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Biomedical subjects

K Tokuyama

Publications and source records attributed to K Tokuyama.

At least 91 records · Page 5Linked to original sources

Effect of dietary fat type on beta-oxidation of brown adipose tissue and Na+ channel density of brain nerve membrane in rats.

Effect of dietary fat type on beta-oxidation of brown adipose tissue and Na+ channel density of brain nerve membrane was studied in rats. Rats were fed an experimental diet containing lard, high oleic safflower oil, safflower oil or linseed oil for 12 weeks. The activities of carnitine palmitoyltransferase and cytochrome oxidase in brown adipose tissue were significantly lower in rats fed the lard diet than in those fed the high-oleic safflower oil diet, safflower oil diet or linseed oil diet. However, the peroxisomal beta-oxidation activity in brown adipose tissue was significantly higher in rats fed the lard diet than in those fed the other diet. The Na+ channel density in brain nerve membrane was not significantly different among the diet groups. These results suggest that intake of the lard diet rich in saturated fatty acids, compared with the vegetable oil diets rich in unsaturated fatty acids decrease mitochondrial beta-oxidation in brown adipose tissue, and that the dietary fat type has a differential effect on mitochondrial and peroxisomal beta-oxidation in brown adipose tissue.

Adipose Tissue, Brown↗

An epidemiologic analysis of parathyroidectomy in chronic dialysis patients. The Okinawa Dialysis Study Group.

Parathyroidectomy (PTX) is one of the treatments of choice for secondary hyperparathyroidism in chronic dialysis patients. Due to the large increase in long-term dialysis patients, hyperparathyroidism is becoming a common clinical problem. Several studies on PTX have reported various surgical procedures, but limited information is available on the incidence and risk factors of the surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based dialysis registry. It covers the entire area of Okinawa from when the use of chronic dialysis began in 1971. By the end of 1990, a total of 1,986 chronic dialysis patients were registered and 128 of these had undergone PTX by the end of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per 1,000 patient-years. About half of the PTX patients underwent the surgery within 10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase significantly with the duration of dialysis, P < 0.0001. Other clinical variables such as sex, age at the start of dialysis and the presence of diabetes mellitus were not significant predictors of PTX. The probability of PTX increased linearly with the duration of dialysis (r = 0.83, p < 0.0001). After the introduction of active vitamin D in 1981, the probability of PTX was significantly decreased (p < 0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the duration of dialysis, the risk of PTX increased steadily and was estimated to be 10 percent in 10 years and 20 percent in 20 years. Other uremic factors determining a pathological transformation of parathyroid tissue from reactive to autonomous growth remained to be investigated.

Adult↗

Effects of endurance training on gene expression of insulin signal transduction pathway.

Alternative splicing of insulin receptor mRNA and gene expression of insulin receptor, IRS-1 and MAP kinase isoforms were examined in skeletal muscle of trained and sedentary rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill: 30 m/min at 6 degrees incline, 90 min/day, 5 days/week. Endurance training increased insulin receptor mRNA level without change in alternative splicing of insulin receptor mRNA in skeletal muscle. The levels of IRS-1 and MAP kinase (ERKI) mRNA were significantly higher in trained rats than sedentary rats. Our findings provide the first evidence that gene expression of insulin receptor and postreceptor signal transduction pathway is enhanced by endurance training, without affecting alternative splicing of insulin receptor isoforms.

Alternative Splicing↗

Effect of high-fat diet on the gene expression of pancreatic GLUT2 and glucokinase in rats.

To define the biochemical and molecular basis of high-fat diet to reduce insulin secretion, the present study examined the effect of high-fat diet on the gene expression of pancreatic GLUT2 and glucokinase. Rats were isoenergetically meal-fed a high-fat or a high-carbohydrate diet for 10 weeks. Plasma glucose concentration was higher, whereas insulin concentration was lower in the rats fed a high-fat diet than in the rats fed a high-carbohydrate diet. The level of GLUT2 and glucokinase mRNA in pancreas was significantly decreased in the rats fed a high-fat diet compared with a high-carbohydrate diet. The rates of reduction in plasma insulin level, pancreatic gene expression of GLUT2 and glucokinase by high-fat feeding were about 50%. These results suggest that high-fat feeding impairs signal transduction mechanism in pancreatic beta-cells to reduce insulin secretion in rats.

Animals↗

Regulation by physical training of enzyme activity and gene expression of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle.

