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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 73 records · Page 4Linked to original sources
PubMed2000

A case of mixed connective tissue disease (MCTD) complicated with MPO-ANCA-related necrotizing glomerulonephritis.

Renal diseases of mixed connective tissue disease (MCTD) are not unusual. Although most of them are SLE-like renal impairment with immune complex deposits, systemic sclerosis- (SSc) like renal impairments with intimal thickening of interlobular arteries or arterioles are also encountered. Several cases of SSc complicated with MPO-ANCA-related necrotizing glomerulonephritis (nGN) are reported. Here we report a case which developed MPO-ANCA-related nGN 16 years after the diagnosis of MCTD. She exhibited pauci-immune focal nGN and significantly high titer of MPO-ANCA. She was successfully treated with prednisolone and cyclophosphamide. We believe this is the first case in which MPO-ANCA-related nGN was demonstrated in a patient with MCTD.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Clinicopathological features of gastric stromal tumors.

Stromal tumors in the gastrointestinal (GI) tract consist of myogenic tumors, neurogenic tumors and gastrointestinal stromal tumors (GISTs). Mutations in the c-kit gene have been found in GISTs, and GISTs with c-kit mutations showed aggressive clinical behavior and histological features. In the present study, we classified stromal tumors into four groups according to histological differentiation and c-kit mutation: myogenic tumors, neurogenic tumors, c-kit mutation (-) GISTs and c-kit mutation (+) GISTs, and examined their clinicopathological importance and validity using data obtained from 125 patients with gastric stromal tumors. There was no difference in preoperative symptoms and signs among the four groups. GISTs with c-kit mutations were large and showed invasion into neighboring structures compared with the other tumors, indicating the clinically aggressive features of mutation (+) GISTs. In histological examinations, c-kit mutation (+) GISTs were higher in cellularity (P < 0.0001) and mitotic cell count (P = 0.0086), and showed frequent histological necrosis (P = 0.0058) and hemorrhage (P = 0.0170), and consequently, were higher in histological grade (P = 0.0001). In prognostic analyses, overall, cause-specific and disease-free survival of patients in the mutation (+) GIST group was the poorest among the four groups. No significant differences were found among the other three groups of myogenic tumors, neurogenic tumors and c-kit mutation (-) GISTs, indicating a similar aggressiveness in clinical presentation and histological features. Thus, this classification is considered to be clinically and pathologically important in the diagnosis of gastric stromal tumors.

Adult↗
PubMed1999

Effect of silane treatment and different resin compositions on biological properties of bioactive bone cement containing apatite-wollastonite glass ceramic powder.

In methylmethacrylate (MMA)-based cements containing bioactive particles, polymethylmetacrylate (PMMA) is known to suppress the bioactivity of Bioglass(R) and apatite-wollastonite glass ceramic (AW-GC). Little is known about the effect of different silane treatment methods on the bioactivity of AW-GC. MMA-based cement plates containing dry silanated AW-GC particles and PMMA particles of different molecular weights (12,000-900,000) were immersed in simulated body fluid (SBF). Cements containing PMMA particles of high molecular weight formed an apatite layer on the surface after 24 h. Using PMMA particles with a molecular weight of 60,000 and AW-GC particles silanated with different methods (dry method vs. slurry method), cement plates were made and immersed in SBF. Only cement plates containing dry silanated AW-GC particles showed apatite formation in SBF after 3 days. In vivo implantation in rat tibias of MMA-based cement containing dry silanated AW-GC particles and PMMA particles (molecular weight 900,000) demonstrated an affinity index of 32.1 +/- 15.8% after 8 weeks of implantation compared to 89.4 +/- 10.7% achieved by bisphenol-A-glycidyl methacrylate based cement containing the same bioactive powder. By using a dry method of silane treatment and high molecular weight PMMA particles, the bioactivity of cement based on MMA monomer was achieved; but further effort is needed to improve the mechanical properties of the composite.

