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Biomedical subjects

I Yamaguchi

Publications and source records attributed to I Yamaguchi.

At least 145 records · Page 8Linked to original sources
PubMed1995

Blasticidin S deaminase gene (BSD): a new selection marker gene for transformation of Arabidopsis thaliana and Nicotiana tabacum.

Arabidopsis thaliana and Nicotiana tabacum were transformed to blasticidin S (BS) resistance with BSD (the BS deaminase gene from Aspergillus terreus) using the Agrobacterium-mediated transformation method. Expression of BSD allowed direct selection of transformants by the fungicide, and both kinds of transgenic plants showed high level of resistance phenotype at 100 ppm of BS sprayed on the leaves. Using Botrytis cinerea, the causal fungus of gray mold disease, it was exemplified that application of BS could control the disease in transgenic tobacco with negligible phytotoxicity.

Aminohydrolases↗
PubMed1995

Studying the dopaminergic system with transfected receptors.

Dopamine receptors are responsible for diverse effects within and outside the central nervous system. The five dopamine receptors that have been cloned (D1A, D1B also known as D5, D2, D3, and D4) belong to two major families; the D1 like and D2 like dopamine receptors. The D1 like receptors are linked to the stimulation while D1 like receptors are linked to the inhibition of adenylyl cyclase. The physiologic role of the dopamine receptors has been difficult to decipher because several of the subtypes co-exist in the same tissue. However, studies of receptors artificially expressed using transfected cDNA have revealed some of the biochemical mechanisms unique to each dopamine receptor subtype.

Animals↗
PubMed1995

Dopamine D1 receptor regulation of phospholipase C.

Dopamine is an endogenous catecholamine which exerts its actions by occupancy of specific receptors. Dopamine receptors are classified into two main groups: the two cloned D1-like receptors (D1A and D1B in rats; D1B is also known as D5 in humans) are linked to stimulation of adenylyl cyclase, while the three cloned D2-like receptors (D2 or D2A, D3 or D2B, D4 or D2C) are linked to inhibition of adenylyl cyclase. All these dopamine receptors originally cloned from the brain are expressed in tissues outside the central nervous system including the kidney. Dopamine regulates many cellular activities, including transmembrane ion transport. Activation of D1-like receptor decreases sodium transport by cAMP dependent and cAMP independent mechanisms. Dopamine, via D1-like receptors, may inhibit Na+/H+ exchange activity in renal brush border membranes by a cAMP independent/Gs alpha-linked mechanism. Another cAMP independent pathway of sodium transport inhibition is mediated by phospholipase C, which has several isoforms (PLC beta, PLC gamma, and PLC delta with several members in each). Catecholamines stimulate expression and activity of phospholipase C isoforms in a concentration, time, and receptor-dependent as well as regional and subcellular compartmental-specific manner. In renal cortical membranes, intrarenal administration of norepinephrine for 3-4 h increases PLC beta expression and activity but has no effect on PLC gamma activity. In contrast, intrarenal administration of a D1 agonist for 3-4 h increases PLC beta 1 but decreases PLC gamma expression and activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The diversity of left ventricular responses to isoproterenol and dibutyryl cyclic AMP infusion in patients with dilated cardiomyopathy.

Sixteen patients with dilated cardiomyopathy were studied to define the abnormality of the beta-adrenergic pathway non-invasively, using echocardiographic left ventricular responses to isoproterenol (ISP; 0.02 microgram/kg/min) and dibutyryl cyclic AMP (DBcAMP; 0.1 mg/kg/min) infusion. The increase in fractional shortening induced by ISP (delta FS-ISP) was 9 +/- 6% and that by DBcAMP (delta FS-DBcAMP) was 7 +/- 3%. The patients could be divided into three groups according to their left ventricular response to each agent: Group A; normal response to ISP (delta FS-ISP > or = 11%), Group B-1; poor response to ISP but better response to DBcAMP (delta FS-ISP < 11%, delta FS-DBcAMP > or = 7%; damage to beta-receptors), and Group B-2; poor response to ISP and DBcAMP (delta FS-ISP < 11%, delta FS-DBcAMP < 7%; damage including post receptor levels). Seven patients were in Group A, four in Group B-1, and five in Group B-2. DCM patients had a diversity of left ventricular responses to ISP and DBcAMP, according to the site of damage in the beta-adrenergic pathway.

