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Akiko Ito

Publications and source records attributed to Akiko Ito.

At least 19 recordsLinked to original sources

Large-scale DNA polymorphism study of Oryza sativa and O. rufipogon reveals the origin and divergence of Asian rice.

Polymorphism over approximately 26 kb of DNA sequence spanning 22 loci and one region distributed on chromosomes 1, 2, 3 and 4 was studied in 30 accessions of cultivated rice, Oryza sativa, and its wild relatives. Phylogenetic analysis using all the DNA sequences suggested that O. sativa ssp. indica and ssp. japonica were independently domesticated from a wild species O. rufipogon. O. sativa ssp. indica contained substantial genetic diversity (pi = 0.0024), whereas ssp. japonica exhibited extremely low nucleotide diversity (pi = 0.0001) suggesting the origin of the latter from a small number of founders. O. sativa ssp. japonica contained a larger number of derived and fixed non-synonymous substitutions as compared to ssp. indica. Nucleotide diversity and genealogical history substantially varied across the 22 loci. A locus, RLD15 on chromosome 2, showed a distinct genealogy with ssp. japonica sequences distantly separated from those of O. rufipogon and O. sativa ssp. indica. Linkage disequilibrium (LD) was analyzed in two different regions. LD in O. rufipogon decays within 5 kb, whereas it extends to approximately 50 kb in O. sativa ssp. indica.

Base Sequence↗

Ethylene-regulation of fruit softening and softening-related genes in peach.

To investigate the role of ethylene in peach fruit softening during ripening, stony hard peach fruit, in which ethylene production is suppressed during ripening, were treated with various concentrations of ethylene. There was no noticeable decrease in flesh firmness without ethylene treatment, while applied ethylene, in the range 0.1-100 microl l(-1), resulted in fruit softening. Furthermore, the fruit softened more rapidly when the applied ethylene concentration was higher. When ethylene treatment was interrupted, the degree of softening was greatly reduced. These results indicated that continuous ethylene treatment was required for the initiation and progression of fruit softening and that ethylene concentration is also an important factor in regulating the rate of softening. Eight genes, which putatively encode cell wall metabolism-related proteins, were investigated for mRNA accumulation patterns in the two different softening phenotypes of melting and stony hard peaches. All of the mRNAs investigated accumulated in fruit of the melting-flesh "Akatsuki" during ripening. By contrast, in the stony hard-flesh "Manami", the mRNAs for a putative endopolygalacturonase (PpPG), an alpha-L-arabinofuranosidase/beta-xylosidase (PpARF/XYL), and an expansin (PpExp3) showed either much lower levels or did not accumulate, and were identified as softening-related genes. Interruption of ethylene treatment indicated that these genes were regulated at the transcriptional level, and quickly responded to the presence or absence of ethylene before the softening response occurred, suggesting that ethylene directly regulates the transcription of these softening-related genes. These results suggested that cell wall metabolism, causing a rapid loss of firmness in peach fruit, may be controlled by ethylene at the transcriptional level.

Cell Wall↗

Hypoxia-inducible factor-1 mediates the expression of DNA polymerase iota in human tumor cells.

Hypoxia generated in tumors has been shown to contribute to mutations and genetic instability. However, the molecular mechanisms remain incompletely defined. Since reactive oxygen species (ROS) are overproduced immediately after reoxygenation of hypoxic cells and generate oxidized guanine, we assumed that the mechanisms might involve translesion DNA polymerases that can bypass oxidized guanine. We report here that hypoxia as well as hypoxia mimetics, desferrioxamine, and CoCl(2), enhanced the expression of DNA polymerase iota (pol iota) in human tumor cell lines. Searching the consensus sequence of hypoxia response element to which HIF-1 binds revealed that it locates in the intron 1 of the pol iota gene. These results suggest that HIF-1-mediated pol iota gene expression may be involved in the generation of translesion mutations during DNA replication after hypoxia followed by reoxygenation, thereby contributing to the accumulation of genetic changes in tumor cells.

Cell Hypoxia↗

SuperSAGE array: the direct use of 26-base-pair transcript tags in oligonucleotide arrays.

