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Biomedical subjects

Y Hiyama

Publications and source records attributed to Y Hiyama.

At least 37 records · Page 2Linked to original sources
PubMed1990

The effect of treatment with interferon-gamma on type II collagen-induced arthritis.

We have investigated the effects of recombinant murine interferon-gamma (rIFN-gamma) on type II collagen-induced arthritis (CA) in DBA/l mice. Therapeutic as well as prophylactic treatment with subcutaneous rIFN-gamma, at 10(5) U/mouse six times a week, inhibited the development of CA without any obvious side effects. The accompanying suppression of anti-CII antibody responses may partly explain the inhibition of CA by rIFN-gamma. The possible role of the anti-inflammatory effect of systemic IFN-gamma in the inhibition of CA is discussed.

Animals↗
PubMed1990

Effects of interferon gamma on cultured synovial cells from patients with rheumatoid arthritis: inhibition of cell growth, prostaglandin E2, and collagenase release.

The effects of recombinant interferon gamma (rIFN gamma) on the in vitro growth of adherent synovial fibroblast-like cells from patients with rheumatoid arthritis (RA) and also on the release of prostaglandin E2 and collagenase from these cells stimulated with recombinant interleukin-1 beta (rIL-1 beta) were investigated. The growth of adherent synovial cells from six of nine samples, determined by [3H]thymidine incorporation, was inhibited by rIFN gamma in a manner dependent on dose. The release of prostaglandin E2 and collagenase from adherent synovial cells stimulated with rIL-1 beta was also suppressed by rIFN gamma in all samples tested, though the basal release of these inflammatory mediators was little influenced. No apparent correlation between inhibition of proliferation by rIFN gamma and either inhibition by rIFN gamma of rIL-1 beta stimulated prostaglandin E2 release or the endogenous synthesis of prostaglandins was found.

Arthritis, Rheumatoid↗
PubMed1990

[Effect of KP-136 on allergic paw edema in the rat].

The pharmacological properties of KP-136, an inhibitor of type I allergy, were studied in rat paw models. In four allergic responses, three of the immediate type and one delayed type, KP-136 (p.o.) produced potent inhibitions on the mast cell-mediated type I allergy (ID30: 1.0 mg/kg) and the neutrophil-infiltrated passive Arthus reaction (ID30: 1.6 mg/kg). In addition, KP-136 (10 mg/kg, 50 mg/kg, p.o.) inhibited the injury of bone tissues in rat adjuvant arthritis, confirming that it was effective on the allergic inflammation with tissue injury. Although KP-136 was a weak inhibitor of carrageenin-induced paw edema, prostaglandin synthesis and complement-mediated hemolysis, the compound inhibited the release of lysosomal enzymes such as lysozyme and beta-glucuronidase in the passive Arthus reaction, suggesting the blockage of inflammatory mediator release for its mode of action.

Animals↗
PubMed1989

Effect of 8-hexyloxy-3-(1H-tetrazol-5-yl)-2H-chromen-2-one [KP-136] on experimental asthma: a comparison with disodium cromoglycate.

The pharmacological properties of 8-hexyloxy-3-(1H-tetrazol-5-yl)-2H-chromen-2-one, KP-136 were compared with those of an antiallergic medicament, disodium cromoglycate (DSCG) in experimental asthma models. KP-136 (0.125-1 mg/kg i.v., 0.5-2 mg/kg p.o.) produced a dose-dependent inhibition to allergic asthma of rats and was more potent than DSCG (1-5 mg/kg i.v.). KP-136 (1 mg/kg, i.v.) was also effective on allergic asthma of guinea pigs, although DSCG was ineffective even at a high dose of 50 mg/kg (i.v.). In rats, both KP-136 and DSCG significantly blocked the reduction of histamine content of the trachea after allergic asthma and inhibited the antigen-induced histamine release from lung fragments (KP-136 0.5 micrograms/ml, DSCG 50 micrograms/ml) and peritoneal exudate cells (KP-136 0.1 micrograms/ml, DSCG 10 micrograms/ml). KP-136 also showed relaxation activity for isolated guinea pig trachea at high doses of 2 and 5 micrograms/ml. The major mechanism of the potent antiasthmatic activity of KP-136 is postulated to be the blocking of bronchoactive mediator release. The relaxation of smooth muscle is also suggested to be an additive mechanism.

