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Biomedical subjects

H Tanaka

Publications and source records attributed to H Tanaka.

At least 253 records · Page 14Linked to original sources

Physicochemical and immunological characterization of hepatitis B virus envelope particles exclusively consisting of the entire L (pre-S1 + pre-S2 + S) protein.

The hepatitis B virus (HBV) envelope (env) protein is composed of three regions; the 108- or 119-residue pre-S1 region involved in the direct interaction with hepatocytes, the 55-residue pre-S2 region associated with the polymerized albumin-mediated interaction, and the major 226-residue S protein region. Thus, to improve the immunogenic potency of conventional HB vaccines, development of a new vaccine containing the entire pre-S1 region in addition to pre-S2 and S is desired. We previously reported the efficient production of the HBV env L (pre-S1 + pre-S2 + S) protein in the recombinant yeast cells [J Biol Chem 267 (1992) 1953]. In this study, the HBV env L protein produced as nano-particles in yeast has been purified and characterized. By equilibrium sedimentation, an average molecular weight of L particle was estimated to be approximately 6.4 x 10(6), indicating that about 110 molecules of L proteins are assembled into an L particle. By atomic force microscopy in a moist atmosphere, the L particles were observed as large spherical particles with a diameter of 50-500 nm. The L particles were stable on short-time heating at a high temperature and long-time storage at a low temperature but rather unstable on repeated freezing and thawing and treatment with dithiothreitol. When immunized in mice, L particles elicited efficiently and simultaneously the anti-S, anti-pre-S2, and anti-pre-S1 antibodies. The ED(50) values in mice for the anti-S and anti-pre-S2 antibodies were similar to those elicited by the M (pre-S2 + S) particles. Furthermore, the anti-pre-S1 rabbit antibodies were found to recognize various segments of the pre-S1 region, including the pre-S1 (21-47) segment. These results show the high ability of L particles to induce all antibodies against HBV env proteins, hence promising the future application of L particles for the next generation HB vaccine.

Animals↗

Doppler-shifted cyclotron absorption of electron Bernstein waves via N( parallel)-upshift in a Tokamak plasma.

Extraordinary (X) waves are perpendicularly injected for electron Bernstein (B) wave heating into an Ohmically heated plasma from the inboard side in the WT-3 tokamak. Measurements show that absorption does not take place at the electron cyclotron resonance layer nor the upper hybrid resonance layer, but does happen midway between them. This is consistent with the ray tracing prediction, i.e., the poloidal field and poloidal inhomogeneity of toroidal field lead the B waves to have a large parallel refractive index N( parallel) (>1), and the B waves are damped away via the Doppler-shifted cyclotron resonance.

Journal Article↗

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53.

Mutations in the p53 gene are the most common genetic alterations found in human tumours, and these mutations result in high levels of p53 protein in the tumour cells. Since the expression levels of wild-type p53 in nonmalignant tissue are usually much lower in contrast, the p53 protein is an attractive target for cancer immunotherapy. We tested p53 encoded HLA-A24 binding peptides for their capacity to elicit anti-tumour cytotoxic T lymphocytes (CTL) in vitro. These peptides were in murine p53-derived cytotoxic peptides, which were being presented to CTL by H-2K(d)and H-2K(b)molecules, because the HLA-A24 peptide binding motifs were similar to the H-2K(d)and H-2K(b). For CTL induction, we used CD8(+)T lymphocytes from the peripheral blood mononuclear cells (PBMC) of healthy donors and the peptides from pulsed dendritic cells as antigen-presenting cells. We identified the peptide, p53-161 (AIYKQSQHM), which was capable of eliciting CTL lines that lysed tumour cells expressing HLA-A24 and p53. The effectors lysed C1RA24 cells (p53(+), HLA-A*2402 transfectant), but not their parental cell lines C1R (p53(+), HLA-A,B null cell). These results strongly indicate that the CTL exerts cytotoxic activity in HLA-A24's restricted manner. The identification of this novel p53 epitope for CTL offers the possibility to design and develop specific immunotherapeutic approaches for treating tumours with p53 mutation in HLA-A24-positive patients.

Animals↗

Magnetic-field-induced superconductivity in a two-dimensional organic conductor.

