Biomedical subjects

Y Tokunaga

Publications and source records attributed to Y Tokunaga.

At least 19 recordsLinked to original sources

PubMed2006

In-plane anisotropy of the electronic structure for the charge- and orbital-ordered state in half-doped manganite with layered structure.

We report on the in-plane anisotropy of the electronic response in the spin-, charge-, and orbital-ordered phase of a half-doped layered-structure manganite. The optical conductivity spectra for a single domain of Eu1/2Ca3/2MnO4 unambiguously show the anisotropic charge dynamics which well corresponds to the theoretical calculation: the optical conductivity with the polarization along the zigzag ferromagnetic chain direction exhibits a smaller gap and a larger intensity at lower energies than that of the perpendicular polarization mostly due to the charge and orbital ordering and the associated quantum interference effect.

Journal Article↗

PubMed2006

Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors.

Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway has been shown to be involved in the progression of human hepatocellular carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is poorly understood. Recently, we identified Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred) as a physiological inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found that the expression levels of Spred-1 and -2 in human HCC tissue were frequently decreased, comparing with those in adjacent non-tumorous tissue. Moreover, Spred expression levels in HCC tissue were inversely correlated with the incidence of tumor invasion and metastasis. Forced expression of Spred-1 inhibited HCC cell proliferation in vitro and in vivo, which was associated with reduced ERK activation. Spred-1 overexpression also reduced the secretion of matrix metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor invasion and metastasis. In addition, Spred-1 inhibited growth factor-mediated HCC cell motility. These data indicate that the reduction of Spred expression in HCC is one of the causes of the acquisition of malignant features. Thus, Spred could be not only a novel prognostic factor but also a new therapeutic target for human HCC.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Current oscillation and low-field colossal magnetoresistance effect in phase-separated manganites.

Current-induced switching from a metallic to an insulating state is observed in phase-separated states of (La(1-y)Pr(y))0.7Ca0.3MnO3 (y=0.7) and Nd(0.5)Ca(0.5)Mn(1-z)Cr(z)O3 (z=0.03) crystals. The application of magnetic fields to this current-induced insulating state causes a pronounced low-field negative magnetoresistance effect [rho(H)/rho(0)=10(-3) at H=1 kOe]. The application of a constant voltage also causes the breakdown of the Ohmic relation above a threshold voltage. At voltages higher than this threshold value, oscillations in currents are observed. This oscillation is well reproduced by a simple model of local switching of a percolative conduction path.

Journal Article↗

PubMed2005

NMR evidence for triple-q multipole structure in NpO2.

In order to elucidate the nature of the exotic ordered phase of NpO2 below T(0)=26 K, we have initiated the first 17O-NMR measurements on this system. From the 17O-NMR spectrum, the occurrence of two inequivalent oxygen sites has been confirmed below T0. It has also been shown that the characteristic features of the hyperfine interaction at the oxygen sites are well explained by invoking a hyperfine interaction with field-induced antiferromagnetic moments which appear as a result of the triple-q antiferroquadrupolar order. The NMR findings strongly support the occurrence of the longitudinal triple-q multipole structure in NpO2.

Journal Article↗

PubMed2005

[Pulmonary thromboembolism after thoracoscopic pulmonary wedge resection; report of a case].

We encountered a case of acute pulmonary embolism after lung cancer surgery. The case was a 64-year-old female. She was admitted to our hospital with an abnormal shadow on chest X-ray. There was a past history of hypopituitarism medicated with steroids. Chest computed tomography (CT) demonstrated ground glass attenuation shadow measuring 10 mm in the left upper lobe. She underwent left thoracoscopic pulmonary wedge resection due to bronchioloalveolar cell carcinoma. Postoperatively, the patient suddenly complained of chest pain and dyspnea the day after surgery. Chest CT showed left and right pulmonary arterial thromboembolism. Thrombolytic and anticoagulation therapy with urokinase and heparin sodium were immediately started. Venography demonstrated thrombus located in the vein of the bilateral lower leg region. We inserted an inferior vena cava filter to prevent aggravation of pulmonary embolism. After 11 days, CT showed completed thrombolysis in the bilateral pulmonary artery. The patient was discharged on the 25th postoperative day, and has been followed with anticoagulation therapy.

Acute Disease↗

PubMed2004

Imaging of percolative conduction paths and their breakdown in phase-separated (La1-yPry)0.7Ca0.3MnO3 with y=0.7.

