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Biomedical subjects

T Sakurada

Publications and source records attributed to T Sakurada.

At least 217 records · Page 12Linked to original sources
PubMed1986

Physical dependence of a dermorphin tetrapeptide analog, [D-Arg2, Sar4]-dermorphin (1-4) in the rat.

The characteristics of an analog of tetrapeptide dermorphin (H-Tyr-D-Arg-Phe-Sar-OH), [D-Arg2, Sar4]-dermorphin (1-4) were examined in comparison with morphine by the appearance of typical withdrawal signs upon cessation of administration or treatment with naloxone, an opioid antagonist. The dose of [D-Arg2, Sar4]-dermorphin (1-4) or morphine in the physical dependence test can be quantified by determining the ED50 to inhibit the tail-flick response to thermal stimuli. Doses from 8 to 64 times the ED50 doses were employed in the subcutaneous injection schedules. The cessation of [D-Arg2, Sar4]-dermorphin (1-4) or naloxone treatment was largely without effect on body weight, in contrast to a marked loss of weight in morphine-dependent rats. The tetrapeptide failed to substitute for morphine in morphine-dependent rats. The physical dependence of [D-Arg2, Sar4]-dermorphin (1-4) was revealed by the behavioral signs of withdrawal precipitated by naloxone. However, the scores of lacrimation, diarrhea and urination were much lower in chronically tetrapeptide-treated rats than in morphine-treated rats, though the score of teeth chatter was higher. These findings indicate that [D-Arg2, Sar4]-dermorphin (1-4) may differ from morphine in physical dependence.

Analgesics↗
PubMed1986

Measurement of TSH in human amniotic fluid: diagnosis of fetal thyroid abnormality in utero.

Using a highly sensitive immunoradiometric assay kit for human TSH, we measured TSH concentrations in unconcentrated amniotic fluids in normal pregnancies and those complicated for example by maternal hyper- and hypothyroidism, and compared them with those in maternal and cord sera. In normal pregnancies the mean concentration of TSH in amniotic fluid samples was 0.129 microU/ml, ranging from 0.065 to 0.278 microU/ml. In patients with premature delivery, the amniotic fluid TSH concentration was higher at 0.218 microU/ml. In four patients with abnormal thyroid function, TSH in amniotic fluid changed in parallel to that in cord serum, and there was a significant positive correlation between the two. No such correlation was observed between the concentrations of TSH in amniotic fluid and maternal serum. These results suggest that TSH in human amniotic fluid reflects fetal rather than maternal thyroid function and that the determination of TSH levels in amniotic fluid is useful in the diagnosis of abnormal thyroid function in fetuses.

Amniotic Fluid↗
PubMed1986

Dermorphin analogues containing D-kyotorphin: structure-antinociceptive relationships in mice.

The antinociceptive effects of synthetic dermorphin and its analogues containing D-Arg in position 2 injected into the lateral cerebroventricle were examined in conscious mice. Intracerebroventricular (i.c.v.) administration of dermorphin and [D-Arg2] dermorphin produced potent and long-lasting antinociceptive activity as assayed by the tail-pressure test. Dermorphin and [D-Arg2] dermorphin were 210 and 52 times more potent than morphine, respectively. The antinociceptive effects produced by these heptapeptides were antagonized by a low dose (0.5 mg kg-1, i.p.) of the opioid antagonist naloxone. The ED50 values for [D-Arg2] dermorphin (1-6), (1-5) and (1-4) were not significantly different from that for [D-Arg2] dermorphin. The potency of the shortest fragment, [D-Arg2] dermorphin (1-2) was found to possess a severely reduced activity, whilst [D-Arg2] dermorphin (1-3) maintained activity and was 10 times more potent than morphine. [D-Arg2] dermorphin analogues showed almost identical effects when tested on the electrically-induced contractions of the guinea-pig isolated ileum. These results led us to conclude that the presence of the N-terminal tripeptide in the structure of [D-Arg2] dermorphin is of crucial importance for the manifestation of the full intrinsic opioid-like antinociceptive activity of [D-Arg2] dermorphin, which is presumably mediated through opioid receptors in the brain.

