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M Ota

Publications and source records attributed to M Ota.

At least 217 records · Page 12Linked to original sources
PubMed1992

Prediction of the tertiary structure of parathyroid-hormone-related protein (residues 1-34) by the island model.

Prediction of the tertiary structure of a 34 residue N-terminal fragment of parathyroid-hormone-related protein was carried out by the island model. This peptide is known as a major causative agent of humoral hypercalcemia of malignancy, but structural information studied by X-ray diffraction has not been reported. We adopted the secondary structure determined by NMR and packed on the basis of island model of protein folding developed by us. Predicted structure is discussed in connection with the interaction of active sites.

Amino Acid Sequence↗
PubMed1992

HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients.

To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4 were significantly more frequent in patients with autoimmune hepatitis than in controls. HLA-DR4 was most frequently associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of Dw between the patients and the controls who were DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.

Adult↗
PubMed1992

Inhibition of tryptophan hydroxylase by (R)- and (S)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines (salsolinols).

The (R)- and (S)-enantiomers of salsolinol, the dopamine-derived tetrahydroisoquinolines, were found to inhibit the activity of tryptophan hydroxylase (TPH), prepared from serotonin-producing murine mastocytoma P-815 cells. Inhibition of TPH by salsolinols was found to be non-competitive with the substrate L-tryptophan. Tryptophan hydroxylase is composed of two elements with different kinetic properties in terms of cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin and these two elements were inhibited by salsolinols in competitive and uncompetitive ways, respectively. Stereoselectivity of salsolinol was not observed, concerning the potency and the type of inhibition on PTH. These data indicate that salsolinols might be naturally occurring inhibitors of indoleamine metabolism.

Animals↗
PubMed1992

Hepatic resection for metastatic squamous cell carcinoma from the uterine cervix.

A solitary hepatic tumor was diagnosed 3.5 years after a 67-year-old woman had undergone radical hysterectomy and postoperative irradiation for stage Ib squamous cell carcinoma of the cervix. Hepatic resection confirmed squamous cell carcinoma that had metastasized from the uterine cervix. One year and 10 months following hepatic resection, this patient is doing well with no evidence of any recurrence. This is a report of successful hepatic resection for metastatic carcinoma from the uterine cervix.

Aged↗
PubMed1992

Cytotoxicities of oxides, phosphates and sulphides of metals.

The cytotoxicities of oxides, phosphates and sulphides, which possibly form on dental alloys, were tested using the 'agar method'. The relative magnitudes of the cytotoxicities of these compounds exhibited tendencies similar to those of the metal components in the compounds. In correlation with dental amalgams, zinc oxide was the most cytotoxic, just as with metallic zinc, while tin oxides and mercury oxides exhibited no cytotoxicity. Zinc was the most influential element in the cytotoxicity of dental amalgams. On the other hand, in correlation with Ni-Cr alloys, Co-Cr alloys, and/or stainless steels a chromium oxide and a cobalt oxide showed serious cytotoxicity, whereas the iron oxides were non-cytotoxic. Sulphides, which possibly form on silver alloys, showed cytotoxicity. Oxides and phosphates of titanium and aluminium, and hydroxyapatite, were not cytotoxic, supporting the use of these materials for implants. Not only the valence of an element but also the chemical species combining with the element affect the cytotoxicity of the alloy containing it.

Biocompatible Materials↗
PubMed1992

Association of the 90-kDa heat shock protein does not affect the ligand-binding ability of androgen receptor.

An N-terminal truncated androgen receptor with putative DNA- and ligand-binding domains (AR438) and that with a ligand-binding domain (AR612) were expressed under control of the T7 promoter in E. coli or translated in vitro with rabbit reticulocyte lysate, and their ligand-binding properties and the interaction with HSP90 were investigated. Bacterially expressed AR438 and AR612 bound a synthetic androgen, [3H]R1881, with apparent dissociation constants of 2.6 +/- 0.2 and 3.1 +/- 0.7 nM, respectively, values which are comparable to those of androgen receptor in target tissues. The recombinant androgen receptors sedimented at the 4-5 S region irrespective of the presence of 10 mM tungstate, indicating that the receptor exists free from HtpG, which is the bacterial homolog of eukaryotic HSP90. The apparent dissociation constant of truncated androgen receptors translated in vitro was 0.1 nM for AR438 and 0.2 nM for AR612. Sedimentation coefficients of in vitro translated molecules were converted from 7-8 S in the presence of tungstate to 3 S in the absence of tungstate. Both AR438 and AR612 translated in vitro were retained by anti-rat HSP90 antibody-protein A Sepharose. Exposure to 0.3 M NaCl in the presence of ligand caused dissociation of AR438 and AR612 from HSP90, and concomitantly, the DNA-cellulose binding ability of AR438 was enhanced. Thus, we conclude that the androgen receptor associates with HSP90 through the ligand-binding domain and that this association prevents the interaction of the androgen receptor with DNA. However, HSP90 seems to have little effect on the ligand-binding characteristics of the androgen receptor.

