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Biomedical subjects

M Isobe

Publications and source records attributed to M Isobe.

At least 19 recordsLinked to original sources

Biological activity of the functional epitope of ciguatoxin fragment AB on the neuroblastoma sodium channel in tissue culture.

It is well established that the targeted receptor for ciguatoxin (CTX) in mammalian tissues is the sodium channel, affecting the influx of sodium into cells and altering the action potential and function of the cell. Since the syntheses of fragments of CTX has become available, our focus has been on the receptor functions of the west sphere AB and east sphere JKLM fragments using the neuroblastoma cell assay, guinea pig atrium assay, and the membrane immunobead assay (MIA). The data presented here suggest that the west sphere AB of the ciguatoxin molecule is the active portion and is responsible for the activation of the sodium channels.

Animals↗

Altered expression of hepatocyte growth factor in cardiac allografts of nonhuman primates.

Hepatocyte growth factor (HGF) plays a critical role in transplant rejection. Herein we addressed whether HGF expression could be used for accurate and early diagnosis of acute and chronic rejection in cardiac transplantation. We used a heterotopic cardiac transplantation model using nonhuman primates (Macaca fuscata, n = 7). The grafts were harvested on days 1, 7, 22, 28, 40, 41, and 95 for histology and immunohistochemistry. Histopathologically, HGF was expressed in the spindle-shaped cells of the acutely rejecting myocardium. The expression of HGF was enhanced in both thickened intima and media of the coronary arteries. Altered HGF expression is a sensitive indicator for acute and chronic cardiac rejection.

Animals↗

Identification of zonal flows in a toroidal plasma.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

Journal Article↗

Orbital and Spin Chains in ZnV2O4.

Our powder inelastic neutron scattering data indicate that ZnV2O4 is a system of spin chains that are three-dimensionally tangled in the cubic phase above 50 K due to randomly occupied t(2g) orbitals of V3+ (3d(2)) ions. Below 50 K in the tetragonal phase, the chains become straight due to antiferro-orbital ordering. This is evidenced by the characteristic wave vector dependence of the magnetic structure factor that changes from symmetric to asymmetric at the cubic-to-tetragonal transition.

Journal Article↗

Sawtooth oscillation in current-carrying plasma in the large helical device.

Sawtooth oscillations have been observed in current-carrying helical plasmas by using electron-cyclotron-emission diagnostics in the Large Helical Device. The plasma current, which is driven by neutral beam injection, reduces the beta threshold of the sawtooth oscillation. When the central q value is increased due to the plasma current, the core region crashes, and, when it is decreased, the edge region crashes annularly. Observed rapid mixture of the plasma in the limited region suggests that these sawtooth crashes are reconnection phenomena. Unlike previous experiments, no precursor oscillation has been observed.

Journal Article↗

Successful ex vivo normothermic liver perfusion with purely artificial products using artificial blood.

We tried to make an ex vivo functioning liver with an artificial perfusate that consisted of artificial blood in the pig liver. A liver graft from a female pig weighing 20 kg was harvested in the usual manner. The perfusion solution consisted of artificial blood, L-15 medium, distilled water, bovine serum albumin, NaHCO3, NaOH, KCl, human regular insulin, 50% glucose solution, and dexamethasone. The isolated liver was perfused with this oxygenated perfusate through the portal vein at a rate of 300 ml/min for 9 hours. Seven livers were perfused for 9 hours in this system. Five of the livers showed mean oxygen consumption of over 8 ml-O2/min during perfusion. Histological findings showed that the hepatic architecture was almost completely preserved and numerous hepatocytes exhibited PAS-positive cytoplasmic glycogen deposits in these livers. These observations indicate that we have succeeded in developing an ex vivo functioning liver with an artificial perfusate employing artificial blood.

Animals↗

Coherent magnetic oscillation in the spin ladder system alpha(')- NaV2O5.

