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Biomedical subjects

K Tokuyama

Publications and source records attributed to K Tokuyama.

At least 37 records · Page 2Linked to original sources
PubMed2000

The role of the body mass index and triglyceride levels in identifying insulin-sensitive and insulin-resistant variants in Japanese non-insulin-dependent diabetic patients.

Using the minimal model approach shown by Bergman, our group had previously shown 2 variants among non-obese mildly diabetic patients, one with normal insulin sensitivity and the other with insulin resistance. The present study examines whether these 2 variants exist in the ordinary Japanese non-insulin-dependent diabetes mellitus (NIDDM) population and compares the clinical profile between the 2 discrete forms of NIDDM. In addition, we investigated the factors responsible for insulin resistance observed in Japanese NIDDM populations. One hundred eleven untreated Japanese NIDDM subjects (fasting glucose < 10 mmol/L) were assessed for insulin action (homeostasis model assessment [HOMA-IR] = fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5) and the fasting lipid profile. Sixty percent of these patients had normal insulin sensitivity (HOMA-IR < 2.5). The insulin-resistant patients had higher serum cholesterol (188.1 +/- 5.2 v 182.2 +/- 3.9 mg/dL, P> .05) and low-density lipoprotein (LDL) cholesterol (501.2 +/- 16.7 v 469.4 +/- 14.8 mg/dL, P > .05) than the insulin-sensitive patients, but the difference was not statistically significant. In contrast, the former group had a significantly higher body mass index ([BMI] 26.6 +/- 0.8 v 21.7 +/- 0.4 kg/m2, P < .0001) and higher serum triglycerides (181.0 +/- 16.4 (range, 79 to 545) v 95.1 +/- 4.1 (range, 36 to 204) mg/dL, P < .0001) and lower high-density lipoprotein (HDL) cholesterol (47.2 +/- 1.7 v 58.2 +/- 2.5 mg/dL, P < .005) than the latter group. HOMA-IR was related to the BMI. Fifteen of 17 (88%) NIDDM patients with a BMI greater than 27.0 were insulin-resistant, whereas 35 of 38 (92%) NIDDM patients with a BMI less than 21.5 were insulin-sensitive. In the midrange BMI (21.5 to 27.0 kg/m2), patients were equally likely to be insulin-resistant or insulin-sensitive. Analysis of the midrange BMI group showed that HOMA-IR was associated with serum triglycerides (P < .0001) but not with the BMI. These data suggest the following conclusions: (1) Japanese NIDDM patients can be classified into 2 populations, one with normal insulin sensitivity and the other with insulin resistance; (2) NIDDM patients with normal insulin action have a low cardiovascular disease risk factor, whereas those with insulin resistance have a markedly increased cardiovascular disease risk factor; and (3) the BMI and serum triglyceride level per se are associated with insulin action in Japanese NIDDM populations.

Adult↗
PubMed2000

Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism.

Bone metabolism is strongly influenced by heredity and environmental factors. To investigate interaction of the effects between vitamin D receptor polymorphism by Fok I and resistance exercise training on bone metabolism, young male subjects with FF genotype (F, n = 10) and Ff or ff genotypes (f, n = 10) followed 1 mo of weight training, and changes in bone metabolism were compared. An additional 14 subjects served as a sedentary control. Biomarkers of bone formation, bone-specific alkaline phosphatase, and osteocalcin were significantly increased by training in both F and f groups. 1, 25-Dihydroxyvitamin D(3), known to upregulate bone formation, was also increased by the training in the f but not in the F group. Bone resorption assessed by cross-linked NH(2)-terminal telopeptide of type I collagen was significantly suppressed by the training, and the decrease in F was greater and longer lasting than that in f group. In conclusion, stimulation of bone formation and suppression of bone resorption occurred within 1 mo in young men. Despite a significant increase in 1,25-dihydroxyvitamin D(3) in the f group but not in the F group, the response of bone metabolism to the training in the F was similar to or greater than that in f group, suggesting a functional difference between vitamin D receptor genotypes f and F.

Adult↗
PubMed2000

Stimulation of the beta(2) integrin, alpha(M)beta(2), triggers tyrosine phosphorylation and cellular degranulation on human eosinophils.

