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T Isono

Publications and source records attributed to T Isono.

At least 37 records · Page 2Linked to original sources

Sequence and diversity of rabbit T-cell receptor gamma chain genes.

The nucleotide sequences of one constant (C), six variable (V), and two joining (J) gene segments coding for the rabbit T-cell receptor gamma chain (Tcrg) were determined by directly sequencing fragments amplified by the cassette-ligation mediated polymerase chain reaction. The Tcrg-C gene segment did not encode a cysteine residue for connection to the Tcr delta chain in the connecting region, and two variant forms of the Tcrg-C gene segment were generated by alternative splicing, like the human Tcrg-C2 gene. Five of six rabbit Tcrg-V gene segments belonged to the same family and displayed similarity to five productive human Tcrg-V1 family genes as well as the mouse Tcrg-V5 gene. The remaining rabbit Tcrg-V gene segment displayed similarity to the human Tcrg-V3 gene. Both rabbit Tcrg-J gene segments displayed similarity to the human Tcrg-J2.1 and 2.3, respectively. These findings suggested that the genomic organization of rabbit Tcrg genes is more similar to that of human than of mouse Tcrg genes.

Amino Acid Sequence↗

Absorption and excretion of paeoniflorin in rats.

The absorption and excretion of paeoniflorin after intravenous and oral administration was studied in rats to evaluate the significance of paeoniflorin in the pharmacological action of Paeony root. The plasma concentration of paeoniflorin after intravenous administration at the doses of 0.5, 2.0 and 5.0 mg kg-1 rapidly decreased, simulated by a biexponential curve, with mean terminal half-lives of 11.0, 9.9 and 12.6 min, respectively. The Vdss values were 0.332, 0. 384 and 0.423 L kg-1 and the CLtot values were 26.1, 31.2 and 30.3 mL min-1 kg-1 at each dose. When given orally at the same doses, the absolute bioavailability values (F) determined by the AUC were 0.032, 0.033 and 0.038, respectively. The cumulative urinary and faecal excretions of paeoniflorin at the dose of 5 mg kg-1 after intravenous administration were 50.5 and 0.22% of the dose within 72 h, and 1.0 and 0.08% of the dose after oral administration within 48 h, respectively. Cumulative biliary excretion after intravenous or oral administration at a dose of 0.5 mg kg-1 was 6.9 and 1.3% of the dose within 24 h, respectively. The total CLR and CLB value after intravenous dosing was less than the CLtot value. These findings suggest that paeoniflorin is metabolized in other organs as well as in the liver. We conclude that paeoniflorin absorbed is excreted mainly in urine, it has a low bioavailability and the metabolites may be involved in the pharmacological action of Paeony root.

Absorption↗

Tolerance to the vascular effect of a novel nitric oxide-donating vasodilator, FK409.

We investigated whether tolerance develops to the vasorelaxant effects of a new vasodilator, (+-)-(E)-4-ethyl-2-[(E)-hydroxy-imino]-5-nitro-3-hexenamide (FK409), in isolated canine coronary artery strips and to its hypotensive effect in rats, and whether FK409 activates soluble guanylate cyclase isolated from vascular tissues in the absence of L-cysteine. No tolerance to FK409 (0.46 nM to 0.46 microM or 1-1000 micrograms/kg, i.v.) or cross-tolerance between FK409 and glyceryl trinitrate was demonstrated in in vitro and in vivo experiments, whereas the tolerance to glyceryl trinitrate (0.44 nM to 4.4 microM or 1-1000 micrograms/kg, i.v.) was marked in both conditions. In addition, FK409 (0.1-10 microM) activated soluble guanylate cyclase without L-cysteine, but glyceryl trinitrate (1-100 microM) required the addition of L-cysteine (5 mM) for the activation of the enzyme. The results suggest that FK409 may be advantageous compared to tolerance-producing nitrates currently in clinical use, and that this property of FK409 is probably due to its independence of a sulfhydryl group donor.

Animals↗

Monoclonal antibody E6G6 recognizes glycolipids as a differentiation antigen in Shope carcinoma cells.

Monoclonal antibody E6G6 preferentially reacted with well differentiated and non-tumorigenic Shope carcinoma cell lines but hardly reacted with undifferentiated and tumorigenic lines as determined by enzyme-linked immunosorbent assay, cytofluorometry and the complement dependent cytotoxicity test. Immunohistochemical analysis of the primary carcinoma tissue revealed that the antibody intensely stained keratinizing carcinoma cells with marked shrinkage whereas it did not stain normal epidermal keratinizing rabbit cells or benign tumor (Shope papilloma) cells, suggesting that the antigen expression in vivo was closely correlated with terminal differentiation of the carcinoma cells. Thin layer chromatography immunostaining revealed that the antigen was comprised of several neutral glycolipids and that differentiated cells contained about ten times more antigen than undifferentiated cells.

