Biomedical subjects

T Onaya

Publications and source records attributed to T Onaya.

At least 127 records · Page 7Linked to original sources

PubMed1991

Thyrotropin receptor non-mediated thyroid stimulating immunoglobulin in Graves' disease.

There exists a consensus that hyperthyroid Graves' disease is caused by thyrotropin receptor (TSH-R) autoantibodies. To test the possibility that the TSH-R is the sole antigen for thyroid stimulating antibodies (TSAb), we compared bioactivities of Graves' IgGs between non-thyroid mammalian cells transfected with human TSH-R cDNA and the reference thyroid bioassay. A Graves' IgG with TSH-binding inhibitor immunoglobulin (TBII) activity (89%) markedly stimulated cAMP formation in both CHO-K1 cells transfected with TSH-R cDNA (340 microU/ml of TSH equivalent) and rat thyroid cells, FRTL-5, (410 microU/ml of TSH equivalent). In contrast, a TBII negative (-1.5%) IgG from another patient with Graves' disease showed a strong thyroid stimulating activity (87 microU/ml of TSH equivalent) when FRTL-5 cells were used for the assay. But no stimulating activity was observed in this IgG when CHO-K1 cells transfected with TSH-R cDNA were used, suggesting a possible existence of TSH-R non-mediated thyroid stimulating immunoglobulin in some cases of Graves' disease.

Animals↗

PubMed1991

Rabbit antibodies against two different extracellular domains of human thyrotropin receptor possess thyroid stimulating activities.

We have produced rabbit antibodies against synthetic peptides corresponding to the mid-region (amino acid residues 172-202, C peptide) and to the unique segment near the transmembrane region (amino acid residues 341-370, P peptide) in the extracellular component of the human thyrotropin (TSH) receptor and evaluated their biological activities. Both anti-C peptide antibodies raised in two rabbits showed strong thyroid stimulating activities (TSAb) (4127% and 2548%). Anti-P peptide antibodies raised in two rabbits were also strongly positive for TSAb activities (359% and 3468%). However, none of these antibodies had TSH-binding inhibitor immunoglobulin (TBII) activities. These results suggest that the domains responsible for TSAb are likely to span the entire extracellular component of the TSH receptor.

Amino Acid Sequence↗

PubMed1991

Role of N-terminal region of the thyrotropin (TSH) receptor in signal transduction for TSH or thyroid stimulating antibody.

To identify the site(s) on the thyrotropin (TSH) receptor that interacts with TSH or thyroid stimulating antibody (TSAb), we examined the effect of the synthetic TSH receptor peptide (termed N2 peptide, No. 35-50) on the cAMP accumulation induced by TSH or TSAb. Preincubation of bovine TSH with N2 peptide resulted in a significant and dose-dependent decrease in cAMP accumulation. This decrease was not observed when bovine TSH was preincubated with P1 peptide, which was used as a control (No. 398-417). In contrast, the N2 peptide did not affect TSAb activity in immunoglobulin fractions from three TSAb-positive patients with Graves' disease. P1 peptide also had no effect on TSAb activity. These results suggest that the N-terminal region of the TSH receptor is important for TSH action, and also that TSAb activity cannot be suppressed only by the application of the synthetic peptide corresponding to the N-terminal region.

Animals↗

PubMed1991

Thyroid stimulating activity of rabbit antibodies toward the human thyrotropin receptor peptide.

We have produced antibodies against a peptide corresponding to the unique N-terminal segment (amino acid residues 29-57) in the extracellular domain of the human thyrotropin (TSH) receptor by immunizing it to rabbits, and evaluated for their thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. Antibody raised in rabbit B showed significant TSAb activity but not TSBAb activity. In contrast, antibody raised in rabbit A lacked TSAb activity but possessed TSBAb activity. None of these antibodies had TBII activity. These results indicate that TSH receptor antibody can successfully mimic the action of TSH and also suggest that the N-terminal region of TSH receptor is substantially associated with both TSAb and TSBAb activities, but not parallel to TBII activity.

Amino Acid Sequence↗

PubMed1991

The mRNA levels of thyrotropin receptor, thyroglobulin and thyroid peroxidase in neoplastic human thyroid tissues.