Activation of human eosinophils by specific extracellular stimuli triggers the cellular degranulation response. Because cellular adhesion is critical for this eosinophil degranulation, we have tested the hypothesis that ligation of the beta(2) integrin, alpha(M)beta(2) (Mac-1, CD11b/CD18), leads to intracellular signaling events that contribute to the eosinophil activation response. Recently, we found that engagement of beta(2) integrin using two different approaches, such as cell adhesion induced by IL-5 or direct ligation of alpha(M)beta(2), triggered tyrosine phosphorylation of Cbl, the product of the c-cbl proto-oncogene, paxillin, a cytoskeletal protein, an unidentified 115-kD protein, and subsequent cellular degranulation. The results of this study indicate that engagement of alpha(M)beta(2) on eosinophils triggers an intracellular signaling cascade leading to cellular degranulation. Tyrosine phosphorylation of Cbl, paxillin, and a 115-kD protein may play important roles in adhesion-dependent cellular functions of eosinophils.

CD18 Antigens↗
PubMed2000

Bronchial hyperresponsiveness before and after the diagnosis of bronchial asthma in children.

OBJECTIVE: To assess at what age bronchial hyperresponsiveness (BHR) is acquired in children with asthma. BACKGROUND: A relationship between BHR and infantile wheezing diseases has been reported. Infants with a genetic predisposition to atopy are more likely to wheeze with respiratory viral infection or bronchiolitis, and it is suspected that the continued BHR after the first attack of asthma may be induced or triggered by some viral infections. Also, recent studies have reported the existence of atopic and BHR-related genes. However, whether BHR is congenital or acquired after asthma attacks, and when BHR in children with asthma is established or acquired remain unclear. METHODS: We performed methacholine inhalation challenge using a transcutaneous oxygen pressure (tcPO(2)) monitoring system in 205 children without asthma from 6 months to 6 years of age. During follow-up, 18 of these participants were diagnosed with asthma (group N-A). This group and 15 age-matched children without asthma (group N-N) were tested twice using methacholine inhalation challenge. For comparison, 39 age-matched atopic-type asthmatic children (group A-A) were also given the inhalation challenge twice. Methacholine inhalation challenge using a tcPO(2) monitoring system was performed while the participants were asleep in the supine position. Sequential doses of inhaled methacholine delivered by oxygen mask were doubled until a 10% decrease in tcPO(2) from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO(2) (minimal dose of methacholine [Dmin]-PO(2)) was considered to represent BHR. RESULTS: In groups N-N and A-A, there was no difference in Dmin-PO(2) between the first and second challenge. However, the Dmin-PO(2) in group N-A significantly decreased from the first challenge to the second challenge. There was no significant difference between the Dmin-PO(2) in group N-N and the first Dmin-PO(2) in group N-A; or between the Dmin-PO(2) in group A-A and the second Dmin-PO(2) in group N-A. CONCLUSIONS: These data suggest that BHR in many infants with asthma is acquired after several asthma attacks.bronchial hyperresponsiveness, childhood asthma, methacholine inhalation challenge, transcutaneous oxygen pressure.

Asthma↗
PubMed2000

Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.

OBJECTIVE: The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. RESULTS: The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. CONCLUSIONS: These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.

Apolipoproteins↗
PubMed1999

Effect of long-term exercise on gene expression of insulin signaling pathway intermediates in skeletal muscle.

To elucidate the molecular mechanism underlying insulin sensitivity, we have thought to investigate gene expression of insulin signaling pathway intermediates in skeletal muscle from sedentary and endurance-trained rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill; 30 m/min at a 6 degrees incline, 90 min/day, 5 days/week. The levels of PI 3-kinase, GLUT4, p70 S6 kinase and Ras mRNA were significantly increased by 89, 40, 38, and 47%, respectively, with running training; however, the Nck mRNA level was decreased by 24%. mRNA levels of SHP-2, Grb2, Sos, Shc, GAP, p62 and p90 S6 kinase were unaltered by running training. We have previously reported that endurance training increases mRNA levels of insulin receptor, IRS-1 and ERK1 in skeletal muscle of rats. Taken together, our data suggest that gene expression of the insulin signal pathway intermediates is modulated by endurance training that may be associated with alteration of insulin sensitivity.

Animals↗
PubMed1999

Successful treatment of a non-haemophilic patient with inhibitor to factor VIII by double-filtration plasmapheresis.

