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Showing papers by "Osaka University published in 1991"


Journal ArticleDOI
Koichi Niihara1
TL;DR: In this paper, intergranular nanocomposites were found to have two to five times higher toughness and strength at room temperature than those of monolithic materials, and the hardness, toughness, strength and fracture resistance for creep and fatigue at high temperatures as well as the thermal shock fracture resistance were also strongly improved for these composites.
Abstract: Ceramic nanocomposites can be divided into three categories: intergranular nanocomposite, intergranular nanocomposite and nano/nano composite. The intra- and intergranular nanocomposites were found to show the two to five times higher toughness and strength at room temperature than those of monolithic materials. The hardness, toughness, strength and fracture resistance for creep and fatigue at high temperatures as well as the thermal shock fracture resistance were also strongly improved for these composites. On the other hand, the new function such as machinability and superplasticity was observed for the nano/nano composites. The fabrication processes of these nanocomposites by sintering methods, micro and nanostructure observations, improvements of mechanical properties were reviewed and the roles of the nano-size dispersoids were discussed. Finally the new approach on structural materials design will be given.

1,218 citations


Journal ArticleDOI
TL;DR: The hydrophobicity profile of the putative polyprotein is similar to those of flaviviruses, but it has limited amino acid homology to polyproteins of flavIViruses and other viruses, indicating that HCV is at most distantly related to flavivIRuses.
Abstract: Hepatitis C virus (HCV) is a major causative agent of posttransfusion non-A, non-B hepatitis, which often develops into malignant chronic diseases, including liver cirrhosis and hepatocellular carcinoma. We have cloned from human carriers overlapping cDNAs (9,416 bp) covering the entire coding region of the HCV genome. The latter encodes a 3,010-amino-acid polyprotein. In addition, there are 332 and 54 bases of 5' and 3' noncoding sequences, respectively. Our HCV strain has a 77% nucleic acid identity to the HCV strain cloned by workers at Chiron Corporation. The hydrophobicity profile of the putative polyprotein is similar to those of flaviviruses, but it has limited amino acid homology to polyproteins of flaviviruses and other viruses, indicating that HCV is at most distantly related to flaviviruses.

1,042 citations


Journal ArticleDOI
04 Apr 1991-Nature
TL;DR: The primary structure of a voltage-dependent cal-cium channel from rabbit brain has been deduced by cloning and sequencing the complementary DNA and it is suggested that it is expressed predominantly in cerebellar Purkinje cells and granule cells.
Abstract: The primary structure of a voltage-dependent cal-cium channel from rabbit brain has been deduced by cloning and sequencing the complementary DNA. Calcium channel activity expressed from the cDNA is dramatically increased by coexpression of the α2 and β subunits, known to be associated with the dihydropyridine receptor. This channel is a high voltage-activated calcium channel that is insensitive both to nifedipine and to ω-conotoxin. We suggest that it is expressed predominantly in cerebellar Purkinje cells and granule cells.

860 citations


Journal ArticleDOI
02 May 1991-Nature
TL;DR: The results suggest that this protein-tyrosine kinase, which might negatively regulate p60c-src, represents a new type of tyrosineKinase, similar to kinases of the src family in that it has two conserved regions, Src-homology regions 2 and 3, upstream of a tyrosining domain.
Abstract: The protein-tyrosine kinase activity of the proto-oncogene product p60c-src is negatively regulated by the phosphorylation of a tyrosine residue close to the C terminus, tyrosine 527. The phosphorylation might be catalysed by a so-far-unidentified tyrosine kinase, distinct from p60c-src. Recently we purified a protein-tyrosine kinase that specifically phosphorylates tyrosine 527 of p60c-src from neonatal rat brain. We have now confirmed the specificity of this enzyme by using a mutant p60c-src that has a phenylalanine instead of tyrosine 527, and cloned a complementary DNA that encodes the enzyme. The enzyme is similar to kinases of the src family in that it has two conserved regions, Src-homology regions 2 and 3, upstream of a tyrosine kinase domain. The amino-acid identity of each region is no more than 47%, however, and the enzyme lacks phosphorylation sites corresponding to tyrosines 416 and 527 of p60c-src and has no myristylation signal. These results suggest that this protein-tyrosine kinase, which might negatively regulate p60c-src, represents a new type of tyrosine kinase.