We developed a new platform for genome-wide gene expression analysis in any eukaryotic organism, which we called SuperSAGE array. The SuperSAGE array is a microarray onto which 26-bp oligonucleotides corresponding to SuperSAGE tag sequences are directly synthesized. A SuperSAGE array combines the advantages of the highly quantitative SuperSAGE expression analysis with the high-throughput microarray technology. We demonstrated highly reproducible gene expression profiling by the SuperSAGE array for 1,000 genes (tags) in rice. We also applied this technology to the detailed study of expressed genes identified by SuperSAGE in Nicotiana benthamiana, an organism for which sufficient genome sequence information is not available. We propose that the SuperSAGE array system represents a new paradigm for microarray construction, as no genomic or cDNA sequence data are required for its preparation.

Base Pairing↗

NKG2D ligation without T cell receptor engagement triggers both cytotoxicity and cytokine production in dendritic epidermal T cells.

NKG2D is an activating receptor that recognizes self-ligands induced on stressed, infected, or transformed cells. In mice, two NKG2D isoforms (NKG2D-S (short) and NKG2D-L (long)) that associate differentially with DAP10 and DAP12 adaptor proteins exist. Differential expression of these isoforms and adaptor proteins depending on the activating state and cell types determines distinct functional outcomes of NKG2D ligation: direct activation of cytotoxicity in natural killer (NK) cells and cytokine production in activated NK cells, but only costimulation in activated CD8+ T cells. Intraepithelial gammadelta T cells of the mouse skin, termed dendritic epidermal T cells (DETCs), were also shown to express NKG2D, but the NKG2D isoform(s) expressed in DETCs have not been determined. Furthermore, functional outcomes of NKG2D ligation in DETCs are largely unknown, although costimulation of DETC-mediated cytotoxicity by NKG2D was demonstrated. Here, we show that DETCs constitutively express NKG2D-S, NKG2D-L, DAP10, and DAP12 transcripts as well as cell surface NKG2D protein. Blocking of NKG2D inhibited DETC-mediated cytotoxicity against target cells that do not express T cell receptor ligands. Cross-linking of NKG2D on DETCs induced IFN-gamma production. These findings demonstrate that DETCs constitutively express NKG2D that acts as a primary activating receptor, and indicate its important role in cutaneous immune surveillance.

Adaptor Proteins, Signal Transducing↗

[A case of dermatomyositis associated with chronic idiopathic myelofibrosis].

A 74-year old woman had been suffering from chronic idiopathic myelofibrosis (CIMF) for three years before noticing skin rash and subsequent muscle weakness. On admission, purplish and erythematous skin rash was seen spreading over large parts of her body, including the face, chest, back and extremities. She could not stand up without assistance due to weakness. On laboratory examination, her hemoglobin was found to be 11.8g/dl, platelet 17,000/microl, WBC 22,500/microl (with blast cells), and CK 1,757 IU/I. Auto-antibodies including antinuclear antibody, Jo-I antibody and rheumatoid factors were negative. Abdominal CT revealed giant splenomegaly. She was diagnosed as having dermatomyositis (DM) associated with CIMF. Although administration of prednisolone followed by methyl-prednisolone pulse therapy ameliorated the weakness and skin rash, WBC increased to 35,000/ microl. In case of worsening of CIMF, azathioprine (AZP) administered. This decreased the WBC count to 13,700/microl and the CK to 49 IU/I 40 days after the administration. Patients with CIMF have an increased incidence of complications of other autoimmune diseases, indicating that the immunological mechanism plays some roles in the progression of the disease. There has been only one other reported case of DM complication. This case suggests usefulness of AZP treatment combined with prednisolone in these patients.

Aged↗

Structural visualization of expert nursing: Diabetes self-management education program.

In the Japanese clinical setting, expert nursing, and at the same time quality and safety assurance, are demanded. To provide nursing service with reliable assurance of nursing quality and safety, structural visualization of the thought, judgment and behavior processes of nursing practice and widespread application through development of IT applied systems are required. We have discussed and developed the structural visualization of programmed care in the field of diabetes self-management education, which is an area of expert nursing care. In this article, we report the programmed care for dietary therapy.

Diabetes Mellitus↗

High-throughput in planta expression screening identifies a class II ethylene-responsive element binding factor-like protein that regulates plant cell death and non-host resistance.

