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Showing papers by "Osaka University published in 1994"


Journal ArticleDOI
24 Mar 1994-Nature
TL;DR: It is concluded that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.
Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.

1,780 citations


Journal ArticleDOI
28 Jan 1994-Cell
TL;DR: Clinical Cancer Research is published monthly, one volume per year, by the American Association for Cancer Research, Inc.

1,290 citations


Journal ArticleDOI
23 Sep 1994-Science
TL;DR: The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops that have a distributed modular architecture resembling local expert architectures of computational learning models during sensorimotor learning.
Abstract: The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

1,257 citations


Journal ArticleDOI
01 Jun 1994-Immunity
TL;DR: It is suggested that CD40 is essential for T cell-dependent immunoglobulin class switching and germinal center formation, but not for in vivo Tcell-dependent IgM responses and T cell -independent antibody responses.

1,149 citations


Journal ArticleDOI
08 Apr 1994-Cell
TL;DR: The purification and cloning of APRF are reported and it is observed that p91 is not tyrosine phosphorylated in response to IL-6, and that selective activation of p91-related factors may explain the diversity of cellular responses to different cytokines.

997 citations


Journal ArticleDOI
TL;DR: The results indicate that T30 is mediated primarily by vagal reactivation, independent of sympathetic withdrawal, and is significantly smaller in athletes and significantly larger in patients with chronic heart failure than that in respective age-matched normal control subjects.

932 citations


Journal ArticleDOI
18 Mar 1994-Science
TL;DR: Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation, and infection with Mycobacterium bovis was more severe in IRf-1-/- mice than in wild-type mice.
Abstract: Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents Interferon (IFN)-gamma and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS) Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation Two adjacent IRF-1 response elements were identified in the iNOS promoter Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice Thus, IRF-1 is essential for iNOS activation in murine macrophages

851 citations


Journal ArticleDOI
TL;DR: A stromal cell line, PA6, was found to produce a soluble mediator, which was distinct from interleukin 7 (IL-7) and stem cell factor and supported the proliferation of a stromAL cell-dependent pre-B-cell clone, DW34.
Abstract: Generation and proliferation of early B-cell progenitors have been known to require stromal cell-derived molecules. A stromal cell line, PA6, was found to produce a soluble mediator, which was distinct from interleukin 7 (IL-7) and stem cell factor and supported the proliferation of a stromal cell-dependent pre-B-cell clone, DW34. A cDNA clone encoding this DW34 growth-stimulating factor was isolated by expression cloning. The nucleotide sequence contained a single substantial open reading frame of 267 nucleotides encoding an 89-amino acid polypeptide. The amino acid sequence of this cytokine, designated pre-B-cell growth-stimulating factor (PBSF), revealed that it is a member of intercrine alpha subfamily. Recombinant PBSF stimulated the proliferation of DW34 cells for itself and, furthermore, synergistically augmented the growth of DW34 as well as bone marrow B-cell progenitors in the presence of IL-7.

833 citations


Journal ArticleDOI
01 Nov 1994-Blood
TL;DR: WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia regardless of the presence or absence of tumor-specific DNA markers.

597 citations


Journal ArticleDOI
TL;DR: A near-field scanning optical microscope with a metallic probe tip was developed for detecting localized photons near the surface of the fine structure of a sample and the removal of stray-light noise contribution.
Abstract: A near-field scanning optical microscope with a metallic probe tip was developed for detecting localized photons near the surface of the fine structure of a sample. In this microscope a metallic probe is used for converting the evanescent photons localized near the sample surface to the propagating scattering light wave; the scattered light is detected in the far field with external condenser optics. During the measurement the probe tip vibrates normal to the surface with an amplitude of ~5 nm at 2.5 kHz, and the light intensity modulated with this frequency is lock-in detected. This operation permits the removal of stray-light noise contribution. Experimental results of the measurements of the exponential decay of the evanescent field produced by total internal reflection are given with and without the probe vibration. Image data of the surface profile of an optical compact disk are also shown.