Animals↗
PubMed1999

A new member of the GTPase superfamily that is upregulated in highly metastatic cells.

Two sublines of B16 melanoma cells, F10 and BL6, are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found a new member of the GTPase superfamily, namely TIB929, which displayed an induction of expression in BL6 cells. It conserved three consensus sequences for GTP-binding site motifs and showed a significant homology to the yeast Gtr2 gene throughout the coding sequence. TIB929 was expressed ubiquitously in human tumor cells, with a marked expression in highly metastatic cells. TIB929 was mapped on mouse chromosome 4D, syntenic to human chromosome 1p. The results suggested an involvement of TIB929 in malignant progression.

Amino Acid Sequence↗
PubMed1999

Upregulation of endogenous heparin-binding EGF-like growth factor and its role as a survival factor in skeletal myotubes.

To investigate the role of heparin-binding EGF-like growth factor (HB-EGF) in skeletal muscle, we studied its function in skeletal myotubes in vitro using mouse C2C12 cells. Expression levels of membrane-anchored HB-EGF (proHB-EGF) protein were increased specifically during their differentiation among epidermal growth factor receptor (EGFR) ligands. Production levels of EGFR on the cell surface were constant. Tyrosine phosphorylation of EGFR, however, was constitutively increased during differentiation. Quenching of endogenous HB-EGF significantly rendered myotubes sensitive to apoptotic cell death induced by hypoxic stress, suggesting that proHB-EGF in the skeletal muscle is specifically upregulated to function as a survival factor.

Animals↗
PubMed1999

Matrix metalloproteinase-9 production, a newly identified function of mast cell progenitors, is downregulated by c-kit receptor activation.

Mast cell precursors invade from the peripheral blood into local tissues where they differentiate to their mature phenotypes. However, the mechanism of this migration process has been unclear. We clearly demonstrated here the production and release of matrix metalloproteinase-9 (MMP-9), a matrix-degrading enzyme necessary for leukocyte transmigration, by interleukin-3-dependent mouse mast cell progenitors: bone marrow-derived cultured mast cells and IC-2 mast cells. Because several interleukin-3-independent mast cell lines with active mutations in the c-kit gene did not release MMP-9, the possible involvement of c-kit receptor activation in downregulation of MMP-9 production was predicted. c-kit receptor activation by stem cell factor led to a significant decrease in MMP-9 production of cultured mast cells and IC-2 mast cells transfected with the c-kit gene. Thus, the present results suggest that mast cell precursors are able to produce MMP-9, which may be essential for mast cell migration into tissues, and that stem cell factor may downregulate the MMP-9 production, resulting in engagement of mast cells to matrix components.

Animals↗
PubMed1999

Analysis of the MEN1 gene in sporadic pituitary adenomas from Japanese patients.

An autosomal-dominant syndrome known as multiple endocrine neoplasia type 1 (MEN1) is characterized by tumors in parathyroid glands, pancreatic endocrine tissues and the anterior pituitary gland. The predisposing gene was identified at 11q13 when germline mutations in the MEN1 gene were detected in affected pedigrees. To investigate a possible role of this gene in tumorigenesis of non-familial pituitary adenomas, we examined 24 sporadic tumors from Japanese patients for loss of heterozygosity (LOH) at the 11q13 region and for somatic mutations in the entire coding region and exon-intron boundaries of MEN1. Although three common sequence variants were detected, none of the tumors exhibited either LOH or somatic mutations of this gene. Our results indicate that inherited and sporadic forms of pituitary adenomas are different in terms of the genetic events that contribute to their development, and that other loci associated with pituitary neoplasia must still be sought.

