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Biomedical subjects

Takayuki Ito

Publications and source records attributed to Takayuki Ito.

15 recordsLinked to original sources

Dynamical simulation of speech cooperative articulation by muscle linkages.

Different kinds of articulators, such as the upper and lower lips, jaw, and tongue, are precisely coordinated in speech production. Based on a perturbation study of the production of a fricative consonant using the upper and lower lips, it has been suggested that increasing the stiffness in the muscle linkage between the upper lip and jaw is beneficial for maintaining the constriction area between the lips (Gomi et al. 2002). This hypothesis is crucial for examining the mechanism of speech motor control, that is, whether mechanical impedance is controlled for the speech motor coordination. To test this hypothesis, in the current study we performed a dynamical simulation of lip compensatory movements based on a muscle linkage model and then evaluated the performance of compensatory movements. The temporal pattern of stiffness of muscle linkage was obtained from the electromyogram (EMG) of the orbicularis oris superior (OOS) muscle by using the temporal transformation (second-order dynamics with time delay) from EMG to stiffness, whose parameters were experimentally determined. The dynamical simulation using stiffness estimated from empirical EMG successfully reproduced the temporal profile of the upper lip compensatory articulations. Moreover, the estimated stiffness variation significantly contributed to reproduce a functional modulation of the compensatory response. This result supports the idea that the mechanical impedance highly contributes to organizing coordination among the lips and jaw. The motor command would be programmed not only to generate movement in each articulator but also to regulate mechanical impedance among articulators for robust coordination of speech motor control.

Computer Simulation↗

Fast force-generation dynamics of human articulatory muscles.

To explore the mechanisms of speech articulation, which is one of the most sophisticated human motor skills controlled by the central nervous system, we investigated the force-generation dynamics of the human speech articulator muscles [orbicularis oris superior (OOS) and inferior (OOI) muscles of the lips]. Short-pulse electrical stimulation (300 micros) with approximately three or four times the sensation threshold intensity of each subject induced the muscle response. The responses of these muscles were modeled as second-order dynamics with a time delay (TD), and the model parameters [natural frequency (NF), damping ratio (DR), and TD] were identified with a nonlinear least mean squares method. The OOS (NF: 6.1 Hz, DR: 0.71, TD: 14.5 ms) and OOI (NF: 6.1 Hz, DR: 0.68, TD: 15.6 ms) showed roughly similar characteristics in eight subjects. The dynamics in the tongue (generated by combined muscles) also showed similar characteristics (NF: 6.1 Hz, DR: 0.68, TD: 17.4 ms) in two subjects. The NF was higher, and the DR was lower than results measured for arm muscles (NF: 4.25 Hz, DR: 1.05, TD: 23.8 ms for triceps long head), indicating that articulatory organs adapt for more rapid movement. In contrast, slower response dynamics was estimated when muscle force data by voluntarily contraction task were used for force-generation dynamics modeling. We discuss methodological problems in estimating muscle dynamics when different kinds of muscle contraction methods are used.

Electric Stimulation↗

Sleep-disordered breathing in patients with idiopathic cardiomyopathy.

BACKGROUND: Sleep-disordered breathing may adversely affect heart function, and thereby contribute to the progression of heart failure. A study was undertaken in patients with idiopathic cardiomyopathy to document the characteristics of sleep-disordered breathing. METHODS AND RESULTS: Thirty-five patients with a diagnosis of idiopathic cardiomyopathy, comprising 20 patients with dilated cardiomyopathy (DCM) and 15 patients with hypertrophic cardiomyopathy (HCM), underwent overnight polysomnography. Of these 35, 16 (80%) of the DCM patients and 7 (47%) of the HCM patients had sleep-disordered breathing. Central sleep apnea-hypopnea syndrome (CSAHS) was seen in 10 DCM patients, but not in the HCM patients, and obstructive sleep apnea-hypopnea syndrome (OSAHS) was seen in 6 DCM patients and 7 HCM patients. CSAHS was seen in DCM patients with a low left ventricular ejection fraction. HCM patients with OSAHS had a significantly greater body mass index (BMI) than those without OSAHS and CSAHS (27.6 +/- 3.8 vs 22.0 +/- 4.0 kg/m2, p<0.05). DCM patients with OSAHS had a larger BMI than those with CSAHS (29.3 +/- 5.8 vs 24.2 +/- 4.0 kg/m2, p<0.05) and those without OSAHS and CSAHS (29.3 +/- 5.8 vs 21.3 +/- 3.1 kg/m2, p<0.05). CONCLUSIONS: Sleep-disordered breathing is common in patients with idiopathic cardiomyopathy; half of DCM patients had CSAHS, which was closely associated with obesity.

