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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 613 records · Page 34Linked to original sources
PubMed1981

Membrane affinity and metabolism of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine into cultured KB cells.

N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (N4-palmitoyl-ara-C), a lipophilic derivative of 1-beta-D-arabinofuranosylcytosine, possessed an affinity for KB cell plasma membrane. Approximately 15 to 25% of the drug incorporated into KB cells was retained in plasma membrane when the cells were treated with the drug for 1 to 32 hr at 10 microM, the concentration required for 50% inhibition of cell growth. Less than 5.3% of the drug was found in the plasma membrane when the cells were treated with 1-beta-D-arabinofuranosylcytosine. N4-Palmitoyl-ara-C in the membrane fraction cosedimented with plasma membrane in a sucrose density gradient at 4 degrees, indicating a close association between the drug and the membrane. The affinity of N4-palmitoyl-ara-C for plasma membrane probably contributes to the efficient uptake rate and the strong cytotoxic effect of N4-palmitoyl-ara-C reported previously. The metabolites of N4-palmitoyl-ara-C in KB cells, treated with the drug for 32 hr at the concentration required for 50% inhibition of cell growth (10 microM), were analyzed by diethylaminoethyl Sepharose CL-6B column chromatography and thin-layer and paper chromatography. This analysis showed that over 98% of the drug present in the KB cell was N4-palmitoyl-ara-C. The active metabolites, 1-beta-D-arabinofuranosylcytosine, 1-beta-D-arabinofuranosylcytosine 5'-monophosphate, N4-palmitoyl-1-beta-D-arabinofuranosylcytosine 5'-monophosphate, and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate, were found in amounts of 0.41, 0.37, 0.17, and 0.05%, respectively, of the total drug found in the cells. Also found were the inactive metabolites 1-beta-D-arabinofuranosyluracil and 1-beta-D-arabinofuranosylcytosine diphosphate choline in amounts of 0.61 and 0.29%, respectively.

Animals↗
PubMed1981

Mechanism of natural resistance to vincristine in rat ascites hepatoma AH66.

It was found that AH66, a rat ascites hepatoma inherently refractory to vincristine, exhibited definite resistance to a different class of antitumor agents- adriamycin and actinomycin D. In comparative studies with AH13, a sensitive strain of rat hepatoma, significantly lower levels of cellular retention as well as uptake of these drugs were observed with AH66 cells. However, in the presence of 2, 4-dinitrophenol in glucose-free medium, the uptake of vincristine by AH66 cells was remarkably increased, and addition of glucose induced a spontaneous efflux of drug that had been taken up. These results, in good accord with those for a subline of P388 mouse leukemia which acquired resistance to either adriamycin or vincristine, suggest that there exists an active efflux system common to these different kinds of antitumor agents in naturally resistant rat tumor cells. Further studies revealed that Tween 80 also enhanced the uptake of vincristine by AH66 cells by interfering with the efflux of this drug and thus partially restored the sensitivity in vitro of AH66 cells to vincristine.

2,4-Dinitrophenol↗
PubMed1980

Enhanced cytocidal action of methotrexate by conjugation to concanavalin A.

A methotrexate/concanavalin-A conjugate (MTX/Con-A) was prepared by covalent cross-linking. The extent of substitution was approximately 5 moles methotrexate (MTX) per mole concanavalin A (Con-A). Inhibition of dihydrofolate reductase by the conjugate was only marginal when compared to MTX. However, MTX/Con-A showed a 7- to 116 times higher cytocidal activity than MTX against cultured KB cells and various established cell lines from mouse colon adenocarcinomas 26 and 38, and Lewis lung carcinoma. The effect of MTX/Con-A was diminished when the conjugate was preincubated with alpha-methyl-D-mannoside, a specific binding sugar to Con-A. MTX/Con-A efficiently incorporated into cells and retained in them for longer periods of time than was MTX. The strong cytocidal action of the conjugate could be explained by the higher incorporation rate and the longer retention time of the conjugate in the cells.

Adenocarcinoma↗
PubMed1980

Suppression of Friend leukemia virus by Bacillus Calmette-Guérin and a streptococcal preparation, OK-432.

OK-432, a streptococcal preparation, and BCG effectively inhibited splenomegaly in Friend leukemia virus (FLV)-infected mice. Divided drug dosage resulted in stronger inhibition than single administration. When the second dose was fixed at the 3rd pre-infection day, the best timing for the first dose was approximately 30 days before infection. The optimal dosages were 100--600 KE/kg for OK-432 and 25--100 mg/kg for BCG. Transfer of peritoneal exudate cells (PEC) from immunomodulator-treated mice, but not PEC from untreated mice, conferred resistance against FLV which was highest when PEC were transferred 1 day before FLV infection. The transfer of PEC on the day of or one day after infection had no protective effect. Inactivation also occurred when FLV was incubated in the presence of PEC from immunomodulator-treated mice, however, no significant effect was observed for PEC from untreated mice.

Animals↗
PubMed1980

Prediction of response to and actual outcome of chlorpromazine treatment in schizophrenic patients.

A blink controlled study evaluated the prediction of response to chlorpromazine treatment in 37 schizophrenics on the basis of actual outcomes. Prior to the initiation of treatment, blood samples were taken three hours after a dose of 50 mg of chlorpromazine for the analyses of the drug and its metabolites. The chlorpromazine therapy was then begun and continued for three months. The results agreed with our previous conclusion that patients who showed high levels of the metabolites after a single dose of chlorpromazine tended to have poor clinical improvement with chlorpromazine and that the responders showed the opposite pattern. The predictability of response to chlorpromazine therapy is significantly high in the patients with very low or high levels of the metabolites. However, this is useful at best in 46% of the subjects studied.

