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Y Eto

Publications and source records attributed to Y Eto.

At least 181 records · Page 10Linked to original sources

[Function, molecular structure and gene expression regulation of erythroid differentiation factor (EDF/activin A)].

Erythroid differentiation factor (EDF), initially found as a differentiation inducer of murine erythroleukemia cells, also acts on normal erythroid progenitors in vitro and in vivo. Furthermore, it is produced endogenously and supporting in vivo erythropoiesis. EDF is structurally identical to activin A, a gonadal protein with follicle stimulating hormone releasing activity, and belongs to TGF beta superfamily. Its activity could be regulated by follistatin, a binding protein with neutralizing activity against EDF/activin A. Molecular cloning of EDF/activin A receptor cDNA has revealed its domain structure characteristic to serine/threonine kinase.

Activin Receptors↗

[A patient with epilepsy presenting developmental regression after seizures--consideration of the mechanism from the findings of CT-scan and SPECT].

We report a 6-month-old female infant with frequent brief seizures who subsequently showed developmental regression. CT-scans right after her seizures revealed enlargement of bilateral subdural space more on the right side with an evidence to suggest destruction of the blood brain barrier in enhanced CT-scan, CT-scan, one month after the onset, showed diffuse brain atrophy. 123I-SPECT, which was performed 11 days after cessation of her seizures, still showed diffuse hypoperfusion predominantly in the right temporal area, and it returned to normal 3 months after the onset. We discussed the mechanisms of developmental regression in this case from the neuroradiological findings.

Child, Preschool↗

[A case of frontal lobe epilepsy presenting with gelastic seizures].

We described a 9-year-old boy with frontal lobe epilepsy presenting with gelastic seizures. CT-scan showed mild widening of the left sylvian fissure. Abnormal findings in the left frontal operculum were detected by both MRI and SPECT. Attacks mainly consisted of gelastic seizures with comfortable feeling followed by screaming with fear. Administration of anticonvulsants resulted in reducing the frequency and severity of seizures. Finally the patient had brief laughter attacks only. In the present case, the clinical course suggests that the gelastic seizures does not occur by way of the spreading of epileptic discharges to the temporal or hypothalamic region; rather it might occur as a focal symptom of the frontal region.

Brain↗

[The neuroendocrinological examinations in mentally retarded boy with self-injurious behavior (SIB) and the effect of naloxone, clomipramine and sulpiride on SIB].

The neuroendocrinological examinations were performed in mentally retarded 7-year-old boy with severe self-injurious behavior (SIB). The thyroid-stimulating hormone (TSH) and prolactine responses to TRH showed lower in the basal and peak levels compared with those in the age matched control group. It is suggested that there may be an enhanced dopaminergic activity. The effects of naloxone, clomipramine and sulpiride on the frequency of SIB were investigated in this case. The frequency of SIB was reduced by sulpiride; a dopamine antagonist. These data suggest dopaminergic supersensitivity and hypothalamic dysregulation as a mechanism underlying SIB.

Child↗

Presence of activin (erythroid differentiation factor) in unfertilized eggs and blastulae of Xenopus laevis.

Activin A, a member of the transforming growth factor beta superfamily, has recently been found to have potent mesoderm-inducing activity on isolated early Xenopus animal-cap cells. We measured the activin activity of the Xenopus egg extract by using an erythroid-differentiating test with Friend leukemia cells. The results showed that an activin homologue is, indeed, contained in unfertilized eggs and blastulae of Xenopus laevis in a considerable amount. This activity was eluted at the same retention time as human activin A when fractionated by reversed-phase HPLC. Furthermore, the fraction containing erythroid-differentiating factor activity had mesoderm-inducing activity on Xenopus animal-cap cells. The mesoderm-inducing activity of this fraction was suppressed when coincubated with follistatin, an activin-binding protein. These results suggest that an endogenous activin may be a natural mesoderm-inducing factor acting in Xenopus embryogenesis.

Activins↗

The vegetalizing factor from chicken embryos: its EDF (activin A)-like activity.

The erythroid differentiation capacity of the HPLC-purified mesoderm- and endoderm-inducing vegetalizing factor from chicken embryos and of recombinant erythroid differentiation factor (EDF = activin A), an evolutionary highly conserved member of the TGF-beta protein superfamily have been compared. Both factors stimulate the synthesis of hemoglobin in erythroleukemia cells in the same concentration range. The EDF-activity of the mesoderm-inducing HPLC-fractions is inhibited by follistatin, an EDF-binding protein. The factor induces in ectoderm of Triturus taeniatus all kinds of mesodermal organs. The wide spectrum of organs is very likely to be induced by secondary interactions. At higher concentration (15 ng/ml), notochord- and endoderm-like tissues are induced in a high percentage.

Activins↗

Psychosine cytotoxicity toward rat C6 glioma cells and the protective effects of phorbol ester and dimethylsulfoxide: implications for therapy in Krabbe disease.

