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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 415 records · Page 23Linked to original sources

Pharmacological action of 5'-methylthioadenosine on isolated rabbit aorta strips.

The effects of 5'-methylthioadenosine (MTA) and adenosine analogues on isolated rabbit thoracic aorta strips were studied in vitro. High concentrations (500-1,000 microM) of adenosine analogues produced dose-dependent relaxation in isolated rabbit thoracic aorta strips. The relative potencies of relaxant effect were MTA greater than N6-phenylisopropyladenosine greater than 2-chloroadenosine on a molar basis. MTA (50-1,000 microM) suppressed the contraction induced by norepinephrine in isolated rabbit thoracic aorta strips in a concentration-dependent manner. Nucleoside uptake inhibitor dipyridamole did not impair the MTA actions. Pretreatment of the aorta strips with theophylline, an adenosine receptor antagonist, blocked the actions of MTA. MTA showed a relaxant effect in KCl-contracted aorta suggesting that MTA did not affect the metabolism or reuptake of norepinephrine. The present experiments suggest that MTA has a pharmacological action on the arterial smooth muscle cells mediated through adenosine receptors.

Adenosine↗

Aneurysms of the distal posterior inferior cerebellar artery: experience with three cases and review of the literature.

We report 3 surgically treated aneurysms of the distal posterior inferior cerebellar artery (PICA) and review 36 cases in the literature. More than half of the distal PICA aneurysms arose distal to the choroidal arch. These lesions often arose at a turning point (i.e., a hairpin curve) of an artery instead of at a junction of vessels. Distal PICA aneurysms are likely to be missed and it is necessary to investigate carefully with four-vessel angiography even if computed tomography is done. Eighty-two per cent of the surgically treated 39 patients had good recoveries and 8% had fair results. The mortality rate was 10%. Although clipping of the aneurysm neck is preferable, trapping is useful when neck clipping is impossible in segments distal to the choroidal arch.

Adult↗

Bilateral internuclear ophthalmoplegia due to hydrocephalus: a case report.

We report a case of bilateral internuclear ophthalmoplegia due to hydrocephalus associated with Arnold-Chiari malformation. The bilateral internuclear ophthalmoplegia in this case was probably caused by brain stem displacement due to hydrocephalus. This patient was considered to have "arrested" hydrocephalus on the basis of the clinical and computed tomographic findings and the results of the continuous intraventricular pressure monitoring. However, the bilateral internuclear ophthalmoplegia gradually improved after ventriculoperitoneal shunting.

Adult↗

Comparative changes in plasma and RBC alpha-tocopherol after administration of dl-alpha-tocopheryl acetate and d-alpha-tocopherol.

Changes in plasma and RBC alpha-tocopherol after intravenous and oral administration of dl-alpha-tocopheryl acetate were investigated using vitamin E-deficient rats and were compared with those following the administration of d-alpha-tocopherol, which is the most active and natural form of tocopherol. Intravenous administration: By the administration of dl-tocopheryl acetate, the elevated plasma tocopherol levels were higher at 6 h than those elevated by d-tocopherol, but the RBC tocopherol was lower 6 h after the infusion of dl-tocopheryl acetate than after d-tocopherol infusion. The tocopheryl acetate incorporated into the RBCs remained for 24 h after the administration of tocopheryl acetate, the acetate then becoming undetectable in plasma. Oral administration: The tocopherol elevated in plasma and RBC was only the alpha-form and not tocopheryl acetate. In both plasma and RBCs, tocopherol levels were higher after the administration of d-tocopherol than after dl-tocopheryl acetate administration, and more was found in RBCs.

Administration, Oral↗

[Effects of chemotherapy of advanced malignant ovarian tumors].

Malignant ovarian tumor is regarded as the disease with the worse prognosis among obstetrical and gynecological malignancies. In the past, a great number of trials have been done with single or combined treatments. Because of the rather low incidence of malignant ovarian tumor in any one hospital over a short period of time and the numerous factors affecting the prognosis of patients, no definite procedures have been established so far. In order to evaluate the effects of chemotherapy, 460 cases were investigated retrospectively. These cases were treated primarily with surgery from 1974 to 1979 and adjuvant chemotherapy was selected freely by the doctors responsible. Cumulative 5-year survival rates were calculated as 88.8% for a low potential malignant group, 65.9% for stage I ovarian cancer, 40.6% for stage II, 9.7% for stage III, 0% for stage IV and 10% for metastatic tumor from other organs. The effects of chemotherapy were investigated especially for stage III and IV and the metastatic tumor group. Cumulative survival curves were justified by generalized Wilcoxon test. An MFC combination, a double-agent, a single-agent and a no-chemotherapy group were compared by survival curves. There were statistical significances between the MFC and no-chemotherapy group, and the double-agent and no-chemotherapy group. Significant tendency was present between the MFC and single-agent group. Several popularly-used combinations in this period such as MFC, VEM, METT, FAMT, METVFC and a group with other combinations were compared. There were no statistical significances among the 6 combinations, but an MFC combination seemed to be a better treatment for malignant ovarian tumors judging from accumulative survival curves.

