[A case of non-icteric middle-lower common bile duct cancer with intraductal superficial spread to the gall bladder].
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Adenocarcinoma, Papillary↗
Biomedical subjects
M Noda
Publications and source records attributed to M Noda.
[A survey of opioid use in preanesthetic medication].
A mailing survey was carried out to assess the current practice of sedative premedication in anesthesia. Questionnaires were sent by mail to 77 university hospitals. We especially evaluated use of opioids for premedication. Sixty-one percent (n = 47) of the hospitals answered these questionnaires and 31 percent (n = 15) of them were using opioids for the preanesthetic medication. Pethidine was used most frequently for premedication of all opioids, and morphine was often used for the premedication before cardiac surgery. All opioids were administrated intramusculary both in adults and children.
Adolescent↗
Osteopontin expression and function: role in bone remodeling.
The cytokine and cell attachment protein osteopontin (OPN) is not necessary for the development and survival of mice in a clean animal facility. The primary role of OPN appears to be that of facilitating recovery of the organism after injury or infection, which generally causes an increase in its expression. It also is essential for some forms of bone remodeling. OPN stimulates cellular signaling pathways via various receptors found on most cell types and can encourage cell migration. OPN modulates immune and inflammatory responses and possibly negatively regulates Ras signaling pathways. Its apparent ability to enhance cell survival by inhibiting apoptosis may explain why the metastatic proficiency of tumor cells increases with increased OPN expression.
Animals↗
An interferon regulatory factor-related gene (xIRF-6) is expressed in the posterior mesoderm during the early development of Xenopus laevis.
Out of a Xenopus neurula cDNA library, we isolated a clone which encodes a 52.4-kDa protein highly similar to the mouse interferon regulatory factor, IRF-6, whose function is unknown. The mRNA of this gene, named xIRF-6, seems to be maternally transmitted, but its amount rapidly decreases after the tailbud stage. Whole-mount in situ hybridization showed that xIRF-6 mRNA is expressed in the presumptive somitic mesoderm in the late gastrula, and then confined to a segment of posterior somite during the neurula through the tailbud stage. The temporally and spatially limited expression of the xIRF-6 gene product may contribute to the transcriptional regulation of specific genes which are necessary for the development of the posterior somites.
Amino Acid Sequence↗
Muscarinic receptor-mediated dual regulation of ADP-ribosyl cyclase in NG108-15 neuronal cell membranes.
Cyclic ADP-ribose (cADP-ribose) is an endogenous modulator of ryanodine-sensitive Ca2+ release channels. An unsolved question is whether or not cADP-ribose mediates intracellular signals from hormone or neurotransmitter receptors. The first step in this study was to develop a TLC method to measure ADP-ribosyl cyclase, by which conversion of [3H]NAD+ to [3H]cADP-ribose was confirmed in COS-7 cells overexpressing human CD38. A membrane fraction of NG108-15 neuroblastoma x glioma hybrid cells possessed ADP-ribosyl cyclase activity measured by TLC. Carbamylcholine increased this activity by 2.6-fold in NG108-15 cells overexpressing m1 or m3 muscarinic acetylcholine receptors (mAChRs), but inhibited it by 30-52% in cells expressing m2 and/or m4 mAChRs. Both of these effects were mimicked by GTP. Pretreatment of cells with cholera toxin blocked the activation, whereas pertussis toxin blocked the inhibition. Application of carbamylcholine caused significant decreases in NAD+ concentrations in untreated m1-transformed NG108-15 cells, but an increase in cholera toxin-treated cells. These results suggest that mAChRs couple to ADP-ribosyl cyclase within cell membranes via trimeric G proteins and can thereby control cellular function by regulating cADP-ribose formation.
ADP-ribosyl Cyclase↗
Identification of a novel suppressive vitamin D response sequence in the 5'-flanking region of the murine Id1 gene.
