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Biomedical subjects

T Sakurada

Publications and source records attributed to T Sakurada.

At least 199 records · Page 11Linked to original sources

[The effect of serum free fatty acid on serum free thyroid hormone fractions in low T3 syndrome].

We studied the role of serum free fatty acid (FFA) in the elevation of serum dializable fraction of T4 (DFT4) and evaluated the serum free T4 (FT4) level in low T3 syndrome. Serum DFT4 and DFT3 were measured by equilibrium dialysis method with phosphate buffer, and serum FFA concentration was obtained by gas chromatography. In patients with nonthyroidal systemic illnesses who showed reduced serum total T3 (TT3) and normal total T4 (TT4) (low T3 group, TT3 48 +/- 14 ng/dl, n = 10), mean (+/- SD) DFT4 value (0.032 +/- 0.05%) was significantly higher than that of the group of systemic illnesses with normal TT3 and TT4 (normal T3 group, TT3 79 +/- 7 ng/dl, n = 10). Mean TT4 value of low T3 group (6.5 +/- 1.0 micrograms/dl) was lower than that of normal T3 group (8.6 +/- 2.4 microgram/dl, p less than 0.02). There was no difference in mean absolute FT4 (AFT4) value between the two groups (2.07 +/- 0.46 vs 2.19 +/- 0.53 ng/dl). On the other hand, there was no significant difference in DFT3 value between the groups (0.274 +/- 0.043 vs 0.247 +/- 0.035%), and mean AFT3 of low T3 group (1.29 +/- 0.39 pg/ml) was low than that of normal T3 group (1.92 +/- 0.26 pg/ml, p less than 0.01). In cases of low and normal T3 groups (n = 20), serum thyroxine binding globulin (TBG) concentration had a negative correlation with DFT3 (r = -0.707, p less than 0.001), but not with DFT4. Although there were no significant differences in serum albumin and TBG concentrations between the two groups, the mean serum total FFA concentration and molar ratio of FFA to albumin in low T3 group (579 +/- 249 microM and 1.31 +/- 0.61) were significantly higher than those in normal T3 group (345 +/- 170 microM and 0.75 +/- 0.32, p less than 0.05 and less than 0.025, respectively). All of FFA concentrations in low T3 group, especially oleate, were higher than those in normal T3 group. Moreover, the higher the total FFA concentration was, the greater was the percent fraction of oleate. DFT4 values were significantly increased by the addition of 1 mM oleate to the sera of low T3 group, and this effect was more marked in the sera of the patients with lower albumin concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Synthesis of N4-substituted CTP by mammalian CTP synthetase.

Highly purified CTP synthetase from Ehrlich ascites tumor cells catalyzes the formation of N4-substituted CTP from UTP and hydroxylamine and its derivatives. The products with hydroxylamine and O-methylhydroxylamine were identified as N4-hydroxyCTP and N4-methoxyCTP by absorption spectra and chromatographic behavior on Dowex column, respectively. The weak nucleophilic amines such as methylamine, ethylamine or diethylamine and a less nucleophilic amine, sulfamic acid, did not react with UTP. These results suggest that the nucleophilicity and basicity of amines are important in the enzymic reaction with UTP.

Animals↗

Behavioural effects of intrathecally injected tachykinins in rats with peripheral nerve transection.

The effect of unilateral sciatic nerve transection on behavioural responses produced by intrathecal administration of substance P (SP), neurokinin A, eledoisin and physalaemin was investigated in the rat. The injection of SP (3 nmol/rat) into the subarachnoid space was followed by reciprocal scratching, biting and licking of the fore- and hind-limbs. There was no observable difference in the behavioural response to SP between rats with nerve transection and sham operated rats at 5 days after operation. Whereas at 10, 20, and 30 days after nerve transection the response to SP was significantly increased as compared with sham operated rats. This phenomenon was also observed with neurokinin A (1.5, 3.0 and 6.0 nmol/rat), eledoisin (0.05 and 0.10 nmol/rat) and physalaemin (0.05 and 0.10 nmol/rat) at 10 days after operation. Ipsilateral depletion of SP from the lumbar (L4-L6) spinal cord was observed at 5, 10, 20, and 30 days after the unilateral transection of the sciatic nerve. These results suggest that sciatic nerve transection may produce an increased response to tachykinins through an enhanced sensitivity of tachykinin receptors in the lumbar cord.