Animals↗
PubMed1992

Demonstration of the requirement for self antigen in the activation of autoreactive T cells.

An HLA-DR4-restricted T cell clone (26G11), which was reactive to autologous non-T cells without any nominal antigens, was established from an unimmunized normal subject that was DR1/4 positive. The reactivity of the clone was examined against L cells (LDR4) transfected with the particular DR4 genes obtained from the same subject. 26G11 cells proliferated slightly in response to LDR4 cells, but the proliferation was markedly augmented by the addition of cell lysate from an autologous B cell line. In addition, 26G11 cells killed LRD4 cells sensitized by preincubation with the cell lysate more efficiently than LDR4 cells without treatment. When LDR4 cells were preincubated with cell lysate from allogenic B cell lines, effective killing of the target cells by clone 26G11 was also observed. These data strongly suggest that this autoreactive T cell clone (26G11) recognizes endogenous antigen in the context of the DR4 molecule. This directly demonstrates the requirement for self antigen in the activation of human autoreactive T cells from a normal subject.

Animals↗
PubMed1992

HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific primers.

We previously introduced HLA-DQA1, -DPB1 and DQB1 genotyping with the modified PCR-RFLP method using some informative restriction enzymes which have either a single cleavage site or alternatively no cleavage site in the amplified DNA region, depending on the HLA alleles, making reading of RFLP band patterns much easier. In this study, 43 HLA-DRB1 alleles, excluding DRB1*1103 and *1104 for which no restriction enzymes are available to distinguish each from the other, could be defined by this modified PCR-RFLP method combined with 7 pairs of group-specific primers. It is impossible to distinguish DRB1*0701 and DRB1*0702 as they are identical for the second exon of DRB1. For DR1-DRB1, DR2-DRB1, DR4-DRB1, DR7-DR1, DR9-DRB1, DRw10-DRB1 or DRw52 associated antigens (DR3, w11, w12, w13, w14, and DRw8)-DRB1 gene amplification, the second exon of the DRB1 gene was selectively amplified using each group-specific primer from genomic DNAs of 70 HLA-homozygous B-cell lines and healthy Japanese by PCR. Amplified DNAs were digested with restriction endonucleases and then subjected to electrophoresis assaying simply for cutting, or no cutting, of the DNA, although some alleles can be distinguished only after examination of RFLP band patterns generated and in some cases using double digestion technique with two restriction enzymes. This modified PCR-RFLP method can be successfully applied to all possible DRB1 heterozygotes, despite the fact that 15 pairs of heterozygotes among them cannot be distinguished theoretically by the PCR-SSO method, because the PCR-RFLP method can tell whether two polymorphic sites are linked to each other (cis position) or located on a different chromosome (trans position) by checking the length of RFLP bands generated with double digestion. Thus, the PCR-RFLP method is technically simple, practical and inexpensive for determination of the HLA-DRB1 alleles for routine HLA typing work.

Alleles↗
PubMed1992

N-methylation of dopamine-derived 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, (R)-salsolinol, in rat brains: in vivo microdialysis study.

N-Methylation of (R)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-salsolinol] derived from dopamine was proved by in vivo microdialysis study in the rat brain. The striatum was perfused with (R)-salsolinol and N-methylated compound was identified in the dialysate using HPLC and electrochemical detection with multichanneled electrodes. N-Methylation of (R)-salsolinol was confirmed in three other regions of the brain, the substantia nigra, hypothalamus, and hippocampus. In the substantia nigra, the amount of N-methylated (R)-salsolinol was significantly larger than in the other three regions. These results indicate that around dopaminergic neurons, particularly in the substantia nigra, (R)-salsolinol was methylated into N-methyl-(R)-salsolinol, which has a chemical structure similar to that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the selective dopaminergic neurotoxin. N-Methylation of tetrahydroisoquinolines and beta-carbolines have already been proven to increase their toxicity to dopaminergic neurons and N-methylation might be an essential step for these alkaloids to increase their toxicity. On the other hand, after perfusion of (R)-salsolinol, release of dopamine and 5-hydroxytryptamine was observed and inhibition of monoamine oxidase was indicated. (R)-Salsolinol and its derivatives may be candidates for being dopaminergic neurotoxins.

