Biomedical subjects

Takayuki Sato

Publications and source records attributed to Takayuki Sato.

13 recordsLinked to original sources

PubMed2003

Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats.

BACKGROUND: Diminished cardiac vagal activity and higher heart rate predict a high mortality rate of chronic heart failure (CHF) after myocardial infarction. We investigated the effects of chronic electrical stimulation of the vagus nerve on cardiac remodeling and long-term survival in an animal model of CHF after large myocardial infarction. METHODS AND RESULTS: Two weeks after the ligation of the left coronary artery, surviving rats were randomized to vagal- and sham-stimulated groups. Using an implantable miniature radio-controlled electrical stimulator, we stimulated the right vagal nerve of CHF rats for 6 weeks. The intensity of electrical stimulation was adjusted for each rat, so that the heart rate was lowered by 20 to 30 beats per minute. The treated rats had significantly lower left ventricular end-diastolic pressure (17.1+/-5.9 versus 23.5+/-4.2 mm Hg, P<0.05) and higher maximum dp/dt of left ventricular pressure (4152+/-237 versus 2987+/-192 mm Hg/s, P<0.05) than the untreated rats. Improvement of cardiac pumping function was accompanied by a decrease in normalized biventricular weight (2.75+/-0.25 versus 3.14+/-0.22 g/kg, P<0.01). Although the 140-day survival of the untreated group was only half, vagal stimulation markedly improved the survival rate (86% versus 50%, P=0.008). Vagal stimulation therapy achieved a 73% reduction in a relative risk ratio of death. CONCLUSIONS: Vagal nerve stimulation markedly improved the long-term survival of CHF rats through the prevention of pumping failure and cardiac remodeling.

Animals↗

PubMed2003

Determination of sugar phosphates and nucleotides related to photosynthetic metabolism by high-performance anion-exchange liquid chromatography with fluorometric and ultraviolet detection.

A high-performance anion-exchange liquid chromatography system was constructed to identify sugar phosphates and nucleotides involved in photosynthetic metabolism. First sugar phosphates and nucleotides were separated by a gradient elution with boric acid and sodium phosphate, then they were detected by a fluorescence detector (as fluorescent derivatives with arginine) and UV detector, respectively. Eight authentic sugar phosphates and 11 authentic nucleotides could be analyzed using the system. The applicability of the system to the determination of the corresponding sugar phosphates and nucleotides in extracts from only five soybean leaf discs (8.95 cm2) was shown.

Chromatography, High Pressure Liquid↗

PubMed2003

OX40 (CD134) and OX40 ligand interaction plays an adjuvant role during in vivo Th2 responses.

The role of OX40-OX40 ligand (OX40L) interaction in Th cell differentiation remains contentious. In vitro studies have revealed a Th2-biased effect by OX40 signals in T cells. However, in vivo studies demonstrated that OX40-OX40L interaction is involved in responses either Th1 or Th2, or both, which appears to be dependent on the experimental conditions used. We document in our report Th cell differentiation in OX40L-deficient and OX40L-transgenic (Tg) mice in response to protein antigens (Ag) and to Leishmania major (L. major) infection. Upon immunization with protein Ag, we demonstrate the adjuvant effect of OX40 signals during in vivo Th2 responses. However, adjuvant treatment to mice ameliorates the Th2-specific effect of OX40-OX40L interaction and rather induces concurrent promotion of both Th1 and Th2 responses via OX40 signals. Thus, previous reports showing promotion of Th1 response by OX40-OX40L interaction may in actual fact be affected by the adjuvant effects mediated by the various experimental conditions. Indeed, constitutive OX40-OX40L interactions in OX40L-Tg mice converted the normally resistant C57BL/6 strain, into a susceptible status following L. major infection due to an extraordinary elevated Th2 response. These results provide convincing evidence demonstrating that the OX40-OX40L interaction is paramount in the development of Th2 responses in vivo.

Animals↗

PubMed2003

Enhanced regional washout of technetium-99m-sestamibi in patients with coronary spastic angina.

