Search PubMed⌕ Search

Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 559 records · Page 31Linked to original sources
PubMed1983

Vincristine-resistant P388 leukemia cells contain a large amount of calcium.

P388 leukemia cells resistant to vincristine contained more calcium in the cells than the parent sensitive line, especially in the form of EGTA-removable (surface-bound) calcium. Although the relationship, if any, between the high cellular calcium of resistant cells and drug-resistant phenotype is not clear, the possible implications of this result for the elucidation of the mechanisms of drug resistance are interesting.

Animals↗
PubMed1983

[CT scan in ruptured intracranial aneurysm--comparative studies of initial bleeding and rebleeding].

The differences between initial bleeding and rebleeding due to ruptured intracranial aneurysm was investigated by CT. The study included 120 cases of ruptured cerebral aneurysm; 71 cases had only one bleeding and 49 cases had rebleeding. All the cases underwent CT examinations within 2 weeks following bleeding. Subarachnoid hemorrhages were classified into three groups according to the CT findings: Diffuse high type--high density areas in the entire basal cistern; Localized high type--high density area in a restricted part of the basal cistern; and Iso or Low type--no high density areas in the basal cistern. CT scans done within 24 hours following initial bleeding showed Diffuse high type in 96% of the cases and Localized high type in 4%. On the other hand, in rebleeding cases, Diffuse high type was 50%, Localized high type 25% and Iso or Low type 25%. In rebleeding cases within three days following initial bleeding, Diffuse high type was 90% and Iso or Low type 10%. However, between day 4 and day 14, Diffuse high type was 14%, Localized high type 42% and Iso or Low type 42%. After day 15, Diffuse high type was 36%, Localized type 36% and Iso or Low type 28%. Intracerebral hematoma and/or ventricular hemorrhage secondary to ruptured aneurysms were also investigated. Following initial bleeding, 18% of cases showed intracerebral and/or ventricular hemorrhage, however, the incidence increased up to 59% in rebleeding cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Memory confinement versus generalization decrement on retrograde amnesia produced by cortical spreading depression].

An examination of memory confinement vs. generalization decrement under unilateral cortical spreading depression was undertaken using a licking suppression to a tone previously paired with a shock. In Experiment I, rats that were trained and tested under normal cortical conditions showed an impairment of memory when KCl-induced depression was given to an unilateral hemisphere within 15 min after the training. In Experiment II, where rats were trained under normal cortical conditions followed by unilateral depression and tested under unilateral cortical depression, the degree of impairment was more severe when the test was performed under depression shifted to the other hemisphere than under depression to the same hemisphere. The results taken together support the memory confinement theory.

Amnesia↗
PubMed1983

[Experimental studies on amniotic fluid embolism].

The circulatory state of the so-called experimental amniotic fluid embolism (AFE) was studied in 39 dogs. The repeated infusion of a large quantity of human amniotic fluid had not produced the symptoms of AFE. But the infusion of human meconium-stained amniotic fluid, meconium suspension, its supernatant or boiled meconium suspension, or canine bile had produced the various typical shock symptoms of AFE. In these cases the shock effects were especially strong in the infusion of meconium suspension and the meconium-stained amniotic fluid. In these shock symptoms, arterial pressure decreased quickly after the infusion. When sudden death was fortunately avoided, right ventricular pressure increased and increases in pulmonary arterial pressure and pulmonary vascular resistance were indicated. In most cases cardiac output decreased. Central venous pressure increased suddenly before death. These experiments suggested that the pulmonary vasoconstriction was produced by the chemical factors in the amniotic fluid and by vasoactive substances released from the embolized lung. It also seemed that this pulmonary vasoconstriction rather than mechanical obstruction of pulmonary arterioles was probably the major cause of the shock symptoms of AFE.

Animals↗
PubMed1983

Potentiation of vincristine and Adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors.

verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant subline of K562 myelogenous leukemia. A maximum of approximate 100-fold increase in VCR cytotoxicity occurred. Heterogeneity in VCR sensitivity (80-fold difference in sensitivity) was observed in vitro among these human tumor cells. BALL and Daudi cells of B-cell type were more susceptible to VCR. At 6.6 or 20 microM of verapamil, the values for the concentration of drug required for 50% inhibition of cell growth for each cell line fell into a rather narrow range, and heterogeneity in VCR sensitivity among cell lines was circumvented in vitro. Verapamil also enhanced the cytotoxicity of Adriamycin, although the extent of enhancement was considerably small. Enhancement of VCR cytotoxicity also occurred with other calcium antagonists and calmodulin inhibitors. At maximum effective concentration of these reagents, a 3- to 5-fold increase in VCR cytotoxicity occurred in K562 cells. In VCR-resistant K562 cells, a more prominent enhancement (20- to 45-fold) was observed with these reagents. VCR resistance was circumvented in vitro. The mechanism of enhancement of VCR cytotoxicity was explained by the enhanced accumulation of VCR in K562, especially in resistant cells.

