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T Urano

Publications and source records attributed to T Urano.

At least 91 records · Page 5Linked to original sources
PubMed1998

Cloning and characterization of the murine P2XM receptor gene.

We have isolated the murine counterpart of the human P2XM gene (mP2XM), a P2X purinoceptor that is expressed predominantly in skeletal muscle. The mP2XM gene, consisting of 12 exons that span 10 kb of genomic DNA, encodes a 379-amino-acid product with 83% identity to the human homologue. Two potential transmembrane domains (M1 and M2) are present in the predicted product, and a segment resembling the H5 region of voltage-gated ion channels is completely conserved between human and mouse P2XM proteins. Predominant expression of mP2XM in murine skeletal muscle was confirmed by Northern-blot analysis, and a low level of expression was detectable in lung tissue, although human lung does not express P2XM.

Amino Acid Sequence↗
PubMed1998

Development of maternal IgG-free chick obtained from surgically bursectomized hen.

IgG-free eggs and chicks were developed, so as to study the role of maternal IgG in the development of the immune system. Surgical bursectomy on the 18th day of incubation deprived chickens of B cells and eliminated IgG synthesis. Bursectomized chickens are usually dead before sexual maturity under conventional conditions. When surgically bursectomized chickens were housed in an isolated clean room and antibiotics were administered to them, they could survive to sexual maturity. Finally, we succeeded in obtaining IgG-free fertilized eggs and maternal IgG-free chicks from surgically bursectomized hens. The amount of yolk IgG in IgG-free eggs was one-ten thousandth less than that in normal eggs. The level of IgM in the serum of maternal IgG-free chicks reached six times higher than that of normal chicks 5 days after hatching.

Animals↗
PubMed1998

Extracellular serotonin in the striatum increased after immobilization stress only in the nighttime.

The release of serotonin (5-HT) in the striatum and the motor activity of rats given the immobilization stress were measured using in vivo microdialysis techniques and locomotion counts. Serotonin release in the striatum did not change in the daytime and nighttime, but motor activity in the nighttime was significantly higher than in the daytime. Serotonin release was not significantly increased during immobilization stress in the daytime or nighttime. In the nighttime, however, after the end of stress, 5-HT release was significantly increased from 0.002 ng/dialysate to 0.47 ng/dialysate. The motor activities were also significantly increased after the stress in the nighttime. These results suggest that the effects of immobilization stress on serotonin release in the striatum were different in the daytime and nighttime. In the nighttime, serotonin release in the striatum and the motor activities increased not during but after immobilization stress.

Animals↗
PubMed1998

Severe heat stroke associated with high plasma levels of plasminogen activator inhibitor 1.

In a 38-year-old man, severe heat stroke caused disseminated intravascular coagulation (DIC) associated with significantly elevated plasma plasminogen activator inhibitor 1 levels. Investigation of the effects of hyperthermia on coagulation and fibrinolysis showed, in apparent conflict with previous reports, a time lag between the initial hypercoagulable and hyperfibrinolytic response (within 24 hr) and hypofibrinolysis shown by a disproportionate increase of PAI-1 (after 24 h), which possibly occurs in correspondence with the recovery of vascular endothelial integrity. The patient was discharged without sequelae although computed tomography (CT) scans indicated the likelihood of venous infarction or posterior inferior cerebellar artery area infarction secondary to DIC.

Adult↗
PubMed1998

Effects of nicotine and footshock stress on dopamine release in the striatum and nucleus accumbens.

We have used a microdialysis technique to analyze the effects of nicotine administration on the release of dopamine in the striatum and the nucleus accumbens (NAC) in rats under footshock stress. In the striatum, neither chronic systemic nicotine administration alone nor stress alone changed the extent of dopamine release. During stress application, however, chronic nicotine administration significantly increased dopamine release. In the NAC, stress did not induce increase in dopamine release in rats given nicotine chronically. However, in rats subjected to stress alone, dopamine release in the NAC was significantly increased after stress. In the striatum, the local infusion of 1.0 mM nicotine increased dopamine release. Furthermore, stress significantly increased nicotine-induced dopamine release. The local infusion of 1.0 mM nicotine into the NAC significantly increased dopamine release, but the levels returned to the baseline 30 min later. On the other hand, stress alone induced the release of dopamine 30 min later and the combination of stress and nicotine induced the release of dopamine during the stress and the effects lasted for 30 min. These results suggest that the responses of nicotine-induced dopamine release were different in the striatum and in the NAC under the stress. Stress and nicotine (systematically or locally administered) induced an immediate effect on dopamine release in the striatum, but in the nucleus accumbens stress alone and the combination of stress and nicotine induced a lasting release of dopamine (DA).