We report the first observation of coherent magnetic excitations in a spin ladder system NaV2O5 by using femtosecond time-domain spectroscopy. A pronounced coherent oscillation is observed at 127 cm(-1) (nearly twice the spin gap energy) and assigned to a two-magnon bound state, based on the temperature dependence of the intensity below the charge ordering phase transition at T(C) = 34 K. This mode can be observable only when circularly polarized light is used as a pump or a probe beam, suggesting that it corresponds to a spin-flip excitation from the singlet ground state. A phonon mode strongly coupled to the spin state is also found at 303 cm(-1).

Journal Article↗

Island dynamics in the large-helical-device plasmas.

In the Large Helical Device plasma discharges, the size of an externally imposed island with mode number ( n/m = 1/1) decreases substantially when the plasma is collisionless ( nu(*)< approximately 1) and the beta is finite ( > approximately 0.1%) at the island location. For the collisional plasmas with finite beta, on the other hand, the size of the island increases. However, there is a threshold in terms of the vacuum island size below which the island enlargement is not seen.

Journal Article↗

Protective and curative effects of topically applied CX-659S, a novel diaminouracil derivative, on chronic picryl chloride-induced contact hypersensitivity responses.

BACKGROUND: CX-659S, a newly discovered anti-inflammatory compound, exerts inhibitory effects against acute contact hypersensitivity responses (CHRs) induced by picryl chloride (PC), oxazolone and dinitrochlorobenzene. The murine model of chronic CHR induced by repeated application of PC is known to mimic many, if not all, events occurring within the lesional skin of patients with atopic dermatitis (AD). OBJECTIVES: To investigate the ability of CX-659S to inhibit PC-induced chronic CHR in mice. METHODS: The protective and curative effects of CX-659S were tested on PC-treated ears of BALB/c mice, and were compared with those of prednisolone. Effects were quantified by measurements of ear thickness, serum IgE and cytokine mRNA expression. RESULTS: Both protectively applied and curatively applied CX-659S significantly inhibited increases in ear thickness and total serum IgE. Inhibition was dose-dependent. Although protectively applied prednisolone showed similar activities to CX-659S against chronic CHR, curatively applied prednisolone did not affect the serum IgE level despite inhibiting increases in ear thickness and inflammatory cell infiltration. Consistent with these results, CX-659S reduced mRNA expression of interleukin (IL)-4 and IL-10 but not of interferon (IFN)-gamma, whereas prednisolone inhibited not only mRNA expression of IL-4 and IL-10 but also that of IFN-gamma in the ear lesion. In contrast to prednisolone, CX-659S did not show any side-effect such as atrophy, alopecia or telangiectasia. CONCLUSIONS: CX-659S is the first promising compound having inhibitory activities against chronic CHR accompanied by a diminishing effect on elevated serum IgE, without any other side-effect. Therefore, CX-659S may be a promising candidate for management of patients with recurring AD who require long-term therapy.

Administration, Topical↗

Expression of basic fibroblast growth factor and its receptor-1 in cardiac myxoma.

BACKGROUND: To clarify the significance of basic fibroblast growth factor (bFGF) in angiogenesis or proliferative activity in cardiac myxoma, the expression of bFGF and its receptor (FGFR-1) were immunohistochemically examined. METHODS: Formalin-embedded tissues of cardiac myxomas were obtained by surgical resection from 15 patients and analyzed by immunostaining of bFGF and FGFR-1. The microvessel density was measured in the 15 myxomas using platelet derived endothelial cell adhesion molecule-1. For evaluation of proliferative activity of the cardiac myxomas, proliferating cell nuclear antigen (PCNA) immunostaining was performed, and the PCNA labeling index was measured in each section. RESULTS: bFGF and FGFR-1 were observed in 73.3% and 67.7% of the myxomas, respectively. There was a close correlation between the expression of bFGF and FGFR-1. This co-expression was frequently observed in the myxoma cells around the microvessels appearing as a ring structure. Regarding possible relationships between the expression of bFGF or FGFR-1 and the clinicopathologic features, there were no parameters excluding the macroscopic type of myxoma. The microvessel density in the myxomas with bFGF or FGFR-1 expression was higher than that in myxomas without it. The PCNA labeling index in myxomas with bFGF expression was higher than that in myxomas without it, and the PCNA labeling index tended to be higher in myxomas with FGFR-1 expression than that in myxomas without it. CONCLUSIONS: bFGF and/or FGFR-1 was expressed in some of cardiac myxoma, and may be an important role for tumor angiogenesis and proliferative activity.

