Biomedical subjects

T Onaya

Publications and source records attributed to T Onaya.

At least 145 records · Page 8Linked to original sources

PubMed1990

Serum IgG from an autoimmune prone mouse C3H/HeJ-gld/gld supports the interleukin-3-dependent cell line through an autocrine mechanism.

C3H/HeJ-gld/gld(C3H/gld) mice have been shown to develop massive lymphadenopathy with autoimmunity. In this study, we tested whether C3H/gld-IgG supports the growth of the IL-3-dependent cell line, FDC-P2/185-4. Serum IgG from C3H/gld mice stimulated FDC-P2/185-4 cells to proliferate. On the other hand, IgG from C3H/HeJ-+/+ did not show such activity. This activity increased with age in both sexes of C3H/gld mice. It was suggested that a monomeric IgG component was responsible for the proliferative activity of C3H/gld mouse sera. The cell-induced growth required Fc gamma receptors on FDC-P2/185-4 cells. FDC-P2/185-4 cells stimulated with C3H/gld-IgG, secreted IL-3, and grew by themselves, indicating an autocrine mechanism. Thus, cytokines produced by serum IgG may play an important role in the development of disease in mice bearing the autosomal recessive mutation gld.

Age Factors↗

PubMed1990

Isoliquiritigenin: a new aldose reductase inhibitor from glycyrrhizae radix.

Traditionally in Japan, some kampo medicines (traditional oriental herbal prescriptions) have long been used for the treatment of diabetic neuropathy. We have found that some aldose reductase inhibitors are included among these drugs. We further investigated the components of glycyrrhizae radix, a constituent of some kampo medicines, and isolated six compounds (GUs 9-17). Among these, GU-17, identified as isoliquiritigenin, had the most potent aldose reductase inhibiting activity. Isoliquiritigenin inhibited rat lens aldose reductase with an IC50 of 3.2 x 10(-7) M, using DL-glyceraldehyde as a substrate. It inhibited sorbitol accumulation in human red blood cells in vitro, with an IC50 of 2.0 x 10(-6) M. Isoliquiritigenin, when administered via an intragastric tube to diabetic rats, suppressed sorbitol accumulation in the red blood cells, the sciatic nerve, and the lens as effectively as ONO-2235. These results suggest that isoliquiritigenin may be effective in preventing diabetic complications.

Aldehyde Reductase↗

PubMed1990

Anti-platelet action of GU-7, a 3-arylcoumarin derivative, purified from glycyrrhizae radix.

We have purified GU-7, a 3-arylcoumarin derivative, from glycyrrhizae radix, which is a crude drug of kampo herbal medicines. This was identified to be a new chemical compound and was found to have an anti-platelet action. GU-7 inhibited platelet aggregation, phosphorylation of 40K and 20K dalton proteins, inositol 1,4,5-trisphosphate production, intraplatelet calcium increase and phosphodiesterase activity in vitro. The data indicate that GU-7 inhibits platelet aggregation by increasing intraplatelet cAMP concentration. We have already reported the existence of aldose reductase inhibitors in some kampo medicines. In addition to the aldose reductase inhibiting action, anti-platelet action may also explain the mechanism by which kampo medicines are effective to diabetic neuropathy.

Coumarins↗

PubMed1990

Cerebral amyloid angiopathy as a cause of subarachnoid hemorrhage.

Cerebral amyloid angiopathy is a pathologic condition characterized by the deposition of amyloid in the walls of small vessels in the cerebral cortex and meninges. Intracerebral hemorrhage is common in persons with this condition, but pure subarachnoid or subdural hemorrhage is rarely seen. Recently, the existence of two types of amyloid proteins related to cerebral amyloid angiopathy, beta protein and cystatin C, has been reported, and immunohistochemical methods using antisera to these proteins have become available. We describe a patient with fatal subarachnoid hemorrhage presumably caused by beta protein-type cerebral amyloid angiopathy, which was demonstrated immunohistochemically by using a monoclonal antibody to a synthetic peptide corresponding to residues 8-17 of beta protein. We suggest that beta protein-type cerebral amyloid angiopathy is a possible etiologic factor in subarachnoid hemorrhage of unknown cause.

Aged↗

PubMed1990

Cloning of malignantly transformed rat thyroid (FRTL) cells with thyrotropin receptors and their growth inhibition by 3',5'-cyclic adenosine monophosphate.

