Biomedical subjects

T Haruna

Publications and source records attributed to T Haruna.

12 recordsLinked to original sources

PubMed2005

Temperature-dependent Luttinger surfaces.

The Luttinger surface of an organic metal (TTF-TCNQ), possessing charge order and spin-charge separated band dispersions, is investigated using temperature-dependent angle-resolved photoemission spectroscopy. The Luttinger surface topology, obtained from momentum distribution curves, changes from quasi-2D (dimensional) to quasi-1D with temperature. The high temperature quasi-2D surface exhibits 4kF charge-density-wave (CDW) superstructure in the TCNQ derived holon band, in the absence of 2kF order. Decreasing temperature results in quasi-1D nested 2kF CDW order in the TCNQ spinon band and in the TTF surface. The results establish the link in momentum space between charge order and spin-charge separation in a Luttinger liquid.

Journal Article↗

PubMed2003

Resonant double excitation observed in the near-threshold evolution of the photoexcited F K alpha satellite intensity in NaF.

We present a precise measurement of the photoexcited F K alpha satellite intensity's evolution for NaF from [1s2p] double excitation threshold to saturation. A direct comparison between the observed evolution and the x-ray absorption spectrum was successfully made, and the contribution of multielectron transitions to the absorption spectrum was clearly resolved for the first time. A resonance-like feature observed in the near-threshold evolution is attributed to the [1s2p]3p(2) resonant double excitation as confirmed by calculations.

Journal Article↗

PubMed2001

Characterization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus.

Numerous mutations in KCNQ1, a gene encoding the alpha -subunit of cardiac delayed rectifier potassium channels, have been found in long QT syndrome (LQTS). Among them, several mutations in the C terminus have been shown to cause autosomal recessive or subclinical autosomal dominant LQTS. Here, we report a heterozygous mutation, T587M, which is also in the KCNQ1 C-terminal domain. The same mutation was found in three independent probands that were clearly symptomatic with family history of cardiac sudden death. Functional assay using a heterologous expression system with a mammalian cell line (COS7 cells) revealed that the mutant displayed neither functional channels when expressed alone nor dominant-negative effect when co-expressed with wild-type (WT) KCNQ1. To examine the cellular trafficking of KCNQ1, green fluorescent protein (GFP) was tagged to the cytoplasmic C terminus of WT or mutant KCNQ1. This procedure did not affect the essential properties of expressed WT KCNQ1 channels. On confocal microscopic images, GFP-tagged WT KCNQ1 showed a plasma membrane fluorescence pattern, whereas the GFP-tagged mutant showed a perinuclear fluorescence pattern. Co-expression of the mutant with GFP-tagged WT KCNQ1 did not influence its normal cellular transport. Therefore, the T587M mutant cannot traffic to the plasma membrane and may form no subunit assembly with WT KCNQ1. These findings provide a novel molecular basis for the clinical finding that this C-terminal mutation produced a severe form of RWS-type LQTS.

Adolescent↗

PubMed2001

Disopyramide and its metabolite enhance insulin release from clonal pancreatic beta-cells by blocking K(ATP) channels.

In an insulin-secreting pancreatic beta-cell line (MIN6), insulin release was caused by disopyramide, an antiarrhythmic drug with Na-channel blocking action, and its main metabolite mono-isopropyl disopyramide (MIP). Insulin secretion, measured as immunoreactive insulin (IRI), was accelerated to 265.7% of the control by disopyramide and to 184.4% by MIP, with half-effective concentrations (EC50) of 30.9 +/- 1.5 microM and 92.4 +/- 2.2 microM. We tested the possibility that these drugs induce insulin release by inhibiting ATP-sensitive K+ (K(ATP)) channels of MIN6 cells. In the cell-attached or ATP-free inside-out mode with patch membranes on MIN6 cells, K-selective channels were recorded with unitary conductance of 70.5 +/- 3.5 pS (150 mM external K+ ions at room temperature). The channels were concluded to be MIN6-K(ATP) channels because they were closed by extracellular high glucose (11.0 mM) or glibenclamide (200 nM) and were reversibly activated by diazoxide (50 microM). In the inside-out patch mode, they were inhibited by micromolar ATP. In both cell-attached and insideout mode, disopyramide and MIP inhibited single MIN6-K(ATP) channels. In the inside-out mode, they produced a dose-dependent inhibition of channel activity: the half-blocking concentrations (IC50) were 4.8 +/- 0.2 microM for disopyramide and 40.4 +/- 3.1 microM for MIP. It was therefore concluded that both agents exert insulinotrphic effect through the inhibition of membrane K(ATP) channels in MIN6 cells.