Animals↗

Behavioural characterization of substance P-induced nociceptive response in mice.

Intrathecal injection of substance P produced a behavioural syndrome, consisting of reciproacal hindlimb scratching and biting or fore- and hind-licking. Pretreatment with either an analogue of substance P, (D-Pro2, D-Trp7,9)-substance P (DPDT-SP) or (D-Arg1, D-Pro2,4, D-Trp7,9, Leu11)-substance P, given intrathecally, reduced the response to substance P in a dose-dependent manner. The behaviour induced by substance P was also inhibited by intrathecal, intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of morphine. Intrathecal or subcutaneous injection of naloxone showed a biphasic effect on substance P response; the substance P-induced nociceptive response was increased by a small dose of naloxone, while it was inversely decreased by a large dose of naloxone. The results with analogues of substance P support the hypothesis that substance P, injected intrathecally, acts directly on substance P receptors in the spinal cord. The nociceptive response induced by substance P appears to be controlled by endogenous opioids in the spinal cord.

Animals↗

Behavioural assessment as substance P antagonists in mice.

A series of eleven undeca- and four hexapeptide antagonists of substance P (SP) have been assayed by the SP-induced behavioural test in mice. When 2 nmol of [D-Arg1, D-Pro, D-Trp, Leu]-SP (SP 1-11 I) was intrathecally injected together with SP (0.1 nmol), SP-induced response which consists of scratching, biting and licking was markedly inhibited. [D-Trp, Leu]-SP 6-11 (SP 6-11 I) given in a dose of 2 nmol was also inhibited the SP-induced response to the same degree as SP 1-11 I. Some of SP 1-11 or SP 6-11 analogues substituted with fluorine in positions 7 and/or 8 maintained the antagonistic effect of SP 1-11 I or SP 6-11 I, though the others were weaker. Intrathecal administration of SP 1-11 I and SP 6-11 I resulted in long-lasting antinociceptive effects as measured by the tail-flick test. Fluorine-containing SP analogues were less potent than the above two analogues in producing antinociception. These results suggest that the antagonistic effect of SP analogues on the SP-induced nociceptive response do not necessarily relate to antinociceptive activity at the spinal cord level.

Analgesia↗

Effect of cadmium on T4 outer ring monodeiodination by rat liver.

The effect of cadmium on thyroxine (T4) outer ring monodeiodination was studied in vivo and in vitro in the rat liver. One microgram of T4 was incubated with rat liver homogenates in 50 mM Tris--HCl buffer, pH 7.4, with or without 0.5, 5, and 50 mM dithiothreitol (DTT) for 60 min in the presence of 10(-8) to 10(-3) M CdCl2, and the amount of 3,5,3'-triiodothyronine (T3) produced was determined by a specific radioimmunoassay. Subcutaneous injection of CdCl2, 1 mg/kg BW/day, 5 days a week for 10 weeks, to the rats resulted in a significant reduction in serum T3 concentration (by 37%) and hepatic T3 production from T4 (by 78 to 92%). In vitro addition of 1 microM to 1 mM CdCl2 to liver homogenates caused a concentration-dependent reduction in T3 generation. Without DTT a 50% reduction in the T4 to T3 converting activity was caused by 4 X 10(-6) M CdCl2. DTT (0.5 to 50 mM) partially restored T3 generation roughly in a concentration-dependent manner. These results indicate that cadmium has some effects on the metabolism of thyroid hormone.

Animals↗

Measurement of thyroid hormone concentrations in human placenta.

Concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) in the placenta were measured in 7 patients with abortion, in 9 patients with premature delivery, in 16 normal pregnancies and in 4 pregnant women with Graves' disease. The placentas, obtained at delivery, were homogenized and centrifuged at 800 X g. T4, T3 and rT3 concentrations in the supernatants were extracted with 3 vol. of 99% ethanol and measured by RIAs. In normal pregnancy, placental T4, T3 and rT3 concentrations were 18.8 +/- 5.9 (mean +/- SD), 0.026 +/- 0.012, and 1.70 +/- 0.49 ng/g tissue, respectively. Ratios of rT3/T3 and rT3/T4 in the placenta were about 12 and 2.3 times as high as those in the fetal sera, respectively. There was a significant positive correlation between the placental T4 and the maternal or cord serum T4 concentrations. However, no correlation was found between the placental T3 or rT3 concentrations and the maternal or cord T3 or rT3 concentrations. In 4 patients with Graves' disease, the placental T4 concentration was elevated. These results indicate that the placental T4 concentration is influenced by both the maternal and fetal serum T4, and elevated ratios of rT3/T3 and rT3/T4 in the placenta might be due to the active placental 5-monodeiodination.

Abortion, Spontaneous↗

Effect of prednisolone and salicylate on serum thyroglobulin level in patients with subacute thyroiditis.

Twelve patients with subacute thyroiditis were divided into two groups and treated with prednisolone or salicylate. The initially elevated T4, T3, free T4 (FT4), free T3 (FT3) and erythrocyte sedimentation rate (ESR) were reduced during the early phase within about 4 weeks in both groups. The serum levels of thyroglobulin (Tg) were elevated in both groups treated with salicylate and prednisolone (252 +/- SD 117 ng/ml and 233 +/- SD 157 ng/ml, respectively) at initial examination. The serum level of Tg declined during the early phase with prednisolone treatment, and it reached normal values at the end of the early phase (17 +/- SD 15 ng/ml). With salicylate treatment, the decline of levels of Tg was delayed and it was elevated (80 +/- SD 34 ng/ml) despite normal levels of thyroid hormones and ESR at the end of early phase. The serum level of Tg at the end of the early phase of prednisolone treated was significantly lower than that of salicylate treatment (P less than 0.01). It is suggested that the effect of prednisolone on rapid decrease of Tg may be related to its inhibitory action of intrathyroid hydrolysis.

Adult↗

[Effects of capsaicin on spontaneous unit discharges in amygdala single neurons of cats].

Effects of capsaicin on spontaneous unit discharges in the amygdala single neurons were studied in 26 gallamine immobilized adult cats. Single units were recorded from the amygdala using a stainless steel microelectrode. Of 63 amygdala neurons, 34 were responsive to both noxious (pinching the skin with toothed forceps) and innoxious (tap and/or hair bending) stimuli, 11 were responsive to only innoxious stimuli and the others did not respond to these stimuli. Of 34 neurons responsive to both noxious and innoxious stimuli, 20 were responsive to both bradykinin and capsaicin, and 7 were responsive to only capsaicin. All neurons responsive to bradykinin were also responsive to capsaicin. All neurons responsive to only innoxious stimuli responded to neither bradykinin nor capsaicin. The latency for bradykinin and capsaicin was 8.05 +/- 0.92 sec and 1.21 +/- 0.33 sec, respectively. The duration for bradykinin and capsaicin was 14.72 +/- 1.78 sec and 26.22 +/- 4.16 sec, respectively. The increase in firing frequency produced by capsaicin was depressed by morphine (1 mg/kg, i.v.). These depressant effects of morphine on the amygdala neurons were antagonized by naloxone (0.2 mg/kg, i.v.).

Action Potentials↗

Thyroid function and antimicrosomal antibody during the course of silent thyroiditis.