Aged↗

cis Element decoy against nuclear factor-kappaB attenuates development of experimental autoimmune myocarditis in rats.

Nuclear factor-kappaB (NFkappaB) plays a significant role in the coordinated transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NFkappaB in this process remains obscure. We examined the role of NFkappaB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFkappaB blockade with a decoy against the cis element of NFkappaB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFkappaB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harvested on day 21. Scrambled decoy was infused on day 0 (group SD0), 7 (group SD7), or 14 (group SD14) and served for control groups. The ratios of myocarditis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF0, 33+/-18% versus SD0, 53+/-14%; group NF7, 19+/-15% versus SD7, 50+/-16%; and group NF14, 34+/-10% versus SD14, 52+/-14%). Immunohistochemical and immunoblot analyses showed expression of ICAM-1, iNOS, IL-2, and TNFalpha in myocardium of scrambled decoy groups, and this expression was effectively suppressed by NFkappaB decoy treatment. Thus, we found that NFkappaB is a key regulator in the progression of EAM and that in vivo transfection of NFkappaB decoy reduces the severity of EAM.

Animals↗

Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone.

Cardiac involvement is an important prognostic factor in sarcoidosis, but reliable indicators of mortality risk in cardiac sarcoidosis are unstudied in a large number of patients. To determine the significant predictors of mortality and to assess the efficacy of corticosteroids, we analyzed clinical findings, treatment, and prognosis in 95 Japanese patients with cardiac sarcoidosis. Twenty of these 95 patients had cardiac sarcoidosis proven by autopsy; none of these patients had received corticosteroids. We assessed 12 clinical variables as possible predictors of mortality by Cox proportional hazards model in 75 steroid-treated patients. During the mean follow-up of 68 months, 29 patients (73%) died of congestive heart failure and 11 (27%) experienced sudden death. Kaplan-Meier survival curves showed 5-year survival rates of 75% in the steroid-treated patients and of 89% in patients with a left ventricular ejection fraction > or = 50%, whereas there was only 10% 5-year survival rate in autopsy subjects. There was no significant difference in survival curves of patients treated with a high initial dose (> 30 mg) and a low initial dose (> or = 30 mg) of prednisone. Multivariate analysis identified New York Heart Association functional class (hazard ratio 7.72 per class I increase, p = 0.0008), left ventricular end-diastolic diameter (hazard ratio 2.60/10 mm increase, p = 0.02), and sustained ventricular tachycardia (hazard ratio 7.20, p = 0.03) as independent predictors of mortality. In conclusion, the severity of heart failure was one of the most significant independent predictors of mortality for cardiac sarcoidosis. Starting corticosteroids before the occurrence of systolic dysfunction resulted in an excellent clinical outcome. A high initial dose of prednisone may not be essential for treatment of cardiac sarcoidosis.

Aged↗

Enhanced platelet sensitivity to prostacyclin in patients in an active stage of Takayasu arteritis.

