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Biomedical subjects

Y Sasai

Publications and source records attributed to Y Sasai.

At least 19 recordsLinked to original sources
PubMed2000

Xenopus kielin: A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline.

The midline tissues are important inductive centers of early vertebrate embryos. By signal peptide selection screening, we isolated a secreted factor, Kielin, which contains multiple cys-rich repeats similar to those in chordin (Chd). Expression of Kielin starts at midgastrula stages in the notochord and is detected in the floor plate of neurula embryos. Kielin is induced in mesoderm and in ectoderm by nodal-related genes. Chd is sufficient to activate Kielin expression in mesoderm whereas Shh or HNF-3beta in addition to Chd is required for induction in ectoderm. Kielin has a distinct biological activity from that of Chd. Injection of Kielin mRNA causes dorsalization of ventral marginal zone explants and expansion of MyoD expression in neurula embryos. Unlike Chd, Kielin does not efficiently induce neural differentiation of animal cap ectoderm, suggesting that the activity of Kielin is not simply caused by BMP4 blockade. Kielin is a signaling molecule that mediates inductive activities of the embryonic midline.

Amino Acid Sequence↗
PubMed2000

Xenopus Xenf: an early endodermal nuclear factor that is regulated in a pathway distinct from Sox17 and Mix-related gene pathways.

We report a novel zygotic gene encoding a Xenopus endodermal nuclear factor, Xenf. Expression of Xenf starts at the late blastula stages and is decreased after gastrulation. Xenf shows no structural homology to any known proteins. When GFP-tagged Xenf is overexpressed in Xenopus cells, Xenf protein is localized to the nucleus, associating closely with the chromosomes. In animal cap assays, Xenf expression is strongly activated by mRNA injection of Vg1 and VegT, maternal vegetal genes that can induce endodermal differentiation. In contrast, Xenf is not induced by endoderm-inducing zygotic transcription factors such as Sox17 and Mix-related genes. In turn, Xenf does not activate expression of Sox17, Mixer or Milk. Thus, Xenf is regulated by maternal vegetal positional information in a parallel manner to Sox17 and Mix-related gene pathways.

Amino Acid Sequence↗
PubMed2000

Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity.

We have identified a stromal cell-derived inducing activity (SDIA) that promotes neural differentiation of mouse ES cells. SDIA accumulates on the surface of PA6 stromal cells and induces efficient neuronal differentiation of cocultured ES cells in serum-free conditions without use of either retinoic acid or embryoid bodies. BMP4, which acts as an antineuralizing morphogen in Xenopus, suppresses SDIA-induced neuralization and promotes epidermal differentiation. A high proportion of tyrosine hydroxylase-positive neurons producing dopamine are obtained from SDIA-treated ES cells. When transplanted, SDIA-induced dopaminergic neurons integrate into the mouse striatum and remain positive for tyrosine hydroxylase expression. Neural induction by SDIA provides a new powerful tool for both basic neuroscience research and therapeutic applications.

Animals↗
PubMed2000

Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm.

From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominant-negative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2-mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2-class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.

Animals↗
PubMed2000

Relationship between breast milk feeding and atopic dermatitis in children.

OBJECTIVE: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR] = 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR = 1.14, 95% CI; 0.95-1.35) showed odds ratios that were higher than unity without statistical significance. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders.

Adult↗
PubMed2000

[Qualitative study of municipalities' maternal and child health promotion planning].

From 1997, basic maternal and child health services have been provided through municipalities. The ministry of Health and Welfare has requested all municipalities to publish a MCH promotion plan. We conducted a qualitative analysis of important contents of the plans using an evaluation index of original dichotomous variables. Out of 3,256 municipalities, 2,873 developed the plans for MCH promotion. Most of the plans present descriptions of the significance of MCH promotion planning, goals of the plans, problems of current MCH statistics and services, and plans of providing services. The proportion was low for plans which have needs assessment of target population, indicators of evaluation of plans, description of the relationship between objectives and services, importance of objectives, action plans, specific chapter or evaluation of the plan, monitoring of the plan, and plans for informing public of the MCH plan. Therefore, the MCH promotion plans have weaknesses in evaluation and action. The MCH promotion plans of middle sized cities were more likely to have these important contents. We will continue to analyze the processes for producing of excellent MCH promotion plans to extract universal promoting factors for producing MCH promotion plans.