Animals↗
PubMed1989

[Pharmacological studies of a non-steroidal analgesic and antipyretic drug of LFP83].

Pharmacological properties of LFP83, a non-steroidal analgesic and antipyretic drug, were studied in mice, rats and rabbits. LFP83 is a prodrug of flurbiprofen (FP) which is its active major metabolite in vivo. In experimental models of acetic acid writhing, the Randall and Selitto method, arthritic pain, yeast fever, LPS fever, carrageenin edema and adjuvant arthritis, LFP83 (i.v.) showed remarkable analgesic, antipyretic and antiinflammatory activities; and it was more potent than ketoprofen (i.m.) and aspirin DL-lysine (i.v.). The analgesic activity of LFP83 was equal to or more potent than that of pentazocine, and its duration was longer than those of aspirin DL-lysine and pentazocine. In addition, the analgesic potency of LFP83 was approximately the same or more potent than that of FP (p.o.), and the onset of this analgesic effect began earlier. On the other hand, the ulcerogenic activity of LFP83 on rat gastric mucosa was less than that of FP (p.o.) in both single and consecutive (7 days) administrations. The safety index (UD50/ED50) of LFP83 was three to ten-fold higher than that of FP (p.o.). As mentioned above, LFP83 is a potent analgesic, antipyretic and antiinflammatory drug; and in comparison to oral FP, it has a more potent and immediate effect, weak gastric irritation and high safety index.

Analgesics↗
PubMed1989

[Effects of antiinflammatory agents on rat paw tuberculin response].

A marked tuberculin response as well as carrageenin edema were induced in rat hind paw to compare the effects of antiinflammatory agents on these responses. Non-steroidal antiinflammatory agents such as diclofenac and piroxicam were very weak inhibitors of the paw tuberculin response. These agents showed only a slight inhibitory effect on tuberculin response even at doses that were four to five times larger than the 50% effective doses for inhibiting carrageenin edema. On the other hand, steroidal antiinflammatory agents, dexamethasone and prednisolone, showed potent inhibitory effects on the paw tuberculin response at the 50% effective doses for inhibiting carrageenin edema. The above findings clearly revealed the difference in characters between non-steroids and steroids by comparing their effects on tuberculin response and carrageenin edema. The different properties of two classes of antiinflammatory drugs may be of significance in evaluating the effect of antiinflammatory agents on delayed-type hypersensitivity.

Animals↗
PubMed1989

Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-bu tyric acid.

Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-buty ric acid (C4C) were studied. C4C is an active principal metabolite of an orally effective antiallergic agent, KP-136. C4C (0.2-1 mg/kg, i.v.) markedly inhibited the mast cell-mediated homologous PCA of rats and the experimental allergic asthma of rats and guinea pigs, although it had almost no effects on heterologous PCA and compound 48/80-induced cutaneous response in rats. C4C (0.2 mg/kg, i.v.) was scarcely effective on cutaneous responses induced by intradermal injection of histamine and serotonin which are principal chemical mediators of rat homologous PCA, and it blocked the decrease of skin histamine content after the PCA. In addition, C4C (0.01-0.5 micrograms/ml) inhibited the increase of 45Ca uptake of mast cells, the histamine release and the degranulation induced by the antigen-antibody interaction. These effects of C4C were much the same as those of KP-136. From the above findings, C4C is considered to be an antiallergic agent that inhibits the mast cell activation by blocking the calcium influx, and it shares similar pharmacological properties with KP-136.

Animals↗
PubMed1988

[Characterization of thyroglobulin and thyroid peroxidase activity in patients with functioning thyroid benign tumors].