Expression levels of thyrotropin receptor (TSH-R), thyroglobulin (Tg) and thyroid peroxidase (TPO) mRNA in normal and neoplastic human thyroid tissues (6 adenomas and 7 carcinomas) were investigated by Northern-blot and slot-blot analyses. We found that TSH-R mRNA levels were significantly lower in carcinoma tissues than in normal tissues. The levels of Tg mRNA were also significantly lowered in adenoma and carcinoma tissues as compared to normal tissues. In contrast, no significant difference was observed in the expression levels of TPO mRNA between these tissues. Furthermore, TSH-R mRNA levels were well-correlated with Tg mRNA levels in neoplastic tissues. These results suggest that mRNAs of TSH-R and Tg are expressed in relation to their degree of differentiation.

Actins↗

PubMed1991

Development of chicken antibodies toward the human thyrotropin receptor peptides and their bioactivities.

We have synthesized four peptides (P2, P4, E3 and P1) corresponding to different segments of human thyrotropin (TSH) receptor. We have obtained antibodies by immunizing them to chickens, and antibodies are evaluated for their thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. None of the antibodies had TSAb activity. Antibodies against human TSH receptor specific region such as P2 and P4 (P2: No. 372-397, P4: No. 341-358) had TSBAb and TBII activities. Anti-E3 antibody (E3: the third putative extracellular loop, No. 649-661) had only TSBAb activity. Anti-P1 antibody (P1: high homology with pig LH/CG receptor, No. 398-417), however, had none. These results suggest that anti-TSH receptor antibodies to different antigenic epitopes show heterogeneity in their biological activities.

Animals↗

PubMed1991

Distribution of parvalbumin immunoreactivity in the human brain.

The cellular distribution of parvalbumin-like immunoreactivity (PA-LI) in the human brain was investigated by peroxidase-antiperoxidase methods using antiserum to rat skeletal muscle parvalbumin. PA-LI was present in non-pyramidal neurons of the cerebral cortices, stellate cells, basket cells and Purkinje cells in cerebellar cortices, and neurons of some nuclei in human brain stem; the distribution of PA-LI in human brain was very similar to that in rat brain. These results indicate that PA-LI is widely distributed in a specific subpopulation of neurons of the human brain.

Aged↗

PubMed1991

Defects in insulin binding and receptor kinase in cells from a woman with type A insulin resistance and from her family.

Defects in insulin receptor function lead to impairment of the insulin response. We treated a patient with the typical phenotype of type A syndrome of insulin resistance whose insulin receptor seemed to lack the transmembrane region and cytoplasmic domain. Hyperinsulinaemia and resistance to exogenous insulin were evident, and insulin binding to cells and uptake of 2-deoxyglucose into fibroblasts were greatly decreased. Molecular weight of the alpha-subunit of the insulin receptor was normal, but autophosphorylation and kinase activity were impaired. In the pedigree analysis, defects in insulin binding were also observed in the mother, maternal grandfather and two maternal aunts, corresponding with the abnormality of the insulin receptor gene and mild insulin resistance. In the mother, much the same kinase defects as were seen in the patient became evident. However, no relatives had clinical symptoms similar to those seen in the patient. In the father there was a mild insulin resistance in the glucose clamp study and a borderline impaired glucose tolerance. Although insulin binding to cells was normal in the father, both autophosphorylation and kinase activity were reduced. Our findings suggest that insulin resistance in the patient may be caused by the defects in insulin receptor kinase activity as well as by a reduction in insulin binding activity.

Adolescent↗

PubMed1991

Vitamin D3 stimulates the production of prostacyclin by vascular smooth muscle cells.

The effects of vitamin D3 on the production of prostacyclin (PGI2) by cultured rabbit vascular smooth muscle cells (VSMCs) were investigated. PGI2 synthesis by VSMCs was significantly increased in the presence of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 1 alpha hydroxyvitamin D3 (1 alpha(OH)D3) at 48 hours [1,25(OH)2D3 greater than 1 alpha(OH)D3]. Physiological concentration of 1,25(OH)2D3 (10(-10) M) significantly increased the synthesis of PGI2. Further, we observed that treatment with 1,25(OH)2D3 significantly induced the activity of cyclooxygenase without changing the activity of phospholipase A2. These findings suggest that the mechanism of action of 1,25(OH)2D3 on the synthesis of PGI2 is mediated by the cyclooxygenase pathway. It seems possible that vitamin D3 is a vasoactive agent and may play a protective role in the development of atherosclerosis.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Clinical efficacy of a stable prostacyclin analog, iloprost, in diabetic neuropathy.

