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Biomedical subjects

K Fuji

Publications and source records attributed to K Fuji.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects of propentofylline, a NGF synthesis stimulator, on alterations in muscarinic cholinergic receptors induced by basal forebrain lesion in rats.

Basal forebrain (BF) lesions induced by ibotenic acid produced increases in the Bmax and Kd values of [3H]QNB binding sites in the frontal cortex, parietal cortex, and hippocampus. Twenty-eight-day successive administration of propentofylline (10 and 25 mg/kg, p.o.) significantly reduced the Kd values of [3H]QNB binding sites, to the levels of those in a sham group, in a dose-dependent manner. Moreover, propentofylline (25 mg/kg, p.o.) significantly reduced the Bmax value of [3H]QNB binding sites compared with that in a vehicle-treated BF-lesioned group. These results suggest that successive administration of propentofylline ameliorates changes in muscarinic cholinergic receptors through improving presynaptic cholinergic dysfunction.

Animals↗
PubMed1993

Effects of cholesterol on the miscibility of synthetic glucosamine diesters in lipid bilayers and the entrapment of superoxide dismutase into the positively charged liposomes.

Methyl-D-glucosamine-3,6-dilauroyl, dimyristoyl, dipalmitoyl or distearoyl esters were synthesized as positively charged lipids. They were incorporated into phosphatidylcholine liposomal membranes and the entrapment of superoxide dismutase (SOD) into the liposomes was attempted. The efficiency of the SOD-entrapment into the positively charged multilamellar vesicles (MLVs), comprising egg yolk phosphatidylcholine and synthetic glucosamine diesters, was enhanced by the addition of cholesterol to the membranes. A differential scanning calorimetric study showed that the miscibility (solubility) of glucosamine diesters in phosphatidylcholine-bilayers increased on the addition of cholesterol to the membranes. Cholesterol assisted in the mixing of phosphatidylcholines with positively charged glucosamine diesters and increased the positive charges on the liposomal membranes. This was confirmed by incremental increases in the zeta-potential of liposomal membranes with an increase in the cholesterol content. Entrapment of SOD thus became more efficient due to the enhanced electrostatic attraction between the positively charged membranes and the negatively charged SOD, and/or the electrostatic repulsive interactions between positively charged membranes; the latter interactions induced a thickening of the water layer in MLVs.

Cholesterol↗
PubMed1992

Effect of naftidrofuryl oxalate on 5-HT2 receptors in mouse brain: evaluation based on quantitative autoradiography and head-twitch response.

The effects of naftidrofuryl oxalate (LS-121) on 5-HT2 receptors in the brain were assessed in mice on the basis of quantitative autoradiography and head-twitch responses. LS-121 inhibited [3H]ketanserin (2 nM) binding in all brain areas assayed in which there were 5-HT2 receptors, such as the frontal cortex, cingulate cortex, parietal cortex, occipital cortex, temporal cortex, nucleus accumbens, caudate-putamen, olfactory tubercle and hippocampus. In the frontal cortex, which has the highest density of 5-HT2 receptors, the Ki value of LS-121 was 6.08 x 10(-8) M. The inhibitory potencies of methysergide and ritanserin for 5-HT2 receptors were about 16- and 60-fold stronger, respectively, than that of LS-121. Moreover, in behavioral studies, LS-121 (12.5-50 mg/kg i.p.) produced dose-dependent and significant inhibitory effects on head twitches induced by 5-hydroxytryptophan (5-HTP) plus pargyline, which is a 5-HT2 receptor-dependent behavior in mice. These results suggest that LS-121 inhibits 5-HTP plus pargyline-induced head twitches by blocking 5-HT2 receptors.

5-Hydroxytryptophan↗
PubMed1992

Suppressant effects of midazolam on responses of spinal dorsal horn neurones in rabbits.

Recordings of noxious intra-arterial bradykinin (BK)-induced chemonociceptive and spontaneous activity from 30 single spinal lamina V neurones of the dorsal horns in non-anaesthetized and decerebrated rabbits, were performed with tungsten microelectrodes. Intravenous injection of midazolam (0.2 mg/kg; 7 neurones) depressed BK-induced neural discharges by 55.0 +/- 6.2% (P less than 0.05) and 57.9 +/- 8.4% (P less than 0.05) 5 and 25 min after administration, respectively. Treatment with flumazenil (0.2 mg/kg, i.v.; 7 neurones), administered 20 min after midazolam, completely reversed the inhibition by midazolam of the BK-induced spinal lamina V neural responses and spontaneous neuronal activity. In contrast, a large dose of naloxone (1.0 mg/kg, i.v.; 6 neurones), administered 20 min after midazolam, failed to alter the midazolam-induced depressant effects on the nociceptive responses, at the spinal dorsal horn. Treatments with flumazenil (5 neurones) and naloxone (5 neurones) did not influence either the spontaneous or the BK-induced neuronal discharges, recorded in spinal lamina V cells. Midazolam depressed the nociceptive responses probably through its agonistic activity on the binding to the GABA-benzodiazepine-barbiturate system in the spinal dorsal horn.

