Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 847 records · Page 47Linked to original sources

PubMed1998

A case of dobutamine-induced coronary arterial spasm with ST-segment elevation.

A 55-year-old Japanese woman demonstrated ST-segment elevation in leads I, aVL, and V3-V6 with chest pain both in an ergometer exercise test and on dobutamine stress echocardiography. Although the baseline coronary arteriogram revealed no organic stenosis, total occlusion of the distal portion of the posterolateral branch of the left circumflex artery was observed during dobutamine infusion with ST-segment elevation and chest pain. This is a rare case of documented dobutamine-induced coronary arterial spasm.

Coronary Vasospasm↗

PubMed1998

Preventive effects of angiotensin-converting enzyme inhibitors on nitrate tolerance during continuous transdermal application of nitroglycerin in patients with chronic heart failure.

This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibitors with and without a sulfhydryl group on intracellular production of cGMP, forearm blood flow, and neurohormonal factors during continuous transdermal application of nitroglycerin in patients with chronic heart failure. Platelet cGMP level and forearm blood flow were measured before and 5 min after sublingual administration of nitroglycerin (NTG) in 20 patients with chronic heart failure during the following 4 phases: (1) baseline phase; (2) NTG phase (1 week after NTG tape 10 mg/day); (3) CPT phase (1 week after both captopril 37.5 mg/day and NTG tape 10 mg/day); and (4) ENL phase (1 week after both enalapril 5 mg/day and NTG tape 10 mg/day). The platelet GMP level before sublingual NTG and forearm blood flow were significantly higher during the 3 phases with NTG tape than during the control phase. The percent increases in platelet cGMP level and forearm blood flow after sublingual NTG were significantly lower during the NTG phase than during the baseline phase. In contrast, concomitant application of ACE inhibitors maintained the percent increase in platelet cGMP level and forearm blood flow. These results indicate that concomitant therapy with ACE inhibitors may be helpful in preventing the attenuation of intracellular cGMP production in patients with chronic heart failure during continuous transdermal application of NTG.

Administration, Cutaneous↗

PubMed1998

Efficacy and rebound phenomenon related to intermittent nitroglycerin therapy for the prevention of nitrate tolerance.

Intermittent transdermal therapy of nitroglycerin (NTG) has been recommended for the prevention of nitrate tolerance, but a rebound phenomenon has been reported to occur following removal of the NTG tape. The present study investigated the effects of intermittent NTG therapy on vasodilatory response and the intracellular production of cyclic GMP (cGMP). The study group comprised 12 healthy adults and measurements were taken of the platelet cGMP level, the venous volume (VV) (by forearm plethysmography) and the plasma levels of neurohormonal factors before and 5 min after administration of 0.3 mg of sublingual nitroglycerin (NTG) during the following 4 phases: (i) the control phase (8.00 h); (ii) the continuous phase (8.00 h; 7 days after continuous application of a 10 mg/24 h NTG tape); (iii) the intermittent application phase (8.00 h; 7 days after intermittent application of NTG tape, applied at 21.00 h and removed at 9.00 h); and (iv) the intermittent removal phase (13.00 h; 4 h after removal of the NTG tape in the intermittent phase). The percentage increase in cGMP (%cGMP) and venous volume (%VV) were significantly lower in the continuous phase than the control phase, but there was no difference between the control and the intermittent application phases. However, in the intermittent removal phase, the cGMP level before sublingual NTG, the %cGMP and the %VV were unchanged, but the VV before sublingual NTG was significantly lower than in the control phase. Plasma renin activity and the plasma level of angiotensin II were significantly increased in the continuous phase, the intermittent application phase, and the intermittent removal phase. In conclusion, intermittent transdermal NTG therapy prevented nitrate tolerance in the production of cGMP and vasodilation, but induced a rebound phenomenon after removal of the NTG tape. The rebound phenomenon following the tape removal may be related to some other mechanism, such as activation of neurohormonal factors.

Administration, Cutaneous↗

PubMed1998

Protective effect of GTS-21, a novel nicotinic receptor agonist, on delayed neuronal death induced by ischemia in gerbils.

