Biomedical subjects

A Nambu

Publications and source records attributed to A Nambu.

At least 19 recordsLinked to original sources

PubMed2006

N doping of TiO2(110): photoemission and density-functional studies.

The electronic properties of N-doped rutile TiO2(110) have been investigated using synchrotron-based photoemission and density-functional calculations. The doping via N2+ ion bombardment leads to the implantation of N atoms (approximately 5% saturation concentration) that coexist with O vacancies. Ti 2p core level spectra show the formation of Ti3+ and a second partially reduced Ti species with oxidation states between +4 and +3. The valence region of the TiO(2-x)N(y)(110) systems exhibits a broad peak for Ti3+ near the Fermi level and N-induced features above the O 2p valence band that shift the edge up by approximately 0.5 eV. The magnitude of this shift is consistent with the "redshift" observed in the ultraviolet spectrum of N-doped TiO2. The experimental and theoretical results show the existence of attractive interactions between the dopant and O vacancies. First, the presence of N embedded in the surface layer reduces the formation energy of O vacancies. Second, the existence of O vacancies stabilizes the N impurities with respect to N2(g) formation. When oxygen vacancies and N impurities are together there is an electron transfer from the higher energy 3d band of Ti3+ to the lower energy 2p band of the N(2-) impurities.

Journal Article↗

PubMed2006

The role of TNFalpha and IL-17 in the development of excess IL-1 signaling-induced inflammatory diseases in IL-1 receptor antagonist-deficient mice.

IL-1 receptor antagonist (IL-1Ra)-deficient mice spontaneously develop several inflammatory diseases, resembling rheumatoid arthritis, aortitis, and psoriasis in humans. As adoptive T cell transplantation could induce arthritis and aortitis in recipient mice, it was suggested that an autoimmune process is involved in the development of diseases. In contrast, as dermatitis developed in scid/scid-IL-IRa-deficient mice and could not be induced by T cell transfer, a T cell-independent mechanism was suggested. The expression of proinflammatory cytokines was augmented at the inflammatory sites. The development of arthritis and aortitis was significantly suppressed by the deficiency of TNFalpha or IL-17. The development of dermatitis was also inhibited by the deficiency of TNFalpha. These observations suggest that TNFalpha and IL-17 play a crucial role in the development of autoimmunity downstream of IL-1 signaling, and excess IL-1 signaling-induced TNFalpha also induces skin inflammation in a T cell-independent manner.

Animals↗

PubMed2005

Mechanism of the CO oxidation reaction on O-precovered Pt(111) surfaces studied with near-edge x-ray absorption fine structure spectroscopy.

The mechanism of CO oxidation reaction on oxygen-precovered Pt(111) surfaces has been studied by using time-resolved near-edge x-ray absorption fine structure spectroscopy. The whole reaction process is composed of two distinct paths: (1) a reaction of isolated oxygen atoms with adsorbed CO, and (2) a reaction of island-periphery oxygen atoms after the CO saturation. CO coadsorption plays a role to induce the dynamic change in spatial distribution of O atoms, which switches over the two reaction paths. These mechanisms were confirmed by kinetic Monte Carlo simulations. The effect of coadsorbed water in the reaction mechanism was also examined.

Journal Article↗

PubMed2005

Focal area of ground-glass opacity and ground-glass opacity predominance on thin-section CT: discrimination between neoplastic and non-neoplastic lesions.

AIM: To reveal differences in thin-section computed tomography (CT) findings between lung neoplastic lesions and non-neoplastic lesions, which showed a focal area of ground-glass opacity or ground-glass opacity predominance. MATERIALS AND METHODS: A total of 82 focal areas of ground-glass opacity and ground-glass opacity predominance, consisting of 38 neoplastic and 44 non-neoplastic lesions, were assessed retrospectively regarding their thin-section CT findings. RESULTS: The frequency of wholly well-defined margin (p=0.001), spiculation (p=0.019), pleural indentation (p=0.016), air bronchograms (p=0.027), air-containing space (p=0.004) was significantly higher in neoplastic lesions than in non-neoplastic lesions. Thirty-four of 38 (89%) neoplastic lesions were well-defined in more than 50% of the circumference, of which nine had an air-containing space other than air bronchogram, whereas only one non-neoplastic lesion had these features. CONCLUSION: A focal area of ground-glass opacity or ground-glass opacity predominance with a well-defined margin and air-containing space is more likely to be a neoplasm.