Adult↗

[Improvement of mental health and the quality of life after catheter ablation for paroxysmal supraventricular tachycardia].

PURPOSE: The aims of this study were to observe change in subjective symptoms, quality of life (QOL) and mental health condition after catheter ablation (CA) for paroxysmal supraventricular tachycardia (PSVT) and to assess patient evaluation of the treatment. METHODS: The questionnaire was sent to 103 patients (86 with the Wolff-Parkinson-White (WPW) syndrome and 27 with atriovetricular nodal reentrant tachycardia (AVNRT)), who had received CA from February 1995 to January 1999. The question encompassed the condition of the patient, his or her evaluation of CA treatment, and a self-rating depression scale (SDS) together with social and subjective as well as non-specific physical points. We scored for improvement of QOL and SDS. Finally, from 82 patients who participated complete responses to the questionnaire were received from 59 (72.0%). The patients (50.5 +/- 15.8 years old, WPW syndrome; 41, AVNRT; 18) almost all (98.3%) RESULTS: gave a positive evaluation of CA. Over half (54.2%) no longer needed hospital consultation for any reason while three-quarters (76.3%) were free of life limitations. The complete cure rate from physicians was 100%. However, subjective symptoms of arrhythmia attack remained in 20.3% of the cases. Social and physical QOL were significantly improved after CA (social: < 0.05, physical: < 0.01) and the SDS score decreased significantly (< 0.05). 1. Self-awareness frequency of tachycardia attack, frequency of going to hospital and life CONCLUSION: limitations of PSVT patients decreased after CA. 2. QOL (social and physical QOL) and mental health condition significantly improved after CA. 3. Almost all patients (98.3%) gave a positive evaluation of CA. 4. Healthcare professionals should be aware that not only drug therapy, but also CA is effective for improvement of mental health and the QOL of patients with PSVT.

Adolescent↗

Angiotensin II type 2 receptor blockade partially negates antihypertrophic effects of type 1 receptor blockade on pressure-overload rat cardiac hypertrophy.

We investigated the effects of angiotensin II type 2 (AT2) receptor blockade on the antihypertrophic effects of type 1 receptor (AT1) blockade in pressure-overload cardiac hypertrophy in adult rats. Cardiac hypertrophy was induced by banding the abdominal aorta above the renal arteries. The rats were treated with either an AT1 receptor antagonist TCV-116 (TCV, 10 mg/kg/day), an AT2 receptor antagonist PD123319 (PD, 20 mg/kg/day), or both for 4 weeks after the aortic banding. We measured systolic and diastolic blood pressure (BP), body weight (BW), left ventricular weight (LVW), and serum and cardiac angiotensin converting enzyme (ACE) activities. Aortic banding increased BP and LVW/BW, and TCV reversed both these increases. PD affected neither BP nor LVW/BW. TCV+PD reversed the increase in BP but not LVW/BW. Thus, PD was considered to counteract the antihypertrophic effect of TCV without affecting BP. All three treatments reduced cardiac ACE activity without affecting serum ACE activity. Our data demonstrated that AT2 receptor blockade negates the antihypertrophic effects of AT1 receptor blockade in an adult rat model of pressure-overload cardiac hypertrophy. AT2 receptors may mediate the signaling pathways involved in growth inhibition, which could counteract mediation of the cellular growth signaling pathways by AT1 receptors.

Angiotensin Receptor Antagonists↗

Inflammatory cytokines and cardiovascular disease.