Adult↗
PubMed1995

RS-22A, B and C: new macrolide antibiotics from Streptomyces violaceusniger. I. Taxonomy, fermentation, isolation and biological activities.

Three novel 36-membered macrolide antibiotics, RS-22A, B and C produced by Streptomyces violaceusniger have been isolated. These antibiotics were purified from an acetone extract of the mycelia followed by butanol extraction, centrifugal partition chromatography and HPLC. RS-22A, B, C showed antimicrobial activity against fungi and Gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed1995

Tiapride attenuates pain transmission through an indirect activation of central serotonergic mechanism.

Tiapride dose-dependently attenuated the biphasic nociceptive responses induced by s.c. injection of formalin to the hindpaw of mice, and its activity on the first (ED50 = 110 mg/kg p.o.) and the second (ED50 = 32.0 mg/kg p.o.) phases paralleled that on the nociceptive response to intrathecal injection of substance P (ED50 = 190 mg/kg p.o.) and somatostatin (ED50 = 56.0 mg/kg p.o.), respectively. Moreover, a similar antinociceptive activity was observed in streptozotocin-induced diabetic or genetically diabetic (db/db) mice. The effects of tiapride (100 mg/kg p.o.) on both phases of the formalin test in normal mice were abolished by pretreatment with p-chlorophenylalanine (800 x 2 mg/kg p.o.), a 5-hydroxytryptamine (5-HT) depletor, or pindolol (1 mg/kg i.p.), a 5-HT1 antagonist, but were scarcely affected by 3-tropanyl-indole-3-carboxylate, a 5-HT3 antagonist. Ketanserin (1 mg/kg i.p.), a 5-HT2 antagonist, attenuated the effect of tiapride on the second phase but not on the first phase. This study on the antinociceptive mechanism of action of tiapride (that blocks painful neuropathy in diabetic patients) has led us to hypothesize that the drug attenuates pain transmission through an indirect activation of central 5-HT1 and 5-HT2 receptors.

Animals↗
PubMed1995

[Significance of clinical examination concerning arteriosclerosis].

According to the number of deaths by major cause, Malignant neoplasma takes the first rank as the cause of death and then heart disease as a second and next rank to cerebrovascular disease since 1985, instead of top rank of cerebrovascular by that time. However, heart disease and cerebrovascular could be supposed as a arteriosclerosis disease fundamentally, arteriosclerosis disease (heart disease plus cerebrovascular) is usually top of rank in the cause of death since the Showa era. Therefore, it is great significance to make studies of risk factor on the arteriosclerosis in the laboratory medicine.

Arteriosclerosis↗
PubMed1995

Different mechanisms mediated by dopamine D1 and D2 receptors are involved etiologically in activity-stress gastric lesion of the rat.

Rats subjected to activity-stress developed gastric lesions and showed excessive running activity with an increase of light/dark ratio. Daily treatment with centrally acting dopamine antagonists, SCH23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol] (0.1-10 mg/kg), haloperidol (0.1-10 mg/kg), sulpiride (32-320 mg/kg), clozapine (1-100 mg/kg) and metoclopramide (1-100 mg/kg) suppressed the lesion formation: ID50 values were 0.9, 0.4, 53, 8.9 and 60 mg/kg, respectively. On the other hand, domperidone (1-100 mg/kg), a peripherally acting dopamine antagonist, failed to suppress the lesion formation and FR64822 [N-(4-pyridylcarbamoyl)amino 1,2,3,6-tetrahydropyridine] (1-32 mg/kg), a central dopamine enhancer, aggravated it. The excessive running activity was reversed dose-dependently by treatment with haloperidol, a specific dopamine D2 antagonist, but not by SCH23390, a specific dopamine D1 antagonist. Conversely, the increased light/dark ratio was attenuated dose-dependently by SCH23390, but not by haloperidol. Neither antisecretory agents nor 5-hydroxytryptamine antagonists were effective against the lesion formation. These results suggest that an activation of central dopamine D1 and D2 receptors is responsible for the increased light/dark ratio and enhanced running activity, respectively, and that both of the changes are involved in the etiology of activity-stress induced lesions.