The application of a sufficiently strong magnetic field to a superconductor will, in general, destroy the superconducting state. Two mechanisms are responsible for this. The first is the Zeeman effect, which breaks apart the paired electrons if they are in a spin-singlet (but not a spin-triplet) state. The second is the so-called 'orbital' effect, whereby the vortices penetrate into the superconductors and the energy gain due to the formation of the paired electrons is lost. For the case of layered, two-dimensional superconductors, such as the high-Tc copper oxides, the orbital effect is reduced when the applied magnetic field is parallel to the conducting layers. Here we report resistance and magnetic-torque experiments on single crystals of the quasi-two-dimensional organic conductor lambda-(BETS)2FeCl4, where BETS is bis(ethylenedithio)tetraselenafulvalene. We find that for magnetic fields applied exactly parallel to the conducting layers of the crystals, superconductivity is induced for fields above 17 T at a temperature of 0.1 K. The resulting phase diagram indicates that the transition temperature increases with magnetic field, that is, the superconducting state is further stabilized with magnetic field.

Journal Article↗

New micro-flow pumping system for liquid chromatography.

This paper deals with the development of practical approaches to a new liquid-delivery system for capillary liquid chromatography. Under different chromatographic conditions, the factors affecting liquid-delivery performance are theoretically described, and the new liquid-delivery system without any splitter is evaluated with its flow-rate accuracy and precision using a variety of solvents. The experimental results demonstrate that the liquid-delivery system is capable of generating accurate, reproducible and conditions-independent micro- and nano-flows.

Chromatography, High Pressure Liquid↗

Nested genomic structure of haploid germ cell specific haspin gene.

The haspin gene specifically expressed in haploid germ cells encodes a unique Ser/Thr protein kinase. We have cloned a mouse haspin genomic clone using cDNA as a probe. Sequencing data showed that the haspin gene was not interrupted by introns and was bordered by appropriate direct repeat. The transcription start site of the gene was not preceded by a TATA box. The whole transcription unit was located at an intron of integrin alphaM290 gene, and transcription direction of these two genes was different. Southern blotting analysis under stringent condition showed that haspin was a single gene. Phylogenetic analysis suggested that the diversion of haspin gene from other kinase family might be very ancient: the early stage of plant-fungus-animal split.

Animals↗

Actinohivin, a novel anti-HIV protein from an actinomycete that inhibits syncytium formation: isolation, characterization, and biological activities.

Blocking human immunodeficiency virus (HIV) entry into target cells is an important goal of HIV and acquired immune deficiency syndrome (AIDS) therapies. We have searched for anti-HIV substances from microorganisms using a syncytium formation assay system constructed with HeLa/CD4/Lac-Z and HeLa/T-env/Tat cells. We discovered a novel anti-HIV protein that inhibits syncytium formation, designated as actinohivin, from a cultured broth of a soil isolate, actinomycete strain K97-0003. ESI mass spectrometry of actinohivin isolated from the culture filtrate showed an ion with molecular mass of 12,520.3 Da. The amino acid sequence was determined by N-terminal Edman degradation of the intact protein and peptide fragments formed by endoproteinase digestions. Actinohivin consists of a 114-amino-acid chain that exhibits internal sequence triplication. Actinohivin inhibited both T-cell and macrophage tropic syncytium formation, with IC(50) values of 60 and 700 nM, respectively, and the cytopathic effect of HIV-1(IIIB) in MT-4 cells, with IC(50) value of 230 nM.

Actinomycetales↗

Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice.

We have recently shown that malignant tumours from the ovary and uterus expressed erythropoietin (Epo) and its receptor (EpoR), and that deprivation of Epo signal in tumour blocks induced death of malignant cells and capillary endothelial cells in vitro (Yasuda et al, submitted). These in vitro results prompted us to examine the effect of Epo-signal withdrawal on tumours in vivo. RT-PCR analysis demonstrated the expression of mRNAs for Epo and EpoR in the transplants of uterine and ovarian tumours in nude mice. Then we injected locally anti-Epo antibody or soluble form of EpoR into the transplants. At 12 h, 1, 7 or 14 days after the injection, all transplants were resected and examined macro- and microscopically. Tumour size was reduced in Epo signal-deprived transplants. Immunohistochemical examinations revealed destruction of Epo-responding malignant and capillary endothelial cells through apoptotic death. The degree of tumour regression correlated well with the dose and frequency of the injections. Control xenografts with saline injection or needle insertion showed well-developed tumour masses. This Epo response pathway will have profound implications for our understanding of the development and progression of malignant tumours and for the use of Epo-signal deprivation as an effective therapy.