Adult↗

[Chemosensitivity test for gynecologic malignancies by in vitro colony assay].

In Vitro Colony Assay was carried out to examine chemosensitivity in 57 specimens from gynecologic malignancies, and following results were obtained. Total of 34 (59.6%) formed adequate colonies for sensitive assay. Among ten anticancer drugs that were tested, Cis-platinum, Adriamycin, 5-FU and Bleomycin were relatively effective for ovarian malignancies. In vivo chemosensitive tests were also performed using five xenograft systems of human gynecologic tumor. These in vivo results were compared with in vitro data, and a 75% true positive and an 87.5% true negative rate were observed. Retrospective correlations between in vitro chemosensitive data and patient responses to chemotherapy were analyzed from 15 evaluable patients, then a 71.5% true positive and a 75% true negative rate were observed. To obtain pharmacokinetic data on anticancer drugs, we measured concentrations of plasma and tumor tissue for Cis-platinum, Adriamycin and Bleomycin in operated patients and xenografts. The in vivo tissue concentrations were higher than the in vitro drug concentrations usually employed in colony assay. By comparing the inhibitory effects on tumor colony growth of 1-hr and continuous drug exposures in colony assay, in vitro continuous exposure schedules were made available for cell cycle specific anticancer drugs.

Animals↗

A new rapid and simple assay for factor XIII activity using dansylcadaverine incorporation and gel filtration.

A new sensitive, reproducible and simple assay for factor XIII activity was developed, in which fluorescent dansylcadaverine (DC) is incorporated into casein and DC-casein is separated from free DC by gel filtration. A good correlation was found between our method and Lorand's. The main advantages of our method are: (1) our assay technique is simple with good reproducibility and takes only a couple of hours; (2) the detectable limit of factor XIII activity is about 1% of normal pool plasma, but, if necessary, can be lowered by increasing the sample amount and lengthening the reaction time.

Cadaverine↗

Relationship between phosphorylation and cytotoxicity of 2-chloroadenosine and 6-methylmercaptopurine riboside in human cells.

2-Chloroadenosine but not 6-methylmercaptopurine riboside was phosphorylated by adenosine kinase negative human B cells, and the adenosine negative cells were resistant to 6-methylmercaptopurine riboside but not to 2-chloroadenosine. Phosphorylation of 6-methylmercaptopurine was totally dependent on adenosine kinase, but 2-chloroadenosine seemed to be phosphorylated by other enzyme(s) as well. The cytotoxicity of both of these analogs depends on the phosphorylation.

2-Chloroadenosine↗

Theophylline increases serum uric acid levels.

The present study was undertaken to investigate the effect of theophylline on serum uric acid and then to elucidate the mechanisms of action of theophylline as a cause of hyperuricemia. There was a significant increase of serum uric acid levels in male asthmatic patients who received theophylline compared to male control subjects without theophylline (6.3 +/- 0.4 mg/ml, mean +/- SEM, versus 4.3 +/- 0.2 mg/ml, p less than 0.01). A significant correlation of serum levels of uric acid and theophylline was demonstrated in asthmatic patients who received 200 to 400 mg sustained-release theophylline (male group, r = 0.480, p less than 0.001; female group, r = 0.398, p less than 0.01). Intravenous administration of aminophylline in three healthy adult male patients did not inhibit uric acid clearance, suggesting that inhibition of excretion of uric acid by theophylline is unlikely. Theophylline slightly inhibited hypoxanthine guanine phosphoribosyltransferase activity in human erythrocyte lysates at concentrations over 5 mM that is considerably more than therapeutic concentrations of theophylline as determined by the conversion of [14C]hypoxanthine to [14C]inosinic acid. Theophylline caused a moderate inhibition of [14C]hypoxanthine uptake by K-562 cells (approximately 50%) at 10mM that is over 100 times as high as those achieved clinically. Further studies remain to be performed to elucidate the exact mechanisms of theophylline-induced hyperuricemia.