We examined the effects of short-term (5 weeks) and long-term (12 weeks) physical training on actual and total activities, protein content and mRNA abundance of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle. The actual and total activities were significantly increased approximately 60% and approximately 40%, respectively, by long-term training. No effects of short-term training on activities were observed. The increase in the total activity corresponded to increased protein content of the E1 alpha and E2 components of the complex. On the other hand, mRNA abundance for E1 alpha and E2 were not affected by the training, but that for E1 beta was slightly, but significantly increased by both short-term and long-term trainings. These divergent alterations of the message levels for the subunits of the complex suggest that posttranslational regulatory mechanisms determine the amount of the complex in skeletal muscle. Since the complex is located in the mitochondrial matrix space, mitochondrial biogenesis in response to the training was examined by determining the content of mitochondrial DNA in the muscle. The mitochondrial DNA was proportionally increased with the total activity as well as the protein content of the complex, suggesting that expression of branched-chain 2-oxo acid dehydrogenase complex in skeletal muscle in response to physical training is associated with mitochondrial biogenesis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Insulin sensitivity, insulin secretion, and glucose effectiveness in obese subjects: a minimal model analysis.

The aim of the present study was to estimate insulin sensitivity (SI), insulin secretion, and glucose effectiveness in 14 obese subjects who were further divided into two groups: one with normal glucose tolerance and the other with impaired glucose tolerance (IGT). Glucose tolerance was determined by criteria of the World Health Organization. All subjects were Japanese. They underwent a modified frequently sampled intravenous glucose tolerance test: glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg body weight given over 5 minutes) was infused from 20 to 25 minutes after administration of glucose. SI and glucose effectiveness at basal insulin (SG) were estimated by Bergman's minimal model method. Body mass index (33.0 +/- 1.8 v 30.9 +/- 1.5 kg/m2, P > .05) and fasting insulin level (127.9 +/- 30.0 v 107.4 +/- 14.4 pmol/L, P > .05) were higher in obese IGT subjects than in normal obese subjects, but were not statistically significant. With regard to fasting glucose level, obese subjects with IGT (5.9 +/- 0.3 mmol/L) had significantly higher levels than those with normal glucose tolerance (5.1 +/- 0.2 mmol/L, P < .01). There was no significant difference in SI between the two groups (0.53 +/- 0.10 v 0.56 +/- 0.13 x 10(-4).min-1.pmol/L-1, P > .05). Pancreatic insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 19 minutes was significantly lower in obese subjects with IGT (3,366 +/- 1,495 pmol/L.min) than in those with normal glucose tolerance (16,400 +/- 4,509 pmol/L.min, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sympathetic activity is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet.

Effects of dietary fats consisting of different fatty acids on sympathetic activity and body fat accumulation were studied in rats. Rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for 8 weeks. Carcass fat content was greater (P < .05) in rats fed the beef tallow diet than in rats fed the safflower oil diet. Norepinephrine (NE) turnover rate was significantly lower (P < .05) in interscapular brown adipose tissue (IBAT) and pancreas in rats fed the beef tallow diet than in rats fed the safflower oil diet, resulting in a decreased (P < .05) diet-induced thermogenesis (DIT) and an increased (P < .05) serum insulin concentration in the former. To confirm the effects of dietary fats on sympathetic activity in relation to body fat accumulation, rats were chemically sympathectomized. Sympathectomy abolished the differences in body fat accumulation, DIT, and serum insulin concentration between the two dietary groups. These results suggest that the beef tallow diet promotes body fat accumulation by reducing sympathetic activity as compared with intake of the safflower oil diet.

Adipose Tissue↗

Relationship between ultrasonically nebulized distilled water-induced bronchoconstriction and acetic acid-induced cough in asthmatic children.