570 citations


Journal ArticleDOI
11 Nov 1994-Science
TL;DR: Interleukin-2 receptor subunits Jak1 and Jak3 were found to be selectively associated with the "serine-rich" region of IL-2R beta and the carboxyl-terminal region ofIL-1R gamma, respectively, which may be a key event inIL-2 signaling.
Abstract: The interleukin-2 receptor (IL-2R) consists of three subunits: the IL-2R alpha, IL-2R beta, and IL-2R gamma chains, the last of which is also used in the receptors for IL-4, IL-7, and IL-9. Stimulation with IL-2 induces the tyrosine phosphorylation and activation of the Janus kinases Jak1 and Jak3. Jak1 and Jak3 were found to be selectively associated with the "serine-rich" region of IL-2R beta and the carboxyl-terminal region of IL-2R gamma, respectively. Both regions were necessary for IL-2 signaling. Furthermore, Jak3-negative fibroblasts expressing reconstituted IL-2R became responsive to IL-2 after the additional expression of Jak3 complementary DNA. Thus, activation of Jak1 and Jak3 may be a key event in IL-2 signaling.

Journal ArticleDOI
TL;DR: High-pressure in situ x-ray-diffraction studies on GaN and InN have been carried out using an imaging-plate technique and a diamond-anvil cell and the trend in the transition pressures of the III-V nitrides is discussed in terms of various ionicity scales.
Abstract: High-pressure in situ x-ray-diffraction studies on GaN and InN have been carried out using an imaging-plate technique and a diamond-anvil cell up to about 60 GPa. The two compounds crystallize in the wurtzite-type structure at ambient conditions. The axial ratio c/a of GaN remains unchanged from the ambient value of 1.626 whereas c/a of InN is considerably decreased from 1.613 to 1.597 with increasing pressure to about 15 GPa. Equation-of-state data obtained for the wurtzite phase have yielded the bulk modulus of GaN to be 237(31) GPa and that of InN to be 125.5(4.6) GPa. Structural phase transition into the rocksalt-type structure takes place in GaN at 52.2 GPa and in InN at 12.1 GPa. The trend in the transition pressures of the III-V nitrides is discussed in terms of various ionicity scales.



Journal ArticleDOI
TL;DR: The results suggest that approximately 50% of the sarcomere compliance of active muscle is due to extensibility of the thin filaments.
Abstract: In order to explain the molecular mechanism of muscle contraction, it is crucial to know the distribution of the sarcomere compliance of active muscle. Here, we directly measure the stiffness of single actin filaments with and without tropomyosin, using a recently developed technique for nanomanipulation of single actin filaments with microneedles. The results show that the stiffness for 1-micron-long actin filaments with and without tropomyosin is 65.3 +/- 6.3 and 43.7 +/- 4.6 pN/nm, respectively. When the distribution of crossbridge forces along the actin filament is taken into account, the elongation of a 1-micron-long thin filament during development of isometric contraction is calculated to be approximately 0.23%. The time constant of force in response to a sudden length change is < 0.2 ms, indicating that the viscoelasticity is negligible in the millisecond time range. These results suggest that approximately 50% of the sarcomere compliance of active muscle is due to extensibility of the thin filaments.

Journal ArticleDOI
17 Jun 1994-Cell
TL;DR: It is reported that embryonic fibroblasts from mice with a null mutation in the IRF-1 gene can be transformed by expression of an activated c-Ha-ras oncogene and could be a critical determinant of oncogen-induced cell transformation or apoptosis.

Journal ArticleDOI
TL;DR: The spin gap observed for Sr $2 and $3 confirms a recent theoretical prediction for the magnetic behavior of spin = \textonehalf{} antiferromagnetically coupled Heisenberg chains.
Abstract: Magnetic properties of Sr${\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.

Journal ArticleDOI
TL;DR: Results indicate that cdc25A is not a mitotic regulator but a novel phosphatase that plays a crucial role in the start of the cell cycle.
Abstract: The cdc25+ tyrosine phosphatase is a key mitotic inducer of the fission yeast Schizosaccharomyces pombe, controlling the timing of the initiation of mitosis. Mammals contain at least three cdc25+ homologues called cdc25A, cdc25B and cdc25C. In this study we investigate the biological function of cdc25A. Although very potent in rescuing the S.pombe cdc25 mutant, cdc25A is less structurally related to the S.pombe enzyme. Northern and Western blotting detection reveals that unlike cdc25B, cdc25C and cdc2, cdc25A is predominantly expressed in late G1. Moreover, immunodepletion of cdc25A in rat cells by microinjection of a specific antibody effectively blocks their cell cycle progression from G1 into the S phase, as determined by laser scanning single cell cytometry. These results indicate that cdc25A is not a mitotic regulator but a novel phosphatase that plays a crucial role in the start of the cell cycle. In view of its strong ability to activate cdc2 kinase and its specific expression in late G1, cdc2-related kinases functioning early in the cell cycle may be targets for this phosphatase.

