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Biomedical subjects

T Fukai

Publications and source records attributed to T Fukai.

At least 19 recordsLinked to original sources
PubMed2005

Antimicrobial activity of isoprenoid-substituted xanthones from Cudrania cochinchinensis against vancomycin-resistant enterococci.

Ten xanthones with one or two isoprenoid groups and a prenylated benzophenone isolated from roots of Cudrania cochinchinensis (Moraceae) were tested for their antimicrobial activities against vancomycin-resistant enterococci (VRE). Among these compounds, gerontoxanthone H exhibited considerable antibacterial activity against five VRE strains (VanA, VanB and VanC) (MICs = 1.56 microg/ml). Four xanthones, 1,3,7-trihydroxy-2-prenylxanthone, gerontoxanthone I, alvaxanthone and isoalvaxanthone, showed weaker antibacterial activity against these VREs (MICs = 3.13-6.25 microg/ml). .

Anti-Bacterial Agents↗
PubMed2004

Antibacterial activity of phytochemicals isolated from Erythrina zeyheri against vancomycin-resistant enterococci and their combinations with vancomycin.

Six phytochemicals were isolated from the roots of Erythrina zeyheri (Leguminosae) by repeated silica gel column chromatography using various eluting solvents. Extensive spectroscopic studies revealed that all were isoflavonoids. The antibacterial activity of the six compounds against vancomycin-resistant enterococci (VRE) was estimated by determining the minimum inhibitory concentration (MIC). Of the six isoflavonoids, erybraedin A ((6aR, 11aR)-3,9-dihydroxy-4,10-di(gamma,gamma-dimethylallyl)pterocarpan) exhibited the highest growth inhibitory potency against VRE with an MIC value of 1.56-3.13 microg/mL, followed by eryzerin C ((3R)-7,2',4'-trihydroxy-6,8-di(gamma,gamma-dimethylallyl)isoflavan) (MIC 6.25 microg/mL). These compounds also inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.13-6.25 microg/mL. The antibacterial effects of the two compounds against VRE and MRSA were based on bacteriostatic action. When erybraedin A or eryzerin C was combined with vancomycin, the fractional inhibitory concentration (FIC) index against VRE ranged from 0.5306 to 1.0 and from 0.5153 to 0.75, respectively. The combinations also showed FIC indices of 0.6125-1.0 against MRSA. The results indicate that, depending on the case, both compounds act either synergistically or additively with vancomycin against VRE and MRSA. Erybraedin A and eryzerin C show evidence of being potent phytotherapeutic agents against infections caused by VRE and MRSA.

Anti-Bacterial Agents↗
PubMed2004

Influences of synaptic location on the synchronization of rhythmic bursting neurons.

We study how the location of synaptic input influences the stablex firing states in coupled model neurons bursting rhythmically at the gamma frequencies (20-70 Hz). The model neuron consists of two compartments and generates one, two, three or four spikes in each burst depending on the intensity of input current and the maximum conductance of M-type potassium current. If the somata are connected by reciprocal excitatory synapses, we find strong correlations between the changes in the bursting mode and those in the stable phase-locked states of the coupled neurons. The stability of the in-phase phase-locked state (synchronously firing state) tends to change when the individual neurons change their bursting patterns. If, however, the synaptic connections are terminated on the dendritic compartments, no such correlated changes occur. In this case, the coupled bursting neurons do not show the in-phase phase-locked state in any bursting mode. These results indicate that synchronization behaviour of bursting neurons significantly depends on the synaptic location, unlike a coupled system of regular spiking neurons.

Animals↗
PubMed2003

Time representing cortical activities: two models inspired by prefrontal persistent activity.

Timing information in the range of seconds is significantly correlated with our behavior. There is growing interest in the cognitive behaviors that rely on perception, comparison, or generation of timing. However, little is known about the neural mechanisms underlying such behaviors. Here we model two different neural mechanisms to represent timing information in the range of seconds. In one model, a recurrent network of bistable spiking neurons shows a quasistable state that is initiated by a brief input and typically lasts for a few to several seconds. The duration of this quasistable activity may be regarded as the neural representation of internal time obeying a psychophysical law of time recognition. Another model uses synfire chains to provide the timing information necessary for predicting the times of anticipated events. In this model, the neurons projected to by multiple synfire chains are conditioned to fire synchronously at the times when an external event (GO signal) is expected. The conditioning is accomplished by spike-timing-dependent plasticity. The two models are inspired by the prefrontal activities of the monkeys engaging in different timing-information-related tasks. Thus, this cortical region may provide the timing information required for organizing various behaviors.

