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Biomedical subjects

K Eto

Publications and source records attributed to K Eto.

At least 55 records · Page 3Linked to original sources

Efficacy of transradial primary stenting in patients with acute myocardial infarction.

We conducted a prospective observational study to assess the effectiveness of "transradial primary stenting" in 33 patients with acute myocardial infarction, along with acute risk stratification and accelerated patient care. With use of adequate inclusion and exclusion criteria, the radial artery can be used as an access site for catheterization, and transradial primary stenting can be performed rapidly and successfully by trained coronary interventionalists.

Aged↗

Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion.

Glucose metabolism in glycolysis and in mitochondria is pivotal to glucose-induced insulin secretion from pancreatic beta cells. One or more factors derived from glycolysis other than pyruvate appear to be required for the generation of mitochondrial signals that lead to insulin secretion. The electrons of the glycolysis-derived reduced form of nicotinamide adenine dinucleotide (NADH) are transferred to mitochondria through the NADH shuttle system. By abolishing the NADH shuttle function, glucose-induced increases in NADH autofluorescence, mitochondrial membrane potential, and adenosine triphosphate content were reduced and glucose-induced insulin secretion was abrogated. The NADH shuttle evidently couples glycolysis with activation of mitochondrial energy metabolism to trigger insulin secretion.

Adenosine Triphosphate↗

Role of polysialic acid on outgrowth of rat olfactory receptor neurons.

Towards elucidating the role of polysialic acid (PSA) in developing olfactory neuron of the rat, we injected neuraminidase (endo-N) into the olfactory nerve pathway under whole embryo culture, then employed immunohistochemistry to (i) detect expression of highly sialylated neural cell adhesion molecules (NCAM-H) and (ii) identify olfactory neurons via anti-microtubule-associated protein 1B (MAP1B) antibody. Olfactory axonal outgrowth from basal lamina occurred at the 31-somite stage and reached the olfactory bulb primordium at the 42-somite stage, being coincident with the timing and expression of NCAM-H immunoreactivity. Enzymatic removal of PSA by endo-N remarkably affected developmental processes of axonal outgrowth, extension, and pathfinding, i.e. individual axons appeared to have become stuck in the mesenchyme. Results indicate that PSA is critically involved with anti-adhesion cues associated with individual axonal growth during olfactory system development.

Animals↗

PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

Adipocytes↗

Morphological changes in periodontal mechanoreceptors of mouse maxillary incisors after the experimental induction of anterior crossbite: a light and electron microscopic observation using immunohistochemistry for PGP 9.5.

Ruffini nerve endings (mechanoreceptors) in the periodontal ligament (PDL) of mouse incisors were examined to elucidate whether experimentally-induced crossbites cause any changes or abnormalities in their morphology and distribution. Anterior guiding planes were attached to the mandibular incisors of 3-week-old C3H/HeSlc mice. At 3 days and 1, 2, 4, 6, and 8 weeks post-attachment of the appliance, the mice were sacrificed by perfusion fixation. Frozen sagittal cryostat sections of the decalcified maxillary incisors were processed for immunohistochemistry of protein gene product 9.5, followed by histochemical determination of tartrate-resistant acid phosphatase activity to reveal sites of alveolar bone resorption. Despite the absence of bone resorption within the lingual PDL of control mice, distinct resorption sites were seen in the respective regions of the experimental animals. Unlike the controls, many Ruffini endings showing vague and swollen contours, with unusually long and pedunculated micro-projections were observed in the affected lingual PDL of the incisors in the experimental animals with short-term anterior crossbite induction. Club-shaped nerve terminations with few, if any, micro-projections were observed in the lingual PDL of experimental animals with long-term induction, as well as in aged control mouse incisors. Differences in the distribution of Ruffini endings were also observed. These results indicate that changing the direction of the force applied to the PDL results in rapid and prolonged changes in the morphology of Ruffini-like mechanoreceptors.

Acid Phosphatase↗

AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes.

The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12 dyne/cm2), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

Acute Disease↗

[Role of the NADH shuttle system in glucose-induced insulin secretion].

To determine the role of the NADH shuttle system composed of the glycerol phosphate shuttle and malate-aspartate shuttle in glucose-induced insulin secretion from pancreatic beta cells, we have generated mice which lack mitochondrial glycerol-3 phosphate dehydrogenase (mGPDH), a rate-limiting enzyme of the glycerol phosphate shuttle. When both shuttles were halted in mGPDH-deficient islets treated with aminooxyacetate, an inhibitor of the malate-aspartate shuttle, glucose-induced insulin secretion was almost completely abrogated. Under these conditions, although the flux of glycolysis and supply of glucose-derived pyruvate into mitochondria were unaffected, glucose-induced increases in NAD(P)H autofluorescence, mitochondrial membrane potential, Ca2+ entry into mitochondria, and ATP content were severely attenuated. This study provides the first direct evidence that the NADH shuttle system is essential for coupling glycolysis with the activation of mitochondrial energy metabolism to trigger glucose-induced insulin secretion and thus revises the classical model for the metabolic signals of glucose-induced insulin secretion.