Local magnetization and current distribution in (La(1-y)Pr(y))0.7Ca0.3MnO3 (y=0.7) crystals are studied by a magneto-optical (MO) imaging technique. MO images below 120 K visualize inhomogeneous magnetization and conduction paths that manifest the percolative conduction originated from the mesoscopic phase separation into ferromagnetic metals and antiferromagnetic insulators. Application of large amounts of current switches the current distribution from inhomogeneous to homogeneous concomitantly with a steep increase in resistivity. These phenomena are discussed in view of current induced collapse of the phase separation through a local heating.

Journal Article↗

PubMed2004

Novel phase separation and spin dynamics of lightly doped La2-xSr2CuO4 probed by La-nuclear quadrupole resonance.

We report novel magnetic properties in the slightly hole-doped Mott-insulator La(2-x)SrxCuO4 via the La-nuclear quadrupole resonance (NQR) measurements. At x=0.018, the antiferromagnetic (AFM) La-NQR spectrum affected by internal fields comes out as the temperature decreases below T(N) approximately 150 K, whereas the nonmagnetic one persists to be observed down to a temperature T(f) approximately 20 K at which the nuclear-relaxation rate has a pronounced peak. This demonstrates that the phase separation of nonmagnetic and AFM phases occurs between T(f) and T(N). The novel phase separation is suggested as due to the partial destruction of the AFM phase caused by mobile holes via the formation of an extended spin-singlet state between Cu-derived spins and hole spins.

Journal Article↗

PubMed2004

Expression of occludin in human rectal carcinoid tumours as a possible marker for glandular differentiation.

AIMS: To examine whether or not the tight junction-associated transmembrane protein occludin is expressed in rosette or gland-like structures in human rectal carcinoid tumours. The tight junction is crucial for the formation and maintenance of organized tubular structures in glandular epithelia. Previous studies have reported the presence of glandular structures in carcinoid tumours, though they are not believed to arise from glandular epithelium. METHODS AND RESULTS: The expression profiles of occludin in 40 carcinoid tumours were examined immunohistochemically, using an anti-occludin monoclonal antibody. In eight (20%) samples of typical carcinoid tumours, a small number of rosette-like tubular structures outlined by occludin were detected. CONCLUSIONS: Tight junction-associated molecules, including occludin, are thought to be one of the most characteristic structural markers of polarized glandular structures. The results of the present study provide supportive evidence that carcinoid tumour cells are capable of glandular differentiation.

Adult↗

PubMed2001

A magnetoencephalographic study on development of the somatosensory cortex in infants.

In order to examine the sensori-motor correlation in infants, we recorded the somatosensory evoked magnetic fields to tactile stimulation by using a 37-channel magnetoencephalograph. Twelve healthy infants were examined at palmar grasp stage and pincers grasp stage. Air-tapping stimulation of the right thumb was performed. Three distinct components (W1-3) emerged, W3, with a latency of approximately 100 ms, being the most prominent. As infants grew up, the correlation coefficient and the amplitude of the equivalent current dipole of W3 for the thumb increased. These developmental changes may be attributable to increases in the stability and reproducibility of the cortex in response to somesthetic inputs. Moreover, this change along with motor development supports the presence of a sensori-motor correlation in infants.

Aging↗

PubMed2001

New phase transition between partially and fully polarized quantum Hall states with charge and spin gaps at nu = 2/3.

The average electron spin polarization Rho of a two-dimensional electron gas confined in GaAs/GaAlAs multiple quantum wells was measured by NMR near the fractional quantum Hall state with filling factor nu = 2/3. Above this filling factor (2/3< or = nu < 0.85), a strong depolarization is observed corresponding to two spin flips per additional flux quantum. The most remarkable behavior of the polarization is observed at nu = 2/3, where a quantum phase transition from a partially polarized (Rho approximately 3/4) to a fully polarized (Rho = 1) state can be driven by increasing the ratio between the Zeeman and the Coulomb energy above a critical value eta(c) = Delta(Z)/Delta(C) = 0.0185.

Journal Article↗

PubMed2001

Nmr evidence for coexistence of superconductivity and ferromagnetic component in magnetic superconductor RuSr2YCu2O8: 99,101Ru and 63Cu NMR.

From Ru- and Cu-NMR studies, we present evidence for coexistence of superconductivity and ferromagnetism in a cuprate superconductor RuSr2YCu2O8 (RuY1212). The observation of a large enhancement of a radio-frequency field for the Ru-NMR signal at zero field reveals the existence of a ferromagnetic (FM) component in the ordered RuO2 plane below a Curie temperature of TM = 150 K. Just below the onset temperature of superconductivity T(onset)c = 45 K, a remarkable decrease of the nuclear spin-lattice relaxation rate 1/T1 was observed within the ordered RuO2 plane as well as the CuO2 plane, revealing that the superconducting gap coexists with the FM component in the RuO2 plane on a microscopic scale. In addition, from the observation of a sharp peak in 101(1/T1) at T(zero)c approximately 23 K where the resistivity becomes zero, we suggest that the motion of self-induced vortices originating from fluctuations of the FM component induces the resistivity between T(onset)c and T(zero)c in RuY1212.

