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Takayuki Itoh

Publications and source records attributed to Takayuki Itoh.

18 recordsLinked to original sources
PubMed2006

Bi-directional control of motor neuron dendrite remodeling by the calcium permeability of AMPA receptors.

Motor neurons express particularly high levels of the AMPA receptor subunit GluR1(Q)flip (GluR1(Q)i) during the period in early postnatal life when their dendritic tree grows and becomes more branched. To investigate how GluR1-containing AMPA receptors contribute to dendrite morphogenesis, we characterized a mutant form of GluR1 (containing a histidine in the Q/R editing site) with unique electrophysiological properties. Most notably, AMPA receptors assembled from GluR1(H)i display less calcium permeability than AMPA receptors assembled from GluR1(Q)i. Expression of GluR1(Q)i in vivo or in vitro led to an increase in dendrite branching with no net change in the overall tree size while GluR1(H)i led to a loss of branches and a net reduction in overall tree size. GluR1(H)i-dependent dendrite atrophy is mediated by protein phosphatase 2B. The results suggest that the electrophysiological properties of cell surface AMPA receptors, specifically their permeability to calcium, can be a central determinant of whether the dendrites undergo activity-dependent branching or atrophy.

Animals↗
PubMed2006

MEK-ERK signaling is involved in interferon-gamma-induced death of oligodendroglial progenitor cells.

Oligodendrocytes are exposed to various cytokines in inflammatory lesions in the central nervous system. In this study, we focused on the direct effects of interferon-gamma (IFNG) on highly purified rat oligodendroglial cultures at different developmental stages. Among the three stages tested, IFNG had direct cytotoxic effects on actively proliferating oligodendrocyte progenitors but much less on immature oligodendrocytes and none on mature oligodendrocytes. This stage-specific susceptibility of progenitors to IFNG-induced cytotoxicity consisted of two components, delay in the G(1)/S transition of the cell cycle and increased cell death at least partly mediated by apoptosis, suggesting that progression of the cell cycle was tightly linked to this toxic mechanism. There was no functional difference in the signal transducers and activators of transcription (STAT) pathways between progenitors and mature oligodendrocytes as determined by induction of IRF1 mRNA in response to IFNG. We found that partial inhibition of the MEK-ERK pathway, one of the mitogen-activated protein kinase phosphorelay modules, by U0126 partially reversed the IFNG-induced cytotoxicity in progenitors. In addition, ERK activity was quickly down-regulated after in vitro differentiation of progenitors to immature oligodendrocytes. Therefore, we concluded that simultaneous activation of the STAT pathway by IFNG and of the ERK pathway by exogenous trophic factors played a role in the stage-specific IFNG-induced cytotoxicity in oligodendroglial progenitors. Our study has implications with respect to the mechanisms of periventricular leukomalacia in infants and of persistent demyelination in multiple sclerosis lesions in adults.

Adult↗
PubMed2005

Multipotency of FBD-103a, a neural progenitor cell line from the p53-deficient mouse.

We previously established cell lines from brains of p53-deficient embryos, and have now characterized one of these lines, FBD-103a, in detail. Recloning FBD-103a yielded 3 types of subclones: 5 generated the neuronal lineage (Type 1), 3 generated the glial lineage (Type 2), and 10 gave rise to both lineages as the parental line (Type 3), indicating that FBD-103a is a multipotent neural progenitor cell line indistinguishable from true neural stem cells. RT-PCR analyses of transcription factor expression indicated that the transition of multipotent Type 3 clones to either neuronally or glially differentiated progeny was marked by down-regulation of Ascl1/Mash1 and Olig1 and up-regulation of Nrsf/Rest. As expected for neural stem cells, FBD-103a and Type 3 clones formed neurospheres when cultured on a non-adhesive substrate in a serum-free medium containing fibroblast growth factor-2 (FGF2). Interestingly, the transition between Type 3 and Type 1 neuronal- or Type 2 glial-specified cells proved to be reversible; Type 1 and Type 2 subclones could also form neurospheres, from which both neuron-generating and glia-generating progenies could be derived. Moreover, when maintained on an adherent substratum that prevented neurosphere formation, but with FGF2 and without serum, Type 2 clones could generate Type 3 multipotent cells. Thus, at least in the absence of p53, specialized cell-cell interactions within neurospheres are not essential for persistence or recapture of the capacity for self-renewal and multipotency by cells differentiating along glial pathways, a result of possible significance to the pathogenesis of malignant brain tumors.

Animals↗
PubMed2005

Functional studies on a ketoreductase gene from Streptomyces sp. AM-7161 to control the stereochemistry in medermycin biosynthesis.