Analgesics, Opioid↗
PubMed1986

Potentiation of dermorphin-induced antinociception by peptidase inhibitors.

We have investigated the effect of amastatin, an aminopeptidase inhibitor, and captopril, an angiotensin converting enzyme inhibitor, on the antinociceptive activity induced by intracerebroventricular administration of dermorphin, a heptapeptide. In addition, the potency of dermorphin was compared with that of one of its metabolites, N-terminal tetrapeptide (Tyr-D-Ala-Phe-Gly), by using the tail pressure test. The antinociceptive activity induced by dermorphin was not potentiated by simultaneous administration of amastatin or captopril. However, there was potentiation when dermorphin was combined with both peptidase inhibitors. Moreover, the N-terminal tetrapeptide was 84 times less potent than its parent heptapeptide when administered intracerebroventricularly. The results suggest that the cleavage of Tyr1-D-Ala2 and Gly4-Tyr5 bonds by brain endopeptidase modulates dermorphin-induced antinociceptive activity.

Analgesics↗
PubMed1986

[Effects of tooth pulp stimulation on single unit activity of the amygdala in cats].

Responses induced by tooth pulp stimulation were studied in 27 gallamine immobilized adult cats. Single units were recorded from the amygdala using stainless steel microelectrodes. Of 57 amygdaloid neurons, 8 were responsive to only non-nociceptive (tap and/or hair bending) stimuli, 7 were responsive to both nociceptive (pinch) and non-nociceptive stimuli, 18 were responsive to nociceptive stimuli, non-nociceptive stimuli and tooth pulp stimulation, and the others did not respond to these stimuli. The neurons in the amygdala responsive to tooth pulp stimulation were localized in the nucleus amygdaloideus centralis (pars lateralis) [Acl], nucleus amygdaloideus centralis (pars medialis) [Acl] and nucleus amygdaloideus basalis (pars magnocellularis) [Abm]. The response induced by tooth pulp stimulation was depressed by morphine and reversed by naloxone. These results suggest that Acl, Acm and Abm in the amygdala may receive pain sensation evoked by tooth pulp stimulation. Moreover, there is a possibility that these nuclei may be related to the emotional component involved in nociceptive processing.

Afferent Pathways↗
PubMed1986

Effect of changes in thyroid state on metabolism of thyroxine by rat placenta.

We studied the effect of the state of the thyroid on T4 monodeiodination in the rat placenta, and it was compared with those in the liver and kidney. The tissues, maternal serum, and amniotic fluid were obtained from pregnant rats. The tissues were homogenized in cold 50 mM Tris-HCl buffer, pH 7.5. The homogenate (1 mg protein) was incubated at 37 degrees C for 60 min with 1 microgram T4 in the presence of 5 mM DTT. The T3 and reverse T3 generated in the reaction mixture were extracted into cold ethanol and measured by RIAs. The conversion of T4 to reverse T3 in rat placenta was not significantly changed in MMI-induced hypothyroidism or T4 induced hyperthyroidism. On the other hand, conversion of T4 to T3 in the liver and kidney were changed in parallel with the thyroid state. The concentration of reverse T3 in the amniotic fluid was increased in accordance with the increase in the maternal serum T4 concentration. These results indicate that the placental T4 inner ring deiodination is not affected by the thyroid state, and that the change in the amniotic fluid reverse T3 concentration in this study is mainly dependent upon the change in maternal thyroid function.

Amnion↗
PubMed1986

Free thyroxine estimation for the screening of hyper- and hypothyroidism in an adult population.