Adenoma↗
PubMed1999

Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Gain-of-function mutations in the juxtamembrane domain of the c-kit gene have been found in several GISTs. In this study, we examined the correlation between the presence of c-kit mutation and prognosis in 124 cases of GIST. DNA samples were extracted from paraffin sections. Exon 11 of the c-kit gene encoding the juxtamembrane domain and exon 17 encoding the kinase domain were amplified by PCR and sequenced. Most GISTs (89%) express the KIT protein, and missense mutations of exon 11 were found in 71 of 124 GISTs (57%). No mutations were detectable in exon 17. These 71 mutation-positive GISTs were larger in size and had more frequently invaded adjacent tissues than did the 53 mutation-negative GISTs. Histologically, the mutation-positive GISTs showed higher mitotic figures and more necrosis and hemorrhage. The patients with mutation-positive GISTs showed more frequent recurrences (P = 0.0005) and higher mortality (P = 0.0001) than did those with mutation-negative GISTs. The c-kit mutation was an independent prognostic factor for overall and cause-specific survival of the patients with GISTs. These results suggest that GISTs may be divided into mutation-positive and -negative subtypes. The prognosis was worse in patients with mutation-positive GISTs than in those with mutation-negative GISTs. Thus, mutation of the c-kit gene may be a good prognostic marker of GISTs.

Amino Acid Sequence↗
PubMed1999

Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene.

The mi locus encodes a member of the basic - helix - loop - helix - leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Although the bHLH-Zip family transcription factors generally recognize and bind CANNTG motifs, the expression of mouse mast cell protease 6 (MMCP-6) gene is regulated by MITF through the GACCTG motif in the promoter region. The GACCTG motif was partly overlapped the TGTGGTC sequence, which was bound by polyomavirus enhancer binding protein 2 (PEBP2). In the present study, the effect of PEBP2 on the expression of MMCP-6 gene was examined. PEBP2 that is composed of alpha and beta subunits was expressed by mast cell lines and cultured mast cells derived from spleen. The overexpression of dominant negative PEBP2 cDNA reduced the expression of MMCP-6. Moreover, the simultaneous transfection of the plasmid containing MITF cDNA and the plasmid containing PEBP2 cDNA increased the MMCP-6 promoter activity. For the synergistic action of PEBP2 and MITF, the intact GACCTG and TGTGGTC motifs were prerequisite. The PEBP2alphaB1 mutant which lacked the region downstream from the Runt domain did not bind MITF and lost the synergistic function. These results indicated that PEBP2 and MITF synergistically transactivated the MMCP-6 gene and that the region downstream from the Runt domain of PEBP2alphaB1 was essential for the physical and functional interactions with MITF.

Animals↗
PubMed1999

Synthesis of sugar fatty acid esters by modified lipase.

A simple synthesis of sugar fatty acid esters was developed in a nonaqueous solution using lipase modified by synthetic detergent. Esterification of sugar was accelerated by continuous removal of water from the reaction mixture with a molecular sieve. When glucose and palmitic acid (1:1 by mole) were used as the starting substrates, more than 90% of glucose was converted to its ester in this system. The resultant product was 6-O-palmitoylglucose. Other mono- or disaccharides were also esterified by the modified lipase with high yield. It was shown that the modified lipase might act as a catalyst for the synthesis of sugar fatty acid esters.

Carbohydrates↗
PubMed1999

Kainic acid-induced inducible cyclooxygenase and c-Jun phosphorylation in the rat hippocampal formation.

Inducible cyclooxygenase (COX-2) was transiently induced in the neurons throughout the entire hippocampus between 6 and 24 h after injection of kainic acid (KA). The induction of COX-2 correlated more closely with the induction of c-Jun than with that of c-Fos. Phosphorylated c-Jun was induced 6-12 h after in the CA3 pyramidal neurons, which undergo apoptosis. Almost all of neurons with phosphorylated c-Jun were colocalized with COX-2. These results suggest that COX-2 and c-Jun phosphorylation may participate in KA-induced neurodegeneration.

Animals↗
PubMed1999

Identification of the region of mi transcription factor which is responsible for the synergy with PEBP2/CBF.

