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Takayuki Sato

Publications and source records attributed to Takayuki Sato.

At least 19 recordsLinked to original sources
PubMed2006

Clinical utility of 2',5'-oligoadenylate synthetase activity measurement: using whole blood as a highly sensitive method to detect the effects of IFN.

Research progress on the pleiotropic effects of interferons (IFN) has thus far required detecting responses by weak IFN signals. The activity of 2',5'-oligoadenylate synthetase (2-5OAS) is a valuable indicator in the prognosis and IFN treatment of patients with viral diseases such as hepatitis B and C. Although serum samples generally are used to measure enzyme activity, their values depend on the exact conditions under which blood is stored and the degree of haemolysis that occurs during blood drawing or serum separation. This study presents an improved method of evaluating 2-5OAS activity by using whole blood samples containing heparin, which are frozen and then thawed, instead of serum samples. This method is more reliable, convenient, and 50-100 times more sensitive than the conventional methods of measuring serum 2-5OAS activity. The reliability and sensitivity of this improved method enables detection of the effects of low doses of oral IFN administration or changes in the IFN and cytokine system by infection or autoimmune diseases.

2',5'-Oligoadenylate Synthetase↗
PubMed2006

Acetylcholine inhibits the hypoxia-induced reduction of connexin43 protein in rat cardiomyocytes.

In a recent study, we demonstrated that vagal stimulation increases the survival of rats with myocardial infarction by inhibiting lethal arrhythmia through regulation of connexin43 (Cx43). However, the precise mechanisms for this effect remain to be elucidated. To investigate these mechanisms and the signal transduction for gap junction regulation, we investigated the effect of acetylcholine (ACh), a parasympathetic nerve system neurotransmitter, on the gap junction component Cx43 using H9c2 cells. When cells were subjected to hypoxia, the total Cx43 protein level was decreased. In contrast, pretreatment with ACh inhibited this effect. To investigate the signal transduction, cells were pretreated with L-NAME, a nitric oxide synthase inhibitor, followed by ACh and hypoxia. L-NAME was found to suppress the ACh effect. However, a NO donor, SNAP, partially inhibited the hypoxia-induced reduction in Cx43. To delineate the mechanisms of the decrease in Cx43 under hypoxia, cells were pretreated with MG132, a proteasome inhibitor. Proteasome inhibition produced a striking recovery of the decrease in the total Cx43 protein level under hypoxia. However, cotreatment with MG132 and ACh did not produce any further increase in the total Cx43 protein level. Functional studies using ACh or okadaic acid, a phosphatase inhibitor, revealed that both reagents inhibited the decrease in the dye transfer induced by hypoxia. These results suggest that ACh is responsible for restoring the decrease in the Cx43 protein level, resulting in functional activation of gap junctions.

Acetylcholine↗
PubMed2006

Reversible vagal blockade in conscious rats using a targeted delivery device.

Reversible methods of nerve blockade greatly aid neurophysiological and behavioral studies. We have developed an implantable device for the local delivery of anesthetics to the area surrounding the vagal nerve in rats. The device consists of a thick silicone tube for insulating the nerves from the surrounding tissue, and a thin silicone tube for the infusion of anesthetics into the insulating tube. The in vivo performance of the device was tested electrophysiologically, and cardiovascular responses to vagal stimulation were measured in conscious animals. Nerve conductivity was completely blocked by injection of a small amount (<20 microl) of 1% lidocaine, with conductivity subsequently recovering gradually after 10-40 min. Electrical stimulation of the right vagus nerve in conscious rats increased arterial pressure while decreasing heart rate. The local blockade of afferent fibers abolished the arterial pressure response but preserved the bradycardic response to vagal nerve stimulation. The targeted delivery device was useful for reversible vagal blockade in conscious rats.

Anesthetics, Local↗
PubMed2006

Artificial baroreflex: clinical application of a bionic baroreflex system.