Serum free thyroxine (FT4), total T4 (T4) and total T3 (T3) were determined by radioimmunoassay in 1,114 adults during a periodic health evaluation to detect unsuspected thyroid dysfunction. As a result, 3 patients with hyperthyroidism, 4 with hypothyroidism, 3 taking thyroid medication, 4 with chronic thyroiditis, 1 with simple goiter and 3 women under estrogen administration were found. Free T4 values were within the normal limits in the present four subjects taking estrogens, but all of them showed high T4 and one high T3 values. FT4 and T4 were low in four patients with hypothyroidism, but two of them showed normal T3 values. For the screening of hyperthyroidism, FT4 was the most reliable measurement and determination of either FT4 or T4 was suitable for the screening of hypothyroidism, but T3 measurement did not diagnose all patients with hypothyroidism, but T3 measurement did not diagnose all patients with hypothyroidism.

Adult↗
PubMed1986

Studies on the hypothermic response of capsaicin and its analogue in mice.

Administration of capsaicin (CAP) and its related pungent, nonanoyl vanillylamide (NVA) produced significant dose-dependent hypothermic response in mice at an ambient temperature of 24 degrees C. CAP was approximately equieffective to NVA in producing hypothermia. After large doses, desensitization occurred to the hypothermic effects of both CAP and NVA. The hypothermia produced by CAP and NVA was prevented by a small dose of thyrotropin-releasing hormone (TRH) (0.25 nmol/animal) which by itself had little effect on body temperature. Histidyl-proline diketopiperazine, a metabolite of TRH, was without effect on the hypothermic response of CAP and NVA. The result suggests that a TRH neuronal system in the brain may explain a part of the mechanism of CAP- and NVA-induced hypothermia in mice.

Animals↗
PubMed1985

On the degradation of dermorphin and D-Arg2-dermorphin analogs by a soluble rat brain extract.

Degradation of dermorphin, [D-Arg2]dermorphin and [D-Arg2, Gly3, Phe4]dermorphin in a soluble rat brain extract was examined. The former two heptapeptides were degraded in a similar fashion to produce corresponding N-terminal tetrapeptide as the main degradation product along with the parallel release of Tyr5, Pro6 and Ser7-NH2. Tyr-D-Arg-Phe-Gly showed a good enzymatic stability. When captopril, an angiotensin-converting enzyme inhibitor, was present in the incubation mixture, hydrolysis of the Gly4-Tyr5 bond was markedly suppressed and resulted in release of the corresponding N-terminal hexapeptide as the main degradation product. Combined use of captopril and amastatin, an aminopeptidase inhibitor, markedly suppressed the hydrolysis of these peptides. On the other hand, [D-Arg2, Gly3, Phe4]dermorphin was hydrolyzed easier than the other two heptapeptides and considerable amounts of Tyr1 and Phe4 were released after 20 hr incubation while the N-terminal tetrapeptide, Tyr-D-Arg-Gly-Phe, showed a good enzymatic stability. On the basis of these results, possible degradation pathways of these heptapeptides were discussed.

Amino Acids↗
PubMed1985

[The relationship between serum IAP and peripheral K cells in patients with subacute thyroiditis].