The mi locus encodes the mi transcription factor (MITF), a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors. MITF binds the alphaB1/AML1 subtype of the alpha subunit of the polyomavirus enhancer binding protein 2 (PEBP2). These two transcription factors synergistically transactivate the mouse mast cell protease 6 (MMCP-6) gene. The interaction of PEBP2 with MITF is mediated through the region carboxy-terminal to the DNA-binding Runt domain. In the present study, we examined the region of MITF that is responsible for the interaction with PEBP2. The MITF mutant that lacked the region aa 67-152 did not bind PEBP2, and the mutant that lacked the region aa 1-152 lost the synergistic function in the transactivation of the MMCP-6 promoter. We conclude that the region amino-terminal to the basic region of MITF is required for physical and functional interactions with PEBP2.

Animals↗
PubMed1999

Different effect of various mutant MITF encoded by mi, Mior, or Miwh allele on phenotype of murine mast cells.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). Mutant alleles of mi, Mior, and Miwh are deletion or point mutation of the basic domain by which MITF binds DNA. The basic domain also has nuclear localization potential. In the present study, we compared the mast cell abnormalities of Mior/Mior and Miwh/Miwh mice with those of mi/mi mice, of which many have been described by us. The number of mast cells in the skin of Mior/Mior suckling mice was remarkably decreased from that observed in mi/mi suckling mice, but the number was normal in the skin of Miwh/Miwh suckling mice. The decrease in skin mast cells was more severe in the mi/mi embryos than in mi/mi suckling mice, but the magnitude of the decrease was comparable between Mior/Mior embryos and Mior/Mior suckling mice. The poor mRNA expression of granzyme B and tryptophan hydroxylase genes was observed in all cultured mast cells (CMCs) derived from the spleens of Miwh/Miwh, Mior/Mior, and mi/mi mice. However, the poor expression of mouse mast cell protease-4 (MMCP-4), MMCP-5, and MMCP-6 was observed only in Mior/Mior and mi/mi CMCs. MITF encoded by Miwh mutant allele (Miwh-MITF) showed deficient but demonstratable DNA binding, but mi-MITF and Mior-MITF did not show any DNA binding ability. Although Miwh-MITF and Mior-MITF showed normal nuclear localization potential, the potential was significantly impaired in mi-MITF. The rank order of mast cell abnormality (mi/mi > Mior/Mior > Miwh/Miwh) appears to be related to the functional abnormality of MITF encoded by each mutant gene.

Alleles↗
PubMed1999

Effects of YM90K, a selective AMPA receptor antagonist, on amygdala-kindling and long-term hippocampal potentiation in the rat.

To investigate the role of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) type glutamate receptors in epileptic seizures, we examined the antiepileptogenic and anticonvulsant effects of YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride], a potent and selective new AMPA receptor antagonist, in the rat amygdala-kindling model of epilepsy. Pretreatment with YM90K (7.5-30 mg/kg i.p.) markedly retarded the evolution of kindling. Once kindling was established, administration of YM90K (7.5-30 mg/kg i.p.) significantly and dose-dependently suppressed fully kindled seizures. The maximal effects were observed 15-30 min after injection. When the intensity of electrical stimulation was increased to twice the generalized seizure-triggering threshold, the anticonvulsant effects of YM90K were reversed, suggesting that they were due to elevation of the generalized seizure-triggering threshold. Furthermore, an anticonvulsant dose (15 mg/kg) of YM90K affected neither field potentials nor long-term potentiation in the hippocampus in vivo. These results indicate that AMPA receptors play an important role in the seizure expression mechanism and the development of kindling-induced epileptogenesis, and suggest the possible clinical usefulness of AMPA receptor antagonists as antiepileptic drugs.

Amygdala↗
PubMed1999

Developmental expression of P-glycoprotein (multidrug resistance gene product) in the rat brain.

