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Biomedical subjects

Y Ochi

Publications and source records attributed to Y Ochi.

At least 91 records · Page 5Linked to original sources
PubMed1991

Involvement of central cholinergic mechanism in RU-24969-induced behavioral deficits.

The present study was undertaken to investigate the role of cholinergic mechanisms in the behavioral effects of RU-24969, a compound with serotonin1B (5-HT1B) receptor agonist properties. RU-24969 caused an increase in locomotion (2-5 mg/kg IP) and an impairment of spontaneous alternation (SA) behavior in a T-maze (0.5-2.0 mg/kg IP) in mice, effects that were also induced by the cholinergic hypofunction with scopolamine treatment (0.5-5.0 mg/kg IP), an acetylcholine (ACh) receptor antagonist. The impairment of the SA behavior by RU-24969 was enhanced by scopolamine. Both the hyperlocomotion and the SA impairment by RU-24969 were markedly reduced by propranolol (20 mg/kg IP) which has 5-HT1A/5-HT1B receptor antagonist properties, as well as by physostigmine (0.05-0.2 mg/kg IP), an ACh esterase inhibitor, and oxotremorine (0.005-0.01 mg/kg IP), an ACh receptor agonist. Moreover, these behavioral deficits of RU-24969 were diminished in mice pretreated intracerebroventricularly with AF64A (30 nmol/body), a presynaptic cholinergic neurotoxin, whereas scopolamine induced the deficits even in animals with the same treatment. These results suggest that the serotonergic behavioral deficits observed after RU-24969 treatment may be caused by an inhibition of ACh release through its action on the presynaptic receptor (particularly RU-24969-sensitive sites) localized on the cholinergic terminals.

Animals↗
PubMed1991

The incidence of thoracic vertebral fractures in a Japanese population, Hiroshima and Nagasaki, 1958-86.

The incidence of thoracic vertebral fractures (TVF) in a Japanese population of 14,607 individuals from Hiroshima and Nagasaki was determined by sex, age, birth cohort, and exposure to atomic bomb radiation. The diagnosis of TVF was based on lateral chest radiographs made from 1 July 1958 to 28 February 1986. The subjects, who were born between 1880 through 1939, were categorized by sex into 10-year birth cohorts. TVF incidence increased by a factor of 1.7 in all birth cohorts with each 10-year increase in age in females, but did not increase with age in males. The incidence was significantly lower in the younger birth cohorts in both sexes. The incidence declined by a factor of 0.5 in males and 0.6 in females for each 10-year decrease in the year of birth. TVF incidence did not differ between the cities, and no correlation with atomic bomb radiation exposure was demonstrated.

Adult↗
PubMed1991

Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders.

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.

Animals↗
PubMed1991

[Effect of AS-2646, a novel antiulcer agent on gastric mucosal defensive factors in rats].

The effects of AS-2646 on the acute gastric mucosal lesions induced by various noxious agents and the gastric mucosal defensive factors were studied in rats, and the following results were obtained: 1) AS-2646 (5-100 mg/kg, p.o.) dose-dependently inhibited the formation of the mucosal lesions induced by ethanol, ethanol-HCl, taurocholate-HCl and serotonin, and its anti-lesion spectrum was the widest among the compounds (cimetidine, pirenzepine, sulpiride and prostaglandin E1) examined here. 2) AS-2646 (5-10 mg/kg, p.o.) not only improved the changes of gastric mucosal hemodynamics induced by the blood removal and/or the reserpine treatment, but also inhibited the mucosal lesions induced by them. 3) AS-2646 (2-20 mg/kg, p.o.) antagonized the decrease in the surface gastric mucus and mucosal hexosamine contents induced by stress and/or aspirin. 4) AS-2646 (2-20 mg/kg, p.o.) caused no significant effect on the gastric mucosal prostaglandin E2 levels. 5) AS-2646 inhibited Campylobacter pylori in vitro. These results indicate that AS-2646 may be useful as a novel antiulcer drug with the defensive factor-potentiating and anti-Campylobacter pylori effects.

Animals↗
PubMed1991

Different binding of stimulatory-type and blocking-type TSH receptor antibody with guinea-pig testis membrane.

