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Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 505 records · Page 28Linked to original sources

The antitumor effects of human lymphoblastoid interferon on human renal cell carcinoma in athymic nude mice.

The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast cancer). A pharmacokinetic study on HLBI was also carried out in non-tumor-bearing nude mice. HLBI therapy was performed with a dose of 10(5) IU/mouse by daily SC or IT (intratumoral) injection for 2-4 weeks. Two renal cell carcinomas, KU-2 and RCC-1, proved to be highly sensitive to HLBI. The growth of these tumors was inhibited not only by IT but also by SC injection of HLBI. In contrast, HLBI exerted only a slight effect or none at all on the other human tumors, namely, MX-1, KB, H.Ep#2, and HeLa, even when given by IT injection. The data show that the antitumor effects of HLBI depend on the types of human tumors and may be relevant to the clinical observation that renal tumors are sensitive to HLBI. The serum HLBI reached a peak level of 4,390 U/ml 1 h after a single SC injection at a dose of 10(5) IU/mouse and declined with a half-life of 4 h to 128 U/ml 24 h later. This time-course was not affected by 10 consecutive daily injections of HLBI. In nude mice, the consecutive administration of HLBI at this dose level appears to result in neither accumulation nor rapid clearance due to antibody formation. From this range of serum HLBI levels and its in vitro anticellular activity, the in vivo antitumor effects of HLBI in nude mice seemed to depend on its direct anticellular action.

Animals↗

Inhibition of spontaneous and experimental tumor metastasis by the calcium antagonist verapamil.

Verapamil, a calcium antagonist, inhibited both experimental (IV inoculation of tumor cells) and spontaneous metastasis (SC inoculation) of the highly metastatic B16 melanoma and colon adenocarcinoma 26 cell lines. Verapamil treatment resulted in a maximum 80% inhibition of metastases, the degree of inhibition varying among the different metastatic systems. Verapamil inhibited platelet aggregation induced by these tumor cell lines, the patterns of inhibition being different for B16 melanoma and colon adenocarcinoma. The inhibition of platelet aggregation induced by tumor cells is proposed as a mechanism by which the calcium antagonist exerts its antimetastatic effect. These results, together with our previous findings that calcium antagonists can increase the cytotoxicity of drugs in tumor cells with induced or inherent drug resistance by inhibiting outward transport of the drug, indicate that calcium antagonists have potential as a new class of adjuvant agents in the field of cancer chemotherapy.

Animals↗

Reversibility of granulocyte adhesion using polyamine-grafted nylon-6 as a new column substrate for granulocyte separation.

Reversibility of leucocytes adhered onto the surface of polyamine-grafted nylon-6 was investigated to estimate its feasibility as a new column substrate for granulocyte separation from whole blood. Polyamine-grafted nylon-6 was synthesized by a radical polymerization of 2-diethylaminoethyl methacrylate monomer onto nylon-6. The surfaces of these graft copolymers were found to show a microphase-separated structure composed of island-like phases of cationic polyamine and continuous phases of nonionic nylon-6. Interaction between leucocytes and these copolymer surfaces was studied by passing rabbit heparinized blood through a column packed with glass beads precoated with these copolymers. Columns of these copolymers showed a selective adhesion of granulocytes among leucocyte populations. Also, the adhering granulocytes were able to be recovered from the column by a gentle elution procedure. From these results, it was concluded that polyamine-grafted nylon-6 having a microphase-separated structure is suitable for use as a column substrate in granulocyte separation from whole blood.

Animals↗

Effects of lesions of prefrontal cortex and dorsomedial thalamus on delayed go/no-go alternation in rats.

The effect of prefrontal cortex (PFC) and/or dorsomedial thalamus (DMT) lesions on a delayed go/no-go alternation task was studied in the rat. The lesion gave rise to the impairment of smooth alternation of one response to another, resulting in the generation of some successive repetitions of either response. However, either type of response was generated in virtually equal frequencies during pre- and post-surgery sessions. These results suggest that the DMT and PFC are involved in the memory and response control process for generating the alternation response, and they do not mediate either one type of response. Furthermore, DMT or DMT/PFC lesions induced a larger behavioral impairment than PFC lesions indicating that the DMT plays a major role in generating the alternation behavior based on the memory for the previous response.