Animals↗
PubMed1992

Studies on the association of NIDDM in Japanese patients with hyperthyroid Graves' disease.

We attempted to analyze the association of hyperthyroid Graves' disease with non-insulin-dependent diabetes mellitus (NIDDM). Forty-nine patients (23 males and 26 females; 7.6%) of a total of 647 patients with hyperthyroid Graves' disease had NIDDM, several years before or after Graves' disease was diagnosed. Only 1 patient had insulin-dependent diabetes mellitus. Compared with the general Japanese population (n = 9,133), the incidence of NIDDM (n = 348; 3.9%) in patients with Graves' disease was higher in all age groups. Only 4 patients (8.2%) of the 49 hyperthyroid patients with NIDDM had a history of being overweight (body mass index > 25). In contrast, 276 (79.9%) of the 348 diabetic patients were currently or previously overweight. Moreover, the incidence of a family history of diabetes (13 of the 49 hyperthyroid Graves' patients with NIDDM; 26.5%) was also lower in the patients with NIDDM in the general Japanese population (50% incidence). The male:female ration in patients with Graves' disease and NIDDM was 1:1.1; much different from that in the total Graves' disease population (1:4.1). Analysis of the HLA loci A, B, C, DR and DQ (35 determinations) in 35 hyperthyroid patients with NIDDM and in 386 subjects from the general population revealed a highly significant difference between them in the incidence of HLA-Cw4, -DR2, -DQw1, -DQw3 and -DQw4. This study suggests that there was an association of Graves' disease with NIDDM. A significant association of HLA-DR and -DQ loci was observed in hyperthyroid Graves' patients with NIDDM.

Adolescent↗
PubMed1992

Effect on vasopressin release of microinjection of cholinergic agonists into the rat supraoptic nucleus.

It is likely that central cholinergic pathways to the paraventricular and supraoptic nuclei participate in the control of vasopressin release. We have shown previously that this is due, in part, to activation of muscarinic, but not nicotinic, receptors in the paraventricular nucleus. There is, however, reason to believe that this cholinergic effect in the supraoptic nucleus may be the result of activation of nicotinic receptors. To test this possibility, we have studied in conscious unrestrained rats the effect of microinjection of muscarinic and nicotinic agonists into the supraoptic nucleus on vasopressin release, mean arterial blood pressure, and heart rate. Under ether anesthesia, a stainless steel guide cannula was placed in the supraoptic nucleus 5-7 days before the experiment, and femoral, arterial, and venous catheters were implanted 1 day before the experiment. Microinjection of nicotine into the supraoptic nucleus at doses of 1 and 10 micrograms resulted in transient increases in the plasma vasopressin concentration that were 7-fold and 11-fold greater, respectively, than control values at 3 min. There were also small transient increases in mean arterial blood pressure, but heart rate was unchanged. The microinjection of 2 and 20 ng of oxotremorine, a muscarinic agonist, into the supraoptic nucleus had no effect on the plasma vasopressin concentration, mean arterial blood pressure, or heart rate. These doses of oxotremorine were previously shown to have potent stimulatory effects on vasopressin release when microinjected into the paraventricular nucleus. These findings suggest that the central cholinergic stimulation of vasopressin release is due, in part, to activation of muscarinic receptors in the paraventricular nucleus and nicotinic receptors in the supraoptic nucleus.

Animals↗
PubMed1992

[A case report of well differentiated fetal adenocarcinoma].

A 32-year-old female, who was admitted with complaints of cough and an abnormal shadow in the left lower lobe, was diagnosed as adenocarcinoma of the lung by TBLB. She underwent left lower lobectomy and lymph node dissection. Histopathological findings showed well differentiated fetal adenocarcinoma (WDFA). Well differentiated fetal adenocarcinomas are considered to have a histogenesis similar to that of pulmonary blastoma and may be a tumor with one-sided development of pulmonary blastoma showing only an epithelial component.