Animals↗
PubMed1995

FR121196, a potential antidementia drug, ameliorates the impaired memory of rat in the Morris water maze.

We investigated the effects of FR121196 N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide on the performance of rats in the Morris water maze using a two-trial-per-day regimen. Escape latency to find the platform was significantly prolonged in young rats subjected to scopolamine (1 mg/kg) treatment or to nucleus basalis magnocellularis (NBM) or fimbria-fornix (FF) lesioning compared with the respective control animals. Similar memory deficit was observed in aged rats (24-26 months old) compared with young rats. Daily treatment with FR121196 (0.1-1.0 mg/kg i.p.) ameliorated all the memory deficits except in the FF-lesioned rats, whereas physostigmine (0.032-0.32 mg/kg) ameliorated the memory deficits in scopolamine-treated rats but not in the NBM-lesioned, FF-lesioned or aged rats. Methamphetamine (0.32-3.2 mg/kg) hardly ameliorated the memory deficits and, rather, aggravated those in the scopolamine-treated, NBM-lesioned and aged rats. Neurochemical analysis of the brain showed that dopamine, norepinephrine and serotonin levels were significantly reduced in the hippocampus of the FF-lesioned rats compared with the sham control, and a significant reduction of dopamine level in the cortex was also observed in the aged rats compared with young rats. None of these parameters were changed after NBM lesioning. We concluded that FR121196 ameliorates the memory deficits of rats with cholinergic dysfunction through the action on the hippocampal monoaminergic (possibly serotonergic) neurons.

Age Factors↗
PubMed1995

Toxicity of the novel anti-peptic ulcer agent polaprezinc in beagle dogs.

A preliminary dose-range finding study, two 13-week studies and a 52-week study were performed in beagle dogs with polaprezinc (catena-(S)-[mu-[Na-(3-aminopropionyl)histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7, Z-103), a novel anti-peptic ulcer agent, as part of a safety evaluation program. In the preliminary single-dose study, treatment-related findings were confined to one animal treated with 200 mg/kg and consisted in emesis and mucosal lesions in the stomach and upper small intestine. Based on these data, dosages were selected for the main 13-week study (0, 50, 120 and 300 mg/kg/day) and additional 13-week study (0, 8 and 20 mg/kg/day). The dosages for the 52-week study were 8, 20 and 50 mg/kg/day. In the 13-week studies, dosages of 50 mg/kg/day and above resulted in emesis, mild diarrhea and salivation; reduced food consumption and associated reduction in body weight gain for high dosed females; increased blood alkaline phosphatase and decreased urinary specific gravity; histopathological changes in the kidney of the high dosed group in males and females. These changes were no longer apparent following the withdrawal period. In the 52-week study, similar but milder and transient results were noted at the high dose of 50 mg/kg/day. From these results, the no-effect dose level was estimated to be 20 mg/kg b.w./day.

Animals↗
PubMed1995

Influence of pulmonary blood pressure and flow on endothelin-1 production in humans.

To investigate the regulation of endothelin-1 (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 +/- 5 months old, mean +/- SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 +/- 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.

Endothelins↗
PubMed1995

Increased endothelin-1 binding sites in the cardiac membranes in rats with chronic heart failure.

