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Biomedical subjects

H Fujimura

Publications and source records attributed to H Fujimura.

At least 145 records · Page 8Linked to original sources

Molecular cloning of the DAC2/FUS3 gene essential for pheromone-induced G1-arrest of the cell cycle in Saccharomyces cerevisiae.

Mating pheromones, known as a and alpha-factors, arrest the division of cells of opposite mating types, alpha and a respectively, in Saccharomyces cerevisiae. I have cloned the DAC2 gene, which is required for both pheromone-induced division-arrest and cell-fusion during conjugation. The constructed dac2::LEU2 null mutation leads to defects in both pheromone-induced division-arrest and cell-fusion during conjugation; it also suppresses the growth defect caused by the gpa1 mutation (a mutation in the alpha subunit of the S. cerevisiae G protein). These results indicate that DAC2 may be the same gene as FUS3, which was recently isolated by Elion et al. (1990) as a gene essential for cell-fusion during conjugation. The dac2::LEU2 null mutant also showed morphological alterations in response to mating pheromones. I show here that the DAC2 product plays an essential role in both the division-arrest signalling pathway of the yeast pheromone response and in cell-fusion during conjugation.

Cloning, Molecular↗

Alterations in neocortical expression of nicotinic acetylcholine receptor mRNAs following unilateral lesions of the rat nucleus basalis magnocellularis.

We investigated the effect of a unilateral lesion of the nucleus basalis magnocellularis (nbm) on the expression of nicotinic acetylcholine receptors (nAChRs) in the rat cerebral cortex. Cortical nAChR concentration as determined by [3H]nicotine binding was unaffected by the nbm lesion. Expression levels of nAChR subunit mRNAs were measured using cDNA clones coding for the receptor subunits, alpha-3, alpha-4, and beta-2. At 1 week postlesion, expression levels of alpha-4, and beta-2 were increased by an average of 82% and 19%, respectively. On the other hand, expression levels of these mRNAs on the lesioned side 4 weeks after lesioning did not differ from those on the control side. Expression of alpha-3 was not altered by the nbm lesion. These results imply regulation of nAChR transcripts by cell to cell interactions. Co-increase of alpha-4 and beta-2 transcripts may provide supporting evidence for the occurrence of supersensitivity in deafferentated cholinergic neurons.

Animals↗

Antiulcer action of Sophora flavescens root and an active constituent. I.

The effect of a methanol extract of Sophora flavescens root was examined on gastric ulcers induced in rats by HCl/ethanol in order to substantiate its reputed protective properties. Oral doses of 1 g/kg completely suppressed ulceration. Results suggest that oral administration of 50 mg/kg of vexibinol, a flavanol found in the extract, inhibited ulceration more effectively than spizofurone at 100 mg/kg.

Animals↗

Vasodilatory active principles of Sophora flavescens root.

Flavanones vexibinol and kurarinone were isolated from an ethyl acetate extract of Sphora flavescens roots and assayed using isolated rabbit and rat thoracic aorta helical strips. These compounds inhibited KCl and norepinephrine maximum contractions in a concentration-dependent manner in the rat but only KCl contractions in the rabbit. Vexibinol and kurarinone weakly inhibited histamine- and serotonin-induced contractions in the rabbit. The results suggest that these flavanones may inhibit Ca2+ influx through a voltage-dependent Ca2+ channel.

Animals↗

Changes in cerebral white matter in a case of congenital muscular dystrophy (non-Fukuyama type).

A 3-year-old Japanese boy with congenital muscular dystrophy (CMD) and normal intelligence is presented. He had not learned to crawl, shuffled on his bottom, and could not walk. At 7 months, his CT-scan had showed periventricular low density and mild ventricular dilatation, and spike or sharp wave discharges were seen on EEG. At three years of age, his CT-scan revealed wide-spread hypodensity in the cerebral white matter, EEG showed multifocal discharges, and MRI showed abnormal high density area in the cerebrum on spin echo image. These findings suggest the existence of an intermediate form of CMD between the Fukuyama type of CMD and the classical occidental type of CMD. The combination of repeated CT and MRI scans seems necessary for the evaluation of CNS abnormalities in CMD.

Biopsy↗

Identification and characterization of a mutation affecting the division arrest signaling of the pheromone response pathway in Saccharomyces cerevisiae.

Mating pheromones, a- and alpha-factors, arrest the division of cells of opposite mating types, alpha and a cells, respectively. I have isolated a sterile mutant of Saccharomyces cerevisiae that is defective in division arrest in response to alpha-factor but not defective in morphological changes and agglutinin induction. The mutation was designated dac2 for division arrest control by mating pheromones. The dac2 mutation was closely linked to gal1 and was different from the previously identified cell type nonspecific sterile mutations (ste4, ste5, ste7, ste11, ste12, ste18 and dac1). Although dac2 cells had no phenotype in the absence of pheromones, they showed morphological alterations and divided continuously in the presence of pheromones. As a result, dac2 cells had a mating defect. The dac2 mutation could suppress the lethality caused by the disruption of the GPA1 gene (previously shown to encode a protein with similarity to the alpha subunit of mammalian G proteins). In addition, dac2 cells formed prezygotes with wild-type cells of opposite mating types, although they could not undergo cell fusion. These results suggest that the DAC2 product may control the signal for G-protein-mediated cell-cycle arrest and indicate that the synchronization of haploid yeast cell cycles by mating pheromones is essential for cell fusion during conjugation.