614 citations


Journal ArticleDOI
TL;DR: Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation ofgp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL- 6-mediated growth signal.
Abstract: Interleukin 6 (IL-6) signal is transduced through gp130 that associates with a complex of IL-6 and IL-6 receptor. Truncations or amino acid substitutions offe introduced in the cytoplasmic region of human gp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL-6-mediated growth signal. In the 277-amino acid cytoplasmic region of gp130, a 61-amino acid region proximal to the transmembrane domain was sufficient for generating the growth signal. In this region, two short segments were significantly homologous with other cytokine-receptor family members. One segment is conserved in almost all members of the family, and the other is found especially in granulocyte colony-stimulating factor receptor, interleukin 2 receptor beta chain, erythropoietin receptor, KH97 (a granulocyte/macrophage colony-stimulating factor receptor-associated molecule), and interleukin 3 receptor. gp130 molecules with mutations in either of these two segments could not transduce growth signal. Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation of gp130.

567 citations


Journal ArticleDOI
14 Jun 1991-Science
TL;DR: Evidence for the formation of a stable complex of IL-2R beta and the lymphocyte-specific protein tyrosine kinase p56lck is presented and data suggest the participation of p56 lck as a critical signaling molecule downstream of IL -2R via a novel interaction are suggested.
Abstract: In the interleukin-2 (IL-2) system, intracellular signal transduction is triggered by the beta chain of the IL-2 receptor (IL-2R beta); however, the responsible signaling mechanism remains unidentified. Evidence for the formation of a stable complex of IL-2R beta and the lymphocyte-specific protein tyrosine kinase p56lck is presented. Specific association sites were identified in the tyrosine kinase catalytic domain of p56lck and in the cytoplasmic domain of IL-2R beta. As a result of interaction, IL-2R beta became phosphorylated in vitro by p56lck. Treatment of T lymphocytes with IL-2 promotes p56lck kinase activity. These data suggest the participation of p56lck as a critical signaling molecule downstream of IL-2R via a novel interaction.

517 citations


Journal ArticleDOI
TL;DR: The tissue distribution of CSK was investigated and whether CSK could phosphorylate the negative regulatory sites of src family kinases other than p60c-src was examined, raising the possibility that CSK might act as a universal regulator for src family Kinases.

491 citations


Journal ArticleDOI
01 Jan 1991-Polymer
TL;DR: In this article, the Young's modulus along the chain axis was calculated for cellulose crystalline forms I and II (native and regenerated celluloses, respectively), and anisotropy of the modulus and linear compressibility in the planes perpendicular to the molecular chain axis were also calculated.

443 citations


Journal ArticleDOI
17 Jan 1991-Nature
TL;DR: It is shown that a Xenopus kinase is phosphorylated and activated during M phase of meiotic and mitotic cell cycles, and that the interphase–metaphase transition of microtubule arrays can be induced by the addition of purified Xenopus M phase-activated MAP kinase or mammalian mitogen-activatedMAP kinase to interphase extracts in vitro.
Abstract: The protein kinase MAP kinase, also called MAP2 kinase, is a serine/threonine kinase whose activation and phosphorylation are induced by a variety of mitogens, and which is thought to have a critical role in a network of protein kinases in mitogenic signal transduction. A burst in kinase activation and protein phosphorylation may also be important in triggering the dramatic reorganization of the cell during the transition from interphase to mitosis. The interphase-metaphase transition of microtubule arrays is under the control of p34cdc2 kinase, a central control element in the G2-M transition of the cell cycle. Here we show that a Xenopus kinase, closely related to the mitogen-activated mammalian MAP kinase, is phosphorylated and activated during M phase of meiotic and mitotic cell cycles, and that the interphase-metaphase transition of microtubule arrays can be induced by the addition of purified Xenopus M phase-activated MAP kinase or mammalian mitogen-activated MAP kinase to interphase extracts in vitro.

402 citations


Journal ArticleDOI
TL;DR: Consistent with its wide-ranging output, the histaminergic neuron system regulates various activities of the brain, such as the arousal state, brain energy metabolism, locomotor activity, neuroendocrine, autonomic and vestibular functions, feeding, drinking, sexual behavior, and analgesia.

