PubMed Health⌕ Search

Biomedical subjects

Y Higaki

Publications and source records attributed to Y Higaki.

At least 19 recordsLinked to original sources
PubMed2001

Insulin alters heterogeneous nuclear ribonucleoprotein K protein binding to DNA and RNA.

The interaction of the multimodular heterogeneous nuclear ribonucleoprotein (hnRNP) K protein with many of its protein and nucleic acid partners is regulated by extracellular signals. Acting as a docking platform, K protein could link signal-transduction pathways to DNA- and RNA-directed processes such as transcription, mRNA processing, transport, and translation. Treatment of hepatocyte culture with insulin increased K protein tyrosine phosphorylation. Insulin altered K protein interaction with RNA and DNA in vitro. Administration of insulin into mice had similar effects on K protein in liver. Coimmunoprecipitations of RNA with K protein revealed preferential in vivo K protein binding of a subset of transcripts, including the insulin-inducible c-fos mRNA. These results suggest a class of insulin pathways that signal nucleic acid-directed processes that involve K protein.

Animals↗
PubMed2001

Granzyme-B-containing lymphocyte involvement in epidermal injury in graft-versus-host disease.

BACKGROUND: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). OBJECTIVE: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. METHODS: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. RESULTS: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. CONCLUSIONS: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.

Acute Disease↗
PubMed2001

Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle.

Insulin, contraction, and the nitric oxide (NO) donor, sodium nitroprusside (SNP), all increase glucose transport in skeletal muscle. Some reports suggest that NO is a critical mediator of insulin- and/or contraction-stimulated transport. To determine if the mechanism leading to NO-stimulated glucose uptake is similar to the insulin- or contraction-dependent signaling pathways, isolated soleus and extensor digitorum longus (EDL) muscles from rats were treated with various combinations of SNP (maximum 10 mmol/l), insulin (maximum 50 mU/ml), electrical stimulation to produce contractions (maximum 10 min), wortmannin (100 nmol/l), and/or the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) (0.1 mmol/l). The combinations of SNP plus insulin and SNP plus contraction both had fully additive effects on 2-deoxyglucose uptake. Wortmannin completely inhibited insulin-stimulated glucose transport and only slightly inhibited SNP-stimulated 2-deoxyglucose uptake, whereas L-NMMA did not inhibit contraction-stimulated 2-deoxyglucose uptake. SNP significantly increased the activity of the alpha1 catalytic subunit of 5'AMP-activated protein kinase (AMPK), a signaling molecule that has been implicated in mediating glucose transport in fuel-depleted cells. Addition of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mg/ml) to the drinking water of rats for 2 days failed to affect the increase in muscle 2-deoxyglucose uptake in response to treadmill exercise. These data suggest that NO stimulates glucose uptake through a mechanism that is distinct from both the insulin and contraction signaling pathways.

Animals↗
PubMed2001

Effect of mild exercise training on glucose effectiveness in healthy men.

OBJECTIVE: To detect whether mild exercise training improves glucose effectiveness (S(G)), which is the ability of hyperglycemia to promote glucose disposal at basal insulin, in healthy men. RESEARCH DESIGN AND METHODS: Eight healthy men (18-25 years of age) underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before as well as at 16 h and 1 week after the last training session. S(G) and insulin sensitivity (S(I)) were estimated using a minimal-model approach. RESULTS: After the exercise training, VO(2max) and VO(2) at LT increased by 5 and 34%, respectively (P < 0.05). The mild exercise training improves S(G) measured 16 h after the last training session, from 0.018 +/- 0.002 to 0.024 +/- 0.001 min(-1) (P < 0.05). The elevated S(G) after exercise training tends to be maintained regardless of detraining for 1 week (0.023 +/- 0.002 min(-1), P = 0.09). S(I) measured at 16 h after the last training session significantly increased (pre-exercise training, 13.9 +/- 2.2; 16 h, 18.3 +/- 2.4, x10(-5). min(-1). pmol/l(-1), P < 0.05) and still remained elevated 1 week after stopping the training regimen (18.6 +/- 2.2, x10(-5). min(-1). pmol/l(-1), P < 0.05). CONCLUSIONS: Mild exercise training at LT improves S(G) in healthy men with no change in the body composition. Improving not only S(I) but also S(G) through mild exercise training is thus considered to be an effective method for preventing glucose intolerance.