Animals↗
PubMed1991

Staurosporine, a protein kinase inhibitor, attenuates basal forebrain-lesion-induced amnesia and cholinergic neuronal deficit.

We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.

Alkaloids↗
PubMed1991

Aged-related changes in learning and memory, choline acetyltransferase activity and number of neuronal cells in rats.

In a water maze task, the goal latency and distance of swimming onto the platform of aged rats (24 months old) were slowly shortened by repeated training compared with those of young rats (8 weeks old). A significant decrease in choline acetyltransferase activity in the frontal cortex, parietal cortex and striatum was observed in aged rats. Moreover, the number of neuronal cells in the hippocampal CA1 subfield and dentate gyrus of aged rats was smaller than that of young rats. The atrophy of striatal cells was observed. These results suggest that age-related delay of acquisition is due to the above-mentioned biochemical and histological changes, and that rates of aging in biochemical and morphological parameters are different in the discrete brain areas.

Aging↗
PubMed1991

Design and synthesis of antitumor compounds based on the cytotoxic diterpenoids from the genus Rabdosia.

Two active sites responsible for antitumor activity, an oxirane ring and an alpha-methylene-cyclopentanone moiety, have been extracted from studies on the structure-activity relationship of the cytotoxic diterpenoids isolated from Rabdosia shikokiana. Series of the simplified cyclopentanone derivatives containing both of the two active sites in the molecule have been synthesized and evaluated for cytotoxicity against P 388 cells. The compounds possessing both of two active sites displayed cytotoxicity at a concentration of 1 microgram/ml, while those possessing a single active site showed no activity.

Animals↗
PubMed1991

Synthesis and characterization of viologen-modified oligodeoxynucleotides.

Several viologen-tagged oligodeoxynucleotides in the form of covalent linkage at the specific site of the phosphorous backbone were synthesized and characterized. Incorporation of viologen molecules was confirmed by the 31P-NMR, 20% PAGE analysis, enzymatic degradation, and uv, ESR spectra of the derived cation radical. The Tm values and CD spectra of the modified strands with their complementary strands indicate that the introduction of the viologen molecule via linker arm causes no significant perturbation in duplex structure.

Base Sequence↗
PubMed1991

Memory impairment and morphological changes in rats after continuous infusion of active fragment of anti-nerve growth factor-antibody.

We report here that the specific Fab' fragment of anti-nerve growth factor (NGF)-antibody (anti-NGF, 12, 120 and 400 micrograms/4 weeks, i.c.v.) impairs learning and memory. The goal latency of the control rats in water maze task was rapidly shortened by training compared to those of the anti-NGF-treated rats. The degree of reduction in movement counts of the anti-NGF-treated rats in habituation task was significantly smaller than that of the control rats. However, the step-through latency of the anti-NGF-treated rats was not significantly shorter than that of the control rats. With regard to the choline acetyltransferase activity, no effects were observed in any of the brain regions. Anti-NGF treatment altered nuclear morphology in the hippocampus and parietal cortex. As a result, it seems that the anti-NGF-induced amnesia could be due to an impairment of nuclear morphology.

Analysis of Variance↗
PubMed1991

Staurosporine facilitates recovery from the basal forebrain-lesion-induced impairment of learning and deficit of cholinergic neuron in rats.

Alzheimer's disease is characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert and by a primary loss of memory function. Since staurosporine has been reported to induce differentiation in human neuroblastoma cells in vitro, we studied the effects of staurosporine on the amnesia induced by basal forebrain-lesion in rats. Staurosporine (0.05 and 0.1 mg/kg intraperitoneal) attenuated the impaired performance of water maze and passive avoidance tasks, even though the drug administration began 2 weeks after the lesion. Moreover, staurosporine (0.1 mg/kg) partially reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex induced by basal forebrain-lesion. These results suggest that staurosporine attenuates impairment of learning through reversal of damage to cholinergic neurons induced by basal forebrain-lesion. This evidence indicates that neurotrophic factor-like substances may be used in novel therapeutic approaches to Alzheimer's disease.

Alkaloids↗
PubMed1990

Neurotoxicity induced by continuous infusion of quinolinic acid into the lateral ventricle in rats.