Patients in an active stage of Takayasu arteritis are often complicated with thrombosis in the affected vessels. We investigated whether alteration of platelet sensitivity to prostacyclin is involved in platelet function in these patients. Twelve female patients in an active stage (48.3+/-11.8 years, mean+/-S.D.), diagnosed clinically by a persistently elevated erythrocyte sedimentation rate (>40 mm/h) with typical symptoms, along with 10 gender- and age-matched patients in an inactive stage and 12 control subjects were enrolled. Half-maximal concentration (EC(50)) for platelet aggregation to collagen was determined in the presence and absence of 1 nM iloprost, a stable prostacyclin analog. Sensitivity of platelets to prostacyclin was quantified by the ratio of EC(50) (R) in the presence of iloprost to that in its absence. Patients in an active stage exhibited enhanced platelet aggregation, as demonstrated by significantly lower EC(50) to collagen and increased plasma thromboxane B(2) concentration. However, R values in these patients were significantly higher (4.00+/-1.05; P<.001) than those in the inactive patients or controls (2.58+/-0.62 and 2.43+/-0.68, respectively), suggesting enhanced sensitivity to prostacyclin in patients with active disease. Plasma 6-keto-PGF1 alpha levels were lower in the active patients than those in other groups of subjects. We conclude that platelets in an active stage of TA may be sensitive not only to collagen but also to prostacyclin. The increase in sensitivity of the platelets to prostacyclin could be a compensatory mechanism against a decrease in the prostanoid production, presumably associated with endothelial dysfunction.

6-Ketoprostaglandin F1 alpha↗

Extensive investigations on oxidized amino acid residues in H(2)O(2)-treated Cu,Zn-SOd protein with LC-ESI-Q-TOF-MS, MS/MS for the determination of the copper-binding site.

The ESI (electrospray ionization)-Q-TOF (tandem quadrupole/orthogonal-acceleration time-of-flight) mass spectrometer combined with the nano-HPLC (high performance liquid chromatography) system was utilized to pinpoint the Cu-binding site in Cu,Zn-SOD (superoxide dismutase) protein. Cu,Zn-SOD was treated with hydrogen peroxide, intended to specifically oxidize histidine residues coordinated to the copper ion as a mass spectrometric probe. The oxidized Cu,Zn-SOD was then fragmented with the successive treatment of endoproteinase Asp-N and DTT (dithiothreitol). Separation of the peptide mixture with the nano-HPLC and the on-line ESI-Q-TOF MS analysis revealed that only two peptide fragments were oxidized to a significant extent. Further analyses of oxidized peptide fragments with LC-ESI-Q-TOF-MS/MS disclosed that three out of four Cu-coordinated histidine residues were specifically oxidized by action of a redox-active copper ion and hydrogen peroxide, demonstrating the copper-catalyzed oxidation of amino acid ligands could be a versatile tool for the mass spectrometric determination of the copper-binding site. In addition, proline and valine residues in the proximity of the Cu ion were found to be oxidized upon H(2)O(2) treatment.

Amino Acid Sequence↗

Bifurcations of a driven granular system under gravity.

The molecular dynamics study on the granular bifurcation in a simple model is presented. The model consists of hard disks, which undergo inelastic collisions; the system is under the uniform external gravity and is driven by the heat bath. The competition between the two effects, namely, the gravitational force and the heat bath, is carefully studied. We found that the system shows three phases, namely, the condensed phase, the locally fluidized phase, and the granular turbulent phase, upon increasing the external control parameter. We conclude that the transition from the condensed phase to the locally fluidized phase is distinguished by the existence of fluidized holes, and the transition from the locally fluidized phase to the granular turbulent phase is understood by the destabilization transition of the fluidized holes due to mutual interference.

Journal Article↗

"Devil's staircase"-type phase transition in NaV2O5 under high pressure.

The "devil's staircase"-type phase transition in the quarter-filled spin-ladder compound NaV2O5 has been discovered at low temperature and high pressure by synchrotron radiation x-ray diffraction. A large number of transitions are found to successively take place among higher-order commensurate phases with 2a x 2b x zc type superstructures. The observed temperature and pressure dependence of modulation wave number q(c), defined by 1/z, is well reproduced by the axial next nearest neighbor Ising model. The q(c) is suggested to reflect atomic displacements presumably coupled with charge ordering in this system.

Journal Article↗