A receptor assay using [125I]bTSH-binding to guinea-pig testis membrane was developed. Unlabelled hCG and FSH inhibited [125I]bTSH binding. In patients with Graves' disease and in untreated hyperthyroid patients, almost all long-acting thyroid stimulators and thyroid-stimulating antibodies, respectively did not inhibit [125I]bTSH binding, which on the other hand was inhibited by thyroid stimulation blocking antibodies in patients with primary hypothyroidism. When the inhibitory effect on the binding of [125I]hCG and 125I-synthetic alpha-subunit peptide (alpha 26-46) of hCG to testis membrane was examined, bTSH resulted in a significant inhibition. However, all three kinds of TSH receptor antibodies had no inhibitory effect. This study demonstrated 1. interaction of alpha-subunit of TSH and hCG with the testicular receptor; 2. binding of thyroid stimulation-blocking antibody and lack of binding of thyroid-stimulating antibody to the testicular TSH receptor in spite of binding of these TSH receptor antibodies to the thyroidal TSH receptor, and 3. lack of binding of thyroid-stimulating antibody and thyroid stimulation-blocking antibody to the testicular gonadotropin receptor.

Amino Acid Sequence↗
PubMed1991

[Immunohistochemical analysis of adenomatoid tumor of the uterine corpus--comparison with mesothelioma].

Immunohistochemical study was carried out in a case of adenomatoid tumor of the uterine corpus. The patient was a 35-year-old female. The tumor showed classical histochemical and immunohistochemical findings of mesothelioma, i.e., presence of hyaluronic acid on the cellular surface and cytokeratin in the cytoplasm. In addition, the tumor showed positive reaction to anti-vimentin. Furthermore, absence of Ber-Ep4 supports mesothelial origin of this tumor. EMA reaction was reported only in one case in the literature. The result was negative as in our case. Therefore, it was suggested that at least some of the adenomatoid tumor were negative for EMA as in malignant mesothelioma, although this tumor was benign. Therefore, it was suggested that loss of EMA in mesothelial tumor was not always related to anaplastic change.

Adenoma↗
PubMed1991

[A case of sarcoidosis with increased CD3+ WT31- CD16+ lymphocytes].

Increase of CD16+ cells in the peripheral blood is not uncommon for sarcoidosis. However, further subclassification of such cells have not been reported yet. Here, we report a case of sarcoidosis developed in 71 year-old female who had abundant CD16+ lymphocytes in the peripheral blood and most of them were revealed to be CD3+ WT31- by analysis using cell sorting. Although exact role of these cells is remained to be solved, they seem to be implicated in the immune disorder of this disease.

Aged↗
PubMed1990

Coexistence of autoantibody to human thyrotropin (TSH) and autoanti-idiotypic antibody to antihuman TSH antibody in a case with simple goiter.

A 70-yr-old woman with simple goiter showed normal serum levels of T4, T3, free T4, TSH receptor antibody (TRAb) and increased TBG. Discrepancy in serum hTSH level was observed by different assay methods. Coexistence of both autoantibodies for hTSH and for anti-hTSH antibody were demonstrated by the reaction of the patient's antibody with both 125I-hTSH and 125I-anti-hTSH (monoclonal antibody; mAb). These two autoantibodies belong to the polyclonal immunoglobulin G (IgG). The autoantibody for hTSH recognized only beta-subunit of hTSH. Neither stimulating type of TRAb in Graves' disease nor blocking type of TRAb in primary hypothyroidism interfered with the binding of the patient's antibody to 125I-hTSH or 125I-anti-hTSH. Anti-idiotypic antibody (anti-ID antibody) for anti-hTSH antibody was purified by anti-hTSH antibody affinity chromatography. The binding reaction of 125I-anti-hTSH (mAb) with this anti-ID antibody could be inhibited by the unlabeled hTSH. This anti-ID antibody might represent the internal image of the nonbiological active site of TSH molecule, because of absence of thyroid stimulating activity. Goiter in this patient may have occurred by the unbound TSH with IgG (free TSH) and the bound TSH with IgG, because TSH levels in both the whole serum and the IgG free serum (the unbound TSH with IgG) were decreased significantly by T4 treatment. Coexistence of these antibodies may participate in the autoimmune mechanism of an idiotype-anti-idiotype network.

Aged↗
PubMed1990

The inhibition by calmodulin of thyroid-stimulating hormone binding to epididymal fat, testis and thyroid membranes in the guinea-pig.

Calmodulin inhibited 125I-labelled TSH binding to the membranes of various target tissues for TSH (thyroid, epididymal fat and testis) of the guinea-pig. This inhibition was abolished by adding EGTA (1 mmol/l). Calmodulin did not inhibit the binding of 125I-labelled epidermal growth factor (EGF) to these membranes. It is suggested that the inhibitory effect of calmodulin on the binding of TSH to the receptor is specific and that this mechanism is due to the direct binding of calmodulin to receptor membranes. The ability of calmodulin to bind to the membranes was calcium-sensitive while that of TSH was not. The binding of 125I-labelled calmodulin to these membranes increased significantly when the endogenous calmodulin in the membranes was removed by EGTA. It was not inhibited by a pure preparation of TSH, but it was inhibited by contaminated calmodulin in a crude TSH preparation. On the other hand, 125I-labelled TSH binding to these membranes did not change after the removal of endogenous calmodulin. In conclusion, exogenous calmodulin has an inhibitory effect on the binding of TSH but not of EGF to the membranes of guinea-pig thyroid, epididymal fat and testis.

