Search PubMed⌕ Search

Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 505 records · Page 28Linked to original sources

Negative chronotropic and inotropic responses to nicotine in rat right and left atria.

1. Comparison between the chronotropic and inotropic effects induced by nicotine in the right and left atrial muscles of rat was investigated. 2. Nicotine (300 microM and 1 mM) significantly produced negative chronotropic and inotropic effects in the right atrium. The effects were concentration-dependent, and reached a maximum about 30 sec after nicotine administration (1 mM). The responses were attenuated with time even during exposure to nicotine (desensitization). 3. In the left atrium, nicotine (300 microM and 1 mM) caused a negative inotropic effect. The depression was decreased with an increase in the frequencies of stimulation (1-3 Hz). The negative inotropic effect reached a maximum at approx. 60 sec later. 4. Nicotine (1 mM) caused a greater negative inotropic response in the right atrium than in the left atrium by 23% (stimulated at 3 Hz). The effects were not modified by atropine (1 microM) and hexamethonium (1 mM). 5. There was no difference between single and cumulative administrations of nicotine in both right and left atrial muscles. 6. These results suggest that the negative chronotropic and inotropic effects of nicotine may be due mainly to a direct action on the cell membrane of rat atria, accompanied with down regulation of nicotinic ACh receptors. The difference between the right and left atria could result from a different innervation of the autonomic nervous system.

Action Potentials↗

Ouabain actions on the spontaneous activity and ionic currents in rabbit sino-atrial node cells.

1. The effects of ouabain on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using the two-microelectrode technique. 2. Cumulative administrations of ouabain (10(-8) to 10(-6) M) caused a negative chronotropic effect in a concentration-dependent manner. The effect was not modified by atropine (10(-7) M). At 10(-6) M, ouabain prolonged the duration of action potentials, but other parameters were unaffected to any significant extent. Ouabain elicited an arrhythmia, and increasing concentrations increased the incidence of arrhythmia (75% at 3 x 10(-7) M). 3. Pretreatment with clonidine (10(-6) M), a selective agonist of presynaptic alpha 2-adrenoceptors, completely blocked the development of arrhythmia induced by ouabain (3 x 10(-7) M). Prazosin (10(-6) M), an alpha 1 antagonist, had similar effects, and yohimbine (10(-6) to 10(-5) M), an alpha 2 antagonist, did not affect the arrhythmias. 4. Ouabain (10(-8) to 10(-6) M) inhibited the slow inward and the time-dependent outward currents, but enhanced the hyperpolarization-activated inward current, in a concentration-dependent manner. The time course of inactivation phase for Isi was composed of two (fast and slow) components. Ouabain decreased the fast component and increased the slow component. The voltage of half-maximum activation for the outward current was not affected. Ouabain elicited a transient inward current on the repolarizing step, and also on the depolarizing step.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Modified combination chemotherapy of cisplatin and 5-fluorouracil in squamous cell carcinomas of the head and neck.

Randomized studies on the efficacy of two courses of different types of chemotherapy, including cisplatin and 5-fluorouracil (5-FU), were performed on 130 previously untreated cases with advanced squamous cell carcinomas of the head and neck. Cisplatin, followed by 120-hr continuous 5-FU infusion given in the conventional way, was administered to 60 patients (Group A), while cisplatin was administered 72 hr after the initiation of continuous 5-FU infusion in 70 other patients (Group B). The overall response rates (complete response plus partial response) were 58% in group A and 69% in group B, respectively. A superior complete response rate was obtained in cases receiving modified chemotherapy (10% in group A vs 20% in group B). There was no significant difference in the incidence of side effects between the two groups. These findings indicate that the modified cisplatin plus 5-FU combination chemotherapy tested here is more efficacious regimen than that of the conventional one to achieve high complete response rate and subsequently, to improve the survival of advanced carcinoma cases of the head and neck.

Adult↗

Imaging study on the mode of development and changes in avascular necrosis of the femoral head in systemic lupus erythematosus: long-term observations.