Medermycin shows the same trans (3S,15R) configuration as actinorhodin in the pyran ring crucial for its bioactivity. One medermycin biosynthetic gene, med-ORF12, is assumed to be involved in the stereochemical control at C-3. Functional complementation suggested that it plays a similar role as actVI-ORF1 previously proved to determine the stereospecificity at C-3 in actinorhodin biosynthesis. Co-expression of med-ORF12 with actinorhodin early biosynthetic genes further demonstrated that med-ORF12 encodes a ketoreductase responsible for the enantioselective reduction at C-3 in the formation of the pyran ring.

Alcohol Oxidoreductases↗
PubMed2005

Subepithelial microvasculature in large airways observed by high-magnification bronchovideoscope.

BACKGROUND: The bronchial vasculature serves important functions and is modified in a variety of pulmonary and airway diseases. The remarkable ability of the bronchial vasculature to undergo remodeling has implications for disease pathogenesis. However, there is very little information on normal bronchial circulation. OBJECTIVES: The aim of this study was to obtain information on bronchial microvessels in large airways using a high-magnification bronchovideoscope. METHODS AND PATIENTS: Recently, we developed a high-magnification bronchovideoscope (XBF-200HM3 [side-viewing type]) in cooperation with Olympus Medical Systems. This bronchovideoscope can provide information on the bronchial mucosa with a maximum magnification of 110 times. Between August 2000 and July 2004, 26 patients without abnormalities in the large airways were enrolled into this study. Patients underwent conventional bronchoscopy and subsequent bronchoscopy with the high-magnification bronchovideoscope. After the bronchoscopic examination, we calculated the vessel area ratios and hemoglobin indexes of images made with the high-magnification bronchovideoscope by using appropriate software. In addition, we compared the findings obtained with the high-magnification bronchovideoscope of the 26 subjects with microscopic findings of autopsied tracheas of two patients without abnormalities. RESULTS: Many ramifying subepithelial microvessels of large airways were mainly observed in intercartilage and membranous portions, whereas only a few microvessels were seen in cartilage portions. Histologically, these subepithelial microvessels were thought to be distributed within approximately 800 and 500 microm beneath the surface of the intercartilage portions and membranous portions, respectively. Vessel area ratios of the intercartilage portions were significantly higher than those of the cartilage and membranous portions. The hemoglobin indexes of the intercartilage portions were significantly higher than those of the cartilage and membranous portions, and these indexes were also significantly higher in the membranous portion than in the cartilage portion. CONCLUSIONS: A dense concentration of subepithelial microvessels was mainly observed in the intercartilage portion, indicating an increase in submucosal circulation. This high-magnification bronchovideoscope is a useful tool for observing and evaluating the subepithelial microvessels in large airways.

Adult↗
PubMed2004

SP3 acts as a positive regulator on the core promoter of human ZPK gene.

ZPK (zipper protein kinase)/MUK/DLK/MAP3K12, a member of mixed-lineage kinases (MLKs), is expressed in a tissue-specific manner, particularly in developing brain, and likely to contribute to cytodifferentiation, apoptotic elimination, and migration. To understand the preferential expression of ZPK in neuronal tissues, we have analyzed the putative core promoter region upstream of the first exon of the human ZPK gene. The core promoter region is TATA-less, but contains several potential transcription factor-binding motifs such as a GC-box, all of which are well conserved between human and mouse. Reporter assays and 'gel-shift' analysis using SH-SY5Y cells revealed that a xenobiotic responsive element (XRE)-like motif (GGGCGTGTCC) was preferentially recognized by Sp3, and enhanced the core promoter activity. However, the core promoter activity was still potent even in HeLa cells which barely express ZPK. Our results suggest that, for the selective expression of ZPK gene, cell-specific negative regulatory element(s) which locate outside of the core promoter region repress the potent basic promoter activity.

Amino Acid Motifs↗
PubMed2004

Peripheral primitive neuroectodermal tumor of the chest wall of a 69-year-old man.

We report a case of peripheral primitive neuroectodermal tumor (pPNET), which belongs to the pPNET/Ewing's sarcoma family, arising in the chest wall of a 69-year-old man. He had high levels of serum neuron-specific enolase and pro-gastrin-releasing peptide, which are believed to be useful diagnostic blood markers for small cell lung carcinoma (SCLC). Microscopically, the tumor was composed of solid nests and sheets of monotous, primitive, small round cells with a few rosettes, making it difficult to distinguish from SCLC. Immunohistochemically, the tumor cells showed intense cell membranous immunoreactivity for MIC2 protein (CD99). EWS/FLI-1 chimeric mRNA that originated from the characteristic t(11;22)(q24;q12) chromosomal translocation was detected by RT-PCR and nucleotide sequence analysis. These results confirmed the diagnostic validity of the present tumor being a pPNET, thus raising the possibility that in the past, pPNETs which have arisen in the chest have been mistakenly diagnosed as SCLC.