Animals↗
PubMed1998

Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers.

Using a bacterial fusion protein, a deleted colorectal carcinoma (DCC)-specific monoclonal antibody (MAb) 127-22 was established. Although MAb 127-22 reacted with almost all normal tissues, it did not react or only weakly reacted with many cancer cell lines, including colonic cancer lines, in flow cytometry. In Western immunoblots, the MAb reacted with a single 190-kDa molecule in a myeloma line Ara-10 extract. This component was scarcely detected in colonic cancer cell lines. Immunoblots of samples from 25 pairs of colonic cancers and adjacent normal tissues and from five adenoma tissues revealed that all normal colonic and adenoma tissues significantly expressed the DCC protein, whereas colonic cancer tissues showed poor expression. These results indicate not only deletion of and lowered mRNA expression of the DCC gene, but also marked reduction of DCC protein occurred in colonic cancer tissues. In addition, colonic cancer patients with liver metastasis expressed significantly lower levels of DCC than those without, suggesting the prognostic value of DCC expression.

Animals↗
PubMed1998

Plasma levels of 5-HT and 5-HIAA increased after intestinal ischemia/reperfusion in rats.

Intestinal ischemia/reperfusion (I/R) causes serious systemic injury, mainly from a variety of bioactive substances released from the injured intestine. To assess the possible roles of serotonin (5-hydroxytryptamine, 5-HT), a bioactive amine mainly stored in the intestine, in I/R injury, we assayed the levels of tryptophan, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) in the blood and intestine in a rat I/R model. Plasma 5-HT increased significantly over time after reperfusion; the plateau level was obtained 4 h after reperfusion and was associated with an increase in 5-HIAA. Plasma tryptophan levels declined gradually after reperfusion. The ratio of 5-HIAA/5-HT was significantly higher in I/R rats than in control rats, suggesting that elevated 5-HT was quickly metabolized in the systemic circulation. In the intestine, 5-HT decreased dramatically, whereas tryptophan increased. This phenomenon was prominent in the severely damaged intestine. These findings suggest that the injured intestine released large amounts of 5-HT, whereas its synthesis in the injured intestine was suppressed. An increase in 5-HT in the circulation may be related to various circulatory disturbances observed in humans after intestinal ischemia.

5-Methoxytryptamine↗
PubMed1998

Effect of chronic furosemide administration on acid-base balance in patients with chronic hypercapnic respiratory failure.

We quantitatively analyzed the effect of long-term administration of oral furosemide on the PaCO2 - H+ relationship in patients with chronic hypercapnic respiratory failure. In this study we measured arterial blood gases of eighteen outpatients (mean duration of visits, 7.6 years; mean rise of PaCO2, 15.4 mmHg). We obtained linear regression lines for PaCO2 - H+, and determined their Y-axis intercepts and slopes. The results indicated that an increase in the administered dose of furosemide decreased linearly the Y-axis intercept of the regression line [(Y-intercept) = - 6.9(dose of furosemide) + 30.9, r = 0.81], and increased linearly the slope of the regression line [(slope) = 0.094(dose of furosemide) + 0.22, r = 0.74]. Thus, the regression line of the PaCO2 - H+ relationship moved downward and became steeper at higher doses of furosemide. The regression lines for each dose of furosemide crossed at a PaCO2 of 75 mmHg. We concluded that there is a mutual interaction between the renal and respiratory mechanisms for acid-base balance in chronic hypercapnia and the effect of furosemide on the PaCO2 - H+ relationship is negligible in severe hypercapnia.

Acid-Base Equilibrium↗
PubMed1998

Human thrombin and calcium bound factor Xa significantly shorten tPA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity.