Adolescent↗
PubMed1980

Immobilization of enzymes for medical uses on plastic surfaces by radiation-induced polymerization at low temperatures.

The immobilization of some medically useful enzymes were studied by means of radiation-induced polymerization at -78 degrees C. Glucose oxidase and glucose peroxidase were immobilized in the form of thin membranes inside polyvinyl chloride tubes and on polyethylene films; these membranes showed considerable activity yield, as well as good activity retention. Two effective methods were adopted to improve the surface properties of the base materials and to facilitate firm immobilization by coating: that is, an undercoating method followed by radiation curing of the undercoating and an irradiation grafting method with a monomer. Both were tested with good results. An immobilization of urokinase was also carried out successfully by similar methods. The thrombogenicity of the immobilized urokinase showed a remarkable effect on thombus formation.

Adhesiveness↗
PubMed1980

Effect and mode of action of N4-behenoyl-beta-D-arabinofuranosylcytosine.

N4-Behenoyl-beta-D-arabinofuranosylcytosine (behenoyl ara-C, NSC 239336) enhanced chemotherapeutic activity against L1210 murine leukemia as compared with 1-beta-D-arabinofuranosylcytosine (ara-C). Behenoyl ara-C was resistant to deamination by cytidine deaminase, which was supposed to be liable for inactivating ara-C in vivo. Behenoyl ara-C exerted chemotherapeutic activity when administered before implantation of leukemic cells, suggesting prolonged circulation in the body fluid. These two findings indicate that the resistance to the enzymatic deamination and hydrophobicity endowed by behenic residue were responsible for the enhanced chemotherapeutic activity of behenoyl ara-C. This idea was supported by the finding that ara-C encapsulated in liposome enhanced chemotherapeutic activity.

Animals↗
PubMed1980

Inhibition of murine colon adenocarcinomas and Lewis lung carcinoma by 1-hexylcarbamoyl-5-fluorouracil.

1-Hexylcarbamoyl-5-fluorouracil (HCFU) and its parent compound 5-fluorouracil (5-FU) were tested PO for antitumor activity against mouse colon adenocarcinoma 26 (colon 26), colon adenocarcinoma 38 (colon 38), and Lewis lung carcinoma. The drugs were given orally at 2--4 days intervals for a total of ten doses. 5-FU was moderately active against colons 26 and 38 but not against Lewis lung carcinoma. In this treatment regimen the most impressive antitumor activity was obtained with HCFU against colons 26 and 38, especially colon 38 tumor. At 300 mg HCFU/kg, one out of seven mice inoculated with colon 26 and five out of ten mice inoculated with colon 38 became tumor-free. HCFU, however, was marginally effective in the prolongation of survival time of mice bearing Lewis lung carcinoma. 5-FU is approximately twice as active as HCFU against cultured cell lines from colon 26, colon 38, and Lewis lung carcinoma. Lewis lung carcinoma cells were most sensitive against HCFU, which is in contrast to the results obtained in the in vivo experiment. The IC50 value of HCFU against Lewis lung carcinoma cells was approximately half that against colon 26 and colon 38 cells. This higher sensitivity of Lewis lung cells against HCFU could be explained by the higher cellular uptake of the drug.

Adenocarcinoma↗
PubMed1980

Correlation between CT findings and subsequent development of cerebral infarction due to vasospasm in subarachnoid haemorrhage.

We have studied the correlations between computed tomograms (CT), clinical severity at the time of onset, and subsequent development of cerebral infarction due to vasospasm in 32 cases with subarachnoid haemorrhage secondary to rupture of cerebral aneurysms. It was found that the clinical severity could be judged by CT as shown by the amount of blood in subarachnoid space. Furthermore, it was possible to predict the subsequent occurrence of cerebral infarction by sequential findings of CT. A Hounsfield number of the high density area over 60 showed good correlation with the development of cerebral infarction.

Adult↗
PubMed1980

Controlled release of multi-component cytotoxic agents from radiation polymerized composites.

Multi-component cytotoxic (anticancer) agents such as mitomycin C (MMC), adryamycin (ADM) and 1-(2-tetrahydrofuryl-5-fluorouracil) (FT-207), were entrapped in a single common composite by radiation-induced polymerization of glass-forming monomers in the presence of polymers. The release profiles of each cytotoxic agent were controlled by the contents and compositions of three cytotoxic agents in the matrix. The release rates of each cytotoxic agent were retarded by addition of an adsorbent and accelerated by addition of a pore-making agent. The release fom the common matrix of a cytotoxic agent and its promoter which have markedly different molecular weights [e.g. MMC and urokinase (UK)] was also investigated. A double entrapping method was successfully used for controlled release in such cases. In conclusion it was found that the release profiles of multi-components in a single matrix could be controlled by using these techniques.

Delayed-Action Preparations↗
PubMed1980

Effect of propranolol on the urinary excretion of prostaglandin E and plasma renin activity in hypertensive patients.

To investigate the role of the renin-angiotensin (R-A) system in the release of renal prostaglandin E (PGE), urinary excretion of PGE, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured before and after the manipulation of the R-A system in hypertensive patients. After 7 days of the control sodium diet, the R-A system was stimulated by a combination of low sodium diet and oral administration of furosemide for 7 days. From the 4th day of sodium restriction, 40 mg/day of propranolol was administered per os for 2 days, and the dose was doubled for the following 2 days. PRA and PAC were significantly increased after the sodium restriction, but no change in urinary excretion of PGE was observed. Additional administration of propranolol for the following 4 days suppressed PRA significantly and PAC moderately, but it also failed to change urinary excretion of PGE. These results may suggest that renal medullary PGE synthesis, as reflected in urinary excretion of PGE, is not strongly dependent on the R-A system in these hypertensive patients.

Adolescent↗