Aged↗
PubMed2003

Invasive thymoma with paraneoplastic retinopathy.

A 60-year-old man was admitted for progressive visual loss in both eyes. He was diagnosed with retinopathy and chest computed tomography revealed an invasive thymoma. In western blot analysis, serum autoantibodies against recoverin, photoreceptor-specific calcium-binding protein, and heat shock cognate protein 70 which were identified as the cause of cancer-associated retinopathy (CAR). Immunofluorescence staining showed that thymoma cells also expressed recoverin. These observations strongly suggested that similar pathogenesis of CAR was involved in the presented case.

Biomarkers, Tumor↗
PubMed2003

Bcl-2-related protein family gene expression during oligodendroglial differentiation.

Oligodendroglial lineage cells (OLC) vary in susceptibility to both necrosis and apoptosis depending on their developmental stages, which might be regulated by differential expression of Bcl-2-related genes. As an initial step to test this hypothesis, we examined the expression of 19 Bcl-2-related genes in purified cultures of rat oligodendroglial progenitors, immature and mature oligodendrocytes. All 'multidomain' anti-apoptotic members (Bcl-x, Bcl-2, Mcl-1, Bcl-w and Bcl2l10/Diva/Boo) except Bcl2a1/A1 are expressed in OLC. Semiquantitative and real-time RT-PCR revealed that Bcl-xL and Mcl-1 mRNAs are the dominant anti-apoptotic members and increase four- and twofold, respectively, with maturation. Bcl-2 mRNA is less abundant than Bcl-xL mRNA in progenitors and falls an additional 10-fold during differentiation. Bcl-w mRNA also increases, with significant changes in its splicing pattern, as OLC mature. Transfection studies demonstrated that Bcl-xL overexpression protects against kainate-induced excitotoxicity, whereas Bcl-2 overexpression does not. As for 'multidomain' pro-apoptotic members (Bax, Bad and Bok/Mtd), Bax and Bak are highly expressed throughout differentiation. Among 'BH3 domain-only' members examined (Bim, Biklk, DP5/Hrk, Bad, Bid, Noxa, Puma/Bbc3, Bmf, BNip3 and BNip3L), BNip3 and Bmf mRNAs increase markedly during differentiation. These results provide basic information to guide further studies on the roles for Bcl-2-related family proteins in OLC death.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome.

A 47-year-old man, who had been diagnosed as myelodysplastic syndrome (MDS), complained of a severe cough and a high-grade fever. Chest CT disclosed scattered small nodules and ground-glass opacities with interlobular septal thickening in both lung fields and a mass lesion in the right lower lobe. Pathological findings of the ground-glass opacities and the mass lesion obtained by video-assisted thoracoscopic surgery revealed the accumulation of eosinophilic amorphous material in the alveoli and confirmed the diagnosis of pulmonary alveolar proteinosis (PAP). Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in sera were below sensitivity, while the GM-CSF level was elevated in bronchoalveolar lavage fluid. He was diagnosed as secondary PAP associated with MDS.

Biopsy, Needle↗
PubMed2003

A rare case of pulmonary bronchogenic cyst associated with bronchial atresia in the same lobe.

A rare case of 49-year-old woman having pulmonary bronchogenic cyst associated with bronchial atresia in the same lobe was presented. The diagnosis was confirmed by aortography and operation specimen. Three-dimensional reconstructed images of computed tomography clearly demonstrated the defference between mucoid impaction of bronchial trees in the left S9 not communicating with hilar bronchus and the cyst in the left S10 oppressing surrounding vessels.

Adult↗
PubMed2002

Differential age-dependent trophic responses of nodose, sensory, and sympathetic neurons to neurotrophins and GDNF: potencies for neurite extension in explant culture.

The age-dependent trophic responses of sympathetic, sensory, and nodose neurons to the neurotrophins NGF, BDNF, and NT-3 and to glial cell line-derived neurotrophic factor (GDNF) were examined by an explant culture system. Superior cervical ganglia (SCG), dorsal root ganglia (DRG), and nodose ganglia (NG) were removed from rat embryos (E18), neonatals (< or = 1 day old), young adults (3-6 months old), and aged adults (> 24 months old). The ganglia were cultured with and without each neurotrophic factor; the neurite extension and neurite density were then assessed. The SCG from rats of all ages were significantly influenced by NGF, NT-3, and GDNF; the effects of NT-3 and GDNF were reduced after maturation. The DRG from embryos and neonates were influenced by all neurotrophic factors; however, the effects of BDNF and NT-3 disappeared after maturation. The GDNF showed little effect on adult DRG and no effect on aged DRG. The effect of NGF was preserved over all ages of DRG. The NG from embryonic rats were significantly responsive to BDNF and GDNF; their effects decreased in the neonatal NG, but a minimum effect remained in the aged NG. These results indicate that age-dependent profiles of trophic effects differ extensively among the lineages of the peripheral nervous system and also among the individual neurotrophic factors.

