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M Terao

Publications and source records attributed to M Terao.

At least 55 records · Page 3Linked to original sources
PubMed1995

Tissue- and cell-specific expression of mouse xanthine oxidoreductase gene in vivo: regulation by bacterial lipopolysaccharide.

The expression of the xanthine oxidoreductase gene was studied in various mouse organs and tissues, under basal conditions and on treatment with bacterial lipopolysaccharide. Levels of xanthine oxidoreductase protein and mRNA were compared in order to understand the molecular mechanisms regulating the expression of this enzyme system. The highest amounts of xanthine oxidoreductase and the respective mRNA are observed in the duodenum and jejunum, where the protein is present in an unusual form because of a specific proteolytic cleavage of the primary translation product present in all locations. Under basal conditions, multiple tissue-specific mechanisms of xanthine oxidoreductase regulation are evident. Lipopolysaccharide increases enzyme activity in some, but not all tissues, mainly via modulation of the respective transcript, although translational and post-translational mechanisms are also active. In situ hybridization studies on tissue sections obtained from mice under control conditions or with lipopolysaccharide treatment demonstrate that xanthine oxidoreductase is present in hepatocytes, predominantly in the proximal tubules of the kidney, epithelial layer of the gastrointestinal mucosa, the alveolar compartment of the lung, the pulpar region of the spleen and the vascular component of the heart.

Animals↗
PubMed1995

[Anesthesia for cesarean section in a patient with intracranial A-V malformation].

We presented a case of intracranial vascular malformations associated with pregnancy. A 32 year-old woman who was at 36 weeks of gestation had been experiencing loss of consciousness and convulsions for 3 years. MRI revealed an intracerebral AVM measuring 3.5 x 3.0cm in the left temporal lobe. Cesarean section was carried out under general anesthesia and epidural anesthesia to prevent the rise of blood pressure and intracranial pressure owing to stress of delivery and labor pain. Intermittent injection of nicardipine was quite effective to control the hypertension during anesthesia.

Adult↗
PubMed1994

Chromosomal mapping, isolation, and characterization of the mouse xanthine dehydrogenase gene.

Xanthine dehydrogenase (XD) is a key enzyme in the catabolism of purines. A recently isolated XD cDNA clone (Terao et al., Biochem. J. 283, 863-870, 1992) was used to analyze the genomic structure and chromosomal location of this gene. XD was found to be a single-copy gene approximately 70 kb long with 36 exons containing the transcribed sequence. The length of the mouse XD gene was much longer and the structure more complex than those of the Drosophila and Calliphora homologs. The locus encoding the XD gene (designated Xd) was mapped to the distal part of mouse chromosome 17 by haplotype analysis of 114 interspecific backcross mice. Although Xd inactivation may be responsible for xanthinuria, a rare human genetic disease, this genetic locus is not a candidate for any previously described mouse mutation. The transcription start site was defined by primer extension and RNase mapping analysis, using liver mRNA. No other transcription start sites were identified in the liver and a variety of other organs after treatment with an interferon inducer. Transient transfection analysis in NIH3T3, tEnd, and COS cells with an appropriate reporter gene demonstrated that a functional promoter is located within the first 268 bp preceding the transcriptional initiation site.

Amino Acid Sequence↗
PubMed1994

Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells.

In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes. In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML), in the stable phase of the disease, a weaker interaction between ATRA and G-CSF was documented. The cross-talk between the cytokine and the retinoid was studied in detail in NB4, an immortalized APL leukemia cell line, retaining the 15-17 chromosomal translocation involving the retinoic acid receptor type alpha. The treatment of NB4 cells with G-CSF alone or ATRA alone leads to no increase and to minor induction in LAP activity, respectively. If the cells are treated with the two compounds simultaneously, a dramatic elevation of LAP is observed after 4 days. The synergism between G-CSF and ATRA is evident at concentrations of the retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine between 1 and 10 ng/mL. The simultaneous presence of the two compounds is necessary to obtain maximal increase of LAP activity and the effect is cell density-dependent. Synergism is specific for G-CSF, and it is not observed with other cytokines and functional inducers of the granulocyte. The augmentation of LAP activity is the consequence of an increased transcriptional rate of the liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by Northern blotting and nuclear run-on analysis using specific cDNA probes. Only one of the two possible alternatively spliced forms of L/B/K-type alkaline phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and ATRA. This mRNA form, which is the one observed in normal polymorphonuclear leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G-CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor effects on the expression of these mRNAs.

Alkaline Phosphatase↗
PubMed1994

Molybdenum(VI) salts convert the xanthine oxidoreductase apoprotein into the active enzyme in mouse L929 fibroblastic cells.