Animals↗

Sequence and diversity of variable gene segments coding for rabbit T-cell receptor beta chains.

The nucleotide sequences of 11 variable gene segments coding for rabbit T-cell receptor beta (Tcrb-V) chains were determined by directly sequencing fragments amplified by the cassette-ligation mediated polymerase chain reaction (CLM-PCR) and by modified anchor PCR without the cloning procedure. The nucleotide sequences in two of these 11 rabbit Tcrb-V gene segments coincided with those in two of the four rabbit Tcrb-V gene segments previously reported; the others have not been described. The percentage similarity of each nucleotide sequence of the 11 rabbit Tcrb-V gene segments was analyzed and the segments were divided into nine families, which were homologous to nine human families (Vb 2, 3, 4, 5, 7, 8, 10, 18, and 22), respectively.

Amino Acid Sequence↗

Antinociceptive mechanism of the aconitine alkaloids mesaconitine and benzoylmesaconine.

We explored the possible role of the specific regions in the brain stem on the antinociceptive actions of mesaconitine (MA) and benzoylmesaconine (BM) by the microinjection of MA and BM into nucleus reticularis paragigantocellularis (NRPG), nucleus raphe magnus (NRM), and periaqueductal gray (PAG). MA microinjected into NRPG, NRM, or PAG elicited a dose-dependent antinociceptive action, whereas BM injected into NRM or PAG elicited a dose-dependent antinociceptive action but not in NRPG. The NRM appeared to be the most sensitive region among the three tested locations.

Aconitine↗

The analgesic mechanism of processed Aconiti tuber: the involvement of descending inhibitory system.

Tsumura-shuchi-bushi-matsu (TJ-3021) is a processed Aconiti tuber which has a potent antinociceptive action. The present study was undertaken to study the analgesic mechanism produced by TJ-3021. RCS (repeated cold stress) rats in hyperalgesia were markedly suppressed by oral administration of TJ-3021. Intrathecal and intraperitoneal administration of a selective alpha 2-adrenoreceptor antagonist, idazoxan (IDA), reduced significantly the analgesic effect of TJ-3021 in RCS rats. Methysergide (METH), a 5-HT receptor antagonist, demonstrated a similar effect, while intraperitoneal administration of opioid receptor antagonist, naloxone, did not produce the effect. Both oral and intracisternal administration of mesaconitine (MA) which is one of the main potent alkaloids contained in TJ-3021 produced analgesic effect in non-RCS rats.

Aconitine↗

Anti-nociceptive effects of aconiti tuber and its alkaloids.

The anti-nociceptive effect of processed aconiti tuber (TJ-3021), one of the traditional oriental herbal medicines (Kampo), was investigated by utilizing various methods including repeated cold stress and adjuvant articular inflammation in rats and mice. Analgesic potency was compared with that of mesaconitine, a potent component of aconitine alkaloids, and other analgesic agents. It was found that mesaconitine was more potent than morphine, and a processed aconiti tuber [(TJ-3021), Tsumura-shuchi-bushi-matsu] showed some analgesic effect, although it was weaker than those of dichlofenac, aminopyrine and indomethacine.

Acetates↗

Vasorelaxant mechanism of the new vasodilator, FK409.

To define the vasorelaxation mechanism of FK409, we examined the effect of the compound on vascular tension and cyclic nucleotide levels in isolated rat thoracic aorta contracted with norepinephrine, and on activities of guanylate cyclase and cyclic GMP phosphodiesterase prepared from rat or rabbit thoracic aorta. FK409 (1 x 10(-9) to 1 x 10(-6) M), like nitroglycerin (1 x 10(-9) to 1 x 10(-6) M), produced a potent vasorelaxant effect associated with an increase in cyclic GMP content of the tissue. There was no change in cyclic AMP levels. The vasorelaxant effect of FK409 was independent of the integrity of the endothelium, and was unaffected by L-NG-monomethylarginine (0.1 mM) or oxyhemoglobin (1 microM). On the other hand, FK409 (3.2 x 10(-7) M) activated soluble guanylate cyclase, and the activating effect was completely inhibited by oxyhemoglobin (10 nM). Cyclic GMP phosphodiesterase was unaffected by FK409 (1 x 10(-7) to 1 x 10(-5) M). Furthermore, in rat aortic soluble fraction FK409 (3 mM) was found to liberate nitric oxide (NO) which was evaluated spectrophotometrically after diazotization of sulfanilic acid and coupling with N-(1-naphthyl)-ethylenediamine. The liberation occurred even in the absence of L-cysteine (5 mM), in contrast to the case with nitroglycerin (3 mM). These results suggest that the vasorelaxant effect of FK409 is associated with an increase in intracellular cyclic GMP, and that the cyclic GMP accumulation is due to activation of soluble guanylate cyclase. The enzyme activation is probably due to NO released from the compound molecule in the vascular smooth muscle cells.