BACKGROUND: We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial baroreflex system to automatically regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we tested its efficacy in a model of sudden hypotension during surgery. METHODS AND RESULTS: The BBS consisted of a computer-controlled negative-feedback circuit that sensed arterial pressure (AP) and automatically computed the frequency (STM) of a pulse train required to stimulate sympathetic nerves via an epidural catheter placed at the level of the lower thoracic spinal cord. An operation rule was subsequently designed for the BBS using a feedback correction with proportional and integral gain factors. The transfer function from STM to AP was identified by a white noise system identification method in 12 sevoflurane-anesthetized patients undergoing orthopedic surgery involving the cervical vertebrae, and the feedback correction factors were determined with a numerical simulation to enable the BBS to quickly and stably attenuate an external disturbance on AP. The performance of the designed BBS was then examined in a model of orthostatic hypotension during knee joint surgery (n=21). Without the implementation of the BBS, a sudden deflation of a thigh tourniquet resulted in a 17+/-3 mm Hg decrease in AP within 10 seconds and a 25+/-2 mm Hg decrease in AP within 50 seconds. By contrast, during real-time execution of the BBS, the decrease in AP was 9+/-2 mm Hg at 10 seconds and 1+/-2 mm Hg at 50 seconds after the deflation. CONCLUSIONS: These results suggest the feasibility of a BBS approach for central baroreflex failure.

Aged↗
PubMed2006

Nitric oxide stimulates vascular endothelial growth factor production in cardiomyocytes involved in angiogenesis.

BACKGROUND: Hypoxia-inducible factor (HIF)-1alpha regulates the transcription of lines of genes, including vascular endothelial growth factor (VEGF), a major gene responsible for angiogenesis. Several recent studies have demonstrated that a nonhypoxic pathway via nitric oxide (NO) is involved in the activation of HIF-1alpha. However, there is no direct evidence demonstrating the release of angiogenic factors by cardiomyocytes through the nonhypoxic induction pathway of HIF-1alpha in the heart. Therefore we assessed the effects of an NO donor, S-Nitroso-N-acetylpenicillamine (SNAP) on the induction of VEGF via HIF-1alpha under normoxia, using primary cultured rat cardiomyocytes (PRCMs). METHODS AND RESULTS: PRCMs treated with acetylcholine (ACh) or SNAP exhibited a significant production of NO. SNAP activated the induction of HIF-1alpha protein expression in PRCMs during normoxia. Phosphatidylinositol 3-kinase (PI3K)-dependent Akt phosphorylation was induced by SNAP and was completely blocked by wortmannin, a PI3K inhibitor, and NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor. The SNAP treatment also increased VEGF protein expression in PRCMs. Furthermore, conditioned medium derived from SNAP-treated cardiomyocytes phosphorylated the VEGF type-2 receptor (Flk-1) of human umbilical vein endothelial cells (a fourfold increase compared to the control group, p < 0.001, n = 5) and accelerated angiogenesis. CONCLUSION: Our results suggest that cardiomyocytes produce VEGF through a nonhypoxic HIF-1alpha induction pathway activated by NO, resulting in angiogenesis.

Acetylcholine↗
PubMed2006

Formaldehyde uptake by Methylobacterium sp. MF1 and Acidomonas methanolica MB 58 with the different formaldehyde assimilation pathways.

Methylobacterium sp. MF1 (an obligate methylotrophic bacterium isolated newly by the authors) and Acidomonas methanolica MB58 (a facultative methylotrophic bacterium) uptake formaldehyde similarly. It was found that the former assimilated formaldehyde via the serine pathway whereas the latter did so via the ribulose-monophosphate pathway from the measurement of the key enzyme activities in each assimilation pathway. That is, hydroxy pyruvate reductase was detected in only the above-mentioned MF1 strain, but hexulose phosphate synthase (HPS) was not. The efficiencies of formaldehyde consumption by both strains under a continuous chemostat cultivation in the steady state were almost the same in spite of their different assimilation pathways. That is, the consumption efficiencies of the MF strain and the MB58 strain were ca. 1.2 g/L/d and ca. 1.8 g/L/d, respectively, under the experimental conditions. In the future, optimal continuous operating conditions will be investigated.