We performed high-throughput screening using the potato virus X (PVX) system to overexpress Nicotiana benthamiana genes in planta and identify positive regulators of cell death. This screening identified NbCD1, a novel class II ethylene-responsive element binding factor (ERF), as a potent inducer of the hypersensitive response (HR)-like cell death. NbCD1 expression was induced by treatments with INF1 elicitor and a non-host pathogen Pseudomonas cichorii. NbCD1 exhibited transcriptional repressor activity through its EAR motif, and this motif was necessary for NbCD1 to cause cell death. We identified 58 genes that displayed altered transcription following NbCD1 overexpression. NbCD1 overexpression downregulated the expression of HSR203, a negative regulator of hypersensitive death. Conditional expression of NbCD1 in Arabidopsis also caused cell death, indicating that NbCD1 downstream cascades are conserved in dicot plants. To further confirm the role of NbCD1 in defense, we used virus-induced gene silencing to demonstrate that NbCD1 is required for non-host resistance of N. benthamiana to the bacterial pathogen P. cichorii. Our data point to a model of transcriptional regulatory cascades. NbCD1 positively regulates cell death and contributes to non-host resistance, possibly by downregulating the expression of other defense response genes.

Amino Acid Sequence↗

SuperSAGE.

The application of transcriptomics to study host-pathogen interactions has already brought important insights into the mechanisms of pathogenesis, and is expanding further keeping pace with the accumulation of genomic sequences of host organisms (human and economically important organisms such as food crops) and their pathogens (viruses, bacteria, fungi and protozoa). In this review, we introduce SuperSAGE, a substantially improved variant of serial analysis of gene expression (SAGE), as a potent tool for the transcriptomics of host-pathogen interactions. Notably, the generation of 26 bp tags in the SuperSAGE procedure allows to decipher the 'interaction transcriptome', i.e. the simultaneous monitoring of quantitative gene expression, of both a host and one of its eukaryotic pathogens. The potential of SuperSAGE tags for a rapid functional analysis of target genes is also discussed.

Animals↗

[Gadolinium enhancement of the anterior portion of the lumbosacral roots in a case of post-irradiation lumbosacral radiculopathy].

A 35-year-old woman, who underwent the removal of her uterus as a result of treatment for cancer of the cervix, developed weakness in the distal lower limbs after 8 months of subsequent radiation therapy. Although she could not walk because of distal dominant weakness and atrophy in the legs, no sensory disturbances were observed. An MRI scan showed gadolinium enhancement of the anterior portion of the lumbosacral roots in the cauda equina, which corresponded to her neurological symptoms. The administration of corticosteroid and warfarin dramatically alleviated her neurological symptoms, and a follow-up MRI scan one month later demonstrated a marked diminution of the gadolinium enhancement. There were only seven reports describing the abnormalities of the MRI findings, all of which noted the gadolinium enhancement of the anterior portion of the lumbosacral roots. Together with the findings in other reports, the enhancement abnormalities seem to be characteristic of post-irradiation lumbosacral radiculopathy.

Adult↗

Up-regulation of cell surface Toll-like receptor 4-MD2 expression on dendritic epidermal T cells after the emigration from epidermis during cutaneous inflammation.

BACKGROUND: Mouse epidermis contains a population of gammadelta T cells, termed dendritic epidermal T cells (DETCs), which uniformly express the invariant Vgamma3 T cell receptor. Certain DETC lines were reported to respond to Gram-negative bacteria in the presence of immobilized anti-CD3 monoclonal antibody or to lipopolysaccharide (LPS) in the presence of B cell lines. OBJECTIVE: To determine whether DETCs express the primary signaling receptor for LPS, Toll-like receptor (TLR) 4-MD2. METHODS: We analyzed expression of TLR4-MD2 in three independent DETC lines as well as in freshly isolated DETCs. RESULTS: All DETC lines expressed TLR4 and MD2 transcripts and TLR4-MD2 protein complex intracellularly, but none expressed TLR4-MD2 on the cell surface. By immunoblotting, only the immature form of TLR4 protein was detected in the DETC lines. The DETC lines did not respond to LPS even in the presence of immobilized anti-CD3 monoclonal antibody. Freshly isolated DETCs and their fetal thymic precursors also lacked cell surface expression of TLR4-MD2, but a small subpopulation of dermal Vgamma3 T cells isolated from croton oil-painted skin expressed TLR4-MD2 on the cell surface. Similarly, Vgamma3 T cells emigrated from organ-cultured epidermis expressed cell surface TLR4-MD2. CONCLUSIONS: These results demonstrate that DETCs do not constitutively express cell surface TLR4-MD2, but TLR4-MD2 expression may be up-regulated when DETCs emigrate from epidermis during cutaneous inflammation.

