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Biomedical subjects

T Endo

Publications and source records attributed to T Endo.

At least 343 records · Page 19Linked to original sources
PubMed1998

A novel thyroid transcription factor is essential for thyrotropin-induced up-regulation of Na+/I- symporter gene expression.

The stimulation of iodide (I-) transport by TSH in FRTL-5 thyroid cells is partly due to an increase in Na+/I- symporter (NIS) gene expression. The identification of a TSH-responsive element (TRE) in the NIS promoter and its relationship to the action of thyroid transcription factor-1 (TTF-1) on the promoter are the subjects of this report. By transfecting NIS promoter-luciferase chimeric plasmids into FRTL-5 cells in the presence or absence of TSH, we identify a TRE between -420 and -370 bp of the NIS 5'-flanking region. Nuclear extracts from FRTL-5 cells cultured in the absence of TSH form two groups of protein-DNA complexes, A and B, in gel mobility shift assays using an oligonucleotide having the sequence from -420 to -385 bp. Only the A complex is increased by exposure of FRTL-5 cells to TSH or forskolin. The addition of TSH to FRTL-5 cells can increase the A complex at 3-6 h, reaching a maximum at 12 h. FRTL-5, but not nonfunctioning FRT thyroid or Buffalo rat liver (BRL) cell nuclear extracts, form the A complex. The TSH-increased nuclear factor in FRTL-5 cells interacting with the NIS TRE is distinct from TTF-1, thyroid transcription factor-2, or Pax-8, as evidenced by the absence of competition using oligonucleotides specific for these factors in gel shift assays. Neither is it the nuclear protein interacting with cAMP response element. The TRE is in the upstream of a TTF-1-binding site, -245 to -230 bp. Mutation of the TRE causing a loss of TSH responsiveness also decreases TTF-1-induced promoter activity in a transfection experiment. The formation of the A complex between FRTL-5 nuclear extracts and the NIS TRE is redox-regulated. In sum, TSH/cAMP-induced up-regulation of the NIS requires a novel thyroid transcription factor, which also appears to be involved in TTF-1-mediated thyroid-specific NIS gene expression.

Animals↗
PubMed1998

Reversal of myogenic terminal differentiation by SV40 large T antigen results in mitosis and apoptosis.

Terminally differentiated skeletal muscle myotubes are arrested in the G0 phase of the cell cycle, and this arrest is not reversed by stimulation with serum or growth factors. The myotubes have been shown to be refractory to apoptosis even under low serum conditions. When the SV40 large T antigen is induced in the C2SVTts11 myotubes, which stably harbor the T antigen gene linked to an inducible promoter, the terminally differentiated cells reenter the cell cycle to resume nuclear DNA replication representing S phase. We show here that the large T-expressing myotubes further proceeded to M phase represented by the appearance of mitotic figures with centrosomes, condensed chromosomes, and mitotic spindles. The myotubes eventually cleaved and midbodies were formed at the cleavage sites of the cytoplasm. In some cases actin filaments, reminiscent of the contractile rings, accumulated at the cleavage furrows. Thus, terminally differentiated myotubes remain able to resume at least one round of the cell cycle and consequently are considered to be capable of dedifferentiation. A subset of myotubes expressing large T did not undergo mitosis. Some of them were degenerative and contained deformed giant nuclei and pulverized nuclei. The others suffered apoptotic cell death, which was identified by morphological changes of the nuclei and the labeling with dUTP at the ends of chromatin DNA fragments. The induction of apoptosis was unlikely to be confined to a particular phase of the cell cycle. These results imply that terminally differentiated myotubes also retain a complete set of machinery for apoptosis.

Animals↗
PubMed1998

Inactivation of blasticidin S by Bacillus cereus. VI. Structure and comparison of the bsr gene from a blasticidin S-resistant Bacillus cereus.