Calcium↗
PubMed1983

Promotion by verapamil of vincristine responsiveness in tumor cell lines inherently resistant to the drug.

Cultured cell lines LL, B16, C26, and C38 established from mouse solid tumors of Lewis lung carcinoma, B16 melanoma, and colon adenocarcinomas 26 and 38, respectively, showed inherently different resistance to vincristine (VCR) in vitro. The inherent resistance to VCR of these cell lines was related to the ability of the cells to accumulate VCR. Verapamil, a calcium antagonist with coronary vasodilator activity, enhanced the cytotoxicity of VCR against these cell lines depending upon their susceptibility to VCR. C26 cells, the most resistant, became the most susceptible to VCR with a nontoxic dose of verapamil. A 12-fold increase in VCR cytotoxicity occurred. Only a 2.5-fold increase in VCR cytotoxicity was observed for B16 cells, the most sensitive cells. VCR cytotoxicity against each cell line reached almost the same level by verapamil (2.2 to 6.6 microM). Thus, the inherent resistance to VCR among the tumor lines was circumvented. Verapamil enhanced the cellular accumulation of VCR. A 3- to 4-fold increase in cellular VCR occurred in C26 cells, while approximately a 2-fold increase was observed for B16 and LL cells. A similar rate of enhancement was observed for both bound and free VCR, indicating that verapamil does not enhance the affinity of VCR to tubulin. Verapamil inhibited the outward transport of VCR from the cells. The most prominent inhibition was observed for C26 cells. Circumvention of inherent resistance of tumor cells to VCR by verapamil could be attained through an enhanced cellular accumulation of VCR in each of the tumor cells. The enhancement of VCR cytotoxicity and circumvention of inherent VCR resistance by verapamil could be explained by the cellular concentration of VCR, and also it might be related to the extent of VCR binding to tubulin in the cell. The chemotherapeutic effect of VCR is significantly enhanced by verapamil in colon adenocarcinoma 26-bearing mice.

Adenocarcinoma↗
PubMed1983

Circumvention of vincristine and Adriamycin resistance in vitro and in vivo by calcium influx blockers.

Calcium influx blockers, diltiazem, nicardipine, nifedipine, niludipine, and nimodipine, which possess coronary vasodilator activity, greatly enhanced the cytotoxicity of vincristine (VCR) in tumor cells and especially in VCR-resistant sublines of P388 leukemia (P388/VCR) and human K562 myelogenous leukemia. The extent of enhancement was different among the drugs, and up to a 50- to 70-fold increase in VCR cytotoxicity occurred in P388/VCR cells with nontoxic or marginally toxic concentrations of diltiazem and nicardipine. A 50- to 100-fold enhancement occurred in VCR-resistant human K562 myelogenous leukemia cells with diltiazem, nicardipine, niludipine, and nimodipine. VCR resistance of these cell lines was circumvented completely by these blockers. Calcium influx blockers also enhanced the cytotoxicity of Adriamycin in P388 leukemia cells and especially in its Adriamycin-resistant subline. The extent of enhancement, however, was lower than that which occurred in VCR-resistant tumor lines with VCR. An approximately 10- to 30-fold increase in Adriamycin cytotoxicity occurred in P388 Adriamycin-resistant subline cells with diltiazem, nicardipine, niludipine, and nimodipine. Although VCR alone at 10 to 200 micrograms/kg did not confer a significant therapeutic effect in P388/VCR-bearing mice, calcium influx blockers in doses of 30 to 125 mg/kg administered daily for 10 days with VCR enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. A maximum of approximately a 40 to 50% increase in life span occurred with diltiazem, nicardipine, niludipine, and nimodipine. The calcium influx blockers also enhanced the therapeutic effect of Adriamycin in P388 Adriamycin-resistant subline-bearing mice, although the extent of enhancement was smaller than that observed with VCR in P388/VCR-bearing mice.

Animals↗
PubMed1983

[Development of antitumor agents: retrospection and perspective].