Action Potentials↗
PubMed2002

The role of Ca2+-dependent cationic current in generating gamma frequency rhythmic bursts: modeling study.

Fast rhythmic bursting pyramidal neuron or chattering neuron is a promising candidate for the pacemaker of coherent gamma-band (25-70 Hz) cortical oscillation. It, however, still remains to be clarified how the neuron generates such high-frequency bursts. Here, we demonstrate in a single-compartment model neuron that the fast rhythmic bursts (FRBs) can be achieved through Ca2+-activated channels in the entire gamma frequency range. In a previous in vitro study, a subset of rat cortical pyramidal cells displayed a long-lasting depolarizing afterpotential (DAP) following a plateau-type action potential when K+ conductances were suppressed with Cs+, and this DAP was found to be mediated by a Ca2+-dependent cationic current. This current appeared also suitable for producing a hump-like DAP, a characteristic of the chattering neurons, because of its reversal potential being approximately -40 mV. In the present theoretical study, we show that the enhancement of such a DAP leads to generation of doublet/triplet spikes seen during FRBs. The firing pattern during FRBs is primarily determined by a Ca2+-dependent cationic current and a small-conductance Ca2+-dependent potassium current, which are differentially activated by a biphasically decaying Ca2+ transient produced by fast buffering and a slow pump extrusion after each spike. With varying intensities of injected current pulses, the interburst frequencies of the FRBs range over the entire gamma frequency band (25-70 Hz) in our model, while the intraburst frequencies remain higher than 300 Hz. Our model suggests that FRBs are essentially generated in the soma, unlike the model based on a persistent sodium current, and that the alteration of Ca2+ sensitivity of Ca2+-dependent cationic current plays an essential role in controlling the FRB pattern.

Action Potentials↗
PubMed2001

Neural mechanism for a cognitive timer.

To examine a possible biological mechanism for a cognitive timer, the stochastic dynamics of a network of neurons possessing two stable states ("on" and "off" states) is studied. The fraction of on neurons existing at t = 0 remains large for an extended interval, and then abruptly falls. The distribution of the lengths of the interval is scale invariant in the following sense: The ratio (k root of (mu(k))/m, with m and mu(k) being the mean and the kth central moment, respectively, is invariant under scale transformations of m and mu(k). In the special case k = 2, this gives Weber's law, a hallmark of cognitive timing.

Animals↗
PubMed2001

Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin.

BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin, which is a critical cofactor for NO synthase (NOS). In addition, previous literature suggests that inactivation of NO(*) by increased vascular production superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states. We sought to determine whether these 2 seemingly disparate mechanisms were related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent relaxation while having no effect in vessels from control mice. Treatment of normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*-) production, seemingly from eNOS, because this effect was absent in vessels lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-) with NO(*) but also through interactions between peroxynitrite and tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase.

Acetylcholine↗
PubMed2001

Collision-induced dissociation of ring-opened cyclic depsipeptides with a guanidino group by electrospray ionization/ion trap mass spectrometry.

The characteristics shown in the electrospray ionization/ion trap mass spectra of ring-opened LI-F antibiotics (cyclic depsihexapeptides with a 15-guanidino-3-hydroxypentadecanoic group as a side-chain) were examined. Collision-induced dissociation (CID) MS of protonated molecules of the depsipeptides produced many fragment ions. Most of these fragment ions contained information for determining the amino acid sequences of antifungal antibiotics. The fragment ions were classified into six groups (b(n'), B(n'), B'(n'), beta(n'), y(n) and Y(n)). According to MS(3) spectra, the B(n'), B'(n) and beta(n) ions can be considered to be derived with a cleavage at each CO--NH in the peptide bonds of [MH--NH(3)](+),[MH--NH(3)--OH](+) and [MH--NH(3)--2H(2)O](+), respectively, in ion trap MS. Losses of NH(3) and H(2)O from the amino acid residues of the depsipeptides in ion trap MS are likely to be smaller than those from the side-chain. The measurements with electrospray ionization (ESI)/ion trap MS of depsipeptides with a side chain containing polar groups may provide useful information for structural determination.

Anti-Bacterial Agents↗
PubMed2001

Noise-tolerant stimulus discrimination by synchronization with depressing synapses.

