[The pharmacokinetical analysis of the fate of naphtidrofuryl oxalate (LS121) in human subjects. I. Single intravenous infusion and multiple intravenous infusion].
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Adult↗
Biomedical subjects
Y Sakurai
Publications and source records attributed to Y Sakurai.
[The pharmacokinetical analysis of the fate of naphtidrofuryl oxalate (LS121) in human subjects. II. Estimation of the first-pass effect after oral administration].
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Administration, Oral↗
[Effects of tannins and some related compounds on ethanol-induced gastric lesions in the rat].
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Animals↗
[Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants].
Electroencephalographic (EEG) effects of 450191-S and its metabolites were investigated in unanesthetized rabbits with chronic electrode implants, and they were compared with those of nitrazepam and estazolam. 450191-S at doses of 0.1-0.5 mg/kg, i.v., induced a drowsy pattern of spontaneous EEG: high voltage slow waves and spindle bursts increased in the cortex and amygdala, while the hippocampal theta rhythm was desynchronized. In addition, low voltage fast waves appeared particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus was markedly suppressed by 450191-S. The photic driving response elicited by a flash light in the visual cortex was significantly suppressed by 450191-S. 450191-S showed no significant effect on the recruiting response. The EEG effects of nitrazepam were qualitatively similar but less potent and shorter in duration of action than those of 450191-S. The effects of estazolam were approximately as potent as those of 450191-S, but its duration of action was much shorter than that of 450191-S. 450191-S was more potent than nitrazepam and approximately equipotent to estazolam in suppressing hippocampal and amygdaloid after-discharges. The EEG effects of M-1 and M-2 were similar to those of 450191-S in both qualitative and quantitative aspects. The effects of M-A were quantitatively similar but less potent and shorter in duration of action than those of 450191-S.
Animals↗
Selective reduction of intracellular guanosine 5'-triphosphate pool by 4-carbamoylimidazolium 5-olate in murine tumor cells.
Ehrlich carcinoma and P388 leukemia cells were rendered resistant to 4-carbamoylimidazolium 5-olate (SM-108), and assessments were made of biochemical and pharmacological determinants for the sensitivity to SM-108 using both sensitive and resistant sublines. We observed that the treatment of cells with SM-108 in vitro caused a remarkable decrease in the intracellular guanosine 5'-triphosphate pool level in sensitive but not in resistant sublines. There was no difference in the ability to take up SM-108 between sensitive and resistant sublines, but the cellular conversion of SM-108 to its nucleotide, which is the putative active anabolite of SM-108, proceeded only in sensitive sublines. Enzymological studies revealed that the activity of adenine phosphoribosyltransferase (EC 2.4.2.7), which is believed to conjugate SM-108 with 5-phospho-alpha-D-ribose 1-diphosphate, was very low in the resistant sublines. These results strongly support our previous hypothesis that SM-108 is activated by adenine phosphoribosyltransferase to SM-108-nucleotide which then inhibits hypoxanthine-5'-monophosphate dehydrogenase (EC 1.2.1.14), a key enzyme for the de novo synthesis of guanosine 5'-monophosphate.
Adenine Phosphoribosyltransferase↗
Evaluation of response rates to various antitumor agents of human gastric tumors implanted in nude mouse.
To ascertain the clinical predictability and, in the long run, the usefulness of the human tumor/nude mouse model as a screening tool for antitumor agents, it seems particularly important to use as many tumor lines as possible and to evaluate the therapeutic effectiveness of antitumor agents in terms of the overall response rate of a range of tumors. In this study, using 11 strains of established human gastric tumor xenografts with various histological characteristics and proliferation behavior, the experimental response rates to 8 typical antitumor drugs (mitomycin C, cyclophosphamide, ACNU, cisplatin, adriamycin, vincristine, vinblastine and 5-fluorouracil) were determined and compared with the clinical values. The experimental response rates to adriamycin, vincristine and 5-fluorouracil were in good accordance with the clinical results. However, with the other drugs, significantly higher response rates were observed with the nude mouse model as compared to clinical therapy, indicating that this model tends to overestimate the responsiveness of human tumor to a number of antitumor agents. These results strongly suggest the importance of using appropriate dose levels in the nude mouse to reproduce clinically equivalent effects in this model.