401 citations


Journal Article
TL;DR: The results indicate that there are human cancer cells in which E-CD-related intercellular adhesion is impaired, and some tumor cells with reduced E- CD expression were located in the cell cytoplasm.
Abstract: E-cadherin (E-CD), a Ca2 + -dependent adhesion molecule, plays a major role in the maintenance of intercellular junctions in normal epithelial cells in most organs. The expression of E-CD in human carcinoma samples (esophagus, stomach, and breast) was investigated using immunohistochemical staining, which was performed on surgical specimens using a monoclonal antibody for human E-CD. Ecadherin was strongly expressed in all normal epithelium examined. However E-CD expression in primary tumors of esophagus (11 of 15: 73%), stomach (5 of 20: 25%), and breast (9 of 20: 45%) was reduced, and 68% of these (esophagus: 8 of 11, stomach: 4 of 5, breast: 5 of 9) displayed heterogeneous E-CD expression. In some tumor cells with reduced E-CD expression, E-CD molecules were located in the cell cytoplasm. These results indicate that there are human cancer cells in which E-CD—related intercellular adhesion is impaired.

Journal ArticleDOI
TL;DR: Hydropathy analysis suggested that the secondary structure of the PHO84 protein consists of two blocks of six transmembrane domains separated by 74 amino acid residues, and nucleotide sequence predicted a protein of 596 amino acids with a sequence homologous to that of a superfamily of sugar transporters.
Abstract: The PHO84 gene specifies Pi-transport in Saccharomyces cerevisiae. A DNA fragment bearing the PHO84 gene was cloned by its ability to complement constitutive synthesis of repressible acid phosphatase of pho84 mutant cells. Its nucleotide sequence predicted a protein of 596 amino acids with a sequence homologous to that of a superfamily of sugar transporters. Hydropathy analysis suggested that the secondary structure of the PHO84 protein consists of two blocks of six transmembrane domains separated by 74 amino acid residues. The cloned PH084 DNA restored the Pi transport activity of pho84 mutant cells. The PHO84 transcription was regulated by Pi like those of the PHO5, PHO8, and PHO81 genes. A PHO84-lacZ fusion gene produced beta-galactosidase activity under the regulation of Pi, and the activity was suggested to be bound to a membrane fraction. Gene disruption of PHO84 was not lethal. By comparison of nucleotide sequences and by tetrad analysis with GAL80 as a standard, the PHO84 locus was mapped at a site beside the TUB3 locus on the left arm of chromosome XIII.

Journal ArticleDOI
TL;DR: The paper presents results on the generative capacity of mcfg's and also on the properties of mcfl's such as formal language-theoretic closure properties and it is shown that the time complexity of the membership problem for multiple context-free languages is O(ne).

Journal ArticleDOI
TL;DR: With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures.
Abstract: A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures.

Journal ArticleDOI
TL;DR: The results suggest that HHV-6 may latently infect monocytes in vivo and in vitro and that it may be reactivated in cells by some factors.
Abstract: Human herpesvirus 6 (HHV-6) DNA was detected in peripheral blood from exanthem subitum patients during the acute and convalescent phases of infection using the polymerase chain reaction. Although DNA could be detected in non-adherent and adherent mononuclear cells during the acute phase, it was detected predominantly in adherent cells during the convalescent phase; furthermore, viral DNA was found in adherent cells of healthy adults. When adherent mononuclear cells were cultured in vitro, virus was found to replicate well in differentiated cells cultured for 7 days in vitro before infection. When cells were cultured for more than 1 month, no detectable antigen and no evidence of virus growth was observed, but viral DNA could be detected. These apparently latently infected monocytes were treated with phorbol ester, after which virus could be recovered from the cultures. Therefore, we have developed an in vitro latency system for HHV-6; our results suggest that HHV-6 may latently infect monocytes in vivo and in vitro and that it may be reactivated in cells by some factors.