Employing a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-1) activity by thrombin and factor-Xa in fibrinolysis. When PAI-1 enriched fibrin clots were formed using increasing concentrations of thrombin (0.1, 0.5, 1.0 IU/ml), their lysis times became shorter (43.8 +/- 4.9, 25.7 +/- 3.7, 13.9 +/- 0.8 h respectively). Times were shortened further by either heparin (43.9 +/- 11.0, 12.1 +/- 2.6, 3.6 +/- 0.2 h respectively) or vitronectin (17.0 +/- 1.6, 1.9 +/- 0.7, 0.9 +/- 0.0 h respectively). Factor-Xa together with Ca++ shortened the clot lysis time further. Fibrin autography revealed that both enzymes dose dependently interfered with complex formation between tPA and PAI-1, making large amounts of tPA remaining to be free form. The mechanism seems to play a role in the coagulation associated enhancement of fibrinolysis.

Anticoagulants↗
PubMed1997

An Eps homology (EH) domain protein that binds to the Ral-GTPase target, RalBP1.

Ral proteins constitute a family of small GTPases that can be activated by Ras in cells. In the GTP-bound state, Ral proteins bind to RalBP1, a GTPase-activating protein for CDC42 and Rac GTPases. We have used the two-hybrid system in yeast to clone a cDNA for a novel approximately 85-kDa protein that can bind to an additional site on RalBP1. This newly identified protein contains an Eps homology (EH) domain, which was first detected in the epidermal growth factor (EGF) receptor substrate Eps15. Recently, the EH domain of Eps15 has been shown to bind to proteins containing an asparagine-proline-phenylalanine motif. Moreover, EH domains have been found in proteins involved in endocytosis and/or actin cytoskeleton regulation. The RalBP1 associated Eps-homology domain protein, Reps1, is tyrosine-phosphorylated in response to EGF stimulation of cells. In addition, Reps1 has the capacity to form a complex with the SH3 domains of the adapter proteins Crk and Grb2, which may link Reps1 to an EGF-responsive tyrosine kinase. Thus, Reps1 may coordinate the cellular actions of activated EGF receptors and Ral-GTPases.

Amino Acid Sequence↗
PubMed1997

Tyrosine phosphorylation of Crk-associated substrates by focal adhesion kinase. A putative mechanism for the integrin-mediated tyrosine phosphorylation of Crk-associated substrates.

Integrin-ligand binding induces the tyrosine phosphorylation of various proteins including focal adhesion kinase (pp125(FAK)) and Crk-associated substrate (Cas). FAK is activated and autophosphorylated by the ligation of integrins, although the substrate of FAK has not been revealed. We show here that p130(Cas) and Cas-L are FAK substrates. FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins. Furthermore, the phosphorylated YDYVHL sequence is a binding site for Src family protein-tyrosine kinases, and the recruited Src family kinase phosphorylates the other tyrosine residues within Cas. The Cas-L YDYVHL sequence is phosphorylated upon integrin-ligand binding, and this integrin-mediated tyrosine phosphorylation is inhibited by the cotransfection of the FAK COOH-terminal domain that does not contain a kinase domain. These findings strongly suggest that FAK initiates integrin-mediated tyrosine phosphorylation of Cas proteins; then, Src family tyrosine kinases, which are recruited to phosphorylated Cas and FAK, further phosphorylate Cas proteins.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Inhibitory effect of selenium on biliary secretion of methyl mercury in rats.

The inhibitory effect of sodium selenite on biliary secretion of methyl mercury was examined in rats. The biliary secretion of methyl mercury in rat treated with 1 mumol/kg of methyl mercury was significantly decreased by administration of selenite at doses of 0.05 mumol/kg or higher. In rats given 10 mumol/kg of methyl mercury, marked depression of biliary secretion of mercury was observed when selenite was injected at a dose of 0.2 mumol/kg. On the other hand, secretion of substantial amounts of selenium was observed when biliary secretion of mercury was depressed. When the concentration of selenium in the bile was higher than 5 nmol/ml, biliary secretion of mercury was markedly depressed independently of the dose of methyl mercury administered (1 mumol/kg or 10 mumol/kg). These results suggest that the degree of inhibitory effect of selenite may be determined by the selenium concentration in the liver or the bile after treatment with selenite rather than the molar ratio of the dose of methyl mercury and selenite. We concluded that the decrease in biliary secretion of methyl mercury induced by selenite may result from inhibition of pathway for secretion of methyl mercury from liver to bile rather than the direct formation of a complex between methyl mercury and selenium. Methyl mercury has been considered to be secreted from liver to bile as a complex with glutathione (GSH). However, administration of selenite did not affect biliary secretion of GSH or hepatic glutathione S-transferase activity. Moreover, gel filtration of liver cytosol demonstrated that the distribution pattern of hepatic methyl mercury between macromolecules and GSH was not significantly changed by administration of selenite. These results suggest that selenite does not affect complex formation of methyl mercury with GSH at least in the liver. Selenite might specifically inhibit the activity of the canalicular transporter(s) which transport complexes of methyl mercury and GSH from the liver to bile.

