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Biomedical subjects

M Takeoka

Publications and source records attributed to M Takeoka.

At least 19 recordsLinked to original sources
PubMed1998

Fosphenytoin in infants.

In comparison with phenytoin preparations, which have a pH value of 11, fosphenytoin, a phosphorylated prodrug of phenytoin, has a pH value of only 8.6, which decreases the risk of cardiovascular and cutaneous side effects. The near-neutral pH value of fosphenytoin allows effective intravenous or intramuscular administration. A 1-mg phenytoin equivalent (PE) of fosphenytoin is converted to 1 mg of phenytoin in adults. We describe four infants whose seizures were treated with intravenous fosphenytoin. We had difficulty maintaining therapeutic serum phenytoin levels of 10 to 20 microg/mL on doses of 5 to 8 mgPE/kg/day, and many bolus doses of 5 to 10 mgPE/kg or maintenance doses of more than 10 mgPE/kg/day were given. Despite increased doses in three out of the four patients, a therapeutic serum phenytoin level was not maintained. From our experience, careful and individual dosing of fosphenytoin in this age group can be considered.

Anticonvulsants↗
PubMed1997

KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells.

Administration of exogenous keratinocyte growth factor (KGF) prevents or attenuates several forms of oxidant-mediated lung injury. Because DNA damage in epithelial cells is a component of radiation pneumotoxicity, we determined whether KGF ameliorated DNA strand breaks in irradiated A549 cells. Cells were exposed to 137Cs gamma rays, and DNA damage was measured by alkaline unwinding and ethidium bromide fluorescence after a 30-min recovery period. Radiation induced a dose-dependent increase in DNA strand breaks. The percentage of double-stranded DNA after exposure to 30 Gy increased from 44.6 +/- 3.5% in untreated control cells to 61.6 +/- 5.0% in cells cultured with 100 ng/ml KGF for 24 h (P < 0.05). No reduction in DNA damage occurred when the cells were cultured with KGF but maintained at 0 degree C during and after irradiation. The sparing effect of KGF on radiation-induced DNA damage was blocked by aphidicolin, an inhibitor of DNA polymerases-alpha, -delta, and -epsilon and by butylphenyl dGTP, which blocks DNA polymerase-alpha strongly and polymerases-delta and -epsilon less effectively. However, dideoxythymidine triphosphate, a specific inhibitor of DNA polymerase-beta, did not abrogate the KGF effect. Thus KGF increases DNA repair capacity in irradiated pulmonary epithelial cells, an effect mediated at least in part by DNA polymerases-alpha, -delta, and -epsilon. Enhancement of DNA repair capability after cell damage may be one mechanism by which KGF is able to ameliorate oxidant-mediated alveolar epithelial injury.

Aphidicolin↗
PubMed1997

Low pulmonary diffusing capacity in subjects with acute mountain sickness.

This study was conducted to investigate whether the changes in the pulmonary diffusing capacity found in individuals with acute mountain sickness (AMS) reflect the early stage of high-altitude pulmonary edema (HAPE). We measured the pulmonary diffusion capacity for carbon monoxide (DCO) by the single-breath method, arterialized capillary blood gas, and spirometry in a group of 32 healthy subjects (24 men, eight women) at an altitude of 2,260 m and after ascent to 4,700 m. Twelve subjects (10 men, two women) had symptoms of AMS (AMS group) by the second day after arrival at 4,700 m, but none had clinical signs of pulmonary or cerebral edema. In the non-AMS group, almost all subjects exhibited an increase in DCO at 2,260 to 4,700 m (delta DCO, 10.7 +/- 1.25 mL/min/mm Hg), while the degree of increase in DCO in the AMS group (n = 12) was significantly lower (delta DCO, 1.26 +/- 1.74 mL/min/mm Hg) than that of the non-AMS group (p < 0.01). In four of the 12 subjects with AMS who had a high AMS score, DCO decreased from 38.4 +/- 4.5 to 33.2 +/- 5.3 mL/min/mm Hg (delta DCO, -5.84 +/- 1.1 mL/min/mm Hg). The AMS group showed significantly lower vital capacity, forced expiratory flow during the middle half of FVC, PaO2, and a greater alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS group. DCO showed a significant negative correlation with AMS score (r = -0.885) and a positive correlation with PaO2 (r = 0.757) at 4,700 m. These results suggest that the decreased pulmonary diffusing capacity in subjects with AMS reflects the presence of pulmonary gas exchange abnormality, which is probably due to subclinical interstitial edema of the lung.