The neuroprotective effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride] were studied and compared with those of nicotine, 9-amino-1,2,3,4-tetrahydroacridine hydrochloride hydrate (THA) and pentobarbital-Na (PB) using a cerebral ischemia model in Mongolian gerbils. The learning performance and memory retention were elucidated by a step-through passive avoidance task at 2 and 3 days after ischemia-reperfusion. In this task, the ischemia-operated gerbils showed impairment of learning performance and memory retention. Neuronal cell death in the hippocampal CA1 area was observed at 7 days after ischemia. When administered i.p. 30 min before ischemia, GTS-21 (5 mg/kg), (-)-nicotine (1.5 mg/kg), THA (5 mg/kg) and PB (50 mg/kg) significantly attenuated the impairment of passive avoidance performance and the neuronal cell death induced by the ischemia. When administered orally twice daily for 2 weeks prior to the ischemia, GTS-21 (10 mg/kg) significantly suppressed both amnesia and neuronal cell death, while (-)-nicotine (10 mg/kg) and THA (10 mg/kg) suppressed only the amnesia. These results suggest that GTS-21 exerts a protective activity on not only impairment of learning and memory but also delayed neuronal death and that the underlying mechanism of GTS-21 differs from that of nicotine or THA.

Animals↗

PubMed1998

Inhibitory effects of corymine-related compounds on glycine receptors expressed in Xenopus oocytes.

We examined the effects of 4 corymine-related compounds on glycine-induced chloride current in Xenopus oocytes. Dihydrocorymine, N-demethyl-3-epi-dihydrocorymine and deformylcorymine dose-dependently decreased the glycine current with IC50 values of 34, 37 and 55 microM, respectively. The effect of these compounds on the glycine current was more potent than that of pleiocarpamine (IC50 > 1 mM). N-demethyl-3-epi-dihydrocorymine and dihydrocorymine, at 100 microM, also decreased the gamma-aminobutyric acid-induced current by 65% and 22%, respectively, whereas deformylcorymine and pleiocarpamine failed. The inhibitory action of deformylcorymine on the glycine current was noncompetitive. These results suggest that deformylcorymine is a novel specific noncompetitive glycine receptor antagonist. The structure-activity relationship of these compounds was discussed.

Alkaloids↗

PubMed1998

Cold exposure enhances nitroxidergic nerve-mediated vasodilatation in canine nasal mucosa.

We have previously reported that there is non-adrenergic, non-cholinergic (NANC) innervation in canine nasal mucosa and that the relaxation response to electrical stimulation of the NANC nerve is mainly mediated by nitric oxide (NO). In the present study, we examined the effect of cold exposure (24 degrees C) on nitroxidergic nerve-mediated vasodilatation in isolated canine nasal mucosa. Nasal mucosa strips, prepared from canine nasal septum and moderately precontracted with methoxamine in the presence of atropine and guanethidine, relaxed in response to transmural electrical stimulation (square pulses of 0.5-msec duration, at 5 Hz and 25 V). The degree of relaxation at 24 degrees C (55.4+/-13.2% of methoxamine-induced contraction, mean+/-S.D., n=6) was significantly greater than that at 34 degrees C (33.8+/-8.6%, n=6). This phenomenon was reversible. In contrast, the magnitude of relaxation responses to an NO donor (sodium nitroprusside of 0.1 and 1 microM) remained unchanged by cold exposure. These results suggest that the release of NO from the nitroxidergic nerve endings is augmented by cold exposure and, thus, vasodilatation of the nasal blood vessel is enhanced, thereby contributing to the swelling of the nasal mucosa in cold conditions.

Animals↗

PubMed1998

A comparative study on the effects of nicotine and GTS-21, a new nicotinic agonist, on the locomotor activity and brain monoamine level.

Effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a selective nicotinic agonist, on locomotor activity and dopamine turnover were examined and compared to those of nicotine to test if GTS-21 exhibits side effects similar to those of nicotine. GTS-21 had no effect on locomotor activity in mice or dopamine turnover in rats. In contrast, nicotine produced a biphasic effect on locomotor activity. It also enhanced dopamine turnover rates in the striatum and cerebral cortex, suggesting the involvement of dopaminergic systems in the nicotine-induced changes in locomotor activity. GTS-21 exhibits fewer adverse effects, suggesting that it has therapeutic potential for cognitive disorders related to central cholinergic dysfunction.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Possible mechanism of hypoglycemic effect of 4-hydroxybenzoic acid, a constituent of Pandanus odorus root.

