PubMed Health⌕ Search

Biomedical subjects

A Akimoto

Publications and source records attributed to A Akimoto.

At least 19 recordsLinked to original sources
PubMed2002

A new delivery system for 5-fluorouracil using prodrug and converting enzyme.

AIMS: To evaluate a new delivery system of 5-fluorouracil (5-FU) using 5-fluorocytosine (5-FC) as a prodrug and cytosine deaminase induced in vitro and in vivo. METHODS: Fibroblastic cells from rabbit Tenon's capsule were cultured. The cells were exposed to 5-FU and 5-FC with or without cytosine deaminase induced by recombinant adenovirus. In the in vitro study, cell proliferation and DNA synthesis were assessed by MTS, BrdU assay. The effect of 5-FC removal after the treatment of 5-FC and cytosine deaminase induction was also assayed. In the in vivo study cells with or without cytosine deaminase induction were transplanted into the subconjunctival space of mice, followed by eye drops of 1000 microg/ml of 5-FC three times a day. The mice were sacrificed at days 1, 5, and 10, then the cells transplanted were evaluated. RESULTS: Cell proliferation was inhibited by exposure to 5-FU in a dose dependent manner; however, up to 1000 microg/ml of 5-FC did not affect cell proliferation. Cell proliferation was inhibited by exposure to 5-FC in a time dependent manner with induction of cytosine deaminase following infection of recombinant adenovirus. When 5-FC was removed 3 or 6 days after the treatment, the cells grew again. The effect was reproduced in the in vivo model of subconjunctival cellular proliferation although 5-FC was administrated as eye drops. There were no cases with corneal erosion. CONCLUSION: Cell proliferation was inhibited by co-exposure of 5-FC and cytosine deaminase. This new delivery system may merit controlled delivery of 5-FU after filtering surgery.

Animals↗
PubMed2001

Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients.

BACKGROUND: Heterozygous mutations of the bestrophin gene are associated with Best macular dystrophy (BMD). The bestrophin gene is specifically expressed in the retinal pigment epithelium. BMD is a hereditary form of macular degeneration that may develop subretinal neovascularisation similar to the wet type of age-related macular degeneration (AMD). PURPOSE: To study whether mutations of the bestrophin gene occur in non-familial Japanese AMD patients. METHODS: A total of 85 non-familial AMD patients (average age 67.5 years; 71 male, 14 female) diagnosed by indocyanine green angiography were screened. Among them, 69 patients (81 %) were classified as having wet type AMD. Genomic DNA was purified from the total blood and used as the template for polymerase chain reaction (PCR). All the exons of bestrophin gene were amplified by PCR. Mutation analysis was performed by SSCP using the ABI Prism 310 Genetic Analyzer (Perkin Elmer). Nucleotide sequence was determined by direct sequencing of the PCR amplicons. As the control, 105 non-AMD patients (average age 62.0 years; 52 male, 53 female) were screened by the same method. RESULTS: Only one AMD patient had a specific polymorphism in exon 2, but no mutations leading to amino acid substitutions were found. In exon 2 and 3, two further polymorphisms were detected in all AMD patients as well as normal controls. CONCLUSION: No mutations were found in the bestrophin gene in nonfamilial Japanese patients with AMD or in normal controls.

Aged↗
PubMed1999

Rat liver in vivo replicative DNA synthesis test for short-term prediction of nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan.

A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.

Animals↗
PubMed1998

ONO-4007, an antitumor lipid A analog, induces tumor necrosis factor-alpha production by human monocytes only under primed state: different effects of ONO-4007 and lipopolysaccharide on cytokine production.

ONO-4007 is a synthetic lipid A analog that exhibits strong antitumor activity in several animal models via intratumoral production of tumor necrosis factor (TNF). In the present study the cytokine-inducing effect of ONO-4007 was investigated in human monocytes that were freshly isolated or had been incubated for 3 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor. ONO-4007 induced slight production of TNF-alpha, Interleukin (IL)-1 beta, IL-6 and IL-12 in fresh monocytes but strongly induced TNF-alpha production in GM-CSF-treated monocytes. Monocytes treated with macrophage colony-stimulating factor were also primed to produce TNF-alpha in response to ONO-4007. In the production of IL-1 beta, IL-6 and IL-12, GM-CSF did not show a priming effect. In contrast to ONO-4007, lipopolysaccharide (LPS) induced significant amounts of all these cytokines in fresh monocytes. In whole blood, ONO-4007 failed to induce TNF-alpha, whereas LPS and LA-15-PP (Escherichia coli-type lipid A) strongly induced TNF-alpha production. In the GM-CSF-treated monocytes, both elimination of serum from the culture medium and anti-CD14 antibody treatment attenuated LPS-induced TNF-alpha production but not ONO-4007-induced TNF-alpha production. This study shows that ONO-4007 activates human monocytes/ macrophages to release TNF-alpha only in a primed state and suggests that ONO-4007 would activate these cells via different pathways from LPS. These differences could mean that ONO-4007 has potent antitumor activity with lower toxicity than LPS.

