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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 595 records · Page 33Linked to original sources
PubMed1981

Enhancement of vinblastine-induced cytotoxicity by lysolecithin and phosphatidylinositol.

Vinblastine inhibited the growth of cultured KB cells 3 days after drug treatment by 55% and 67% at 2.7 ng/ml and 3.5 ng/ml of the medium, respectively. Lysolecithin and phosphatidylinositol showed only a marginal inhibitory effect on the growth of KB cells at respective concentrations of 35-125 microgram/ml and 50-150 microgram/ml of the medium. Lysolecithin, however, enhanced the cytotoxicity of vinblastine. Depending upon the concentrations of lysolecithin (35-125 microgram/ml), the growth of KB cells was inhibited by 60-91% and 86-98% at respective vinblastine concentrations of 2.7 ng/ml and 3.5 ng/ml. Enhancement of vinblastine-induced cytotoxicity also occurred similarly for phosphatidylinositol. The mechanism could be explained partly by an elevated amount of intracellular vinblastine. Other possible mechanisms can only be speculated.

Cells, Cultured↗
PubMed1981

A circadian variation in the excretion of urinary kinin, kallikrein and prostaglandin E in normal volunteers.

The present study shows that there is a circadian variation in the excretion of urinary kinin, kallikrein and prostaglandin E (PGE) as well as urine flow, urinary sodium excretion and urinary potassium excretion in recumbent healthy volunteers. The present data, that the acrophase of urinary kallikrein excretion was 1.5 hr later than that of plasma aldosterone concentration (PAC) and that a significant positive correlation was found in circadian variations between urinary kallikrein and PAC, suggest that the circadian variation of urinary kallikrein excretion may be regulated by aldosterone. The pattern of circadian variation of average urinary kinin excretion coincided with those of average urine flow, urinary sodium excretion and urinary PGE excretion, suggesting that renal kinin and PGE may be involved in the regulation of water-sodium excretion. The present data that the phase of circadian variation of urinary kinin was delayed from that of urinary kallikrein and that there was a mirror image between the circadian variation in urinary kinin and kallikrein suggest that there may be a feedback mechanism in renal kallikrein-kinin system.

Adult↗
PubMed1981

Inhibition of lymph node metastasis of P388 leukemia by bestatin in mice.

Bestatin, a chemically defined immunostimulant of low molecular weight, suppressed the gradually-occurring lymph node metastasis of P388 leukemia in CDF1 mice when administered i.p. at the doses of 1 approximately 30 micrograms/mouse. It could not, however, suppress the established large metastasis of P388 leukemia. Lymph node cells isolated from the mice given bestatin i.p. at 1 and 30 microgram/mouse showed cytostatic activity against P388 leukemic cells in vitro than those from the untreated mice.

Animals↗
PubMed1981

Antitumor activity of 7-n-(p-hydroxyphenyl)-mitomycin C in experimental tumor systems.

The antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) was compared with that of mitomycin C (MMC) in rodent tumor systems. M-83 exhibited more potent activity than MMC against the ascitic form of lymphocytic leukemia P388 and fibrosarcoma Meth 1, and doses of over 5 mg/kg of M-83 (1/6 LD50) resulted in some 60-day survivors. The chemotherapeutic ratio (optimal dose/MED) of M-83 was around 64 and was estimated to be approximately 5 to 8 times higher than that of MMC. Upon intravenous administration, M-83 also gave a better survival and showed a higher chemotherapeutic ratio than MMC against intravenously implanted P388. M-83 inhibited the growth of solid form of sarcoma 180 to the same extent as MMC at an equivalent dose, but showed a higher safety margin than MMC. M-83 was as effective as MMC against Lewis lung carcinoma at dose levels giving the same degree of toxicity. In vitro studies on tumor growth inhibition demonstrated that the cytotoxic effects of M-83 against leukemia P388 and fibrosarcoma Meth 1 cells were similar to and stronger than those of MMC, respectively.

Animals↗
PubMed1981

Comparison of the hematologic toxicity of 7-N-(p-hydroxyphenyl),-mitomycin C and mitomycin C.

7-N-(p-Hydroxyphenyl)-mitomycin C (M-83), a new analog of mitomycin C (MMC) with equivalent or greater antitumor potencies against various experimental tumors, was investigated to determine its hematologic toxicity in mice. M-83 showed a significantly lower toxicity than MMC with respect to myelosuppression and leukopenia when compared at equivalent effective doses. In M-83-treated mice, the damage to the bone marrow was much milder at the nadir point and the recovery from myelosuppression to the normal level was faster as compared with that in the case of MMC. As a result, the number of white blood cells in the peripheral blood of the M-83-treated groups was considerably greater than that in the MMC-treated ones. These findings suggest that M-83 may be effective in clinical use.

Animals↗
PubMed1981

Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil.

A noncytotoxic dose of verapamil, a coronary vasodilator, enhances the cytotoxicity of vincristine (VCR) and vinblastine in P388 leukemia and its VCR-resistant subline, P388/VCR. When 2.2 to 6.6 microM verapamil was added along the VCR to the P388/VCR culture in vitro, VCR resistance was completely overcome. Verapamil in doses of 50 to 100 mg/kg administered daily for 10 days with VCR also enhances the chemotherapeutic effect of VCR in P388- and, especially, P388/VCR-bearing mice. When approximately 3 times the amount of VCR was given to a P388/VCR bearer as compared to a P388 bearer, VCR resistance was almost completely overcome in vivo with 50 to 100-mg/kg doses of verapamil. The amount of VCR incorporated into P388 cells was larger than that in P388/VCR cells. Verapamil (6.6 microM) enhanced the cellular level of VCR in P388 cells 2-fold and enhanced the level of VCR in P388/VCR cells 10-fold. The amount of VCR in P388/VCR cells reached the same level as that found in P388 cells. The overcoming of VCR resistance in vivo and in vitro could be explained by the effective accumulation of VCR by verapamil in P388/VCR cells mediated by the inhibition of a VCR efflux function of the cells, a mechanism which remains to be solved.