ATP-Binding Cassette Transporters↗

PubMed2000

Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes.

Sarcolemmal adenosine 5'-triphosphate-sensitive K+ channels (K(ATP)) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5-bisphosphate (PIP2). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the K(ATP) channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 microM) inhibited KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC50) fell from 62.0+/-2.7 to 30.3+/-5.5 microM]. In contrast, PIP2 attenuated the ATP sensitivity (IC50 343.6+/-54.4 microM) and restored Ca2+-induced inactivation of KATP channels (94.1+/-13.7% of the control current immediately before the Ca2+-induced inactivation). Pretreatment of the patch membrane with 1 microM L-PC, however, reduced the magnitude of the PIP2-induced recovery to 22.7+/-6.3% of the control (P<0.01 vs. 94.1+/-13.7% in the absence of L-PC). Conversely, after the PIP2-induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP2-mediated decrease in the ATP sensitivity (IC50 fell from 310+/-19.2 to 93.1+/-9.8 microM). Thus, interaction between L-PC and PIP2 in the plasma membrane appears to regulate K(ATP) channels.

Adenosine Triphosphate↗

PubMed1999

Intracisternal type A particle-mediated activation of the Notch4/int3 gene in a mouse mammary tumor: generation of truncated Notch4/int3 mRNAs by retroviral splicing events.

The int3 oncogene was discovered as a frequent target in mouse mammary tumor virus-induced mammary tumors and encodes the intracellular domain of a Notch4/int3 protein. In one spontaneous mammary tumor, no. 9, that developed in a BALB/c mouse, we have found an insertion of a 1.2-kb sequence, consisting of a 5' long terminal repeat and gag sequences of an intracisternal type A particle (IAP) as well as an extra copy of the Notch4/int3 genomic sequences containing exons 23 and 24, into the intron between exons 24 and 25 of the Notch4/int3 gene. In this tumor, unique splicing events between the IAP and the Notch4/int3 sequences generated two types of IAP-Notch4/int3 fusion transcripts encoding two different portions of the intracellular domain of Notch4/int3 proteins: one with a RAM domain and the other without. Interestingly, these two proteins showed different subcellular localizations in a mouse mammary epithelial cell line, HC-11.

Alleles↗

PubMed1998

Functional communication between cardiac ATP-sensitive K+ channel and Na/K ATPase.

INTRODUCTION: Functional interaction between K(ATP) channel and Na/K ATPase was studied in single guinea pig ventricular myocytes because both membrane molecules are known to be involved in ischemic episodes. METHODS AND RESULTS: K(ATP) channel currents were recorded at 36 degrees C by using whole cell, cell-attached, inside-out, and open cell-attached modes of patch clamp techniques on enzymatically isolated ventricular myocytes. In the whole cell mode, ouabain (1 microM) reversibly inhibited the K(ATP) currents induced by metabolic stress (ATP-free pipette solution and 1 mM NaCN), but not those activated by cromakalim (100 microM), a K(ATP) channel opener. In the cell-attached mode, ouabain concentration dependently inhibited K(ATP) channel opening induced by metabolic suppression (5.5 mM 2-deoxyglucose and 1 mM CN-). Half-inhibition concentration for ouabain was 21.0 +/- 5.5 nM and the Hill coefficient was 0.8 +/- 0.1 (n = 26). However, ouabain did not have an effect on the channel activity induced by cromakalim (100 microM). In the inside-out mode, ouabain applied to the internal side of membrane did not affect the channel. In the open cell-attached mode made by preincubation with streptolysin-O (0.08 U/mL), the K(ATP) channels were not activated by the metabolic inhibitors but were by reducing extracellular ATP concentrations, because subsarcolemmal ATP concentration could be controlled through tiny membrane holes. The channels thus activated were not suppressed by ouabain. CONCLUSION: The inhibition of Na/K ATPase by ouabain appeared to block the K(ATP) channels by accumulating subsarcolemmal ATP caused by a decrease of the transition from ATP to ADP. In the presence of ischemic episodes, the administration of digitalis compounds may affect the opening of K(ATP) channels, which is primarily protective against the development of irreversible myocardial damage.