Formaldehyde↗
PubMed2005

Postexercise VO2 "Hump" phenomenon as an indicator for inducible myocardial ischemia in patients with acute anterior myocardial infarction.

OBJECTIVES: At exercise testing with respiratory gas analysis in patients with inducible myocardial ischemia, we have occasionally observed abnormal transient oxygen uptake (VO2) components with a characteristic "Hump"-shaped morphology early after exercise, which may serve as an index for inducible ischemia. We examined this hypothesis in patients with anterior q-wave myocardial infarction in whom the accuracy to identify ischemia by exercise ECG is limited. DESIGN: From patients with acute anterior q-wave infarction but without clinically overt heart failure who underwent pre-discharge exercise testing, we examined patients with (Group-I, n = 30) and without (Group-N, n = 29) inducible ischemia. To identify "Hump", postexercise VO2 (up to 4 min) standardized for peak VO2 was exponentially fitted with use of peak VO2 and VO2 of 90-240 s, yielding "expected VO2". "D-curve" was obtained by subtracting "expected VO2" from measured VO2. RESULTS: Although exercise-induced ST depressions more frequently appeared in Group-I (27%) than in Group-N (3%, p < 0.05), the prevalence was low. D-curve peaked later (p < 0.01) and its value was greater (p < 0.05) in Group-I than in Group-N. When "Hump" was defined to be present if D-curve peaked > or =40 s and its peak value > or =15%, it was far more frequently found in Group-I (n = 17/30) than in Group-N (n = 1/29, p < 0.01). Thus, "Hump" could diagnose inducible ischemia with a sensitivity of 57% and a specificity of 97%. CONCLUSIONS: Although not highly sensitive, postexercise VO2 "Hump" with its peak occurring around 60 s after exercise is a specific marker for inducible ischemia. The identification may be useful, particularly in patients with limited accuracy of exercise ECG such as those with q-wave anterior infarction.

Exercise Test↗
PubMed2005

Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein.

BACKGROUND: Myocardial ischemia (MI) leads to derangements in cellular electrical stability and the generation of lethal arrhythmias. Vagal nerve stimulation has been postulated to contribute to the antifibrillatory effect. Here, we suggest a novel mechanism for the antiarrhythmogenic properties of vagal stimulation during acute MI. METHODS AND RESULTS: Under anesthesia, Wistar rats underwent 30 minutes of left coronary artery (LCA) ligation with vagal stimulation (MI-VS group, n=11) and with sham stimulation (MI-SS group, n=12). Eight of the 12 rats in the MI-SS group had ventricular tachyarrhythmia (VT) during 30-minute LCA ligation; on the other hand, VT occurred in only 1 of the 11 rats in the MI-VS group (67% versus 9%, respectively). Atropine administration abolished the antiarrhythmogenic effect of vagal stimulation. Immunoblotting revealed that the MI-SS group showed a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the MI-VS group showed only a slight reduction compared with the sham operation and sham stimulation group (37+/-20% versus 79+/-18%). Immunohistochemistry confirmed that the MI-induced loss of Cx43 from intercellular junctions was prevented by vagal stimulation. In addition, studies with rat primary-cultured cardiomyocytes demonstrated that acetylcholine effectively prevented the hypoxia-induced loss of phosphorylated Cx43 and ameliorated the loss of cell-to-cell communication as determined by Lucifer Yellow dye transfer assay, which supports the in vivo results. CONCLUSIONS: Vagal nerve stimulation exerts antiarrhythmogenic effects accompanied by prevention of the loss of phosphorylated Cx43 during acute MI and thus plays a critical role in improving ischemia-induced electrical instability.

Acetylcholine↗
PubMed2005

Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1alpha.

