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Biomedical subjects

H Okamoto

Publications and source records attributed to H Okamoto.

At least 55 records · Page 3Linked to original sources

N1m recovery from decline after exposure to noise with strong spectral contrasts.

Comb-filtered noise (CFN, derived from white noise by suppressing regularly spaced frequency regions) was presented for 3 s followed by two types of test stimuli. One test stimulus (SB) was comprised of spectra centered in the stop-band regions of the CFN and the other test stimulus (PB) of spectra centered in the band pass regions of the CFN. Magnetoencephalographically recorded N1m responses evoked by SB stimuli were decreased relative to the N1m response evoked by PB stimuli. This effect was maximal when the interval between the CFN and test stimuli was short (0.5 s) but was detected at intervals up to 2 s. The results suggest lateral inhibition in the auditory cortex and point to a decay of inhibition lasting on the order of seconds.

Acoustic Stimulation↗

Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac xenotransplantation.

BACKGROUND: CTLA4 immunoglobulin (CTLA4 Ig), which binds with high affinity to B7-1 and B7-2, interrupts T-cell activation by inhibiting the costimulatory signal. CTLA4Ig has been used to achieve antigen-specific tolerance induction in cardiac allografts. On the other hand, we have shown that short-term administration of deoxyspergualin (DSG) and daily cyclosporine (CsA) induces long-term survival of cardiac xenotransplants. We hypothesized that the combination therapy of DSG and adenovirus-mediated CTLA4IgG might induce long-term, survival or tolerance in cardiac xenotransplantation. OBJECTIVES: Syrian hamster hearts were transplanted heterotopically into Lewis rats. We compared the survival time and immunopathology of the following five groups: (1) no treatment; (2) DSG (5 mg/kg per day intramuscularly [IM], days -1 to +7) alone; (3) CsA (15 mg/kg per day IM, day 0 to rejection) plus DSG; (4) AdexLacZ (LacZ-adenovirus 1 x 10(9) (PFU intravenously [IV], day -7) plus DSG; and (5) AdexCTLA4IgG (CTLA4IgG-adenovirus 1 x 10(9) PFU IV, day -7) plus DSG. RESULTS: The survival times were: (1) no treatment, 3.7 days; (2) DSG alone, 12.4 days; (3) CyA plus DSG, >100 days; (4) AdexLacZ plus DSG, 11.0 days; and (5) AdexCTLA4IgG plus DSG, 23.6 days. Adenovirus-mediated CTLA4IgG therapy with DSG prolonged survival time significantly compared with DSG alone or AdexLacZ plus DSG, but CTLA4IgG therapy was not as effective as CsA. Immunopathology showed the deposition of C3 and IgM on the endothelium in the AdexCTLA4IgG plus DSG group. CONCLUSIONS: We showed that the effectiveness of adenovirus-mediated CTLA4IgG gene therapy in cardiac xenotransplantation in less than that of CsA. Combination therapy with inhibition of the B7/CD28 constimulatory signal and DSG administration might not be sufficient for long-term survival or tolerance in cardiac xenotransplantation.

Abatacept↗

Lateral inhibition and habituation of the human auditory cortex.

The goal of this study was to compare the lateral inhibition and the habituation in the human auditory cortex, two important physiological effects during auditory processing that can be reliably measured by means of magnetoencephalography when recording auditory evoked fields. Applying 40-Hz amplitude-modulated stimuli allowed us to record simultaneously the slow transient evoked and the steady-state fields and thus to characterize the lateral inhibition and the habituation effect in primary and non-primary auditory cortical structures. The main finding of the study is that the lateral inhibition effect of non-primary auditory areas as measured on the major component of the slow transient auditory evoked field (N1) is significantly stronger than the corresponding habituation effect. By contrast, this effect was not observed for the 40-Hz steady-state fields, characterizing the activation of the primary auditory cortex in humans. The results might be interpreted as (i) evidence that the inhibition mediated by lateral connections is stronger than the habituation of excitatory neurons in the non-primary auditory cortex and (ii) the processing hierarchy in the human auditory cortex is demonstrated by the different behaviour of lateral inhibition and habituation in primary and non-primary auditory cortical structures.