Cell Division↗

The antiulcer action of sophora and the active constituent in Sophora. II. The antiulcer action of vexibinol.

The inhibitory effect of vexibinol, one of the flavanols found in Sophora, on gastric ulcers induced by HCl-ethanol has been reported previously. In the present study, the effect of vexibinol was examined in various experimental ulcer models in order to determine the mechanism of its antiulcer action. The results indicated that the oral administration of vexibinol at 25-50 mg/kg significantly inhibited the development of ulcers induced by HCl-ethanol, 0.6 N HCl 0.2 N NaOH, absolute ethanol and 1% NH3. In addition, an intraduodenal administration of vexibinol at 300 mg/kg significantly inhibited Shay's ulcer. Further, intraduodenal administration at 300 mg/kg significantly inhibited acid secretion caused by 2-deoxy-D-glucose. These results suggest that vexibinol has not only gastric mucosal protective action but also an inhibitory effect on the secretion of gastric acids.

Animals↗

Antianoxic action and active constituents of atractylodis lanceae rhizoma.

The screening test was carried out to identify new drugs from natural products for the KCN-induced anoxia model in mice. Acetone extract of Atractylodis Lanceae Rhizoma (Atractylodes lancea DC. var. Chinensis Kitamura) had a significant effect in the KCN-induced anoxia model and therefore the extract was selected for further study in order to identify the active principles. The result showed that beta-eudesmol was the active component in Atractylodis Lanceae Rhizoma.

Animals↗

Gastrointestinal motility enhancing effect of ginger and its active constituents.

The effect of ginger root (Zingiberis Rhizoma) on gastrointestinal motility was examined based on its ability to enhance charcoal meal transport in mice. Oral administrations of the acetone extract of ginger (which contains volatile oils and bitter substances) at 75 mg/kg, [6]-shogaol at 2.5 mg/kg, or a [6]-, [8]- or [10]-gingerol at 5 mg/kg enhanced the transport of a charcoal meal. The effects of these substances were similar to or slightly weaker than those of metoclopramide and donperidone.

Animals↗

Vascular dilatory action of Artemisia capillaris bud extracts and their active constituent.

In perfusion experiments, the acetone extract of Artemisia capillaris buds significantly inhibited the response to norepinephrine of helical strips of rabbit thoracic aorta. The acetone extract was fractionated by column chromatography to identify the active constituent. Kinetic experiments using rabbit thoracic aorta showed that 6,7-dimethoxycoumarin (scoparone) has a marked inhibitory effect on the contractions induced by norepinephrine, 5-hydroxytryptamine, histamine and angiotensin II. Like nitroglycerin, scoparone appeared to be a competitive antagonist of norepinephrine.

Animals↗

Antianoxic action of evodiamine, an alkaloid in Evodia rutaecarpa fruit.

In order to determine the antianoxic potential of evodiamine, its effects were compared to those of vinpocetine (VPT), using a series of animal models of anoxia. In mice, evodiamine was equivalent to VPT in the KCN-induced anoxia model but was greater than VPT in the low-pressure-induced anoxia model. Its effectiveness was increased by combined treatment with physostigmine, suggesting the involvement of a cholinergic mechanism in the antianoxic action of evodiamine.

Alkaloids↗

Synthesis and analgetic activity of sulfur-containing morphinans and related compounds.

3-Acylthiomorphinans, 3-carbamoylthio-3-deoxydihydromorphine and 3-benzoylthio-9-aza-17-carbamorphinan were synthesized by Newman-Kwart rearrangement of the corresponding O-thiocarbamates. The analgetic activities were lower than that of pentazocine, and the opioid receptor binding affinities were very weak. These acylthiomorphinans showed low antinociceptive activity compared with corresponding sulfur-containing benzomorphans. 3-Carbamoylthio-deoxydihydromorphine had no significant analgetic activity.

Analgesics↗

The effect of scoparone, a coumarin derivative isolated from the Chinese crude drug Artemisiae capillaris flos, on the heart.

In the present study, scoparone isolated from Artemisia Capillaris Flos has been investigated to determine its pharmacological properties on the heart. Scoparone was found to cause the increase in coronary flow and heart rate, but did not affect cardiac output, left ventricular pressure or left ventricular work in the isolated perfused heart. Scoparone at 25 mg/kg and 50 mg/kg, p.o. had a marked inhibitory effect on the ST wave depression. Consequently it is suggested that scoparone has antianginal action.

Animals↗

Antianoxic action and active constituents of evodiae fructus.

In order to develop new drugs from natural products, constituents of natural medicines were examined for their effectiveness in the KCN-induced anoxia model in mice. Methanol extract from a Chinese medicine, evodia (fruits of Evodia rutaecarpa Benth. or E. officinalis Dode), had a significant effect in the KCN-induced anoxia model in mice and therefore the active constituents were further examined. The results indicated that the antianoxic action of evodia was found in the fraction containing evodiamine. Further analysis of the active constituent indicated that evodiamine and rutaecarpine, indole-alkaloids found in large amounts in the Chinese medicine evodia, were mainly responsible for the antianoxic action.

Animals↗