Electrical stimulation of the vagal efferent nerve improves the survival of myocardial infarcted rats. However, the mechanism for this beneficial effect is unclear. We investigated the effect of acetylcholine (ACh) on hypoxia-inducible factor (HIF)-1alpha using rat cardiomyocytes under normoxia and hypoxia. ACh posttranslationally regulated HIF-1alpha and increased its protein level under normoxia. ACh increased Akt phosphorylation, and wortmannin or atropine blocked this effect. Hypoxia-induced caspase-3 activation and mitochondrial membrane potential collapse were prevented by ACh. Dominant-negative HIF-1alpha inhibited the cell protective effect of ACh. In acute myocardial ischemia, vagal nerve stimulation increased HIF-1alpha expression and reduced the infarct size. These results suggest that ACh and vagal stimulation protect cardiomyocytes through the PI3K/Akt/HIF-1alpha pathway.

Acetylcholine↗
PubMed2005

Acinic cell carcinoma of the parotid gland in a child.

Acinic cell carcinoma of the parotid gland in children is an extremely rare occurrence. We present a 13-year-old girl with acinic cell carcinoma of the parotid gland. Removal of the superficial lobe of the parotid gland (superficial parotidectomy) was performed because the tumor was completely encapsulated by fibrous tissue and had not invaded the deep parotid gland. There is no clinical evidence of recurrence or metastasis 4 years after surgery. In our view, when tumors are completely encapsulated and do not adhere to the facial nerves, superficial parotidectomy is the best surgical treatment in children.

Adolescent↗
PubMed2005

Hypoxia-inducible factor-1alpha is involved in the attenuation of experimentally induced rat glomerulonephritis.

BACKGROUND/AIM: Among various kidney disease models, there are few rat glomerulonephritis (GN) models that develop in a short time, and with mainly glomerular lesions. Hypoxia-inducible factor (HIF)-1alpha is a transcriptional factor that induces genes supporting cell survival, but the involvement of HIF-1alpha in attenuating the progression of GN remains to be elucidated. We developed a new model of rat GN by coadministration of angiotensin II (AII) with Habu snake venom (HV) and investigated whether HIF-1alpha is involved in renal protection. METHODS: Male Wistar rats were unilaterally nephrectomized on day 1, and divided into 4 groups on day 0; N group (no treatment), HV group, A group (AII), and H+A group (HV and AII). To preinduce HIF-1alpha, cobalt chloride (CoCl2) was injected twice before injections of HV and AII in 11 rats. RESULTS: GN was detected only in the H+A group; observed first on day 2 and aggravated thereafter. HIF-1alpha was expressed in the glomeruli and renal tubules in the A and H+A groups. In the H+A group, GN was remarkably reduced by CoCl2 pretreatment (44.9 to 12.2%, p < 0.01). CONCLUSION: Both HV and AII were critical for the development of GN, and HIF-1alpha remarkably attenuated the progression of GN.

Angiotensin II↗
PubMed2005

[Simulation of airbag impact on eyes after trabeculectomy by finite element analysis method].

PURPOSE: A finite element computer model of the human eye after trabeculectomy was used in an experiment of simulated airbag ocular injury. METHODS: A half-layer-incised scleral flap was created on the limbus and the strength of its adhesion to the outer sclera was set at 30%, 50% and 100%. The simulations were performed at a workstation using the finite element analysis program PAM CRASH (Nihon ESI, Tokyo, Japan), and the airbag was set to hit the surface of the post-trabeculectomy eye at various velocities in two directions, straight to the corneal center or straight to the scleral flap. RESULTS: In the case of airbag impact on the corneal center, the scleral flap was unlikely to rupture except when the airbag impact velocity was 40 m/sec. In the case of airbag impact on the scleral flap, at the lowest impact velocity of 20 m/sec, partial scleral flap rupture was likely to occur only at the lower adhesion strength, and scleral laceration extending to the posterior sclera was observed at impact velocities of over 30 m/sec. CONCLUSIONS: These simulation results suggest that current airbags may induce globe rupture in eyes after trabeculectomy treatment.

