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Biomedical subjects

I Yamaguchi

Publications and source records attributed to I Yamaguchi.

At least 19 recordsLinked to original sources
PubMed1995

Response to isoproterenol as a prognostic indicator of evolution from hypertrophic cardiomyopathy to a phase resembling dilated cardiomyopathy.

OBJECTIVES: We sought to assess whether isoproterenol stress echocardiography could detect in advance in which patients hypertrophic cardiomyopathy would progress to a phase resembling dilated cardiomyopathy. BACKGROUND: In a few patients, hypertrophic cardiomyopathy has been reported to progress to a phase characterized by systolic dysfunction and left ventricular dilation, resembling dilated cardiomyopathy. METHODS: Echocardiograms were recorded before and immediately after intravenous infusion of isoproterenol (0.02 microgram/kg body weight per min) for 5 min in 18 patients with typical hypertrophic cardiomyopathy (i.e., hypertrophied, hyperdynamic and nondilated) to determine the difference in fractional shortening. The patients were categorized into those with a good response (difference in fractional shortening > 7%, 14 patients) and those with a poor response (difference < or = 7%, 4 patients). Changes in left ventricular end-diastolic diameter and fractional shortening were evaluated by using serial echocardiography over an average follow-up period of 5.4 years. RESULTS: In the good response group, neither end-diastolic diameter nor fractional shortening changed significantly during the follow-up period. In the poor response group, end-diastolic diameter significantly increased from a mean +/- SD of 41 +/- 5 to 53 +/- 5 mm (p < 0.05), and fractional shortening significantly decreased from 40 +/- 12% to 29 +/- 10% (p < 0.05). All patients in the poor response group showed a substantial decrease (> or = 5%) in fractional shortening and an increase (> or = 5 mm) in end-diastolic diameter. One patient developed congestive heart failure due to systolic dysfunction during the observation period. CONCLUSIONS: The present study confirmed that impaired responses to isoproterenol infusion are related to future deterioration of left ventricular performance in patients with typical hypertrophic cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1995

Continuous measurement of left ventricular volume in rabbit, using a two-electrode catheter.

We developed a device for monitoring instantaneous left ventricular (LV) volume using an alternating-current excitation two-electrode conductance catheter. Instantaneous conductance between a pair of electrodes was amplified by a non-inverting circuit. The level of conductance was linearly related to changes in blood volume from 0.8 to 2.0 ml in a latex balloon (r2 = 0.95), and to changes in blood volume from 0.4 to 2.2 ml in a post-mortem rabbit left ventricle (r2 = 0.99). The difference between the maximal and minimal conductance of the LV in situ during a cardiac cycle was closely correlated with changes in stroke volume, measured by an electromagnetic flow probe (r2 = 0.97). The endsystolic pressure-conductance relation (ESPCR) was highly linear (r2 = 0.92). Changes of the slope (Ees) of the ESPCR correlated directionally with changes of the time derivative of LV pressure (LVdP/dt) during intravenous infusions of dobutamine and propranolol. Accordingly, the two-electrode conductance catheter was useful in vivo in rabbits for continuously assessing changes in the LV volume.

Animals↗
PubMed1995

Changes in brain somatostatin in memory-deficient rats: comparison with cholinergic markers.

To clarify the functional role of the brain somatostatinergic system in cognitive processes, changes in the performance in passive avoidance and water maze tasks and in brain somatostatin contents were comparatively investigated in young Fischer rats subjected to brain cholinergic and somatostatinergic depletion, and in aged Fischer rats. Lesioning of the nucleus basalis magnocellularis and administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin, resulted in significant deficits in passive avoidance, but complete transection of the fimbria-fornix hardly affected the performance in the task. When cognitive performance was assessed in the Morris water maze, lesions of the nucleus basalis magnocellularis and the fimbria-fornix, and administration of cysteamine, significantly impaired the acquisition of navigatory spatial memories of rats. On the other hand, aged rats (24-27 months) showed severe impairments of memory acquisition in both tasks. Neurochemistry measurements showed that lesions of the nucleus basalis magnocellularis produced a selective reduction both in the cortical cholinergic marker choline acetyltransferase and in striatal somatostatin level, whereas lesioning of the fimbria-fornix caused a marked loss of choline acetyltransferase in the hippocampus and posterior cortex, and a significant reduction in hippocampal somatostatin. On the other hand, treatment with cysteamine significantly reduced the contents of somatostatin in all the brain regions examined, but minimally affected choline acetyltransferase activity. However, significant reduction in the striatal choline acetyltransferase activity and elevation in somatostatin content in the frontal cortex were found in aged rats compared with young rats. Taken together, these results strongly suggest that changes in the brain somatostatinergic transmission are involved in the cognitive deficits in the experimental animal models of dementia presently employed. Furthermore, the present comparative study further implies that there are differences in the relative involvement of the cholinergic and somatostatinergic systems in the performance of rats on two different tests of mnemonic function.

Aging↗
PubMed1995

Sulpiride specifically attenuates psychological stress-induced gastric lesions in rodents.