Adenosine Diphosphate↗

PubMed1997

Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant-negative Zeste-White 3 leads to elevated DE-cadherin in Drosophila clone 8 wing disc cells.

Drosophila genetic studies suggest that in the Wingless (Wg) signaling pathway, the segment polarity gene products, Dishevelled (Dsh), Zeste-white 3 (ZW-3), and Armadillo (Arm), work sequentially; wg and dsh negatively regulate zw-3, which in turn down-regulates arm. To biochemically analyze interactions between the Wg pathway and Drosophila E-cadherin (DE-cadherin) which bind to Arm, we overexpressed Dsh, ZW-3, and Arm, in the Drosophila wing disc cell line, clone 8, which responds to Wg signal. Dsh overexpression led to accumulation of Arm primarily in the cytosol and elevation of DE-cadherin at cell junctions. Overexpression of wild-type and dominant-negative forms of ZW-3 decreased and increased Arm levels, respectively, indicating that modulation in zw-3 activity negatively regulates Arm levels. Overexpression of an Arm mutant with an amino-terminal deletion elevated DE-cadherin levels, suggesting that Dsh-induced DE-cadherin elevation is caused by the Arm accumulation induced by Dsh. Moreover, the Dsh-, dominant-negative ZW-3-, and truncated Arm-induced accumulation of DE-cadherin protein was accompanied by a marked increase in the steady-state levels of DE-cadherin mRNA, suggesting that transcription of DE-cadherin is activated by Wg signaling. In addition, overexpression of DE-cadherin elevated Arm levels by stabilizing Arm at cell-cell junctions.

Adaptor Proteins, Signal Transducing↗

PubMed1994

[A case of minocycline-induced pneumonitis with bronchial asthma].

We report a case of minocycline-induced pneumonitis. A 30-year-old woman was treated with minocycline for mycoplasma pneumonia of the right upper lobe. About 15 days after starting treatment, she developed a productive cough, stridor, and dyspnea. The chest X-ray film showed pulmonary infiltration in the left middle lung field. Based on the clinical history and the detection of eosinophilia in the bronchoalveolar fluid, drug-induced pneumonitis was suspected. Treatment with minocycline was discontinued and prednisolone (20 mg/day) was started, after which her symptoms subsided and there was marked regression of the pulmonary infiltrates on chest X-ray films. The lymphocyte stimulation test for minocycline was negative, but the diagnosis was confirmed by a positive oral provocation test.

Adult↗

PubMed1992

Interaction of antisense DNA with nucleic acids/proteins.

In order to study interaction of various types of labeled antisense DNAs were prepared. Fluorescein and 2,2,6,6-tetramethypiperidine-N-oxyl were the label molecules, which were introduced to 5'-end of oligonucleotides and their analogs. Interactions of labeled antisense DNAs with nucleic acids or proteins such as HSA, HIG and TF, were studied by UV, fluorescence depolarization spectroscopy, and ESR spectroscopy. Hybrid formation of antisense DNAs with oligonucleotides in solution could be monitored by the increase in fluorescence anisotropy (r) and by intensity change in ESR spectra. When phosphorothioate type antisense molecules anchoring fluorescein (F-OPT) were mixed with proteins, r drastically increased, whereas ODN slightly increased. These results suggest that OPTs have much more affinity for proteins than ODNs.