Air Bags↗
PubMed2004

Effects of learning on color-form conjunction in macaque inferior temporal neurons.

Many neurons in area TE of the macaque respond selectively to colors or forms. One problem remaining is how these neurons contribute to conjunctive perception of these features when there are many objects in their receptive fields. In order to investigate the effects of learning on neural activities for the conjunction of color and form, neurons were recorded during a visual fixation task and two go/no-go visual discrimination tasks. One discrimination task involved conjunction of color and form for successively presented colored patterns. In this task, the monkeys were required to hold two "go" stimuli in the transient memory. The other task involved associative discrimination between the form of gray patterns and the color of irregular textures when the two features were presented simultaneously at separate locations. Each of the two stimuli was neutral in the go/no-go behavior in the latter task. One third of responsive neurons showed a significant interaction of color and form in response to the colored patterns during the conjunction task. Responses of these neurons were mostly enhanced for a particular colored pattern, which was usually one of the go stimuli. The response enhancement was preserved when the go stimulus was presented with a distractor. However, this change was not seen during the associative discrimination task. During the fixation task, the neurons that showed interaction of color and form in the conjunction task were usually selective either for the forms of gray patterns or colors of irregular textures, and only a few neurons were selective for both. The results indicate that neurons in area TE can conjoin color and form actively for an object held in the working memory, suppressing illusory conjunction.

Action Potentials↗
PubMed2004

Neutral rains at Athens, Greece: a natural safeguard against acidification of rains.

Samples of all rains in a period from October, 1998 to January, 1999 at Athens, Greece, were collected. The pH values of almost all of these rains clustered in a high range of 7.0-7.5, with no relation between pH and their SO(4)(2-), NO(3)(-) and Cl(-) contents. In addition, a few rains with low contents of chemical components similar to pure water also were observed, giving a pH (approx. 5.5) of rain caused by dissolution of only atmospheric CO(2) in it. These results indicate that the level of air pollution of Athens by human activity has become lower during the last decade, restoring the neutral condition of rain in this area. Furthermore, the Ca contents and Ca/Mg ratios in these rains, as well as their chemical and isotopic behavior, suggest that particles of calcium carbonate taken in as dust act as a neutralizer of rains. The dust must be derived not only from the urban area of Athens but also from its environs or areas distant from it. Such a mechanism causing universally neutral rains throughout the rainy season at Athens must have worked as a natural safeguard against rains acidified naturally and artificially from ancient times up to recent years, keeping the remains of ancient Greece in a good state of preservation during such a long period.

Calcium Carbonate↗
PubMed2004

Bionic epidural stimulation restores arterial pressure regulation during orthostasis.

A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control arterial pressure (AP) for the treatment of baroreflex failure. To apply this system clinically, an appropriate efferent neural (sympathetic vasomotor) interface has to be explored. We examined whether the spinal cord is a candidate site for such interface. In six anesthetized and baroreflex-deafferentiated cats, a multielectrode catheter was inserted into the epidural space to deliver epidural spinal cord stimulation (ESCS). Stepwise changes in ESCS rate revealed a linear correlation between ESCS rate and AP for ESCS rates of 2 pulses/s and above (r2, 0.876-0.979; slope, 14.3 +/- 5.8 mmHg.pulses(-1).s; pressure axis intercept, 35.7 +/- 25.9 mmHg). Random changes in ESCS rate with a white noise sequence revealed dynamic transfer function of peripheral effectors. The transfer function resembled a second-order, low-pass filter with a lag time (gain, 16.7 +/- 8.3 mmHg.pulses(-1).s; natural frequency, 0.022 +/- 0.007 Hz; damping coefficient, 2.40 +/- 1.07; lag time, 1.06 +/- 0.41 s). On the basis of the transfer function, we designed an artificial vasomotor center to attenuate hypotension. We evaluated the performance of the BBS against hypotension induced by 60 degrees head-up tilt. In the cats with baroreflex failure, head-up tilt dropped AP by 37 +/- 5 mmHg in 5 s and 59 +/- 11 mmHg in 30 s. BBS with optimized feedback parameters attenuated hypotension to 21 +/- 2 mmHg in 5 s (P < 0.05) and 8 +/- 4 mmHg in 30 s (P < 0.05). These results indicate that ESCS-mediated BBS prevents orthostatic hypotension. Because epidural stimulation is a clinically feasible procedure, this BBS can be applied clinically to combat hypotension associated with various pathophysiologies.