Animals↗

[Aggressive diagnostic and therapeutic approach for acute coronary syndrome].

The purpose of this article is to propose an "aggressive strategy" in the treatment of patients with acute coronary syndrome (ACS), especially unstable angina. The indication and timing of emergent coronary angiography in patients with ACS remains to be validated. The results of TIMI III B trial, a randomized, controlled trial about this issue, show that an early invasive strategy reduced the average length of initial hospitalization and the incidence of rehospitalization within 6 weeks. However, the same kind of clinical trial named VANQWISH reported that no benefit was obtained from such an aggressive strategy. It is of paramount importance to note that these 2 studies were performed in the era of plain old balloon angioplasty. Now we can use many kinds of coronary stent which impart both excellent radial strength and flexibility. Recent studies have demonstrated that culprit lesions of ACS can be treated at the same success rate as those of stable effort angina. In our hospital, use of coronary stents in patients with ACS dramatically reduced the recurrence of ACS and the incidence of angiographic restenosis with the same initial procedure success rate. Since the mid-nineties, the radial artery has been used as a vascular access site of coronary intervention. The major advantage of this technique is lesser access site-related complications and increased patient comfort, which reduced hospital stay and cost. Recently it was demonstrated that ad-hoc transradial intervention can be applied in patients with unstable angina or even those with acute myocardial infarction by trained angioplasters. Thus, we would like to conclude that the best strategy in the management of ACS is to perform emergent coronary angiography from the radial artery as soon as possible after admission, and to do ad-hoc intervention using coronary stents suitable for the lesion anatomy.

Aged↗

Endothelium-dependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia.

BACKGROUND: Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. METHODS AND RESULTS: Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 microg of a plasmid encoding VEGF or ss-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 microm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6+/-17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1+/-8.4% in VEGF-treated animals (P<0.05). CONCLUSIONS: These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.

Acetylcholine↗

Significance of development of late potentials after anterior wall acute myocardial infarction despite successful primary angioplasty of the left anterior descending coronary artery.

We classified 33 patients with a first anterior infarction and single-vessel disease who had undergone successful primary angioplasty and had a patent infarct-related artery into groups based on the development of late potentials. Left ventricular function improved between 1 and 3 months after angioplasty only in patients without late potentials; the development of late potentials after acute anterior infarction was associated with prolonged left ventricular dysfunction despite successful revascularization with primary angioplasty.

Aged↗

Immunohistochemical and ultrastructural characterization of ubiquitinated eosinophilic fibrillary neuronal inclusions in sporadic amyotrophic lateral sclerosis.

We found eosinophilic fibrillary neuronal inclusions (EFNI) that were argyrophilic and immunoreactive for anti-ubiquitin in the cerebral cortex of a patient with sporadic amyotrophic lateral sclerosis (ALS) and mild personality changes. Both hematoxylin and eosin and Bodian's preparations revealed the EFNI to be rod-, flame-shaped, or spherical structures existing within the swollen neuronal perinuclear region in the third, fifth, and sixth layers of the fronto-parieto-temporal cortices including the primary motor cortex. On electron microscopy, filamentous profiles aggregated and formed a single bundle or globule in the neuronal perikaryon without any limiting membrane. Most EFNI had a characteristic multiple layer arrangement. The inner core consisted of randomly oriented granule-free tubules with a fuzzy outer contour, measuring 15-20 nm in diameter. The surrounding layer was made up of granule-associated filaments, electrondense free granules, and small vesicular profiles. Large autolysosome-like membrane-bound vesicular profiles were found scattered at the periphery. Neurofilaments were usually mingled with in the surrounding cytoplasm. Many EFNI were also found in dendrites, but only a few in axons. Both granule-free tubules and granule-associated filaments expressed ubiquitin protein epitopes. Aberrant phosphorylation of neurofilament protein and induction of alphaB-crystallin were shown to exist in EFNI-bearing swollen neurons. Despite having a variety of histological appearances, our observations revealed that EFNI all have common immunocytochemical and ultrastructural characteristics, and thus we assume that EFNI represent a series of cytological alterations in the motor and extra-motor cortices of ALS patients.

Amyotrophic Lateral Sclerosis↗

Preferential inhibition of Ikr by MCI-154, a putative cardiotonic Ca2+ sensitizer, in guinea pig atrial cells.