Animals↗
PubMed1997

Cloning of P2XM, a novel human P2X receptor gene regulated by p53.

Through cloning of functional p53-binding sites (p53-tagged sites) from the human genome, we isolated a novel gene inducible by wild-type p53. Its cDNA sequence contained an open reading frame encoding a 431-amino acid peptide that showed a significant homology with members of the P2X family. This protein also revealed a similarity to RP-2, a gene activated in thymocytes undergoing programmed cell death. Northern blot analysis showed that it was expressed predominantly in skeletal muscle. Hence, we designated the gene P2XM (P2X specifically expressed in skeletal muscle). P2XM was localized to chromosomal band 22q11, where frequent loss of heterozygosity has been observed in rhabdoid tumors. Although we detected no genetic alteration in the coding sequences, one of four rhabdomyosarcoma cell lines examined had completely lost expression of this gene. Furthermore, a minor splice variant lacking a part of exon 1 that would encode residues corresponding to transmembrane domain M1 was relatively more abundant in two of seven sarcoma cell lines, one of which was derived from a rhabdomyosarcoma, and the other was derived from an osteosarcoma. The results suggest that P2XM may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and that its altered expression may be involved in the development of some sarcomas.

Alternative Splicing↗
PubMed1997

Genomic structure and chromosomal localization of GML (GPI-anchored molecule-like protein), a gene induced by p53.

Among its known functions, tumor suppressor gene p53 serves as a transcriptional regulator and mediates various signals through activation of downstream genes. We recently identified a novel gene, GML (glycosylphosphatidylinositol (GPI)-anchored molecule-like protein), whose expression is specifically induced by wildtype p53. To characterize the GML gene further, we determined 35.8 kb of DNA sequence that included a consensus binding sequence for p53 and the entire GML gene. The GML gene consists of four exons; and the p53-binding sequence is present in the 5'-flanking region. In genomic organization this gene resembles genes encoding murine Ly-6 glycoproteins, a human homologue of the Ly-6 family called RIG-E, and CD59; products of these genes, known as GPI-anchored proteins, are variously involved in signal transduction, cell-cell adhesion, and cell-matrix attachment. FISH analysis revealed that the GML gene is located on human chromosome 8q24.3. Genes encoding at least two other GPI-anchored molecules, E48 and RIG-E, are also located in this region.

Animals↗
PubMed1997

A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis.

The genetic alteration of p53 is associated with neovascularization during progression of glioma to its more malignant form, glioblastoma. Hence, one or more of the genes transactivated by p53 is likely to function as an angiogenesis inhibitors. We isolated a novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospondin type 1 (TSP-type 1) repeats and is specifically expressed in the brain. A recombinant protein corresponding to the TSP-type 1 repeats of this gene product inhibited in vivo neovascularization induced by bFGF in the rat cornea. The expression of this gene, designated BAI1 (brain-specific angiogenesis inhibitor 1) was absent or significantly reduced in eight of nine glioblastoma cell lines, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.

Amino Acid Sequence↗
PubMed1997

Rapid response to inhaled frusemide in severe acute asthma with hypercapnia.

We report 7 patients with severe acute asthma unresponsive to standard medication, including sympathomimetic agents, aminophylline and corticosteroids, who responded to inhaled frusemide. All were hypercapneic with a mean PaCO2 of 7.7 kPa (57.7 mm Hg) [range 6.2-8.8 kPa (46.2-66.3 mm Hg)]. Following nebulization of 20 mg frusemide, clinical response was rapid, and the mean PaCO2 fell significantly to 5.4 kPa (40.6 mm Hg) [range 5.0-6.2 kPa (37.5-46.5 mm Hg)] within 20-60 min. No adverse effect was recognized. Inhaled frusemide should be considered for treatment of acute asthma refractory to conventional therapy.

Acute Disease↗