Journal ArticleDOI
TL;DR: The results indicate that a large part of the sarcomere compliance of an active muscle is caused by the extensibility of the actin and myosin filaments; 42% of the compliance resides in the act in filaments, and 27% of it is in the myosIn filaments.

Journal ArticleDOI
TL;DR: It is suggested that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.

Journal ArticleDOI
TL;DR: The data indicate that FcεRI–β, subject to maternal modification, may be the atopy–causing locus on chromosome 11q, and lle181Leu within the 4th transmembrane domain is identified.
Abstract: The β–subunit of the high–affinity IgE receptor (FceRI–β) on chromosome 11 is maternally linked to atopy, the state of enhanced IgE responsiveness underlying allergic asthma and rhinitis. We have identified a common variant of FceRI–β, lle181Leu within the 4th transmembrane domain. Leu181 shows significant association with positive IgE responses in a random patient sample. Amongst 60 unrelated nuclear families with allergic asthmatic probands, Leu181 is identified in 10 (17%), is maternally inherited in each, and shows a strong association with atopy. Our data indicate that FceRI–β, subject to maternal modification, may be the atopy–causing locus on chromosome 11q.

Journal ArticleDOI
TL;DR: It is demonstrated that the chicken IGF-I gene promoter is controlled by estrogen through a unique pathway involving Fos, Jun, and the DNA binding domain of ER, providing support for the existence of a unique function of the DNA binders in facilitating some protein-protein interaction.

Journal ArticleDOI
TL;DR: Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction.
Abstract: Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction. Moreover, exogenous HGF stimulated DNA synthesis of renal tubular cells after renal injuries caused by HgCl2 administration and unilateral nephrectomy and induced reconstruction of the normal renal tissue structure in vivo. Taken together with our previous finding that expression of HGF was rapidly induced after renal injuries, these results allow us to conclude that HGF may be the long-sought renotropic factor for renal regeneration and may prove to be effective treatment for patients with renal dysfunction, especially that caused by cisplatin.

Journal ArticleDOI
15 Jul 1994-Science
TL;DR: The results suggest that the primate nigrostriatal system modulates expression of neuronal response plasticity in the striatum during sensorimotor learning.
Abstract: Dysfunction of the nigrostriatal dopamine system results in marked disorders of movement such as occur in Parkinson's disease. Functions of this dopamine-containing projection system were examined in monkeys trained in a classical conditioning task, and the effects of striatal dopamine depletion were tested. Unilateral dopamine loss substantially reduced the acquired sensory responsiveness of striatal neurons monitored electrophysiologically. This effect was ipsilateral and selective, and could be reversed by apomorphine. These results suggest that the primate nigrostriatal system modulates expression of neuronal response plasticity in the striatum during sensorimotor learning.

Proceedings ArticleDOI
12 Sep 1994
TL;DR: The proposed visual servoing control scheme ensures the convergence of the image-features to desired trajectories, by using the estimated Jacobian matrix, which is proved by the Lyapunov stability theory.
Abstract: Proposes a versatile visual servoing control scheme with a Jacobian matrix estimator. The Jacobian matrix estimator does not need a priori knowledge of the kinematic structure and parameters of the robot system, such as camera and link parameters. The proposed visual servoing control scheme ensures the convergence of the image-features to desired trajectories, by using the estimated Jacobian matrix, which is proved by the Lyapunov stability theory. To show the effectiveness of the proposed scheme, simulation and experimental results are presented. >

Journal Article
TL;DR: There is a definite gender difference in the age-related changes in whole-body fat distribution, especially in the abdominal fat tissues, and the accumulation of visceral fat is markedly accelerated by menopause in women.
Abstract: We performed a cross-sectional study using whole-body computerized tomographic (CT) scans in order to clarify age-related changes in whole-body fat distribution in both genders. The subjects were 66 men and 96 women, whose body mass index (BMI) was over 25 kg/m2. CT scans were performed at seven levels (head, fore-arms, upper arms, chest, abdomen, thighs and calves), and the fat volumes of the segments were calculated from the cross-sectional areas of the fat tissues. After calibrating to the total fat volumes, the relationship between age and the relative segmental fat volumes was analysed. In both genders, the relative intra-abdominal visceral fat volume increased and that of the legs decreased with age. The relative abdominal subcutaneous fat volume decreased with age only in male subjects. The increase in the relative visceral fat volume with age was about 2.6 times larger in males than in pre-menopausal females, while post-menopausal females showed the same increase as male subjects. These data suggest that there is a definite gender difference in the age-related changes in whole-body fat distribution, especially in the abdominal fat tissues. In addition, the accumulation of visceral fat is markedly accelerated by menopause in women.