BACKGROUND: Reverse redistribution and rapid washout of 99mTc-sestamibi are observed in patients with acute myocardial infarction and may indicate viable myocardium. However, the clinical significance of this phenomenon has not been rigorously examined in other cardiac diseases. Thus, we investigated whether reverse redistribution and washout of 99mTc-sestamibi could be used in the diagnosis and follow-up of patients with coronary spastic angina. METHODS: Thirty patients diagnosed as coronary spastic angina were examined. During coronary arteriography, spasm was induced by provocation test with ergonovine, and only total or subtotal occlusion was considered positive. Myocardial perfusion tomography was obtained 45 min (early) and 3 hr (delayed) after 99mTc-sestamibi injection. Segmental defect score was visually graded from 0 (normal) to 4 (defect), and a total defect score was determined as the sum of defect scores for all segments. Washout rate of 99mTc-sestamibi from the myocardium was calculated for each segment. After medical treatment with calcium antagonists and nitrates for 3 months, 99mTc-sestamibi imaging was repeated. RESULTS: Out of 30 patients, on the early images 17 (57%) patients demonstrated decreased 99mTc-sestamibi uptake in spastic segments; on the other hand, 24 (80%) patients did decreased 99mTc-sestamibi uptake in spastic segments on delayed images. Total defect scores in delayed images were higher than those in early images (6.9 +/- 0.3 vs. 3.6 +/- 0.4, p < 0.01). Reverse redistribution of 99mTc-sestamibi was observed in 17 out of 30 patients (57%) with coronary spastic angina. Washout rate of 99mTc-sestamibi from spastic segments was higher than that from non-spastic segments (16 +/- 2% vs. 11 +/- 5%, p < 0.01). After medical treatment, washout rate from spastic segments was decreased to 10 +/- 4 (p < 0.01), and left ventricular ejection fraction was increased from 63 +/- 8% to 73 +/- 4% (p < 0.01). CONCLUSION: Rapid washout of 99mTc-sestamibi was observed in patients with coronary spastic angina and might indicate that the ability of myocyte to retain the tracer was impaired due to repetitive brief ischemia by coronary spasm. The early and delayed 99mTc-sestamibi imaging provides useful information for the diagnosis and responses to the treatment in patients with coronary spastic angina.

Adult↗

PubMed2003

Dynamics of sympathetic baroreflex control of arterial pressure in rats.

By a white noise approach, we characterized the dynamics of the sympathetic baroreflex system in 11 halothane-anesthetized rats. We measured sympathetic nerve activity (SNA) and systemic arterial pressure (SAP), while carotid sinus baroreceptor pressure (BRP) was altered randomly. We estimated the transfer functions from BRP to SNA (mechanoneural arc), from SNA to SAP (neuromechanical arc), and from BRP to SAP (total arc). The gain of the mechanoneural arc gradually increased about threefold as the frequency of BRP change increased from 0.01 to 0.8 Hz. In contrast, the gain of the neuromechanical arc rapidly decreased to 0.4% of the steady-state gain as the frequency increased from 0.01 to 1 Hz. Although the total arc also had low-pass characteristics, the rate of attenuation in its gain was significantly slower than that of the neuromechanical arc, reflecting the compensatory effect of the mechanoneural arc for the sluggish response of the neuromechanical arc. We conclude that the quantitative estimation of the baroreflex dynamics is vital for an integrative understanding of baroreflex function in rats.

Animals↗

PubMed2003

Biphasic response of action potential duration to sudden sympathetic stimulation in anesthetized cats.

