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Biomedical subjects

M Ema

Publications and source records attributed to M Ema.

At least 55 records · Page 3Linked to original sources
PubMed1996

[The Human Menopausal Gonadotrophin Reference Standard (Control 961) of the National Institute of Health Sciences].

Raw human menopausal gonadotrophin (HMG) material was examined for preparation of the "Human Menopausal Gonadotrophin Reference Standard (Control 961)". The candidate material was assayed its follicle stimulating hormone (FSH) activity and luteinizing hormone (LH) activity against the 3rd International Standard for FSH and LH, urinary (71/264) by the augmented ovarian weight gain assay and the seminal vesicle weight gain test, respectively. The potency of the new standard was defined as 56 international units of FSH activity per mg and 61 international units of LH activity per mg as the result of 13 and 5 assays, respectively, in four collaborative laboratories.

Animals↗
PubMed1995

Further evaluation of the developmental toxicity of tributyltin chloride in rats.

The objective of this study was to further evaluate the developmental toxicity of tributyltin chloride (TBTCl) in rats. Pregnant rats were given TBTCl by gastric intubation at a dose of 25, 50 or 100 mg/kg on days 7-9, days 10-12 or days 13-15 of pregnancy. A significant increase in the incidence of post-implantation loss was found in the groups treated with TBTCl on days 7-9 at 25 and 50 mg/kg and on days 10-12 at 100 mg/kg, but not in the groups treated with TBTCl on days 13-15. No significant increase in the incidence of malformed fetuses was observed after treatment with TBTCl on days 7-9. A significant increase incidence of malformed fetuses was detected when TBTCl was given on days 10-12 at 100 mg/kg and on days 13-15 at 25, 50 and 100 mg/kg. The most predominant malformation was cleft palate. It could be concluded that the manifestation of deviant development induced by TBTCl varies with the developmental stage at the time of administration and TBTCl possesses teratogenic potential with developmental phase specificity.

Abnormalities, Drug-Induced↗
PubMed1995

Comparative developmental toxicity of n-butyl benzyl phthalate and di-n-butyl phthalate in rats.

n-Butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) were evaluated and compared for their developmental toxic potential. Pregnant rats were given either BBP or DBP by gastric intubation at a dose of 0.75, 1.0 and 1.25 g/kg on days 7-9, days 10-12 and days 13-15 of pregnancy. Regardless of the days of treatment, a significantly increased incidence of postimplantation loss was found at all doses of BBP and DBP. While treatment with BBP and DBP at doses of 0.75 g/kg and above on days 7-9 or days 13-15 resulted in a significant increase in the incidence of fetuses with malformations, no increase in the incidence of malformed fetuses was found after treatment with BBP and DBP on days 10-12. The incidences of postimplantation loss and malformed fetuses increased as the doses of BBP and DBP were increased. Deformity of the vertebral column and ribs commonly occurred after treatment with BBP and DBP on days 7-9. Cleft palate and fusion of the sternebrae were predominantly observed after treatment with BBP and DBP on days 13-15. The similarity in dependence of gestational days of treatment on the manifestation of developmental toxicity and on the spectrum of fetal malformations caused by BBP and DBP suggests that they may act by the same mechanism, possibly via a common metabolite of these two parent compounds.

Abnormalities, Drug-Induced↗
PubMed1995

Developmental toxicity evaluation of mono-n-butyl phthalate in rats.

Mono-n-butyl phthalate (MBuP) was evaluated for developmental toxicity in Wistar rats. Rats were given MBuP by gastric intubation at 0, 250, 500 or 625 mg/kg on days 7-15 of pregnancy. Significant decreases in the maternal body weight gains and food consumption during pregnancy were found at 500 and 625 mg/kg. Significant increase in the incidence of postimplantation loss per litter and decreases in the number of live fetuses per litter and fetal weight were also detected at 500 mg/kg and above. The incidence of fetuses with malformations in the 500 and 625 mg/kg groups was higher than that in the control group. Cleft palate, deformity of the vertebral column and dilatation of the renal pelvis were frequently observed.