BACKGROUND: Although wheezing and cough are the most common complaints in asthmatic persons, the mechanisms of hyperresponsiveness to bronchoconstriction and cough are nevertheless still unclear. OBJECTIVE: To investigate the common mechanisms between them, we studied the relationship between ultrasonically nebulized distilled water (UNDW) inhalation challenge and acetic acid (AA) inhalation challenge. In addition, we evaluated the effect of inhaled furosemide on both provocation tests by means of a placebo-controlled study. METHOD: In study 1 the UNDW, AA, and histamine inhalation challenges were performed in 40 asthmatic children (26 boys, aged from 7 to 16 years; mean +/- SD, 11.2 +/- 2.0 years). In study 2, 12 of the study 1 subjects (9 boys, 11.3 +/- 2.4 years) were subjected to each challenge test after inhalation of furosemide (10 mg/body square meters), or placebo (0.9% saline solution) on separate days. RESULTS: There was a good correlation between the provocative dose causing a 20% fall in forced expiratory volume in 1 second in the UNDW inhalation challenge (UNDW-PD20) and threshold dose causing cough in the AA inhalation challenge (R = 0.527; p < 0.001). There was no relationship either between UNDW-PD20 and the provocative concentration causing a 20% fall in the histamine inhalation challenge (histamine-PC20)(R = 0.384; p > 0.1), or between histamine-PC20 and the cough threshold (R = 0.308; p > 0.05). In study 2 neither bronchoconstriction nor bronchodilation after inhalation of furosemide was observed. Inhaled furosemide exerted a protective effect on UNDW-PD20 and cough threshold of the AA inhalation challenge (p < 0.01 and p < 0.01, respectively), but did not attenuate histamine-PC20 (p > 0.1). CONCLUSION: These data suggest that a common mechanism may cause hyperresponsiveness against both UNDW-induced bronchoconstriction and AA-induced cough in asthmatic children.

Acetates↗

Diet-induced thermogenesis is lower in rats fed a lard diet than in those fed a high oleic acid safflower oil diet, a safflower oil diet or a linseed oil diet.

The objectives of the present study were to examine the effects of dietary fats differing in fatty acid composition on diet-induced thermogenesis, sympathetic activity in brown adipose tissue and body fat accumulation in rats. Rats were meal-fed for 12 wk an isoenergetic diet based on lard, high oleic acid safflower oil, safflower oil or linseed oil, and norepinephrine turnover rates in brown adipose tissue were then estimated. Whole-body oxygen consumption after the meal indicated that diet-induced thermogenesis was significantly lower in rats fed the lard diet than in those fed the other diets. The norepinephrine turnover rate in the interscapular brown adipose tissue was also significantly lower in the lard diet group than in the other diet groups. The carcass fat content was significantly higher in the lard diet group than in the other diet groups, whereas the abdominal adipose tissue weights were the same in all diet groups. These results suggest that the intake of animal fats rich in saturated fatty acids, compared with the intake of vegetable oils rich in monounsaturated or polyunsaturated fatty acids, decreases diet-induced thermogenesis by a decline of sympathetic activity in brown adipose tissue, resulting in the promotion of body fat accumulation.

Adipose Tissue, Brown↗

Serum triiodothyronine concentration and Na+,K(+)-ATPase activity in liver and skeletal muscle are influenced by dietary fat type in rats.

It has been shown previously that dietary fat type influences body fat accumulation in rats. The effects of dietary fat type on serum thyroid hormone, activity of Na+,K(+)-ATPase and lipoprotein lipase were studied. Rats were fed an experimental diet containing lard, high oleic safflower oil, safflower oil or linseed oil for 12 wk. Carcass fat content was significantly higher in rats fed the lard diet than in those fed the other diets. However, intra-abdominal adipose tissue weights were not affected by type of dietary fat. The serum triiodothyronine concentration and the activity of Na+,K(+)-ATPase in the liver and skeletal muscle were significantly lower in the lard diet group than in the other diet groups. The lipoprotein lipase activity of abdominal subcutaneous fat was significantly higher in rats fed the lard diet than in rats fed the other diets, but the activity of lipoprotein lipase in intra-abdominal fat was not significantly different. These results suggest that the intake of lard, compared with the intake of the vegetable oils, may decrease Na+,K(+)-ATPase activity in the liver and skeletal muscle by lowering serum triiodothyronine concentration, resulting in the promotion of body fat accumulation.

Adipose Tissue↗

Ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to attenuate eicosanoid-induced airflow obstruction and airway microvascular leakage.