Although certain roles of the sympathetic nervous system have been suggested as possible mechanisms of life-threatening arrhythmias and sudden cardiac death, the dynamic electrophysiological response to sympathetic activation remains unclear. The aim of this study was to investigate the dynamic response of action potential duration (APD) to sudden sympathetic stimulation (SYM) using monophasic action potential (MAP) recording. In 10 anesthetized cats, MAPs were continuously recorded from the right ventricular endocardium under constant pacing. The dynamic response of the APD to SYM (3 Hz) were examined before and after the administration of propranolol (0.5 mg/kg i.v.) (n=5) or phentolamine (1.0 mg/kg i.v.) (n=5). In response to SYM, the APD was transiently prolonged by 5.5+/-3.2 ms at 7.0+/-1.3 s, and monotonically shortened toward a steady-state level (-14.5+/-6.9 ms). Propranolol almost abolished both the transient prolongation (6.6+/-4.5 to 0.2+/-0.4 ms, p<0.05) and the steady-state shortening (-13.7+/-3.6 to -1.1+/-2.4 ms, p<0.005), whereas phentolamine did not have a significant effect on the response of APD to SYM. These findings might partly account for the propensity of ventricular arrhythmias to occur immediately after sudden sympathetic activation.

Action Potentials↗

PubMed2002

Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases.

The interaction between OX40 and OX40 ligand (OX40L) is suggested to provide T cells with an effective costimulatory signals during T cell-APC interaction. To examine the in vivo effect of constitutive OX40/OX40L interaction during immune regulation, we report the establishment of OX40L-transgenic (OX40L-Tg) mice that constitutively express OX40L on T cells. Markedly elevated numbers of effector memory CD4(+) T cells, but not CD8(+) T cells, were observed in the secondary lymphoid organs of OX40L-Tg mice. Upon immunization with keyhole limpet hemocyanin in the absence of adjuvant, profound T cell proliferative responses and cytokine productions were seen in the OX40L-Tg mice as compared with wild-type mice. Furthermore, in OX40L-Tg mice administrated with superantigen, this constitutive OX40/OX40L interaction on CD4(+) T cells completely prevented normal in vivo clonal T cell deletion. Interestingly, OX40L-Tg mice on the C57BL/6 background spontaneously developed interstitial pneumonia and inflammatory bowel disease that was accompanied with a significant production of anti-DNA Ab in the sera. Surprisingly, these diseases were not evident on the OX40L-Tg mice on the BALB/c strain. However, such inflammatory diseases were successfully reproducible in recombination-activating gene (RAG)2-deficient mice upon transfer of OX40L-Tg CD4(+) T cells. Blockade of OX40/OX40L interaction in the recipient RAG2-deficient mice completely prevented disease development. The present results orchestrated in this study indicate that OX40/OX40L interaction may be a vital link in our understanding of T cell-mediated organ-specific autoimmunity.

Adoptive Transfer↗

PubMed2002

Bionic technology revitalizes native baroreflex function in rats with baroreflex failure.

BACKGROUND: We developed a bionic technology for the treatment of baroreflex failure and tested its efficacy in restoration of arterial pressure against head-up tilt (HUT) in rats with baroreflex failure. METHODS AND RESULTS: The bionic baroreflex system (BBS) was a negative feedback system controlled by a computer, the artificial vasomotor center. It sensed systemic arterial pressure (SAP) through a micromanometer placed in the aortic arch and automatically computed the frequency of a pulse train to stimulate sympathetic efferent nerves. We selected the celiac ganglion as the sympathetic vasomotor interface. To make this system bionic, the operational rule of the artificial vasomotor center (H(BRP-->STM); BRP indicates baroreceptor pressure; STM, electrical stimulation) was actively matched to that of the native center. First, we identified the open-loop transfer functions of the native baroreflex control of SAP (H(Native)) and the response of SAP to electrical stimulation of the celiac ganglion (H(STM-->SAP)). We computed H(BRP-->STM) from H(Native)/H(STM-->SAP) and transplanted the operational rule into the computer. In 10 rats with baroreflex failure, we evaluated the performance of the BBS during rapid hypotension induced by HUT. Abrupt HUT dropped SAP by 34+/-6 mm Hg in 2 seconds and by 52+/-5 mm Hg in 10 seconds. During real-time execution of the BBS, on the other hand, the fall in SAP was 21+/-5 mm Hg at 2 seconds and 15+/-6 mm Hg at 10 seconds after HUT. These arterial responses controlled by the BBS were indistinguishable from those by the native baroreflex. CONCLUSIONS: We concluded that the BBS revitalized the native baroreflex function in rats with baroreflex failure.