Psychosine cytotoxicity was tested as to its effects on rat C6 glioma cells. At a low concentration--below 40 microM--psychosine appeared to stimulate cell proliferation. Above the concentration range of 40 microM-60 microM, however, it showed a cytotoxic effect. When phorbol ester (PDB) or dimethylsulfoxide (DMSO) was supplemented to cultures being exposed to psychosine, the total number of live cells, protein content and CNPase activity dramatically increased as compared with the levels in cultures treated with psychosine alone. The results of these basic studies suggest another approach as to therapy for globoid cell leukodystrophy.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

[A clinical study on liver dysfunction in patients with acute measles infection].

Liver dysfunction in patients with measles infection is reported commonly in European and American literatures, but those in Japan are relatively rare. We observed the abnormal elevation of serum transaminase in 17 of 18 juvenile patients with measles from December 1989 to February 1990, however severe complications such as pneumonia or meningitis were not observed. A diagnosis of measles was made by typical clinical symptoms and the elevation of IgM antibody against measles (EIA method). Ninety four percent of the patients showed the elevation of serum transaminase, (GOT 118.6 +/- 96.2 IU/l, GPT 161.5 +/- 167.6 IU/l), and all patients recovered completely in 30.5 +/- 12.8 days after the onset. The abnormal evaluation of serum LDH was seen in 94% of the patients, (mean value was 872.2 +/- 216.2 IU/l). LDH4 mainly elevated in most cases, however, LDH5 elevated only in 4 cases. The intensity of liver dysfunction did not correlate to the severity of measles in the present cases. It is considered to be characteristic to the patients with measles that the serum level of LDH is markedly high as compared with that of transaminase.

Adolescent↗

A new glucocerebrosidase-gene missense mutation responsible for neuronopathic Gaucher disease in Japanese patients.

We have identified a new T-to-A single-base substitution at nucleotide 3548 (in the genomic sequence) in exon 6 in the glucocerebrosidase gene from a patient with Gaucher disease type 3. This mutation caused a substitution of isoleucine for phenylalanine at amino acid residue 213 (of 497 residues in the mature protein). By in vitro expression study in cultured mammalian cells, this mutation resulted in deficient activity of glucocerebrosidase. By allele-specific oligonucleotide hybridization of selectively PCR-amplified DNA from eight unrelated Japanese Gaucher disease patients, this mutant allele was observed in other neuronopathic Japanese Gaucher disease patients, in moderately frequent occurrence (three of six neuronopathic patients). This observation suggests that this allele was one of severe [corrected] alleles which were related to the development of neurological manifestations of Gaucher disease.

Base Sequence↗

Phorbol ester-treated human acute myeloid leukemia cells secrete G-CSF, GM-CSF and erythroid differentiation factor into serum-free media in primary culture.

Upon treatment with the phorbol ester, tetradecanoylphorbol 13-acetate (PMA), peripheral mononuclear blood cells from patients with acute myeloid leukemia secrete into serum-free cell-conditioned media (PMA-CCM) at least three distinct nondialysable 'hematopoietic' factors: granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage-colony-stimulating factor (GM-CSF) and erythroid differentiation factor (EDF, activin A). G-CSF was identified by its stimulation of [3H]thymidine incorporation into a G-CSF-responsive cell line, NSF-60, and the inhibition of its stimulation by a G-CSF-specific monoclonal antibody (MAB). GM-CSF was identified by its stimulation of [3H]thymidine incorporation into a GM-CSF-responsive line, TALL-101, and the inhibition of its stimulation by a GM-CSF-specific MAB. EDF was identified by its ability to stimulate erythroid differentiation in mouse erythroleukemia cell lines, its identical retention times to those of authentic EDF on three successive reverse-phase HPLC columns and characterization of its penultimate N-terminal residue as leucine which is the same as that of authentic EDF. Both authentic EDF and the erythroid-stimulating activity in PMA-CCM were found to act synergistically with a suboptimal inducing concentration of a well-studied inducing agent, dimethyl sulfoxide, in inducing erythroid differentiation. In addition, a fourth activity was observed in PMA-CCM: normal human fetal bone marrow cell-proliferation stimulating activity (FBMC-PSA). FBMC-PSA was identified by its ability to stimulate the growth of granulocytes and macrophages in FBMC suspension cultures, which neither recombinant G-CSF or GM-CSF were found to do.

Activins↗

Synergistic action of activin A and hexamethylene bisacetamide in differentiation of murine erythroleukemia cells.