P-Glycoprotein (PGP), a product of the multidrug resistance gene (mdr), acts as an adenosine triphosphate-dependent drug efflux system in cells. Initially, PGP was found in cancer cells, but it is now known that PGP is richly distributed in the adult brain. Passage to the central nervous system is limited by the blood-brain barrier (BBB), and mdr1 gene-deficient mice showed up-regulation of BBB permeability. In this study, we examined the expression and localization of PGP in the rat brain during development. PGP protein was predominantly detected in the membrane fraction of the adult rat brain, although it was also faintly detected in the cytosolic fraction. PGP protein in the membrane fraction was undetectable in the embryo and early stages of postnatal development by immunoblotting studies, was first detected on postnatal day (P) 7, and then gradually increased to reach a plateau. Such changes were observed commonly in the cerebral cortex, hippocampus, and cerebellum. Immunohistochemical studies showed that PGP immunoreactivity was first detected on P7, and intense PGP immunoreactivity was observed in the adult rat brain. Double-immunolabeling studies revealed that PGP was colocalized with von Willebrand factor-immunoreactive capillaries. We further examined the colocalization of PGP and astrocytes using glial fibrillary acidic protein (GFAP) as a marker. Three-dimensional analysis showed that the GFAP-immunoreactive astrocytes possessed fine processes which ensheathed capillaries, but the PGP immunoreactivity did not colocalize with the GFAP immunoreactivity. These results indicate that PGP expression increased with postnatal development and is localized in the brain capillaries.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

4-hydroxycinnamoyl-CoA hydratase/lyase (HCHL)--An enzyme of phenylpropanoid chain cleavage from Pseudomonas.

The enzyme 4-hydroxycinnamoyl-CoA hydratase/lyase (HCHL), which catalyzes a hydration and two-carbon cleavage step in the degradation of 4-hydroxycinnamic acids, has been purified and characterized from Pseudomonas fluorescens strain AN103. The enzyme is a homodimer and is active with three closely related substrates, 4-coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA (Km values: 5.2, 1.6, and 2.4 microM, respectively), but not with cinnamoyl-CoA or with sinapinoyl-CoA. The abundance of the enzyme reflects a low catalytic center activity (2.3 molecules s-1 at 30 degrees C; 4-coumaroyl-CoA as substrate).

Acyl Coenzyme A↗
PubMed1999

Tyrosine phosphorylation of p62(Dok) induced by cell adhesion and insulin: possible role in cell migration.

Dok, a 62-kDa Ras GTPase-activating protein (rasGAP)-associated phosphotyrosyl protein, is thought to act as a multiple docking protein downstream of receptor or non-receptor tyrosine kinases. Cell adhesion to extracellular matrix proteins induced marked tyrosine phosphorylation of Dok. This adhesion-dependent phosphorylation of Dok was mediated, at least in part, by Src family tyrosine kinases. The maximal insulin-induced tyrosine phosphorylation of Dok required a Src family kinase. A mutant Dok (DokDeltaPH) that lacked its pleckstrin homology domain failed to undergo tyrosine phosphorylation in response to cell adhesion or insulin. Furthermore, unlike the wild-type protein, DokDeltaPH did not localize to subcellular membrane components. Insulin promoted the association of tyrosine-phosphorylated Dok with the adapter protein NCK and rasGAP. In contrast, a mutant Dok (DokY361F), in which Tyr361 was replaced by phenylalanine, failed to bind NCK but partially retained the ability to bind rasGAP in response to insulin. Overexpression of wild-type Dok, but not that of DokDeltaPH or DokY361F, enhanced the cell migratory response to insulin without affecting insulin activation of mitogen-activated protein kinase. These results identify Dok as a signal transducer that potentially links, through its interaction with NCK or rasGAP, cell adhesion and insulin receptors to the machinery that controls cell motility.

Adaptor Proteins, Signal Transducing↗