Journal ArticleDOI
TL;DR: A powerful genomic scanning method that is useful for analysis of the genomic DNA of higher organisms using restriction sites as landmarks, indicating that the genome of mammals can be scanned at approximately 1-megabase intervals.
Abstract: We have developed a powerful genomic scanning method, termed "restriction landmark genomic scanning," that is useful for analysis of the genomic DNA of higher organisms using restriction sites as landmarks. Genomic DNA is radioactively labeled at cleavage sites specific for a rare cleaving restriction enzyme and then size-fractionated in one dimension. The fractionated DNA is further digested with another more frequently occurring enzyme and separated in the second dimension. This procedure gives a two-dimensional pattern with thousands of scattered spots corresponding to sites for the first enzyme, indicating that the genome of mammals can be scanned at approximately 1-megabase intervals. The position and intensity of a spot reflect its locus and the copy number of the corresponding restriction site, respectively, based on the nature of the end-labeling system. Therefore, this method is widely applicable to genome mapping or detection of alterations in a genome.

Journal ArticleDOI
TL;DR: The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'iscemic tolerance'.

Journal ArticleDOI
TL;DR: In this article, the authors studied the natural history of avascular necrosis of the femoral head (ANFH) in 115 hips in 87 patients, 69 steroid-induced, 21 related to misuse of alcohol and 25 idiopathic.
Abstract: We studied the natural history of nontraumatic avascular necrosis of the femoral head (ANFH) in 115 hips in 87 patients, 69 steroid-induced, 21 related to misuse of alcohol and 25 idiopathic. The average length of follow-up was over five years. Collapse occurred most often when the focus of bone necrosis occupied the weight-bearing surface of the femoral head. Flatness of the head due to subchondral fracture was an early manifestation of collapse. Classification into six types based upon the radiographic findings provided an accurate prognosis for individual cases of ANFH which is useful in planning treatment and in assessing its outcome.


Journal ArticleDOI
TL;DR: In this article, a new method for quantifying irregularity of EEGs is proposed, which is measured by the entropy of the power spectrum, called an irregularity index (II).

Journal ArticleDOI
01 Dec 1991-Blood
TL;DR: Results indicate that c-kit proto-oncogene is expressed in most cases of AML and is functional in terms of supporting proliferation.

Proceedings ArticleDOI
09 Apr 1991
TL;DR: A visual feedback control scheme, called image-based visual servo, is proposed for manipulators with cameras on their hands that is stable even under noisy conditions, while the conventional position-based servo tends to be unstable.
Abstract: A visual feedback control scheme, called image-based visual servo, is proposed for manipulators with cameras on their hands. To accomplish specific tasks in unstructured environments, it is essential to have capabilities of recognizing the object position with respect to the manipulator hand. Using the Jacobian matrix relating the camera motion to the object position change in the acquired image, a state space formulation of a visual feedback system is established. On the basis of the task defined in the image plane, the desired motion of the hand is achieved by time-variant state feedback. The image-based scheme is applied to a task of tracking a moving object by the camera (and the hand). Simulations show that the control scheme is stable even under noisy conditions, while the conventional position-based servo tends to be unstable. Experiments on a PUMA 560 show the validity and the effectiveness of the image-based visual servo. >

Journal ArticleDOI
TL;DR: The data suggest that the survival of cultured tyrosine hydroxylase- positive, mesencephalic, and acetylcholinesterase-positive, septal neurons from postnatal two-week-old rats was supported by interleukin-6, just as there was a different dose dependency on the cultured postnatal neurons compared with embryonic neurons.

Journal ArticleDOI
TL;DR: This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule, however, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance.
Abstract: 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance.

Journal ArticleDOI
TL;DR: The cerebellar inositol 1,4,5-trisphosphate (InsP3) receptor is a high molecular weight glycoprotein abundantly expressed in Purkinje cells and the subunit structure of the InsP3 receptors was examined by cross-linking experiments.

