Search PubMed⌕ Search

Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 73 records · Page 4Linked to original sources

Localization of odor-induced oscillations in the bumblebee antennal lobe.

Odor-induced oscillatory signals have been reported in odor discrimination in various insects. To understand dynamic olfactory coding in the first order olfactory center, the antennal lobe, localization of oscillatory signals was investigated using an optical recording technique with a voltage-sensitive dye. We present here the first report of visualization of the spatial distribution pattern of odor-induced oscillations in the bumblebee antennal lobe. Analysis of the odor-induced optical responses by a maximum entropy method allowed visualization of oscillatory regions in the antennal lobe. The oscillatory signals were usually localized to regions corresponding to a single or several glomerular structures. Our results suggest that glomerular structures may be functional units of odor processing from the viewpoint of odor-induced population responses, the oscillations.

Action Potentials↗

A homeobox gene, PRESSED FLOWER, regulates lateral axis-dependent development of Arabidopsis flowers.

It is postulated that the symmetric organization of plant lateral organs is based on two crossed axes, the abaxial-adaxial and the lateral axes. The PRESSED FLOWER (PRS) gene, the expression and function of which are dependent on the lateral axis, is reported in this study. In the prs mutant, growth of the lateral sepals is repressed, and although the size and shape of the abaxial and adaxial sepals are normal, the cell files at the lateral margins are missing. Double-mutant analyses showed that the PRS gene functions independently of the determinations of both floral organ identity and floral meristem size. The PRS gene, encoding a putative transcriptional factor with a homeodomain, was shown to be required for cell proliferation. PRS gene expression is spatially and temporally unique and is expressed in a restricted number of L1 cells at the lateral regions of flower primordia, floral organ primordia, and young leaf primordia. Our study strongly suggests that the PRS gene is involved in the molecular mechanism of lateral axis-dependent development of lateral organs in Arabidopsis.

Alleles↗

Aprotinin but not epsilon-aminocaproic acid decreases interleukin-10 after cardiac surgery with extracorporeal circulation: randomized, double-blind, placebo-controlled study in patients receiving aprotinin and epsilon-aminocaproic acid.

BACKGROUND: Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation. METHODS AND RESULTS: Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon-aminocaproic acid achieved statistical significance. Both aprotinin and epsilon-aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups. CONCLUSIONS: These data suggest that aprotinin and epsilon-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes.

Aminocaproic Acid↗

Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection.

Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a pivotal role in the pathogenesis of acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopulations especially within T-cell subpopulations are unclear in these EBV-related disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV. EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations were quite different between acute EBV-HLH and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV-infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disorders, and self-limited acute infectious mononucleosis. These results showing differential virus-cell interactions between acute EBV-HLH and CAEBV indicated different pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical manifestations between the 2 diseases.

Acute Disease↗

Enhanced homologous recombination caused by the non-transcribed spacer of the rDNA in Arabidopsis.

The problem of the low frequency of homologous recombination observed in higher plants has been approached in several ways. Here, we report a new strategy to enhance homologous recombination in Arabidopsis. In Escherichia coli and Saccharomyces cerevisiae, hotspots that enhance homologous recombination nearby have been identified in regions close to sites associated with the blocking of DNA replication forks or with intensive transcriptional activity. In yeast, a recombination hotspot (HOT1) was found in a region spanning two non-transcribed spacers (NTS) between ribosomal RNA genes (rDNA), which contains both a replication fork barrier ( RFB) and the promoter for transcription of the 35S rRNA gene. Since rDNA has a common structure among eukaryotes, we analyzed the effect of the endogenous NTS on homologous mitotic recombination in a higher plant. We constructed transgenic lines of Arabidopsis containing this NTS and a recombination substrate, in which two 3'- and 5'-deleted uidA (beta-glucuronidase) genes with partially overlapping sequences are separated by a Hyg(r) gene. Reconstitution of functional uidA genes by homologous recombination was monitored by histochemical GUS staining. We found that recombination occurred more frequently in all organs tested in F (Fork block) lines transgenic for the NTS than in C (Control) lines without the NTS. The average number of GUS+ spots on leaves in F lines was more than nine-fold higher than in C lines. Furthermore, by genomic Southern analysis, post-recombinational molecules were detected in a transgenic line, F43, which had an extremely high number of GUS+ blue spots. These results strongly suggest that NTS-dependent enhancement of homologous recombination may be a common feature of higher plants as well as yeast.

Arabidopsis↗

Preparation and crystallization of the stimulatory and inhibitory complexes of GTP cyclohydrolase I and its feedback regulatory protein GFRP.