A concept of antitumor screening with rodent tumor models is discussed through the experience in the past 30 years, together with an introduction of a new system of antitumor screening in NCI, U.S.A., including a recently adopted mouse ovary tumor model. It is suggested that the more minute and elaborate studies of mode of action of the effect and toxicity of the antitumor drugs which are already clinically evaluated are useful to get new structures of compounds with antitumor activity into our minds. A new approach in studying drug resistance of tumor cells proposed by Ling is introduced that some of the acquired drug resistance is closely related to natural resistance of tumor cells which occurs by spontaneous mutation of the cells during proliferation.

Animals↗
PubMed1983

[Interferon as a treatment tool of cancer].

Characteristics of beta-IFN (Interferon) and alpha-IFN with its subspecies are described, which are produced by cell cultivation process or by gene cloning. beta-IFN exhibited far stronger cytostatic effect in vitro on the human epitherioid cells than hematologic malignant cells which were very sensitive to alpha-IFN. Pharmacokinetic study in man indicated that alpha-IFN appeared in the blood at a detectable concentration after i.m. injection of 3-6 X 10(6) iu/body, but beta-IFN did not. beta-IFN was less stable than alpha-IFN in the blood, tissues, and also medium for cell culture. The preliminary clinical data of alpha- and beta-IFNs indicates that there is a little difference in effect and side-effect of the both IFNs. At the moment, beta-IFN seems to show a stable therapeutic effect on brain tumor by using Ommaya reservoir, and malignant melanoma on the skin disappeared in some cases by intratumoral injection of beta-IFN.

Cell Line↗
PubMed1982

Enhancement of vincristine- and adriamycin-induced cytotoxicity by verapamil in P388 leukemia and its sublines resistant to vincristine and adriamycin.

A calcium antagonist, verapamil, enhanced the cellular uptake and cytotoxicity of vincristine (VCR) in adriamycin-resistant P388 leukemia (P388/ADM) cells and also enhanced the cellular uptake and cytotoxicity of adriamycin (ADM) in vincristine-resistant P388 leukemia (P388/VCR) and P388/ADM cells. The enhancement of cytotoxicity and cellular uptake of VCR in P388 and P388/VCR cells has been reported previously. [1]. VCR and ADM resistance was circumvented by verapamil. A common transport mechanism for VCR and ADM, which is responsive to verapamil, seems to exist in VCR- and ADM-resistant cells. However, the enhancement of ADM cytotoxicity and cellular uptake by verapamil was not evident in P388 cells.

Animals↗
PubMed1982

Enhancement of [3H]dopamine release and its [3H]metabolites in rat striatum by nicotinic drugs.

Recent evidence has identified directly muscarinic acetylcholine receptor (m-ACh R) and nicotinic acetylcholine receptor (n-ACh R) in the brain utilizing receptor binding assay. Several studies suggest that release of dopamine (DA) in the striatum is regulated by presynaptic receptors present on dopaminergic terminals. In the present study, the effects of cholinergic drugs on [3H]DA release were examined using micropunched tissue and synaptosomes obtained from rat striatum. ACh (5 x 10(-4) M) significantly increased spontaneous [3H]DA release, and the overflow was partially inhibited by D-tubocurarine (1 mM) but not atropine. Nicotine, lobeline, coniine and spartein, nicotinic agonists, significantly increased spontaneous and 25 mM K + evoked [3H]DA release almost in a dose-dependent manner. In contrast, oxotremorine (2 x 10(-4) M), muscarinic agonist, did not any change in [3H]DA efflux. Furthermore, the metabolites of [3H]DA were separated by column chromatography. The main metabolite of [3H]DA in the spontaneous release from rat striatal synaptosomes was [3H]DOPAC (3,4-dihydroxyphenylacetic acid). Lobeline (5 x 10(-5) M) accelerated the outflow of [3H]DOPAC and [3H]OMDA metabolites (O-methylated and deaminated metabolites). These results could give rise to the suggestion that there was n-ACh R on the dopaminergic nerve terminals in the striatum and n-ACh R might have related to a directly excitatory effect on the DA release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Reduction of lethal toxicity of chloroethylnitrosoureas by sugar alcohols without loss of antitumor activity.