Iloprost, a stable prostacyclin analog, was evaluated clinically for its ability to ameliorate the symptoms of peripheral neuropathy associated with diabetes. In an open, nonrandomized trial, 13 diabetic patients with neuropathy but without proliferative retinopathy received an intravenous infusion of Iloprost at a dose of 10 micrograms, at a rate of 0.1 micrograms/kg/h, twice daily for two weeks. The administration of Iloprost relieved the majority of such subjective symptoms as pain, numbness or sensation of cold and to a lesser extent, such autonomic symptoms as dizziness. In contrast, there was little evidence of objective improvement, e.g., in motor nerve conduction velocity. Iloprost treatment significantly inhibited the platelet aggregation rate stimulated by collagen in vitro. In the one patient tested, thermography revealed an increase in skin temperature by more than 2 degrees C. Side effects associated with Iloprost included headache (3 patients) or aggravation of pain in the extremities (2 patients) and could be ameliorated by slowing the infusion rate or by discontinuing the drug (one patient). Iloprost appears to be safe and effective for relieving the symptoms of diabetic neuropathy. Our results provide the rationale for a double-blind, clinical trial in larger populations of diabetics with peripheral neuropathy.

Aged↗

PubMed1991

Effects of aldose reductase inhibitors on prostacyclin (PGI2) synthesis by aortic rings from rats with streptozotocin-induced diabetes.

The effects of aldose reductase inhibitors (ARIs) on the synthesis of prostacyclin (PGI2) by aortic rings from diabetic rats were examined. The ARIs studied were ONO-2235 and isoliquiritigenin, a new compound extracted from glycyrrhizae radix. The content of sorbitol in the sciatic nerve of diabetic rats induced by streptozotocin was significantly increased as compared with that of controls. This increase was significantly inhibited by the administration of an ARI. On the other hand, there was a marked decrease in the synthesis of PGI2 by the diabetic rats compared with the control rats. The decrease in PGI2 synthesis was significantly reversed by the administration of an ARI. Furthermore, the synthesis of PGI2 by the aortic rings was inversely correlated with the content of sorbitol in sciatic nerves. Those observations suggest that an ARI may have a beneficial effect on the vascular synthesis of PGI2 in diabetes mellitus.

Aldehyde Reductase↗

PubMed1991

Augmented interleukin 6 production by rat thyrocytes (FRTL5): effect of interleukin 1 beta and thyroid-stimulating hormone.

This study shows that rat thyroid follicular (FRTL5) cells can produce interleukin 6 (IL-6) spontaneously and that IL-1 beta enhanced the production of IL-6 dose-dependently. In addition, 10 ng/mL of IL-1 beta in combination with 10 to 1,000 microU/mL of thyroid-stimulating hormone (TSH) synergistically enhanced IL-6 production. It is suggested that IL-6 released from thyroid follicular cells may be a costimulator of autoreactive B and T cells in autoimmune thyroid disease and may constitute another link between the immune and endocrine systems.

Animals↗

PubMed1991

Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells.

Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I.

Actins↗

PubMed1991

Thyrotropin stimulates the expression of an acidic ribosomal protein, P0, messenger ribonucleic acid in cultured rat thyroid (FRTL) cells.

Acidic ribosomal proteins, P0, P1, and P2 in eukaryotic 60S subunits play an important role in polypeptide chain elongation during the translational step. To investigate the role of TSH in protein synthesis in the thyroid, we examined the effect of TSH on ribosomal P-protein biogenesis in FRTL cells. First, we investigated the influence of TSH on P0-protein gene expression. RNA slot blot hybridization revealed that the effect of TSH on P0-protein mRNA accumulation in the quiescent FRTL cells was time- and dose-related. This stimulatory effect of TSH was mimicked by (Bu)2cAMP. Nuclear run-off transcription assays revealed that TSH increased the transcriptional activity of the P0-protein mRNA without an increase in beta-actin transcriptional activity. On the contrary, the stability of P0-protein mRNA decreased after the addition of TSH. Cycloheximide markedly inhibited TSH-induced P0-protein mRNA accumulation in FRTL cells. Second, using a synthetic oligonucleotide probe, we have shown that TSH also increased P2-protein mRNA levels in FRTL cells. Furthermore, immunodetection of P-proteins using anti-P-protein antibody showed that TSH significantly increased the amount of P-proteins in the cells. These results suggest that TSH can increase the amount of acidic ribosomal P-proteins at least in part through an increase in the level of P-protein gene transcripts. This effect occurs via a transcriptional mechanism and requires ongoing protein synthesis. Thus, TSH might play an important role in ribosome biogenesis in FRTL cells.

