Search PubMed⌕ Search

Biomedical subjects

Y Eto

Publications and source records attributed to Y Eto.

At least 127 records · Page 7Linked to original sources
PubMed1995

Initiation of insulin secretion in glucose-free medium by activin A.

Activin A is a multifunctional protein known to stimulate insulin secretion (Yasuda H et al., (1993) Endocrinology 133, 624-630). The present study was conducted to determine whether activin A augments insulin secretion in the absence of ambient glucose. In the presence of 2.7 mM glucose, and 1.25 mM calcium, activin A induced a biphasic secretory response of insulin. In the absence of glucose in perifusate, activin A induced a small but significant release of insulin. The effect of activin A was monophasic in the absence of glucose. In contrast, glucagon-like peptide-1 (GLP-1) had no effect on insulin secretion under the same conditions. However, GLP-1 could enhance insulin secretion induced by activin A in glucose-free medium. Activin A induced a transient increase in cytoplasmic-free calcium concentration, [Ca2+]c, in a fura-2-loaded islet superfused with glucose-free buffer. Again, GLP-1 was without effect on [Ca2+]c by itself in glucose-free buffer. In the presence of activin A, however, GLP-1 could induce an elevation of [Ca2+]c. Finally, GLP-1, but not activin A, increased cAMP content in islets incubated in glucose-free medium. These results indicate that activin A, but not GLP-1, induces insulin secretion in glucose-free medium. Activin A is able to reproduce partly the effect of glucose to support the action of GLP-1 in glucose-free medium.

Activins↗
PubMed1995

Activin induces the expression of the Xenopus homologue of sonic hedgehog during mesoderm formation in Xenopus explants.

The Xenopus homologue of sonic hedgehog (Xhh) was detected in Xenopus embryos at stages 13 and 31 by RT-PCR, but it was not expressed in explants isolated from the animal hemisphere of Xenopus embryos at stage 8-9. Treatment of the animal cap with activin (1-100 ng/ml) induced the expression of Xhh. However, it was not induced by 100 ng/ml basic fibroblast growth factor (bFGF). Whole mount in situ hybridization confirmed the expression of Xhh in the animal cap treated with activin. The expression of Xhh induced by activin was not inhibited in the presence of cycloheximide, suggesting that Xhh is an early response gene induced by activin.

Activins↗
PubMed1995

Characteristics of gene mutations among 32 unrelated Japanese Gaucher disease patients: absence of the common Jewish 84GG and 1226G mutations.

The prevalence of seven different mutations (84GG, IVS2 + 1, 754A, 1226G, 1342C, 1448C, and 1504T) was investigated in 32 unrelated Japanese Gaucher patients of which 20 were type I, 6 were type II, and 6 were type III). These mutations constitute 95% of the mutations observed in Jewish patients with Gaucher disease and 75% of the mutations in non-Jews (European). The most frequent mutation, 1448C (L444P), accounted for 26 alleles (40.6%); the second most prevalent mutation was 754A (F213I), accounting for 7 alleles (10.9%); 27 alleles (42.2%) were unidentified. To data, neither the 1226G (N370S) nor 84GG mutations have been identified in the Japanese population though these alleles account for approximately 70% and 10% of mutations in the Jewish population. These data suggest that mutant alleles identified from the Japanese population are distinct from those observed in Jewish and non-Jewish (European) patients with Gaucher disease.

Alleles↗
PubMed1995

Induction of apoptosis in B lineage cells by activin A derived from macrophages.

A factor produced by P388D1 cell line murine macrophages showed a profound suppressive effect on the in vitro proliferation of B lineage cells. It was purified to homogeneity from conditioned media of P388D1 cells stimulated with phorbol 12-myristate 13-acetate for 48 h by a three-step procedure. The purified factor gave a single band of protein with a molecular mass of 16 kD on SDS-polyacrylamide gel electrophoresis. We show here that exposure of B lineage cells to this factor results in the induction of a cytotoxic effect and a significant increase in the proportion of fragmented DNA. DNA fragmentation was detected in B lineage cells after 3 h culture with the factor in the quantitative colorimetric determination. The mechanism of cell death was characterized by a ladder-like electrophoretic pattern of degraded chromosomal DNA, indicating that the factor induces apoptosis. The NH2-terminal amino acid sequence of this factor was identical with that of activin A over the 26 amino acid residues identified. We sought to determine whether apoptosis could be modulated by two kinds of inhibitor of protein kinases, H7 and HA1004, in concentrations that are below their toxicity limits. Apoptosis induced by the factor was suppressed by H7 but was relatively unaffected by HA1004. These findings suggest that the signals by protein kinases may regulate apoptotic B cell death by the factor activin A, derived from macrophages.