Two types of recombinant plasmids containing 600 bp Nde I fragments that coded the bsr gene in opposite directions were obtained. Nucleotide sequencing shows that the bsr encodes a 140 amino acid protein with a putative molecular weight of 15560, the same as that of purified blasticidin S (BS)-deaminase (BSR), on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (15500). Upstream of the open reading frame, a Shine-Dalgarno (SD) sequence, frequent inverted repeats, and the sigmaA and sigmaB promoter sequences are observed. The transcriptional start point was determined to be the A located 7 bases downstream from the putative sigmaA promoter (91TTGATC and 113TAAAAT) by the primer extension method and site directed mutagenesis at the -10 or -35 promoter region. A comparison of the amino acid sequence of BSR with that of BS-deaminase from Aspergillus terreus (BSD) showed 27.2% homology. Low degrees of homology were also observed with cytidine deaminase and deoxy cytidine monophosphate (CMP) deaminase. Four conserved amino acid motifs were observed, VGAx6G, C(orH)AEx6A, SPCGxCR, and Gx8ELIP (x(n) indicates a nonspecific residue and its position). It is possible that the three Cys residues and the Glu in the conserved motifs comprise the active center. Site-directed mutagenesis of the Cys residues supports this possibility.

Amino Acid Sequence↗
PubMed1998

Discovery of a structurally novel opioid kappa-agonist derived from 4,5-epoxymorphinan.

A new type of kappa-agonist, 17-cyclopropylmethyl-3, 14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl) acrylamido]morphinan hydrochloride (1, TRK-820), was discovered by a new working hypothesis. The "message-address concept" for opioid antagonists and the "accessory site" for general antagonists were applied to design TRK-820. A unique structural feature of TRK-820, which is different from other prototypical kappa-opioid receptor agonists, is the existence of the 4,5-epoxymorphinan structure with a tyrosine-glysine moiety for endogenous opioid peptides such as dynorphins. TRK-820 exhibited high potency and high kappa-selectivity in guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. In the mouse acetic-acid-induced writhing model and mouse tail flick model of antinociception, TRK-820 was 85-140 times more potent than morphine and 85-350 times more potent than U-50488H. This structurally novel kappa-agonist showed neither aversion nor preference in the Conditioned Place Preference test, in spite of the fact that prototypes of kappa-agonists (U-50488H derivatives) demonstrated aversion.

Animals↗
PubMed1998

Purulent pericarditis with tamponade caused by Salmonella enteritidis.

The incidence of purulent pericarditis has declined. However, mortality remains high. We describe a case of purulent pericarditis with tamponade caused by Salmonella enteritidis, and emphasize the importance of early recognition, prompt institution of appropriate antibiotic therapy, and early surgical drainage for survival.

Adult↗
PubMed1998

[Signal transduction of serotonin release from enterochromaffin cells in mouse ileal crypts].

Although serotonin (5-HT) release from enterochromaffin (EC) cells is considered to be regulated by multiple receptor-mediated mechanisms, little is known about the signal transduction in EC cells. We investigated the effects of adrenoceptor stimulation on 5-HT release from ileal tissue and intracellular calcium dynamics of epithelial cells in isolated ileal crypts in mice. Ileal tissues placed in organ bath were perfused with a buffered solution. Released 5-HT was measured using HPLC-ECD. Ileal crypts were isolated by collagenase digestion followed by moderate pipetting. Intracellular calcium dynamics were analyzed by digital video-imaging system using fura-2. NE, but not isoprenaline (Iso), induced 5-HT release from mouse ileal tissue. NE-induced 5-HT release was antagonized by yohimbine and rauwolscine, but not by prazosin and bunazosin. NE, but not Iso, also elicited a transient elevation of intracellular calcium in some EC cells. The effect of NE (1 microM) was slightly suppressed by prazosin and bunazosin, but was remarkably suppressed by yohimbine and rauwolscine. UK 14,304 and Clonidine at 10 microM significantly induced an increase in intracellular calcium concentration. NE-induced intracellular calcium dynamics was not significantly affected by timolol, Ro20-1724, rolipram and 8-bromo-cAMP. These results suggest that NE-induced 5-HT release from ileal EC cells is mediated predominantly via alpha 2-, but not beta-adrenoceptors, by a mechanism dependent on elevation of intracellular calcium concentration.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1998

Selective induction of interleukin-1 production and tumor killing activity of macrophages through apoptosis by the inhibition of oxidative respiration.