Acute Disease↗
PubMed1997

Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.

We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.

Animals↗
PubMed1996

Influence of hypoxia and pulmonary air embolism on lung injury in perfused rat lungs.

We investigated the influence of low oxygen ventilation, air-bubble infusion into the pulmonary artery and their synergistic effect on pulmonary hemodynamics and microvascular permeability in isolated perfused rat lungs. Pulmonary arterial pressure was significantly increased by 70 min of ventilation with 3% O2 (hypoxia, group H); by 0.2-ml air-bubble infusion (pulmonary air embolism, group AE), and by 0.2-ml air-bubble infusion and 70 min of 3% O2 ventilation (hypoxia and pulmonary air embolism, group H & AE) compared with that of a control group (0.2 ml saline infusion, group C). Neither total (TPR) nor arterial (Ra) pulmonary vascular resistance in group H showed any difference compared to control values. TPR and Ra in groups AE and H & AE were significantly higher than those in group C. However, there was no significant difference in TPR or Ra between groups AE and H & AE. The pulmonary capillary fluid filtration coefficient, dry lung to wet lung weight ratio and white blood cell count in the perfusate of group H were not changed, while those of the groups AE and H & AE were significantly increased compared to those of controls. However, there was no significant difference in these values between groups AE and H & AE. Since hypoxia did not damage isolated perfused rat lungs, as determined by hemodynamics and permeability, nor enhance lung injury caused by air embolism, it was suggested that air embolism contributed more to high-altitude lung injury than low oxygen.

Analysis of Variance↗
PubMed1996

Sound stimulation-induced vasomotor reflex in the central artery of the rabbit ear.

Effects of sound stimulation on the central artery of the rabbit ear were studied as a somato-autonomic reflex. Vasoconstriction and dilatation, caused by metronome sound stimulation, were estimated from the temperature fluctuations in the central artery of the ear, measured by a thermistor. To enhance the detection of temperature rises, moderately high background levels of arterial tone were established by exposing the tips of the ears to water at a temperature of 10 degrees C or 5 degrees C, prior to sound stimulation. A fall in arterial temperature due to vasoconstriction was observed immediately after the start of the 1-min sound stimulation, with a subsequent temperature rise which overshot the original basal level due to vasodilatation. A positive correlation between the ear temperature before sound stimulation and the temperature fall (p < 0.01), and a negative correlation between the ear temperature and the temperature rise (p < 0.05) were obtained. The temperature fall was blocked by phenoxybenzamine (9 mg/kg, i.p., p < 0.01). The subsequent rise was not influenced by atropine (3 mg/kg, i.p.) or phenoxybenzamine, however, it was attenuated by hexamethonium (6 mg/kg, i.p., p < 0.05). The temperature fall at the beginning of sound stimulation was related to alpha-adrenergic mechanism. The subsequent temperature rise was thought to be related to parasympathetic mechanism, excluding cholinergic mechanism.

Acoustic Stimulation↗
PubMed1995

Cardiopulmonary function in bicycle racing over mountainous terrain at moderate altitude.

To examine cardiopulmonary function during exercise in a mountainous region at moderate altitude, we measured cardiac frequency, oxygen consumption (VO2), and percentage arterial hemoglobin oxygen saturation (%SaO2) before and after a bicycle race with a starting point at 638 m and finishing point at 1980 m. The time required to ascend an elevation of 10 m was prolonged with increasing altitude, and heart rate also increased with altitude. The %SaO2 at the starting point and at the finishing point differed significantly (P < 0.01). Faster cyclists exhibited higher %SaO2 and lower VO2, while slower cyclists exhibited a reduction in %SaO2 and an increase in VO2 immediately after the race. The %SaO2 recovery time was significantly correlated with the racing time (r = 0.54, P < 0.001). Therefore, the faster cyclists' oxygen debt upon completion of the race may be small and recovery of cardiopulmonary function may be fast, while the slower cyclists' oxygen debt may be large and recovery of cardiopulmonary function may be slow.

Adult↗
PubMed1995

Cardio-pulmonary function of cyclists competing on an ascending mountain course between altitudes of 1400 m and 2800 m.