Acoustic Stimulation↗

Inhibitory influences of xanthine oxidase inhibitor and angiotensin I-converting enzyme inhibitor on multinucleated giant cell formation from monocytes by downregulation of adhesion molecules and purinergic receptors.

BACKGROUND: Allopurinol, a xanthine oxidase inhibitor, and captopril, an inhibitor of angiotensin I-converting enzyme, are widely used for hyperuricaemia and hypertension, respectively. There have been reported cases showing that these two agents are effective for the treatment of granulomatous diseases such as sarcoidosis, although the mode of action is not elucidated. OBJECTIVES: We examined the in vitro effects of these agents on the formation of multinucleated giant cells (MGC) from human monocytes by concanavalin A-stimulated mononuclear cell supernatants (conditioned medium). METHODS: We cultured monocytes with conditioned medium and each agent and compared the rate of MGC formation as well as the expression of adhesion molecules and P2X7 receptor, which are involved in MGC formation. RESULTS: The addition of 25 or 100 microg mL(-1) allopurinol or 0.125-1.0 microg mL(-1) captopril inhibited MGC formation. Monocytes treated with these agents exhibited less expression of intercellular adhesion molecular-1 (ICAM-1) than untreated monocytes. The susceptibility of monocytes cultured in conditioned medium for 24 h to 2'-and 3'-o-(4-benzoyl-benzoyl)adenosine triphosphate-mediated cytolysis was significantly lower in monocytes treated with these agents than in untreated monocytes. CONCLUSIONS: Allopurinol and captopril have a therapeutic effect on granulomatous disorders by a direct action on monocyte/macrophage lineage cells partly through downregulation of ICAM-1 and P2X7 receptor.

Allopurinol↗

Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients.

BACKGROUND: Regenerating gene (Reg) product, Reg, acts as an autocrine/paracrine growth factor for beta-cell regeneration. The presence of autoimmunity against REG may affect the operative of the regenerative mechanisms in beta cells of Type 1 and Type 2 diabetes patients. We screened sera from Type 1 and Type 2 diabetes subjects for anti-REG autoantibodies, searched for correlations in the general characteristics of the subjects with the presence of anti-REG autoimmunity, and tested the attenuation of REG-induced beta-cell proliferation by the autoanitibodies. MATERIAL AND METHODS: We examined the occurrence of anti-REG autoantibodies in patients' sera (265 Type 1, 368 Type 2 diabetes patients, and 75 unrelated control subjects) by Western blot analysis, and evaluated inhibitory effects of the sera on REG-stimulated beta-cell proliferation by a 5'-Bromo-2'-deoxyuridine (BrdU) incorporation assay in vitro. RESULTS: Anti-REG autoantibodies were found in 24.9% of Type 1, 14.9% of Type 2 and 2.7% of control subjects (P = 0.0004). There were significant differences between the autoantibody positive and negative groups in the duration of disease in the Type 1 subjects (P = 0.0035), and the age of onset in the Type 2 subjects (P = 0.0274). The patient sera containing anti-REG autoantibodies significantly attenuated the BrdU incorporation by REG (35.6 +/- 4.06% of the control), whereas the nondiabetic sera without anti-REG autoantibodies scarcely reduced the incorporation (88.8 +/- 5.10%). CONCLUSION: Anti-REG autoantibodies, which retard beta-cell proliferation in vitro, are found in some diabetic patients. Thus, autoimmunity to REG may be associated with the development/acceleration of diabetes in at least some patients.

Adolescent↗

Ultrafast optical switching to a metallic state by photoinduced mott transition in a halogen-bridged nickel-chain compound.

We demonstrate the ultrafast photoinduced Mott transition from a charge transfer insulator to a metal in a halogen-bridged Ni-chain compound by pump-probe reflection spectroscopy. Upon the irradiation of a 130-femtosecond laser pulse, the spectral weight of the gap transition is transferred to the inner-gap region. When the photoexcitation density exceeds 0.1/Ni site, the Drude-like high-reflection band appears in the infrared region, signaling the formation of a metallic state. The photogeneration of the metallic state and the subsequent recovery to the original gapped state occur within a few picoseconds.

Journal Article↗

Photoinduced phase transition in an organic radical crystal with room-temperature optical and magnetic bistability.