3',5'-Cyclic-GMP Phosphodiesterases↗

Comparative study of human and rabbit cell infection with cell-free HTLV-I.

Infection of human and rabbit cells with cell-free HTLV-I was studied by PCR analysis. Both human and rabbit PBL were infected similarly by cell-free virus of both human and rabbit cell origin. Cells were infected with the cell-free virus without prior treatment and regardless of the concentration of the culture supernatant containing the virus. Human and rabbit cell lines were also infected similarly by the cell-free virus, the proviral DNA persisting for more than two months. The culture supernatants of HTLV-I-producing cells could thus be a potential cause of laboratory infections.

Animals↗

[Analgesic effect of benzoylmesaconine].

"Tsumura Shuchi-Bushi Powder for Ethical Dispensing" (TJ-3021) is an herbal drug of processed Aconiti tuber that attenuates its toxicity. A greater part of mesaconitine which is regarded as a main analgesic component in processed Aconiti tuber is hydrolyzed into benzoylmesconine (BM) by its processing. In this study, the analgesic effect of BM was examined in comparison with that of TJ-3021 in mice and rats. BM (10 mg/kg, p.o.) depressed the acetic acid-induced writhing significantly. Its analgesic activity was almost similar in magnitude to that of TJ-3021 (300 mg/kg, p.o.). BM (30 mg/kg, p.o.) significantly increased the pain threshold ratio of paw pressure in repeated cold stress (RCS) rats, and its analgesic potency appeared to be equivalent to that of TJ-3021 (1000 mg/kg, p.o.). These results suggest that the analgesic activity of BM is strong enough for explanation of the analgesic effect of TJ-3021, and it might contribute to that of TJ-3021.

Aconitine↗

Effect of FK409, a novel nitric oxide donor, on acute experimental myocardial ischemia.

The anti-ischemic heart effect of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]- 5-nitro-3-hexenamide (FK409), a novel nitric oxide donor, was studied in dog and rat preparations in vivo and in vitro. In anesthetized dogs with partially occluded coronary artery that were subjected to atrial pacing at a constant blood pressure, FK409 (1-100 micrograms/kg, i.v.) suppressed the ST-segment elevation on epicardial electrocardiograms. Glyceryl trinitrate (GTN; 10, 32 micrograms/kg) or dipyridamole (1000 micrograms/kg) failed to suppress the ST-segment elevation, although continuous i.v. infusion of GTN (32, 100 micrograms/kg/min) was effective. FK409 also suppressed the ST-segment elevation induced by methacholine in anesthetized rats by both i.v. (10, 100 micrograms/kg) and intraduodenal (i.d., 100, 1000 micrograms/kg) injections, while GTN (100 micrograms/kg, i.v.; 1000 micrograms/kg, i.d.) was effective only by the i.v. route. FK409 (0.32 microgram/kg/min, i.v.) and GTN (10 micrograms/kg/min) increased the blood flows of the endomyocardium (ENDO) and the epicardium (EPI) and the flow ratio of ENDO/EPI in the ischemic zone in anesthetized dogs with occluded coronary artery. Furthermore, in isolated dog vascular preparations, FK409 (4.6 x 10(-10)-4.6 x 10(-7) M) had a greater vasorelaxing effect on the large coronary artery [2.0-2.5-mm outer diameter (od)] than on the small coronary artery (0.3-0.5-mm od) or the saphenous artery. The results suggest that FK409 protects against acute experimental myocardial ischemia through relaxation of the large conductive coronary artery, and may be a useful oral drug for the treatment of angina pectoris.

Animals↗

Short-term treatment with synchronized coronary venous retroperfusion before full reperfusion significantly reduces myocardial infarct size.

