Showing papers by "Kyoto University published in 1994"

CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1

Abstract: We have identified a novel gene containing CAG repeats and mapped it to chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD). In normal individuals the gene contains between 13 and 36 CAG repeats, whereas most of the clinically diagnosed patients and all of the affected members of a family with the clinical and pathological diagnosis of MJD show expansion of the repeat-number (from 68-79). Southern blot analyses and genomic cloning demonstrates the existence of related genes. These results raise the possibility that similar abnormalities in related genes may give rise to diseases similar to MJD.

Kodaira-Spencer theory of gravity and exact results for quantum string amplitudes

Abstract: We develop techniques to compute higher loop string amplitudes for twistedN=2 theories withĉ=3 (i.e. the critical case). An important ingredient is the discovery of an anomaly at every genus in decoupling of BRST trivial states, captured to all orders by a master anomaly equation. In a particular realization of theN=2 theories, the resulting string field theory is equivalent to a topological theory in six dimensions, the Kodaira-Spencer theory, which may be viewed as the closed string analog of the Chern-Simons theory. Using the mirror map this leads to computation of the ‘number’ of holomorphic curves of higher genus curves in Calabi-Yau manifolds. It is shown that topological amplitudes can also be reinterpreted as computing corrections to superpotential terms appearing in the effective 4d theory resulting from compactification of standard 10d superstrings on the correspondingN=2 theory. Relations withc=1 strings are also pointed out.

Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure.

Abstract: BACKGROUNDB-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure.METHODS AND RESULTSWe measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL...

False vacuum inflation with Einstein gravity

Abstract: We present a detailed investigation of chaotic inflation models which feature two scalar fields such that one field (the inflaton) rolls while the other is trapped in a false vacuum state. The false vacuum becomes unstable when the magnitude of the inflaton field falls below some critical value, and a first or second order transition to the true vacuum ensues. Particular attention is paid to the case termed ``hybrid inflation'' by Linde, where the false vacuum energy density dominates so that the phase transition signals the end of inflation. We focus mostly on the case of a second order transition, but treat also the first order case and discuss bubble production in that context for the first time. False-vacuum-dominated inflation is dramatically different from the usual true vacuum case, both in its cosmology and in its relation to particle physics. The spectral index of the adiabatic density perturbation originating during inflation can be indistinguishable from 1, or it can be up to ten percent or so higher. The energy scale at the end of inflation can be many orders of magnitude less than the value ${10}^{16}$ GeV, which is ususal in the true vacuum case. Reheating occurs promptly at the end of inflation. Cosmic strings or other topological defects are almost inevitably produced at the end of inflation, and if the inflationary energy scale is near its upper limit they contribute significantly to large scale structure formation and the cosmic microwave background anisotropy.Turning to particle physics, false vacuum inflaton occurs with the inflaton field far below the Planck scale and is therefore somewhat easier to implement in the context of supergravity than true vacuum chaotic inflation. The smallness of the inflaton mass compared with the inflationary Hubble parameter still presents a difficulty for generic supergravity theories. Remarkably, however, the difficulty can be avoided in a natural way for a class of supergravity models that follow from orbifold compactification of superstrings. This opens up the prospect of a truly realistic superstring-derived theory of inflation. One possibility, which we show to be viable at least in the context of global supersymmetry, is that the Peccei-Quinn symmetry is responsible for the false vacuum.

Generation of lymphohematopoietic cells from embryonic stem cells in culture

Abstract: An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9. This cell line does not express functional macrophage colony-stimulating factor (M-CSF). The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other than macrophages. Embryoid body formation or addition of exogenous growth factors was not required, and differentiation was highly reproducible even after the selection of ES cells with the antibiotic G418. Combined with the ability to genetically manipulate ES cells, this system will facilitate the study of molecular mechanisms involved in development and differentiation of hematopoietic cells.

The role of hydrated silica, titania, and alumina in inducing apatite on implants.

Abstract: Pure soluble silica prepared by a sol-gel method induced bone-like hydroxyapatite formation onto its surface when the silica was immersed in a simulated body fluid (SBF), whereas silica glass and quartz did not. This finding directly supports the hypothesis that hydrated silica plays an important role in biologically active hydroxyapatite formation on the surfaces of bioactive glasses and glass-ceramics, which leads to bone-bonding. Gel-derived titania is also a hydroxyapatite inducer because of its abundant TiOH groups. These results provide further insight into the unique osseointegration of titanium and its alloys. It is suspected that gel-derived titania develops an apatite layer by taking calcium and phosphate from the body fluid, thus producing bone-bonding. Although sufficient AlOH groups may remain in the alumina gel, they do not serve to initiate apatite generation when immersed in SBF. This phenomenon explains the fact that an intermediate fibrous tissue is usually found to separate the alumina implant from bone. One may infer that both abundant OH groups and negatively charged surfaces of gel-derived silica and titania are important for hydroxyapatite induction. material which possesses and/or develops both a negatively charged surface and abundant OH groups in a physiologically-related fluid is most likely to be an efficient apatite inducer. Such materials are suitable candidates to serve as bone-bonding biomaterials.