Acute intrastriatal injection of quinolinic acid (QA) caused a significant reduction of choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities as well as a decrease of the specific binding of [3H]hemicholinium-3. Pretreatment with MK-801 completely blocked the QA-induced neurotoxicity. Continuous infusion of QA into the lateral ventricle resulted in a reduction of hippocampal and cortical ChAT activities while GAD activities were unchanged. These results suggest that continuous infusion of QA into the lateral ventricle could be a useful technique for the study of chronic neurodegenerative diseases including Alzheimer's disease.

Animals↗
PubMed1989

Terpenoids. LIII. Antitumor activity of trichorabdals and related compounds.

Among the three types, enmein-, oridonin-, and trichorabdal-type, of diterpenoids from Rabdosia trichocarpa, the latter showed the highest antitumor activity against Ehrlich ascites carcinoma in mice. Their potent activities were attributed to synergistic increase arising from the presence of two active sites in one molecule. In vitro activity against HeLa cells and in vivo activity against P 388 lymphocytic leukemia of diterpenoids and related compounds were also determined, but no synergistic increase in activity due to plural active sites was observed in those cases.

Animals↗
PubMed1989

Radiosensitizing hypoxic cells with new 3-nitro-1,2,4-triazole derivatives in vitro and in vivo.

The new regioisomer derivatives 4a-f and 5a-f of 3-nitro-1,2,4-triazole (3-NTR) were synthesized for the development of new radiosensitizers of hypoxic cancer cells for radiotherapy. N(2)-Substituted 3-NTR derivatives 5a-f were stronger radiosensitizers of hypoxic cells in vitro (Chinese hamster V79 cells) than N(1)-substituted 3-NTR derivatives 4a-f, but in vivo they were weaker (SCCVII carcinoma cells inoculated into C3H/He mouse).

Animals↗
PubMed1989

[Study on serum levels of immunosuppressive acidic protein (IAP) as a marker of renal cell carcinoma].

Immunosuppressive acidic protein (IAP) exhibits various types of immunosuppressive activity and is said to increase in cancer hosts. Based on measurements of IAP levels in normal subjects, cases of renal cysts and 46 cases of renal cell carcinoma we reached the following conclusions: The IAP levels in normal subjects ranged from 250-530 micrograms/ml, with a mean +/- S.D. of 362.5 +/- 68.9 micrograms/ml, which was comparable to the values in renal cyst cases (250-470 micrograms/ml, mean +/- S.D.: 353 +/- 70 micrograms/ml). 475 micrograms/ml was taken as the upper limit of the normal range. The pretreatment IAP values for cases of renal cell carcinoma ranged from 330-1,780 micrograms/ml, with a mean +/- S.D. of 820 +/- 820 and 73% were considered positive (i.e. beyond the 475 micrograms/ml limit). There was a statistical significance of p less than 0.01 between normal subjects and renal cell carcinoma cases and also between renal cyst cases and renal cell carcinoma cases. When the cases of renal cell carcinoma were divided into those with a pretreatment IAP level of 475 micrograms/ml or less and those with more than 475 micrograms/ml, the 3-year survival of the former was 90%, whereas that of the latter group was 39%, showing a statistically significant difference with p less than 0.05. Comparison of the IAP levels in the group of total nephrectomy cases that did not develop recurrence and those in which recurrence was recognized, revealed significantly higher IAP levels in the latter (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effect of oridonin, a Rabdosia diterpenoid, on radiosensitization with misonidazole.

The radiosensitization brought about by oridonin, one of the Rabdosia diterpenoids, alone or in combination with misonidazole, was investigated in Chinese hamster V79 cells. The enhancement ratio of 1.92 was obtained when 0.01 mM oridonin and 1 mM misonidazole were administered to hypoxic cells under radiation. The enhancement ratios of oridonin and misonidazole for hypoxic cells were 1.16 and 1.59 respectively. Hence, a supra-additive effect was obtained by the combined treatment with these two drugs. Under aerobic conditions, no effect of 0.01 mM oridonin on the radiosensitization caused by misonidazole was observed.

Animals↗
PubMed1986

Steroidogenic effect of ent-kaur-16-en-15 beta-ol (kaurenol) on isolated rat adrenal cells.

In an in vitro bioassay system for adrenocorticotropic hormone using isolated rat adrenal cells, kaurenol, a diterpene alcohol, stimulated corticosterone production and augmented the steroidogenic effect of adrenocorticotropin or forskolin, dose-dependently. Kaurenol had no effect on cyclic AMP production by the cells. The diterpene also had no stimulatory effect on the adrenal adenylate cyclase activity in a cell free system. The results suggest that this particular diterpene exerts a steroidogenic effect through a mechanism independent of cyclic AMP generation.

Adenylyl Cyclases↗