Some synapses between cortical pyramidal neurons exhibit a rapid depression of excitatory postsynaptic potentials for successive presynaptic spikes. Since depressing synapses do not transmit information on sustained presynaptic firing rates, it has been speculated that they are favorable for temporal coding. In this paper. we study the dynamical effects of depressing synapses on stimulus-induced transient synchronization in a simple network of inhibitory interneurons and excitatory neurons, assuming that the recurrent excitation is mediated by depressing synapses. This synchronization occurs in a temporal pattern which depends on a given stimulus. Since the presence of noise is always a potential hazard in temporal coding, we investigate the extent to which noise in stimuli influences the synchronization phenomena. It is demonstrated that depressing synapses greatly contribute to suppressing the influences of noise on the stimulus-specific temporal patterns of synchronous firing. The timing-based Hebbian learning revealed by physiological experiments is shown to stabilize the temporal patterns in cooperation with synaptic depression. Thus, the times at which synchronous firing occurs provides a reliable information representation in the presence of synaptic depression.

Action Potentials↗
PubMed2001

A possible functional organization of the corticostriatal input within the weakly-correlated striatal activity: a modeling study.

Recently, it was reported in an in vivo study that pairs of the striatal projection neurons (medium-sized spiny neurons) of the basal ganglia show asynchronous spiking within weakly-correlated subthreshold depolarized states. In this computational study, we investigate a possible functional organization of corticostriatal inputs that accounts for the experimental observations within known anatomical and physiological constraints. In a pair of medium-sized spiny neurons, a small fraction of corticostriatal fibers is common to both neurons. To explain the weak correlations in sub- and supra-threshold activities of the neuron pair, we postulate that the two input channels, common or specific to the individual neurons, have distinct functional roles. The common input channel delivers random spike trains and is primarily responsible for the initiation and maintenance of the depolarized states. In contrast, the input through the neuron-specific channels elicit postsynaptic spikes by delivering intermittently-synchronized spikes. The results of this model were compared with those derived from a newly-performed analysis of the previous double-intracellular recording data. We show that the behavior of this model agrees qualitatively and quantitatively with that of the medium-sized spiny neurons observed in the experiments in a certain range of the coincident time window.

Action Potentials↗
PubMed2001

Cytotoxic flavonoids with isoprenoid groups from Morus mongolica.

A new pyranoflavanone, sanggenol L (1), a Diels-Alder type adduct regarded as a cycloaddition product of a dehydrogeranylflavanone and a prenylchalcone, sanggenol M (2), along with four new 2-arylbenzofurans with isoprenoid units, mulberrofurans W-Z (3-6), were isolated together with 10 known flavonoids from Chinese Morus mongolica. The structures of these novel compounds were elucidated by spectroscopic methods. All flavanones investigated here showed higher cytotoxicity against human oral tumor cell lines (HSC-2 and HSG) than against normal human gingival fibroblasts (HGF). Among them, the cytotoxicity of compound 2 and the Diels-Alder type flavanone sanggenon C (7) isolated from Morus cathayana were the most potent. On the other hand, seven 2-arylbenzofurans exhibited lower cytotoxicity and tumor specificity as compared with flavanones.

Antineoplastic Agents↗
PubMed2001

Benzophenones and xanthones with isoprenoid groups from Cudrania cochinchinensis.

Four new benzophenones with two isoprenoid groups, cudraphenones A-D (1-4), and three new xanthones also with two isoprenoid units, cudraxanthones P-R (5-7), were isolated from the roots of Cudraniacochinchinensis, together with 19 known phenolic compounds. The structures of the new compounds were elucidated by spectroscopic methods. Some compounds exhibited weak cytotoxicity against human oral squamous carcinoma cells (HSC-2) and normal human gingival fibroblasts (HGF). Among them, benzophenones 1-4 showed more potent cytotoxic activities against HSC-2 cells than against HGF cells. On the other hand, xanthones bearing isoprenoid groups showed much lower tumor specificity as compared with the benzophenones, except for geronthxanthone H and isoalvaxanthone. The presence of two sets of hydrophobic and hydrophilic groups in separate domains in each molecule might play a role in the mediation of tumor-specific action.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Neuronal communication within synchronous gamma oscillations.

The gamma-band oscillatory activity notably appears in the primary sensory and motor cortical areas. Because both sensory and motor responses are characterized by many static and dynamic variables, questions are raised regarding how cortical neurons manage to transmit analog information within the gammaoscillatory activity. Here, a possible way of communication among pyramidal neurons in the gamma frequency range is proposed based on the sampling theorem in communication theory.

Animals↗
PubMed2000

A model for neural representation of temporal duration.