Animals↗

PubMed2002

Acute ischemia causes 'dark cell' change of strial marginal cells in gerbil cochlea.

The cochlear stria vascularis produces the endolymph and generates the endocochlear DC potential, two indispensable ingredients of an auditory transduction process. The marginal cell, one of the several cell types constituting the stria vascularis, is called 'the dark cell' on the basis of its appearance by transmission electron microscopy (TEM). To clarify whether this commonly observed 'dark appearance' is a normal characteristic of marginal cells, as conjectured in the literature, or an experimental artifact, we developed an in vivo fixation method for minimizing ischemic tissue damages. While under sustained systemic circulation with oxygenated blood, the stria vascularis of gerbils was chemically fixed by perilymphatic perfusion with a fixative, and the stria vascularis was observed by TEM. In contrast to a number of previous reports, the cytoplasm of marginal cells was not dark, and quantitative analysis showed that the difference between the cytoplasmic electron density of marginal cells and that of intermediate cells (another type of strial cells) was not statistically significant. For comparison, the gerbils were allowed to undergo 3 min of ischemia following decapitation. Under these conditions, marginal cells showed typical 'dark appearance', as reported previously, and their cytoplasmic electron density was 1.7 times higher than that of the intermediate cells. In addition, the volume of mitochondria in marginal cells undergoing 3 min of ischemia was higher than that fixed in vivo. We therefore conclude that the widely recognized 'dark cell' appearance of marginal cells following conventional fixation procedures reflects cell injury due to ischemia, which is inherent in the standard fixation procedures, but can be avoided by our fixation protocol here introduced.

Animals↗

PubMed2002

Consequences of OX40-OX40 ligand interactions in langerhans cell function: enhanced contact hypersensitivity responses in OX40L-transgenic mice.

Langerhans cells (LC) represent the dominant antigen-presenting cells (APC) in the epidermis and thus play an important role in cutaneous immune responses to approaching pathogens. These responses are mediated by several costimulatory molecules after antigenic challenge. OX40 ligand (OX40L), a member of TNF superfamily, is expressed on several APC such as splenic dendritic cells (DC) and activated B cells. This molecule has been reported to provide potent costimulation in APC-T cell interactions upon binding to its cognate receptor, OX40, on activated T cells. Little is known, however, regarding OX40L expression and function on LC. In the present study, we report the expression of both OX40L and OX40 on differentiated LC derived from draining lymph nodes in the FITC-sensitized mice. During contact hypersensitivity responses, OX40L-deficient mice demonstrated a significant reduction in both hapten-induced ear swelling and hapten-specific T cell responses despite intact migratory responses. Conversely, these responses were markedly increased in two different OX40L-transgenic strains with variations in OX40L overexpression. In the LC-induced MLR, OX40L-deficient and OX40L-overexpressing LC were capable of reducing and elevating the responses of allogeneic CD4+ T cells, respectively. Thus the requirement of OX40L during the antigen presentation function of LC in T cell priming is here demonstrated.

Animals↗

PubMed2002

Reduction in the endocochlear potential caused by Cs(+) in the perilymph can be explained by the five-compartment model of the stria vascularis.