Animals↗

Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells.

Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin; CPT-11) is a widely used potent antitumor drug that inhibits mammalian DNA topoisomerase I (Topo I); however, overexpression of ABCG2 (BCRP/MXR/ABCP) can confer cancer cell resistance to SN-38, the active form of CPT-11. We have recently demonstrated that plasma membrane vesicles prepared from ABCG2-overexpressing PC-6/SN2-5H cells transported SN-38 and its glucuronide conjugate in an ATP-dependent manner (Nakatomi et al., Biochem Biophys Res Commun 2001;288:827-32). In the present study, we have characterized a total of 14 new camptothecin (CPT) analogues with respect to both the inhibition of Topo I and the substrate specificity of ABCG2. All of the tested CPT analogues, which have different substitutions at positions 10 and 11, strongly inhibited the Topo I activity in a cell-free system, as did SN-38. Their antitumor activities in the SN-38-resistant PC-6/SN2-5H2 cell line greatly varied, however, being correlated with intracellular accumulation levels. We have examined ATP-dependent transport of those CPT analogues by using plasma membrane vesicles prepared from both PC-6/SN2-5H2 cells and ABCG2-transfected HEK-293 cells. Based on the substrate specificity of ABCG2 thus evaluated, it is strongly suggested that CPT analogues with high polarity are good substrates for ABCG2 and are therefore effectively extruded from cancer cells. In this context, to circumvent ABCG2-associated drug resistance, low-polarity CPT analogues are considered to be potent lead compounds. The present study provides a practical approach to discover new CPT-based drugs for the chemotherapy of drug-resistant human cancer.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

A subset of hypersensitive response marker genes, including HSR203J, is the downstream target of a spermine signal transduction pathway in tobacco.

A cellular signal transduction pathway induced by the polyamine, spermine (Spm), and transmitted by mitochondrial dysfunction is proposed in tobacco. In this investigation, we further resolve the pathway by identifying a subset of hypersensitive response (HR) marker genes as downstream components. In a previous report, we identified harpin-induced 1 (HIN1) and two closely related genes as responsive to Spm. Other HR marker genes, HSR203J, HMGR, HSR201, and HSR515, are also Spm-responsive. Induction of these HR marker genes, including HIN1, by Spm was suppressed by pre-treatment with antioxidants, calcium channel blockers, inhibitor of mitochondrial permeability transition pore openings, and blockers of amine oxidase/polyamine oxidase. Such quenching is also observed for Spm-induced activation of two mitogen-activated protein kinases (MAPKs), salicylic acid-induced protein kinase (SIPK), and wound-induced protein kinase (WIPK), and upregulation of the WIPK gene, suggesting that all these components are part of the same signaling pathway. Furthermore, gain-of-function and loss-of-function studies on MAPK cascade members reveal that the expression of Spm-induced HR marker genes varies with respect to involvement of SIPK/WIPK activation.

Antioxidants↗

[Drug resistance mediated by ABC transporters].

Remarkable advances have been made in cancer chemotherapy by developing new anticancer drugs and pharmacogenomics strategies. However, multidrug resistance in human cancers is the major obstacle to long-term, sustained patient response to chemotherapy. Several ATP-binding cassette (ABC) transporters cause multidrug resistance in cancer cells by actively extruding the clinically administered chemotherapeutic drugs. P-glycoprotein (ABCB1/MDR1/P-gp) and MRP1 (ABCC1/GS-X pump) have been well characterized in terms of their molecular structure and function. In addition, ABCG2/breast cancer resistance protein (BCRP) is the most recently identified/ABC transporter, and is also reportedly associated with cellular resistance against chemotherapeutic agents, such as DNA topoisomerase I, II inhibitor. It is important to note that these ABC transporters are expressed not only in cancer cells but also in normal tissues to play a pivotal role in the absorption, distribution, and excretion of endogenous substances as well as xenobiotics. ABC transporters are key factors that can affect the pharmacokinetic profiles of drugs. Recent studies have revealed that many single nucleotide polymorphisms (SNPs) reside in these ABC transporter genes. Functional analysis of the genetic polymorphism of ABC transporters would greatly contribute to our understanding of individual differences in the drug response and also to the development of personalized medicine in the near future.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Gene expression analysis of plant host-pathogen interactions by SuperSAGE.