Adult↗

PubMed2005

Down-regulation of metabotropic glutamate receptor 1alpha in globus pallidus and substantia nigra of parkinsonian monkeys.

Enhanced glutamatergic neurotransmission via the subthalamopallidal or subthalamonigral projection seems crucial for developing parkinsonian motor signs. In the present study, the possible changes in the expression of metabotropic glutamate receptors (mGluRs) were examined in the basal ganglia of a primate model for Parkinson's disease. When the patterns of immunohistochemical localization of mGluRs in monkeys administered systemically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were analysed in comparison with normal controls, we found that expression of mGluR1alpha, but not of other subtypes, was significantly reduced in the internal and external segments of the globus pallidus and the substantia nigra pars reticulata. To elucidate the functional role of mGluR1 in the control of pallidal neuron activity, extracellular unit recordings combined with intrapallidal microinjections of mGluR1-related agents were then performed in normal and parkinsonian monkeys. In normal awake conditions, the spontaneous firing rates of neurons in the pallidal complex were increased by DHPG, a selective agonist of group I mGluRs, whereas they were decreased by AIDA, a selective antagonist of group I mGluRs, or LY367385, a selective antagonist of mGluR1. These electrophysiological data strongly indicate that the excitatory mechanism of pallidal neurons by glutamate is mediated at least partly through mGluR1. The effects of the mGluR1-related agents on neuronal firing in the internal pallidal segment became rather obscure after MPTP treatment. Our results suggest that the specific down-regulation of pallidal and nigral mGluR1alpha in the parkinsonian state may exert a compensatory action to reverse the overactivity of the subthalamic nucleus-derived glutamatergic input that is generated in the disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Reaction-path switching induced by spatial-distribution change of reactants: CO oxidation on Pt(111).

We studied the mechanism of CO oxidation on O-covered Pt(111) surfaces during CO exposure by means of time-resolved near edge x-ray absorption fine structure spectroscopy. Two distinct reaction processes were found to occur sequentially; isolated O atoms and island-periphery O atoms contribute to each process. Combination of in situ monitoring of the reaction kinetics and Monte Carlo simulations revealed that CO coadsorption plays a role of inducing the dynamic change in spatial distribution of O atoms, which switches over the two reaction paths.

Journal Article↗

PubMed2004

Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys.

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.

Animals↗

PubMed2004

Role of ionotropic glutamatergic and GABAergic inputs on the firing activity of neurons in the external pallidum in awake monkeys.

The neurons in the external segment of the pallidum (GPe) in awake animals maintain a high level of firing activity. The level and pattern of the activity change with the development of basal ganglia disorders including parkinsonism and hemiballism. The GPe projects to most of the nuclei in the basal ganglia. Thus exploring the mechanisms controlling the firing activity is essential for understanding basal ganglia function in normal and pathological conditions. To explore the role of ionotropic glutamatergic and GABAergic inputs to the GPe, unit recordings combined with local injections of receptor antagonists were performed in awake monkeys. Observations on the effects of local application of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide, the N-methyl-D-aspartic acid (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and the GABAA antagonist gabazine as well as the effects of muscimol blockade of the subthalamic nucleus on the spontaneous firing rate, firing patterns, and cortical stimulation induced responses in the GPe suggested the following: sustained glutamatergic and GABAergic inputs control the level of the spontaneous firing of GPe neurons; both AMPA/kainate and NMDA receptors are activated by glutamatergic inputs; some GPe neurons receive glutamatergic inputs originating from areas other than the subthalamic nucleus; no GPe neurons became silent after a combined application of glutamate and GABA antagonists, suggesting that GPe neurons have intrinsic properties or nonionotropic glutamatergic tonic inputs that sustain a fast oscillatory firing or a combination of a fast and a slow oscillatory firing in GPe neurons.

Animals↗

PubMed2003

Excitatory GABA input directly drives seizure-like rhythmic synchronization in mature hippocampal CA1 pyramidal cells.

