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Biomedical subjects

Y Ochi

Publications and source records attributed to Y Ochi.

At least 109 records · Page 6Linked to original sources
PubMed1987

Involvement of calmodulin and calmodulin binding site in the TSH receptor of thyroid.

Calmodulin (CaM) antagonists, W-7 and W-5, chlorpromazine and haloperidol, especially W-7 inhibited 125I-bovine TSH binding to human and porcine thyroid receptors dose-dependently in the presence of calcium ion. This inhibitory effect of W-7 was diminished by the addition of ethylenglycol tetraacetic acid (EGTA) or ethylendiamine tetraacetic acid (EDTA). CaM also dose-dependently inhibited the binding of 125I-TSH to thyroid receptor in the presence of calcium ion. TSH binding to thyroid receptor was completely inhibited by more than 30 micrograms of CaM, and this inhibition was abolished by adding EGTA. On the other hand, the antibody to CaM inhibited partially 125I-TSH binding to its receptor. These results suggest involvement of CaM and CaM-binding sites in the TSH receptor of thyroid.

Animals↗
PubMed1987

Characteristics of antibodies to calmodulin in patients with Graves' disease.

We detected an antibody to calmodulin (CaM) in sera from patients with Graves' disease. Four sera out of 300 from patients with Graves' disease demonstrated increased CaM binding activity as compared with 300 sera from normal subjects, while no binding activity was detected in sera from autoimmune thyroiditis. The binding could be demonstrated as due to the antibody to CaM by the double antibody method, polyethyleneglycol method, gel filtration and radioimmunoelectrophoresis, respectively. These antibodies were thought to be polyclonal immunoglobulins (IgG and/or IgA). CaM has proven to be a poor antigen because of the structural identity of CaM from different species. The incidence of the antibody to CaM in Graves' disease is low and the pathophysiological significance of this antibody to CaM had remains obscure.

Antibodies↗
PubMed1987

General pharmacology of the novel antiepileptic compound zonisamide. 1st communication: effects on central nervous system.

The effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide, AD-810, CI-912), an antiepileptic compound, on the central nervous system were compared with those of carbamazepine and acetazolamide in experimental animals. 1. Zonisamide at an oral dose of 100 mg/kg was without effect on general behavior in mice except lowerings of pelvic, tail and body positions and ptosis. In rats, zonisamide slightly decreased the body temperature at the same dose. 2. Zonisamide (50 mg/kg p.o.) did not affect spontaneous alteration behavior and active avoidance performance in mice, although it impaired the acquisition of step-down passive avoidance behavior in mice. Carbamazepine (50 mg/kg) deteriorated the spontaneous alternation behavior. 3. Zonisamide (40 mg/kg i.v.) did not affect the relative power of cortical EEGs in gallamine-immobilized cats. Caudate spindles and recruiting responses, induced by electrical stimulation of the head of the caudate nucleus and the ventralis anterior thalamus, respectively, were not affected with the same dose of zonisamide in cats. On the other hand, carbamazepine (5 mg/kg) decreased the beta 2 relative power in the cortex, and enhanced both caudate spindles and recruiting responses. 4. Zonisamide (10 mg/kg i.v.) and carbamazepine (3 mg/kg) showed a tendency to depress the flexor reflex without affecting the neuromuscular transmission in anesthetized cats. 5. The central effects of zonisamide clearly differed from those of acetazolamide. Namely, acetazolamide markedly decreased brain pH at 25 mg/kg i.v., and increased regional cerebral blood flow at 100 mg/kg p.o. in rats. Zonisamide at 50 mg/kg i.v. and 100 mg/kg p.o. did not affect brain pH and regional cerebral blood flow, respectively. In addition, zonisamide (100 mg/kg p.o.) decreased brain contents of dopamine metabolite, DOPAC, with slight increase of a serotonin metabolite, 5-HIAA, in mice, and decreased brain contents of dopamine metabolites, DOPAC and HVA, in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

A possible role of endogenously formed cerebral prostaglandins in the development of adaptive protection against cerebral hypoxia/ischemia in mice.