Journal Article↗

PubMed2001

Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS).

We have newly synthesized osteotropic diclofenac with bisphosphonic moiety (DIC-BP) based on the concept of Osteotropic Drug Delivery System (ODDS) and investigated its potency of site-specific and controlled delivery of diclofenac to the bone in rats. After intravenous injection into rats, DIC-BP was predominantly distributed in the skeleton. DIC-BP once incorporated in the bone was gradually eliminated (t(1/2)=9.7 days), releasing diclofenac into the bone compartment. As a result, the bone concentration of regenerated diclofenac was apparently constant over 28 days. Furthermore, we evaluated the anti-inflammatory effects of DIC-BP compared with diclofenac (sodium salt) in adjuvant-induced arthritic rats. The mean effective doses (ED(50)) were 0.55 mg/kg and 1.3 mg/kg for daily oral administration of diclofenac and weekly intravenous injection of DIC-BP, respectively. Considering the frequency of medication of 17 times for diclofenac and 4 times for DIC-BP in the experimental period, ED(50) was corrected to 9.4 and 5.2 mg/kg (per experimental period) for diclofenac and DIC-BP, respectively. Moreover, DIC-BP exhibited no side effects of gastrointestinal damage, typical of non-steroidal anti-inflammatory drugs. Thus, ODDS of diclofenac shows promise as an approach for highly potent and non-toxic therapy of diclofenac, with less frequent medication.

Animals↗

PubMed2001

Antibacterial activity of bactenecin 5 fragments and their interaction with phospholipid membranes.

Bactenecin 5 (Bac 5) is an antibacterial 43mer peptide isolated from bovine neutrophils. It consists of an Arg-rich N-terminal region and successive repeats of Arg-Pro-Pro-Ile (or Phe). We synthesized Bac 5(1-23) and several related peptides to clarify the roles these regions play in antibacterial activity. An assay of antibacterial activity revealed that such activity requires the presence of Arg residues at or near the N-terminus, as well as a chain length exceeding 15 residues. None of the peptides exhibited haemolytic activity. Polyproline II-like CD curves were observed for most of the peptides. Measurements of the membrane perturbation and fusion indicated that the perturbation and fusogenic activities of the peptides were, generally, parallel to their antibacterial activities. Amino acid substitution in the repeating region had some effect on antibacterial activity.

Amino Acid Sequence↗

PubMed2001

Intracellular cytokine profile of CD14 positive cells in patients with hematologic malignancies and solid tumors during hematologic recovery phase after intensive chemotherapy designed to mobilize peripheral blood stem cells.

We studied intracellular cytokines in monocytes by flow cytometry from 28 patients with hematologic malignancies and solid tumors to analyze the role of monokines in the hematologic recovery phase for peripheral blood stem cell harvest. The patients were divided into three groups: the first group, A, had a documented infection; the second group, B, had fever of unknown origin; and the third group, C, was afebrile. We found an increase in intracellular IL-1alpha, IL-6, IL-8 and TNF-alpha positive monocytes as CD14 positive gated cells cultured with lipopolysaccharide in all groups, but no increase was found with medium only when cultured for 4 h. We also found an increase in intracellular IL-1a, IL-6, IL-8 and TNF-alpha positive monocytes cultured with autologous serum for 4 h, but only in group A. The rate of intracellular cytokine positive cells was higher in monocytes cultured with only autologous serum from group A patients compared to those cells from the other groups; the data concerning IL-1a, IL-6 and TNF-alpha reached statistical significance (P < 0.05). However, increasing intracellular cytokine levels in the control group of patients exhibiting only infectious disease were observed. Thus, it appear that pro-inflammatory intracellular cytokine levels in monocytes are only related to microbial infections.

Adult↗

PubMed2001

Moyamoya syndrome with spherocytosis: effect of splenectomy on strokes.

A 3-year-old male patient with hereditary spherocytosis who developed moyamoya syndrome, presenting hemiplegia, and slurred speech is reported. Transient ischemic attacks occurred repeatedly with hemolytic crises. Magnetic resonance imaging and angiography revealed bilateral occlusion of the internal carotid and middle cerebral arteries with the formation of moyamoya vessels and multiple infarctions in the basal ganglia. Although splenectomy can increase the risk of stroke, no stroke occurred after splenectomy. On aspirin and dipyridamole therapy the patient has been free of neurologic deficits and progression of the vasculopathy for 5 years. This rare observation suggests that anemic hypoxia more greatly contributes to the progression of moyamoya syndrome than postsplenectomy thrombocytosis or reduced deformability of spherocytes.