Animals↗
PubMed1981

Production of N4-succinyl-1-beta-D-arabinofuranosylcytosine, a novel metabolite of N4-behenoyl-1-beta-D-arabinofuranosylcytosine, in mice and its biological significance.

A novel metabolite was found in the urine and bile of mice given i.v. injections of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (behenoyl-ara-C). Acid and alkaline hydrolysis of this metabolite resulted in the production of 1-beta-D-arabinofuranosylcytosine and succinic acid, as determined by thin-layer chromatography and high-performance liquid chromatography. Mass spectrometry identified this metabolite as N4-succinyl-1-beta-D-arabinofuranosylcytosine (succinyl-ara-C). This conclusion was supported by thin-layer chromatography and by the ultraviolet spectrum, upon which the characteristics of this metabolite agreed with those of succinyl-ara-C. Only a very small amount, if any, of this metabolite was found in the urine and bile of mice given injections of N4-stearoyl- or N4-palmitoyl-1-beta-D-arabinofuranosylcytosine, suggesting that behenoyl-ara-C was metabolized differently from the other two analogs. Comparison of the metabolites of behenoyl-ara-C, radiolabeled at different positions of the behenoyl-residue, suggested that behenoyl-ara-C was degraded by omega-oxidation and then by beta-oxidation, resulting in the production of succinyl-ara-C. This metabolite was more potent than behenoyl-ara-C in suppressing the in vitro proliferation of murine L1210 cells. The high therapeutic potency of behenoyl-ara-C in L1210-bearing mice may be ascribable to the contribution of succinyl-ara-C to the efficacy of behenoyl-ara-C, either by suppressing the proliferation of L1210 cells or by protecting 1-beta-D-arabinofuranosylcytosine, the possible eventual metabolite, from inactivation by deaminase.

Animals↗
PubMed1981

[Direct surgical treatment of giant intracranial aneurysms (author's transl)].

This report discusses the surgical techniques employed in the 27 cases of giant aneurysm of the brain in which direct operations were performed at the Department of Neurosurgery of Tohoku University from 1961 to 1979. The report also provides a review of the operative results and long-term result of these cases. The conclusions are as follows: 1) Whenever possible, direct operation was implemented in all cases with the exception of infraclinoid ones. The propriety of the neck treatment greatly affected the mortality of the operation. 2) In most cases, there are more difficulties involved in radical surgery on giant aneurysms than on ordinary aneurysms. Temporary occlusion of the afferent and or efferent arteries under the administration of 800 to 1000 microliters 20% mannitol is thought to be a safe and effective method for procedures such as treatment of the aneurysmal neck. 3) In the case of a giant aneurysm of the internal carotid artery, STA-MCA anastomosis was performed before the ligation of the internal carotid artery and this method gave better results than direct operation.

Adolescent↗
PubMed1981

Effect of imipramine on high potassium evoked 3H-dopamine release in the rat striatum.

The effects of three different types of dopamine (DA) uptake inhibitor, imipramine, cocaine and nomifensine, were examined on high potassium evoked 3H-DA release using tissues obtained from rat striatum by a micropuncture technique. Imipramine caused an increase in 3H-DA efflux and this imipramine-induced efflux is Ca2+-independent. Moreover, imipramine reduced the high potassium evoked release, and at 50 microM, the release by potassium stimulation was entirely abolished. These results support that imipramine depletes vesicular DA which is released by potassium stimulation as well as an inhibitory effect on DA uptake. However, nomifensine dose not have such an effect.

Animals↗
PubMed1981

[Continuous measurement of regional cerebral blood flow using krypton-81 m (author's transl)].

In order to obtain sequential change of cerebral blood flow using the intracarotid 81mKr infusion method, we devised a new method by using the radiation from cervical internal carotid artery as the concentration of radioisotope in the blood perfused to the brain. Under continuous intracarotid injection of 81mKr, the radio activity obtained from the surface of the skull is proportional to the cerebral blood flow. However, since the method depends upon the infusion of a given volume of radioisotope per unit of time into the internal carotid artery, changes in the blood flow through the internal carotid artery result in changes in the concentration of radioisotope perfused to the brain. Under such conditions, the radioactivity obtained from the surface of the skull does not indicate the changes in blood flow. In such a case, the value obtained from the radioactivity (count rate) in the ROI of the brain divided by concentration of radioisotope in the blood perfused to the brain indicates the changes in cerebral blood flow. Our attention was drawn to the fact that the radioactivity measured from a constant area of the cervical internal carotid artery per unit of time is an indicator of the blood concentration of radioisotope following in the internal carotid artery, provided that, there are no changes in the size of lumen of internal carotid artery. According to this method devised by us, it had been possible to follow extremely short period changes in cerebral blood flow following CO2 inhalation, change of blood pressure (autoregulation) and administration of various drugs.

Adult↗