The content and chemical and immunological properties of thyroglobulin (Tg) and the activity of thyroid peroxidase (TPO) were studied in nodular and extranodular (periphery) thyroid tissue from patients with functioning thyroid tumors (hot nodules). From the present observations, the tumor extracts contained fairly large amounts of Tg, similar to that in the periphery tissue, while the content of Tg was markedly decreased in non-functioning thyroid tumors (cold nodules). The iodine content of Tg was significantly higher in nodular tissue compared with periphery tissue. These observations were in contrast to the results seen in the cold nodules in which hormone synthesis was defective. On the nature of carbohydrate moiety as compared with normal tissue, oligosaccharides of Tg from the periphery tissues changed in a manner similar to that of tumor oligosaccharides. That is, high-mannose type oligosaccharides were markedly decreased whereas multiantennary and unidentified oligosaccharides were increased. These observations were similar to those of non-functioning tumors. The content of sialic acid decreased markedly both in the tumor and periphery tissues. Immunologically, Tg preparations of the tumor and periphery tissue did not show the same affinity to the antibodies, depending on the content of iodine. Therefore, it seems that the contribution of the iodine content and iodo-amino acid has little or no significance in the heterogeneous nature of Tg-immunogenecity. Benign tumors and the periphery tissue were subjected to assay for thyroid peroxidase activity by the method employing guaiacol as the second substrate. The specific activities of the tumors were generally higher than those of periphery tissues, both in functioning and non-functioning benign tumors. In non-functioning carcinoma, on the other hand, TPO activities were lower in tumor portions than in periphery portions. This indicates that non-functioning thyroid carcinomas have a different characteristic.

Adenoma↗
PubMed1988

The protective effect of a new antiallergic agent, KP-136 on mast cell activation: a comparison with disodium cromoglycate.

The protective effects on mast cell activation were compared between a new antiallergic agent, KP-136 and disodium cromoglycate (DSCG), both of which inhibited the immunological degranulation of rat peritoneal mast cells. The IC50 was 0.03 micrograms/ml for KP-136 and 4.7 micrograms/ml for DSCG. KP-136 predominantly acted on the early stage of mast cell activation processes and inhibited the immunological increase in 45Ca uptake. KP-136 also inhibited A23187- and heat-induced degranulation and heat-induced hemolysis. In addition, KP-136 was effective on phospholipase A2-induced degranulation, although the compound did not directly affect the enzyme activity. In all tests for comparison, KP-136 and DSCG had similar profiles of action and the parallel experiments indicated that KP-136 was a more potent inhibitor of mast cell activation than DSCG, having a DSCG-like membrane stabilizing activity.

Animals↗
PubMed1988

Thyroglobulin and thyroid peroxidase share common epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis.

Monoclonal antibodies specific for human thyroid peroxidase (TPO) were prepared by the hybridoma technique using hyperimmune spleen cells from mice immunized with TPO purified from thyroid glands from patients with Graves' disease. Use of the microenzyme-linked immunosorbent assay method revealed that some of the monoclonal antibodies cross-reacted strongly with human thyroglobulin (Tg). Conversely, monoclonal anti-Tg antibodies cross-reacted with TPO, albeit to a lesser degree. Some anti-Tg autoantibodies in serum from patients with chronic autoimmune thyroiditis purified by Tg affinity chromatography bound TPO, and such binding was completely inhibited by Tg. Western blotting experiments revealed that thyroid microsomal 103K proteins recognized by mouse monoclonal and polyclonal anti-TPO antibodies were recognized by some monoclonal anti-Tg antibodies and anti-Tg autoantibodies, and conversely, that 19S Tg was recognized by some monoclonal anti-TPO antibodies. TPO was immunoprecipitated by anti-Tg autoantibodies isolated by Tg affinity chromatography. On the other hand, the specificity for TPO of the anti-Tg autoantibodies was not identical with that of anti-TPO autoantibodies. These cross-reactivities were not due to contamination of TPO with Tg or vice versa, or to contamination of the anti-Tg autoantibody preparations with anti-TPO autoantibodies. Taken together, these data indicate that Tg and TPO share common antigenic determinants and that some of those determinants are recognized by autoantibodies in the serum of patients with chronic autoimmune thyroiditis.