Adult↗
PubMed2001

[Clinical analysis of 16 cases of malignant head and neck melanoma].

Subjects were 16 patients--5 men and 11 women aged 46-82 years (mean: 61 years)--with malignant melanoma of the head and neck treated at our clinic from 1972 to 1988. Histologically, 1 subjects was amelanotic and 15 melanotic type. Primary lesions were 10 involving the nasal cavity, 2 the paranasal sinus, 2 the gingiva, 1 the lip, and 1 primary unknown. They were treated with or without multimodal surgery, radiation, chemotherapy, and immunotherapy. Of 12 treated using local surgery, local recurrence was seen in 6 in 7 areas. Two-year survival was 44% and 5-year survival 22%. The prognosis of malignant head and neck melanoma is poor but has gradually improved due to preoperative decisions on disease spread and the introduction of multimodal therapy.

Aged↗
PubMed2000

Interaction of two multifunctional proteins. Heterogeneous nuclear ribonucleoprotein K and Y-box-binding protein.

The heterogeneous nuclear ribonucleoprotein (hnRNP) K, a component of the hnRNP particles, appears to be involved in several steps of regulation of gene expression. To gain insight into mechanisms of K protein action, we performed two-hybrid screens using full-length hnRNP K as a bait. Several novel protein partners were identified, including Y-box-binding protein (YB-1), splicing factors 9G8 and SRp20, DNA-methyltransferase, hnRNP L, and hnRNP U. In vitro binding studies and co-immunoprecipitation from cellular extracts provided evidence for direct interaction between hnRNP K and YB-1. Two distinct domains in YB-1 were responsible for binding to K protein. Each protein was able to transactivate transcription from a polypyrimidine-rich promoter; however, this effect was reduced when K and YB-1 proteins were coexpressed suggesting a functional interaction between these two proteins.

Animals↗
PubMed2000

Role of tyrosine phosphorylation in the regulation of the interaction of heterogenous nuclear ribonucleoprotein K protein with its protein and RNA partners.

The heterogeneous nuclear ribonucleoprotein K protein recruits a diversity of molecular partners and may act as a docking platform involved in such processes as transcription, RNA processing, and translation. We show that K protein is tyrosine-phosphorylated in vitro by Src and Lck. Treatment with H(2)O(2)/Na(3)VO(4), which induces oxidative stress, stimulated tyrosine phosphorylation of K protein in cultured cells and in intact livers. Tyrosine phosphorylation increased binding of Lck and the proto-oncoprotein Vav to K protein in vitro. Oxidative stress increased the association of K protein with Lck and Vav, suggesting that tyrosine phosphorylation regulates the ability of K protein to recruit these effectors in vivo. Translation-based assay showed that K protein is constitutively bound to many mRNAs in vivo. Native immunoprecipitated K protein-mRNA complexes were disrupted by tyrosine phosphorylation, suggesting that the in vivo binding of K protein to mRNA may be responsive to the extracellular signals that activate tyrosine kinases. This study shows that tyrosine phosphorylation of K protein regulates K protein-protein and K protein-RNA interactions. These data are consistent with a model in which functional interaction of K protein is responsive to changes in the extracellular environment. Acting as a docking platform, K protein may bridge signal transduction pathways to sites of nucleic acid-dependent process such as transcription, RNA processing, and translation.

HeLa Cells↗
PubMed2000

[Bone mineral density of the calcaneus and related factors in men].

In this cross-sectional study, the bone mineral density of the calcaneus was investigated in healthy young (n = 35, 22-33 years) and middle-aged (n = 49, 45-59 years) men. The relationships among the bone mineral density, body fatness, physical fitness, physical activity in recent and past days, smoking, alcohol, and sex hormones (free testosterone, estradiol, and dehydroepiandrosterone-sulfate; DHEA-S) and sex hormone binding globulin were evaluated. The speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured by ultrasonic measurement. There was no association between age and bone density in each group. In the young group, there was a positive correlation between the body mass index (BMI) and BUA and between the training time during junior high school and BUA, and an inverse correlation between alcohol consumption and SOS after adjustment for the confounding factors using partial correlation analysis. The level of DHEA-S was weakly but not significantly associated with BUA. In the middle-aged group, there was an inverse correlation between the waist to hip ratio and SOS, and between the height of jump and SOS after adjustment for the confounding factors using partial correlation analysis. These results suggest that different factors may affect bone density in the young and middle-aged men. In young men, the higher BMI and the longer training time during boyhood may have a positive effect, and heavy alcohol consumption may have a negative effect on bone density. In middle-aged men, abdominal fat accumulation has a negative effect and leg muscle power has a positive effect on bone density.