Differentiated rat thyroid cells, designated FRTL, are totally dependent on TSH for their growth. We continuously cultured FRTL cells in the absence of TSH and found that another type of cell appeared in the culture. The new cells were large, flattened and epithelial-like, and none of them exhibited thyroglobulin immunoreactivity. Since they grew independently of TSH, we further cloned these mutated cells by the limited dilution method in the absence of TSH. cAMP production in the cloned cells (FRTL-Tc) was stimulated dose-dependently by TSH. The TSH concentration that produced a maximal level of cAMP in FRTL-Tc cells was 1 order of magnitude higher than in FRTL cells. A [125I]TSH binding study confirmed that the FRTL-Tc cells had TSH receptors with the same binding capacity but a higher Kd than those of FRTL cells. A [125I]cyanopindolol binding study revealed that the FRTL-Tc cells had acquired beta 2-adrenergic receptors and that isoproterenol or epinephrine could stimulate cAMP production in the cells. TSH or beta-adrenergic agonists inhibited the growth of these cells, as did (Bu)2cAMP. When FRTL-Tc cells were transplanted into the sc tissue in Fisher rats, they grew as a tumor in all of the animals (n = 10). Metastasis of the tumors to the lung and liver occurred. These results indicate that FRTL-Tc cells are malignantly transformed cells with TSH receptors derived from thyroid epithelial cells and also suggest that the role of cAMP in the proliferation of the transformed cells might be different from that in normal cells.

Adenylyl Cyclases↗

PubMed1990

Characterization of alpha 1-adrenergic receptor subtypes linked to iodide efflux in rat FRTL cells.

We have characterized alpha 1-adrenergic receptor subtypes in functional rat thyroid cells, FRTL, with relation to iodide efflux, and have also examined the effect of TSH on alpha 1 receptor subtypes. FRTL cells grown in a medium containing 5 mU TSH/ml (6H cells) had five times the number of alpha 1 receptors of those maintained in TSH-free medium (5H cells) (11.2 fmol/10(6) cells compared with 2.0 fmol/10(6) cells). Pretreatment with chlorethylclonidine (CEC; 10 mumols/l), which inactivates only alpha 1b receptors, caused 98.8% and 97.0% decreases in the density of specific [3H]prazosin-binding sites in 5H and 6H cells respectively. LIGAND computer program analysis of the displacement curves for 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4 benzodioxane (WB4101) showed that FRTL cells contained mostly low-affinity WB4101 sites. Using the phenoxybenzamine inactivation method, we found a linear relationship between alpha 1 receptor density and the cytosolic free Ca2+ concentration response in FRTL cells. Pre-exposure of intact FRTL cells to CEC caused a 98.7% decrease in noradrenaline-stimulated maximal increase in cytosolic free Ca2+. Also, CEC and 3,4,5-trimethoxy-benzoic acid 8-(diethylamino) octyl ester (TMB-8), but not nicardipine, inhibited noradrenaline-stimulated iodine efflux. The results suggest that FRTL cells contain mostly the alpha 1b-adrenergic receptor subtype; that the alpha 1b receptors mediate cytosolic free Ca2+ and iodide efflux responses, and that TSH enhances these responses by increasing the alpha 1b receptor density without affecting the post-receptor mechanism.

Animals↗

PubMed1990

Thyrotrophin increases the alpha 1b-adrenergic receptors in rat thyroid gland in vivo.

Using chlorethylclonidine (CEC), an alpha 1b-adrenergic receptor-selective antagonist, we characterized alpha 1-adrenoceptor subtypes in rat thyroid gland, and investigated the effect of methimazole (MMI)-induced high TSH levels on alpha 1 receptor subtypes and noradrenaline-induced iodide organification. The density of thyroid alpha 1-adrenergic receptors was increased about sixfold in rats treated with MMI for 3 weeks compared with controls. Pretreatment of thyroid membrane preparations with CEC (10 mumol/l) caused an 83% decrease in specific 2-[beta-(hydroxy-3-[125I]iodophenyl) ethylaminomethyl]tetralone binding sites in MMI-treated rats, but only a 43% decrease in control rats. The density of CEC-insensitive alpha 1 receptors (alpha 1a) was similar in MMI-treated and control rats, so MMI was shown to increase CEC-sensitive alpha 1 receptors (alpha 1b). Noradrenaline-stimulated iodide organification was threefold greater in MMI-treated rats than in control rats when values were expressed as a per cent increase over basal levels. Pretreatment of thyroid lobes with 10 mumol CEC/l for 30 min caused a 66% decrease in maximal noradrenaline-induced iodide organification in MMI-treated rats, but a significantly lower decrease (49%) in control rats. These results suggest that the rat thyroid gland contains both alpha 1a and alpha 1b receptors, both of which mediate noradrenaline-induced iodide organification, and also that TSH enhances noradrenaline-induced iodide organification by increasing alpha 1b receptor density.