In an earlier publication (Takeuchi et al., Biophys. J. 79 (2000) 2572-2582), we proposed that K(+) channels in intermediate cells within the stria vascularis may play an essential role in the generation of the endocochlear potential (EP), and we presented an extended version of the five-compartment model of the stria vascularis. In search of further evidence supporting the five-compartment model, we studied the effects of Cs(+) added to the perilymph on guinea pig EP. Cs(+) is known as a competitive K(+) channel blocker. Both the scala tympani and the scala vestibuli of four cochlear turns were perfused at a flow rate of 10 microl/min, and the EP was recorded from the second cochlear turn. Cs(+) at 30 mM caused a biphasic change in the EP; the EP increased transiently from a control level of 89.6 mV to 94.8 mV within 10 min, and then decreased to a steady level of 24.5 mV within the next 40 min. We propose that the initial transient increase in the EP results from Cs(+)-mediated blockade of K(+) conductance in the basolateral membrane of hair cells, and that the subsequent EP decrease is due to effects of Cs(+) on the stria vascularis. We believe that Cs(+) in the perilymph is able to access the stria vascularis by being taken up by fibrocytes in the spiral ligament and then being transported to intermediate cells because it is known that Cs(+) is taken up via Na(+),K(+)-ATPase and that gap junctions connect fibrocytes in the spiral ligament to basal cells and basal cells to intermediate cells. To clarify the effect of intracellular Cs(+) on the electrophysiological properties of intermediate cells, these cells were dissociated from guinea pigs and studied by the whole-cell patch-clamp method. Intracellular Cs(+) depolarized intermediate cells in a dose-dependent manner. In addition, efflux of Cs(+) from the intermediate cell was much less than the efflux of K(+). Thus, Cs(+) may accumulate in the intermediate cell, which depolarizes the cell, which in turn decreases the EP. We conclude that the five-compartment model of the stria vascularis can explain the EP decrease caused by Cs(+) in the perilymph.

Animals↗

PubMed2002

Convenient automated conductance volumetric system.

Conventional conductance volumetric systems require ex-vivo calibrations for blood conductivity and parallel conductance. It is often impractical to repeat blood sampling and hypertonic saline infusion for these calibrations. To overcome these limitations, we developed a useful, self-calibrating conductance volumetric system that does not require ex-vivo calibrations. On a conventional 6-electrode catheter, we added an extra electrode close to one of the recording electrodes to estimate blood conductivity. These two electrodes were placed close (0.5 mm) enough so that conductance between them reflected only blood conductivity regardless of cardiac volume. We estimated parallel conductance by the dual-frequency excitation (2 and 20 kHz) method. In 18 anesthetized rabbits, blood conductivity (sigma(est)) thus estimated agreed well with that (sigma(conv)) measured by the conventional ex-vivo blood sampling method (sigma(est) = 1.04sigma(conv)-0.25, R(2) = 0.98, SEE = 0.01 mS/cm, 1.2% error). Parallel conductance (G(p est)) estimated by dual-frequency excitation also agreed well with that (G(p conv)) estimated by the saline injection method (G(p est) = 0.95G(p conv)+4.25, R(2) = 0.87, SEE = 4.0 mS, 6.0% error). Estimated ventricular volume (V(est)) by our system agreed reasonably well with that (V(conv)) by the conventional method (V(est) = 0.93V(conv)+0.01, R(2) = 0.86, SEE = 0.22 ml, 14.7% error). The fact that this self-calibrating conductance volumetric system drastically simplifies volume measurement makes it an attractive tool for the assessment of cardiac function where significant changes in blood conductivity and parallel conductance are inevitable, such as in cardiac surgery.

Animals↗

PubMedDate not supplied

Elevated sphingomyelinase and hypercytokinemia in hemophagocytic lymphohistiocytosis.

PURPOSE: Ceramide generated from sphingomyelinase activation has been reported to play a role in cytokine-mediated events. Secretory sphingomyelinase (S-SMase), a product of the acid sphingomyelinase gene, has been found to be derived from many cell types and to exist in human serum. The purpose of the current study was to investigate the serum level of S-SMase. PATIENTS AND METHODS: Three patients with hypercytokinemia caused by hemophagocytic lymphohistiocytosis (HLH) were studied. Serum samples were collected from the three patients with HLH, patients with a deficiency of acid sphingomyelinase, or type B Niemann-Pick disease, and normal controls. The S-SMase activities were determined using 14C-sphingomyelin as a substrate. RESULTS: The serum S-SMase activities were increased 10-to 20-fold in the sera from the three patients with HLH (P < 0.0001). The high S-SMase activity was decreased to the normal level along with the clinical improvement of HLH. CONCLUSIONS: Increased release of S-SMase from cells into the circulation is observed in patients with active HLH. The authors suggest that S-SMase is related to the pathophysiology of hypercytokinemia.

Antineoplastic Agents, Phytogenic↗