A phase control by photoirradiation is successfully achieved in a spin-Peierls system of the organic radical crystal, 1,3,5-trithia-2,4,6-triazapentalenyl (TTTA), which exhibits optical and magnetic bistability around room temperature with a large hysteresis loop. A nanosecond laser pulse is found to induce a transition from a diamagnetic low-temperature phase to a paramagnetic high-temperature phase both inside (296 K) and outside (11 K) the hysteresis loop. Comparison of the excitation energy dependence between transition efficiency and photoconductivity suggests that the photoinduced transition is driven by suppression of the spin-Peierls instability by the accumulation of photocarriers.

Journal Article↗

Nonlinear magneto-optical kerr rotation of an oxide superlattice with artificially broken symmetry.

Simultaneously broken time-reversal and spatial-inversion symmetries can be realized in the epitaxially grown oxide "tricolor" superlattices composed of three sequential kinds of perovskite layers including a ferromagnetic one (manganese oxide). As a generic feature of such a system, the magnetic-field-induced second-harmonic generation and the resultant Kerr rotation of second-harmonic light were demonstrated. The signal intensity probes the interface magnetization of the superlattice, where temperature variation is shown to be distinct from the bulk feature.

Journal Article↗

Oscillating Coulomb chain in a storage ring.

The dynamic behavior of a bunched one-dimensional crystalline beam is studied theoretically. It is shown that, owing to the existence of momentum dispersion, a Coulomb chain traveling in a storage ring performs a complex periodic oscillation whenever it is exposed to a longitudinal radio-frequency force. The equations of motion are derived to predict the oscillation pattern in an arbitrary lattice structure. The validity of the present theory is confirmed through multiparticle simulations. Various features of an oscillating string beam, such as the lattice-parameter dependence of the orbit, the stability, and critical line density, etc., are also discussed.

Journal Article↗

Novel optical and magnetic bistability and photoinduced transition in a one-dimensional halogen-bridged binuclear pt complex.

In iodine-bridged binuclear Pt compounds, R(4)[Pt(2)(pop)(4)I]nH(2)O and R(')(2)[Pt(2)(pop)(4)I]nH(2)O (pop=P(2)O5H2-2), electronic structures on the PtPtI chains have been controlled between a diamagnetic charge-density-wave (CDW) state and a paramagnetic charge-polarization (CP) state by modification of the counterions (R, R') located between chains. In the R=(C2H5)2NH+2 compound, a pressure-induced CP to CDW transition with a drastic color change is identified. This transition is accompanied by a large hysteresis loop within which photoinduced transition between CDW and CP can be driven by selecting the excitation photon energy.

Journal Article↗

Amelioration of hyperalgesia by kinin receptor antagonists or kininogen deficiency in chronic constriction nerve injury in rats.

OBJECTIVE: The present study was designed to examine the involvement of bradykinin in thermal and mechanical hyperalgesia induced by chronic constriction nerve injury (CCI) using B1 and B2 receptor antagonists and mutant kininogen-deficient rats. METHODS: Sprague-Dawley (SD) rats and Brown Norway (B/N-) rats given CCI treatment on day 0, were used as a model of neuropathic pain. Either a kinin B1 antagonist des-Arg9-[Leu8]-bradykinin or the receptor B2 antagonist HOE-140 was constantly infused into the left jugular vein of SD rats on days 15 to 22 after CCI. Vehicle-treated rats and sham-operated rats without nerve injury were also prepared as controls. In all rats, we observed pain behavior, and measured the latency period of paw withdrawal from the thermal stimuli and, with von Frey filaments, the mechanical pain threshold, before surgery and on days 14 and 22 after CCI. B/N-Katholiek rats, which congenitally lack plasma kininogen and release no kinin, were also tested for hyperalgesic parameters. Expression of kinin receptor mRNA in the dorsal root ganglia was detected by RT-PCR. RESULTS: Most of the rats (88%) showed some pain behavior, which was reduced to 67% by a B1 antagonist and to 57% by a B2 antagonist infused between days 15 to 22. Thermal hyperalgesia was significantly reduced from 7.25 +/- 0.41 sec (mean +/- SEM) to 8.36 +/- 0.41 sec in paw withdrawal latency on day 22 by a B1 antagonist and from 7.24 +/- 0.19 sec to 8.23 +/- 0.21 sec by a B2 antagonist (P < 0.05). Mechanical hyperalgesia was also ameliorated from 0.02 +/- 0.007 g force to 0.16 +/- 0.08 g force in pain threshold by a B1 antagonist and from 0.03 +/- 0.007 g force to 0.10 +/- 0.003 g force on day 22 by a B2 antagonist. Moreover, deficient B/N-Katholiek rats showed a low incidence of thermal and mechanical hyperalgesia on day 14. Expression of both B1 and B2 receptor mRNAs was detected in the lumbar dorsal ganglia ipsilateral to the site of the nerve injury. CONCLUSION: These data suggests that kinin were at least partly involved in yielding nociceptor hypersensitivity up to day 14 after CCI. Bradykinin and its B1 and B2 receptors were involved in the maintenance of hyperalgesia.