Animals↗
PubMed1990

Binding of bovine and porcine pituitary glycoprotein hormone alpha-subunit to TSH antibody in serum of patients with Graves' disease.

The characteristics of autoantibodies reactive with bovine (b) TSH were examined in the sera of six patients with Graves' disease selected on the basis of highly negative values in the TSH receptor assay. Test sera were incubated with other 125I-labeled pituitary glycoprotein hormones and their isolated subunits (alpha and beta) [human (h) TSH, bTSH, porcine (p) TSH, pFSH, bFSH, bLH and equine (e) chorionic gonadotropin (CG)] (purity was confirmed by gel-filtration on Sephadex G-100 and SDS-PAGE), and the antibody bound fraction was precipitated by the addition of anti-human gamma-globulin (goat). Almost all sera showed detectable binding to bTSH, pTSH, pFSH, pTSH-alpha, bFSH-alpha, bLH-alpha, but not to hTSH, hTSH-alpha, hTSH-beta, hFSH, hLH, hCG, pTSH-beta, bLH-beta, eCG-alpha. Exceptions were very low binding to bLH-beta by one serum and to pTSH-beta, by two sera. The level of binding (B/T%) of the patients' sera to pTSH-alpha, bFSH-alpha and bLH-alpha was 3.0-27.7%, 2.6-45.3% and 2.2-39.0%, respectively; that of sera from normal healthy adults was 1.9 +/- 0.3%, 0.8 +/- 0.2% and 0.9 +/- 0.2% (mean +/- SD), respectively. These results indicate that the TSH antibodies recognize mainly an epitope in the alpha subunit of bovine and porcine pituitary glycoprotein hormones (TSH, FSH, LH).

Animals↗
PubMed1990

[Determination and clinical significance of anti-idiotypic antibody--in model experiments of thyroglobulin and TSH].

Anti-idiotypic (anti-ID) antibody in test serum was determined by the direct binding assay using 125I-anti-human thyroglobulin (hTg). Several positive cases were found in Graves' disease and thyroiditis chronica. Positive anti-ID antibodies could be classified into two types. Type 1 showed the positive anti-hTg antibody and high Tg levels by RIA using double antibody method. Type 2 showed the positive anti-hTg antibody but low Tg levels by RIA. The binding of 125I-hTg to anti-hTg antibody was displaced by anti-ID antibody in type 1, but was not anti-ID antibody in type 2. A case of coexistence of autoantibody to hTSH and auto-anti-ID antibody to anti-hTSH antibody was found. She showed normal thyroid function (T4, T3), but TSH level showed discrepancy by different assay methods. Both autoantibodies for hTSH and for anti-hTSH antibody were demonstrated by the reaction of patient's antibody with both 125I-hTSH and 125I-anti-hTSH (MoAb). These two autoantibodies belong to the polyclonal IgG. The autoantibody for hTSH recognized only the beta-subunit of hTSH. Neither stimulating type of TSH receptor antibody (TRAb) nor blocking type of TRAb interfered with the binding of patient's anti-ID to 125I-anti-hTSH. This binding reaction could be inhibited by the unlabeled hTSH. This anti-ID might represent the internal image of the non-biological active site of TSH molecule, because of absence of thyroid stimulating activity. These anti-ID antibodies may provide evidence supporting a network theory of the immune system.

Adolescent↗
PubMed1990

[Flow cytometric analysis of nuclear DNA contents in human hepatocellular carcinoma].

The nuclear DNA contents in fresh surgical specimens in cases of 34 hepatocellular carcinoma were measured by flow cytometry. The frequency of aneuploid and relation of ploidy with degree of malignancy (stage and portal vein thrombosis, etc.) were examined. The incidence of aneuploidy of human hepatocellular carcinoma was 53%, these cases were at a significantly higher stage than the diploid cases (P less than 0.05). Among aneuploid cases, 61% (11 out of 18 cases) were associated portal vein thrombosis, this incidence was also significantly higher than the 6% (one of 16 cases) for the diploid cases (P less than 0.01). These findings demonstrated flow cytometric analysis are not only useful to diagnose to hepatocellular carcinoma, but useful to evaluate the prognosis.

Aged↗
PubMed1989

Clinical significance of mucin-like high molecular weight glycoprotein originated from lung cancer as tumor marker.