Adolescent↗
PubMed1987

Molecular dynamics of collagen side chains in hard and soft tissues. A multinuclear magnetic resonance study.

We have prepared samples of (a) intact calvaria collagen (cross-linked and mineralized), (b) intact tendon collagen (cross-linked but not mineralized), and (c) reconstituted chick calvaria collagen (not cross-linked and not mineralized) containing [methyl-2H3]methionyl, [4,4-2H2]pyrrolidinyl, (4-fluorophenyl)alanyl, and [6-15N]lysyl residues. Using multinuclear magnetic resonance spectroscopy, we have investigated the molecular dynamics of the labeled amino acids. Guided by model compound studies, we reached the following conclusions regarding collagen side chain dynamics from our analysis of line shapes and relaxation rates. At 22 degrees C, imino residues in all samples have flexible rings with root mean square angular fluctuations in the 11-30 degree range. Nearly all labeled amino acid side chains reorient about at least two side chain single bonds. At temperatures below -30 degrees C, most of these side chain motions are absent in all the samples. Surprisingly, in contrast with results obtained for backbone motions, side chain motions are only marginally more hindered in mineralized samples as compared with nonmineralized samples, a result we discuss with reference to collagen-mineral interactions. We also discuss the possible relationship between collagen dynamics and function.

Achilles Tendon↗
PubMed1987

[The pharmacological properties of a new anti-allergic agent, KP-136, in cutaneous models].

The pharmacological properties of KP-136 were studied using cutaneous reactions in rats and guinea pigs. KP-136 remarkably inhibited the passive cutaneous anaphylaxis (PCA) with intravenous and oral dosing. However, the inhibitory effect of KP-136 had an apparent species difference. Thus, KP-136 was more effective on rat PCA than that of guinea pig. In four rat cutaneous reactions produced by three allergic reactions and compound 48/80, KP-136 was remarkably effective on two homologous PCA induced by IgE and IgGa. The intravenous and oral doses for 50% inhibition on the PCA were 0.2 mg/kg to 0.4 mg/kg and 0.5 mg/kg to 0.9 mg/kg, respectively. KP-136 was scarcely effective on cutaneous reactions elicited by intradermal injection of histamine and serotonin which are main chemical mediators in rat homologous PCA. However, KP-136 blocked the degranulation of mast cells and decrease of histamine content in skin elicited by the PCA. In addition, KP-136 showed a potent inhibition on the immunological release of histamine from rat peritoneal exudate cells. The concentration for 50% inhibition on the histamine release was 5 ng/ml. These findings indicate that KP-136 is an oral potent inhibitor on PCA, and it acts by blocking the release of chemical mediator(s) from mast cells.

Administration, Oral↗
PubMed1987

[Functional improvement produced by transplantation of fetal neuronal cell suspensions in the rat striatum with 6-hydroxydopamine lesions].

Behavior improvement from apomorphine-induced rotation, morphological features of nerve cells and in vivo release of dopamine (DA) were examined after the implantation of neuronal cell suspensions into the striatum of female rats with 6-hydroxydopamine lesions. Apomorphine-induced rotation was significantly suppressed in 11 out of 26 rats from two through ten weeks after the implantation. In 3 out of 26 rats, the rotation was significantly suppressed for four weeks after the implantation, although the suppression was reversed by the fifth week. In the remaining 12 rats, the rotation was not inhibited after the implantation. Behavior improvement was concurrent with extension of neurites from anti-DA immunopositive cells to the host caudate. Anti-DA cells were very scant in the absence of behavior improvement. In vivo release of DA and the metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, was detected in the perfusates of the striatum of the animals that were functionally improved by the transplant. Methamphetamine caused an increase in DA release and a decrease in the release of the metabolites in those animals. These results suggest that grafted neuronal cells which are sensitive to methamphetamine probably innervate neuronal elements in the host caudate, and the release of DA from these grafted cells functionally affects behavior improvement.

Animals↗