In a previous study, we showed that the percentage of peripheral K cells of patients with subacute thyroiditis (SAT), determined by a plaque-forming cell technique, was significantly lower than that of normal controls, and that ther sera from SAT significantly inhibited the activity of K cells in normal lymphocytes, suggesting that in the sera of SAT there is some factor which inhibits K cell activity. In this study, we investigated the relationship between K cells and the serum immunosuppressive acidic protein (IAP), the sex difference in percentage of K cells, and the absolute count of K cells in patients with SAT. In normal controls, there was a sex difference in the percentage of K cells in total lymphocytes; the percentage was significantly lower in women (mean +/- S.D., 5.0 +/- 2.0%; n = 12; p less than 0.01) than in men (8.4 +/- 2.9%; n = 20). However, there was no sex difference in the absolute count of peripheral K cells. In the acute phase of SAT, the percentages of K cells wee 2.4 +/- 1.8%; 2.4 +/- 1.9% and 2.7 +/- 1.0% in 19 patients, 16 females and 3 males, respectively, which were significantly lower than 6.8 +/- 3.0%, 5.0 +/- 2.0% and 8.4 +/- 2.9% in 25 controls, 12 females and 13 males, respectively. The absolute counts of K cells in the acute phase of SAT were 56 +/- 45/mm3 and 58 +/- 48/mm3 in 13 patients including 11 females, respectively, which were significantly lower than 165 +/- 63/mm3 and 153 +/- 73/mm3 in 12 patients including 5 female controls, respectively. It was observed that serum IAP values in SAT were correlated negatively with the percentage of K cells and positively with the inhibition rate of SAT sera on K cells from normal subjects. Moreover, purified IAP showed a dose-related inhibition on the K cells from the control subjects. These results suggest that IAP in the sera of SAT seems to be one of the factors which inhibits the activity of K cells.

Adult↗
PubMed1985

The antinociceptive effects of histidyl-proline diketopiperazine and thyrotropin-releasing hormone in the mouse.

Intracerebroventricular (i.c.v.) injection of histidyl-proline diketopiperazine [cyclo (His-Pro)], an active metabolite of thyrotropin-releasing hormone (TRH) in mice produced an antinociceptive effect in a dose-dependent manner as measured in four antinociceptive tests; tail-pressure, tail-flick, hot-plate and acetic acid writhing. The antinociceptive effect of cyclo (His-Pro) reached a maximum at 5 min and lasted for 30 min. The ED50 values for the tests were 760.0 (598.4-965.2), 540.0 (442.6-658.8), 595.0 (487.7-725.9) and 370.0 (286.8-477.3) nmol/mouse and the slope functions were 1.61, 1.56, 1.57 and 1.66, respectively. Pretreatment with naloxone (0.5, 2 and 8 mg/kg), an opioid antagonist, administered subcutaneously antagonized the antinociceptive effect of cyclo (His-Pro). TRH injected i.c.v. to mice also exerted a dose-dependent antinociceptive action as measured in three antinociceptive tests; tail-pressure, hot-plate and acetic acid writhing. The antinociceptive effect of TRH was only seen at 5 min. The ED50 values for each test were 112.0 (47.5-264.3), 19.2 (10.4-35.5) and 0.2 (0.1-0.4) nmol/mouse and the slope functions were 8.89, 4.14 and 3.94, respectively. TRH was without effect in the tail-flick test. In contrast to cyclo (His-Pro), TRH-induced antinociception was not antagonized by pretreatment with naloxone (0.5, 2 and 8 mg/kg). The data suggest that the two peptides have a different mechanism of antinociceptive action in relation to the involvement of the opioid system in the central nervous system.

Acetates↗
PubMed1985

CTP synthetase from Ehrlich ascites tumor cells. Subunit stoichiometry and regulation of activity.

CTP synthetase (UTP: glutamine ligase (ADP-forming), EC 6.3.4.2) was purified from Ehrlich ascites tumor cells to near homogeneity and found to be a dimer composed of two seemingly identical 66 kDa subunits. The formation of CTP was accompanied by the production of equivalent amounts of ADP from ATP and glutamate from glutamine. The reaction product, CTP, was a potent inhibitor generating sigmoidal kinetics as a function of UTP with an n value of 2.0. UTP and CTP pools in the ascites cells were elevated in an early period (12-16 h) following implantation into the intraperitoneal cavity of mice, whereas ATP, GTP and glutamine pools did not change. Kinetic data and analysis of the nucleotide pools in the cells growing in vivo suggested that the biosynthesis of CTP is regulated at the level of CTP synthetase by UTP and CTP.

Adenosine Triphosphate↗
PubMed1985

[An epidemiological study of subacute thyroiditis in northern Japan].