Mammalian GTP cyclohydrolase I is a decameric enzyme in the first and rate-limiting step in the biosynthesis of tetrahydrobiopterin, which is an essential cofactor for enzymes producing neurotransmitters such as catecholamines and for nitric oxide synthases. The enzyme is dually regulated by its feedback regulatory protein GFRP in the presence of its stimulatory effector phenylalanine and its inhibitory effector biopterin. Here, both the stimulatory and inhibitory complexes of rat GTP cyclohydrolase I bound to GFRP were crystallized by vapour diffusion. Diffraction data sets at resolutions of 3.0 and 2.64 A were collected for the stimulatory and inhibitory complexes, respectively. Each complex consists of two GTPCHI pentamer rings and two GFRP pentamer rings, with pseudo-52 point-group symmetry.

Animals↗

Structures of Escherichia coli branched-chain amino acid aminotransferase and its complexes with 4-methylvalerate and 2-methylleucine: induced fit and substrate recognition of the enzyme.

The following three-dimensional structures of three forms of Escherichia coli branched-chain amino acid aminotransferase (eBCAT) have been determined by the X-ray diffraction method: the unliganded pyridoxal 5'-phosphate (PLP) form at a 2.1 A resolution, and the two complexes with the substrate analogues, 4-methylvalerate (4-MeVA) as the Michaelis complex model and 2-methylleucine (2-MeLeu) as the external aldimine model at 2.4 A resolution. The enzyme is a trimer of dimers, and each subunit consists of small and large domains, and the interdomain loop. The active site is formed by the residues at the domain interface and those from two loops of the other subunit of the dimer unit, and binds one PLP with its re-face directed toward the protein side. Upon binding of a substrate, Arg40 changes its side-chain direction to interact with the interdomain loop, and the loop, which is disordered in the unliganded form, shows its ordered structure on the active-site cavity, interacts with the hydrophobic side chain of the substrate, and shields it from the solvent region. The substrate binds to the active-site pocket with its alpha-hydrogen toward the protein side, its side-chain on the side of O3 of PLP, and its alpha-carboxylate on the side of the phosphate group of PLP. The hydrophobic side-chain of the substrate is recognized by Phe36, Trp126, Tyr129, Tyr164, Tyr31*, and Val109*. The alpha-carboxylate of the substrate binds to the unique site constructed by three polar groups (two main-chain NH groups of the beta-turn at Thr257 and Ala258 and the hydroxy group of Tyr95) which are activated by the access of Arg40 to the main-chain C=O group of the beta-turn and the coordination of Arg97 to the hydroxy group. Since Arg40 is the only residue that significantly changes its side-chain conformation and directly interacts with the interdomain loop and the beta-turn, the residue plays important roles in the induced fit of the interdomain loop and the alpha-carboxylate recognition of the substrate.

Bacillus↗

TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer.

Caspase-associated recruitment domains (CARDs) are protein interaction domains that participate in activation or suppression of CARD-carrying members of the caspase family of apoptosis-inducing proteases. A novel CARD-containing protein was identified that is overexpressed in some types of cancer and that binds and suppresses activation of procaspase-9, which we term TUCAN (tumor-up-regulated CARD-containing antagonist of caspase nine). The CARD domain of TUCAN selectively binds itself and procaspase-9. TUCAN interferes with binding of Apaf1 to procaspase-9 and suppresses caspase activation induced by the Apaf1 activator, cytochrome c. Overexpression of TUCAN in cells by stable or transient transfection inhibits apoptosis and caspase activation induced by Apaf1/caspase-9-dependent stimuli, including Bax, VP16, and staurosporine, but not by Apaf1/caspase-9-independent stimuli, Fas and granzyme B. High levels of endogenous TUCAN protein were detected in several tumor cell lines and in colon cancer specimens, correlating with shorter patient survival. Thus, TUCAN represents a new member of the CARD family that selectively suppresses apoptosis induced via the mitochondrial pathway for caspase activation.

Adaptor Proteins, Signal Transducing↗

Arabidopsis nph1 and npl1: blue light receptors that mediate both phototropism and chloroplast relocation.