Child Health Services↗
PubMed1999

Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia.

We examined polymorphisms of glutathione S-transferase (GST) genes in 159 Japanese patients with myelodysplasia and compared the incidence with that in 43 normal individuals to clarify their pathogenetic significance in myelodysplasia. In individuals with the GSTT1 null genotype, the odds ratios for disease risk were elevated to 2.65 (95%CI; 1.27-5.52) in de novo MDS, 4.62 (1.48-14.4) in therapy-related AML, and 2.94 (1.07-8.07) in AML with triliniage dysplasia. Other representative polymorphisms of GSTs had a similar incidence among patients with myelodysplasia, and those of the controls and other hematological disorders. To further investigate the genetic pathway of myelodysplasia, the association between GST genotype and karyotype or configurations of TP53 and NRAS was evaluated, but no relationship was noted. These results suggest that the GSTT1 null genotype may play a role in an increased risk of myelodysplasia unrelated to other mechanisms of myelodysplasia, such as chromosomal alterations or mutation of TP53 or NRAS.

Acute Disease↗
PubMed1999

Distinct genetic involvement of the TP53 gene in therapy-related leukemia and myelodysplasia with chromosomal losses of Nos 5 and/or 7 and its possible relationship to replication error phenotype.

We examined chromosomes and molecular aberrations in 21 patients with therapy-related leukemias (t-AML) or myelodysplastic syndromes (t-MDS). All patients showed abnormal karyotypes, and chromosomal losses of No. 5 and/or No. 7 (-5/5q- and/or -7/7q-) were identified in 12 patients. Among these 12, six patients (50%) harbored a TP53 mutation, and two of five examined showed microsatellite instability, suggesting replication error (RER+) phenotype. Meanwhile, among the other nine patients without -5/5q- and/or -7/7q-, none harbored a TP53 mutation, and none of five examined showed RER+ phenotype. Thus, TP53 mutations and RER+ phenotype were preferentially associated with specific chromosomal losses in t-AML/MDS. We then screened for mutational events in representative DNA mismatch repair genes; exons 5-7 and 12-15 of the hMSH2 gene and exon 9 of hMLH1. Notably, two unrelated patients showing RER+ phenotype had an identical missense alteration at codon 419 of hMSH2 in their marrow cells and fibroblasts, which were not found in 120 DNA samples from healthy volunteers or patients with other hematological disorders. Consequently, this study revealed a possible relationship of RER+ phenotype accompanying an hMSH2 alteration to the development of therapy-related AML/MDS in association with TP53 mutations and specific chromosomal losses, and suggests that some patients may be predisposed to myelodysplasia after chemotherapy for their primary tumor.

Adult↗
PubMed1999

[Syngeneic peripheral blood stem cell transplantation for chronic myelogenous leukemia associated with Klinefelter's syndrome].