Physiological changes were investigated in the cardio-respiratory function of competitors in a bicycle race which involved not a flat course but ascending a mountain, from 1400 m to 2800 m. Heart rate throughout the race, arterial oxygen saturation and pulmonary function before and after the race of well trained competitors were measured. The individual's maximal heart rate during the race was designated as HRmax for the calculations. (1) There were significant correlations between the age and the mean %HRmax during the race, between mean %HRmax and time, and between age and time (n = 15); the mean %HRmax had a 3.90 times greater effect on time than did age. (2) The individuals who performed best had lower values of oxygen saturation just after finishing the race (n = 51). (3) At 1 min after reaching the finishing line, oxygen saturation levels had recovered to the value of 20 min after finishing the race, whereas the heart rate was still in the process of recovery (n = 18). (4) Maximum expiratory flow at 50% vital capacity measured 30 min after reaching the finishing line was significantly higher than at the starting point. The intensity of the load on the cardiac system produced by completion of this course was estimated to be almost the same as that of a full marathon on a flat course. The time depended on both the youth of the cyclist and on his ability to maintain a high value of %HRmax during the race.

Adolescent↗
PubMed1995

Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs.

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.

Animals↗
PubMed1994

Higher exercise performance and lower VO2max in Tibetan than Han residents at 4,700 m altitude.

To examine the hypothesis that the pathway of adaptation to high altitude in natives differs considerably from that in newcomers, we measured maximal O2 uptake (VO2max), minute ventilation, anaerobic threshold (AT), blood lactate, and blood gases during maximal exercise in 17 lifelong Tibetan residents and 14 acclimatized Han Chinese newcomers living at the altitude of 4,700 m. The two groups were similar in age, height, and weight, and the subjects were nonathletes. Although VO2max was significantly lower in the Tibetans than in the Hans (30.4 +/- 1.5 vs. 36.0 +/- 1.9 ml.min-1.kg-1 STPD; P < 0.05), at maximal exercise effort the exercise workload was greater (167.7 +/- 4.2 vs. 150.0 +/- 5.9 W; P < 0.05). The mean AT values (in % VO2max) in the Tibetan and Han subjects were 84.1 and 61.6%, respectively (P < 0.01). Minute ventilation at maximal exercise was significantly lower in the Tibetans than in the Hans (68.4 +/- 3.4 vs. 79.7 +/- 4.1 l/min BTPS; P < 0.05), whereas heart rate at maximal effort was equivalent in the two groups. The Tibetans showed lower blood lactate value than did the Hans both before and at the end of exercise. We conclude that the Tibetan natives have higher exercise performance and AT but lower VO2max and blood lactate concentration than do acclimatized Han newcomers. These results may reflect the effects of genetic or peripheral adaptation factors in the Tibetan natives.

Acclimatization↗
PubMed1994

Effects of exercise training at 1,500 m on arterial oxygen saturation and pulse rate.

We compared the effects of exercise training at a low (610 m) altitude with those at moderate (1,500 m) altitude on arterial oxygen saturation (SaO2) and pulse rate (PR) between two groups of men: five subjects in the low altitude group (LG), and five other subjects in the moderate-altitude group (MG), after giving them a series of bicycle training in a hypobaric chamber. Training intensity was 75% HRmax for 60 min/day, 3 times per week for 5 weeks. Before and after the training, Sao2 and PR were measured with a pulse oximeter during step-tests under various air pressures, corresponding to 610 m, 2,000 m, and 4,000 m, respectively, in the chamber. We found that: 1) Sao2 during the step-test carried out at 2,000 m and 4,000 m in the hypobaric chamber was significantly increased in MG compared with that in LG; and 2) PR during the step-tests at 610 m, 2,000 m, and 4,000 m was significantly decreased in MG compared with that in LG. Thus, we conclude that exercise training at a moderate altitude is a useful method for increasing Sao2 and decreasing PR and may prevent mountain sickness.

Adult↗
PubMed1993

Effects of high altitudes on finger cooling test in Japanese and Tibetans at Qinghai Plateau.