Suppression of mitochondrial respiration and increased glycolysis are characteristic features of activated macrophages. We show here that antimycin A, a respiratory inhibitor, induced interleukin-1 synthesis and tumoricidal activity without inducing tumor necrosis factor or nitric oxide. The induction of tumoricidal activity was resistant to inhibitors of tyrosine-specific protein kinases and intracellular glycoprotein transport. The cognate interaction between macrophages and target cells was not a prerequisite for the tumoricidal activity. In contrast, lipopolysaccharide induced the production of interleukin-1, tumor necrosis factor and nitric oxide, the induction of tumoricidal activity being sensitive to genistein and brefeldin A. Antimycin A, like lipopolysaccharide, induced the release of a cytoplasmic enzyme and apoptosis of macrophages. Antimycin A showed anti-metastatic activity in vivo. These results suggest that the inhibition of oxidative respiration would induce apoptosis and the resultant release of soluble effector molecules of macrophages which inhibit tumor metastasis in vivo.

Animals↗
PubMed1998

Identification of a structural gene encoding a metallothionein-like domain that includes a putative regulator protein for Streptomyces protease gene expression.

An open reading frame (termed ORF-PR) encoding a metallothionein-like domain-including protein was found upstream of a previously identified Streptomyces chymotrypsin-type protease gene (sam-P20). Promoter and terminator activities of ORF-PR were detected using the promoterless Streptomyces tyrosinase gene as a reporter gene and expression of ORF-PR was supposed to occur before that of sam-P20 gene. Frameshift mutation analysis showed that the ORF-PR product might act as a repressive regulator of the sam-P20 gene.

Amino Acid Sequence↗
PubMed1998

Subacute and chronic toxicity studies of triethylenetetramine dihydrochloride (TJA-250) by oral administration to F-344 rats.

Triethylenetetramine dihydrochloride (trientine-2HCl, TJA-250), a copper chelating agent used to treat Wilson's disease, was administered orally to male and female F-344 rats for 4 or 8 weeks at dosages of 0, 100, 350 or 1200 mg/kg/day or for 26 weeks at dosages of 50, 175 or 600 mg/kg/day. 4 or 8-week study. Two males receiving 1200 mg/kg/day died during week 8 of treatment. In males receiving 1200 mg/kg/day during weeks 5 to 8 of treatment, body weight gain and food consumption were decreased and hunched posture and thin build were observed. During week 4 or 8 of treatment urinalysis revealed, for males receiving 100 mg/kg/day or animals receiving 350 mg/kg/day or more, increased electrolyte outputs possibly due to the hydrochloride nature of trientine-2HCl, with low plasma alkaline phosphatase activities evident in animals receiving 350 or 1200 mg/kg/day. After 4 and 8 weeks, and during 8 weeks of treatment, high lung weights and bronchiolar epithelium hypertrophy and broncho-alveolar pneumonia were recorded for animals receiving 1200 mg/kg/day, and submucosal acute inflammation within the glandular region of the stomach was recorded for males receiving 350 or 1200 mg/kg/day and in all treated female groups. 26-week study. One male receiving 175 mg/kg/day and three males receiving 600 mg/kg/day died, showing lung changes. The body weight gain of animals receiving 600 mg/kg/day was slightly decreased. Blood chemistry and urinalysis examinations showed changes similar to those indicated in the 4- or 8-week study. The low plasma copper concentrations seen in males receiving 600 mg/kg/day, the slightly low liver copper concentrations found in animals receiving 600 or 175 mg/kg/day and the high urinary copper concentrations found in all treated groups, are attributed to the pharmacological action of trientine-2HCl. Histopathology revealed a dosage-related incidence and severity of focal chronic interstitial pneumonitis accompanied by fibrosis of the alveolar walls in females receiving 175 mg/kg/day or more and all treated male groups, but no significant pathological changes in the stomach. Apart from the histological changes found in the lung, all the above changes were reversible. In conclusion, the NOAEL of trientine-2HCl in this 26-week study was considered to be 50 mg/kg/day for females and less than 50 mg/kg/day for males.

Administration, Oral↗
PubMed1998

Transient isolated thyrotropin deficiency associated with cavernous sinus syndrome.