It is difficult to study subacute thyroiditis epidemiologically since it occurs sporadically and infrequently. Information about 1,127 cases (108 males, 1,019 females, from 1967 to 1982) of subacute thyroiditis in northern Japan was obtained through a questionnaire. It was found that the usual age for the disease was forty, that females predominated in a ratio of 10.6:1, and that the prevalent month was July. In clinical features, the frequencies of the inflammatory symptoms were high in the acute phase of the disease, and the frequencies of hyperthyroid symptoms increased with the progress of the disease. According to the course of the disease (days after the onset without treatment), the patients were divided into seven subgroups, such as 1 approximately 7 days, 8 approximately 14 days, 15 approximately 21 days, 22 approximately 28 days, 29 approximately 42 days, 43 approximately 56 days and over 57 days, respectively. Compared with the 1 approximately 7 days group, the erythrocyte sedimentation rate, serum T4 and T3 concentrations in the 15 approximately 21 days group showed a significant increase from 64 +/- 35 to 75 +/- 30 mm/h (p less than 0.001), 14.6 +/- 5.5 to 17.6 +/- 5.6 micrograms/100 ml (p less than 0.001) and 218 +/- 124 to 263 +/- 109 ng/100 ml (p less than 0.05), respectively, but the BMR showed as insignificant increase from 20 +/- 15 to 24 +/- 14%. The 24-hr 131I-thyroid uptake and resin sponge uptake (RSU) in the 21 approximately 28 days group were 1.2 +/- 1.5% and 35.1 +/- 6.7%, respectively; the former was significantly lower (p less than 0.02) and the latter was insignificantly higher than the values (2.0 +/- 2.6% and 33.9 +/- 7.9%, respectively) in the 1 approximately 7 days group. The recovery time in the steroid-treated group was 57.2 +/- 47.6 days, which showed a statistically insignificant difference from 64.8 +/- 50.5 days of the sodium salicylate-treated group. But the recovery time of 78.2 +/- 64.9 days in other anti-inflammatory drug-treated groups was significantly longer than that of the steroid and sodium salicylate-treated groups (p less than 0.001 and p less than 0.05). Among 9 viral diseases, such as measles, varicella, erythema infection, hand-foot and mouth disease, rubella, mumps, influenza, epidemic keratoconjunctivitis and acute hemorrhagic conjunctivitis observed in northern Japan and Miyagi prefecture in the past 4 years, mumps, hand-foot and mouth disease and epidemic keratoconjunctivitis were prevalent in summer.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1985

Long-term high frequency transcutaneous electrical nerve stimulation (hi-TNS) in chronic pain. Clinical response and effects on CSF-endorphins, monoamine metabolites, substance P-like immunoreactivity (SPLI) and pain measures.

Eighteen patients with chronic pain syndromes of organic origin were treated by means of high frequency transcutaneous nerve stimulation (hi-TNS). The CSF levels of receptorassayable Fraction I and II endorphins, substance P-like immunoreactivity (SPLI), and the monoamine metabolites 5-HIAA, HVA and MOPEG were measured before and after one week of daily treatment. Furthermore, the effects on experimental pain measures were determined. The therapeutic effect was evaluated after 30 days and 3 months of treatment. Patients with low initial concentrations of endorphins in CSF, lower than those observed in healthy volunteers, tended to have the best response to hi-TNS. There were significant increases in Fraction I endorphins and SPLI in CSF, most pronounced in the patients who responded. There were no significant changes in 5-HIAA, HVA or MOPEG in CSF. However, in early responders, the serotonin metabolite 5-HIAA tended to decrease as contrasted to an increase in non-responders. The difference between the groups was statistically significant. Confirming our earlier studies, the therapy induced changes in pain measures showed a significant, positive correlation with increasing Fraction I endorphins in CSF. Our results suggest that hi-TNS induces central changes in the endorphinergic, serotonergic and possibly substance-P-ergic systems.

Adult↗