OBJECTIVE: To define the electrophysiologic mechanism(s) by which MCI-154, a putative Ca2+ sensitizer, produces a positive inotropic response without a positive chronotropic response, we examined effects of MCI-154 on the action potential of atrial preparations and the membrane currents of atrial myocytes. METHODS: The action potentias were recorded from left atrial and sinoatrial node preparations of guinea pigs by the use of standard microelectrode techniques. The whole-cell membrane currents were recorded from enzymatically-dissociated guinea pig atrial myocytes using conventional patch clamp techniques. RESULTS: In isolated left atria, MCI-154 increased the developed tension in a concentration-dependent manner. MCI-154 at concentrations of 10 and 100 microM increased the action potential duration (APD) in left atria stimulated at 0.5 Hz. In sinoatrial node preparations MCI-154 at a concentration of 100 microM produced a negative chronotropic response and prolonged APD. In single right atrial myocytes, MCI-154 at concentrations of 10 and 100 microM failed to increase the inward L-type Ca2+ current, but decreased the delayed rectifier K+ current (IK) in a concentration-dependent manner. MCI-154 decreased IK elicited by short depolarizing pulses more markedly than that induced by long depolarizing pulses. In addition, MCI-154 produced only a little inhibition of IK in the presence of E-4031, a specific blocker of rapidly activating component of IK (IKr). CONCLUSIONS: MCI-154 preferentially blocks IKr and the inhibitory action on IKr may be partly involved in the negative chronotropic and positive inotropic responses in atrial preparations.

Action Potentials↗

Platelet aggregation in acute coronary syndromes: use of a new aggregometer with laser light scattering to assess platelet aggregability.

OBJECTIVE: Platelet aggregation has been implicated in the pathogenesis of acute coronary syndromes. Small aggregates consisting of < or = 100 platelets cannot be quantified with a conventional aggregometer employing optical density. Using a recently developed aggregometer based on laser light scattering, we studied platelet aggregability in patients with acute coronary syndromes. METHODS: Peripheral blood samples were obtained from 39 patients with acute myocardial infarction or unstable angina who had received no prior antiplatelet or anticoagulant therapy, to be assayed immediately using a PA-100 platelet aggregometer. Blood samples from 14 healthy volunteers were used as controls. RESULTS: Spontaneous formation of platelet aggregates was observed only in patients with acute coronary syndromes. The size of these aggregates was small, consisting of < or = 100 platelets (primary aggregation). Agonist-induced aggregation consisted of two phases. In the first few minutes, the number of small aggregates increased markedly (primary aggregation), followed by an increase in larger aggregates (secondary aggregation). The EC50 of epinephrine for primary aggregation was nearly 50 times lower in acute coronary patients than in controls (P < 0.001), while the EC50 for secondary aggregation was only 2 times lower (P < 0.001). CONCLUSIONS: Aggregometry using light scattering suggests that platelet hyperaggregability and hypersensitivity in acute coronary syndromes may occur in primary but not secondary aggregation.

Acute Disease↗

Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat embryos.

Classical transplantation experiments with various amphibian tissues have shown that tooth development requires not only oral ectoderm and neural crest but also foregut endoderm. In addition, histological observation of oral membrane showed that the tooth germs are initiated in some ectodermal cells and neural crest cells adjacent to foregut endoderm. These studies suggest that tooth initiation requires the presence and cooperation of these three components. In mammals, however, there is no direct evidence that tooth formation is involved in the region of oral ectoderm adjacent to foregut endoderm. In order to elucidate the contribution of foregut endoderm to tooth formation, we established a new type of endodermal cell tracing system with a recombinant adenovirus called Adex-lacZ, and performed endodermal cell tracing in a long-term culture system. Cells labelled with Adex-lacZ were seen next to non-labelled thickening epithelium, presumptive incisor epithelium. These findings show the first direct evidence in mammals that tooth formation takes place in the specified part of oral ectoderm adjacent to foregut endoderm, suggesting that foregut endoderm plays a role in tooth initiation.

Adenoviridae↗

Accumulation of p300 mediates transcriptional repression of simian virus 40 enhancer in undifferentiated F9 embryonal carcinoma cells.

The SV40 enhancer is repressed in embryonal carcinoma (EC) cells, and it is also repressed by the adenovirus E1A oncoprotein. Repression by E1A is mediated by the binding of E1A to the p300 transcriptional coactivator. Thus, we examined the role of p300 in the repression of the SV40 enhancer activity in EC cells. We demonstrated that high levels of p300 protein are accumulated in undifferentiated EC cells and that the levels decline dramatically upon differentiation because of the changes of protein stability. Furthermore, we showed that overexpression of p300 does not stimulate the SV40 enhancer activity in undifferentiated F9 cells. However, the activity of a p300 mutant deficient for E1A binding can be restored by the presence of excess E1A. In addition, low-level expression of E1A causes derepression of the enhancer activity in F9 cells. These results indicate that the accumulation of p300 protein participates in repression of the SV40 enhancer activity in undifferentiated F9 cells.

Activating Transcription Factor 1↗