Activins↗
PubMed1995

Hurler syndrome with severe complication in post-bone marrow transplantation course: life threatening interstitial pneumonitis and hypertension.

Bone marrow transplantation (BMT) was performed in a 3 year old patient with Hurler syndrome. The post-BMT course was complicated by interstitial pneumonitis and severe hypertension, which were life threatening. The patient responded well to therapy and recovered. BMT in this patient resulted in significant clinical improvement in the signs and symptoms of Hurler syndrome. Biochemical improvement, including elevated alpha-L-iduronidase activity in white blood cells and decreased urinary glycosaminoglycan excretion was significant. However, skeletal and neurological impairment were not improved. We conclude that BMT for Hurler syndrome should be performed at an earlier stage, before severe neuronal damage has occurred. Moreover, BMT is a high risk procedure and there will always be a possibility that life threatening complications will occur, as in our case.

Bone Marrow Transplantation↗
PubMed1995

Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment.

Activin A is a homodimeric protein structurally and functionally related to transforming growth factor beta (TGF-beta), and the expression of activin A is modulated by TGF-beta. Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs. ICR mice were treated with BLM intraperitoneally for 10 days, whereas saline vehicle was injected into control mice. Intra-alveolar fibrotic changes were observed in the lung tissue obtained from the mice at day 14 after the final BLM administration. Immunohistochemical studies using a polyclonal antibody to activin A revealed the presence of activin A in the bronchiolar epithelium and smooth muscle cells of veins in both control and BLM-treated mice. In the BLM-treated mice at days 7 and 14, the marked infiltration of immunoreactive alveolar macrophages was observed in the area of fibrotic changes. Bioactivity of activin A measured by erythroid differentiation factor assay in the conditioned medium of alveolar macrophages obtained from BLM-treated mice at day 14 was significantly increased. These findings indicate that alveolar macrophages are a potent source of activin A after BLM treatment. The present study demonstrates for the first time the abundant expression of activin A in murine lung tissues after BLM administration, suggesting that activin A may play a role in the pathogenesis of BLM-induced pulmonary fibrosis.

Activins↗
PubMed1995

Expression of immunoreactive activin A in fetal rat pancreas.

Expression of activin A in fetal rat pancreas was studied immunohistochemically by using anti-activin A antibody. On embryonic day 12 (E12), cells in cap-like pancreatic anlage were stained with anti-activin A antibody. In these sections, no immunoreactive insulin or glucagon was observed. On E13.5, cells containing immunoreactive activin A were observed in pancreatic anlage. These cells were also stained by both anti-glucagon and anti-insulin antibodies. On E15, a cluster of cells could be recognized as a primitive islet. In the primitive islet, cells containing immunoreactive activin A were observed. Activin-positive cells were located mainly in the mantle of the primitive islet but some were located in the core of the primitive islet. These activin-positive cells also expressed glucagon. Among them, cells also containing insulin were observed. In addition to activin-positive cells, cells containing only insulin were detected in the core of the primitive islet. These results indicate that immunoreactive activin A is expressed in fetal pancreas. The expression of activin A is an early event during the development of pancreatic endocrine cells.

Activins↗
PubMed1995

Overexpression of arylsulfatase A gene in fibroblasts from metachromatic leukodystrophy patients does not induce a new phenotype.