Adult↗
PubMed1997

Restoration of immune responses in tumor-bearing mice by ONO-4007, an antitumor lipid A derivative.

ONO-4007, a synthetic lipid A derivative, has been found to exhibit potent antitumor activity in several animal models. In the present study, we examined the effects of ONO-4007 on delayed-type hypersensitivity (DTH) reaction and antibody production in Meth A sarcoma-bearing BALB/c mice. The DTH reaction to sheep red blood cells (SRBC) and the IgG production against keyhole limpet hemocyanin (KLH), were depressed in tumor-bearing mice as well as in normal mice given Mitomycin C (MMC). However, ONO-4007 restored these immune responses to normal levels. In addition, in vitro studies showed that ONO-4007 induced the production of tumor necrosis factor-alpha (TNF-alpha) in splenic adherent cells of tumor-bearing mice more than those in normal mice. Though ONO-4007 alone had little effect on the induction of IL-2 production in spleen cells, it augmented the Concanavalin A (Con A)-stimulated IL-2 production. Moreover, ONO-4007 had a mitogenic effect on spleen cells. These results suggest that ONO-4007 may improve immunocompetence in tumor-bearing hosts and contribute to the induction of antitumor immunity and prevention of bacterial infections.

Adjuvants, Immunologic↗
PubMed1987

[Effect of OU-1308 on uterine motility in pregnant rats and monkeys].

Effect of OU-1308 (17s, 20-dimethyl-6-oxo-prostaglandin E1 methyl ester) on uterine motility in anesthetized rats and monkeys was examined by means of the balloon catheter or open-end catheter method and compared with that of PGF2 alpha. OU-1308 and PGE2 alpha exhibited uterine contractile activity at the dose of 30 micrograms/kg, i.v., on day 8 of pregnancy and 10 micrograms/kg, i.v., on day 20 of pregnancy in rats. In monkeys on day 50 approximately 120 of pregnancy, both compounds enhanced uterine motility at 10 micrograms/kg, i.v. Intragastric administration of OU-1308 at 500 micrograms/kg, however, was without effect in monkeys. These results indicate that when administered intravenously, OU-1308 was as potent as PGF2 alpha in terms of uterine contractile activity in pregnant rats and monkeys.

Administration, Oral↗
PubMed1987

[Reproductive pharmacology of prostaglandins].

Effects of prostaglandins and their analogues in reproduction were investigated using rats and Japanese monkeys. Prostaglandin of the F series exerted uterine contractile, luteolytic, anti-nidation and abortifacient effects. Prostaglandins of the E series exhibited a potent uterine contractile effect, although their luteolytic, anti-nidation and abortifacient effects were much less potent than those of the PGF series. A comparison of animal and human data on prostaglandins and their analogues indicated a good cor-relationship between the uterine contractile effect in animals (rates and monkeys) and the abortifacient or labor inducing effect in humans.

Abortifacient Agents↗
PubMed1981

[Effects of 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802) on uterine motility (author's transl)].

In rats on day 20 of pregnancy, ONO-802 exerted a uterine contractile effect when 0.2 microgram/kg was given i.v. and also with an intrauterine administration of 0.5 ng, s.c. administration of 1 microgram/kg and vaginal administration of 10 microgram/kg. The contractile activity of ONO-802 was 100-1000 times more potent than that of PGE2 alpha and was long-acting. Intravenous PGE1 or PGE2 induced a transient contraction followed by inhibition of spontaneous uterine motility in nonpregnant rats and in those with an early pregnancy. In nonpregnant hamsters, a relaxation was seen. ONO-802, similar to PGF2 alpha, showed a contractile effect regardless of states of nonpregnancy and pregnancy, both rats and hamsters. IN rats, a contractile threshold dose of ONO-802 was similar from day 15 to day 21 of pregnancy. Oxytocin produced an acute decrease in this threshold dose on phentolamine or methysergide, but was inhibited by papaverine, dibutyryl cAMP, salbutamol and verapamil. These results suggest that uterine contraction induced by ONO-802 differs from the contractions induced by PGE1, PGE2, and oxytocin, that ONO-802 does not induce endogenous PGs, and that the effect of ONO-802 is not mediated by the autonomic nervous system.