Sugar alcohols, such as mannitol, sorbitol, galactitol, and inositol, selectively reduced the acute lethal toxicity of 1-(2-chloroethyl)-3-(methyl alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU) without reducing its antitumor activity. Fifty mg MCNU/kg killed all CD2F1 mice within about 10 days, while the administration of 3,000 mg sugar alcohols/kg immediately prior to MCNU protected mice from the lethal toxicity and all survived. The amelioration of MCNU toxicity by sugar alcohols was dose-dependent. Pretreatment with mannitol 1 day before MCNU administration was effective. In addition, a series of five daily treatments with lower doses of mannitol was also effective. This protection was accompanied by the reduction of both body weight loss and myelosuppression. The antitumor effects of MCNU on P388 leukemia and Lewis lung carcinoma were not significantly altered by mannitol treatment. These phenomena were not limited to MCNU, the lethal toxicity of GANU, ACNU, Me-CCNU, and mitomycin C also being reduced by mannitol treatment.

Animals↗
PubMed1982

Characteristics of in vitro antiproliferation activity of human interferon-beta.

We compared the in vitro antiproliferative activity of highly purified interferon (IFN)-beta (greater than 10(7) U protein/mg in antiviral activity) with that of IFNs-alpha and lymphoblastoid, using human cells of malignant and non-malignant origin. IFN-beta was the least active of three IFNs in suppressing Daudi cell proliferation. Three hematological cells other than Daudi cells cultivated in suspension were insensitive to each of three IFNs. IFN-beta was more active than IFNs-alpha and lymphoblastoid in suppressing all eight epithelioid cells tested and, particularly with respect to five epithelioid cells sensitive to IFN, IFN-beta was seven to 49 times as active as IFN-alpha. These results indicate that suppression of cell proliferation by IFN depends not only on the target cell species but also on the IFN species, and emphasize the need for careful selection of the most appropriate IFN species in therapy. We found that the antiproliferative characteristics of the present IFN-beta preparation were consistent with those reported previously, supporting the idea that IFN-beta molecules in the present preparation were responsible for suppressing cell proliferation. The antiproliferation activity of our preparation was species-specific but not selective for cells of malignant origin; it was absorbable by IFN-sensitive but not by IFN-insensitive cells; and it was achieved by a cytostatic effect.

Absorption↗
PubMed1982

A new therapeutic method for acute brain infarction: revascularization following the administration of mannitol and perfluorochemicals--a preliminary report.

Ten patients were treated with systemic administration of mannitol followed by blood substitute (perfluorochemicals) in the acute period of cerebral infarction in order to suppress the development of infarction and progressive deterioration. This chemotherapy was followed by reconstructive vascular surgery. There were 8 patients with cerebral infarction and 2 others in whom cerebral vascular occlusion occurred during an operation. Due to this treatment, there was no case in which the patient's condition was aggravated or in which death occurred. At examination two months later, 8 of the 10 patients had returned to productive lives. We consequently believe that this therapeutic method may prove to be an effective means of treating cerebral infarction in the acute stage. It is also thought that this method is applicable in surgical cases in which long-term vascular occlusion is required.

Adult↗
PubMed1982

Effect of microphase separated structure of polystyrene/polyamine graft copolymer on adhering rat platelets in vitro.

Rat platelet adhesion on microphase separated surface of polystyrene/polyamine graft copolymers (SA copolymers) was investigated. Shapes of adhering platelet were very much changeable in response to the mode of microphase separation of SA copolymer surfaces. We assume that the microphase separated structure of SA copolyer may regulate the shape change of platelet through its effect on a redistribution of proteins and/or lipids present at the plasma membrane of platelets.

Animals↗
PubMed1982

Studies on 125I-alpha bungarotoxin binding sites in rat brain.

The distribution and properties of 125I-alpha bungarotoxin (125I-alpha BTX) binding in rat brain using micropunched tissue homogenates were examined with a binding technique. Highest level of 125I-alpha BTX binding was observed in the hypothalamus, followed by hippocampus, cortex, globus pallidus, nucleus caudatus and nucleus accumbens. Although high levels of 3H-quinuclidinyl benzilate (3H-QNB) binding in the striatum were found at dorso-lateral sites and low levels in the central regions, the level of 125I-alpha BTX binding within the striatum was almost equal. There was no significant correlation between 125I-alpha BTX binding and choline uptake which could be useful as a marker for functional cholinergic nerve terminals. The inhibition of specific 125I-alpha BTX binding to the hippocampal homogenates by nicotine, d-tubocurarine and other nicotine drugs was studied. The results of these studies suggest that alpha BTX binding sites in the brain are not likely the binding sites of nicotine or the physiological ACh R sites.

Animals↗