Animals↗
[Dental stain removal (III)].
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Dental Prophylaxis↗
[Management of oxygen inhalation therapy of asthma practiced at home--the current status and future problems at our hospital].
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Adult↗
[Treatment of carotid-cavernous sinus fistula by the balloon technique combined with a by-pass procedure using a vein graft-technical note note].
A case with spontaneous carotid-cavernous fistula treated by balloon catheter technique combined with a extra-intracranial by-pass using a saphenous vein graft between the common carotid artery and the middle cerebral artery is reported. A 72-year-old female was admitted with complaints of recurrent symptoms of carotid-cavernous fistula 4 months after spontaneous remission. Angiograms showed the presence left internal carotid-cavernous sinus fistula. Poor cross-filling from the right internal carotid artery to the territory of the left internal carotid artery via the hypoplastic right A1 and left posterior communicating artery was also observed. Symptoms such as chemosis, exophthalmos and visual disturbance gradually progressed during the hospitalization. A common carotid-middle cerebral artery anastomosis was performed with a saphenous vein graft and the carotid cavernous fistula was occluded directly with a balloon catheter. The blood flow via the graft, cortical blood flow, cortical tissue O2 and CO2 were continuously measured during the operation. After the internal carotid artery occlusion, sufficient blood flow via the graft and no significant changes of the cortical blood flow, cortical tissue O2 and CO2 were observed. The postoperative angiogram showed that the by-pass was patent and all branches of the left internal carotid artery were filled via the by-pass. The postoperative course was uneventful and the progressive symptoms improved except for visual disturbance on the left. She is in good condition one year after the operation. The usefulness of this surgical procedure with monitoring of cerebral blood flow and metabolism during operation is also discussed.
Aged↗
[A case of aneurysm at the junction of the vertebral artery and a spinal arterial branch].
A 68-year-old male suffered from severe occipitalgia, nausea, and vomiting was admitted to our hospital. On admission, he complained only of headache and displayed no evidence of disturbed consciousness or neurological deficits. A computed tomographic (CT) scan revealed a subarachnoid hemorrhage in the basal subarachnoid cisterns, with the thickest, densest area in the bilateral ambient cisterns. Four-vessel angiograms disclosed no pathological findings. The patient was treated with bed rest and his blood pressure was maintained below 120 mmHg. Fortunately, no untoward events occurred during the period of bed rest, and a second vertebral angiogram was obtained 4 weeks after admission. At that time a vertebral artery aneurysm was discovered. At surgery a 3 X 3 X 3 mm aneurysm was found at the junction of the vertebral artery and a branch of the spinal artery. Small clots surrounding the aneurysm were removed. The aneurysm itself was easily clipped without destruction of the caudal cranial nerves and the patient recovered fully. The incidence of vertebral artery aneurysms is very small--about 5%. Moreover, to our knowledge an aneurysm on the proximal portion of the intracranial vertebral artery at the junction of the posterior-inferior cerebellar artery has never before been reported. On the other hand, our case might have been included among cases of subarachnoid hemorrhage of unknown etiology. The first cerebral angiogram revealed no aneurysm; it was found on the second set of angiograms. This case illustrates the importance of repeat angiography when the CT scan clearly shows a subarachnoid hemorrhage.
Aged↗
[A case of agenesis of the corpus callosum accompanied by a ruptured azygos anterior cerebral artery aneurysm and lipoma--a case report].
A 53-year-old woman suffered from sudden onset of severe headache on February 28 in 1982. She was admitted to our hospital soon after onset. On admission, she had a severe headache and nausea, and her consciousness was drowsy. CT scan showed a marked subarachnoid hemorrhage with intracerebral and intraventricular hematoma, a separation of the lateral ventricles with enlargement of posterior horns, and deformity of anterior horn. By these findings, the patient was diagnosed as an agenesis of the corpus callosum with subarachnoid hemorrhage. Left carotid arteriogram revealed an azygos anterior cerebral artery and an aneurysm at the terminal portion of this artery. Surgery was performed on the 24 th day after subarachnoid hemorrhage. Operative finding revealed a little finger's head-sized tumor was situated over the right frontobasal artery. An azygos anterior cerebral artery aneurysm was clipped and tumor was removed. Pathological diagnosis of the tumor was a lipoma. Namely, she had an agenesis of the corpus callosum, an azygos anterior cerebral artery, an aneurysm and a lipoma. There are some reports in which an agenesis of the corpus callosum is accompanied with a lipoma and an azygos anterior cerebral artery is accompanied with an aneurysm. But a case of agenesis of the corpus callosum with an azygos anterior cerebral artery was rarely reported. So this rare case with these anomalies was reported and pathogenesis about the development of 4 anomalies was also discussed.