The influences of both hypobaric hypoxia and cold on peripheral circulation were studied using the finger cooling test (measurement of the decrease in finger temperature, measured at the dorsal surface of the finger, during immersion of the hand in 0 degrees C water for 20 min) at Qinghai Plateau. The same test was carried out at simulated altitudes in a 25 degrees C climatic chamber to separate the hypobaric hypoxia influence from that of cold. In Japanese subjects at Qinghai Plateau there was a significant difference between finger skin temperatures (FSTs) during 20 min of 0 degrees C water immersion at altitudes of 2260 m and 4860 m by ANOVA. Mean finger skin temperature during the 20-min immersion (5-20 min, MST) measured at 4860 m was significantly lower than that at 2260 m. In Tibetan subjects, there was also a significant difference between FSTs at 2260 m and at 4860 m by ANOVA. MST at 4860 m tended to be lower than that at 2260 m. In the 25 degrees C climatic chamber, there was a significant difference between FSTs of Japanese expedition members at 2000 m and at 4000 m by ANOVA. MST was higher at 4000 m than at 2000 m, contrary to the data obtained in Qinghai. In conclusion, the higher skin temperature in response to local cold immersion, which would have been caused by stronger hypobaric hypoxia, must have been masked by the lower ambient temperature.

Acclimatization↗
PubMed1992

Microcirculation and high altitude edema.

Physiological functions are a conglomeration of cell functions, and all cells are regulated by information processing and energy distributing systems. The former consists of nervous systems and the latter consists of respiro-circulatory systems. Defensive reactions appear in response to local cold stress which can induce frostbite or edema. We analyzed the cold vasoreaction time course in which rhythmical changes and trends were found using rabbit's ear blood vessels. In sheep, hypobaric hypoxia corresponding to 6600 m altitude was applied for 3 hrs. Lung lymph volume increased in response to this stress. Most sheep exposed recovered later. The factors influencing the increase in lung lymph flow and the conditions to induce interstitial edema were analyzed. Simulated-altitude symptoms were, then, analyzed by Sampson's method. In eight subjects exposed to 3700 m condition, the nervous system symptoms were well correlated with the respiro-circulatory symptoms. Thus we concluded that the distinction between system-specific diseases, viz., that between acute mountain sickness cerebral type (AMS-C) and respiratory type (AMS-R) was somewhat fuzzy. A common AMS condition, AMS-general, exists. Lastly, a case of 22-year-old male who died of lung and cerebral edema on a winter mountain was reported. The lung weighed 1506 g and the brain 1610 g.

Adult↗
PubMed1990

Novel pathways of oleic and cis-vaccenic acid biosynthesis by an enzymatic double-bond shifting reaction in higher plants.

The novel pathways of oleic acid formation from cis-vaccenic (cis-11-octadecenoic) acid and of cis-vaccenic acid formation from oleic acid by enzymatic positional isomerization have been proposed in higher plants, based on stable-isotope experiments using [2,2-2H2]cis-vaccenate or [2,2-2H2]oleate as an immediate precursor. A pulp homogenate and also pulp slices prepared from developing kaki (Diospyros kaki) fruit could catalyze these hitherto unknown isomerizations. This suggests the presence of a new type of isomerase responsible for the double-bond shifting reaction without cis-trans isomerization in the middle of fatty acid carbon chains.

Chemical Phenomena↗
PubMed1990

Seasonal variation of cold-induced vasooscillation on rabbit ear central artery.

We studied the seasonal variation of vasooscillation of a rabbit ear central artery induced by exposure of the earlobes to - 7 degrees C liquid. The data were collected over a period of 10 years and analyzed by month. a) The index of arterial temperature fluctuation (IATF), i.e., activation index of cold-induced vasooscillation (CIVO), ranged from 114.5 +/- 26.7 (mean +/- SE) in January to 386.7 +/- 36.1 in June. A significant variation over all 12 months was revealed by analysis of variance (P less than 0.01). The values measured in May (317.1 +/- 47.3), June (386.7 +/- 36.1), and July (315.1 +/- 36.0) were significantly larger than those of other months. b) The monthly IATFs were correlated with the open air temperatures (r = 0.7017, P less than 0.05); however, the peak IATF occurred in June, while the peak open air temperature was in August. c) There was no seasonal variation of the arterial temperature either before or at 18-20 min after -7 degrees C immersion. Arterial temperature was not related to IATF during -7 degrees C exposure. d) When measuring-site temperature was steady, the thermistor temperature changed in parallel with the output from a laser blood volume meter. e) The CIVO was independent of systemic blood pressure and heart rate, which suggested that the occurrence of CIVO was regulated by changes in local vascular resistance.

Animals↗