To find out when and how avascular necrosis of the femoral head (ANFH) develops in patients with SLE who are receiving corticosteroids, we carried out a 3-yr prospective study using imaging methods. Twenty-three patients with SLE who were free of hip pain and radiographically negative were enrolled in the study. Initially, abnormal findings characteristic of ANFH were detected in eight (35%) and six (26%) patients on MRI and radionuclide uptake bone scanning, respectively. During a 3-yr observation period abnormalities on MRI, bone scanning and radiography were found in four, five and four patients, respectively and three patients developed hip pain. Analyses of imaging changes demonstrated that only a small proportion of patients (2/8, 25%) who initially showed abnormal MRI progressed to be radiographically positive for ANFH over the 3 years. High doses of corticosteroids over the 3-yr period were to be responsible for the emergence of change in MRI abnormalities. It is also suggested that abnormal MRI findings tend to develop either within a relatively short interval after the start of corticosteroid treatment or are associated with the exacerbation of SLE.

Adolescent↗

Residual neurobehavioural effects associated with chronic exposure to mercury vapour.

To find the residual effects of long term exposure to mercury vapour, neurobehavioural tests were given to ex-mercury miners about 18 years after the end of mercury exposure. Seventy six male ex-mercury miners who had been exposed to high concentrations of mercury vapour (over 1.0 mg/m3) and with a history of mercury intoxication were compared with controls matched for age (within 3 years), sex, and education. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, decreased considerably after the end of exposure, matched paired comparison showed that performances of motor coordination, simple reaction time, and short term memory had deteriorated significantly in the exposed group. Multiple linear regression analysis of exposure variables with neurological examination measures showed positive correlations between poorer neurological performance and variables related to mercury exposure. Thus the duration of exposure correlated with poorer performance of hand-eye coordination, tapping, and a colour card reading test. Job categories classified by exposure to mercury also had a significant negative correlation with these performances. The period of years after the end of exposure had a significant correlation with better performance of reaction time and digit span. On the other hand, the history of intoxication itself had no significant correlation with any of the current neurobehavioural performances. These results suggest that there are slight but persistent effects on neurobehavioural function, especially on motor coordination, among mercury miners even more than 10 years after the end of exposure.

Aged↗

Simultaneous measurement of intracellular Na+ and Ca2+ during K(+)-free perfusion in isolated myocytes.

To study the relationship between intracellular Na+ concentration ([Na+]i) and intracellular Ca2+ concentration ([Ca2+]i), guinea pig ventricular myocytes were loaded with both the Na(+)-sensitive probe, sodium-binding benzofuran isophthalate (SBFI), and the Ca(2+)-sensitive probe, fluo 3. [Na+]i was measured from the ratio image at 510 nm when excited at 340/380 nm. [Ca2+]i, expressed as the percent change of corrected fluo 3 fluorescence, was measured at 540 nm when excited at 500 nm. The fluorescent spectra of these probes were sufficiently different to allow for simultaneous measurement. After 30 min perfusion of K(+)-free solution, [Na+]i of rod-shaped cells increased from 6.4 +/- 0.5 to 20.6 +/- 2.6 mM, and [Ca2+]i increased to 256 +/- 36% of the control. [Ca2+]i was higher in spontaneously contracting cells and shortened cells than in rod-shaped cells at similar levels of [Na+]i. When Ca(2+)-free solution or Ni2+ (5 mM) was applied, [Ca2+]i was lower than in cells perfused with K(+)-free solution alone. It was suggested that extracellular Ca2+ and the Na(+)-Ca2+ exchange were involved in the increase in [Ca2+]i. In conclusion, we have developed a new method for the simultaneous measurement of [Na+]i and [Ca2+]i in isolated myocytes, which should be useful to study the relation between [Na+]i and [Ca2+]i.

Aniline Compounds↗

Regulation of [Na+]i and [Ca2+]i in guinea pig myocytes: dual loading of fluorescent indicators SBFI and fluo 3.