Beta-2 adrenoceptor agonists are widely used as bronchodilators in the treatment of asthma mainly via inhalation. In the present study, we evaluated the ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to reduce eicosanoid-induced airway microvascular leakage, and compared the ability with its inhibitory effect against bronchoconstriction. Tracheostomized guinea-pigs were given aerosolized procaterol (10 or 100 micrograms/ml) for 10 min under spontaneous breathing. Immediately after the end of inhalation, the animals were mechanically ventilated. Fourteen minutes after the end of inhalation, Evans blue dye (20 mg/kg) was given i.v. One minute later, 2 nmol/kg leukotriene D4 (LTD4), 50 nmol/kg U-46619, a thromboxane A2 mimetic, or vehicle was administered i.v. LTD4- or U-46619-induced increase in lung resistance was measured for 6 min. After removing the lungs, the amount of extravasated Evans Blue due in the lower airways was examined as an index of microvascular leakage. Inhaled procaterol significantly attenuated increases in both lung resistance and Evans Blue dye extravasation caused by these eicosanoids. The degree of inhibition was almost complete for lung resistance (approximately 90%), but it was only partial (range 18.5-61.2%) for the dye extravasation. No significant changes in mean systemic blood pressure and in heart rate was observed after an inhalation of 10 micrograms/ml procaterol. These results suggest that inhaled beta 2 adrenoceptor agonists may reduce airway microvascular leakage caused by inflammatory mediators such as eicosanoids without affecting systemic circulation.

Adrenergic beta-Agonists↗

Effect of procaterol, a beta 2-adrenoceptor agonist, on skin whealing response caused by inflammatory mediators in asthmatic children.

BACKGROUND: Beta 2-adrenoceptor agonists have been shown to reduce allergen-induced skin whealing responses via inhibition of mediator release. OBJECTIVE: To study whether beta 2-adrenoceptor agonists have a direct action against inflammatory mediator-induced skin whealing responses. METHODS: We examined the effect of procaterol, a beta 2-adrenoceptor agonist, on skin whealing responses to histamine, platelet-activating factor (PAF), substance P, or bradykinin in eight asthmatic children in a double-blind, randomized, cross-over study. Two hours after taking procaterol (50 micrograms) or placebo orally, the subjects were given these mediators intradermally at a concentration of 10(-5) M. RESULTS: Procaterol has a small but significant inhibitory effect on wheal formation following the intradermal injection of histamine and PAF by an average of 15% (P < .05) and 18% (P < .05) respectively but not against substance P or bradykinin. CONCLUSIONS: Our results suggest that although beta 2-adrenoceptor agonists may have an inhibitory effect against plasma exudation from microvasculature in the human skin, bronchodilatory effects are more prominent.

Adolescent↗

Clinical and immunologic surveys of Hymenoptera hypersensitivity in Japanese forestry workers.

BACKGROUND: The increased incidence of bee-sting allergy among beekeepers is well known, whereas Hymenoptera hypersensitivity among forestry workers, who are frequently stung by Hymenoptera, is not well understood. OBJECTIVE: To elucidate the nature of Hymenoptera hypersensitivity among forestry workers and analyze the mechanism involved in Hymenoptera-induced systemic reactions. METHODS: A questionnaire was administered and yellow jacket venom-specific IgE antibody titers measured in 323 forestry workers and 100 age-matched office workers with little occupational exposure to Hymenoptera stings as a control group. RESULTS: From the questionnaire it was found that the percentage of systemic reactions to Hymenoptera stings was significantly greater in the forestry workers than in the control subjects (P < .01). The number of sting exposures was significantly higher in the forestry workers than in the control subjects (P < .01) and was closely correlated with episodes of systemic reaction. Yellow jacket venom-specific IgE antibody titers were significantly higher in forestry workers with episodes of systemic reaction compared with those with only local or large local reactions to Hymenoptera (P < .05), although more than half of these subjects had undetectable IgE antibody titers to yellow jacket venom. IgE antibody titers against yellow jacket venom were closely correlated with those of paper wasp (rs = .802, P < .001), which is another frequent source of Hymenoptera stings. In workers with episodes of sting exposure within the most recent 3 years, the period from the last sting was not correlated with yellow jacket venom-specific IgE antibody titers. CONCLUSIONS: The number of sting exposures may contribute to systemic reactions to Hymenoptera sting, and some mechanism other than IgE mediated hypersensitivity may also be involved in Hymenoptera-induced systemic reactions.

Adult↗

Effect of high-fat diet on gene expression of GLUT4 and insulin receptor in soleus muscle.

Gene expression of GLUT4 and insulin receptor in soleus muscle of high-fat and high-carbohydrate diet fed rats was studied by measuring mRNA. High-fat diet feeding increased plasma glucose but decreased plasma insulin level. Glucose uptake in soleus muscle measured by 2-deoxy-D-glucose technique was lower in high-fat than high-carbohydrate diet fed rats. GLUT4 mRNA level in soleus muscle was significantly decreased but insulin receptor mRNA was similar in high-fat compared with high-carbohydrate diet fed rats. Insulin receptor exists in two forms generated by alternative splicing of a primary gene transcript. There was no difference in the relative expression of insulin receptor isoform mRNAs between high-fat and high-carbohydrate diet fed rats. These results suggest that high-fat diet impairs glucose metabolism in muscle by reducing transcription of GLUT4 without affecting gene expression of insulin receptor.