Vitamin D promotes differentiation of cells either by simply enhancing phenotypic gene expression and/or by suppressing expression of inhibitors of differentiation. Previously, we reported that expression of a gene encoding Id1, a negative type helix-loop-helix transcription factor, was transcriptionally suppressed by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (1). To identify the sequence required for the negative regulation by 1, 25(OH)2D3, a 1.5-kilobase 5'-flanking region of murine Id1 gene was examined by transiently transfecting luciferase reporter constructs into ROS17/2.8 osteoblastic cells. The transcriptional activity of this construct was repressed by 10(-8) M 1,25(OH)2D3. Deletion analysis revealed that a 57-base pair (bp) upstream response sequence (URS) (-1146/-1090) was required for the suppression by 1,25(OH)2D3. This sequence conferred negative responsiveness to 1,25(OH)2D3 to a heterologous SV40 promoter. The 57-bp URS contained not only Egr-1 consensus sequence (2) but also four direct repeats of a heptamer sequence (C/A)CAGCCC. Electrophoresis mobility shift assay revealed that the 57-bp URS formed specific nuclear protein-DNA complexes, which were neither competed by previously known positive and negative vitamin D response elements nor supershifted by anti-vitamin D receptor antibody, suggesting the absence of vitamin D receptor in these complexes. These results indicate the involvement of the novel 57-bp sequence in the vitamin D suppression of Id1 gene transcription.
Animals↗
Overexpression of a single helix-loop-helix-type transcription factor, scleraxis, enhances aggrecan gene expression in osteoblastic osteosarcoma ROS17/2.8 cells.
Cell differentiation is determined by a certain set of transcription factors such as MyoD in myogenesis. However, transcription factors that play a positive role in phenotypic gene expression in skeletal cells are largely unknown, except the recently identified CBFA1. Scleraxis is a helix-loop-helix-type transcription factor whose transcripts are expressed in sclerotome and in a certain set of skeletal cells; however, nothing is known about its function with regard to the regulation of cell function. To examine possible roles of scleraxis, we overexpressed scleraxis in osteoblastic ROS17/2.8 cells, which express low levels of scleraxis. Scleraxis overexpression enhanced expression of the aggrecan gene, which is not normally expressed at high levels in these osteoblastic cells. Overexpression of scleraxis also increased mRNA levels of type II collagen and osteopontin while suppressing expression of osteoblast phenotype-related genes encoding type I collagen and alkaline phosphatase. Transient transfection experiments indicated that scleraxis enhanced the chloramphenicol acetyltransferase activity of the reporter construct AgCAT-8, which contained an 8-kilobase pair (kb) fragment of the aggrecan gene including both the promoter and its first intron. Deletion analysis identified a 1-kb region that is responsive to scleraxis within the aggrecan gene. This region contains two adjacent E-box sequences. A 29-base pair DNA fragment (AgE) containing these E-box sequences bound to proteins in the ROS17/2.8 cell nuclear extracts as well as to in vitro translated scleraxis. This binding was competed with unlabeled AgE, but not with a mutated E-box DNA sequence (mAgE), indicating the specificity of the binding activity. The AgE binding activity in the ROS17/2.8 cell nuclear extracts was enhanced in the cells overexpressing scleraxis and was supershifted by the antiserum raised against scleraxis. Furthermore, AgE, but not mAgE, conferred responsiveness to scleraxis overexpression to a heterologous promoter. Finally, replacement mutation of the AgE sequence within the 2.5-kb AgCAT-1 construct significantly reduced its responsiveness to scleraxis. These results indicate that overexpression of a single helix-loop-helix-type transcription factor, scleraxis, enhances aggrecan gene expression via binding to the E-box-containing AgE sequence in ROS17/2.8 cells.
Aggrecans↗
Scleraxis messenger ribonucleic acid is expressed in C2C12 myoblasts and its level is down-regulated by bone morphogenetic protein-2 (BMP2).