Abnormalities, Drug-Induced↗
PubMed1995

Polymorphic forms of the Ah receptor and induction of the CYP1A1 gene.

Induction of cytochrome P4501A1 (CYP1A1) by certain xenobiotics is mediated by the Ah receptor/Arnt complex. The present knowledge about the molecular process of induction is summarized with special attention to our recent work on characterization of the polymorphic forms of the Ah receptor.

Cloning, Molecular↗
PubMed1995

[The human chorionic gonadotrophin reference standard (Control 941) of the National Institute of Health Sciences].

Raw human chorionic gonadotrophin material was examined for preparation of the "Human Chorionic Gonadotrophin Reference Standard (Control 941)". The candidate material was assayed against the 3rd International Standard by the rat ovarian weight method. The potency of the new standard was defined as 1180 international units per ampoule as the result of 18 assays in four collaborative laboratories.

Chorionic Gonadotropin↗
PubMed1994

Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors.

The genetic difference in the susceptibility of mice to environmental toxicities induced by dioxin and related chemicals is governed by polymorphism of the arylhydrocarbon receptor (AhR) (Poland, A., and Knutson, C. (1982) Annu. Rev. Pharmacol. Toxicol. 22, 517-554). cDNA cloning of AhR cDNA from responder (C57BL/6) and non-responder (DBA/2J) mice allowed us to analyze the structure and function of these AhRs. Both of the AhRs, which were expressed in COS-7 cells transfected with their expression plasmids, showed a clear 9 S complex with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) in a linear glycerol gradient centrifugation, consistent with the result of the endogenously expressed AhR in Hepa-1 cells. This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. Scatchard plot analysis revealed that the dissociation constant (Kd) of C57BL AhR for TCDD is 0.27 nM, while that of DBA AhR is elevated up to six times that high. Chimeric plasmids between the two cDNAs and site-directed mutagenesis revealed two critical alterations responsible for the reduced ligand binding activity: an Ala375 to Val alteration and an elongated carboxyl-terminal sequence due to a T to C mutation at the first letter of the termination codon of C57BL AhR. Two variants with reduced and intermediate ligand binding activity were also found in human AhRs with amino acid alterations equivalent to those of the DBA AhR. Importance of the amino acid at position 381 of human AhR (equivalent to position 375 of mouse AhR) in the ligand binding was confirmed by the fact that the mutation of Val381 to Asp completely abolished the ligand binding activity of human AhR.

Amino Acid Sequence↗
PubMed1994

Characterization of the developmental toxicity of di-n-butyl phthalate in rats.

The objective of this study was to determine the characterization of the developmental toxicity of di-n-butyl phthalate (DBP) in rats. Pregnant rats were given DBP by gastric intubation at a dose of 0.75, 1.0 or 1.5 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. Postimplantation loss was 100% for each period of dosing at 1.5 g/kg. A significant increase in the postimplantation loss was found in dams given DBP at doses of 0.75 and 1.0 g/kg regardless of the days of treatment. No evidence of teratogenicity was detected when DBP was given on days 10-12. Treatment on days 7-9 with DBP at doses of 0.75 and 1.0 g/kg caused a significant increase in the number of skeletal malformations such as deformity of the vertebral column in the cervical and thoracic regions and of the ribs, but neither external nor internal malformations. Treatment with DBP on days 13-15 at doses of 0.75 and 1.0 g/kg resulted in a significant increase in the incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The frequency of malformations increased as the dose of DBP was increased. The highest incidence of malformed fetuses occurred after treatment with DBP on days 13-15. It could be concluded that susceptibility to the teratogenicity of DBP varies with the developmental stage at the time of administration.

Abnormalities, Drug-Induced↗
PubMed1994

Human arylhydrocarbon receptor: functional expression and chromosomal assignment to 7p21.