The effects of experimental chronic heart failure (CHF) on the density and affinity for endothelin-1 (ET-1) binding was studied in the rat heart. Because it has been reported that ET-1 binding sites on cultured cardiocytes are downregulated by pretreatment with ET-1, we also studied the plasma concentrations of ET-1 in rats with CHF. Three weeks after ligation of the left coronary artery, rats developed chronic heart failure (CHF rats). The plasma concentrations of ET-1, as measured by a sandwich-enzyme immunoassay, were significantly higher in CHF rats than in sham-operated rats [4.80 +/- 0.33 vs. 0.91 +/- 0.11 (mean +/- SEM) pg/ml; p < 0.01]. [125I]ET-1 binding experiments on rat cardiac membranes revealed that the binding site density (Bmax) was significantly higher in the CHF rats than in the sham-operated rats (243.0 +/- 20.0 vs. 154.8 +/- 17.4 fmol/mg protein; p < 0.05), whereas the values for the dissociation constant (Kd) were not different between the two groups (28.7 +/- 7.0 vs. 29.8 +/- 1.9 pM). Therefore, in the CHF rats, although plasma concentrations of ET-1 were elevated, the density of myocardial ET receptors was increased. Because ET-1 has potent inotropic and hypertrophic effects on cardiac myocytes, it is suggested that the effects of endogenous ET-1 in the heart are different between the CHF rats and the sham-operated rats.

Animals↗
PubMed1995

Altered production of endothelin-1 in the hypertrophied rat heart.

Although endothelin-1 (ET-1) has been shown to have potent hypertrophic effects in cultured cardiac myocytes, there is no evidence that the production of ET-1 is altered in the hypertrophied heart in vivo. We investigated mRNA and peptide levels of ET-1 in the rat heart hypertrophied due to pressure or volume overload. One week after surgery of abdominal aortic banding (AB) or aortic valve regurgitation (AR; the aortic valve was destroyed by a polyethylene catheter), the rats were sacrificed. Control sham-operated rats were also studied (AB-sham and AR-sham). The left ventricular (LV) weight to body weight ratio was significantly higher in AB rats than in AB-sham rats. It was also significantly higher in AR rats than in AR-sham rats. Therefore, AB rats and AR rats developed LV hypertrophy due to pressure and volume overload, respectively. The expression of ET-1 mRNA in the LV was markedly higher in AB rats than in AB-sham rats. The peptide level of ET-1 was also significantly higher in the LV of AB rats than in that of AB-sham rats. However, the expression of ET-1 mRNA in the LV of AR rats was similar to that of AR-sham rats. The present findings suggest that the production of ET-1 in the heart differs between pressure and volume overload-induced hypertrophy in rats.

Animals↗
PubMed1995

Plasma endothelin-1 levels after exercise in patients with congenital heart disease.

We have previously reported that plasma endothelin-1 (ET-1) levels were significantly increased after exercise in healthy athletes. In the present study, venous plasma ET-1 levels were measured to investigate whether the role of ET-1 during exercise differs between healthy athletes and patients with congenital heart disease. Seven patients (mean age 13 years) performed symptom-limited treadmill exercise (Bruce protocol). All patients were in class I of the NYHA functional classification. The mean end-exercise O2 utilization was 32 ml/min/kg (166% of ventilatory threshold). Blood sampling was carried out in the seated position. The plasma ET-1 level was 1.21 pg/ml before exercise and did not alter immediately after or 30 min after exercise. The plasma level of norepinephrine was markedly elevated immediately after exercise and returned to the basal level 30 min after exercise. The present study demonstrated that exercise failed to alter plasma ET-1 levels in patients with congenital heart disease.

Adolescent↗
PubMed1994

Blasticidin S deaminase gene from Aspergillus terreus (BSD): a new drug resistance gene for transfection of mammalian cells.