We tested the influence of overexpression of arylsulfatase A (ASA) on the activity of other sulfatases in fibroblasts from patients with metachromatic leukodystrophy (MLD). We demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of glycosaminoglycan. Our results indicate that influence of ASA overexpression on other sulfatases is different from that of N-acetyl-galactosamine-4-sulfatase overexpression reported by Anson et al. We conclude that gene therapy for MLD based on the transfer of a normal ASA gene to mutant cells will be feasible because the overexpression of ASA peptides in cells does not lead to profound deficiency of other sulfatases or result in a new phenotype.

Cells, Cultured↗
PubMed1995

Successful transduction of oligodendrocytes and restoration of arylsulfatase A deficiency in metachromatic leukodystrophy fibroblasts using an adenovirus vector.

Metachromatic leukodystrophy (MLD) is an inherited metabolic disease which is characterized by deficient activity of arylsulfatase A (ASA). This deficiency causes progressive accumulation of cerebroside sulfate (CS) in oligodendrocytes (OLs) in the brain resulting in dysmyelination. We are developing approaches for treating MLD based on direct delivery of ASA genes to brain. In this paper, we report a recombinant adenovirus (Adex1SRLacZL) that efficiently transduces OLs. Moreover, transduction and expression of the human transgene was efficient in primary fibroblasts from MLD patients exposed to similar recombinant adenovirus carrying the ASA gene (Adex1SRASA) In addition, the expressed ASA protein was correctly targeted to lysosomes and was immunoreactive to anti-ASA antibody. The enzymatic activity of ASA in MLD patient cells is corrected from the deficient state to 2.3 to 5.0 times the activity of normal control cells. These results demonstrate the correction of ASA deficiency by a recombinant adenovirus that is potentially useful for transferring the gene to brain.

Adenoviridae↗
PubMed1995

[A case in which bronchorrhea was alleviated by oral erythromycin and inhalation of beclomethasone and furosemide].

A 55-year-old woman with bronchorrhea and bronchial asthma was admitted to our hospital in June, 1992. On admission, she was producing a large volume of sputum (200 ml) each day. The volume decreased with oral administration of erythromycin and inhalation of beclomethasone. Next, inhalation of furosemide was added to the regimen, which lead to symptomatic improvement in mucus clearance, although the sputum increased in volume. The concentrations of albumin, fucose, sialic acid, and phosphatidylcholine in the sputum changed with these treatments, as did the lecithin/sphingomyelin ratio. These observations suggest that these drugs affect not only the quantity but also the quality of sputum.

Administration, Inhalation↗
PubMed1995

[Metachromatic leukodystrophy (MLD) and Multiple sulphatase deficiency (MSD)].

MLD is caused by a deficiency of arylsulfatase A and hence sulfolipids are accumulated in various patient's tissues. Various clinical phenotypes including activator deficiency, pseudodeficiency and MSD. Recently, molecular basis of these disorders have been identified. Clinical phenotype in MLD is well correlated with their genotype. Most common mutation in Caucasian MLD is caused by 609A mutation which produces late infantile MLD. In Japanese, most common mutation is 445A mutation. Essential treatment of MLD is recently carried out by bone marrow transplantation. On the hand, MSD is caused by multiple deficiencies of various sulfatases and hence accumulated various sulfated compounds such as sulfatide and acid mucopolysaccharides. The clinical features have combined characteristics of MLD and mucopolysaccharidosis. The cause of this disorder is recently identified as abnormal modification of various sulfatase.

Base Sequence↗
PubMed1994

Regulated expression of Brachyury(T), Nkx1.1 and Pax genes in embryoid bodies.

Embryonic stem cells (ES) can be exploited to analyze in vitro mechanisms of cellular differentiation. We have utilized ES-derived embryoid body formation in an attempt to study cell types resulting from in vitro differentiation. To this end, a variety of molecular markers, preferably those which have been associated with regulatory events during mouse embryogenesis, was employed. Specifically, Brachyury (T), Pax-3 and Pax-6 genes as well as Nkx-1.1 were used. We could demonstrate that the expression of these genes in vitro was regulated by growth factors such as activin A or bFGF. Implications of these findings and the possible applications for identifying new genes are discussed.

Animals↗
PubMed1994

Autoinduction of activin genes in early Xenopus embryos.