The efficacy of short-term synchronized coronary venous retroperfusion (SRP) before full arterial reperfusion was studied in a canine model. A control group (n = 6) was subjected to 90 minutes of occlusion of the left anterior descending coronary artery, which was followed by 6 hours of reperfusion. In another group (n = 6) the left anterior descending coronary artery was occluded for 2 hours followed by 5.5 hours of reperfusion. In this group SRP was applied for 30 minutes before full reperfusion. Myocardial regional blood flow was measured with the use of colored microspheres. During occlusion of the left anterior descending coronary artery, there was severe myocardial ischemia in both groups. Blood flow in the subendocardial area was, however, significantly better in the SRP group (0.51 +/- 0.17 ml/min/gm after 3.5 hours of reperfusion) than in the control group (0.29 +/- 0.16 ml/min/gm) after 4 hours of reperfusion (p less than 0.05). Left ventricular function was assessed as global ejection fraction from a left ventriculogram. Ejection fraction was reduced during ischemia in both groups (control = 38% +/- 3%, SRP = 32% +/- 8%). This dysfunction remained after 4 hours of reperfusion. Infarct size was assessed by means of triphenyltetrazolium chloride staining. The myocardial area at risk was similar in the two groups (control = 33.1% +/- 5.3%, SRP = 30.6% +/- 6.5%). Infarct size, which was expressed as the percent of the area at risk, was significantly smaller in the SRP group (17.2% +/- 14.6%) than in the control group (36.0% +/- 8.1%; p = 0.0197).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Analgesic effects of Tsumura-shuuji-bushi-matsu and mesaconitine].

"Tsumura-shuuji-bushi-matsu" (TJ-3021) is a herbal medicine produced from Aconiti tuber through autoclaving to decrease its toxicity. In this study, the analgesic effects of TJ-3021 and mesaconitine (MA) was examined in rats and mice. TJ-3021 (300 mg/kg, p.o.) or MA (0.5 mg/kg, p.o.) depressed the acetic acid-induced writhing significantly. In Randall-Selitto's method, TJ-3021 (1000 mg/kg) increased the pain threshold ratio in the inflamed foot significantly but not in the normal foot. In the hot plate method or on adjuvant-induced arthritic pain, TJ-3021 (1000 mg/kg) significantly increased the pain threshold, and its effect was less than that of "nama-bushi-matsu" (TNB), which was produced from the same Aconiti tuber without autoclaving. Repeated cold stress (RCS) for 65.5 hr decreased the pain threshold ratio on the paw pressure in rats by 60%. TJ-3021 (300 mg/kg) significantly increased the pain threshold ratio in RCS rats, and its activity was almost the same degree as that of TNB. MA (0.5 mg/kg) significantly increased the pain threshold ratio in RCS rats or on the adjuvant-induced arthritic pain; and in RCS rats, it was more potent than morphine (1 mg/kg, p.o.).

Aconitine↗

A 5-lipoxygenase inhibitor, FR110302, suppresses airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles in rats.

To study the role of chemical mediators in airway hyperresponsiveness and simultaneous eosinophilia, we examined effects of a potent 5-lipoxygenase inhibitor FR110302 and those of prednisolone, indomethacin, platelet-activating factor (PAF) antagonist (RP-59227) and leukotriene C4 (LTC4) antagonist (ONO-1078) on airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles. Sephadex G200 particles (2.5 mg/kg) were injected intravenously to rats and 3 days later the airway hyperresponsiveness to acetylcholine (ACh) and the eosinophilia in the bronchoalveolar lavage (BAL) fluids were observed. FR110302 (10 mg/kg b.i.d.p.o.) significantly suppressed both of these indicators of asthma. The amounts of immunoreactive LTB4,C4 (i-LTB4, C4) in the BAL fluid were measured by radioimmunoassay. The amounts of i-LTB4,C4 in the FR110302-treated rats were significantly less compared with that in the Sephadex-injected controls. Prednisolone completely inhibited the airway hyperresponsiveness. PAF antagonist and LTC4 antagonist partially inhibited the airway hyperresponsiveness, and indomethacin had no effect. The results indicate that 5-lipoxygenase products play important roles in the Sephadex-induced airway hyperresponsiveness and lung eosinophilia in rats.

Acetylcholine↗

Antitumor effects of vitamin A against Shope carcinoma cells.

The antitumor effects of retinol were tested on three cell lines which were derived from a single Shope carcinoma and differed in their degree of differentiation. Addition of retinol to cultures induced growth retardation and morphological changes of these sublines. On removal of retinol from the culture medium, reversion of the undifferentiated subline was observed, but the two differentiated sublines did not revert. The tumorigenic potential of the differentiated sublines was lost or greatly reduced when they were injected into nude mice after 7 days of culture with retinol, whereas the potential of the undifferentiated subline was only slightly reduced. These results suggest that retinol may be effective against differentiated squamous cell carcinomas, but not against undifferentiated tumors.

Animals↗