Animals↗

[Behavioral pharmacology of amantadine with special references to the effect on abnormal behavior in mice and rats].

Behavioral effects of amantadine, especially on abnormal behavior in mice and rats, were reevaluated, in comparison with those of tricyclic antidepressants, methamphetamine and L-DOPA. 1) Amantadine at 10 approximately 50 mg/kg, i.p., tended to decrease ambulation and rearing in rats and mice. The drug at 50 mg/kg, i.p., caused piloerection and hyperirritability and at doses over 80 mg/kg, i.p., it impaired coordinated motor activity in rats. 2) Amantadine inhibited methamphetamine-induced hyperactivity, but apomorphine-induced stereotyped behavior was unaffected in rats. 3) Amantadine was equipotent to imipramine in suppressing haloperidol-induced catalepsy in rats, but L-DOPA was without effect. On the other hand, amantadine was 40 and 400 times as potent as imipramine and L-DOPA, respectively, in suppressing delta 9-tetrahydrocannabinol (THC)-induced catalepsy in rats. 4) Amantadine was as potent as imipramine in suppressing the muricide of olfactory bulbectomized rats, but was 3.5, 8.8 and 225.5 times as potent as methamphetamine, imipramine and L-DOPA, respectively, in inhibiting THC-induced reversible muricide in rats. 5) Amantadine at 50 mg/kg did not elicit circling behavior in the rat with unilateral nigral lesion induced by 6-hydroxydopamine. 6) Amantadine at high doses caused irritable aggression characterized by squealing in rats pretreated with intraventricular 6-hydroxydopamine. The most important characteristic of amantadine is its prominent effect suppressing the THC-induced catalepsy and muricide. This may be a reflection of the feature of amantadine activating the dopaminergic as well as the serotonergic systems.

Aggression↗

[Behavioral and electroencephalographic effects of lormetazepam].

Behavioral and electroencephalographic effects of lormetazepam were investigated in rats, mice and rabbits, in comparison with those of diazepam, nitrazepam and flurazepam. Locomotor activity of mice in an open-field situation was decreased with large doses of lormetazepam and diazepam, while it was increased with nitrazepam and flurazepam. The anticonflict effect of lormetazepam in rats was much more potent than those of diazepam, nitrazepam and flurazepam. In suppressing the muricide of olfactory bulbectomized and raphe lesioned rats, lormetazepam was more potent than diazepam, nitrazepam and flurazepam. Lormetazepam, diazepam and flurazepam prevented both maximal electroshock and pentetrazol convulsions in mice, the effects on the latter being much more potent than those on the former. Lormetazepam was more potent than diazepam and flurazepam in potentiating thiopental-, ether- and ethanol anesthesia, impairing rotarod performance and in muscle relaxant activity. In conscious rabbits with chronically implanted electrodes, lormetazepam induced a drowsy EEG pattern and suppressed the EEG arousal responses not only to auditory stimulation but also to electrical stimulation of the midbrain reticular formation or hypothalamus. Lormetazepam also inhibited afterdischarges induced by electrical stimulation of the hippocampus and amygdala. These results indicate that lormetazepam has pharmacological properties characteristic of benzodiazepines and that the activity is more potent than those of diazepam, nitrazepam and flurazepam.

Anesthetics↗

A study of insulin and glucagon secretion from adult rat pancreatic monolayer islets.

The present study confirms and extends previous observations that whole pancreatic islets form a monolayer culture in vitro. Our technique, using a medium containing 3-isobutyl-1-methylxanthine (IBMX), clearly demonstrated enzymatic disruption of the islets and cellular organization of isolated pancreatic islets. Insulin or glucagon secretion of monolayer culture was measured during incubation in a medium containing 5.5 mM D-glucose, then in 16.7 mM D-glucose, and finally in a combination of 16.7 mM D-glucose and IBMX, or of low glucose and 20 mM L-arginine. Clearly, such a technique might permit the recovery of collagenase-isolated pancreatic islets during the culture period and also an increase in glucose-induced insulin secretion and arginine stimulated glucagon secretion.