The type III restriction endonuclease EcoP15I was used in isolating fragments of 26 bp from defined positions of cDNAs. We call this substantially improved variant to the conventional serial analysis of gene expression (SAGE) procedure "SuperSAGE." By applying SuperSAGE to Magnaporthe grisea (blast)-infected rice leaves, gene expression profiles of both the rice host and blast fungus were simultaneously monitored by making use of the fully sequenced genomes of both organisms, revealing that the hydrophobin gene is the most actively transcribed M. grisea gene in blast-infected rice leaves. Moreover, SuperSAGE was applied to study gene expression changes before the so-called hypersensitive response in INF1 elicitor-treated Nicotiana benthamiana, a "nonmodel" organism for which no DNA database is available. Again, SuperSAGE allowed rapid identification of genes up- or down-regulated by the elicitor. Surprisingly, many of the down-regulated genes coded for proteins involved in photosynthesis. SuperSAGE will be especially useful for transcriptome profiling of two or more interacting organisms like hosts and pathogens, and of organisms, for which no DNA database is available.

Base Sequence↗

A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport.

Overexpression of the ATP-binding cassette transporter ABCG2 reportedly causes multidrug resistance, whereas altered drug-resistance profiles and substrate specificity are implicated for certain variant forms of ABCG2. At least three variant forms of ABCG2 have been hitherto documented on the basis of their amino acid moieties (i.e., arginine, glycine and threonine) at position 482. In the present study we have generated those ABCG2 variants by site-directed mutagenesis and expressed them in HEK-293 cells. Exogenous expression of the Arg(482), Gly(482), and Thr(482) variant forms of ABCG2 conferred HEK-293 cell resistance toward mitoxantrone 15-, 47- and 54-fold, respectively, as compared with mock-transfected HEK-293 cells. The transport activity of those variants was examined by using plasma-membrane vesicles prepared from ABCG2-overexpressing HEK-293 cells. [Arg(482)]ABCG2 transports [(3)H]methotrexate in an ATP-dependent manner; however, no transport activity was observed with the other variants (Gly(482) and Thr(482)). Transport of methotrexate by [Arg(482)]ABCG2 was significantly inhibited by mitoxantrone, doxorubicin and rhodamine 123, but not by S -octylglutathione. Furthermore, ABCG2 was found to exist in the plasma membrane as a homodimer bound via cysteinyl disulphide bond(s). Treatment with mercaptoethanol decreased its apparent molecular mass from 140 to 70 kDa. Nevertheless, ATP-dependent transport of methotrexate by [Arg(482)]ABCG2 was little affected by such mercaptoethanol treatment. It is concluded that Arg(482) is a critical amino acid moiety in the substrate specificity and transport of ABCG2 for certain drugs, such as methotrexate.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Fetal hepatic hemangioma representing non-reassuring pattern in fetal heart rate monitoring.

To the best of our knowledge, this is the first report of a non-reassuring fetal pattern caused by a hepatic hemangioma that was found during fetal heart rate monitoring. A 37 weeks' gestation, a 32-year-old-woman was referred to our hospital for evaluation of a rapidly growing fetal abdominal tumor. Fetal heart rate monitoring revealed a non-reassuring pattern, and a cesarean section was performed as a result. Examination of the 2820 g female infant suggested a hepatic hemangioma accompanying an intratumor hemorrhage and coagulopathy. The infant died 2 days after birth. The autopsy confirmed that the cause of death was a result of a hepatic hemangioma. Frequent monitoring of fetuses and ultrasound examinations are necessary for determining the timing of delivery and for a favorable prognosis.

Adult↗