Activin exhibits a potent mesoderm inducing activity towards the ectodermal tissue (animal cap) of Xenopus laevis blastulae. Thus in order to investigate the role of activin in morphogenesis of early Xenopus embryos, activation of genes for activin beta A and beta B was examined by the reverse transcription polymerase chain reaction. In vivo, activin beta B mRNA appears to be present in embryonic stage 1 whereas beta A mRNA is undetectable prior to gastrulation. beta B and beta A mRNAs were noted to accumulate after stages 9 and 15 respectively. Activin gene expression in Xenopus animal caps was examined after treatment with various concentrations of activin A. Under these treatment conditions, both activin beta A and beta B mRNAs accumulated in a dose-dependent fashion after 24 h. The same effect was noted for treatment with similar concentrations of activin B. Accumulation of mRNAs was inhibited by the addition of cycloheximide to the culture medium, consistent with the proposition that activin gene expression requires certain protein factors. In total, therefore, these data suggest that an autoinduction mechanism is involved in the regulation of activin mRNA levels in normal Xenopus embryos and that this mechanism may play a pivotal role during early embryonic development.

Activins↗
PubMed1994

The attenuated elevation of cytoplasmic calcium concentration following the uptake of low density lipoprotein in type C Niemann-Pick fibroblasts.

In Niemann-Pick disease type C fibroblasts, the deficiency of cholesterol esterification has been reported. In this experiment, we detected the attenuated elevation of cytoplasmic calcium concentration following low density lipoprotein uptake in the fibroblasts. Moreover, we administered calcium channel agonist (0.5 microM YC-170) and calcium channel antagonists to the fibroblasts. YC-170 improved the attenuated elevation of calcium concentration and the deficient cholesterol esterification by 40% and 90% respectively. Calcium channel antagonists decreased the cholesterol esterification in normal and affected fibroblasts. These data indicated that the attenuated elevation of cytoplasmic calcium concentration was strongly related to the etiology of this disease.

Calcium↗
PubMed1994

Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing.

The arylsulfatase A gene of a Japanese patient who has the juvenile form of metachromatic leukodystrophy, and who has been previously reported as a heterozygote of the 1070A mutation, was investigated. Nucleotide sequence analysis revealed the presence of a previously unreported C-to-T substitution (designated 2330T), 22 nucleotides downstream from the exon 8 splice acceptor site. Although the 2330T mutation itself results in a single amino acid substitution of Thr409 by Ile, the analysis of the patient's cDNA fragments amplified by the reverse transcription-polymerase chain reaction revealed that transcripts of the 2330T allele were spliced both normally and aberrantly. The aberrant splicing produced a 27-nucleotide deletion from the usual exon 8 splice acceptor site. These results indicate that the new mutation is a rare case of an exon mutation affecting splice site selection. The mechanism of this aberrant pre-mRNA splicing is discussed.

Adolescent↗
PubMed1994

Type C Niemann-Pick disease fibroblasts and their transformed cell lines are hypersensitive to HMG-CoA reductase inhibitors.

The deficiency of exogenous cholesterol transport within fibroblasts of Niemann-Pick disease type C (NPC) has been addressed. In this report we confirmed that the endogenous synthesis of cholesterol within cells was markedly increased in NPC fibroblasts and those transformed by origin-defective simian virus 40. The transformed fibroblasts and those of the primary culture were hypersensitive to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors as a consequence of their dependence on endogenous cholesterol biosynthesis. The transformed fibroblasts should help further biochemical and genetic research in this condition.

Cell Line, Transformed↗
PubMed1994

Early onset of cecal perforation in neonatal, recto-sigmoid type Hirschsprung's disease.

Hirschsprung's disease has been considered to cause intestinal perforation in rare cases. Even if a perforation occurs, the majority of cases are associated with the long-segment or total colonic type. Our case developed the perforation in the neonatal period in spite of being of the recto-sigmoidal type, and it affected the cecum. We do not have a good explanation for this condition. However, the pathological examination of the specimens of the perforated cecum revealed some necrosis (ulceration, subcutaneous hemorrhage, congestion and severe edema) which was considered to be caused by ischemia, secondary to a localized vascular accident in the wall of the distended intestine.

Age of Onset↗