Activin A, a peptide homologous to transforming growth factor beta, induced erythroid differentiation of murine erythroleukemia cells in a dose-dependent manner, as judged by the proportion of benzidine-positive cells. The extent of differentiation induced by activin A depended on the cell density in the initial inoculum; the percentage of benzidine-positive cells markedly decreased at an increasing cell density. In contrast, the hexamethylene bisacetamide (HMBA)-induced differentiation was affected only to a little extent by the cell density. Furthermore, the effects of activin A and HMBA were different in sensitivity to the inhibition by dexamethasone; the HMBA-induced differentiation was reduced by about 90% in the presence of dexamethasone, whereas the activin A-induced differentiation was reduced by 40 to 50%. Activin A and HMBA induced the differentiation in a synergistic manner. Especially when the maximal response to activin A was suppressed at high cell density, the simultaneous presence of a suboptimal concentration of HMBA markedly recovered this suppression. This synergism seemed to be generated at the commitment process. Taken together, these results indicate that activin A and HMBA exert their actions, at least in part, through different pathways, and that these pathways interact with each other, resulting in synergistic induction of murine erythroleukemia cell differentiation. Clinical implications of these findings are discussed.

Acetamides↗

Effect of erythroid differentiation factor on erythroid differentiation and proliferation of K-562 cells.

The effects of erythroid differentiation factor (EDF) on the levels of zeta-globin and several proto-oncogene mRNAs and transferrin receptors (Tf-R) of K-562 cells were examined. EDF decreased Tf-R expression and increased the level of zeta-globin mRNA. The mRNA level of c-fos began to rise within 3 hours and continued to increase up to 72 hours, but the levels of c-myb and c-abl decreased to 23 and 19%, respectively, of their initial levels after 48 hours. In contrast, the mRNA levels of c-myc and c-fms decreased transiently, but recovered within 48 hours. The modulation of several proto-oncogene mRNA levels was observed much earlier than the differentiation induction and the growth inhibition of K-562 cells by EDF.

Activins↗

Differentiation-inducing and growth-inhibitory activities of erythroid differentiation factor (EDF/activin A) toward mouse erythroleukemic cells in vivo.

The in vivo differentiation-inducing activity of a purified human erythroid differentiation factor (EDF) toward mouse erythroleukemic cells (MEL cells) was examined. BDF1 mice with diffusion chambers implanted in the peritoneal cavity were treated with continuous i.p. administration of EDF. MEL cells within a diffusion chamber differentiated into hemoglobin-positive cells when treated with EDF, the percentage of the positive cells being 32.3 +/- 28.3 on day 5 as compared to 0.2 +/- 0.3 in the controls. The anti-tumor activity of EDF was also examined in a nude mouse MEL solid tumor model. Daily intra-tumor treatment with EDF for 10 days resulted in 73% suppression of tumor growth on day 25. A histological study revealed that EDF-treated solid tumor cells became hemoglobin-positive, indicating the anti-tumor activity of EDF through induction of differentiation in vivo. EDF could induce in vitro the differentiation of human erythroleukemic cell lines K562 and HEL, as well as the murine cell line. These results indicate the possibility of differentiation therapy for erythroleukemia using EDF.

Activins↗

Inducible gene expression of activin A/erythroid differentiation factor in HL-60 cells.

Treatment of HL-60 cells with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) for 48 h induced expression of mRNA of beta A chain of activin A/erythroid differentiation factor. Under the same condition, interferon-gamma caused a slight increase in beta A chain mRNA, whereas 1 alpha, 25-dihydroxyvitamin D3, dimethylsulfoxide and all-trans-retinoic acid failed to induce this mRNA in HL-60 cells. Furthermore, 4 h-treatment with TPA or lipopolysaccharide (LPS) induced a marked increase in beta A chain mRNA levels in interferon-gamma-pretreated HL-60 cells. In the cells pretreated with 1 alpha, 25-dihydroxyvitamin D3, TPA and LPS induced as little increase in beta A chain mRNA as in the control cells. Neither alpha nor beta B chain mRNA was detected in any sample. These results indicate that interferon-gamma has a priming effect on the activation of activin A/erythroid differentiation factor gene by TPA or LPS in HL-60 cells.

Activins↗

Activin-binding protein from rat ovary is follistatin.

Activin, a member of the transforming growth factor beta protein family, was originally isolated from gonadal fluids and stimulates the release of pituitary follicle-stimulating hormone (FSH). Activin has numerous functions in both normal and neoplastic cells. Various cells synthesize activin and have a specific binding site for this peptide. However, the molecular basis for its actions is unknown. A binding protein for activin was purified from rat ovary and was identical to follistatin, a specific inhibitor of FSH release. It is likely that the binding protein participates in the diverse regulatory actions of activin.

Activins↗

Activin A stimulates meiotic maturation of the rat oocyte in vitro.

The effect of activin A on meiotic maturation was analyzed in oocytes from immature rats treated with PMSG. Activin A, which was purified as the erythroid differentiation factor, accelerated the maturation of not only follicle-enclosed oocytes and oocyte-cumulus complexes, but also denuded oocytes, as measured by an increase in the percentage of oocytes with germinal vesicle breakdown (GVBD). Oocyte maturation was not accelerated by activin A in the presence of the inhibitor of GVBD such as cyclic-AMP. These results showed activin A is a potent in vitro stimulator of oocyte maturation.

Activins↗