GABA, which generally mediates inhibitory synaptic transmissions, occasionally acts as an excitatory transmitter through intense GABA(A) receptor activation even in adult animals. The excitatory effect results from alterations in the gradients of chloride, bicarbonate, and potassium ions, but its functional role still remains a mystery. Here we show that such GABAergic excitation participates in the expression of seizure-like rhythmic synchronization (afterdischarge) in the mature hippocampal CA1 region. Seizure-like afterdischarge was induced by high-frequency synaptic stimulation in the rat hippocampal CA1-isolated slice preparations. The hippocampal afterdischarge was completely blocked by selective antagonists of ionotropic glutamate receptors or of GABA(A) receptor, and also by gap-junction inhibitors. In the CA1 pyramidal cells, oscillatory depolarizing responses during the afterdischarge were largely dependent on chloride conductance, and their reversal potentials (average -38 mV) were very close to those of exogenously applied GABAergic responses. Moreover, intracellular loading of the GABA(A) receptor blocker fluoride abolished the oscillatory responses in the pyramidal cells. Finally, the GABAergic excitation-driven afterdischarge has not been inducible until the second postnatal week. Thus, excitatory GABAergic transmission seems to play an active functional role in the generation of adult hippocampal afterdischarge, in cooperation with glutamatergic transmissions and possible gap junctional communications. Our findings may elucidate the cellular mechanism of neuronal synchronization during seizure activity in temporal lobe epilepsy.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2001

Somatotopic arrangement and corticocortical inputs of the hindlimb region of the primary motor cortex in the macaque monkey.

Using Japanese monkeys, we examined the somatotopic organization of the hindlimb region of the primary motor cortex (MI) with intracortical microstimulation. In the hindlimb region of the MI, areas representing distal movements (digits and ankle joints) were basically surrounded by those representing proximal movements (knee and hip joints). Thus, the hindlimb region of the MI has a nested or horseshoe-like somatotopic representation. We then examined the topographic organization of corticocortical projections to the hindlimb region of the MI by the retrograde double-labeling technique: one monkey received paired injections of Fast blue (FB) and Diamidino yellow (DY) into hindlimb or forelimb representation of the MI, respectively, while two monkeys received those of FB and DY into proximal or distal representation of the hindlimb region of the MI, respectively. The neurons projecting to the hindlimb region of the MI were located in cortical areas largely separate from those projecting to the forelimb region of the MI. On the other hand, we found a substantial overlap of corticocortical neurons projecting to the proximal and distal parts of the hindlimb region of the MI in the dorsal division of the premotor cortex and the cingulate motor areas.

Animals↗

PubMed2001

Organization of inputs from cingulate motor areas to basal ganglia in macaque monkey.

The cingulate motor areas reside within regions lining the cingulate sulcus and are divided into rostral and caudal parts. Recent studies suggest that the rostral and caudal cingulate motor areas participate in distinct aspects of motor function: the former plays a role in higher-order cognitive control of movements, whereas the latter is more directly involved in their execution. Here, we investigated the organization of cingulate motor areas inputs to the basal ganglia in the macaque monkey. Identified forelimb representations of the rostral and caudal cingulate motor areas were injected with different anterograde tracers and the distribution patterns of labelled terminals were analysed in the striatum and the subthalamic nucleus. Corticostriatal inputs from the rostral and caudal cingulate motor areas were located within the rostral striatum, with the highest density in the striatal cell bridges and the ventrolateral portions of the putamen, respectively. There was no substantial overlap between these input zones. Similarly, a certain segregation of input zones from the rostral and caudal cingulate motor areas occurred along the mediolateral axis of the subthalamic nucleus. It has also been revealed that corticostriatal and corticosubthalamic input zones from the rostral cingulate motor area considerably overlapped those from the presupplementary motor area, while the input zones from the caudal cingulate motor area displayed a large overlap with those from the primary motor cortex. The present results indicate that a parallel design underlies motor information processing in the cortico-basal ganglia loop derived from the rostral and caudal cingulate motor areas.

Action Potentials↗

PubMed2000

A cortical motor region that represents the cutaneous back muscles in the macaque monkey.