Adipose Tissue↗
PubMed1999

Insulin receptor substrate-2 is not necessary for insulin- and exercise-stimulated glucose transport in skeletal muscle.

Insulin receptor substrate-2-deficient (IRS2(-/-)) mice develop type 2 diabetes. The purpose of this study was to determine whether there is a defect in basal, insulin-, and exercise-stimulated glucose transport in the skeletal muscle of these animals. IRS2(-/-) and wild-type (WT) mice (male, 8-10 weeks) exercised on a treadmill for 1 h or remained sedentary. 2-Deoxyglucose (2DG) uptake was measured in isolated soleus muscles incubated in vitro in the presence or absence of insulin. Resting blood glucose concentration in IRS2(-/-) mice (10.3 mM) was higher than WT animals (4.1 mM), but there was a wide range among the IRS2(-/-) mice (3-25 mM). Therefore, IRS2(-/-) mice were divided into two subgroups based on blood glucose concentrations (IRS2(-/-)L < 7.2 mM, IRS2(-/-)H > 7.2 mM). Only IRS2(-/-)H had lower basal, exercise-, and submaximally insulin-stimulated 2DG uptake, while maximal insulin-stimulated 2DG uptake was similar among the three groups. The ED(50) for insulin to stimulate 2DG uptake above basal in IRS2(-/-)H was higher than WT and IRS2(-/-)L mice, suggesting insulin resistance in the skeletal muscle from the IRS2(-/-) mice with high blood glucose concentrations. Furthermore, resting blood glucose concentrations from all groups were negatively correlated to submaximally insulin-stimulated 2DG uptake (r(2) = 0.33, p < 0.01). Muscle GLUT4 content was significantly lower in IRS2(-/-)H mice compared with WT and IRS2(-/-)L mice. These results demonstrate that the IRS2 protein in muscle is not necessary for insulin- or exercise-stimulated glucose transport, suggesting that the onset of diabetes in the IRS2(-/-) mice is not due to a defect in skeletal muscle glucose transport; hyperglycemia may cause insulin resistance in the muscle of IRS2(-/-) mice.

Animals↗
PubMed1999

Decreased skeletal muscle capillary density is related to higher serum levels of low-density lipoprotein cholesterol and apolipoprotein B in men.

The relationships between skeletal muscle morphology, particularly muscle fiber capillary density, and serum lipid profiles were evaluated in 25 non-obese men aged 18 to 36 years (body mass index [BMI], 22.7 +/- 2.5 kg/m2; body fat, 13.6% +/- 4.0%, maximal oxygen uptake [VO2max], 46.2 < or = 6.3 mL/kg/min). Skeletal muscle samples were taken from the vastus lateralis using the needle-biopsy method. The fiber types (I, IIa, and IIx) and their percent distribution, the indices of capillary density, and the diffusion index expressed as the cross-sectional area occupied by one capillary were determined. Blood samples were drawn from the antecubital vein after a 12-hour fast. Based on Pearson's correlation analysis, the number of capillaries around type IIx fiber correlated inversely with the serum level of low-density lipoprotein cholesterol ([LDL-C] r = -.50, P < .05). The number of capillaries per fiber (cap/fiber ratio), number of capillaries per area (cap/mm2), and capillaries around each fiber type correlated inversely with the serum level of apolipoprotein B ([apo B] r = -.40 to -.54, P < .05 to .01). Further, the diffusion index for each fiber type correlated positively with LDL-C and apo B (r = .42 to .50, P < .05 to .01). Among 14 subjects in whom high-density lipoprotein cholesterol (HDL-C) subfractions were analyzed, a positive correlation was found between cap/mm2 and HDL2-C (r = .64, P < .05). Partial correlation analysis showed that these correlations either remain or improve after adjusting for age, VO2max, and body fatness. These results indicate that skeletal muscle capillary density and diffusion capacity are related to lipid and apolipoprotein concentrations for both type I and type II fibers.

Adipose Tissue↗
PubMed1999

Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma.