We isolated the human arylhydrocarbon receptor (AhR) cDNA from a human lung cDNA library, by using mouse AhR cDNA as a labeled probe. The nucleotide sequence of cloned human AhR cDNA is identical to the previously reported human AhR sequence [Dolwick et al. (1993), Mol. Pharmacol. 44, 911-917] from cell line HepG2. The overall amino acid identity with mouse AhR from cell line Hepa-1 is 72.5%. The human AhR expressed either in COS-7 cells or in a reticulocyte lysate in vitro translation system showed specific dioxin-binding activity and Arnt-dependent DNA-binding activity. Chromosomal localization of the AhR gene was determined to be chromosome 7p21 by fluorescent in situ hybridization and DNA blot hybridization using 23 human x mouse or Chinese hamster hybrid cell DNAs.

Amino Acid Sequence↗
PubMed1994

A complete structure of the mouse Ah receptor gene.

A complete sequence of the Ah receptor gene was cloned from a mouse genomic library by using the Ah receptor cDNA as a probe. The Ah receptor gene is 37.5 kb long and is split into 11 exons by 10 introns. Sequence analysis of the 5' flanking region of the Ah receptor gene reveals that there is neither a TATA box nor a CAAT box in the promoter region. Instead, this gene has a few GC boxes and other enhancer elements in the 5' upstream flanking region. Southern blot analysis indicated that the Ah receptor gene is a unique gene.

Animals↗
PubMed1994

Ah receptor: a novel ligand-activated transcription factor.

Two years have passed since the Ah receptor (AhR) and the AhR nuclear translocator (Arnt) were revealed to constitute a novel ligand-activated transcription factor by molecular biological studies on cloned cDNAs. Many interesting properties of the AhR/Arnt system have begun to be elucidated. We present here a brief summary of the molecular biology of AhR and Arnt.

Amino Acid Sequence↗
PubMed1994

[The Human Insulin Reference Standard (Control 921) of the National Institute of Health Sciences].

Raw human insulin material was examined for preparation of the "Human Insulin Reference Standard". The candidate material was evaluated by a domestic collaborative study in which four laboratories participated. The biological activity was determined to be 26.0 Unit/mg against the International Human Insulin Reference Standard (Code 83/500), based on the rabbit blood-glucose method specified in the JP XII (1991). Because of the possibility of application as a chemical reference standard for assay by the HPLC method, a physico-chemical evaluation of the candidate material was also performed. The total desamide form, dimer and oligomer impurities were estimated to be about 1% by HPLC. Based on the above findings, this raw material was authorized as the Human Insulin Reference Standard of the National Institute of Health Sciences.

Animals↗
PubMed1994

[Elcatonin Reference Standard (Control 921) of National Institute of Health Sciences].

The raw material of elcatonin was examined for preparation of the "Elcatonin Reference Standard". The candidate material was evaluated by a domestic collaborative study in which five laboratories participated. The biological activity was determined to be 11.3 Unit/Amp. against the International Elcatonin Reference Standard (Code 84/614), based on one hour hypocalcaemia rat bioassay. In spite of the differences in rat strain, sex, administration method, dosage and assay method for serum calcium etc., the separately obtained biological activities for the candidate agreed closely with each other (95% confidence limits 11.08-11.53 Unit/Amp.). The physico-chemical evaluation of the candidate material was also performed, by using HPLC and amino acid chromatography. Based on the above results, this raw material was authorized to be the Elcatonin Reference Standard of the National Institute of Health Sciences.

Amino Acids↗
PubMed1993

A factor binding to the xenobiotic responsive element (XRE) of P-4501A1 gene consists of at least two helix-loop-helix proteins, Ah receptor and Arnt.