We examined the mRNA expression of scleraxis, a non-myogenic helix-loop-helix type transcription factor in C2C12 myogenic cells. Scleraxis mRNA has been shown to be expressed in sclerotome and perichondrium of the embryos. We found that C2C12 cells express 1.2 kb scleraxis mRNA constitutively. Since BMP was reported to induce ectopic bone formation when implanted in muscle, we examined the effects of BMP on scleraxis expression. Scleraxis mRNA expression in C2C12 cells was suppressed by the treatment with BMP2. This suppression was observed at 200 ng/ml but not at the lower concentrations. BMP2 treatment suppressed scleraxis mRNA level within 24 h and lasted at least up to 48 h. Electrophoresis mobility shift assay showed that the proteins in the crude nuclear extracts prepared from C2C12 cells bound to an Scx-E-box sequence, CATGTG, which is preferentially recognized by scleraxis. This binding was competed out by 100-fold molar excess of cold Scx-E-box sequence but not by the one with mutations in the E-box. This band was supershifted by the addition of antiserum raised against scleraxis. BMP2 treatment suppressed the Scx-E binding activity in C2C12 cells. This suppression of the Scx-E-box binding activity was in parallel to the BMP2 suppression of the transcriptional activity of the Scx-E-CAT reporter gene transfected into C2C12 cells. These data indicated that although the default pathway for C2C12 cells is to differentiate into muscle cells, these cells do express non-myogenic transcription factor, scleraxis, whose expression is suppressed by BMP2.
Animals↗
Stimulated activation of platelet-derived growth factor receptor in vivo in balloon-injured arteries: a link between angiotensin II and intimal thickening.
BACKGROUND: Growth factors such as platelet-derived growth factor (PDGF) have been postulated to be important mediators of neointimal formation in balloon-injured artery. Binding of growth factors to their receptors activates intrinsic receptor tyrosine kinase, resulting in tyrosine phosphorylation of receptors themselves and cellular substrate proteins. We investigated in vivo activities of growth factors by determining the extent of tyrosine phosphorylation of growth factor receptors and substrate proteins in injured artery. METHODS AND RESULTS: Rat balloon-injured carotid artery was analyzed for phosphotyrosine content of PDGF alpha- and beta-receptors, epidermal growth factor (EGF) receptors, and insulin receptor substrate-1 (IRS-1) by immunoprecipitation and anti-phosphotyrosine Western blot. The development of intimal thickening after deendothelializing balloon catheterization of rat carotid artery was accompanied by transient twofold to threefold increases in the extent of tyrosyl phosphorylation of PDGF alpha- and beta-receptors but not EGF receptor or IRS-1. The AT1 angiotensin II (Ang II) receptor antagonist TCV-116 markedly inhibited both tyrosyl phosphorylation of PDGF alpha- and beta-receptors and intimal thickening. The AT1 antagonist reduced mRNA levels of both PDGF-A and -B chains in injured arteries. CONCLUSIONS: The present study provides direct evidence for increased PDGF activities in injured artery in situ and the involvement of Ang II in stimulated activation of PDGF receptors. These results are consistent with the pathogenetic role for PDGF in intimal thickening.
Amlodipine↗
Serum NAD glycohydrolase activities in normal subjects and in patients with chronic liver diseases.
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Adolescent↗
A novel gene encoding a ferredoxin reductase-like protein expressed in the neuroectoderm in Xenopus neurula.
In an attempt to elucidate the molecular mechanisms of early neural development in Xenopus laevis, we identified, using a differential display method, several genes that are induced after Concanavalin A treatment in the animal caps prepared from stage 9 blastula. One such gene was found to encode a possible type IIIa membrane protein of 66.2 kDa sharing similarities with several prokaryotic and eukaryotic redox enzymes, hence the putative product was named Nfrl, neurula-specific ferredoxin reductase-like protein. Northern blot analysis confirmed that the expression of the Nfrl gene is up-regulated around the neurula stage, and is much lower in embryos of earlier stages and in adult tissues. The temporally limited expression of this gene implies neurula- and early larva-specific redox reactions of certain substrates, the nature of which remains to be elucidated.
Animals↗
Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures.