Calcium channel β-subunit binds to a conserved motif in the I-II cytoplasmic linker of the α1-subunit

Abstract: THE β-subunit is an integral component of purified voltage-sensitive Ca2+ channels1–3. Modulation of Ca2+ channel activity by the β-subunit, which includes significant increases in transmembrane current and/or changes in kinetics, is observed on coexpression of six α1-subunit genes with four β-subunit genes in all α1- β combinations tested4–12. Recent reports suggest that this regulation is not due to targeting of the α1-subunit to the plasma membrane but is probably a result of a conformational change induced by the β-subunit11,13. Here we report that the β-subunit binds to the cytoplasmic linker between repeats I and II of the dihydropyridine-sensitive α1-subunits from skeletal (α1S) and cardiac muscles (α1C-a), and also with the more distantly related neuronal α1A and ω-conotoxin GVIA-sensitive aα1B-subunits. Sequence analysis of the β-subunit binding site identifies a conserved motif (QQ-E--L-GY--WI---E) positioned 24 amino acids from the IS6 transmem-brane domain in each α1-subunit. Mutations within this motif reduce the stimulation of peak currents by the β-subunit and alter inactivation kinetics and voltage-dependence of activation. Conser-vation of the β-subunit binding motif in these functionally distinct calcium channels suggests a critical role for the I-II cytoplasmic linker of the α1-subunit in channel modulation by the β-subunit.

The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro.

Abstract: B7-2 is a recently discovered, second ligand for the CTLA-4/CD28, T cell signaling system. Using the GL-1 rat monoclonal antibody (mAb), we monitored expression of B7-2 on mouse leukocytes with an emphasis on dendritic cells. By cytofluorography, little or no B7-2 was detected on most cell types isolated from spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, expression of B7-2 could be upregulated in culture. In the case of epidermal and spleen dendritic cells, which become highly immunostimulatory for T cells during a short period of culture, the upregulation of B7-2 was dramatic and did not require added stimuli. Lipopolysaccharide did not upregulate B7-2 levels on dendritic cells, in contrast to macrophages and B cells. By indirect immunolabeling, the level of staining with GL-1 mAb exceeded that seen with rat mAbs to several other surface molecules including intercellular adhesion molecule 1, B7-1, CD44, and CD45, as well as new hamster mAbs to CD40, CD48, and B7-1/CD80. Of these accessory molecules, B7-2 was a major species that increased in culture, implying a key role for B7-2 in the functional maturation of dendritic cells. B7-2 was the main (> 90%) CTLA-4 ligand on mouse dendritic cells. When we applied GL-1 to tissue sections of a dozen different organs, clear-cut staining with B7-2 antigen was found in many. B7-2 staining was noted on liver Kupffer cells, interstitial cells of heart and lung, and profiles in the submucosa of the esophagus. B7-2 staining was minimal in the kidney and in the nonlymphoid regions of the gut, and was not observed at all in the brain. In the tongue, only rare dendritic cells in the oral epithelium were B7-2+, but reactive cells were scattered about the interstitial spaces of the muscle. In all lymphoid tissues, Gl-1 strongly stained certain distinct regions that are occupied by dendritic cells and by macrophages. For dendritic cells, these include the thymic medulla, splenic periarterial sheaths, and lymph node deep cortex; for macrophages, the B7-2-rich regions included the splenic marginal zone and lymph node subcapsular cortex. Splenic B7-2+ cells were accessible to labeling with GL-1 mAb given intravenously. Dendritic cell stimulation of T cells (DNA synthesis) during the mixed leukocyte reaction was significantly (35-65%) blocked by GL-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrostatic solitary waves (ESW) in the magnetotail: BEN wave forms observed by GEOTAIL

Abstract: Wave forms of BEN (Broadband Electrostatic Noise) in the geomagnetic tail were first detected by the Wave Form Capture reciever on the GEOTAIL spacecraft. The results show that most of the BEN in the plasma sheet boundary layer (PSBL) are not continuous broadband noise but are composed of a series of solitary pulses having a special form which we term 'Electrostatic Solitary Waves (ESW)'. A nonlinear BGK potential model is proposed as the generation mechanism for the ESW based upon a simple particle simulation which considers the highly nonlinear evolution of the electron beam instability. The wave forms produced by this simulation are very similar to those observed by GEOTAIL and suggest that the nonlinear dynamics of the electron beam play an essential role in the generation of ESW.