Animals↗

Detection of Salmonella enteritidis in shell and liquid eggs using enrichment and plating.

Detection methods using various enrichment and plating media and immunoconcentration for Salmonella enteritidis in shell and liquid eggs were evaluated. For liquid egg samples naturally contaminated with S. enteritidis, pre-enrichment in 225 ml of buffered peptone water with cysteine followed by selective enrichment in 10 ml of tetrathionate broth was the superior, resulting in the detection of S. enteritidis in all samples on six of the seven types of selective agar substrate investigated. This enrichment procedure also enabled detection of S. enteritidis in most of artificially inoculated shell egg and pasteurized liquid egg samples.

Animals↗

Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K+ channel Kv1.5 current.

NIP-142 was shown to prolong atrial effective refractory period and to terminate atrial fibrillation and flutter in in vivo canine models. To obtain information on its antiarrhythmic action, we examined the effect of NIP-142 on cloned human cardiac K+ channel Kv1.5 (hKv1.5) currents stably expressed in a human cell line using whole-cell voltage clamp methods. NIP-142 inhibited the hKv1.5 current in a concentration-dependent and voltage-independent manner. The inhibition was larger at the end of depolarizing pulse than at the outward current peak. The IC50 for inhibition of the steady-state phase was 4.75 microM. A cross-over phenomenon was observed when current traces in the absence and presence of NIP-142 were superimposed. Inhibition of hKv1.5 current by NIP-142 was frequency-independent; changing the depolarizing pulse frequencies (0.1, 0.2, 1 Hz) and little effect on the degree of inhibition. NIP-142 decreased the maximal peak amplitude of kHv1.5 current at the first command pulse after 3 min rest in the presence of the drug. These results suggest that NIP-142 has inhibitory effects on the hKv 1.5 current through interaction with both open and closed states of the channel, which may underlie its antiarrhythmic activity in the atria.

Anti-Arrhythmia Agents↗

Preparation and catalytic performance of surfactant-manganese peroxidase-Mn(II) ternary complex in organic media.

A novel preparation method for surfactant-MnP-Mn(II) ternary complex utilizing water-in-oil emulsions has been developed. The surfactant-MnP complex was spectroscopically characterized, strongly suggesting that the heme environment of the surfactant-MnP complex in benzene is identical to that of native MnP in the aqueous buffer. o-Phenylenediamine oxidation catalyzed by the surfactant-MnP-Mn(II) ternary complex was performed in benzene. The ternary complex efficiently catalyzed the oxidation, and the complex was catalytically stable. Kinetic experiments revealed that the reaction mechanism was as follows: MnP is oxidized by H(2)O(2) and the oxidized intermediate catalyzes the oxidation of Mn(II) to Mn(III) and the latter, after complexed with malonate, readily oxidizes o-PDA inside the complex. Thus, the organic substrate o-PDA, but not Mn(III), shuttled between the surfactant-MnP-Mn(II) ternary complex and organic solvent.

Journal Article↗

Theory of spin-polarized optical potential.

We develop an approximation for the non-local spin-polarized optical potential theory for atoms in solids at intermediate and high energy. The present approximation for the optical potential builds on the GW-expression. We separate the RPA polarization propagator into a core electron and a valence electron part, and can then achieve a corresponding separation of the optical potential. For the valence electron optical potential we use a local density approximation because the charge density changes fairly slowly, whereas we use a non-local optical potential for the core electron part. Both of them depend on the spin-polarization. We apply this method to electron-Fe elastic scattering in solid, and discuss the results.

Journal Article↗

Age-related decreases in basal limb blood flow in humans: time course, determinants and habitual exercise effects.