Journal ArticleDOI
TL;DR: The model is made to account for the excitonic effects at these CP's; the results are in satisfactory agreement with the experiment over the entire range of photon energies.
Abstract: We have studied the optical response of ZnSe in the 1.5--5.3-eV photon-energy range at room temperature by spectroscopic ellipsometry. The measured dielectric-function spectra reveal distinct structures at energies of the ${\mathit{E}}_{0}$, ${\mathit{E}}_{0}$+${\mathrm{\ensuremath{\Delta}}}_{0}$, ${\mathit{E}}_{1}$, and ${\mathit{E}}_{1}$+${\mathrm{\ensuremath{\Delta}}}_{1}$ critical points (CP's). These data are analyzed on the basis of a simplified model of the interband transitions. The ${\mathit{E}}_{0}$-(${\mathit{E}}_{0}$+${\mathrm{\ensuremath{\Delta}}}_{0}$) structures are characterized by a three-dimensional ${\mathit{M}}_{0}$ CP, the ${\mathit{E}}_{1}$-(${\mathit{E}}_{1}$+${\mathrm{\ensuremath{\Delta}}}_{1}$) structures by a two-dimensional ${\mathit{M}}_{0}$ CP, and the ${\mathit{E}}_{2}$ structure by a classical Lorentzian oscillator (damped harmonic oscillator). The experimental data could not be explained within the framework of the one-electron approximation, since excitonic effects may profoundly modify the CP singularity structure. The model is thus made to account for the excitonic effects at these CP's; our results are in satisfactory agreement with the experiment over the entire range of photon energies. Dielectric-function-related optical constants of ZnSe, such as the refractive index, the extinction coefficient, and the absorption coefficient, are also presented and analyzed.

Journal ArticleDOI
TL;DR: In this paper, a review is made of Ultraprecision metal cutting techniques which aim at micrometer or sub-micrometer form accuracy and nanometric surface roughness in optical, electronic and mechanical components.


Journal Article
TL;DR: The results indicate that TGF-beta produced by tumor cells induces deleterious effects on T cell, especially on the CD4- Th subset, and provide an explanation for the molecular mechanism underlying the previously observed CD4+ Th-selective suppression in the tumor-bearing state.
Abstract: The present study investigates the nature of humoral component(s) generated in tumor-bearing hosts to induce immune dysfunction of T cells. Cell-free ascitic fluid and culture supernatant (SN) were obtained from the ascites and cultures allowing MH134 hepatoma cells to grow. These ascites and SN samples were tested for their abilities to influence the generation of CTL responses to TNP and alloantigens. The generation of the anti-TNP CTL responses that require self H-2-restricted CD4+ Th cells was markedly suppressed by addition of the ascites or SN under conditions in which these samples did not inhibit anti-allo CTL responses capable of using alternate pathways of allo-restricted CD4+ and CD8+ Th. The activation of CD8+ CTL precursors and CTL activity were also resistant to the ascites or SN. The ascites- or SN-induced suppressive effect to which CD4+ Th were most susceptible was found to be mediated by transforming growth factor-beta (TGF-beta) activity, because: 1) the TGF-beta activity was detected in the MH134 ascites and culture SN; 2) the suppression of CD4+ Th function required for anti-TNP CTL responses was almost completely prevented by addition of anti-TGF-beta antibody to cultures and; 3) rTGF-beta also induced similar patterns of immunosuppression to those observed by ascites or SN. These results indicate that TGF-beta produced by tumor cells induces deleterious effects on T cell, especially on the CD4+ Th subset, and provide an explanation for the molecular mechanism underlying the previously observed CD4+ Th-selective suppression in the tumor-bearing state.

Journal ArticleDOI
01 Nov 1991-Spine
TL;DR: Neurologic complications resulting from surgery for 384 cases of cervical myelopathy (cervical soft disc herniation, spondylosis, ossification of the posterior longitudinal ligament) were reviewed and paralysis of the deltoid and biceps brachii muscles was an exclusive feature of deterioration in the nerve root group.
Abstract: Neurologic complications resulting from surgery for 384 cases of cervical myelopathy (cervical soft disc herniation, spondylosis, ossification of the posterior longitudinal ligament) were reviewed. Surgical procedures performed included 134 anterior interbody fusions (Cloward or Robinson-Smith technique), 70 subtotal corpectomies with strut bone graft, 85 laminectomies, and 95 laminoplasties. Twenty-one patients (5.5%) sustained neurologic deterioration related to surgery. The deterioration was classified into two types on the basis of the neurologic signs observed: deterioration of spinal cord function or of nerve root function. Manifestations of the former varied from weakness of the hand to tetraparesis. Paralysis of the deltoid and biceps brachii muscles was an exclusive feature of deterioration in the nerve root group. Causes of this paralysis included malalignment of the spine related to graft complications, and a tethering effect on the nerve root following major shifting of the spinal cord after decompression. The causes of deterioration of the cord function included spinal cord injury during surgery, malalignment of the spine associated with graft complication, and epidural hematoma.