The designation of atherosclerosis as a chronic inflammatory process represents an interesting paradigmatic shift for cardiologists. The plasma concentrations of interleukin-6 and its hepatic byproduct, C-reactive protein, may reflect the intensity of occult plaque inflammation and the vulnerability to rupture. Monocyte chemoattractant protein-1 and interleukin-8 play a crucial role in initiating atherosclerosis by recruiting monocytes/macrophages to the vessel wall, which promotes atherosclerotic lesions and plaque vulnerability. In addition, circulating levels of these proinflammatory cytokines increase in patients with acute myocardial infarction and unstable angina, but not in those with stable angina. Also, the plasma concentrations of these cytokines increase after percutaneous coronary intervention, causing late restenosis after the procedure. Angiotensin II and other atherogenic factors induce these cytokines in the cardiovascular tissues through the activation of transcription factors, such as nuclear factor-kappaB or peroxisome proliferator-activated receptors. Conversely, HMG-CoA reductase inhibitors (statins) can potently inhibit these proinflammatory factors in the vessels. A small GTP-binding protein, Rho, may be a key molecule to explain the anti-inflammatory effects of statins. Interleukin-10 also exerts anti-inflammatory effects on the cardiovascular tissues, possibly by deactivating proinflammatory cytokines and inducible nitric oxide synthase. Gene therapy using interleukin-10 may be a promising means for untreatable or complicated cases of cardiovascular diseases. Thus, therapeutic modulations of these inflammatory cytokines may be useful in the prevention of atherosclerosis and future cardiovascular events.

Animals↗

[Intravascular ultrasound guided polytetrafluoroethylene coronary stent graft implantation in a patient with a large coronary pseudoaneurysm at eight months after coronary intervention: a case report].

A 67-year-old man with exertional angina presented with a large pseudoaneurysm of the right coronary artery at eight months after balloon angioplasty. Intravascular ultrasound revealed a large saccular pseudoaneurysm of 10.9 x 5.7 mm diameter at the proximal segment of the right coronary artery. Complete closure of the coronary pseudoaneurysm was successfully obtained using a coronary stent graft consisting of a thin flexible polytetrafluoroethylene (PTFE) membrane placed between two stents using a unique sandwich technique. Follow-up angiography and intravascular ultrasound revealed no significant restenosis in the PTFE stent graft segment. PTFE coronary stent graft implantation is a feasible, safe and useful method to treat a large coronary pseudoaneurysm after coronary intervention.

Aged↗

Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid synthesis and inhibits neointimal formation in rat balloon-injured arteries.

Previous studies have shown that prostacyclin (PGI(2)) synthase (PCS) gene transfer inhibits neointimal formation in balloon-injured arteries. However, the role of each cyclooxygenase (COX) isoform in this healing mechanism remains unknown. We hypothesized that overexpression of PCS may modulate COX-2-mediated prostaglandin (PG) metabolism. That is to say, excessive PGH(2) derived from COX-2 after balloon injury may be converted into PGI(2) rather than PGE(2) or thromboxane (TX) A(2) by overexpressed PCS. We examined the expression of COX isoforms and evaluated the role of COX-2 with regard to the effects of PCS gene transfer by using 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide (JTE-522), a selective COX-2 inhibitor. Rats were divided into 4 groups in conjunction with PCS gene transfer and JTE-522 treatment. The PCS gene (30 microg) was transfected into rat balloon-injured arteries by a lipotransfection method. JTE-522 (30 mg/kg per day) was administered for 14 days after balloon injury. Immunohistochemical analysis demonstrated marked COX-2 expression on the neointima. PCS gene transfer markedly inhibited neointimal formation, but JTE-522 reversed this beneficial effect. PCS gene transfer augmented PGI(2) production and decreased PGE(2) production without affecting TXA(2) production, but JTE-522 inhibited this increase in PGI(2) production. In conclusion, PCS gene transfer modulated COX-2-mediated prostanoid synthesis and inhibited neointimal formation after balloon injury.

Angioplasty, Balloon↗

Regulation of interleukin-8 expression by HMG-CoA reductase inhibitors in human vascular smooth muscle cells.

Interleukin-8 (IL-8) is a potent chemotactic factor that has been implicated in atherogenesis. HMG-CoA reductase inhibitors (statins) may reduce the cardiovascular risk and vulnerability of atherosclerotic plaque through nonlipid mechanisms such as inhibition of cytokine expression. In this study, we investigated the effects of statins on IL-8 synthesis in human vascular smooth muscle cells (VSMCs). Addition of angiotensin II (Ang II) increased IL-8 production in VSMCs in a time (0-24 h)- and dose (10(-8)-10(-6) mol/l)-dependent manner with increased IL-8 mRNA accumulation. The Ang II type 1 receptor (AT1R) antagonist candesartan, but not the Ang II type 2 receptor (AT2R) antagonist PD123319, significantly blocked Ang II-induced IL-8 production. Addition of fluvastatin decreased the basal and Ang II-induced IL-8 production in VSMCs in a dose (10(-8)-10(-5) mol/l)-dependent manner with a decrease in IL-8 mRNA accumulation. The effect of fluvastatin on IL-8 production was completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not in the presence of squalene or farnesyl-pyrophosphate. Lipophilic cerivastatin also significantly decreased IL-8 production, while hydrophilic pravastatin showed no effect on IL-8 levels. In conclusion, we demonstrated for the first time that Ang II increased IL-8 production and fluvastatin decreased the basal and Ang II-induced IL-8 production in human VSMCs. These findings suggested that Ang II may exacerbate atherosclerosis through induction of IL-8 in VSMCs, while statins may exert therapeutic effects by modulating IL-8 synthesis in patients with atherosclerotic disease.