Animals↗
PubMed2004

Effect of electrical modification of cardiomyocytes on transcriptional activity through 5'-AMP-activated protein kinase.

Endothelin-1 (ET-1) is known as an aggravating factor of the failing cardiomyocytes and, therefore, a therapeutic method is indispensable to decrease cardiac ET-1 expression. To study the mechanisms of how cardiac ET-1 gene expression can be modified, we investigated the effect of electrical stimulation against cardiomyocytes. Considering the physiology of cardiomyocytes, in vitro cultured cardiomyocytes demonstrate distinctive features from in vivo cardiomyocytes (i.e. the absence of a stretch along with electrical stimulation). In this study, we especially focused on the effect of electrical stimulation. The electrical stimulation reduced the gene expression of ET-1 mRNA in rat primary cultured cardiomyocytes. Furthermore, this effect on the transcriptional modification of ET-1 was also identified in H9c2 cells. Luciferase activity using H9c2 cells was decreased by electrical stimulation in the early phase, suggesting that the attenuation of the ET-1 gene transcription by electrical stimulation should be due to a transcriptional repression. To further investigate a trigger signal involved in the transcriptional repression, phosphorylation of 5'-AMP-activated protein kinase (AMPK) was evaluated. It was revealed that AMPK was phosphorylated in the early phase of electrical stimulation of H9c2 cells as well as in rat primary cultured cardiomyocytes, and that AMPK phosphorylation was followed by ET-1 transcriptional repression, suggesting that electrical stimulation directly regulates AMPK. This study suggests that AMPK activation in cardiomyocytes plays a crucial role in the transcriptional repression of ET-1.

AMP-Activated Protein Kinases↗
PubMed2004

A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats.

Using Bluetooth wireless technology, we developed an implantable telemetry system for measurement of the left ventricular pressure-volume relation in conscious, freely moving rats. The telemetry system consisted of a pressure-conductance catheter (1.8-Fr) connected to a small (14-g) fully implantable signal transmitter. To make the system fully telemetric, calibrations such as blood resistivity and parallel conductance were also conducted telemetrically. To estimate blood resistivity, we used four electrodes arranged 0.2 mm apart on the pressure-conductance catheter. To estimate parallel conductance, we used a dual-frequency method. We examined the accuracy of calibrations, stroke volume (SV) measurements, and the reproducibility of the telemetry. The blood resistivity estimated telemetrically agreed with that measured using an ex vivo cuvette method (y=1.09x - 11.9, r2= 0.88, n=10). Parallel conductance estimated by the dual-frequency (2 and 20 kHz) method correlated well with that measured by a conventional saline injection method (y=1.59x - 1.77, r2= 0.87, n=13). The telemetric SV closely correlated with the flowmetric SV during inferior vena cava occlusions (y=0.96x + 7.5, r2=0.96, n=4). In six conscious rats, differences between the repeated telemetries on different days (3 days apart on average) were reasonably small: 13% for end-diastolic volume, 20% for end-systolic volume, 28% for end-diastolic pressure, and 6% for end-systolic pressure. We conclude that the developed telemetry system enables us to estimate the pressure-volume relation with reasonable accuracy and reproducibility in conscious, untethered rats.

Animals↗