Basal whole-limb blood flow is lower in older than in young healthy sedentary men due to a lower limb vascular conductance. In Study 1, we determined whether age-associated reductions in basal whole-leg (femoral artery) blood flow and vascular conductance are modulated by habitual physical activity by studying 89 healthy men aged 20-35 or 55-75 years (26 sedentary, 31 physically active and 32 endurance exercise trained). Femoral blood flow (duplex Doppler) and vascular conductance were approximately 20-30 % lower (P < 0.01) in the older men in all three physical activity groups. In Study 2, to determine the temporal pattern and relation to local metabolism and lean tissue mass of the age-associated reductions in femoral blood flow, we studied 142 healthy men aged 18-79 years. Femoral blood flow (r = -0.40) and vascular conductance (r = -0.51) were linearly and inversely related to age (both P < 0.001). Leg fat-free mass (r = -0.48) and estimated leg oxygen consumption (r = -0.49) declined with advancing age (both P < 0.001), and were strongly and positively related (r = 0.75; P < 0.001). The age-associated decline in femoral blood flow correlated with the corresponding reductions in leg fat-free mass and estimated leg oxygen consumption (both r = 0.47; P < 0.001). We concluded that: (1) basal whole-limb blood flow and vascular conductance decrease progressively with advancing age in healthy men; (2) reductions in both limb fat-free mass and oxygen consumption are related to the decline in whole-limb blood flow with age; and (3) habitual aerobic exercise does not appear to modulate the age-related reductions in basal limb blood flow and vascular conductance.

Adult↗

X-ray diffraction study on ordered, disordered and reconstituted intercellular lipid lamellar structure in stratum corneum.

From small angle X-ray diffraction for the stratum corneum of hairless mouse, it was obtained that in the normal stratum corneum, the 1st, 2nd and 3rd order diffraction peaks for the intercellular lipid lamellar structure appear at 13.8, 6.87 and 4.59 nm, respectively and also a broad hump for the 4th order reflection appears as observed by the previous researchers. In the damaged stratum corneum prepared by the treatment of sodium dodecyl sulfate, these small-angle diffraction peaks disappear and only the broad maxima remain around the 1st, 2nd and 3rd order diffraction peaks. These facts indicate that in the normal stratum the lamellar structure is ordered and in the damaged stratum corneum the lamellar structure is disordered. Furthermore, in the reconstituted lamellar structure obtained by immersing into the dilute suspension of the mixture of ceramide 3, cholesterol and stearic acid, the 1st, 2nd and 3rd order diffraction peaks reappear at 13.3, 6.67 and 4.44 nm, respectively. This fact indicates that the reorganization of the ordered lamellar structure takes place by adding the mixture to the damaged stratum corneum.

Animals↗

Structure of a full-length cDNA clone for the pro-alpha1(V/XI) collagen chain of red seabream.

The cDNA of type V/XI collagen alpha1 (rsCOL) chain has been isolated from cells established from eyed-period eggs of red seabream, Pagrus major, and sequenced. The amino acid sequence deduced from red seabream alpha1(V/XI) chain resembles that of type XI collagen alpha1 chain. On the other hand, tissue distribution of rsCOL resembles that of type V collagen based on RT-PCR analysis. This is the first report of the cloning of the full-length cDNA of type V/XI collagen alpha1 chain from fish.

Amino Acid Sequence↗

Reductive cross-coupling of 3-substituted delta 3-cephems with alkenyl halides in an Al/PbBr2/NiBr2(bpy) triplemetal redox system. Synthesis of 3-alkenyl-delta 3-cephems.

Synthesis of 3-alkenyl-delta 3-cephems was performed successfully by cross-coupling 3-(trifluoromethylsulfonyloxy or chloro)-delta 3-cephem with alkenyl halides, e.g., vinyl bromide, trans-1-bromo-1-propene, and trans-beta-bromostyrene in an Al/cat.PbBr2/cat.NiBr2(bpy)/NMP (or DMF) system. Reduction of 3-(trifluoromethylsulfonyloxy)-delta 3-cephem into norcephalosporin was also achieved by a similar reaction in the presence of 5 molar equiv of water. Scope and a plausible mechanism of the Al/Pb/Ni triplemetal-redox promoted reactions are discussed.

Anti-Bacterial Agents↗