UV-A/blue light acts to regulate a number of physiological processes in higher plants. These include light-driven chloroplast movement and phototropism. The NPH1 gene of Arabidopsis encodes an autophosphorylating protein kinase that functions as a photoreceptor for phototropism in response to low-intensity blue light. However, nph1 mutants have been reported to exhibit normal phototropic curvature under high-intensity blue light, indicating the presence of an additional phototropic receptor. A likely candidate is the nph1 homologue, npl1, which has recently been shown to mediate the avoidance response of chloroplasts to high-intensity blue light in Arabidopsis. Here we demonstrate that npl1, like nph1, noncovalently binds the chromophore flavin mononucleotide (FMN) within two specialized PAS domains, termed LOV domains. Furthermore, when expressed in insect cells, npl1, like nph1, undergoes light-dependent autophosphorylation, indicating that npl1 also functions as a light receptor kinase. Consistent with this conclusion, we show that a nph1 npl1 double mutant exhibits an impaired phototropic response under both low- and high-intensity blue light. Hence, npl1 functions as a second phototropic receptor under high fluence rate conditions and is, in part, functionally redundant to nph1. We also demonstrate that both chloroplast accumulation in response to low-intensity light and chloroplast avoidance movement in response to high-intensity light are lacking in the nph1 npl1 double mutant. Our findings therefore indicate that nph1 and npl1 show partially overlapping functions in two different responses, phototropism and chloroplast relocation, in a fluence rate-dependent manner.

Arabidopsis↗

Cyclooxygenase-2 expression in the hippocampus of genetically epilepsy susceptible El mice was increased after seizure.

It has been suggested that cyclooxygenase (COX)-2 and prostaglandin play a role in epilepsy. We studied the expression of COX-2 in the hippocampus and the effect of oral administration of indomethacin, a COX inhibitor, on seizure activity in genetically seizure-susceptible El mice. COX-2 protein significantly increased in the hippocampi of El mice after epileptic seizure. Indomethacin did shorten the duration from seizure onset to full recovery in El mice although the threshold and the duration of seizure were not changed.

Animals↗

Arabidopsis NPL1: a phototropin homolog controlling the chloroplast high-light avoidance response.

Chloroplasts relocate their positions in a cell in response to the intensity of incident light, moving to the side wall of the cell to avoid strong light, but gathering at the front face under weak light to maximize light interception. Here, Arabidopsis thaliana mutants defective in the avoidance response were isolated, and the mutated gene was identified as NPL1 (NPH-like 1), a homolog of NPH1 (nonphototropic hypocotyl 1), a blue light receptor used in phototropism. Hence, NPL1 is likely a blue light receptor regulating the avoidance response under strong light.

Alleles↗

Theory of oxygen 1s resonant X-ray emission spectroscopy in copper-based oxides.

Many-body effects on the oxygen 1s resonant x-ray emission spectrum (O 1s RXES) in copper-based oxides, such as Sr2CuO3 and La2CuO4, are discussed on the basis of cluster-model calculations. The Zhang-Rice singlet excitation, which is a typical many-body state in Cu-based oxide systems, can be detected at low temperatures where the antiferromagnetic correlation between the neighboring Cu spins is strong. Thus the present study emphasizes that the O 1s RXES can be a good tool to obtain information on the Cu 3d states. In particular the polarization-dependent RXES gives the symmetry-decomposed information.

Journal Article↗

Prostaglandin E2 up-regulates macrophage-derived chemokine production but suppresses IFN-inducible protein-10 production by APC.

PGE(2) has been known to suppress Th1 responses. We studied the role of PGE(2) in two representative chemokines, macrophage-derived chemokine (MDC) and IFN-inducible protein-10, production by LPS- or CD40-stimulated spleen cells. The production of MDC, one of the ligands for CCR4 preferentially expressed on Th2, was enhanced in nonstimulated, LPS-, CD40-, or CD3-stimulated spleen cells by the pretreatment with PGE(2), while the production of IFN-inducible protein-10, a representative ligand for CXC chemokine receptor 3 expressed on Th1, was suppressed. MDC production was also enhanced by IL-4, IL-5, and intracellular cAMP-elevating agents such as dibutyryl cAMP and 3-isobutyl-1-methylxanthine, and the effect of IL-4, IL-5, and PGE(2) was additive. However, the pretreatment with IL-6, IL-10, or TGF-beta, or the neutralization of IFN-gamma or IL-12 had no effect on MDC production. B cells, macrophages, and dendritic cells were main producers of MDC, while T cells produced only a small amount of MDC. MDC production by B cells was equally stimulated by LPS and anti-CD40 Ab, while that by macrophages and dendritic cells was more markedly stimulated by anti-CD40 Ab, and PGE(2) further enhanced MDC production by these stimulated cells. These results indicate that PGE(2) regulates Th1/Th2-related chemokine production by B cells, macrophages, and dendritic cells, and that this is a new function of PGE(2) for the regulation of Th2 immune responses at the induction and activation stages.

Adjuvants, Immunologic↗