1-Methyl-3-isobutylxanthine↗

Cure of mice bearing P388 leukemia by vincristine in combination with a calcium channel blocker.

Mice inoculated with P388 leukemia were treated initially with vincristine (VCR) at a dose of either 1.5 or 2.0 mg/kg. After 1 week, VCR alone (0.1 mg/kg) was given daily for ten treatments, but no mice were cured with this regimen. However, when the calcium channel blocker verapamil (75 mg/kg) was administered with VCR at 1.5 or 2.0 mg/kg, lifespans were prolonged and one of ten or six of ten mice were cured, respectively. As reported previously, verapamil renders less sensitive or resistant tumor cells susceptible to VCR by inhibiting the VCR efflux mechanism, especially in resistant cells. Therefore, verapamil in combination with VCR apparently can result in total cell kill under the conditions used.

Animals↗

[Antitumor activities of orally administered 4-carbamoylimidazolium-5-olate (SM-108)].

We investigated the antitumor effect of orally administered SM-108. The drug showed strong antitumor activities against Ehrlich carcinoma, sarcoma 180, P388 leukemia, L1210 leukemia, colon 26 adenocarcinoma, colon 38 adenocarcinoma, and Lewis lung carcinoma. The antitumor activity of SM-108 against Ehrlich carcinoma was so remarkable, in fact, that all mice in a group survived for a long time. The antitumor effect of SM-108 depends on its administration schedule. Treatment involving a schedule of one dose every 6 h for 24 h at intervals of 3 days brought about a much stronger effect than daily single treatment. The maintenance of a high serum level of SM-108 for 24 h by the former treatment is responsible for the strong therapeutic effects, because the action of SM-108 is time-dependent. The antitumor activities of SM-108 administered orally are excellent enough to be comparable with those obtained by intraperitoneal administration as previously reported.

Administration, Oral↗

[A case of sigmoid-vesical fistula complicating diverticulitis of the colon].

The clinical course of sigmoidvesical fistula due to rupture of colonic diverticulitis is described. The patient, a 72-year-old-man, had chief complaints of cloudy urine, pneumaturia and fecaluria. The fistula was diagnosed by cystoscopy. In this case, primary resection of the sigmoid colon and wedge resection of the bladder including fistula were performed, and the sigmoidvesical fistula was completely cured. Statistical analysis was made on 43 cases of colovesical fistula due to diverticulitis in Japan including our own case.

Aged↗

[Clinical analysis of vitreous hemorrhage combined with ruptured aneurysm].

Eight cases of vitreous hemorrhage with ruptured intracranial aneurysm (Terson's syndrome) were experienced in our clinic from April, 1978 to April, 1983. They consisted of five males and three famales between 45 and 69 years old. All cases had unconscious attacks and three of them experienced repeated episodes of subarachnoid hemorrhage within 24 hours. CT scan, performed 24 hours within the attack, revealed remarkable high density areas at prepontine and suprasellar cisterns, interhemispheric and sylvian fissures. Ruptured aneurysms, confirmed by cerebral angiography and operative findings, were three anterior communicating artery aneurysms, three internal cerebral artery aneurysms, one middle cerebral artery aneurysm and one anterior cerebral artery aneurysm. We performed radical operation for the ruptured aneurysm, six cases at acute atage, one at 11 days and one at 18 days after the attack. Postoperative courses were all good. Five cases had bilateral vitreous hemorrhages and three had unilateral ones. At first they were treated conservatively. Visual acuity of six cases, 13 eyes improved gradually, but three cases, four eyes did not improve after four or five months after the attack. So we let ophthalmologist to perform vitrectomy, which showed effective results. Vitreous hemorrhage following a ruptured intracranial aneurysm is not a so rare complication than has been assumed and also its prognosis is not so poor. In most cases vitreous hemorrhage following a ruptured intracranial aneurysm should be treated conservatively, but in selected cases effective results would be given by vitrectomy.

Aged↗