A Collective Fear of the Collective: Implications for Selves and Theories of Selves

Abstract: Drawing on recent analyses of the self in many cultures, the authors suggest that the cultural ideal of independence of the self from the collective has dominated European-American social psychological theorizing. As a consequence, the existence of considerable interdependence between the self and the collective has been relatively neglected in current conceptual analysis. The authors (a) argue that a group's cultural ideal of the relation between the self and the collective is pervasive because it is rooted in institutions, practices, and scripts, not just in ideas and values; (b) show how a given cultural ideal whether it is independence or interdependence, can shape the individual's experience and expression of the self; and (c) discuss how a comparative approach may enrich and expand current theory and research on the interdependence between the self and the collective.

The Low Energy Particle (LEP) Experiment onboard the GEOTAIL Satellite

Abstract: The low energy particle (LEP) instrument onboard GEOTAIL is designed to make comprehensive observations of plasma and energetic electrons and ions with fine temporal resolution in the terrestrial magnetosphere (mainly magnetotail) and in the interplanetary medium. It consists of three units of sensors (LEP-EA, LEP-SW and LEP-MS) and a common electronics (LEP-E). The Energy-per-charge Analyzers (EA) measure three-dimensional velocity distributions of electrons (with EA-e) and ions (with EA-i), simultaneously and separately, over the. energy-per-charge range of several eV/q to 43 keV/q. Emphasis in the EA design is laid on the large geometrical factor to measure tenuous plasma in the magnetotail with sufficient counting statistics in the high-time-resolution measurement. On the other hand, the Solar Wind ion analyzer (SW) has smaller geometrical factor, but fine angular and energy resolutions, to measure energy-per-charge spectra of the solar wind ions. In both EA and SW sensors, the complete three-dimensional velocity distributions can only be obtained in a period of four spins, while the velocity moments up to the third order are calculated onboard every spin period (nominally, 3 sec). The energetic-ion Mass Spectrometer (MS) can provide three-dimensional determinations of the ion composition. In this paper, we describe the instrumentation and present some examples of the inflight measurements.

Increased circulating cytokines in patients with myocarditis and cardiomyopathy.

Abstract: OBJECTIVES--To elucidate the potential role of cytokines in the pathogenesis of cardiomyopathy and myocarditis BACKGROUND--Experimental studies show that certain cytokines depress myocardial contractility and that tumour necrosis factor-alpha plays an important part in the pathogenesis of myocardial injury in animal models of viral and autoimmune myocarditis METHODS--Plasma interleukin 1-alpha, interleukin 1-beta, interleukin-2, interleukin-6, tumour necrosis factor-alpha, tumour necrosis factor-beta, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, macrophage colony stimulating factor, interferon-alpha and interferon-gamma were measured in 13 patients with acute myocarditis, 23 patients with dilated cardiomyopathy, 51 patients with hypertrophic cardiomyopathy, nine patients with acute myocardial infarction, 18 patients with angina pectoris, 12 patients with essential hypertension and 17 healthy controls RESULTS--Increased concentrations of cytokines were not detected in the controls In patients with acute myocarditis, interleukin 1-alpha was detected in 23% (mean (SD) 25 (11) pg/ml), tumour necrosis factor-alpha in 46% (61 (31) pg/ml), and macrophage colony stimulating factor was 25 (18) ng/ml (normal 19 (04)) In patients with dilated cardiomyopathy, tumour necrosis factor-alpha was detected in 35% (402 (555) pg/ml) In patients with hypertrophic cardiomyopathy, interleukin-2 was detectable in 14% (2318 (4738) pg/ml) and tumour necrosis factor-alpha ws detected in 20% (992 (1517) pg/ml) The concentration of macrophage colony stimulating factor was raised in patients with acute myocardial infarction Granulocyte colony stimulating factor was often increased in myocarditis, cardiomyopathies, acute myocardial infarction, and angina pectoris--suggesting activation of macrophages and/or endothelial cells--but this increase was not specific to these diseases Increased concentrations of cytokines were not found in patients with essential hypertension CONCLUSION--These results suggest that cytokines may play a part in the pathogenesis of myocardial injury in myocarditis and cardiomyopathies and that further studies to explore the potential pathogenetic role of cytokines in myocardial diseases may be warranted

Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite

Abstract: A potent immunosuppressive activity was found in the culture broth of the fungus Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin) suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction, but had no effect on the growth of human tumor cell lines. It also suppressed the appearance of plaque-forming cells in response to sheep red blood cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after intraperitoneal or oral administration. The metabolite was 10- to 100-fold more potent than cyclosporin A as an immunosuppressive agent of the immune response in vitro and in vivo, and appears to be a candidate for clinical application as a powerful immunosuppressant.

Observation of a spin gap in SrCu2O3 comprising Ssin-12 quasi-1D two-leg ladders.