BACKGROUND: A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma. METHODS: Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. Another group of eight asthmatic children served as control subjects. Aerobic capacity and the degree of EIB were assessed by both cycle ergometer and swimming ergometer before and after swimming training. RESULTS: The mean (SD) aerobic capacity at LT increased by 0.26 (0.11) kp after training when assessed with the swimming ergometer and by 10.6 (4.5) W when assessed with the cycle ergometer, and these changes were significantly different from the control group. The mean (SD) maximum % fall in forced expiratory volume in one second (FEV1) to an exercise challenge (cycle ergometer) set at 175% of LT decreased from 38.7 (15.4)% before training to 17.9 (17.6)% after training, but with no significant difference from the control group. There was, however, no difference in histamine responsiveness when compared before and after the training period. CONCLUSION: A six week swimming training programme has a beneficial effect on aerobic capacity but not on histamine responsiveness in children with asthma.

Asthma↗
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

Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice.

Physical exercise promotes glucose uptake into skeletal muscle and makes the working muscles more sensitive to insulin. To understand the role of insulin receptor (IR) signaling in these responses, we studied the effects of exercise and insulin on skeletal muscle glucose metabolism and insulin signaling in mice lacking insulin receptors specifically in muscle. Muscle-specific insulin receptor knockout (MIRKO) mice had normal resting 2-deoxy-glucose (2DG) uptake in soleus muscles but had no significant response to insulin. Despite this, MIRKO mice displayed normal exercise-stimulated 2DG uptake and a normal synergistic activation of muscle 2DG uptake with the combination of exercise plus insulin. Glycogen content and glycogen synthase activity in resting muscle were normal in MIRKO mice, and exercise, but not insulin, increased glycogen synthase activity. Insulin, exercise, and the combination of exercise plus insulin did not increase IR tyrosine phosphorylation or phosphatidylinositol 3-kinase activity in MIRKO muscle. In contrast, insulin alone produced a small activation of Akt and glycogen synthase kinase-3 in MIRKO mice, and prior exercise markedly enhanced this insulin effect. In conclusion, normal expression of muscle insulin receptors is not needed for the exercise-mediated increase in glucose uptake and glycogen synthase activity in vivo. The synergistic activation of glucose transport with exercise plus insulin is retained in MIRKO mice, suggesting a phenomenon mediated by nonmuscle cells or by downstream signaling events.

Animals↗
PubMed1999

[Clinical analysis of parotid cancer].

A clinical study was performed on 42 patients with parotid cancers initially treated in our hospital from 1972 to 1997. The five-year cumulative survival rate was 69% in the whole group and 72% in the radical surgical treatment group (n = 40). The five-year survival rates according to stage were as follows: stage I, 95% (21); stage II, 75% (4); stage III, 0% (1); and stage IV, 37% (16). The factors influencing prognosis were cases of T3 and T4 (p < 0.05), stage III and IV (p < 0.01), and cervical lymph node metastasis (p < 0.01). Regarding treatment modalities, a partial parotidectomy appeared to be a curable surgical procedure for T1 cases. However, a lobectomy is recommended for T2 cases. Furthermore our study proposed that prophylactic supraomohyoid neck dissection should be necessary for mucoepidermoid carcinoma (high-grade malignancy) and undifferentiated carcinoma of T4N0 cases.

Adult↗
PubMed1998

Intravenous glucose tolerance test-derived glucose effectiveness in strength-trained humans.

The effect of long-term strenuous resistance training on glucose effectiveness (SG) was examined by comparing 11 strength-trained and 20 sedentary males by a minimal model approach. Lean body mass (LBM) was measured by hydrostatic weighing. The LBM in strength-trained subjects (65.7 +/- 3.1 kg) was significantly larger than in sedentary subjects (56.6 +/- 1.2 kg, P < .01). The glucose disappearance constant ([KG] 3.07% +/- 0.45% min(-1)) and insulin sensitivity ([SI] 17.5 +/- 2.0 x 10(-5) x min(-1) x pmol/L(-1)) in strength-trained subjects were significantly higher than in sedentary subjects (2.06% +/- 0.14% x min(-1) and 10.3 +/- 1.2 x 10(-5) x min(-1) x pmol/L(-1), P < .05). SG in strength-trained subjects (0.024 +/- 0.003 min(-1)) was significantly higher than in sedentary subjects (0.018 +/- 0.001 min(-1), P < .05). These results thus suggest that the improved glucose tolerance in strength-trained subjects was due to increased SG and SI.

Adult↗