Adrenergic alpha-Antagonists↗

PubMed1990

Clinical significance of erythrocyte sorbitol-blood glucose ratios in type II diabetes mellitus.

The polyol pathway has been implicated in the pathogenesis of diabetic complications. To determine the activity of the polyol pathway, the ratio of erythrocyte sorbitol to blood glucose, which reflects aldose reductase activity, was evaluated in 329 patients with type II (non-insulin-dependent) diabetes mellitus and in 100 nondiabetic age-matched control subjects. Although erythrocyte sorbitol levels were markedly elevated, sorbitol-glucose ratios were significantly lower in diabetic patients than in nondiabetic subjects. Sorbitol-glucose ratios in diabetic patients decreased progressively as blood glucose and hemoglobin A1c (HbA1c) levels increased. Sorbitol-glucose ratios were also studied during a 75-g oral glucose tolerance test. Ratios were again lower in diabetic patients than those in nondiabetic subjects and significantly decreased 120 min after glucose loading. The ratio in diabetic patients also fell with increasing age of the patients. In diabetic patients with neuropathy, retinopathy, or nephropathy, however, sorbitol-glucose ratios were significantly higher than in those without these complications; ratios increased further as complications became more severe. Our findings suggest that the affinity of aldose reductase for glucose in patients with diabetic complications may be increased and that the polyol pathway is implicated in the pathogenesis of diabetic complications.

Biomarkers↗

PubMed1990

Transcriptional regulation of messenger RNA for ferritin heavy chain by thyrotropin.

Thyrotropin increased the steady state levels of ferritin heavy chain messenger RNA in cultured Fisher rat thyroid (FRTL5) cells by about 2.5-fold. Thyrotropin also stimulated the transcription rate of ferritin H gene determined by "nuclear run-on" assay by roughly the same extent as mRNA levels. Thyrotropin showed no effect on the stability of the ferritin heavy chain mRNA, which was suggested using actinomycin D. The results suggest that thyrotropin increases ferritin heavy chain mRNA expression in FRTL5 cells by affecting the step of transcription.

Animals↗

PubMed1989

Localized myxedema on the nasal dorsum in a patient with Graves' disease: report of a case.

We report the case of a 56-year-old Japanese female with Graves' disease associated with localized myxedema on the nasal dorsum. The patient developed localized myxedema concomitantly with hyperthyroidism before antithyroid therapy was given. The lesion was totally removed surgically, as it was small and well circumscribed. Although unusual locations of localized myxedema have been reported elsewhere, there is to date no case of localized myxedema on the nasal dorsum without involvement of the pretibial area reported in the literature. We discuss this unique feature of our patient.

Autoantibodies↗

PubMed1989

The effects of sex hormones on the synthesis of prostacyclin (PGI2) by vascular tissues.

The effects of estradiol and testosterone on prostacyclin (PGI2) release (measured as 6-keto-PGF1 alpha) by vascular tissues using rat aortic rings and cultured rabbit aortic smooth muscle cells (SMC) were investigated. Aortic SMC were prepared from either explants of atherosclerotic intima or those of normal media. Aortic rings obtained from male and female rats which had been treated with estradiol resulted in increased PGI2 synthesis. Furthermore, PGI2 synthesis by cultured medial SMC was significantly increased in the presence of estradiol (10(-7), 10(-9) M). An increased tendency in PGI2 synthesis was also observed in intimal SMC. On the other hand, aortic rings obtained from female rats treated with testosterone resulted in a significant decrease in PGI2 synthesis. However, aortic rings from testosterone-treated male rats and cultured medial and intimal SMC treated with testosterone (10(-6), 10(-8) M) for 48 hr did not show any significant changes in PGI2 synthesis. We also found greater PGI2 synthesis by intimal SMC compared with that by medial SMC. These results suggest that estradiol and testosterone may have opposite functions in the development of atherosclerosis, that is, estradiol for anti-atherosclerotic and testosterone for atherogenic, by modulating PGI2 synthesis by vascular tissues.