We found recently that exogenously administered PGD2, PGE1 and PGI2 showed a protective effect against cerebral hypoxia/ischemia in mice. In the present study, to find out whether these PGs play a pathophysiological role in cerebral hypoxia/ischemia, we examined a possible role of PGs in the development of adaptive protection against cerebral hypoxia/ischemia. Mice were pretreated with a sublethal dose of KCN, hypoxic gas mixture and electroshock 10-120 min before tests. Ten to thirty min after pretreatment with a sublethal dose of KCN, mice proved to be significantly protected against cerebral hypoxia/anoxia in all models studied: KCN-induced anoxia, normobaric hypoxia and decapitation-induced gasping. Similar results were observed when hypoxic gas and electroshock were used as pretreatments. These facts indicate that the protective effect does not depend on how cerebral hypoxia/anoxia is induced but on the substances formed in the brain after hypoxia/anoxia as well as electroshock. Brain concentrations of cyclooxygenase products markedly increased subsequent to hypoxia/anoxia as well as electroshock. The increase in PGs formation as well as resistance to hypoxia was prevented by pretreatment with indomethacin. These findings suggest that endogenously formed PGs at least including the three PGs, PGD2, PGE1 and prostacyclin in mouse brain during or after hypoxia/ischemia are responsible for the increase of resistance to hypoxia/ischemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Protective effect of a new prostacyclin analogue OP-2507 against cerebral anoxia and edema in experimental animals.

Protective effects of OP-2507 [15-cis-(4-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deoxy -9 alpha, 6-nitrilo-PGF1 methyl ester] against cerebral anoxia and edema were investigated in a variety of experimental models in mice and rats. OP-2507 given s.c. or p.o. led to a consistent and dose-dependent prolongation of survival time against cerebral anoxia in hypobaric and normobaric hypoxia, KCN-induced anoxia and decapitation-induced gasping. Furthermore, treatment with 0.03-0.1 mg/kg s.c. or 0.3 mg/kg p.o. of OP-2507 was found to be effective against the changes of cerebral energy metabolites and cyclic nucleotides in hypoxic brain. In brain ischemia induced by bilateral ligation of common carotid arteries of rats, a reduction in specific gravity of cortex and an increase in water content of brain were observed, in accordance with changes of cerebral energy metabolites. These edematous and biochemical changes were prevented by the treatment with 0.01-0.03 mg/kg s.c. of OP-2507. These results indicate a potential usefulness of OP-2507 in protecting the brain from oxygen insufficiency resulting from cerebral ischemia.

Animals↗
PubMed1986

Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice.

The protective effect of prostaglandins (PGs) against cerebral hypoxia/anoxia was investigated with a variety of experimental models in relation to their CNS depressant effects in mice. Furthermore, the effect of PGs on the changes of cerebral energy metabolites and cyclic nucleotide was examined in hypoxic mice. Mice were given s.c. doses of PGs 30 min before tests. Among the PGs tested, treatment with PGD2, PGE1 and PGI2 Na showed a consistent and dose-dependent protection against cerebral anoxia induced by all models studied: histotoxic anoxia by KCN, hypobaric hypoxia, normobaric hypoxia and decapitation-induced gasping. However, PGA1, PGA2, PGB1, PGB2, PGE2, PGF1 alpha, PGF2 alpha and 6-keto-PGF1 alpha at a dose of 3 mg/kg were without effect against normobaric hypoxia and gasping duration. The three PGs, i.e. PGD2, PGE1 and PGI2 which showed anti-hypoxic effects decreased locomotor activity and potentiated hexobarbital-induced sleep. On the other hand, PGE2, PGA1, PGA2 and PGB2 also caused a decrease in locomotor activity. Similarly, PGE2 and PGA1 caused a potentiation of hexobarbital-induced sleep, but interestingly they did not cause clear-cut increase in cerebral resistance to hypoxia, in contrast with the former three PGs. Thus general depression of CNS function appears not to be responsible for the PGD2-, PGE1- and PGI2-induced increase in cerebral resistance to hypoxia. The levels of Cr-P and ATP were significantly reduced and those of ADP and AMP were markedly elevated in hypoxic brain, resulting in a decrease in a calculated energy charge potential. The lactate level and lactate/pyruvate ratio increased and the glucose level decreased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1986

Inhibition of TSH binding to chicken thyroid by some cases of LATS (long acting thyroid stimulator).