We studied the hypoglycemic effect of 4-hydroxybenzoic acid, a constituent of the root of Pandanus odorus Ridl. (Pandanaceae, Thai name: Toei-hom), in streptozotocin-diabetic rats. Oral administration of 4-hydroxybenzoic acid caused a decrease in plasma glucose levels dose-dependently in the diabetic rat. The constituent did not affect serum insulin level and liver glycogen content in the diabetic model, but increased glucose consumption in normal and diabetic rat diaphragms. These results suggest that 4-hydroxybenzoic acid produces a hypoglycemic effect mediated by an increase in the peripheral glucose consumption.

Animals↗

PubMed1998

GTS-21, a nicotinic agonist, attenuates multiple infarctions and cognitive deficit caused by permanent occlusion of bilateral common carotid arteries in rats.

We examined the effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a nicotinic agonist, on histopathological changes of the brain and radial maze learning performance in rats with permanent occlusion of the bilateral common carotid arteries (2VO) and elucidated whether this compound has a protective effect against the neuronal degeneration and spatial cognitive deficit caused by chronic ischemia. Rats were administered GTS-21 (1 and 10 mg/kg, p.o.) or vehicle 24 hr and 30 min before the 2VO operation and then once daily for 2 months after the operation. The 2VO rats given vehicle had multiple infarctions in the cerebral cortex, hippocampus and striatum and rarefaction in the white matter at 2 months after the operation, although the number and distribution of infarctions varied among individual animals. In addition, the 2VO rats given vehicle showed a higher rate of errors in the acquisition trials of the 8-arm radial maze task than sham-operated controls. However, 2VO rats treated with GTS-21 (1 and 10 mg/kg, p.o.) showed significantly decreased neuropathological changes and less errors in the acquisition trials compared to the vehicle-treated 2VO rats. These results indicate that GTS-21 attenuates impairment of spatial cognitive deficit and progressive neuronal degeneration induced by 2VO and suggest that this compound is beneficial for the treatment of neurodegenerative diseases following chronic cerebral hypoperfusion.

Animals↗

PubMed1998

Enhancement of serotonin 2C receptor mRNA expression by antidepressants possessing the receptor-blocking activity in the rat brain.

The effects of repeated oral administration of antidepressants on the serotonin 2C receptor subtype (5-HT2CR) mRNA level in the rat brain were examined. Imipramine (20 mg/kg, p.o.) enhanced the hybridization signal in a time (days)-dependent manner, reaching a maximum at day 4 and maintaining a high level until day 14. Desipramine and mianserin, which have 5-HT2CR antagonistic activity, also stimulated the mRNA expression to about same extents as imipramine, but nomifensine, which has no effect on 5-HT2CR, was ineffective. These results suggest that long-term treatment with antidepressants, which act as 5-HT2CR antagonists, stimulates 5-HT2CR mRNA expression.

Animals↗

PubMed1998

Molecular analysis of carbon ion-induced mutations in Arabidopsis thaliana.

In order to elucidate the characteristics of the mutations induced by ion particles at the molecular level in plants, mutated loci in carbon ion-induced mutants of Arabidopsis were investigated by PCR and Southern blot analyses. In the present study, two lines of gl1 mutant and two lines of tt4 mutant were isolated after carbon ion-irradiation. Out of four mutants, one had a deletion, other two contained rearrangements, and one had a point-like mutation. From the present result, it was suggested that ion particles induced different kinds of alterations of the DNA and therefore they could produce various types of mutant alleles in plants.

Arabidopsis↗

PubMed1998

Establishment and characterization of a hypocatalasemic mouse cell strain.