Blasticidin S deaminase (BSD) is a drug inactivating enzyme produced by Aspergillus terreus, which convert blasticidin S (BS) to a non-toxic deamino-hydroxy derivative. The BSD gene was fused to SV 40 transcriptional regulatory elements and the resulting vector was used to transfect FM3A cells. Expression of BSD conferred resistance to BS and allowed efficient isolation of integrative transfectants which have stably maintained the BS-resistance phenotype after repeated transfer to fresh selective medium. The frequency of transfection was comparable to that with neo and about 80-times greater than with bsr, a BS-resistance gene of bacterial origin which can be used to isolate efficiently transfectant HeLa cells. Using BSD as a selectable marker, we obtained several stable cell lines expressing the firefly luciferase gene. Four independent transfectants among the randomly selected 5 BS-resistance colonies exhibited detectable luciferase activity under the control of dexamethasone-inducible promoter in the expression vector. The successful application of BSD strongly suggests the usefulness of BS as a versatile selective reagent for introduction of cloned DNA sequences into mammalian cells.

Aminohydrolases↗
PubMed1994

Possible involvement of the septo-hippocampal cholinergic and raphe-hippocampal serotonergic activations in the penile erection induced by fenfluramine in rats.

Fenfluramine (0.1-10 mg/kg, i.p.) induced penile erection in naive rats with a bell-shaped dose response curve. The response to fenfluramine (1 mg/kg) was antagonized by scopolamine (0.032-1 mg/kg) but not by methyl-scopolamine (0.032-1 mg/kg) pre-treatment. The septo-hippocampal cholinergic deafferentations by medial septum lesion or fimbria-fornix transection also attenuated the penile erection induced by fenfluramine, whereas dopaminergic blockade by sulpiride (3.2-100 mg/kg) had hardly any effect. Pindolol (0.1-3.2 mg/kg), a 5-HT1 antagonist, and ICS205-930, a 5-HT3 antagonist, but not ketanserin, a 5-HT2 antagonist, inhibited the penile erection induced by fenfluramine. Depletion of 5-HT not only by systemic injections of p-chlorophenylalanine (150 mg/kg i.p. at 72, 48 and 24 h before the test) but also by the injections of 5,7-dihydroxytryptamine (5,7-DHT), a serotonergic neurotoxin, into the median- and dorsal-raphe nuclei significantly attenuated the fenfluramine-induced penile erections. Neurochemical analyses revealed that the raphe-lesion significantly reduced the contents of serotonin (5-HT) and its major metabolite, 5-hydroxyindole acetic acid (5-HIAA) but not choline acetyltransferase (ChAT) activities in all the cortical and subcortical regions examined. The results suggest that fenfluramine facilitates the expression of penile erection in rats through an activation of the septo-hippocampal cholinergic pathway as a consequence of excitation of the raphe-hippocampal serotonergic pathway in which 5-HT1 and/or 5-HT3 receptors appear to play a regulatory role.

Adrenergic beta-Antagonists↗
PubMed1994

Possible involvement of brain somatostatin in the memory formation of rats and the cognitive enhancing action of FR121196 in passive avoidance task.

Using the passive avoidance learning task in rats, the role of brain somatostatin in cognitive function was investigated with special reference to that of the brain cholinergic system. In addition, the involvement of both the brain somatostatinergic and cholinergic systems in the anti-amnesic action of a newly introduced cognitive enhancer, FR121196 [N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide], was examined. Treatment with cysteamine (50, 100, 200 mg/kg, s.c.), a depletor of somatostatin, significantly and dose-dependently reduced the retention of single trial passive avoidance task. Similar memory impairments were found in rats which received central cholinergic blockade either by scopolamine (0.1-1 mg/kg) or by lesioning of the nucleus basalis magnocellularis (NBM). Intracerebroventricurally (i.c.v.) administered somatostatin (1-14) (10-1000 ng/rat) significantly ameliorated the memory impairments induced not only by cysteamine (200 mg/kg) but also by scopolamine (1 mg/kg) and NBM-lesioning. Although physostigmine (0.01-1 mg/kg) also ameliorated the memory impairments induced by cysteamine and scopolamine, it failed to affect the memory impairment seen in the NBM-lesioned rats. Administration of FR121196 (0.1-10 mg/kg) significantly ameliorated the memory deficits produced by scopolamine and NBM lesioning but not that induced by cysteamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