TSH receptor antibody (TRAb) activity using chicken thyroid receptor (c-TRAb) and porcine thyroid receptor (p-TRAb) was determined by the incubation of 125I-bovine TSH with each receptor. Both c-TRAb and p-TRAb activity in LATS positive and negative Graves' sera were compared. 15 out of 39 LATS positive sera and 4 out of 46 LATS negative sera had positive c-TRAb activity. On the other hand, all LATS positive sera and 33 out of 46 LATS negative sera had positive p-TRAb activity. No relationship between c-TRAb and p-TRAb activity was observed, and there was also no correlation between c-TRAb and LATS activity. Changes in c-TRAb, p-TRAb and LATS activity in the clinical course of patients with Graves' disease were examined. These activities were parallel in some cases, but in others they were not. A weak c-TRAb activity was observed in 4 out of 29 Hashimoto's disease, but all cases with thyroid cancer and subacute thyroiditis showed no activity. Sera with positive c-TRAb activity did not stimulate chicken thyroid in chick bioassay. These results suggest that some cases of TRAb in Graves' disease (mainly LATS) inhibit TSH binding to chicken thyroid receptor (non-mammalian species) in the same way as mammalian thyroid, but may not have any stimulatory action on thyroid hormone synthesis. It is interesting to note that TRAb including LATS have the similar effect on TSH receptor even in nonmammalian species.

Animals↗
PubMed1985

Immunological study of tissue polypeptide antigen (TPA)--demonstration of keratin-like sites and blood group antigen-like sites on TPA molecules.

We examined the immunological cross-reactivity between tissue polypeptide antigen (TPA) and keratin protein because of the reported sequence homology between these two proteins. TPA showed positive immuno-reactivity against both polyclonal and monoclonal antibodies for keratin. The binding of [125I]TPA with anti-keratin could be displaced dose-dependently by unlabeled keratin. However, no cross-reaction between keratin and anti-TPA was found. TPA also showed the positive immuno-reactivity with antibodies for blood group antigens (A, B and Lewis substances), but keratin did not. A standard solution of Lewis substance reacted with neither anti-TPA nor with anti-keratin. These data strongly suggest that TPA has an immunological similarity with both keratin protein and blood group antigens. When [125I]TPA and [125I]keratin were gel-filtered on a Sephadex G-200 column, the radioactivities of TPA and keratin were found mainly in the void volume fraction (MW greater than 200 000) and the MW of approximately 60 000, respectively. Chromatography on Sepharose 6B suggested that the MW of [125I]TPA was 320 000. When sera of cancer patients were gel-filtered on a Sephadex G-200 column, TPA activity was distributed mainly in the void volume fraction in all tested cases. This experiment suggests that TPA may be a glycoprotein (MW is 320 000) with both keratin-like and blood group antigen-like determinants.

Antibody Specificity↗
PubMed1985

Studies on circulating antibody against carcinoembryonic antigen (CEA) and CEA-like antigen in cancer patients.

Characteristics of auto-antibodies for carcinoembryonic antigen (CEA) detected in sera from 3 cancer patients (2 colorectal and 1 breast cancer) were examined. The antibodies belonged to polyclonal immunoglobulin G (IgG). The binding of auto-antibodies with the labeled CEA was inhibited by not only the unlabeled CEA but also NCA-2 (feces and meconium). However, no binding with NCA was observed. Among these auto-antibodies the antibody directed against blood group Lewis determinants which are known to be present in many purified CEA preparations was not found. Previously we had suggested that CEA, NCA-2 and NCA may contain immune determinant in common with alpha 1-acid glycoprotein (AG). These auto-antibodies showed significantly enhanced reactivity for the labeled CEA preparation after purification by anti-AG affinity chromatography in spite of no immunological reaction with AG. These results suggest that auto-antibodies are raised against the common antigenic determinants of both CEA and NCA-2 which do not exist in NCA. These antibodies might be directed to common amino acid sequence shared by CEA and NCA-2, though not excluding the carbohydrate moiety. We surveyed about 500,000 cancer patients but could find only 3 patients who showed a difference in the values of CEA by the indirect and direct method. Thus, the existence of this type auto-antibody to CEA in cancer patients is a rare phenomenon.

Aged↗
PubMed1985

Increased ferritin levels in the fluid of thyroid cyst.