Blood Proteins↗

PubMed1986

A novel FAD-protein that allows effective reduction of methyl viologen by NADH (NADH-methyl viologen reductase) from photosynthetic bacterium, Rhodospirillum rubrum: purification and characterization.

It was found that the cytoplasm of light-grown cells of Rhodospirillum rubrum could catalyze the reduction of methyl viologen (MV) (Em, 7 = -0.44 V) by NADH and NADPH. In the present study, the enzyme capable of catalyzing MV reduction by NADH (NADH-MV reductase) was purified 1,500-fold from an extract of cells with a yield of 4.4%. The purification procedure comprised (NH4)2SO4 fractionation, and chromatographies on Sepharose CL-6B, DEAE-Sepharose CL-6B, phenyl-Sepharose CL-4B, Blue-Cellulofine, and TSK-Gel G3000SW. Two NADPH-MV reductases were separated during the purification. The NADH-MV reductase obtained was nearly homogeneous, as judged on polyacrylamide gel electrophoresis both in the presence and absence of sodium dodecyl sulfate. The enzyme has a molecular weight of 220,000 and an isoelectric point of 4.8; it is composed of four subunits with a molecular weight of 57,000, and is bound with about 1 mol FAD/mol subunit. The activity is optimum at pH 8. The Km values for NADH and MV are 115 microM and 1.3 mM, respectively, with a molecular activity of 13,000 min-1. The activity was stimulated 2.4-fold in the presence of 20-100 mM ammonium ions. The enzyme also catalyzed the reduction of benzyl viologen, methylene blue and 2,6-dichlorophenol-indophenol (Em, 7 = -0.36, +0.011, and +0.217 V, respectively) at comparable rates. The ratios of the activity with NADH to that with NADPH were 80, 133, 41, and 5.5 with MV, benzyl viologen, methylene blue and 2,6-dichlorophenolindophenol, respectively. The enzyme was significantly stable in the presence of both 5mM 2-mercaptoethanol and 20% (w/v) glycerol. The activity was not appreciably influenced by the presence of 2 M urea, although the reagent caused dissociation to the subunits.

Chromatography↗

PubMedDate not supplied

Coordinate interaction between ATP-sensitive K+ channel and Na+, K+-ATPase modulates ischemic preconditioning.

BACKGROUND: We reported that digoxin abolishes the infarct size (IS)-limiting effect of ischemic preconditioning (IPC). Because ATP-sensitive K+ (KATP) channels are involved in IPC, we studied whether Na+,K+-ATPase and KATP channels functionally interact, thereby modulating IPC. METHODS AND RESULTS: Rabbits received 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. IPC was elicited by 5 minutes of occlusion followed by 10 minutes of reperfusion. The IS, expressed as a percentage of the area at risk, was 40.2+/-2.8% in control and 39.8+/-5.0% in digoxin pretreatment rabbits. Both IPC and pretreatment with cromakalim, a KATP channel opener, reduced IS to 11.8+/-1.8% and 13.4+/-2.6% (P<0. 05 versus control). Digoxin abolished the reduction in IS induced by IPC (33.5+/-3.3%), whereas it did not change that induced by cromakalim (18.8+/-3.0%). In patch-clamp experiments, digoxin was found to inhibit the opening of KATP channels in single ventricular myocytes in which ATP depletion had been induced by metabolic stress. In contrast, digoxin had little effect on the channel opening induced by cromakalim. Moreover, the inhibitory action of digoxin on channel activities was dependent on subsarcolemmal ATP concentration. CONCLUSIONS: The IS-limiting effect of IPC is modulated by an interaction between KATP channels and Na+,K+-ATPase through subsarcolemmal ATP.

Animals↗