Adenocarcinoma↗
PubMed1992

[Phase II study of 254-S (cis-diammine glycolato platinum) for gynecological cancer].

A phase II study of 254-S was conducted in 134 patients with gynecological malignancies by the gynecology section of the 254-S cooperative study group. The drug was administered at least twice at a dose of 100 mg/m2 by intravenous infusion at 4 week intervals. Forty-two of the 102 evaluable patients responded, including 8 CRs and 34 PRs, with a response rate of 41.2%. The response rate was 37.7% for ovarian cancer and 46.3% for cervical cancer. The response rate of 46.3% for cervical cancer was the highest reported for any single anticancer agent available in Japan. The major side effect was hematotoxicity, in particular thrombocytopenia and leukopenia, while nephrotoxicity was rarely observed. These results suggest that 254-S is an active cisplatin analogue with reduced nephrotoxicity and is a very promising anticancer agent for the treatment of ovarian and cervical cancer.

Adult↗
PubMed1992

Effects of androgen on phosphorylation of chromosomal proteins in mouse submandibular gland.

The effect of androgen on intranuclear distribution of androgen receptor binding sites was studied. The level of the androgen receptor complex in dinucleosomes increased 1 h after androgen treatment and those in the mono- and trinucleosomes increased 3 h after androgen treatment. Investigation by 32P incorporation into the nuclei and active chromatin showed that androgen resulted in an increase in the rate of phosphorylation at 3 h and reduced to the control level at 6 h. These data suggest that association of androgen receptor with the acceptor sites and activities of protein kinase in active chromatin are simultaneously stimulated for activating the transcription by androgen.

Animals↗
PubMed1991

Retinoic acid receptor in subclone of human salivary gland adenocarcinoma cell line HSG and effect of retinoic acid on cellular growth.

Retinoic acid (RA) binding has been detected in the nuclei of a subclone (CL-1) of human submandibular adenocarcinoma cell line HSG conditioned to grow in a serum-free defined medium. Competition assay confirmed the specificity of the RA binding. Scatchard analysis showed the binding molecule to have a high affinity and low capacity. From the analyses by gel-filtration and glycerol density gradient centrifugation, the nuclear binding molecule appears to be distinct from cellular RA binding protein (CRABP) in terms of molecular weight. Furthermore, immunoblotting analysis revealed a band (Mr 47,000) reactive with specific antibody to RA receptor (RAR) alpha in the gel containing the nuclear fraction of CL-1 cells. Northern blotting analysis with specific cDNA probes revealed the expression of RAR alpha and RAR gamma in CL-1 cells. These results indicate that CL-1 cells express two types of RAR subtype, suggesting that these receptor molecules may mediate biological effects of RA. Treatment of CL-1 cells with RA resulted in an increase in the incorporation of [3H]thymidine into TCA-insoluble materials. The maximal increase was observed at 10(-6) M around 48 h. Previously, we demonstrated the autocrine growth of HSG cells mediated by epidermal growth factor (EGF) receptors and EGF-like molecules (Kurokawa et al. (1989) Cancer Res. 49, 5136-5142) and showed that RA had no significant effect on the secretion of the EGF-like molecule. RA induced an increase in [125I]EGF binding to CL-1 cells. The increase in the EGF binding was maximal at 24 h at 10(-6) M RA. RA also increased the amount of [3H]leucine-labeled EGF receptor dose-dependently. No significant change was observed in total protein synthesis of CL-1 cells by treatment with RA. These results suggest that RA stimulates the growth of CL-1 cells by increasing EGF receptor levels.

Adenocarcinoma↗
PubMed1991

Inhibition of tryptophan hydroxylase by food-derived carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole.

Food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were found to inhibit the activity of tryptophan hydroxylase (TPH) prepared from serotonin-producing murine mastocytomas, P-815 cells. Inhibition of TPH by Trp-P-2 was found to be competitive with the substrate L-tryptophan and non-competitive with the cofactor (6R)-L-erythro-5,6,7, 8-tetrahydrobiopterin. The inhibition proved to be reversible; by dialyzing the sample incubated with Trp-P-2, the enzyme activity could be fully recovered. Among a series of heterocyclic amines examined, Trp-P-1, Trp-P-2 and some other heterocyclic amines inhibited TPH activity. Trp-P-2 and other heterocyclic amines were the newly discovered naturally occurring inhibitors of the indoleamine metabolism.

Animals↗