A cortical motor region that represented the cutaneous muscles on the back was identified on the medial wall of the frontal lobe in the macaque monkey. In this region, neurons responded to somatosensory stimuli such as light touch or squeezing of the back skin, and intracortical microstimulation elicited contraction of the back skin. Such a region was located primarily on the dorsal bank of the cingulate sulcus, corresponding to the dorsal cingulate motor area.

Animals↗

PubMed2000

Direct projections from the magnocellular division of the basal nucleus of the amygdala to the principal part of the cortical masticatory area in the macaque monkey.

Direct projections from the amygdala to the cortical masticatory area were found in the macaque monkey. Under the guidance of intracortical microstimulation, retrograde tracers were injected into multiple jaw movement-related regions of the frontal lobe. The cortical masticatory area, especially its principal part, stimulation of which elicited rhythmic jaw movement, was the only site of injection that produced neuronal labeling in the amygdala. The cells of origin of such projections were localized in the medial aspect of the magnocellular division of the basal nucleus through its rostral level. No labeled neurons were observed in the amygdala after tracer injection into any other cortical jaw movement-related region. The present results suggest that the amygdaloid input to the cortical masticatory area may exert some modulatory influence on the generation of masticatory rhythm.

Amygdala↗

PubMed2000

Two-dimensional thick-slice MR digital subtraction angiography for assessment of cerebrovascular occlusive diseases.

Although spatial resolution of current MR angiography is excellent, temporal resolution has remained unsatisfactory. We evaluated clinical applicability of 2D thick-slice, contrast-enhanced subtraction MR angiography (2D-MR digital subtraction angiography) with sub-second temporal resolution in cerebrovascular occlusive diseases. Twenty-five patients with cerebrovascular occlusive diseases (8 moyamoya diseases, 10 proximal internal carotid occlusions, and 2 sinus thromboses ) were studied with a 1.5-T MR unit. The MR digital subtraction angiography (MRDSA) was performed per 0.97 s continuously just after a bolus injection of 15 ml of gadolinium chelates up to 40 s in sagittal (covering hemisphere) or coronal planes. Subtraction images were generated at a workstation. We evaluated imaging quality and hemodynamic information of MRDSA in comparison with those of routine MR imaging, non-contrast MR angiography, and X-ray intra-arterial DSA. Major cerebral arteries, all of the venous sinuses, and most tributaries were clearly visualized with 2D MRDSA. Also, pure arterial phases were obtained in all cases. The MRDSA technique demonstrated prolonged circulation in sinus thromboses, distal patent lumen of proximal occlusion, and some collateral circulation. Such hemodynamic information was comparable to that of intra-arterial DSA. Two-dimensional thick-slice MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics equivalent to that of intra-arterial DSA and may play an important role for evaluation of cerebrovascular occlusive diseases.

Adult↗

PubMed2000

Time-resolved two-dimensional thick-slice magnetic resonance digital subtraction angiography in assessing brain tumors.

The aim of this study was to evaluate clinical applicability of two-dimensional (2D) thick-slice, contrast-enhanced magnetic resonance digital subtraction angiography (MRDSA) with high temporal resolution in diagnosis of brain tumors. Forty-four patients with brain tumors including, 15 meningiomas, 8 gliomas, 6 metastatic tumors, 4 neuromas, and 2 hemangioblastomas, were studied with 2D MRDSA with frame rate approximately 1 s. Images were continuously obtained following the initiation of bolus injection of gadolinium chelates for 40 s and subtraction images were generated in a workstation. We evaluated visualization of normal cranial vessels on MRDSA and compared MRDSA and intra-arterial digital subtraction angiography (IADSA) with regard to hemodynamic information. Large cerebral arteries, all venous sinuses, and most tributaries were clearly visualized. A stain was present in hypervascular tumors including all 15 meningiomas and 2 hemangioblastomas on MRDSA. Presence of a stain demonstrated on MRDSA and that on IADSA coincided in 16 of 20 cases (Spearman rank correlation value was 0.85). The location, shape, and phase of the stain on MRDSA were similar to those on IADSA. Two-dimensional MRDSA with high temporal resolution has a unique ability to demonstrate cerebral hemodynamics, such as IADSA, and can play an important role in assessing brain tumors.

Adolescent↗

PubMed2000

B-mode and color Doppler ultrasound imaging for localization of microelectrode in monkey brain.