To investigate the mechanisms regulating intracellular Na+ and Ca2+ concentrations ([Na+]i and [Ca2+]i, respectively), we monitored both ion concentrations simultaneously using fluorescent probes, Na(+)-binding benzofuran isophthalate (SBFI) and fluo 3, in unstimulated guinea pig ventricular myocytes. After the addition of 500 microM strophanthidin, [Na+]i increased gradually from 6.6 +/- 0.6 to 20.1 +/- 1.6 mM (mean +/- SE) at 50 min. [Ca2+]i, expressed as the percentage change of corrected fluo 3 fluorescence, was kept at the low level during the first 20 min and then began to increase to 447 +/- 81% of the control at 50 min. The addition of 1 microM hexamethylene amiloride prevented the increases in both [Na+]i and [Ca2+]i. The perfusion of Ca(2+)-free solution or 5 mM Ni(2+)-containing solution suppressed the increase in [Ca2+]i. In cells that exhibited spontaneous contractile activities, [Ca2+]i increased further than that in quiescent cells, whereas [Na+]i levels were similar. In the presence of 1 microM ryanodine, both the spontaneous contractile activities and the further increase in [Ca2+]i were eliminated. These findings indicated that 1) the pathway of Na+ entry was mainly through Na(+)-H+ exchange and that the elevated [Na+]i induced Ca2+ entry mediated by the reverse mode of Na(+)-Ca2+ exchange, and 2) the entered Ca2+ triggered the ryanodine-sensitive Ca2+ release from the sarcoplasmic reticulum, causing the dissociation in the relationship between [Na+]i and [Ca2+]i.

Amiloride↗

The RB gene locates on chromosome 15 at band 15q13 in the Syrian hamster.

The retinoblastoma susceptibility gene, which encodes a nuclear phosphoprotein (Rb), plays an important role in cell-cycle progression in both normal development and tumorigenesis. Using a Syrian hamster cDNA probe homologous to the human retinoblastoma gene (RB), we have localized the gene to chromosome band 15q13 by conventional in situ hybridization.

Animals↗

Effect of nilvadipine on the development of neurological deficits in stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Several types of antihypertensive drugs have been reported to protect stroke-prone spontaneously hypertensive rats from stroke. However, the clinical relevance remains unclear. This study was performed to investigate the effect of nilvadipine, a calcium channel blocker, on the development of neurological deficits in stroke-prone spontaneously hypertensive rats. In addition, plasma levels of nilvadipine were measured to determine the clinical relevance. METHODS: Salt-loaded stroke-prone spontaneously hypertensive rats were orally administered nilvadipine mixed with a powder diet (0.01% and 0.03%, wt/wt). Non-salt-loaded rats were maintained on tap water. Chronological changes in neurological deficit scores and systolic blood pressure were recorded. After 6 weeks of medication, measurement of plasma levels of nilvadipine, serum biochemical analysis, and pathological observation of both the brain and the kidney were performed. RESULTS: In the salt-loaded control group, both severe hypertension and neurological deficit developed, and the final survival rate was 30%. Systolic blood pressure decreased significantly in the high-dose nilvadipine-treated group but not in the low-dose nilvadipine-treated group. However, the development of neurological deficit was almost completely inhibited in both nilvadipine-treated groups that had no deaths (P < .01). The mean plasma levels of nilvadipine in the low-dose group and in the high-dose group at the time of death were 0.21 ng/mL and 0.61 ng/mL, respectively. CONCLUSIONS: Nilvadipine inhibited the development of neurological deficit in stroke-prone spontaneously hypertensive rats at plasma concentrations lower than that in clinical use. Thus, nilvadipine might prevent cerebral vascular disorders at doses routinely used for essential hypertension.

Animals↗

Anti-proliferative effects of benidipine hydrochloride in porcine cultured vascular smooth muscle cells and in rats subjected to balloon catheter-induced endothelial denudation.