Journal ArticleDOI
01 Jul 1994-Nature
TL;DR: This work reports the self-assembly of double-stranded inclusion complexes of poly(ethylene glycol) with γ-cyclodextrin, in which two polymer chains are threaded through the macrocycles, which might be useful precursors to more complex supramolecular assemblies such as polycatenanes.
Abstract: MUCH attention has been focused recently on the design and construction of nanoscale structures by supramolecular assembly1–5. One of the most promising approaches to constructing nanoscale structures is the use of specific interactions between polymers and receptors, as exemplified by biological systems. Recently, polyrotaxanes—complexes in which several cyclic molecules are threaded on the main chains6–11 or side chains12 of polymers—have been synthesized with crown ethers or cyclodextrins as the cyclic components. Here we report the self-assembly of double-stranded inclusion complexes of poly(ethylene glycol) with γ-cyclodextrin, in which two polymer chains are threaded through the macrocycles. These complexes might be useful precursors to more complex supramolecular assemblies such as polycatenanes.

Journal ArticleDOI
TL;DR: Results suggest that human herpesvirus 7 is one of the causative agents of exanthem subitum, and five of seven patients had seroconversion to HHV-7 just after having typical signs and symptoms ofExanthemSubitum.

Journal ArticleDOI
TL;DR: After composite incorporating MDPB was cured, no elution of the antibacterial components was observed from the material, even after 90 days' immersion in water or other solvents, and influence of incorporation of M DPB had no significant influence on the mechanical properties of the composite.
Abstract: Attempts to produce resin composite with antibacterial properties by incorporation of an antibacterial agent such as chlorhexidine have been reported, but problems can arise due to release of the inhibitory agent from the composite. Such problems may include toxic effects, influence on mechanical properties, and loss of effectiveness. A new monomer, methacryloyloxydodecylpyridinium bromide (MDPB), was synthesized by combining an antibacterial agent and methacryloyl group. The monomer was incorporated into resin composite to develop a non-releasing antibacterial composite. The ability of composite incorporating MDPB to inhibit growth and plaque accumulation by Streptococcus mutans in vitro was assayed, elution of antibacterial components from the material was investigated, and the influence of incorporation of MDPB on the mechanical properties of composite was studied. Uncured MDPB revealed antibacterial activity against S. mutans and six other species of oral streptococci, with the minimum inhibitory concentration for S. mutans being comparable with that of triclosan. After composite incorporating MDPB was cured, no elution of the antibacterial components was observed from the material, even after 90 days' immersion in water or other solvents. Growth of S. mutans on agar under specimens of MDPB-containing composite was inhibited compared with controls. In a bacterial accumulation study, S. mutans accumulated to a lesser degree on the surface of composite incorporating MDPB (p < 0.05) than on control. Incorporation of MDPB had no significant influence on the mechanical properties of the composite.

Journal ArticleDOI
TL;DR: Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRf-2 gene was affected by both transient and stableIRF-1 expression, which may shed light on the complex gene network involved in regulation of the IFN system.
Abstract: Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; the former functions as a transcriptional activator, and the latter represses IRF-1 function by competing for the same cis elements. More recent studies have revealed new roles of the two factors in the regulation of cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities, respectively. In this study, we determined the structures and chromosomal locations of the human IRF-1 and IRF-2 genes and further characterized the promoters of the respective genes. Comparison of exon-intron organization of the two genes revealed a common evolutionary structure, notably within the exons encoding the N-terminal portions of the two factors. We confirmed the chromosomal mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to 4q35.1, using fluorescence in situ hybridization. The 5{prime} regulatory regions of both genes contain highly GC-rich sequences and consensus binding sequences for several known transcription factors, including NF-{kappa}B. Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRF-2 gene was affected by both transient and stable IRF-1 expression. In addition, one potential IFN-{gamma}-activatedmore » sequence was found within the IRF-1 promoter. Thus, these results may shed light on the complex gene network involved in regulation of the IFN system. 61 refs., 7 figs.« less