Agenesis of Corpus Callosum↗
[Intracerebral hemorrhage and characteristic angiographic changes associated with methamphetamine--a case report].
A case of intracerebral hemorrhage and characteristic angiographic changes associated with methamphetamine is reported. A 23-year-old woman suddenly complained of headache, nausea, vomiting and gait disturbance several minutes after intravenous injection of 30 mg of methamphetamine. She was admitted with consciousness disturbance, aphasia and right hemiparesis 26 hours after the onset. CT scan revealed subcortical hemorrhage in the left fronto-parietal region. Left carotid angiogram showed irregular segmental arterial narrowing, "beading" of the anterior and middle cerebral arteries. Emergency craniotomy was performed and a left fronto-parietal hematoma was removed totally. Histologically, the surgical specimen showed many vessels in which included thrombi with perivascular hemorrhage. Post-operative course was uneventful. Repeat carotid angiogram 4 months after the operation revealed normal anterior and middle cerebral arteries. We discussed about associations between the abuse of methamphetamine and the occurrence of intracranial hemorrhage and characteristic angiographic changes. As far as we know, there were 23 reports in an extensive review of the literature on intracranial hemorrhage associated with methamphetamine abuse. In the present case "beading" of the intracranial vessels may be related to angiitis induced by methamphetamine. Both the presence of arterial inflammation and increased blood pressure caused by sympathomimetic action of methamphetamine are probably the important factors in the occurrence of intracranial hemorrhage associated with methamphetamine.
Adult↗
[Traumatic anterior cerebral artery aneurysms--experiences in 4 cases and review of the literature].
Five cases of traumatic anterior cerebral artery aneurysms are reported with special emphasis on the initial CT findings of these cases. One case was already reported by Endo (1974). The cases are three in children and two in adults, male four cases and female one case. Four cases had closed head injury, one open. Consciousness level on admission were diversely from clear to semicomatose. Three cases experienced rupture of aneurysms. Time of diagnosis from trauma was from two days to 34 days. Location of aneurysms were near the junction of callosomarginal artery three cases, frontopolar artery one case, and A1-A2 junction one case. Operation was performed in four cases. Results were good in three cases and fair in a case. A case of no operation had fracture of anterior skull base and died from massive nasal and oral bleeding. Autopsy showed an aneurysm of A1-A2 junction, extending to sphenoid sinus. Histological findings of aneurysmal walls were pseudoaneurysm in all cases. There were 48 cases of traumatic anterior cerebral artery aneurysms in the literature. Most of cases are near the junction of callosomarginal artery. As the etiology of the aneurysm it is said that falx cerebri damages the arterial wall. We consider tear of junction of callosomarginal artery is a important factor, since the brain can easily move at the anterior portion of falx. It is very difficult to diagnosis traumatic aneurysms before rupture. But in our three cases of traumatic anterior cerebral artery aneurysms, computed tomographies of very early stage of trauma showed interhemispherical high density area, hematoma and hemorrhage of corpus callosum.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Injuries↗
Biochemical mode of cytotoxic action of neplanocin A in L1210 leukemic cells.
Neplanocin A, a novel antitumor antibiotic, was investigated to determine the biochemical mode(s) of its cytotoxic action. The molecule is an adenosine analogue with a unique cyclopentane structure in its ribose moiety. Both sublines of L1210 and P388 leukemia resistant to neplanocin A were cross-resistant in vitro to bredinin and 9-beta-D-arabinofuranosyladenine, which have been reported to be activated by adenosine kinase. The adenosine kinase activity was markedly reduced in the resistant sublines as compared with that of the respective sensitive lines. Furthermore, neplanocin A competitively inhibited the phosphorylation reaction of adenosine in a cell-free system. The results indicate that neplanocin A is activated by adenosine kinase. Regarding the target site for neplanocin A, the antibiotic suppressed RNA synthesis to a significantly greater extent than DNA synthesis. This RNA-preferential effect is unique among common antimetabolic antitumor agents.