Animals↗

PubMed1989

Effect of insulin on the production of prostacyclin and cell proliferation in cultured smooth muscle cells.

We have investigated the effects of insulin on the synthesis of prostacyclin and cell proliferation in cultured vascular smooth muscle cells, which have been thought to play important roles in the development of atherosclerosis. Prostacyclin was measured as 6-keto-PGF1 alpha in the culture medium, and cell proliferation as incorporation of [3H]thymidine into DNA. Our studies showed that insulin reduced production of prostacyclin and stimulated cell proliferation in SMC. Like insulin, dibutyryl cAMP inhibited the production of prostacyclin, whereas it did not stimulate cell proliferation. No significant changes in cAMP levels were found on the addition of insulin into the culture medium. Therefore, cAMP does not appear to be involved in the mechanisms of these insulin effects. These results again suggest that hyperinsulinemia could be one of the important factors in atherosclerosis.

1-Methyl-3-isobutylxanthine↗

PubMed1989

The existence of aldose reductase inhibitors in some kampo medicines (Oriental herb prescriptions).

Traditionally in Japan, some kampo medicines which contain Glycyrrhizae radix (GR) and Paeoniae radix (PR) have long been used for the treatment of diabetic neuropathy. Since we have previously shown that GR und PR have potent aldose reductase inhibitory activities, we further investigated the constituents of these two. The boiled water extract of GR was applied to Sephadex LH-20 column chromatography and 6 fractions (Frs. A, B, Cs, Cp, D, and E) were obtained. Frs. Cp and D were retreated in the same manner and 7 pure compounds (GUs 1-7) were obtained. The boiled water extract of PR was fractionated with ethyl acetate followed by n-butanol and 3 fractions (Frs. 1-3) were collected. Fr. 1 was retreated in the same manner and 2 pure compounds (PRs 1 and 2) were obtained. Among the GU compounds, GU-2 was the most potent inhibitor of rat lens aldose reductase (RLAR) by inhibiting 86% at the concentration of 1.0 microgram/ml. The IC50 of GU-2 was 7.2 x 10(-7) M. Furthermore, GU-2 markedly inhibited sorbitol accumulation in human red blood cells, having an IC50 of 2.9 x 10(-5) M. GU-5 and PR-1 also inhibited RLAR (IC50: 5.6 x 10(-7) M and 6.3 x 10(-7) M, respectively). The structures of GU-2, GU-5, and PR-1 were identified as isoliquiritin, licuraside, and 1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

PubMed1989

Enhancement of the activity of thyroid-stimulating antibodies by anti-human IgG antibodies in vitro.

In an attempt to determine whether or not anti-human IgG antibodies could influence the activity of thyroid-stimulating antibodies (TSAb), we investigated the effects of anti-human Fc antibody (anti-Fc antibody) and IgG from rheumatoid arthritis patients (RA-IgG) on TSAb activity using FRTL-5 cells. It was found that these anti-human IgG antibodies enhanced the TSAb activity in vitro. FRTL-5 cells were first incubated with Graves' disease IgG for 30 min at 37 degrees C, then washed and incubated in Hanks' balanced salt solution with anti-human IgG antibodies for 60 min at 4 degrees C, and then for a further 120 min at 37 degrees C. The level of cAMP accumulated in the medium was determined by RIA. Anti-Fc antibody significantly augmented the cAMP formation stimulated by 16 out of 24 Graves' IgGs, whereas anti-F(ab')2 antibody did not potentiate cAMP accumulation. Three of five RA-IgGs, which are usually defined as specific antibodies for the Fc fragment of human IgG, mimicked these stimulatory effects. Protein A also potentiated the cAMP formation stimulated by Graves' IgGs. Furthermore, there was a significant correlation between the TSAb titres of these Graves' IgGs and the potentiating effects of anti-Fc antibody (r = 0.495, P less than 0.05, n = 21). These results suggest that the interaction of TSH receptor antibody with anti-human IgG antibodies might modulate thyroid function in Graves' disease.