Aging↗
PubMed2002

AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes.

Cells of the oligodendroglial lineage express Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-preferring glutamate receptors (AMPA-GluR) during development. Prolonged activation of their AMPA-GluR causes Ca2+ overload, resulting in excitotoxic death. Prior studies have shown that oligodendroglial progenitors and immature oligodendrocytes are susceptible to excitotoxicity, whereas mature oligodendrocytes are resistant. An unresolved issue has been why Ca2+-permeability of AMPA-GluR varies so markedly with oligodendroglial development, although the level of expression of edited GluR2, an AMPA-GluR subunit which blocks Ca2+ entry, is relatively constant. To address this question, we performed Ca2+ imaging, molecular and electrophysiological analyses using purified cultures of the rat oligodendroglial lineage. We demonstrate that transient up-regulation of expression of GluR3 and GluR4 subunits in oligodendroglial progenitors and immature oligodendrocytes results in the assembly by these cells, but not by oligodendroglial pre-progenitors or mature oligodendrocytes, of a population of AMPA-GluR which lack GluR2. This stage-specific up-regulation of edited GluR2-free, and hence Ca2+-permeable, AMPA-GluR explains the selective susceptibility to excitotoxicity of cells at these stages of oligodendroglial differentiation, and is likely to be important to these cells in the trans-synaptic Ca2+-signaling from glutamatergic neurons, which occurs in hippocampus

Animals↗
PubMed2002

Pulmonary MALT lymphoma with amyloid production in a patient with primary Sjögren's syndrome.

A 53-year-old woman was admitted to our hospital complaining of cough, low grade fever, chest pain and sicca symptoms. A chest radiograph showed an abnormal shadow and chest computed tomography revealed a tumor in left S6. She was diagnosed as Sjögren's syndrome by sialography and histological findings of labial biopsy. The surgically resected tumor specimen showed proliferation of lymphoid cells with lymphoepithelial lesions, which were positive for CD20 and kappa light chain. Kappa light chain-positive amyloid was found within the tumor. The tumor showed rearranged kappa light chain genes. The diagnosis was pulmonary mucosa associated lymphoid tissue lymphoma with amyloid production.

Amyloid↗
PubMed2002

Pulmonary lymphangioleiomyomatosis; unusual radiological manifestation of multiple large nodules.

A 44-year-old woman was admitted to our hospital in August 1999 for multiple large nodules detected on chest roentgenogram in an annual health check. Chest CT scans showed bilateral large nodules (>10 mm in diameter) with irregular margins and multiple thin walled cystic lesions. From these radiologic examinations, we suspected pulmonary Langerhans cell histiocytosis. Histological examination of the biopsy specimen by video-assisted thoracoscopy revealed a marked proliferation of the spindle cells, which were immunologically positive for alpha-smooth muscle actin and HMB-45, in the cyst walls and lung parenchyma. The large nodules consisted of proliferation of the smooth muscle cells surrounded by a dense layer of hemosiderinladen macrophages. During the two years subsequent to these 1999 examinations, the opacities have gradually diminished and the patient was found to have pulmonary lymphangioleiomyomatosis. This case exhibited rare radiologic manifestations of multiple large nodules mimicking Langerhans cell histiocytosis.

Actins↗
PubMedDate not supplied

Visualization of large-scale aqueous solubility data using a novel hierarchical data visualization technique.

It is a difficult task to recognize the trends in molecular physical properties relevant to a specific chemical class and find a way to optimize potential compounds. We present here a novel hierarchical data visualization technique, named "HeiankyoView", to visualize large-scale multidimensional chemical information. HeiankyoView represents hierarchically organized data objects by mapping leaf nodes as colored square icons and nonleaf nodes as rectangular borders. In this way, data objects can be expressed as equishaped icons without overlapping one another in the two-dimensional display space. HeiankyoView has been applied to visualize aqueous solubility data for 908 compounds collected from the published literature. When the results of a recursive partitioning analysis and hierarchical clustering analysis were visualized, the trends hidden in the solubility data could be effectively displayed as intuitively understandable visual images. Most interestingly, the data visualization technique, without any statistical computations, was able to assist us in extracting from such large-scale data meaningful information establishing that ClogP and the molecular weight are critical factors in determining aqueous solubility. Thus, HeiankyoView is a powerful tool to help us understand structure-activity relationships intuitively from a large-scale data set.

Cluster Analysis↗