High ferritin levels in the aspirate of thyroid cyst (Six yellow clear, 4 yellow turbid and 10 chocolate colored turbid) without apparent sings of malignancy were found. The mean concentration in the 3,000 X g supernatant of the fluid was 40,116 ng/ml, and the 3,000 X g precipitate was 11,147 ng/ml. All cases showed normal levels of serum ferritin. Con A binding with ferritin was distributed from low to high. These ferritins showed a molecular weight of approximately 450,000 which was the same as found in human spleen and liver. The continuous increase in ferritin levels in thyroid cyst fluid was found by a chronological study in some cases. When tumor markers such as CEA, NCA, CA 19-9 and alpha 1-acid glycoprotein (alpha 1-AG, acute phase reactant) were examined simultaneously, an increase in some of the cyst fluid was observed. However, the incidence and the rate of increase of these tumor markers and acute phase reactant were low compared to ferritin. Neither a correlation between ferritin and CEA, nor between ferritin and CA 19-9 was found. The increase in ferritin in thyroid cyst fluids may be due to the increased synthesis, release and storage by the inflammatory cells.

Antigens, Neoplasm↗
PubMed1985

Differential effects of haloperidol decanoate, a long-acting neuroleptic, in behavioral and biochemical tests.

The pharmacological activities of haloperidol decanoate in several behavioral and biochemical tests for neuroleptics were pursued to validate its clinical mode of action. Haloperidol decanoate itself was about 40 times less potent than haloperidol in inhibiting 3H-spiperone binding to rat striatum in vitro and its direct application into the cerebral ventricle of mice showed no effect on brain concentrations of dopamine metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). When injected intramuscularly, haloperidol decanoate exhibited various behavioral and biochemical effects together with prolonged accumulation of the parent drug haloperidol in dopamine-rich areas of the brain, but there was a clear difference in the time-course patterns of the effects. Conditioned avoidance responses in mice and rats were suppressed for a long period of days in the time-course pattern parallel to the elevation of brain haloperidol levels; the effect reached the peak a couple of days after the treatment and remained there over a week with gradual recovery towards 1 month after the injection. On the other hand, tolerance developed as rapidly as within 7 days to the antagonistic effects on apomorphine-induced stereotyped behaviours in mice and rats and to prolactin-releasing activity in rats. Biochemically, there was a regional difference in the brain in the time-course of effect of haloperidol decanoate. Namely, the initial increase in dopamine metabolites was no longer seen in the striatum on day 21, whereas it still persisted in the frontal cortex. Thus, the present study has confirmed on the one hand the assumption that haloperidol decanoate is a pro-drug which itself has no neuroleptic activity and validated on the other hand the clinical results that it exhibits long-lasting antipsychotic activities with minimum and tolerable extrapyramidal and prolactin-related side effects.

Animals↗
PubMed1984

Immunochemical identification of an alpha 1-acid glycoprotein-antigenic determinant on carcinoembryonic antigen (CEA) and non-specific cross-reacting antigen (NCA).

An immunochemical characterization of carcinoembryonic antigen (CEA) and NCA (non-specific cross-reacting antigen) was performed. Positive reactions of CEA and NCA (Mr 60 000) with some antibodies to alpha 1-acid glycoprotein (AG) were observed. Thus, both antigens may contain immune determinants in common with alpha 1-acid glycoprotein. CEA showed positive reactivity with anti-NCA. NCA showed positive reactivity with either polyclonal or monoclonal antibodies to CEA, but negative reactivity with auto-antibodies to CEA. 125I-Tetracosapeptide (synthetic peptide-24 corresponding to the amino terminal sequence of CEA) failed to react with any antisera against CEA, NCA and AG. 125I-AG also showed no immuno-reaction with any antibody against CEA, NCA and tetracosapeptide. These results suggest that some monoclonal antibodies to CEA are directed against a common antigenic determinant of both CEA and NCA in addition to AG and tetracosapeptide, and that the auto-antibody to CEA is directed against a unique immune determinant which is not common to NCA. Thus, CEA appears to contain a unique determinant not found in NCA. Similarities in the composition of both amino acids and carbohydrates of CEA and NCA suggest that CEA is 'big-big' AG and NCA is 'big' AG.

Antibodies, Monoclonal↗