Animals↗

PubMed1991

Thyrotropin stimulates glucose-regulated protein (GRP78) gene expression in rat functional thyroid epithelial cells, FRTL.

We cloned a 1.2-kilobase cDNA (C17-16) from a transformed FRTL thyroid cell library. Northern blot analysis revealed that the size of the corresponding mRNA was 2.0 kilobases. C17-16 mRNA was found in all tissues investigated, but interestingly, its expression was 5- to 10-fold higher in the thyroid glands than in other tissues. Addition of TSH to FRTL cells showed a time- and dose-dependent increase in the steady state level of C17-16 mRNA, and the effect was mimicked by (Bu)2cAMP. An in vitro nuclear run-off assay demonstrated that the stimulatory effect was due to an increase in the transcription rate of the C17-16 gene. TSH had no effect on the half-life of the C17-16 mRNA. Transcriptional induction of the C17-16 gene was inhibited when the cells were treated with cycloheximide. Nucleotide sequencing revealed that C17-16 was identical to the cDNA of rat glucose-regulated protein (GRP78), a member of the heat shock protein family. These results suggest that the expression of GRP78 in thyroid cells is regulated by TSH via cAMP, for which cycloheximide-sensitive protein synthesis might be required, and that more GRP78 might be needed to assist in the synthesis and transport of glycoprotein molecules in TSH-stimulated cells.

Animals↗

PubMed1990

Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene.

The insulin-receptor genes from a 16-year-old girl with type A insulin resistance, who presented with fasting hyperinsulinaemia, acanthosis nigricans, and reduced insulin binding, and from her family were examined. One allele of her insulin-receptor gene inherited from her mother contained a 1.2 kb deletion arising from a recombination between two Alu elements. The deletion removed the 14th exon in the beta subunit and altered the reading frame, to produce a stop codon after aminoacid 867. Pedigree analysis indicated that this mutation alone will not cause diabetes, and the proband is possibly a compound heterozygote. 4 other members of her family were heterozygous for the same mutation; all 4 had a decrease in insulin binding and slight impairment of glucose tolerance. Perhaps the same mutation is an underlying feature of some cases of non-insulin-dependent diabetes mellitus.

Adolescent↗

PubMed1990

Transcriptional regulation of ferritin heavy chain messenger RNA expression by thyroid hormone.

The effect of 3,5,3'-triiodo-L-thyronine (T3) on the steady state levels of ferritin heavy chain (ferritin H) mRNA in cultured rat glioma C6 cells and various rat tissues was examined. Addition of T3 to cultured C6 cells showed the time and dose-dependent increase in the steady-state level of ferritin H mRNA. In vitro nuclear run-on assay revealed that the stimulatory effect was due to the increase in the transcription rate of ferritin H gene. T3 had no effect on the half life of ferritin H mRNA. In hyperthyroid rats, the level of ferritin H mRNA in the kidney was elevated. On the contrary, that was decreased in hypothyroid rats. The results suggest the involvement of T3 in the regulation of ferritin H gene expression.

Animals↗

PubMed1990

T4-thyroid storm after CT-scan with iodinated contrast medium.

A 62-year-old woman had thyroid storm 5 h after a CT examination (contrast enhancement with 65% meglumine amidotrizoate, Angiografin). At the time of admission to our hospital, serum T4 and serum free T4 levels were markedly elevated (29 micrograms/dl and 9.6 ng/dl, respectively); serum T3 and serum free T3 levels were within normal limits (144 ng/dl and 5.9 pg/ml, respectively). These findings suggest that thyroid storm can occur with excess T4 only (T4-thyroid storm), and that T4-thyroid storm can be caused by administration of iodinated contrast medium.

Diatrizoate Meglumine↗