The mouse Nedd5 gene encodes a 41.5-kD GTPase similar to the Saccharomyces and Drosophila septins essential for cytokinesis. Nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody. Microinjection of anti-Nedd5 antibody interferes with cytokinesis, giving rise to binucleated cells. In interphase and postmitotic cells, Nedd5 localizes to fibrous or granular structures depending on the growth state of the cell. The Nedd5-containing fibers are disrupted by microinjection of GTPgammaS and by Nedd5 mutants lacking GTP-binding activity, implying that GTP hydrolysis is required for its assembly. The Nedd5-containing fibers also appear to physically contact actin bundles and focal adhesion complexes and are disrupted by cytochalasin D, C3 exoenzyme, and serum starvation, suggesting a functional interaction with the actin-based cytoskeletal systems in interphase cells.
3T3 Cells↗
A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity.
We have characterized a nontoxic mutant of cholera toxin (CT) as a mucosal adjuvant in mice. The mutant CT was made by substitution of serine with phenylalanine at position 61 of the A subunit (S61F), which resulted in loss of ADP ribosyltransferase activity and toxicity. Mice were intranasally immunized with ovalbumin, tetanus toxoid, or influenza virus either alone or together with mutant CT S61F, native CT, or recombinant CT-B. Mice immunized with these proteins plus S61F showed high serum titers of protein-specific IgG and IgA antibodies that were comparable to those induced by native CT. Further, high protein-specific IgA antibody responses were observed in nasal and vaginal washes, saliva, and fecal extracts as well as increased numbers of IgG and IgA antibody forming cells in cervical lymph nodes and lung tissues of mice intranasally immunized with these proteins and S61F or native CT, but not with recombinant CT-B or protein alone. Both S61F and native CT enhanced the induction of ovalbumin-specific CD4(+) T cells in lung and splenic tissues, and these T cells produced a Th2-type cytokine pattern of interleukin 4 (IL-4), IL-5, IL-6, and IL-10 as determined by analysis of secreted proteins and by quantitation of cytokine-specific mRNA. These results have shown that mutant CT S61F is an effective mucosal adjuvant when administrated intranasally and induces mucosal and systemic antibody responses which are mediated by CD4(+) Th2-type cells.
Animals↗
Mutants in the ADP-ribosyltransferase cleft of cholera toxin lack diarrheagenicity but retain adjuvanticity.
Cholera toxin (CT), the most commonly used mucosal adjuvant in experimental animals, is unsuitable for humans because of potent diarrhea-inducing properties. We have constructed two CT-A subunit mutants, e.g., serine-->phenylalanine at position 61 (S61F), and glutamic acid-->lysine at 112 (E112K) by site-directed mutagenesis. Neither mutant CT (mCT), in contrast to native CT (nCT), induced adenosine diphosphate-ribosylation, cyclic adenosine monophosphate formation, or fluid accumulation in ligated mouse ileal loops. Both mCTs retained adjuvant properties, since mice given ovalbumin (OVA) subcutaneously with mCTs or nCT, but not OVA alone developed high-titered serum anti-OVA immunoglobulin G (IgG) antibodies (Abs) which were largely of IgG1 and IgG2b subclasses. Although nCT induced brisk IgE Ab responses, both mCTs elicited lower anti-OVA IgE Abs. OVA-specific CD4+ T cells were induced by nCT and by mCTs, and quantitative analysis of secreted cytokines and mRNA revealed a T helper cell 2 (Th2)-type response. These results now show that the toxic properties of CT can be separated from adjuvanticity, and the mCTs induce Ab responses via a Th2 cell pathway.
Adjuvants, Immunologic↗
cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene.