Using the [3H]thymidine incorporation technique, the anti-proliferative effects of benidipine, a long-acting calcium antagonist, on porcine cultured vascular smooth muscle cells (VSMCs) were determined and compared with those of other calcium antagonists. Benidipine inhibited serum-stimulated [3H]thymidine incorporation into VSMCs (IC50, 0.2 microM), and this inhibitory effect was significantly more potent than that of nitrendipine, felodipine, nisoldipine, manidipine, amlodipine, nifedipine, verapamil and diltiazem. When growth-arrested cells were stimulated with platelet-derived growth factor followed by insulin, benidipine, administered with either stimulation, inhibited [3H]thymidine incorporation into VSMCs. This suggests that it acts in both the G0/G1 and G1/S phases. In another series of experiments, the anti-proliferative effect in vivo was investigated using rats subjected to balloon catheter-induced endothelial denudation of the aorta. Benidipine (5 mg/kg, p.o., b.i.d.) significantly reduced the incorporation of [3H]thymidine into aortic DNA 48 h after balloon injury, whereas it did not affect incorporation into bone marrow, suggesting that it inhibits arterial DNA synthesis. From our results, benidipine was shown to exert antiproliferative effects on VSMCs in vivo as well as in vitro. The drug may be useful for the treatment of vascular proliferative diseases such as restenosis following percutaneous transluminal angioplasty and atherosclerosis.

Animals↗

Protective effects of KW-3635, a thromboxane A2 antagonist, on arachidonic acid-induced transient cerebral ischemia in dogs.

We investigated the effect of KW-3635, a selective thromboxane (TX) A2-receptor antagonist, on the arachidonic acid (AA)-induced transient cerebral ischemia in anesthetized dogs. Intracarotid-arterial injection of AA (0.25-1 mg/kg) produced a transient and reversible decrease in electroencephalographic (EEG) activity. The reduction of EEG power was inhibited by the intravenous injection of KW-3635 or aspirin, a cyclooxygenase inhibitor. Local cortical perfusion (LCP) measured by a laser-doppler flow meter was also reduced concomitantly with the reduction of EEG power. Although KW-3635 at 1 and 3 mg/kg (i.v.) did not affect the maximum reduction of LCP, the duration of the reduction period of LCP was significantly shortened by KW-3635. On the other hand, aspirin at 1 and 3 mg/kg (i.v.) inhibited both the maximum and the delay of LCP reduction. The intravenous administration of KW-3635 or aspirin caused dose-dependent inhibition of ex vivo platelet aggregation stimulated by AA (150 microM) at the doses that improve the EEG activity. These data suggest that TXA2 is one of the important factors in the AA-induced transient reduction of EEG activity in anesthetized dogs. The TXA2-receptor antagonist may be useful for protection against the ischemic brain damage following transient ischemic attack.

Animals↗

Inhibitory action of benidipine on balloon catheterization-induced intimal thickening of the carotid artery in rats.

We examined the effect of benidipine, a long lasting Ca2+ channel blocker, on balloon catheterization-induced intimal thickening of the carotid artery in rats. In the carotid arteries of vehicle-treated rats, neo-intima formation and elevation of DNA content was observed at 14 days after the surgery. Benidipine (5 mg/kg, p.o., b.i.d.) halved the intimal thickening and suppressed the elevated DNA-content in the balloon catheter-injured artery. These results suggest that benidipine may be useful for the treatment of vascular proliferative diseases like restenosis following percutaneous transluminal angioplasty.

Animals↗

Induction of lung tumors in C3H strain mice after single or fractionated irradiation with X-rays.

