rats.

Freely moving rats with chronically implanted electrodes were used and the electroencephalogram (EEG) from the occipital cortex and the dorsal hippocampus, the electromyogram (EMG) and the electrooculogram (EOG) were simultaneously recorded. The REM (rapid eye movement) sleep stage was significantly shortened without a marked change of the Non-REM sleep from the 24th to the 32nd hr following injection of 40 microgram of SPD. The waking stage significantly increased, and the Non-REM sleep and REM sleep markedly decreased immediately after the injection of 40 microgram of SPM to the 8th, and from the 24th to the 32nd hr. The amount of total sleep significantly shortened from the 72nd to the 80th hr following injection of 40 microgram of SPD. The administration of 40 microgram of SPM significantly reduced the amount of total sleep in every period measured for 8 hr. Marked change was observed from the 24th to the 32nd hr following injection of 100 microgram of PUT, and Non-REM sleep and total sleep produced a significant decrease. These results show that the intraventricular administration of polyamines including PUT inhibits the amount of normal sleep.

Animals↗
PubMed1978

Correlation between per cent discharge of thiocyanate test and thyroid functions in patients with Hashimoto's disease.

The thiocyanate test was carried out in 18 patients with Hashimoto's disease. Thiocyanate was given orally several hours after the administration of tracer doses of 131I when the thyroid counts seemed to have reached a plateau. The per cent discharge of thiocyanate test was significantly higher in the groups with lower level of T4 (less than 5.5 microgram/100 ml), RSH (less than 25.5%) and BMR (less than +2.5%), and higher levels of TSH (greater than 10.0 muU/ml). A chi-square (chi2) test with Yates correction led to chi2 = 3.56 (1 df) with P = 0.06 (per cent discharge vs T4, RSU, BMR and TSH). Then the per cent thiocyanate discharge was increased with the degree of hypothyroidism in patients with Hashimoto's disease. The correlation between the per cent discharge and 131I 24 h uptake was not significant. It was apparent that the iodide concentration mechanism was present even in the severe hypothyroid stage of Hashimoto's disease. This disproportion between the uptake of iodide and the iodide organification may result in the increase in unbound iodide. It is concluded that the hypothyroidism in Hashimoto's disease may not be caused by a defect in iodide organification, even if it correlated to the degree of hypothyroidism.

Adult↗
PubMed1978

Partial purification of thyroid hormone receptor from mitochondrial inner membrane: evidence for a physiologic role.

Recently we described a protein component, from the inner mitochondrial membrane, which binds thyroid hormone with high affinity, low capacity (saturable) characteristics. This partially purified rat liver mitochondrial membrane component appears to be a 150,000 daltons lipoprotein complex. Phospholipids, tentatively identified as lecithin, phosphatidyl ethanoamine, and cardiolipin, appear to constitute 50% of this complex. A similar hormone binding marcomolecule was also found in mitochondria from rabbit kidney, as well as human liver and kidney. In the rat this saturable thyroid hormone binding component was found in mitochondria from liver, kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from the mitochondria of adult brain, spleen and testis, organs known to be calorigenically unresponsive to thyroid hormones injected in vivo. In contrast, neonatal rat brains contain the protein with binding constants similar to those of neonatal or adult rat liver mitochondria, but in older rat brains (14 and 17 days) the saturable binding was no longer present, as in adult brain. These data provide strong support for the biological relevance of the mitochondrial component as a thyroid hormone receptor.

Animals↗
PubMed1978

[Effects of diazepam on evoked potential recorded from basal medial amygdaloid nucleus, lateral hypothalamus and midbrain reticular formation (author's transl)].

The evoked potential in the lateral hypothalamus (LH) recorded by stimulation of basal medial amygdaloid nucleus (Abm) showed a triphasic pattern and diazepam (2 mg/kg, i. p.) decreased the late component. The evoked potential in the midbrain reticular formation (MRF) recorded by stimulation of Abm showed a fast component with a relatively short latency followed by a biphasic late component and diazepam decreased the late component. Though the evoked potential in the Abm recorded by stimulation of LH showed a triphasic pattern, diazepam had no influence on the amplitude. Diazepam increased markedly the amplitude of evoked potential in the MRF recorded by stimulation of LH. Diazepam was ineffective on the evoked potential in the Abm recorded by stimulation of MRF. Diazepam decreased markedly the late component of evoked potential in the LH recorded by stimulation of MRF. These results suggest that the depression of emotional behavior by diazepam may be particularly related to the fact that the evoked potential in the LH recorded by stimulation of Abm was decreased by diazepam.

Amygdala↗
PubMed1977

Xanthine oxidase and guanase activities in normal and psoriatic epidermis.

Xanthine oxidase and guanase activities in normal and psoriatic epidermis were demonstrated and accurately assayed by the new micro-assay methods which rely on the isolation of 14C-labelled end-products, xanthine and uric acid, from the substrates, hypoxanthine and guanine, by electrophoresis on cellulose acetate membrane using 0.1 M borate buffer, pH 9.0. The average specific activities of xanthine oxidase and guanase in normal epidermis were 10.2 and 55.0 pmol/min/mg protein, respectively, and in psoriatic epidermis, 52.1 and 980.6 pmol/min/mg protein, respectively. Increased activities of these enzymes in psoriatic epidermis suggested that urate formation might be enhanced in the psoriatic lesions resulting from an increased turn-over of nucleic acids.