Administration, Oral↗

Differential inhibition of lymphocyte function by 2-chloroadenosine.

The effects of 2-chloroadenosine, a poorly metabolized adenosine analogue, on some human lymphocyte functions were studied. Mixed lymphocyte responses were strongly inhibited by very low concentrations of 2-chloroadenosine. The mitogen-induced proliferation of human lymphocytes was also generally suppressed by 2-chloroadenosine in a dose dependent manner. Blastogenesis induced by Con A and PWM was severely inhibited by low doses of 2-chloroadenosine while its inhibition of that induced by PHA was less marked. Natural killer cell activity was inhibited only about 55% by high concentrations of 2-chloroadenosine. These results suggested that many subsets of human lymphocytes are controlled by adenosine receptor.

2-Chloroadenosine↗

Immunochemical characteristics of Streptococcus mutans serotype h carbohydrate antigen.

Serotype h carbohydrate antigen was prepared from cell walls of Streptococcus mutans strain MFe28 of monkey origin. The h antigen was extracted from the cell walls with 5% trichloracetic acid at 4 C, and purified by DEAE-Sephadex A-25 ion exchange chromatography followed by Sephacryl S-300 gel filtration. The purified antigen was composed of galactose (75%), glucose (16%), and rhamnose (3%). Although the antiserum against whole cells of S. mutans MFe28 gave a strong cross reaction with serotype d S. mutans, serotype h-specific antiserum could be obtained by adequate adsorption. The precipitin reactions and hapten inhibition test using serotype h-specific antiserum showed that galactose, glucose, and their derivative sugars were markedly potent inhibitors. It was concluded that the serotype h antigen is immunologically distinguishable from the known serotypes of S. mutans, although it is closely related to serotype d antigen of S. mutans.

Antigens, Bacterial↗

Hypouricaemic effect after oral administration in chickens of polyethylene glycol-modified uricase entrapped in liposomes.

Liposomal-entrapped methoxypolyethyleneglycol (PEG) modified uricase was used to study the plasma urate lowering effect after its oral administration to chickens. Plasma uric acid concentrations fell gradually and were accompanied by a rise in plasma uricolytic activity. Serum from chickens given PEG-modified uricase liposomes did not react with native uricase in immunodiffusion plates. These results suggested the clinical usefulness of liposome-entrapped PEG modified uricase in the treatment of hyperuricaemia.

Animals↗

A thiol protease inhibitor released from cultured human malignant melanoma cells.

A thiol protease inhibitor (TPI) was found in culture media of human malignant melanoma cells (Bowes) at 1.5 to 2.3 units/day/flask (full sheet, 75 sq cm). This amount well exceeded that for cultured nonmalignant cells (human fetal lung fibroblasts). In the intracellular region of the melanoma cells, TPI activity was localized mainly in the cytosol fraction. The difference in specific activities between the intracellular and extracellular TPI and the TPI accumulation in the culture media indicated that cultured melanoma cells release TPI. Partial purification and characterization of the TPI by column chromatography using Sephadex G-150, papain-Sepharose, and Sephadex G-50, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed two distinct TPIs with molecular weights of 56,000 and 9,800 to 10,800. The latter (main) TPI had a high specificity for thiol proteases and was heat stable (60 degrees for 60 min), like previously reported normal human TPIs. The inhibitor, however, differed from normal human TPIs in that it had a lower molecular weight than any normal TPI, was unable to inhibit bromelain, and exhibited a mosaic pattern; namely, the low-molecular-weight TPI resembled liver-type TPI but the pH stability curve resembled serum-type TPI. The thiol protease, cathepsin B, was not detected in culture media of this human melanoma cell line.

Cell Line↗

Enhancement of the rate of spontaneous mutation to 6-thioguanine resistance in mammalian cells by polyamine depletion.

Several lines of evidence have suggested, but not proved, that polyamines are associated with DNA in intact cells. In an attempt to investigate the roles of polyamines in gene-associated functions, we examined the effects of polyamine depletion on the spontaneous mutation rate in a rat basophilic leukemia cell line. The frequency of 6-thioguanine-resistant mutant cells increased by approximately 9-fold as a result of the treatment with alpha-difluoromethylornithine, a potent inhibitor of ornithine decarboxylase (EC 4.1.1.17). This increase was prevented by supplementing the cultures with putrescine, suggesting that polyamine depletion, but not the direct mutagenic action of the enzyme inhibitor, is responsible for the mutant-increasing effect. These results suggest that polyamines may participate in the conservation of genetic information at either the chromosome or gene level.

Animals↗