Xenobiotic responsive element (XRE) is an inducible enhancer element that drives inducible expression of P-4501A1 gene in response to xenobiotic inducers. The XRE-binding factor appears in the nuclei of Hepa-1 cells treated with 3-methylcholanthrene (3-MC). Association of the Ah receptor and Arnt (Ah receptor nuclear translocator) in an XRE-binding complex was examined by anti-Ah receptor and Arnt antibodies. Both antibodies inhibited the sequence-specific XRE-binding activity of nuclear extracts from 3-MC-treated Hepa-1 cells and of the cytosolic fraction which was prepared from the nontreated cells and treated in vitro with 3-MC. These results indicate that Ah receptor and Arnt proteins are components of the XRE-binding factor and suggest that Arnt as well as the Ah receptor are localized in the cytosol of nontreated cells. The Ah receptor present in C4 cells, a mutant of Hepa-1 cells defective in the Arnt function, showed an inducer-dependent association with Arnt synthesized in an in vitro translation system. Co-transfection of the expression plasmids of the Ah receptor and Arnt exhibited synergistically more activated transcription from a reporter gene pMC6.3k consisting of the P-4501A1 gene promoter and enhancer than transfection with either of the two plasmids alone. These findings indicate that the Ah receptor and Arnt proteins form a complex that activates transcription in an inducer-dependent manner.

Animals↗
PubMed1993

Teratogenic phase specificity of butyl benzyl phthalate in rats.

Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0.6, 0.75 or 1.0 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. While treatment with BBP on days 7-9 or 13-15 at doses of 0.75 and 1.0 g/kg was significantly teratogenic, no evidence of teratogenicity was detected when BBP was given on days 10-12. The incidence of malformed fetuses was proportional to the dose of BBP. Treatment on days 7-9 with BBP at doses of 0.75 g/kg and above caused a significant increase in the number of skeletal malformations, such as fusion of the cervical vertebral arches and deformity of the thoracic vertebrae, but neither external nor internal malformations. Treatment on days 13-15 with two higher doses of BBP resulted in a significantly increased incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The highest incidence of malformed fetuses occurred after treatment with BBP on days 13-15. It could be concluded that the susceptibility to the teratogenicity of BBP varies with the developmental stage at the time of administration.

Abnormalities, Drug-Induced↗
PubMed1993

Teratogenic evaluation of di-n-butyl phthalate in rats.

Pregnant rats were given di-n-butyl phthalate (DBP) by gastric intubation at a dose of 0, 0.5, 0.63, 0.75 or 1.0 g/kg on days 7-15 of pregnancy. A significant decrease in the maternal body weight gain after treatment with DBP was found at a dose of 0.63 g/kg and above. Maternal death and complete resorption of implanted embryos in all the surviving dams were observed in the 1.0 g/kg group. Significantly increased incidence of postimplantation loss and decreased fetal weight were detected at doses of 0.63 and 0.75 g/kg. The incidence of fetuses with malformations was higher in the 0.63 and 0.75 g/kg groups than in the control group, and the difference was significant in the 0.75 g/kg group. Cleft palate were predominantly observed.

Abnormalities, Drug-Induced↗
PubMed1993

Teratogenic evaluation of p-tert-butylphenol formaldehyde resin (novolak type) in rats following oral exposure.

The teratogenicity of p-tert-butylphenol formaldehyde resin, novolak type, (PTBP-FR) was examined in Wistar rats. Pregnant rats were fed diets containing 0, 2.5, 5 or 10% of PTBP-FR ad libitum from day 6 to day 15 of pregnancy. Maternal toxicity, as evidenced by a decreased maternal body weight gain and food consumption, was observed in the 5 and 10% dose groups. However, treatment-related clinical signs were not observed. No significant reductions in the fetal body or placental weights were observed in any dose group. There were no significant differences in the number of live fetuses, intrauterine deaths (dead fetuses and resorptions), or fetal sex ratios found between the PTBP-FR-treated and control groups. Although external and internal malformations including short tail, dilatation of the cerebral ventricle and the renal pelvis and dextrocardia, and some skeletal variations were observed in fetuses at some groups treated with PTBP-FR, the incidences of these morphological alterations were not statistically different from controls. In conclusion, PTBP-FR administered orally to Wistar rats during days 6-15 of gestation produced no related signs of developmental toxicity.

Abnormalities, Drug-Induced↗