The mouse L929 fibroblastic cell line presents low, but detectable, levels of the mRNA encoding xanthine oxidoreductase under basal conditions, and it responds to type I and type II interferons by inducing the expression of the transcript [Falciani, Ghezzi, Terao, Cazzaniga, and Garattini (1992) Biochem. J. 285, 1001-1008]. This cell line, however, does not show any detectable amount of xanthine oxidoreductase enzymic activity, either before or after treatment with the cytokines. Molybdenum(VI) salts, in the millimolar range, are capable of activating xanthine oxidoreductase in L929 cells both under basal conditions and after treatment with interferon-alpha. The increase is observed in mouse L929 as well as in clones derived from it, but not in many other human and mouse cell lines. The induction observed in L929 cells is post-translational in nature and it is insensitive to cycloheximide, indicating that the molybdenum ion converts a pool of inactive xanthine oxidoreductase apoenzyme into its holoenzymic form. When grown in the absence of sodium molybdate, the L929 cell line has undetectable intracellular levels of the molybdenum cofactor, since the cell extracts are unable to complement the nitrate reductase defect of the nit-1 mutant of Neurospora crassa. L929 cells grown in the presence of millimolar concentrations of sodium molybdate, however, become competent to complement the nit-1 defect. L929 cells accumulate molybdenum ion inside the intracellular compartment as efficiently as TEnd cells, a mouse endothelial cell line that expresses xanthine oxidoreductase activity both under basal conditions and after treatment with interferon-gamma, suggesting that L929 cells have a defect in one or more of the metabolic steps leading to the synthesis of the molybdenum cofactor.

3T3 Cells↗
PubMed1993

Retinoic acid and cyclic AMP synergistically induce the expression of liver/bone/kidney-type alkaline phosphatase gene in L929 fibroblastic cells.

In L929 mouse fibroblastic cells, liver/bone/kidney type alkaline phosphatase (L/B/K-ALP) enzymic activity is induced by all-trans-retinoic acid at concentrations between 10(-6) and 10(-5) M. At lower concentrations, retinoic acid is incapable of inducing this enzymic activity per se, but increases cyclic AMP (cAMP)-mediated induction. This effect is observed after incubation of the retinoid with dibutyryl cAMP, 8-bromo cAMP or forskolin. The synergism is dependent on the order of addition of retinoic acid and the activator of the cAMP pathway. Contemporaneous addition of the two agents, or addition of cAMP prior to retinoic acid (but not addition of retinoic acid before cAMP), is necessary to produce this synergistic interaction. The synergism results in increased steady-state levels of L/B/K-ALP mRNA and it is the consequence of increased transcriptional activity of the gene. The expression of the mouse L/B/K-ALP gene is regulated by the presence of two leader exons, 1A and 1B, resulting in the synthesis of two alternatively spliced mRNAs that are different only in part of their 5' untranslated region [Studer, Terao, Giannì and Garattini (1991) Biochem. Biophys. Res. Commun. 179, 1352-1360]. PCR amplification and nuclear run-on experiments performed using probes specific for each leader exon demonstrate that treatment of these cells with retinoic acid, forskolin or dibutyryl cAMP, and with the combination of the retinoid and one of the cAMP-elevating agents, leads to the accumulation of nascent and mature L/B/K-ALP mRNA containing exon 1B. The synergistic induction of the transcription of the L/B/K-ALP gene is well correlated with quantitative and qualitative changes of retinoic-acid-receptor mRNAs mediated by cAMP.

Alkaline Phosphatase↗
PubMed1993

Effects of synthetic retinoids and retinoic acid isomers on the expression of alkaline phosphatase in F9 teratocarcinoma cells.

Expression of ALP in F9 teratocarcinoma cells is induced by all-trans retinoic acid (ATRA) (Gianni' et al., Biochem. J. 274: 673-678, 1991). The specific ligand for retinoic acid related receptors (RXRs), 9-cis retinoic acid (9-cis RA), and three synthetic analogs binding to the alpha, beta and gamma forms of the retinoic acid receptors (RARs), AM580, CD2019, and CD437, were used to study their effects on alkaline phosphatase (ALP) enzymatic activity and mRNA levels. At concentrations close to the Kd for their respective receptors, 9-cis RA, AM580 (the RAR alpha agonist) and CD437 (the RAR gamma agonist) clearly upregulate the expression of the ALP gene, whereas the effect of CD2019 (the RAR beta agonist) is very modest. A specific inhibitor of the RAR alpha, Ro 41-5253, completely blocks the induction of ALP triggered by AM580, while it has minor effects on the upregulation caused by ATRA, 9-cis RA, CD437 and CD2019. The induction of ALP observed with the various retinoids is inhibited by the contemporaneous treatment with dibutyryl cAMP. The levels of the RAR alpha and gamma transcripts are unaltered, while RAR beta mRNAs are induced by ATRA, AM580, CD437 and to a lower extent by 9-cis RA and CD2019.