Animals↗

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↗

Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor.

The present study was undertaken to examine the effects of the antidepressant, amitriptyline, and brain-derived neurotrophic factor (BDNF) on activator protein-1 (AP-1) DNA binding activity in the rat brain. Acute administration of amitriptyline (5 or 10 mg/kg) initially increased but then decreased AP-1 DNA binding activity in the rat frontal cortex and hippocampus. Chronic administration of amitriptyline (5 or 10 mg/kg, once daily for 3 weeks) initially decreased AP-1 DNA binding activity but ultimately resulted in its persistent elevation in the rat frontal cortex. In contrast, the chronic administration of amitriptyline did not affect the low activity of AP-1 DNA binding in the hippocampus. However, chronic administration of amitriptyline (10 mg/kg, once daily for 3 weeks) significantly increased BDNF protein levels in the hippocampus (by 26.9%) and frontal cortex (by 24.6%). Direct infusion of BDNF (1 microg) into the hippocampal dentate gyrus significantly increased hippocampal AP-1 DNA binding activity. These results suggest that AP-1 transcription factor may be modulated by BDNF and that it may be an important target for the action of antidepressants.

Amitriptyline↗

Receptor signaling mechanisms underlying muscarinic agonist-evoked contraction in guinea-pig ileal longitudinal smooth muscle.

1 In guinea-pig ileal longitudinal muscle, muscarinic partial agonists, 4-(N-[3-chlorophenyl]-carbomoyloxy)-2-butynyl-trimethylammonium (McN-A343) and pilocarpine, each produced parallel increases in tension and cytosolic Ca(2+) concentration ([Ca(2+)]c) with a higher EC(50) than that of the full agonist carbachol. The maximum response of [Ca(2+)]c or tension was not much different among the three agonists. The Ca(2+) channel blocker nicardipine markedly inhibited the effects of all three agonists 2 The contractile response to any agonist was antagonized in a competitive manner by M(2) receptor selective antagonists (N,N'-bis[6-[[(2-methoyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride and 11-[[2-[(diethlamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4] benzodiazepine-6-one), and the apparent order of M(2) antagonist sensitivity was McN-A343>pilocarpine>carbachol. M(3) receptor selective antagonists, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide and darifenacin, both severely depressed the maximum response for McN-A343, while darifenacin had a similar action in the case of pilocarpine. Both M(3) antagonists behaved in a competitive manner in the case of the carbachol response. 3 McN-A343 failed to release Ca(2+) from the intracellular stores, and the Ca(2+)-releasing action of pilocarpine was very weak compared with that of carbachol. All three agonists were capable of increasing Ca(2+) sensitivity of the contractile proteins. 4 McN-A343 rarely produced membrane depolarization, but always accelerated electrical spike discharge. Pilocarpine effect was more often accompanied by membrane depolarization, as was usually seen using carbachol. 5 The results suggest that muscarinic agonist-evoked contractions result primarily from the integration of Ca(2+) entry associated with the increased spike discharge and myofilaments Ca(2+) sensitization, and that Ca(2+) store release may contribute to the contraction indirectly via potentiation of the electrical membrane responses. They may also support the idea that an interaction of M(2) and M(3) receptors plays a crucial role in mediating the contraction response.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