The cause and course of isolated thyrotropin (TSH) deficiency are not well understood. We report a 65-year-old man with a transient, probable isolated TSH deficiency associated with cavernous sinus syndrome secondary to tympanitis. On his admission, serum TSH and triiodothyronine levels were very low. No TSH response to thyrotropin releasing hormone (TRH) was observed. However, 6 years later, TSH response to TRH was restored. The present case showed that inflammation in the cavernous sinus could be one of the causes of TSH deficiency. Further, it demonstrated that TSH deficiency is not always permanent and the reevaluation of pituitary function is necessary.

Aged↗
PubMed1998

Evaluation of a sulfobutyl ether beta-cyclodextrin as a solubilizing/stabilizing agent for several drugs.

To evaluate the potential use of beta-cyclodextrin sulfobutyl ether, 7 sodium salt (SBE7-beta-CD) as a drug solubilizing and stabilizing agent, the solubilizing effects of SBE7-beta-CD on 22 different poorly water-soluble drugs were compared with those of intact beta-CD and heptakis-(2,6-di-O-methyl)-beta-CD (DMCD). SBE7-beta-CD was generally a more effective solubilizer for poorly water-soluble drugs than was intact beta-CD, but SBE7-beta-CD was not as effective as DMCD. The effects of SBE7-beta-CD on the acid hydrolysis rate of prostaglandin I2, the alkaline hydrolysis rate of indomethacin, the dehydration of prostaglandin E1, and the isomerization of prostaglandin A1 were also investigated and compared to those for intact beta-CD, DMCD, and 2,3,6 partially methylated-beta-CD (PMCD). The stabilizing effects of SBE7-beta-CD on chemically unstable drugs were generally higher than those of other CDs.

Acids↗
PubMed1998

Effects of estradiol and an aromatase inhibitor on progesterone production in human cultured luteal cells.

The human corpus luteum produces both estradiol and progesterone. It is well known that there are both autocrine and paracrine systems for the regulation of the corpus luteum and that estradiol regulates the progesterone production of the corpora lutea of some other species. To assess the direct effects of estrogen on human luteal function, we performed cell culture experiments. A low concentration of estradiol, almost equal to the amount of estradiol produced by human cultured luteal cells, directly stimulated progesterone production. 4-Cyclohexylaniline, an aromatase inhibitor, significantly reduced both progesterone production and estradiol production. Levels of estradiol higher than the levels that cultured human luteal cells themselves produced significantly reduced basal progesterone production and also significantly reduced human chorionic gonadotropin (hCG), forskolin and dibutyryl-cyclic AMP-stimulated progesterone production. According to these data, high doses of estradiol produced a luteolytic action which widely inhibited the steroidogenesis process. In conclusion, our results indicated that estradiol in part regulates progesterone production physiologically and blocks progesterone production in a pharmacological or pathological state in the human corpus luteum.

Aniline Compounds↗
PubMed1998

Effects of granisetron, a selective 5-HT3 receptor antagonist, on ouabain-induced emesis in ferrets.

The antiemetic effect of granisetron, a selective 5-HT3 receptor antagonist, on ouabain-induced emesis was studied using ferrets. In order to clarify the relationship between ouabain-induced emesis and serotonin (5-HT), we examined its effects on 5-HT release from the isolated ileum. Afferent vagal nerve activity was also determined. An intravenous bolus injection of ouabain (0.1-1.0 mg/kg) produced emesis in a dose-dependent manner. Ouabain-induced emesis was inhibited by pretreatment with granisetron. In the isolated ileum, ouabain induced a concentration-dependent increase of 5-HT. This release of 5-HT was suppressed by granisetron. Increases in vagal nerve discharges were observed immediately after the intravenous administration of ouabain (0.1-1.0 mg/kg). These increases were suppressed by granisetron. Taken together, ouabain activates 5-HT release from the mucosa in the gastrointestinal tract. Released 5-HT may activate the vagal afferent nerves, resulting in vomiting. Granisetron inhibited the ouabain-induced elevation of 5-HT and vagal nerve activity. Ouabain may induce emesis as well as negative chronotropic effects by activating the vagus. Our results suggest that ouabain-induced emesis is in part mediated by the 5-HT3 receptors of the peripheral gastrointestinal tract.

Abdomen↗
PubMed1998

Gastric mucosal function following withdrawal of omeprazole in rats.