Aspirin↗

PubMed2001

Relationship between physicochemical and osteotropic properties of bisphosphonic derivatives: rational design for osteotropic drug delivery system (ODDS).

PURPOSE: The objective of this investigation is to develop a rational design of Osteotropic Drug Delivery System (ODDS), which we have proposed as a novel method for drug delivery to the skeleton via bisphosphonic prodrug, based on the relationship between physicochemical and pharmacokinetic properties of bisphosphonates. METHODS: The theoretical octanol/water partition coefficients (clog P) of 13 bisphosphonates were calculated by computer software, CLOGP ver. 3.05 (Daylight C.I.S., Inc. Irvine, CA) and related to pharmacokinetic or osteotropic parameters after intravenous injection into rats. On the other hand, to optimize ODDS of diclofenac (DIC-BP), the effects of doses or infusion rates on the in vivo disposition were investigated in relation to solubility product value (Ksp) of DIC-BP-calcium complex. RESULTS: Clog P had good correlations with total plasma clearance, apparent distribution volume and the fraction dose delivered to the whole skeleton after bolus injection into rats (r = -0.868 approximately -0.914). The targetability of bisphosphonates to the skeleton was linearly decreased with an increase in clog P value and the more hydrophilic bisphosphonates were suitable for ODDS in bolus administration. On the other hand, DIC-BP, a relatively lipophilic bisphosphonate, was effectively and selectively delivered to the skeleton only when administered as a slow infusion to keep plasma concentration lower than that calculated from Ksp value where DIC-BP could precipitate with calcium in the plasma circulation. CONCLUSIONS: Our results suggest the possibility of a rational design of ODDS via bisphosphonic prodrugs, after consideration of compound lipophilicity and precipitability of bisphosphonate-calcium complex.

Algorithms↗

PubMed2001

Interaction of pleurocidin and its analogs with phospholipid membrane and their antibacterial activity.

A 25-mer cationic peptide pleurocidin, isolated from the winter flounder, has broad antibacterial activity. To clarify the structure-activity relationship, its properties and biological activity were examined. CD measurements showed that pleurocidin took an alpha-helical structure in the presence of DOPC/DOPG (3:1, anionic) vesicles. Very weak hemolytic activity of pleurocidin was observed and its antibacterial activity was moderate. Tryptophan fluorescence shift measurements showed that pleurocidin interacted weakly with a neutral phospholipid, but strongly with an acidic phospholipid. The peptide exhibited weak dye-leakage activity for DOPC (neutral) vesicles and moderate activity for acidic vesicles. From experiments on dye-leakage activity and membrane translocation of the peptide, it seemed likely that pleurocidin, like magainin 2, forms pores in the lipid membrane. A study of amino acid substitution in pleurocidin revealed that alpha-helicity, rather than hydrophobicity, affects the properties and activity of the peptide.

Animals↗

PubMed2001

Embryological consideration of drainage of the left testicular vein into the ipsilateral renal vein: analysis of cases of a double inferior vena cava.

The right gonadal vein (GV=testicular vein in men, ovarian vein in women) usually drains into the inferior vena cava (IVC) while the left gonadal vein drains into the left renal vein (RV). This anatomical difference induces relatively weak haemodynamics in the left testicular vein (TV) and is considered to be a cause of a left varicocele. In textbooks on embryology, it has been documented that bilateral supracardinal veins (=origin of right and left IVC) and the subcardinal sinus (=origin of RVs and GVs) symmetrically develop during early embryogenesis. However, persistence and regression of the right and left supracardinal veins, respectively, results in drainage of the left GV into the ipsilateral RV. A double IVC (DIVC) commonly originates from a failure of disappearance of the left supracardinal vein. Although there have been a considerable number of case reports on DIVC, little attention has been paid to the anatomy of the left GV in such cases. We report here an autopsy case, a 72-year-old Japanese man, with a DIVC. This case belongs to type BC of McClure and Butler's classification. In this case, it was observed that the right TV drained into the confluence of the right IVC with the ipsilateral RV, while the left TV drained into the left RV in spite of the presence of the left IVC. This case indicates that the embryonic anastomosis point between the subcardinal sinus and the supracardinal vein on the left side is different from that on the right side. Statistical analysis of many case reports of DIVC also suggests that the bilateral supracardinal veins tend to asymmetrically anastomose with the subcardinal sinus during embryogenesis. These data imply that drainage of the left GV into the ipsilateral RV leads to regression of the left supracardinal vein but also to asymmetrical anastomosis between the supracardinal veins and the subcardinal sinus.

Aged↗