Contact-inhibited catalase-deficient fibroblast cell strain has been established from the homozygous hypocatalasemic C3H/Csb mutant mouse. This cell strain has low level of catalase enzyme activity and has normal level of enzyme activities of both glutathione peroxidase and superoxide dismutase. Catalase-deficient C3H/Csb mutant cell strain is markedly more sensitive to the toxicity of hydrogen peroxide compared to wild-type C3H/Csa cell strain. In addition, mutant cell strain is sensitive to X-rays and near-UV compared to wild-type cell strain, but shows the same sensitivities to topoisomerase II inhibitors, adriamycin and 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA), and the DNA cross-linking agents, cisdiamminedichloroplatinum (II) (cis-Pt) and trans-diamminedichloroplatinum (II) (trans-Pt). These cell strains will be of use in the study of the roles which catalase plays in the intracellular prevention of DNA damage induced by oxidative stress.

Acatalasia↗

PubMed1998

Comparison of tumorigenesis between accelerated heavy ion and X-ray in B6C3F1 mice.

The effects of heavy ion and X-ray irradiation on tumorigenesis in B6C3F1 mice were compared. Six-week-old animals were divided into 6 groups and exposed to 0.426 Gy heavy ion irradiation of 290 MeV/u carbon-ion beam (LET 60-210 KeV/micron) at the dose rate of 0.4 +/- 0.2 Gy/min; 0.5 Gy of X-ray irradiation at 0.1 Gy/min or 5 Gy of X-ray irradiation at 1 Gy/min. The mice were killed and an autopsy performed 13.5 months after the whole body irradiation. Body weights were heaviest for both sexes in the 0.5 Gy group and lightest in the 5 Gy one. Total tumor incidences in the males were 30, 56 and 13% respectively in the heavy ion, 5 Gy and 0.5 Gy X-irradiated groups, stomach tumors, lymphomas and adrenal tumors being the most common outcome of the high dose X-rays. Liver tumor induction did not differ significantly among the groups. In the females tumorigenicity was significantly lower for heavy ion than for 0.5 Gy and 5 Gy X-ray irradiation (P < 0.05), the respective incidences, mainly ovary one, being 73%, 17% and 41%. Non-cancerous lesions, such as graying of the hair, glomerular sclerosis and amyloidosis appeared in the 5 Gy group. These findings indicate that 0.426 Gy of heavy ion irradiation induced lower carcinogenicity than 5 Gy of X-irradiation and higher carcinogenicity than that of 0.5 Gy X-irradiation in male mice.

Animals↗

PubMed1998

Prevalence of antibodies of field pseudorabies virus in pigs of herd vaccinated with live vaccine.

This trial was performed in a 350-sow farrow-to-finish pig farm in which animals had been vaccinated against Aujeszky's disease with glycoprotein gC deletion (gC(-)) vaccine. The prevalence of antibodies against field pseudorabies virus (PRV) in serum samples collected from sows and fattening pigs during the period March 1995 to May 1997 was determined by using a commercial assay kit. The frequencies with which PRV-positive sows were found were 28.9% and 25.0% in March and October of 1995, 12.5% and 2.5% in April and October of 1996, and 0% in May of 1997. The fattening pigs tested at these times had no antibody to field PRV. These results thus indicate the probability that the PRV infection at the farm was eliminated by the gC(-) vaccine.

Animals↗

PubMed1998

Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients.

Hypophosphatasia (HOPS) is an inherited disorder characterized by defects in skeletal mineralization due to the deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). To date, various mutations in the TNSALP gene have been identified. Especially, a deletion of T at position 1735 (1735T-del) located in exon 12 has been detected in three genetically unrelated Japanese patients, which seems to be one of the hot spots among the causative mutations in Japanese HOPS patients. 1735T-del causes a frame shift downstream from codon 503 (Leu), and consequently the normal termination codon at 508 is eliminated. Since a new inframe termination codon appears at codon 588 in the mutant DNA, the resultant protein is expected to have 80 additional amino acids. Expression of the mutant TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant 1735T-del had undetectable ALP activity, and its molecule size was larger than normal, as expected. Interestingly, an immunoprecipitation study of patients' sera using antibody against TNSALP revealed an abnormal protein which corresponded in size to the mutated TNSALP expressed by COS-1 cells, suggesting that the abnormal TNSALP is made by HOPS patients. The detection of TNSALP in cells transfected with 1735T-del using an immunofluorescent method exhibited only a faint signal on the cell surface, but an intense intracellular fluorescence after permeabilization.