In the following study the function of gastric mucosa after withdrawal of 4-week suppression of acid secretion was examined. Rats were treated orally for 4 weeks with omeprazole (CAS 73590-58-6, 150 mg/kg/day). While elevated plasma gastrin levels during the treatment returned to normal 4 days after the last dosing, exogenously applied pentagastrin induced higher acid secretion compared with the vehicle-treated controls. Acetylsalicylic acid induced mucosal lesion 3.6-fold over the control as well. In contrast, the HCl-induced lesion was inhibited by 24.4%. These results indicate that not only the acid secretion but also the mucosal protection is enhanced after 4-week treatment with omeprazole in rats.

Analgesics, Non-Narcotic↗
PubMed1998

Immunohistochemical detection of MUC2 mucin core protein in ulcerative colitis.

MUC2 mucin is predominantly expressed in the colon and is considered to play an important role in the protection of that organ. Recent findings suggested that MUC2 protein levels are significantly decreased in active ulcerative colitis (UC). We therefore performed an immunohistochemical study to reveal if the expression of MUC2 protein is altered in UC. Seventy-nine biopsy tissue specimens from 31 UC patients, along with normal colon tissues, were immunostained with anti-MUC2 mucin core protein monoclonal antibody (MoAb) CCP58 (IgG1). UC tissue specimens were divided into two groups based on the histological severity of inflammation, i.e., 64 with active inflammation (grades 2-5) and 15 without (grade 1). In the former group, 52 out of 64 (81.3%) tissue specimens contained sections of glands with a few cells positive for MoAb CCP58. These glands were small and consisted of MUC2 negative-short cells and a few positive cells without apparent mucus formation, considered to be immature regenerative glands. In contrast, the staining pattern was almost the same as that of the normal colon and no immature glands were seen in the group without active inflammation. The sections of immature regenerative glands with a few MUC2-positive cells were exclusively found in the UC tissues with active inflammation, but not in those without it, suggesting that the expression of MUC2 protein may be decreased in active UC.

Adolescent↗
PubMed1998

[A case of isoniazid-induced pneumonitis].

A 55-year-old man was given a diagnosis of pulmonary tuberculosis. He was treated with isoniazid (INH), rifampicin (RFP), ethmbutol (EB) and pyrazinamide (PZA). After three weeks of treatment, he developed fever, dyspnea and dry cough. A chest X-ray taken at that time showed new reticulo-nodular shadows bilaterally and right pleural effusion. Ga scintigram showed strong uptake in both lungs. Transbronchial lung biopsy revealed alveolitis, suggesting drug-induced pneumonitis. Drug lymphocyte stimulation tests for INH, RFP, EB and PZA were negative. Because his symptoms were severe, all drugs were discontinued and daily predonisolone (30 mg) therapy was started. The symptoms and bilateral reticulo-nodular shadows soon resolved. The antituberculosis drugs were changed to streptomycin and levofloxacin, but these were ineffective. Therefore, EB, RFP and PZA, which only rarely induce pneumonitis, were carefully restarted in that order. Pneumonitis did not recur and the pulmonary tuberculosis improved. This clinical course suggests INH-induced pneumonitis.

Antitubercular Agents↗
PubMed1998

Thrombopoietin supports in vitro erythroid differentiation via its specific receptor c-Mpl in a human leukemia cell line.

Thrombopoietin (TPO) acts on megakaryopoiesis and erythropoiesis in vitro and in vivo. We isolated a novel subline, UT-7/GMT, from the human leukemia cell line UT-7/GM (N. Komatsu, et al., Blood, 89: 4021-4033, 1997). A small population of UT-7/GM cells positively stained for hemoglobin (Hb) after a 7-day exposure to TPO. More than 50% of TPO-treated UT-7/GMT cells positively stained for Hb. Using UT-7/GMT cells, we examined how TPO promotes hemoglobinization. TPO induced tyrosine phosphorylation of the TPO receptor but not the erythropoietin (EPO) receptor. There was no competition between TPO and EPO for binding to EPO receptor. These findings suggest that TPO has a direct effect on hemoglobinization via a specific receptor on UT-7/GMT cells. Isoelectric focusing demonstrated that TPO induced fetal and adult Hb synthesis, whereas EPO induced embryonic, fetal, and adult Hb synthesis. Thus, our data suggest that TPO has a distinct action on erythropoiesis.

Binding, Competitive↗