The Nedd4 gene was initially identified by a subtraction cloning approach as a highly expressed transcript in the mouse embryonic brain. Cloning of the Nedd4 cDNA indicated that it can encode a protein of approximately 103 kDa, consisting of a Ca2+ and phospholipid binding domain, three putative protein-protein interaction domains (the WW domains), and a carboxyl-terminus region similar to the ubiquitin-protein ligase domain (hect domain). In mouse embryos, the expression of Nedd4 in the central nervous system is highest during neurogenesis and decreases as development progresses. In addition to the central nervous system, the expression of Nedd4 is detected in various embryonic tissues and persists in most adult tissues. Using an antibody raised against a fusion protein, we show that Nedd4 protein is localized to the cellular cytoplasm. We have mapped the mouse Nedd4 gene to chromosome 9 using an interspecific backcross panel. Nedd4 maps to a previously defined homologous region between human and mouse chromosomes and thus provides additional information regarding interspecies comparative mapping.
Amino Acid Sequence↗
The contribution of endogenous mono-ADP-ribosylation to kindling-induced epileptogenesis.
We examined the alteration of endogenous mono ADP-ribosylation in the hippocampus of amygdaloid kindled rats to clarify the neurochemical basis of epilepsy. A significant increase of the ADP-ribosylation on the 38 kDa protein was observed in the hippocampal membrane of the kindled rat. Several antiepileptics (phenytoin, phenobarbital, carbamazepine, sodium valproate) significantly decreased the ADP-ribosylation on the 38 kDa protein and effaced the increase in the kindled group. The ADP-ribosylation was largely increased by sodium nitroprusside, a nitric oxide generating compound, in both the kindled and control groups. Carbamazepine could not affect the ADP-ribosylation in the presence of sodium nitroprusside. Twenty amino acids from the N-terminus of the ADP-ribosylated 38 kDa protein were determined by sequential analysis. The sequence was completely identical to that of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that the endogenous mono-ADP-ribosylation which increased in the kindled group and decreased by the antiepileptics might be a specific reaction associated with the mechanisms of epileptogenesis.
Adenosine Diphosphate Ribose↗
Characterization of rat receptor-like protein tyrosine phosphatase gamma isoforms.
We identified four isoforms of receptor-like protein tyrosine phosphatase gamma (RPTPgamma) from rat brain by cDNA cloning. We designated these molecules RPTPgamma-A, -B, -C, and -S. RPTPgamma-A was the longest form and had the same structure as human and mouse RPTPgamma. RPTPgamma-B lacked the intracellular juxtamembrane 29 amino acids of RPTPgamma-A. RPTPgamma-C had a single phosphatase domain. RPTPgamma-S is an extracellular variant of RPTPgamma. mRNAs of the four isoforms were expressed in the brain, kidney, lung, and heart. Transfection of RPTPgamma-A and -S expression plasmids into COS7 cells resulted in the expression of membrane-bound 190-kDa proteins and secreted 120-kDa proteins, respectively. These molecules were similar to PTPzeta/RPTPbeta with regard not only to structure but also to the presence of both secretory and transmembrane forms. However, RPTPgamma isoforms were not expressed as proteoglycans.
Amino Acid Sequence↗
Loss of biological activity due to Glu-->Arg mutation at residue 11 of the B subunit of cholera toxin.
Since it has been reported that a single amino acid mutation of Gly-->Arg in the CAGYC region of the beta chain of human thyroid stimulating hormone (hTSH) was responsible for congenital isolated TSH deficiency, and that the same amino acid substitution in this site of hTSH and human chorionic gonadotropin (hCG) introduced by site-directed mutagenesis resulted in loss of activity, the authors studied the role of glutamic acid at position 11 (Glu-11) from the N-terminus of the B subunit of cholera toxin (CT), which corresponds to the glycine in the CAGYC region of the beta chain of hTSH and hCG. A mutant CT constructed by site-directed mutagenesis in which Glu-11 was replaced by Arg (CT-E11R) did not induce either morphological changes or accumulation of cytosolic cyclic AMP in Chinese hamster ovary cells, although it formed the holotoxin AB5, retained the ability to bind to GM1-ganglioside and showed ADP-ribosyltransferase activity. Weak assembly of the B subunits in mutant CT-E11R demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-heating conditions might explain the loss of biological activity.
Amino Acid Substitution↗