Alkaline Phosphatase↗
PubMed1993

Cytokine induction of haem oxygenase mRNA in mouse liver. Interleukin 1 transcriptionally activates the haem oxygenase gene.

Accumulation of the mRNA coding for haem oxygenase (HO, EC 1.14.99.3) was stimulated by treating mice with endotoxin (lipopolysaccharide, LPS; 20 micrograms/mouse intraperitoneally), suggesting that haem catabolism is a target of infection and inflammation in vivo. Therefore various cytokines, possible mediators for the biological responses to LPS, were administered intraperitoneally to mice, and the levels of HO mRNA were measured by Northern-blotting analysis using the rat HO cDNA as a probe [Shibahara, Müller, Taguchi and Yoshida (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7865-7869]. Marked induction of HO mRNA was observed 2 h after administration of interleukin 1 (IL-1) (34-fold) and tumour necrosis factor (19.5-fold) (5 micrograms/mouse), whereas interleukin 6 (6.2 micrograms/mouse) was much less active (3.5-fold) and interleukin 2 (25 micrograms/mouse) and interferon-gamma (3 micrograms/mouse) were ineffective. HO mRNA induced by the cytokines of LPS accumulated rapidly (maximum at 1-2 h after administration), preceding the elevation of HO enzymic activity. Treatment of mice with IL-1 stimulated the transcription of the HO gene by 4-fold, as assessed by in vitro nuclear-run-on assay. These results indicate that enzymic haem catabolism in the liver is a process inducible in vivo by inflammatory cytokines, which up-regulate HO synthesis at the transcriptional level. Increased removal of haem might be part of the protective mechanisms elicited by the acute-phase response, possibly to reduce the pro-oxidant state of the cell.

Animals↗
PubMed1993

A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma.

cis-Diamminedichloroplatinum (II) (cisplatin: CDDP) suppositories containing NaCl at different concentrations were prepared as a local chemotherapeutic agent for the treatment of uterine endometrial carcinoma and were administered to rabbits implanted with uterine VX2 tumor. The intrauterine CDDP histological level, as well as the antitumor effects and side effects of the suppositories to the liver and kidney were studied. The results showed high intrauterine tissue CDDP level in all suppository administrations. In particular, the NaCl-added suppositories enhanced the intrauterine CDDP level. As for antitumor effects, while the tumor growth rate of the NaCl-added suppository group was likely to be suppressed, the suppositories could not suppress tumor growth completely. The plasma platinum (Pt) level was 1.5 micrograms/ml or less and that of the liver and kidney was as low as 0.31 to 0.48 micrograms/g. No difference in levels depending on NaCl concentration was observed, nor was any abnormality found in the biochemical analysis including glutamate oxaloacetate transaminase (GOT) and blood urea nitrogen (BUN). Histopathological study revealed the degeneration of tumor cells in the NaCl-added suppository group. Minimal congestion and hemorrhage were observed in the endometria, possibly resulting from CDDP. By adding NaCl to CDDP suppositories, the uterine CDDP level and antitumor effects increased while no serious renal dysfunction was noted. Therefore, we conclude that NaCl-added CDDP suppositories are a useful local chemotherapy for endometrial carcinoma.

Animals↗
PubMed1993

Percutaneous absorption of acemetacin from a membrane controlled transdermal system and prediction of the disposition of the drug in rats.

To avoid development of a lesion on the small intestine by acemetacin (ACM) following oral administration of the drug, we developed a new device for its percutaneous application. The device for transdermal application of ACM consisted of a silicon O-ring, a backing of aluminum foil and adhesive tape, and rate-controlling membranes with three different pore sizes (HP-1100, 2100 and 4050). Two percent ACM gel ointment was contained in the device. In the in vitro release experiment, the ACM release from the device was limited by these membranes with release rate constants of 0.630 +/- 0.052, 0.289 +/- 0.012, 0.098 +/- 0.11 and 0.083 +/- 0.011 h-1 for no membrane, HP-4050, HP-2100 and HP-1100 membranes, respectively. In the in vitro penetration experiment, the ACM penetrating through the skin appeared in the reservoir cell without the metabolic conversion to indomethacin (IM). After the application of the ACM device with the HP-2100 rate-controlling membrane on the rat abdominal skin, ACM was not detected in the plasma but the therapeutic plasma concentration of IM could be maintained over a 54 h period. These results indicate that the device with a rate-controlling membrane may be useful for the percutaneous application of ACM as an anti-inflammatory drug and its clinical application. For the percutaneous absorption of ACM after application of the ACM devices, the values estimated by the proposed model which consisted of 6 compartments well fit to the data obtained from this in vivo experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Interferons induce xanthine dehydrogenase gene expression in L929 cells.