Using alert monkeys, we attempted ultrasound imaging after partial craniotomy to localize a metal microelectrode in the brain. B-mode ultrasonography provided images of sulcus and gyrus patterns of the cerebral cortex, and locations of the ventricles and subarachnoid cisterns. As the microelectrode proceeded in the brain, the position of the microelectrode was clearly identified. Electrolytic microlesions generated by delivering direct currents via the microelectrode could also be detected. Color Doppler imaging of blood vessels of the brain was helpful to demarcate deep brain structures and to avoid accidental injury of the blood vessels by the microelectrode. The ultrasonography will make it possible to place recording microelectrodes or injection needles accurately in target regions of the brain in physiological, anatomical or behavioral experiments.

Animals↗

PubMed2000

Organization of somatic motor inputs from the frontal lobe to the pedunculopontine tegmental nucleus in the macaque monkey.

To reveal the somatotopy of the pedunculopontine tegmental nucleus that functions as a brainstem motor center, we examined the distribution patterns of corticotegmental inputs from the somatic motor areas of the frontal lobe in the macaque monkey. Based on the somatotopical map prepared by intracortical microstimulation, injections of the anterograde tracers, biotinylated dextran amine and wheat germ agglutinin-conjugated horseradish peroxidase, were made into the following motor-related areas: the primary motor cortex, the supplementary and presupplementary motor areas, the dorsal and ventral divisions of the premotor cortex, and the frontal eye field. Data obtained from the present experiments were as follows: (i) Corticotegmental inputs from orofacial, forelimb, and hindlimb representations of the primary motor cortex tended to be arranged orderly from medial to lateral in the pedunculopontine tegmental nucleus. However, the distribution areas of these inputs considerably overlapped; (ii) The major input zones from distal representations of the forelimb and hindlimb regions of the primary motor cortex were located medial to those from their proximal representations, although there was a substantial overlap between the distribution areas of distal versus proximal limb inputs; (iii) The main terminal zones from the forelimb regions of the primary motor cortex, the supplementary and presupplementary motor areas, and the dorsal and ventral divisions of the premotor cortex appeared to overlap largely in the mediolaterally middle aspect of the pedunculopontine tegmental nucleus; and (iv) Corticotegmental input from the frontal eye field was scattered over the pedunculopontine tegmental nucleus.Thus, the present results indicate that the pedunculopontine tegmental nucleus is likely to receive partly separate but essentially convergent cortical inputs not only from multiple motor-related areas representing the same body part, but also from multiple regions representing diverse body parts. This suggests that somatotopical representations are intermingled rather than segregated in the pedunculopontine tegmental nucleus.

Animals↗

PubMed2000

Protection against dopaminergic nigrostriatal cell death by excitatory input ablation.

The importance of enhanced glutamatergic neurotransmission in the basal ganglia and related structures has recently been highlighted in the development of Parkinson's disease. The pedunculopontine tegmental nucleus (PPN) is the major origin of excitatory, glutamatergic input to dopaminergic nigrostriatal neurons of which degeneration is well known to cause Parkinson's disease. Based on the concept that an excitatory mechanism mediated by glutamatergic neurotransmission underlies the pathogenesis of neurodegenerative disorders, we made an attempt to test the hypothesis that removal of the glutamatergic input to the nigrostriatal neurons by PPN lesions might prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the macaque monkey. The PPN was lesioned unilaterally with microinjection of kainic acid, and, then, MPTP was administered systemically. In these monkeys, the degree of parkinsonian motor signs was behaviourally evaluated, and the histological changes in the dopaminergic nigrostriatal system were analysed by means of tyrosine hydroxylase immunohistochemistry. The present results revealed that nigrostriatal cell loss and parkinsonian motor deficits were largely attenuated in the MPTP-treated monkey group whose PPN had been lesioned, compared with the control, MPTP-treated monkey group with the PPN intact. This clearly indicates that the onset of MPTP neurotoxicity is suppressed or delayed by experimental ablation of the glutamatergic input to the nigrostriatal neurons. Such a protective action of excitatory input ablation against nigrostriatal cell death defines evidence that nigral excitation driven by the PPN may be implicated in the pathophysiology of Parkinson's disease.

Animals↗