Adult↗
PubMed1977

Role of endogenous calcitonin in the secretion of gastrin and gastric acid in rats.

Following pyloric ligation, serum immunoreactive gastrin levels and gastric acid accumulation in acutely thyroidectomized rats with autotransplanted parathyroid glands were significantly higher than those in thyroid intact rats. Furthermore, serum immunoreactive gastrin levels were higher in the absence than in the presence of the thyroid gland following the oral administration of glycine or rat chaw. These results suggest that endogeneous calcitonin has an inhibitory action on gastric acid secretion probably through the inhibitory action on gastrin secretion in rats.

Animals↗
PubMed1977

Purine phosphoribosyltransferase activities in guinea pig epidermis.

Purine phosphoribosyltransferase activities in normal and experimental hyperkeratotic epidermis of guinea pig skin were demonstrated quantitatively by a new microassay method. The ratio of HGPRTase with hypoxanthine as a substrate to APRTase activity in normal and hyperkeratotic epidermis was found to be 0.94 and 0.60, respectively. The HGPRTase and APRTase activities expressed as micromoles per gram wet weight per min. were increased in experimental hyperkeratotic epidermis and it is suggested that the salvage pathway for purine nucleotide biosynthesis is activated in experimental hyperkeratotic epidermis. The pH optimum of these enzymes and their stability in the frozen state were also demonstrated.

Animals↗
PubMed1977

Effects of p-chlorophenylalanine (p-CPA) on sleep in olfactory bulb lesioned rats.

The effect of p-CPA and 5-HTP followed by p-CPA on sleep was studied in rats with olfactory bulb lesions (O.B. lesioned rats). In these rats, electrodes were chronically implanted to record the EEG (frontal cortex and dorsal hippocampus), the cervical electromyogram and eye movements. The REM sleep stage was selectively decreased from 24 to 32 hours after 200 mg/kg of p-CPA in the sham lesioned rats, whereas both the slow wave sleep and REM sleep stages were markedly decreased by the same dose of p-CPA in the O.B. lesioned rats. In both sham and O.B. lesioned groups, the slow wave sleep and REM sleep stages decreased from 24 to 32 hours after 400 mg/kg of p-CPA and the percentage of decrease in the slow wave sleep stage was much larger with 400 mg/kg of p-CPA than with 200 mg/kg and 400 mg/kg of p-CPA. In the O.B. lesioned rats, the insomnia produced by 200 mg/kg and 400 mg/kg of p-CPA disappeared with 5-HTP (5 mg/kg). On the other hand, the insomnia produced by 200 mg/kg of p-CPA did not recur with 5-HTP in the sham lesioned rats, but with 400 mg/kg there was a recurrence. These results suggest that the enhanced effect of p-CPA and 5-HTP followed by p-CPA in the O.B. lesioned rats is due to changes in the sensitivity of the serotonergic system in the brain.

Animals↗
PubMed1977

Pharmacological actions of intracerebrally administered polyamines in mice.

Pharmacological actions of spermidine (SPD) and spermine (SPM) in mice given these polyamines by intracerebral injection (i.c.) were investigated. The spontaneous motor activity (SMA) assessed by the photocell counter method did not change immediately following injection of 80 mug SPD, but was enhanced 24 hours after the injection of 40 or 80 mug. A significant decrease of SMA was not immediately evident after the administration of 40 mug SPM but was demonstrated 24 hours later. Mice given single doses of 20 mug SPD exhibited increase in weight gain and those given 40 mug showed no significant difference, whereas a conspicuous decrease in weight occurred in mice given 80 mug of SPD. The body weights of mice given single doses of 10 mug SPM remained much the same, while significant weight losses occurred in both the SPM 20 mug and 40 mug dosed groups. There was a significant prolongation of pentobarbital induced sleep 6 days after the injection of high doses of SPD or SPM. Similar prolongation of sleeping time was also evident 30 minutes after the injection of SPM. A maximal hypothermic response with a fall by about 1 degree C was observed immediately following injection of 80 mug of SPD and 24 hours after the injection of 40 mug SPM, respectively.

Animals↗
PubMed1977

The thyroid reserve in patients with breast cancer.

Patients with breast cancer were studied with regard to changes in the levels of serum thyroxine (T4) and serum triidothyronine (T3) after intramuscular administration of TSH for three days to investigate the thyroid reserve in these patients. The changes were examined also in normal subjects, in patients with Hashimoto's thyroiditis and primary hypothyroidism. In primary hypothyroidism no increase was seen in serum T4 and T3 levels after TSH administration, and the thyroid reserve was considered to be absent. In Hashimoto's thyroiditis the serum T3 levels after TSH administration were the same as in normal subjects, but the serum T4 levels were significantly lower than normal. This suggests that in patients with Hashimoto's thyroiditis the thyroid reserve is decreased and is in a state of so-called low thyroid reserve. In patients with breast cancer, however, the levels of serum T4 and T3 showed no difference as compared with those in normal subjects after TSH administration, and this implies that the thyroid reserve is well maintained.

Adult↗