A high molecular weight, mucous glycoprotein (MG) from the pleural fluid of lung adenocarcinoma was purified by the DEAE-cellulose, gel-filtration and wheat germ agglutinin affinity chromatography. Protein portion of the molecule was composed of amino acids rich in serine, threonine and proline, but methionine and tyrosine concentrations were relatively low. About 65% of the weight, was composed of galactose, galactosamine, glucosamine, fucose and sialic acid. The gel-filtration pattern on Sepharose 4B revealed Mr greater than 10(6) Da. The SDS-PAGE pattern revealed a main band at the position of the Mr about 350 kDa under the reducing condition. Rabbit antibody against this molecule recognized mainly the peptide portion, and the radioimmunoassay (RIA) using the double antibody method was developed by this antibody. Serum MG level was low in healthy subjects and in benign diseases (0.8 +/- 0.7 U/ml; mean +/- SD and 1.1 +/- 2.3 U/ml, respectively). Thus, 3 U/ml was used as the cut-off value. The mean of serum MG levels and positive rates in malignant diseases were significantly high; 4.4 U/ml and 32.3% in lung cancer, 20.1 U/ml and 77.5% in pancreas cancer 11.6 U/ml and 64.3% in gastric cancer, 12.9 U/ml and 57.1% in hepatoma, 12.3 U/ml and 77.8 in colon cancer. Other malignancies such as ovarial and uterus cancer showed also high levels. Elevated values in these malignancies were observed frequently in patients with metastasis. On the other hand, the false positive cases were found in 10% of benign diseases. Determination of MG seems to be useful for the detection of several kinds of malignancies, but it is not adequately sensitive as a screening method for early cancer detection.

Adenocarcinoma↗
PubMed1989

Anti-TSH antibodies in Graves' disease and their failure to interact with TSH receptor antibodies.

The occasional occurrence in sera of patients with Graves' disease of negative values in the assay for TSH receptor antibodies led to the discovery of endogenous antibodies to TSH. We examined the sera of approximately 2500 patients with Graves' disease. Eight positive sera were found. The IgG in all 8 sera showed higher binding with both bTSH and porcine TSH (pTSH) than with human TSH (hTSH). This means that autoantibodies to TSH in sera from patients with Graves' disease are rare and often directed towards heterologous bovine and porcine TSH. When hTSH levels were determined in sera of hyperthyroid patients with positive antibodies to hTSH, discrepancies in serum hTSH levels were observed when using different assay methods, i.e. hTSH levels were higher with the double-antibody technique, and lower with immunoradiometric assays. Antibodies in these sera showed higher binding to pTSH-alpha subunit than to -beta subunit. The binding of the two pTSH subunits with antibodies could be displaced by intact bTSH. Neither stimulation in Graves' disease nor blocking in primary hypothyroidism of TSH receptor antibodies interfered with the binding of the anti-TSH antibodies to 125I-labelled pTSH, pTSH-alpha, and pTSH-beta. Consequently, using this type of autoantibodies to TSH we were unable to obtain evidence that the TSH receptor antibodies of patients with Graves' disease was an anti-idiotype antibody against anti-TSH antibodies.

Graves Disease↗
PubMed1989

L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide as a novel thyrotropin releasing hormone analogue with improving effects on impaired central nervous systems functions.

Psychopharmacological activities of L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202) were compared with those of the parent peptide, thyrotropin releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide, Pyr-His-Pro amide) in rodents. RGH-2202 caused qualitatively similar effects to TRH in a variety of tests for the activity on the central nervous system. The compound as well as TRH increased the spontaneous motor activity, enhanced the conditioned avoidance response, and antagonized the avoidance suppression by haloperidol and the sleep-inducing effect of pentorbarbital in mice. It was also efficacious against the deficits of consciousness in mice with concussive head injury and the EEG disturbance in rats with basilar artery occlusion. Besides, it antagonized the cycloheximide-or anoxia-induced amnesia and enhanced the habituation of exploratory activity in mice. Biochemically, it enhanced, like TRH, the turnover of norepinephrine and dopamine in the cerebral cortex, nucleus accumbens and striatum of mice and rats, and increased cyclic GMP levels in the cerebellum of rats. In spite of the global similarity between the pharmacological profiles of RGH-2202 and TRH, there were some intriguing differences between them. RGH-2202 was 2-5 times more effective than TRH in improving the deficits of active avoidance performance and retention in mice, while it was weaker than TRH in modifying the haloperidol-induced catalepsy in mice and enhancing the spinal reflexes in rats. Besides, its thyrotropin releasing activity was about 30 times less potent than that of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