Human interferon-alpha A/D (Bg/II) (IFN-alpha A/D) and mouse interferon-gamma (IFN-gamma) are shown to induce xanthine dehydrogenase (XD) mRNA in L929 fibroblastic cells. XD mRNA accumulation after IFN-alpha A/D treatment is relatively fast, being already evident after 4 h and reaching its maximum after 24 h. IFN-alpha A/D is active in inducing XD mRNA at 0.1 unit/ml and it is maximally active at 10(3) units/ml. The half-life of the XD message is unaffected by IFN-alpha A/D treatment, whereas the transcriptional activity of the XD gene and the concentrations of XD heterogeneous nuclear RNA are increased by 2- and 6-fold respectively. The effect of IFN-alpha A/D on XD mRNA is insensitive to cycloheximide, suggesting that protein synthesis de novo is not required. Experiments conducted with specific inhibitors suggest that protein kinase C, cyclic AMP and arachidonic acid metabolites derived from lipoxygenase or cyclooxygenase do not act as second-messenger molecules in the induction of XD mRNA by IFN-alpha A/D. XD mRNA is also induced in NIH3T3 fibroblastic cells, but not in F9 teratocarcinoma or B16 melanoma cells after treatment with IFN-alpha A/D. NIH3T3 are the only cells so far tested that have detectable XD and xanthine oxidase activities under basal conditions and after IFN-alpha A/D treatment, although their responsiveness to the cytokine is much less than that observed in L929 cells.

Bucladesine↗
PubMed1992

Molecular cloning of a cDNA coding for mouse liver xanthine dehydrogenase. Regulation of its transcript by interferons in vivo.

The cDNA coding for xanthine dehydrogenase (XD) is isolated from mouse liver mRNA by cross-hybridization with a DNA fragment of the Drosophila melanogaster homologue. Two lambda bacteriophage overlapping clones represent the copy of a 4538-nucleotide-residue-long transcript with an open reading frame of 4005 nucleotide residues, coding for a putative polypeptide of 1335 amino acid residues. Comparison of the deduced amino acid sequence of the mouse XD with those of the Drosophila and the rat homologues shows a high conservation of this protein (55% identity between mouse and Drosophila, and 94% identity between mouse and rat). RNA blotting analysis demonstrates that interferon-alpha (IFN-alpha) and its inducers, i.e. poly(I).poly(C), bacterial lipopolysaccharide (LPS) and tilorone (2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one), increase the expression of XD mRNA in liver. Poly(I).poly(C) also induces XD mRNA in several other tissues in vivo. Protein synthesis de novo is not required for the elevation of XD mRNA after IFN-alpha treatment, since cycloheximide does not block the induction. The elevation of XD mRNA concentration is relatively fast and precedes the induction of both XD and xanthine oxidase (XO) enzymic activities.

Amino Acid Sequence↗
PubMed1992

Inhibition of melanogenesis by BMY-28565, a novel compound depressing tyrosinase activity in B16 melanoma cells.

The mechanism of a novel melanin synthesis inhibitor, BMY-28565, was studied using mouse B16 melanoma cells. This compound was active in depressing the intracellular accumulation of melanin with an IC50 of 5 microM. At dose levels causing no cytotoxicity, the melanolytic effect of this compound was correlated strongly with depression of the enzymatic activity of tyrosinase (monophenol oxygenase, EC 1.14.18.1), the key enzyme in the melanin synthesis pathway. Transcription of the tyrosinase gene was not inhibited by BMY-28565, as determined by RNA blotting analysis. BMY-28565 and three other active derivatives of this compound caused increased glycosylation of proteins in B16 melanoma cells, as assessed by radioactive mannose incorporation. It is, thus, suggested that the mechanism of inhibition of tyrosinase might be related to modifications of the sugar moiety of this enzyme or of a protein(s) that is essential for the expression of its enzymatic activity.

Animals↗
PubMed1991

Characterization of a second promoter for the mouse liver/bone/kidney-type alkaline phosphatase gene: cell and tissue specific expression.

The second leader exon and the relative promoter of the mouse liver/bone/kidney-type alkaline phosphatase gene were identified and characterized. The transcription initiation site was determined by S1 mapping analysis. The differential expression of the two alternatively spliced transcripts was assessed in cell lines of different origin and in various tissues by polymerase chain reaction and RNase mapping analysis. The first promoter is active in embryo derived cells, whereas the second promoter is silent in basal conditions but it is activated by dibutyryl cAMP in fibroblastic cells. In the whole animal, the transcript driven by the first promoter is found in most tissues albeit at different levels, while the one driven by the second promoter is specifically expressed at high levels only in the heart.

Alkaline Phosphatase↗