Factor VIII (FVIII) inhibitors appear in 3-20% of haemophilia A patients after injection of FVIII concentrates. However, autoantibodies to FVIII are also reported in non-haemophiliacs. In these patients FVIII inhibitor disappears spontaneously or diminishes in response to immunosuppressive therapy. However, a few patients show resistance to immunosuppressive therapy. We describe a non-haemophilic elderly patient with acquired FVIII inhibitor who failed to respond to prednisolone. He was treated with double-filtration plasmapheresis (DFPP) which resulted in a very rapid reduction in inhibitor levels and resolution of symptoms.

Aged↗
PubMed1999

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.

Adult↗
PubMed1999

Effect of ultrasonically nebulized distilled water on airway epithelial cell swelling in guinea pigs.

To investigate the pathogenesis of ultrasonically nebulized distilled water-induced airway narrowing, we studied the role of airway epithelial cells during a distilled water-inhalation challenge in an animal model of airway inflammation. Guinea pigs were divided into four groups: 1) a sham/saline (S/S) group: sham ozone followed by saline inhalation; 2) a sham/water (S/W) group: sham ozone followed by water inhalation; 3) an ozone/saline (O/S) group: ozone followed by saline inhalation; and 4) an ozone/water (O/W) group: ozone followed by water inhalation. After exposure to either 3.0 parts/million ozone or air at the same flow rate for 2 h, guinea pigs were anesthetized and tracheostomized, and then lung resistance (RL) was measured. For morphometric assessment, tissues were fixed with formaldehyde, stained with hematoxylin and eosin, and cut into transverse sections. Airway dimensions were either measured directly or calculated from the internal perimeter, the external perimeter, and airway wall area. There were no statistical differences in the values of RL before distilled water inhalation between the sham groups and the ozone groups. RL increased significantly after 10 min of distilled water inhalation in both the S/W group and the O/W group. In the S/W group, epithelial cells were swollen, and intercellular spaces were wider, resulting in significant increase in epithelial wall thickness, but there was no significant infiltration by inflammatory cells. In the O/S group, the epithelium showed infiltration by inflammatory cells without change in cell volume. In the O/W group, the epithelium showed both infiltration and a greater increase in epithelial wall thickness compared with the S/W group. These results suggest that airway epithelial cell swelling, induced by inhaled distilled water, increases with RL in guinea pigs and that this reaction may be accelerated by airway inflammation.

Administration, Inhalation↗
PubMed1999

Influence of mild exercise at the lactate threshold on glucose effectiveness.

The effect of a single bout of mild exercise on glucose effectiveness (S(G)) and insulin sensitivity (S(I)) was studied in six young male subjects by using a minimal model. An intravenous glucose tolerance test was performed under two conditions as follows: 1) 25 min after a bout of exercise on a cycle ergometer at the lactate threshold level for 60 min (Ex) and 2) without any prior exercise (Con). Leg blood flow (LBF) was also measured by strain-gauge plethysmography simultaneously with blood sampling. S(I) did not significantly change after exercise (18.1 +/- 1.5 vs. 17.7 +/- 1.9 x 10-(5) min/pM), whereas S(G) significantly increased (0.016 +/- 0.002 vs. 0.025 +/- 0.002 min(-1), P < 0.01). The increased blood flow after exercise remained high during the time period for measurement of the glucose disappearance constant and may be a determinant of S(G). The incremental lactate area under the curve until insulin loading was also significantly higher in Ex than in Con (2.6 +/- 0.9 vs. -3.5 +/- 1.5 mM/min, P < 0.05). These results suggest that increased S(G) after mild exercise may be due, at least in part, to increased LBF and lactate production under a hyperglycemic state.

Adult↗
PubMed1999

Intracellular signaling pathways in human eosinophil activation: role of a beta2 integrin, alphaMbeta2.

Cellular adhesion is crucial roles for eosinophil effector functions such as degranulation. Here, we focused on the role of a beta2 integrin, alphaMbeta2, in intracellular signaling pathways of human eosinophil activation. We found that the ligation of alphaMbeta2 triggers the activation of an intracellular signaling cascade, including protein tyrosine phosphorylation and phosphoinositide turnover, and subsequent cellular degranulation in human eosinophils. These signaling events may play important roles in adhesion-dependent cellular functions of eosinophils.

Cell Adhesion↗