Alkaline Phosphatase↗

PubMed1998

Practical assay method of cytosolic acetoacetyl-CoA thiolase by rapid release of cytosolic enzymes from cultured lymphocytes using digitonin.

We designed a simple approach to determine cytosolic acetoacetyl-CoA thiolase (CT) activity for differential diagnosis of ketone body catabolic defects, using rapid cell-subfractionation of cultured lymphocytes with digitonin. Efficiency of cell subfractionation was determined by measurement of lactate dehydrogenase and citrate synthetase as marker enzymes for cytosol and organelle fractions, respectively, and confirmed by immunotitration and immunoblotting using antibodies against cytosolic and mitochondrial thiolases, respectively. In the condition of best separation taken in the presence of 1 mg/ml digitonin, acetoacetyl-CoA thiolase activities in the presence of K+ ion in the cytosol and organelle fractions were 138.3+/-39.2 and 84.0+/-16.2 nmol/min/ml, respectively. The thiolase activity in the organelle fraction was doubled by the presence of K+ ion, whereas that in the cytosol fraction was not affected. The thiolase activity in the organelle fraction was reduced by the treatment of anti-mitochondrial acetoacetyl-CoA thiolase (T2) antibody but not by anti-CT antibody. On the other hand, that in the cytosol fraction was significantly decreased by anti-CT antibody but not by anti-T2 antibody. These data suggested that T2 was collected in the organelle fraction, and that CT activity could be assessed by measurement of the thiolase activity in the cytosolic fraction. Succinyl-CoA: 3-ketoacid CoA transferase (SCOT), whose defect is the third inherited disorder of ketone body catabolism, was collected in the organelle fraction. Hence, this method will prove to be useful for accurate assessment of defects of CT as well as T2 or SCOT, all involved in ketone body catabolism.

Acetyl-CoA C-Acetyltransferase↗

PubMed1998

Progression of prostatic cancer in relation to age in patients detected by mass screening program.

With the aim of revealing the natural history of prostatic cancer, the distribution of age was examined in relation to disease progression in patients detected by mass screening programs. Between 1975 and 1996, such programs detected a total number of 132 patients with prostatic cancer. The mean ages of patients with Stage B, Stage C and Stage D disease were 71.2, 73.8 and 75.3 years, respectively. This might suggest that the difference of 3 years in mean age between Stage B and Stage C disease reflects the time interval of the progression of prostatic cancer from the early (Stage B) to the advanced (Stage C) stage. These results coincided well with the natural history of prostatic cancer, which we proposed previously based upon the "size of ranking" analysis of latent prostatic cancer and doubling time obtained from ultrasonic measurement of prostatic volume. An epidemiological study of prostatic cancer detected by mass screening would offer data of value for the elucidation of the natural history of that disease.

Aged↗

PubMed1998

Effects of exercise at different ages on bone density and mechanical properties of femoral bone of aged mice.

We determined the bone density and mechanical properties of bone specimens from 5 groups of aged mice, which had been subjected to voluntary exercise at different ages. ICR 10-week-old female mice were divided into control (C), and exercise-trained during age periods of 10-70 weeks (EE), 10-30 weeks (GPE), 30-50 weeks (MPE) and 50-70 weeks (APE). It was found that in the exercise-trained groups body weight gain was suppressed during the exercise-training period, and that de-training accelerated weight gain. Bone density was significantly higher in all the exercise-trained groups than in the C group and cortical thickness index (CTI) was higher in the exercise-trained groups, except for the APE group. Maximum breaking force, ultimate stress and elasticity in the exercise-trained groups were higher than in the C group except for the APE group, whereas deformation in the APE group had a tendency to be higher than in the other groups. Blood C-terminal parathyroid hormone, calcitonin and calcium concentrations were similar among every group, but phosphorus concentrations tended to be higher in the exercise-trained groups than in the C group. These observations suggest that exercise-training at every age suppresses age-associated bone loss, and that the effect of exercise during youth is greater than that during old age. The results of this study suggest that the effect of exercise on bone at an older age is different from that at other ages.

Aging↗