To address how temporal duration is encoded in neural systems, we put forward a simple model for recurrent neural networks. Particular assumptions are only the following two: (1) neuronal bistability and; (2) environmental effects described by a heat bath. The results of Monte Carlo simulation show that population activity triggered at an initial time continues for a prolonged duration, followed by an abrupt self-termination. This time course seems highly suitable for neural representation of temporal duration. The time scale of this prolonged duration is much longer than the time scale of neuronal firing which is of the order of ms. The former time scale implies that of interval timing in cognition and behaviour. Thus, the model provides a possible explanation for a link between these two separated time scales. The Weber law, a hallmark of humans and animals' interval timing, can also be reproduced in our model.

Animals↗
PubMed2000

Accurate mass measurement of low molecular weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

We report the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the accurate measurement of mass of low molecular weight compounds (smaller than 1500 Da), a linear peptide, two types of cyclic depsipeptides, a polyhydroxy-macrocyclic lactone, and two prenylated flavonoids, with delayed extraction in the reflector mode. The performance of the MALDI-TOF instrument was less than those of fast atom bombardment and Fourier-transform ion cyclotron resonance mass spectrometry instruments and insufficient to give acceptable accuracy for literature reporting. Nevertheless, when combined with NMR spectrometry and/or amino acid analysis to give information on the numbers of carbon atoms and index of hydrogen deficiency, MALDI was useful for determination of the elemental composition of the low molecular weight compounds available in small quantities.

Angiotensin II↗
PubMed2000

Early effects of arterial hemodynamic conditions on human saphenous veins perfused ex vivo.

Exposure to the arterial hemodynamic environment is thought to be a potential trigger for the pathological remodeling of saphenous vein grafts. Using matched pairs of freshly isolated human saphenous vein, we analyzed the early effects of ex vivo hemodynamic conditions mimicking the venous (native) compared with arterial (graft) environment on the key components of vascular remodeling, ie, matrix metalloproteinase (MMP)-9 and MMP-2 and cell proliferation. Interestingly, we found that arterial conditions halved latent MMP-9 (50+/-11%, P=0.01) and MMP-2 (44+/-6%, P=0.005) levels relative to matched vein pairs maintained ex vivo under venous perfusion for up to 3 days. Immunostaining supported decreased MMP levels in the innermost area of arterially perfused veins. Either decreased synthesis or increased posttranslational processing may decrease MMP zymogen levels. Biosynthetic radiolabeling showed that arterial perfusion actually increased MMP-9 and MMP-2 production. When we then examined potential pathways for MMP zymogen processing, we found that arterial conditions did not affect the expression of MT-MMP-1, a cell-associated MMP activator, but that they significantly increased the levels of superoxide, another MMP activator, suggesting redox-dependent MMP processing. Additional experiments indicated that increased superoxide under arterial conditions was due to diminished scavenging by decreased extracellular superoxide dismutase. Arterial perfusion also stimulated cell proliferation (by 220% to 750%) in the majority of vein segments investigated. Our observations support the hypothesis that arterial hemodynamic conditions stimulate early vein graft remodeling. Furthermore, physiological arterial flow may work to prevent pathological remodeling, particularly the formation of intimal hyperplasia, through rapid inactivation of secreted MMPs and, possibly, through preferential stimulation of cell proliferation in the outer layers of the vein wall.

Arteries↗
PubMed2000

Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training.

The bioactivity of endothelium-derived nitric oxide (NO) reflects its rates of production and of inactivation by superoxide (O(2)(*-)), a reactive species dismutated by extracellular superoxide dismutase (ecSOD). We have now examined the complementary hypothesis, namely that NO modulates ecSOD expression. The NO donor DETA-NO increased ecSOD expression in a time- and dose-dependent manner in human aortic smooth muscle cells. This effect was prevented by the guanylate cyclase inhibitor ODQ and by the protein kinase G (PKG) inhibitor Rp-8-CPT-cGMP. Expression of ecSOD was also increased by 8-bromo-cGMP, but not by 8-bromo-cAMP. Interestingly, the effect of NO on ecSOD expression was prevented by inhibition of the MAP kinase p38 but not of the MAP kinase kinase p42/44, suggesting that NO modulates ecSOD expression via cGMP/PKG and p38MAP kinase-dependent pathways, but not through p42/44MAP kinase. In aortas from mice lacking the endothelial nitric oxide synthase (eNOS), ecSOD was reduced more than twofold compared to controls. Treadmill exercise training increased eNOS and ecSOD expression in wild-type mice but had no effect on ecSOD expression in mice lacking eNOS, suggesting that this effect of exercise is meditated by endothelium-derived NO. Upregulation of ecSOD expression by NO may represent an important feed-forward mechanism whereby endothelial NO stimulates ecSOD expression in adjacent smooth muscle cells, thus preventing O(2)(*-)-mediated degradation of NO as it traverses between the two cell types.

Animals↗