Murine model for lung tumor induction was studied in C3H/He male mice, a strain with low spontaneous incidence of lung tumors. Dose-response relationships in lung tumor induction were compared following irradiation with single doses and split doses of X-rays to the thorax either at night or in the daytime. The tumor incidence after a single 1.25 Gy dose at night during the period of nocturnal activity almost reached the maximum level after a 5 Gy dose in the daytime. Proliferative activity determined by observing the labeling index with tritiated thymidine in the normal lung was low as a whole, but tended to decrease in the daytime. When the proliferative response was induced by X-irradiation, significantly higher activity was observed at night. These circadian fluctuations were thought to affect radiosensitivity and lung tumor induction in mice. When split doses or fractionated doses of X-rays were applied to the thorax, lung tumor incidence definitely increased. The incidence after two 7.5 Gy doses with a 12 hr-interval was 41%, 3-fold higher than that after a single 15 Gy dose. Moreover, fractionated whole body irradiations (three times at 3 Gy with 3-month-interval) after a single 7.5 Gy thoracic irradiation was most effective in increasing not only the incidence (47%) but also the multiplicity of the lung tumor. More than 30% of tumor-bearing mice had two or more tumors following thoracic and whole body irradiations, while only 10% of tumor-bearers had multiple tumors after single or fractionated thoracic irradiation alone.

Animals↗

Successful pregnancy after curative therapy for advanced lung cancer.

We report a single case in which two successful pregnancies occurred in a young woman following curative management of an advanced adenocarcinoma of the lung with resectional surgery and high-dose postoperative radiotherapy. This is the first case of advanced lung cancer with a favorable outcome.

Adenocarcinoma, Papillary↗

Ca2+ waves and intracellular Ca2+ concentration in guinea pig and rat myocytes.

We measured [Ca2+]i of guinea pig and rat myocytes with Ca2+ waves, using fura-2 fluorescence image processing. In guinea pig myocytes, Ca2+ waves were absent during the control perfusion period, but could be induced by the addition of strophanthidin (100 microM) or sodium cyanide (NaCN: 2 mM) to the perfusate. The [Ca2+]i increased from the control values of 69 +/- 5 nM and 46 +/- 2 nM, to 263 +/- 9 (p < 0.05 vs. control) nM and 225 +/- 20 (p < 0.05) nM, respectively, when cells exhibited Ca2+ waves. Although 13% (16 of 121) of the rat myocytes displayed Ca2+ waves during the control perfusion, the [Ca2+]i with Ca2+ waves (56 +/- 9 nM) did not differ from [Ca2+]i in the absence of Ca2+ waves (54 +/- 3 nM). Ca2+ waves were induced by the perfusion with a high Ca2+ solution (24.5 microM) or NaCN (2 microM), and [Ca2+]i increased from the control values of 67 +/- 11 nM and 74 +/- 5 nM, to 231 +/- 41 (p < 0.05 vs. control) nM and 266 +/- 64 nM, respectively, when cells exhibited Ca2+ waves. The Ca2+ waves were abolished by the removal of extracellular Ca2+, or by the perfusion with ryanodine (10 microM) or caffeine (20 mM). In conclusion, it was shown that Ca2+ waves were due to oscillatory Ca2+ release and that the absolute value of [Ca2+]i is important for the appearance of Ca2+ waves in guinea pig and rat myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical usefulness of serum assay of EIA-CYFRA 21-1 in lung cancer].

Enzyme immunoassay CYFRA 21-1, a novel lung tumor marker presented in serum (upper limit of normal values: 3.5 ng/ml) was measured in 84 patients with lung cancer and 141 patients with benign respiratory diseases. The positive rate for CYFRA 21-1 in primary lung cancer was 70.3% and the false positive rate in respiratory diseases was 24.1%. In respect to the histological types of lung cancer, CYFRA 21-1 was elevated in 85.0% of squamous cell carcinoma and in 64.8% of other cell types of primary lung cancer. Elevated CYFRA 21-1 levels were found in 40% of Stage I-II, in 80.0% of Stage IIIA-B, and in 73.5% of Stage IV. The overall diagnostic efficiency was 53.4% for CYFRA 21-1 and 44.5% for CEA, respectively. Receiver operating characteristic (ROC) curve analysis suggested that CYFRA 21-1 test has an advantage over CEA. From the results of this study, CYFRA 21-1 was more efficient than CEA as primary diagnostic marker in lung cancer.

Biomarkers, Tumor↗