The thyroid function and antithyroidal antibody were studied in 17 patients with silent thyroiditis unrelated to pregnancy. The antimicrosomal hemagglutination antibody (MCHA) was negative in ten of them (group I) and was positive in seven (group II). At one month after the thyrotoxicosis, thyroid function became normal in both groups. At two months after the onset of thyrotoxicosis, in group I T4 (8.1 +/- 1.8 micrograms/dl, Mean +/- SD), T3 (113 +/- 25 ng/dl) and TSH were normal. At that time T4 (2.8 +/- 2.2 micrograms/dl) was significantly decreased (p less than 0.001) compared with those of group I and the levels of TSH were strikingly increased in 6 patients in group II. The level of T3 (96 +/- 29 ng/dl) in group II was not different from that of group I. Therefore MCHA was negative in patients who did not develop hypothyroidism and MCHA was positive in patients who developed hypothyroidism. The development of hypothyroidism two months after thyrotoxicosis and positive MCHA are correlated. The Tg was elevated in 7 out of 13 patients (54%) with negative antithyroglobulin hemagglutination antibody and in the remainder was normal during thyrotoxicosis. The discrepancy between the level of Tg and thyroid hormones was discussed.

Adult↗

Characteristics of anti-TSH receptor antibodies in two patients who developed spontaneous hypothyroidism after antithyroid drug therapy for hyperthyroid Graves' disease.

Spontaneous hypothyroidism was developed in two patients with Graves' hyperthyroidism 1.8 or 1 years after antithyroid drug therapy. In these patients anti-thyrotropin (TSH) receptor antibodies were detected. Thyrotropin receptor antibody (TRAb) index measured with TSH radioreceptor assay was 61.0% in case 1 and 68.0% in case 2 (normal value: -10 to 10%), and human thyroid adenylate cyclase stimulating activities (HTACS) were 154% in case 1 and 190% in case 2 (normal value: 70 to 130%). IgG from case 1 suppressed the stimulating activity of bovine TSH (bTSH) on thyroid adenylate cyclase in low concentrations in vitro. These results indicate that a blocking type of anti-TSH receptor antibodies as well as concomitant chronic thyroiditis might be a causative factor in patients who developed spontaneous hypothyroidism shortly after the cessation of antithyroid drugs.

Adenylyl Cyclases↗

Opioid activities of D-Arg2-substituted tetrapeptides.

The antinociceptive effects and mechanisms of action of H-Tyr-D-Ala-Phe-Gly-OH, H-Tyr-D-Arg-Phe-Gly-OH and H-Tyr-D-Arg-Phe-sarcosine(Sar)-OH have been investigated. The ED50 values of these peptides were 510.0, 8.2 and 2.0 pmol, respectively, when administered i.c.v. in the mouse tail-pressure test (dermorphin = 5.7 pmol and morphine = 1.2 nmol). These activities were remarkably potent and relatively long lasting. Their IC50 values were 676.8, 23.1 and 6.6 nM, respectively (dermorphin = 3.75 and morphine = 214.3 nM) in the guinea pig isolated ileum assay, and 138.50, 5.25 and 1.10 nM, respectively (dermorphin = 3.80 and morphine = 28.00 nM) in the radioreceptor assay utilizing [3H]naloxone as the opioid receptor ligand. In the evaluation of their inhibitory effects to enkephalin-degrading enzymes, the IC50 values of H-Tyr-D-Arg-Phe-Gly-OH, H-Tyr-D-Arg-Phe-Sar-OH and H-Tyr-D-Ala-Phe-Gly-OH were 5.4, 14.5 and more than 50.0 microM, respectively (bestatin = 0.1 microM) against aminopeptidase and 1.18, 1.40 and more than 50.0 microM, respectively (captopril = 0.38 and D-Phe-2S-, 3R-3-amino-2-hydroxy-4-phenylbutanoic acid = more than 100 microM) against the cleaving enzymes of enkephalin at its Gly3-Phe4 bond. The authors suggest that the marked antinociceptive potency of H-Tyr-D-Arg-Phe-Gly-OH and H-Tyr-D-Arg-Phe-Sar-OH is mainly due to high opioid receptor affinity. Their inhibitory effects on enkephalin-degrading enzymes and enzymatic stability also greatly contribute to their potent and long-lasting opioid activities.

Animals↗