Gastric lesions were developed in the communication box paradigm (CB) in mice as well as in the activity-stress paradigm (AS) in rats. Treatment with sulpiride (10-320 mg/kg, p.o.) attenuated these psychological stress-induced gastric lesions in a dose-dependent manner, while it failed to suppress those induced by physical stress such as restraint water-immersion (WI) and indomethacin treatment (IND). In contrast, treatment with famotidine (0.32-10 mg/kg, p.o.) dose-dependently attenuated the gastric lesions induced by physical stress but not those by psychological stress. Pylorus-ligation study revealed that famotidine strongly reduced gastric acid secretion, whereas sulpiride minimally affected that. It was also demonstrated that physical stress (WI) enhanced acid secretion while psychological stress (CB and AS) rather depressed that. These results suggest that the mechanisms of gastric lesion formation are clearly different between physical and psychological stress and that sulpiride specifically attenuates psychological stress lesions possibly through a central mechanism.

Animals↗
PubMed1995

Involvement of raphe-hippocampal serotonergic and septo-hippocampal cholinergic mechanisms in the penile erection induced by FR121196, a putative cognitive enhancer.

FR121196 (N-[4-acetyl-1-piperazinyl]-4-fluorobenzenesulfonamide), a putative cognitive enhancer, induced penile erection in naive rats; the dose-response curve was bell-shaped with the maximum response obtained at the dose of 3.2 mg/kg. The response to FR121196 was abolished in rats treated with intra-raphe injections of 5,7-dihydroxytryptamine or systemic injections of p-chlorphenylalanine (150 mg/kg, i.p. for three consecutive days) as well as in rats with electrolytic medial-septum lesion or surgical fimbria-fornix lesion. In addition, the penile erection induced by FR121196 (3.2 mg/kg) was dose-dependently attenuated by pindolol (0.1-3.2 mg/kg), a serotonin (5-HT)1 antagonist with beta-antagonistic activity, but not by metoprolol, a selective beta=antagonist. The inhibitory activity was shared by ICS205-930, a 5-HT3 antagonist, but not by ketanserin, a 5-HT2 antagonist, or sulpiride, a dopamine D2 antagonist. Scopolamine (0.032-1 mg/kg), but not methyl-scopolamine (0.032-1 mg/kg), also attenuated the penile erection induced by FR121196. Neurochemical analysis revealed that intraperitoneal injection of FR121196 significantly elevated the levels of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and that raphe-lesion significantly reduced both 5-HT and 5-HIAA levels without affecting choline-acetyltransferase activity in all cortical and subcortical regions examined. It is thus postulated that FR121196 facilitates the raphe-hippocampal serotonergic pathway resulting in an activation of the septo-hippocampal cholinergic pathway and finally induces the penile erectile response.

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↗
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 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↗
PubMed1994

Role of renal dopamine D1 receptors in natriuresis induced by calcium channel blockers.

The direct tubular natriuretic effect of calcium channel blockers (CCBs) may be due to an interaction between CCBs and a renal tubular dopamine receptor. We therefore studied the effects of two chemically unrelated CCBs, diltiazem and isradipine, infused into the right renal artery of 5% saline-loaded anesthetized rats alone or in the presence of a D1 antagonist, SKF-83742. Isradipine (0.03 microgram.kg-1.min-1) or diltiazem (20 but not 10 micrograms.kg-1.min-1) alone produced an increase in urine flow and an approximate doubling of absolute and fractional sodium excretion, which was not seen in the left kidney or in the control animals (analysis of variance, Scheffé's test, P < 0.05). SKF-83742 alone given systemically or into the right renal artery did not affect these parameters but did block the actions of diltiazem or isradipine. There was no change in mean arterial pressure, renal blood flow, or glomerular filtration rate in any of the experiments. In additional studies, we found that a combined infusion of dopamine (0.1 microgram.kg-1.min-1) and diltiazem (10 micrograms.kg-1.min-1) (doses that by themselves did not alter renal function) produced a twofold or greater increase in urine flow and absolute and fractional sodium excretion; glomerular filtration rate was not significantly changed. Intrarenal arterial CCBs, without a change in renal hemodynamics, produce a natriuresis that is blocked by a D1 antagonist. Concomitant administration of diltiazem and dopamine (each in subeffective doses when used alone) produces a synergistic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The possible role of age-related increase in the plasma glucagon/insulin ratio in the enhanced hepatic gluconeogenesis and hyperglycemia in genetically diabetic (C57BL/KsJ-db/db) mice.

Genetically diabetic db/db mice and their normoglycemic littermates (+/+ mice) were studied to determine plasma levels of glucose, glucagon and insulin and hepatic gluconeogenic enzyme activities. Plasma glucose levels did not differ significantly between the 5-week-old db/db and +/+ mice, but increased with age in the former until the animals were 16-week-old. Similar age-associated changes were observed in the activities of the gluconeogenic enzymes, glucose-6-phosphatase (G-6-Pase) and fructose-1,6-diphosphatase (F-1,6-DPase). While the plasma levels of insulin and glucagon that peaked at 7 weeks of age did not parallel the hyperglycemia, the plasma glucagon/insulin (G/I) ratio roughly paralleled the hyperglycemia. Analysis of individual values for the db/db mice revealed statistically significant (P < 0.001) correlations between plasma glucose levels and hepatic G-6-Pase (r = 0.78) or F-1,6-DPase (r = 0.74) activity. There were also significant correlations between the G/I ratio and plasma glucose levels (P < 0.001, r = 0.66), hepatic G-6-Pase (P < 0.01, r = 0.48) or F-1,6-DPase (P < 0.01, r = 0.57) activity. It is thus concluded that the relative predominance of glucagon over insulin action plays an important role in the age-associated development of hyperglycemia in db/db mice. Glucagon presumably activates the hepatic gluconeogenic enzymes to enhance hepatic glucose output.

Age Factors↗