Analysis of Variance↗

HMG-CoA reductase inhibitors reduce interleukin-6 synthesis in human vascular smooth muscle cells.

Interleukin-6 (IL-6) is a key molecule in chronic inflammation and has been implicated in the progression of atherosclerosis. HMG-CoA reductase inhibitors (statins) may reduce the cardiovascular risk and vulnerability of atherosclerotic plaque through nonlipid as well as lipid-lowering mechanisms, but their anti-inflammatory effects on the vascular tissue have not been fully elucidated. We investigated the effects of fluvastatin on IL-6 synthesis in human vascular smooth muscle cells (VSMCs). Addition of fluvastatin decreased IL-6 synthesis in VSMCs in a time (0-24 hours)- and dose (10(-8)-10(-5) mol/L)-dependent manner. Fluvastatin also decreased IL-6 mRNA expression in VSMCs. The effects of fluvastatin on IL-6 expression were completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not squalene. Inhibition of Rho by C3 exoenzyme or Rho kinase by Y-27632 significantly decreased IL-6 expression in VSMCs. In conclusion, fluvastatin decreases IL-6 synthesis in human VSMCs through inhibition of Rho pathway. These findings suggested that reduction of IL-6 expression by statins may partially explain their therapeutic effects in patients with coronary artery disease.

ADP Ribose Transferases↗

Decrease in renal medullary endothelial nitric oxide synthase of fructose-fed, salt-sensitive hypertensive rats.

We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low- or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg. kg(-1). day(-1)), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129+/-4 mm Hg, versus LS-F rats, 115+/-3 mm Hg, P<0.05; or versus HS-C rats, 116+/-5 mm Hg, P<0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129+/-4 mm Hg, versus HS-FP rats, 113+/-3 mm Hg, P<0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension.

Animals↗

Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats.

1. Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve insulin-resistance both experimentally and clinically. We therefore investigated the effects of quinapril, which has high tissue specificity for ACE, regarding the contribution of insulin to vascular contractions, as well as insulin sensitivity in a dietary rat model of insulin resistance. 2. Male Sprague-Dawley rats were divided into three groups: (i) rats fed normal chow (normal diet group); (ii) rats fed fructose-rich chow containing 40% fructose and 7% lard (fructose diet group); and (iii) rats fed fructose-rich chow plus quinapril (10 mg/kg per day; quinapril-treated group). 3. After 2 weeks, we evaluated systolic blood pressure, insulin sensitivity as assessed by steady state plasma glucose (SSPG) levels, response of aortic rings to phenylephrine (10-9 to 10-6 mol/L) in the presence or absence of insulin and the response of aortic rings to acetylcholine. 4. Feeding rats fructose-rich chow resulted in an elevation of blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment significantly prevented increases in both blood pressure and SSPG, with a return to the levels seen in the normal diet group. 5. In the absence of insulin, the maximal contractile response to phenylephrine did not differ between the three groups. However, in the presence of insulin (100 mU/mL), the contractile response to phenylephrine (10-6 mol/L) was reduced by 22.8 +/- 1.2% in the normal diet group, although no insulin effects were observed in the fructose diet group (P < 0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine-induced contractions. 6. In addition, the reduction in relaxation induced by acetylcholine in the fructose diet group was significantly reversed by quinapril treatment. 7. It is concluded that the fructose diet impairs the vasodilator effects of insulin as well as acetylcholine-induced relaxation in rat thoracic aortas. Quinapril prevented deterioration in the responses of the aortic rings, suggesting that ACE inhibitors may be useful for treating vascular insulin resistance.

Acetylcholine↗