Alternative Splicing↗

Effect of maturation on airway plasma exudation induced by eicosanoids in guinea pig.

Airway reactivity to bronchoconstrictor mediators changes with age. We studied the effects of maturational change on airway responses induced by a thromboxane A2 mimetic, U-46619 (2, 6 and 20 nmol/kg; i.v.), leukotriene D4 (0.6 and 2 nmol/kg; i.v.) or vehicle (0.9% NaCl; i.v.) in immature (196 +/- 3 g: 2 weeks) and adult guinea pigs (512 +/- 5 g: 11 weeks). In the same animals, we measured both lung resistance (RL) to monitor airflow obstruction and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. For a comparison, changes in RL in response to acetylcholine (5, 15 and 50 nmol/kg; i.v.) were also examined in both age groups. The order of potency to induce an increase in RL did not change with age (leukotriene D4 > U-46619 > acetylcholine). In immature animals, the peak RL after U-46619 (2, 6 and 20 nmol/kg; P < 0.05, P < 0.005 and P < 0.01, respectively) and leukotriene D4 (2 nmol/kg; P < 0.01) was significantly higher than in adult animals. U-46619 and leukotriene D4 produced significant extravasation of Evans Blue dye in both immature and adult animals. The order of potency to induce extravasated dye also did not change with age (leukotriene D4 > U-46619). The amount of extravasation of Evans Blue dye after U-46619 (6 and 20 nmol/kg) and leukotriene D4 (0.6 and 2 nmol/kg) was significantly smaller in immature animals than adults at all airway levels.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Modulation of branched-chain 2-oxo acid dehydrogenase complex activity in rat skeletal muscle by endurance training.

Effects of endurance training and high-fat diet intake on the branched-chain 2-oxo acid dehydrogenase complex in skeletal muscle were examined in rats. The basal activities of the enzyme complex (approximately 4% in active form of the total enzyme) in the muscle of rats under the fed conditions were not different between trained and untrained rats. The basal activity in the muscle was elevated by 24 h starvation in both groups of rats, but the level of the elevation was significantly greater in the trained rats than in the untrained rats. On the other hand, high-fat diet intake did not alter the basal activity of the enzyme complex in the muscle or the profile of activation of the enzyme complex by muscle contractions elicited by the electrical stimulation, suggesting that the fat content in the diet does not affect the enzyme activity in the muscle. Neither training nor diet affected the total enzyme activity or the amount of enzyme protein. Activation by leucine administration of the enzyme complex in the muscle was greater in the trained rats than in the untrained rats, suggesting that the activity state of the enzyme complex is more responsive to regulation by the 2-oxo acid derived from leucine in the muscles of endurance-trained rats.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

The effect of non-steroidal anti-inflammatory drugs on the electrical properties of cultured dog tracheal epithelial cells.

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the electrical properties of primary cultures of dog tracheal epithelium has been studied. The cells used were grown with an air interface in a serum-free medium on membranes coated with human placental collagen. When mounted in Ussing chambers at 37 degrees C, mean values for the baseline short circuit current (Isc) and the transepithelial resistance of 65 tissue specimens from 18 dogs were 24.0 +/- 3.2 microA/cm2 and 458 +/- 128 omega.cm2, respectively. These tissues had been pretreated with amiloride to abolish active Na+ absorption. Under these conditions, the Isc value serves as a measure of active Cl- secretion. The results of this study revealed that the Isc across a cultured monolayer of trachea was attenuated by the tested NSAIDs, indomethacin, fulfenamic acid, mefenamic acid, aspirin, and acetaminophen, with Ki's that ranged from 6.0 x 10(-5) to 2.51 x 10(-3) M. Salicylic acid had no effect on baseline Isc. The Isc sensitivity sequence to the Cl- channel inhibitors tested was: fulfenamic acid >> indomethacin > mefenamic acid >> aspirin > acetaminophen > salicylic acid. The NSAIDs also significantly inhibited both the transient, Ca(2+)-dependent and the sustained, cAMP-dependent increases in Isc elicited by isoproterenol. Thus, the tested NSAIDs appeared to have an effect on the electrical properties of the cells. A similar effect of NSAIDs on ion transport across the human airway epithelium may help to reduce airway fluid secretion.

Animals↗