Adenosine↗
[The United States and Japan Cooperative Cancer Research Program].
The U.S.-Japan Cooperative Cancer Research Program was initiated in 1974 between the National Cancer Institute (NCI) and the Japan Society for the Promotion of Science (JSPS), with a view to eventually conquering cancer. The two countries respectively developed cancer research under different academic systems, and, furthermore, the cancers in the two countries show different characteristics from the viewpoint of geographic pathology. The special significance of cooperative study between the two countries with such different backgrounds was therefore mutually recognized. The cooperative program has involved scientific seminars, mutual dispatch of scientists, and exchange of research materials and information, covering specified areas of cancer research. In the program, four major areas for cooperation were established, resulting in an effective and flexible methodology for carrying out cooperative research. These areas were etiology of cancer, biology and diagnosis of cancer, treatment of cancer, and interdisciplinary areas of cancer research. Notable progress was witnessed throughout the ten years of the program. Especially, the program made it possible for a large number of cancer researchers from the two countries to become acquainted with each other through personal contact in cooperative investigations. After termination of the second term in 1983, the program entered into its third five-year period in 1984, and is currently still in progress.
International Cooperation↗
delta 9-Tetrahydrocannabinol elicited ipsilateral circling behavior in rats with unilateral nigral lesion.
The present study was designed to examine the influence of delta 9-tetrahydrocannabinol (THC) on the central dopaminergic system using circling behavior. THC 5 mg/kg i.p. produced ipsilateral circling in rats with unilateral nigral lesion by 6-hydroxy-dopamine. THC-induced ipsilateral circling was completely antagonized by 0.2 mg/kg of haloperidol. These findings suggest that THC may cause a presynaptic stimulation of nigrostriatal dopaminergic neurons.
Animals↗
Amino acid sequence of the non-collagenous globular domain (NC1) of the alpha 1(IV) chain of basement membrane collagen as derived from complementary DNA.
NC1, the C-terminal non-collagenous globular domain of collagen IV, represents one of the two end regions responsible for the assembly and cross-linking of the extracellular network of basement membrane collagen. Several cDNA clones for the NC1 domain of the alpha 1(IV) collagen chain of mouse have been isolated by using synthetic oligonucleotides as screening probes for mouse libraries. The oligonucleotides were synthesized according to known stretches of the corresponding protein sequence. Sequencing of the overlapping cDNA clones allowed the complete amino acid sequence of the NC1 domain to be deduced as well as the C-terminal 165 amino acid residues of the triple helix. It consists of 229 amino acid residues which comprise two homologous regions with a high content of cysteine. These DNA and protein sequences are compared to the corresponding sequences of other collagens and discussed with respect to their structural and biological significance.
Amino Acid Sequence↗
Potentiation of antitumor agents by calcium channel blockers with special reference to cross-resistance patterns.
The calcium channel blockers verapamil, diltiazem, nicardipine, and niludipine potentiated the antitumor activities of mitotic poison antitumor agents, such as vincristine, vinblastine, vindesine, VP16-213, and taxol in P388 leukemia cells resistant to vincristine. The potentiating effect was generally dependent on the extent of cross-resistance seen in the cell line for these drugs. Calcium channel blockers also potentiate the antitumor activities of several DNA-interacting drugs, such as adriamycin, THP-adriamycin, daunomycin, aclacinomycin A, mitomycin C, actinomycin D, mitoxantrone, and nogalamycin derivatives in P388 leukemia resistant to adriamycin. Greater potentiation was observed for those antitumor agents to which the ADM-resistant cell line had become markedly cross-resistant, with the exception of the nogalamycin derivatives. Only a two-fold enhancement was observed for mitomycin C and aclacinomycin, as the cell line was only weakly cross-resistant to these agents. These results suggest the potential for therapeutic gain through the use of calcium channel blockers in combination with classic chemotherapeutic agents.
Animals↗