Antibodies, Anti-Idiotypic↗

PubMed1989

Blotting method using nitrocellulose sheets for immunohistochemical detection of soluble thyroid antigens.

We introduce a new method for immunofluorescence detection of soluble material by blotting unfixed antigens onto nitrocellulose (NC) sheets. Human thyroid sections cut with a cryostat were mounted on NC sheets instead of glass slides and were air-dried. They were stained by immunofluorescence techniques, using autoantibodies to thyroid antigens obtained from 13 patients with chronic thyroiditis. The structures of the follicle lumen and epithelium were visualized by localization of specific antibodies. This tissue-blotting method sensitively detected soluble antigens, such as thyroglobulin, which are difficult to detect by conventional methods.

Antigens↗

PubMed1989

Isolated ACTH deficiency associated with transient thyrotoxicosis and hyperprolactinemia.

A 43-year-old woman with isolated ACTH deficiency in association with transient thyrotoxicosis is reported. The initial evaluation revealed that plasma ACTH and cortisol did not respond to corticotropin-releasing hormone (CRH) in the presence of hyperthyroxinemia and hyperprolactinemia. During the replacement therapy with dexamethasone, she developed transient hypothyroxinemia with persistent hyperprolactinemia. Although thyroid open biopsy did not show any evidence of autoimmune thyroiditis or subacute thyroiditis, the data appear to provide other evidence of a possible relationship between acute adrenal insufficiency and transient thyroid dysfunction.

Adrenocorticotropic Hormone↗

PubMed1989

[An autopsy case of multiple system atrophy with many senile plaques].

A 60 year-old man was admitted to our hospital because of gait disturbance and dizziness. At 57 years of age, he noticed his walking unstable. After then, he had dizziness due to orthostatic hypotension, urinary difficulty, loss of livid, and forgetfulness. Neurological examination revealed he had severe orthostatic hypotension, cerebellar ataxia, dysarthria, hyperreflexia of four limbs, myoclonus of right leg, and atonic bladder. His brain CT showed cerebellar atrophy. Thereafter he had recurrent syncopic attacks. His gait disturbance progressed steadily, so he became bedridden. In his terminal stage, his limbs showed rigidity. About 3 years later he died of pneumonia and sepsis. At autopsy brain weighted 1,230 g. Glossly the putamens was bilaterally shrunken, the color of the substantia nigra and locus ceruleus became pale. Base of the pons and the cerebellum were atrophic. Microscopical examination confirmed the degeneration of striato-nigral and olivo-ponto-cerebellar systems without Lewy body. In the spinal cord there was depletion of neuronal cells in the intermediolateral nuclei and Onufrowitz nuclei. In addition to the conventional neuropathological staining methods, we performed the immunohistochemical studies using monoclonal antibody against synthetic peptide of beta protein which detected senile plaque of every stages with formic acid pretreatment, and compared to the modified Bielschowsky method and Congo red method. Our case showed many very primitive and primitive senile plaque in neocortices and hippocampal region. A few neurofibrally tangle were seen in hippocampus. We supposed our case might combine multiple system atrophy and Alzheimer' pathology.

Alzheimer Disease↗

PubMed1988

The mechanism for the inhibitory action of N-(3',4'-dimethoxycinnamoyl)anthranilic acid (tranilast) on the release reaction in platelets.

The molecular basis for the inhibitory action of the antiatopic drug, N-(3',4'-dimethoxycinnamoyl)anthranilic acid (Tranilast), on the thrombin-induced release of a lysosomal enzyme, beta-N-acetylglucosaminidase, from washed rabbit platelets was investigated. Tranilast dose dependently increased cyclic AMP and cyclic GMP levels in thrombin-stimulated platelets, parallel with the inhibition of beta-N-acetylglucosaminidase release. There was no significant effect of Tranilast on adenylate or guanylate cyclase activity. Tranilast inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterases in a cell-free system. The data suggest that the inhibitory action of Tranilast on the release reaction in platelets was due at least in part to inhibition of cyclic nucleotide phosphodiesterases followed by an elevation of cyclic AMP and cyclic GMP levels.

Acetylglucosaminidase↗