Abstract: Magnetic properties of Sr${\mathrm{Cu}}_{2}$${\mathrm{O}}_{3}$ and ${\mathrm{Sr}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{5}$, containing two-leg and three-leg $S=\frac{1}{2}$ ladders made of antiferromagnetic Cu-O-Cu linear bonds, were investigated. The susceptibility of the two-leg ladder material, Sr${\mathrm{Cu}}_{2}$${\mathrm{O}}_{3}$, is characteristic of thermal excitation from a nonmagnetic ground state with a spin gap of about 420 K, while the susceptibility of ${\mathrm{Sr}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{5}$, containing three-leg ladders, reflects a gapless spin excitation spectrum. The temperature dependence of the nuclear-spin lattice relaxation rate, $\frac{1}{{T}_{1}}$, of $^{63}\mathrm{Cu}$ NMR also indicates the existence of a spin gap only for Sr${\mathrm{Cu}}_{2}$${\mathrm{O}}_{3}$. The spin gap we observed for Sr${\mathrm{Cu}}_{2}$${\mathrm{O}}_{3}$ confirms a recent theoretical prediction for the magnetic behavior of spin = \textonehalf{} antiferromagnetically coupled Heisenberg chains.

Telomere-led premeiotic chromosome movement in fission yeast.

Abstract: The movement of chromosomes that precedes meiosis was observed in living cells of fission yeast by fluorescence microscopy. Further analysis by in situ hybridization revealed that the telomeres remain clustered at the leading end of premeiotic chromosome movement, unlike mitotic chromosome movement in which the centromere leads. Once meiotic chromosome segregation starts, however, centromeres resume the leading position in chromosome movement, as they do in mitosis. Although the movement of the telomere first has not been observed before, the clustering of telomeres is reminiscent of the bouquet structure of meiotic-prophase chromosomes observed in higher eukaryotes, which suggests that telomeres perform specific functions required for premeiotic chromosomal events generally in eukaryotes.

Molecular diversity and functions of glutamate receptors

Abstract: RECEPTORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 MULTIPLICITY OF GLUTAMATE RECEPTORS .. . .. . .. . . . .... . .. . .. . . . 321 Gene Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 Alternative Splicing . . . ... . .. . . ... . . ... .. ... . .. .. . . . ... . . . . . . . . . .. .. . . 327 RNA Editing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 Heteromeric Formation . . . . . . . .. .. . . , ,. 331 Expression Pattern . . . . .. . .. . . . .. ... . . . . . . . . .. . . . .. . .. . .. .. . . . .. . . . . . . 332 STRUCTURES OF GLUTAMATE RECEPTORS . . . . . . . . . . . . . . . . . . . . . . . . . . 333 Transmembrane Topology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 Glutamate-Binding Domain ... . . .. . . . . .. .. . . . . . . . . . .. . .. . .. . . . ..... ... 334 Channel Pore . . . . .. . .. . .. ... . . . . . . . . .. . . . . . . .. . ... . . .. .. . .. . .. .... . .. 336 Phosphorylation Site . . . . . . .. . .. . . . . .. .. . .. .. . .. . .. . . . .. . .. .. . ... .. . . . 337 Other Possible Regulatory Sites . .. . . . .. . . . . . . .. ... . . .. . . . . .. ... ... . .. . 338 IMPLICATIONS OF GLUTAMATE RECEPTOR DIVERSITY AND FUTURE PROSPECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338

Differential expression of five n-methyl-d-aspartate receptor subunit mrnas in the cerebellum of developing and adult rats

Abstract: Five N-methyl-D-aspartate (NMDA) receptor subunits have been identified thus far: NR1, NR2A, NR2B, NR2C, and NR2D. Here, we have analyzed the expression patterns of mRNAs for the NMDA receptor subunits in the developing and adult rats by in situ hybridization. The developmental changes of the expression patterns were most salient in the cerebellum. In the external granular layer, hybridization signals of mRNAs for NR1, NR2A, NR2B, and NR2C appeared by postnatal day 3, but no NR2D mRNA was expressed at any developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stages examined. The signals for the NR2A mRNA appeared in Purkinje cells and granule cells during the second postnatal week. The signals for the NR2B mRNA in granule cells were seen transiently during the first 2 weeks after birth. The signals for NR2C mRNA appeared in granule cells and glial cells during the second postnatal week. The signals for NR2D mRNA appeared transiently in Purkinje cells during the first 8 postnatal days; in adult rats, these were seen in stellate and Golgi cells. In the cerebellar nuclei, mRNAs for NR1, NR2A, NR2B, and NR2D were more or less expressed on postnatal day 0, while expression signals for the NR2C mRNA were first detected in postnatal day 14. Thus, the most conspicuous changes of expression patterns were observed in the cerebellar cortex during the first 2 weeks after birth, when development and maturation of the cerebellum proceed most rapidly.