Alprostadil↗
PubMed1981

[Effects of 16,16-Dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802) on uterine, placental and ovarian circulation (author's transl)].

Doses of the drugs which produce uterine contraction were given intravenously to various species of animals. Placental and ovarian circulations were measured by the thermocouple method and/or microangiography. Uterine arterial blood flow (UABF) was measured by the electromagnetic flowmeter. Both placental blood flow (PBF) and UABF decreased with the administration of ONO-802, PGE1 or PGF2 alpha to to rabbits and dogs. Oxytocin and noradrenaline also decreased PBF in rabbits. ONO-802 or PGE1 lowered arterial blood pressure (BP) in rats, rabbits and dogs. PGE2 alpha elevated BP in rats and dogs and lowered it in rabbits. Oxytocin produced no changes in PB while noradrenaline elevated BP in rabbits. Ovarian blood flow in pregnant rabbits was reduced by ONO-802, PGE1 or PGF2 alpha. Little influence was seen with oxytocin. Regarding the luteal microvasculature in pregnant rats, ONO-802, PGF2 alpha and noradrenaline exhibited vasoconstricting effects. PGF2 alpha induced abortion and decreased plasma progesterone levels. These results suggest that the inhibitory effects of ONO-802 on the uterine and placental circulation are strongly influenced by the uterine contractile effect and that the inhibitory effect on the ovarian circulation in rats is one of pharmacological effects not concerned with the abortifacient or luteolytic effect.

Alprostadil↗
PubMed1975

[Effect of [ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY) on kinin formation and fibrinolysis activity].

Inibitory effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY) on kinin formation (in vitro and in vivo) and the fibrinolytic activity (in vivo) were examined and compared with otherinhibitors. Inhibitory effect on kinin forming activity (in vitro) of various enzymes was measured in the guinea pig ileum. FOY and Trasylol inhibited the kinin forming activities of trypsin, pancreas kallikrein and plasma kallikrein. Soybean trypsin inhibitor inhibited kinin like substance was formed in the perfusate when the rat's paw was heated at 46 degrees C. FOY and T-asylol added to the perfusion fluid produced a potent inhibition of the formation of bradykinin-like substance. When administered i.v., FOY and Trasylol did not inhibit the formation of bradykinin-like substance. In the dog, activation of plasmin in the circulatory blood and increase of hemorrhagic tendency were caused by the i.v. administration of human serum plus streptokinase. Such responses were inhibited with a previous i.v. infusion of FOY and t-AMCHA. From the above findings, it may be concluded that FOY has inhibitory effects on kinin formation and fibrinolytic activity.

Animals↗
PubMed1975

[Pharmacological action of [ethyl p(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY)].

General pharmacological effects of [Ethyl p-(6-guanidinohexanoyloxy)benzoate] methanesulfonate (FOY), a new antiproteolytic agent, were studied and the following results were obtained. Acute administration of large doses of FOY in conscious dogs and rabbits caused a decrease in spontaneous motility, ataxia, cyanosis, collapse, mydriasis, and respiratory paralysis. The agent had no effect on the central nervous system and exhibited hypotensive effects in dogs in doses of more than 1 mg/kg. Hypotensive responses were not inhibited by treatment with atropine or hexamethonium. FOY had no effects on ECG in the rabbit at doses of less than 30 mg/kg and at doses from 10(-6) to 10(-4)g/ml, distinctly reduced the amplitude of the spontaneous and rhythmic contractions of the isolated rabbit ileum, guinea-pig ileum and rat uterus preparation. The contractile response to nerve stimulation, noradrenaline and barium was suppressed in isolated guinea-pig vas deferens. FOY had no effects on the twitch response of gastrocnemius muscle to sciatic nerve stimulation in rats. The drug caused local irritant effects in rabbits and rats.

Acetylcholine↗