We report on a patient with Klinefelter's syndrome who underwent successful syngeneic peripheral blood stem cell transplantation (PBSCT) for chronic myelogenous leukemia (CML). A-46-year-old man was given a diagnosis of chronic phase CML in May 1994 on the basis of findings of leukocytosis (54,000/microliter) and bone marrow chromosomal abnormalities [47, XXY, t(9; 22; 14) (q34; q11; q24)]. Hydroxyurea and interferon alpha were administered. In August 1996, a syngeneic transplant was performed following myeloablative therapy, using peripheral blood stem cells collected from the patient's identical twin brother, who had been pretreated with rhG-CSF. Following transplantation (4.0 x 10(6) CD34+ cells/kg) and the subsequent administration of rhG-CSF, the patient rapidly achieved normal tri-lineage hematopoiesis. A post-transplant chromosomal analysis of the patient's bone marrow cells detected the 47, XXY karyotype. Although the major BCR-ABL gene had been detected in bone marrow by RT-PCR methods prior to the syngeneic PBSCT (August 1996), it was not detected after PBSCT (January 1997). In March 1998, interphase fluorescence in situ hibridization (FISH) procedures disclosed XXY signal patterns in peripheral blood lymphocyte samples from the patient and donor, at frequencies of 96% and 97%, respectively. Both the patient and donor had high levels of serum FSH and LH and low levels of serum testosterone.

Diseases in Twins↗
PubMed1998

A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner.

The formation of Spemann organizer is one of the most important steps in dorsoventral axis determination in vertebrate development. However, whether the organizer forms autonomously or is induced non-cell-autonomously is controversial. In this report we have isolated a novel zebrafish homeobox gene, dharma, capable of inducing the organizer ectopically. The expression of dharma was first detected in several blastomeres at one side of the margin soon after the mid-blastula transition and continued in the dorsal side of the yolk syncytial layer (YSL) under the embryonic shield, the zebrafish organizer, until the onset of gastrulation. Furthermore, dharma expressed in the YSL induced the organizer in a non-cell-autonomous manner. These results provided the first identification of a zygotic gene to be implicated in the formation of an organizer-inducing center.

Amino Acid Sequence↗
PubMed1998

Significance of chromosomal alterations and mutations of the N-RAS and TP53 genes in relation to leukemogenesis of acute myeloid leukemia.

We examined chromosomes and mutations of the N-RAS and TP53 genes in 73 patients with acute myeloid leukemia (AML). Twenty-six patients showed a reciprocal chromosomal translocation or an inversion, and 34 patients showed only unbalanced aberrations. Balanced aberrations were predominantly detected in the AML patients who did not have myelodysplasia, preceding myelodysplastic syndrome, and a history of chemotherapy or radiation therapy. In contrast, unbalanced aberrations were more frequently seen in the patients with AML with trilineage myelodysplasia, AML transformed from MDS, and therapy-related AML. Twenty-two mutations of the N-RAS and TP53 genes were detected, and these mutations were frequently associated with unbalanced chromosomal aberrations. Furthermore, the spectrum of mutations was suggestive of an exposure to alkylating chemicals.

Acute Disease↗
PubMed1998

SoxD: an essential mediator of induction of anterior neural tissues in Xenopus embryos.

Vertebrate neurogenesis is initiated by the organizer factors that inhibit antineuralizing activities of bone morphogenetic proteins (BMPs) in the ectoderm. Here, we report a candidate mediator of neuralization, SoxD. Expression of SoxD starts at late blastula stages widely in the prospective ectoderm and becomes restricted to the dorsal ectoderm by mid-gastrula stages. SoxD expression is enhanced by the neural inducer Chordin and is suppressed by BMP4 and its downstream genes. Microinjection of SoxD mRNA causes ectopic formation of neural tissues in vivo and induces neural and neuronal markers in the isolated animal cap. Injection of a dominant-negative form of SoxD mRNA can block neuralization of ectoderm caused by attenuation of BMP signals and can strongly suppress formation of anterior neural tissues in vivo. These data show that SoxD functions as an essential mediator of downstream signaling of neural induction.

Amino Acid Sequence↗
PubMed1998

Rare alteration of genomic structure or expression of the DPC4 gene in myelogenous leukemias.

We examined homozygous deletion, point mutation and expression of DPC4 gene, a recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of chronic myelogenous leukemia including 22 in the chronic phase, 3 in the accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous leukemia including 9 at the initial presentation and 10 at relapse. Polymerase chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single strand conformation polymorphism study for the entire coding region were carried out. Homozygous deletion or subtle mutation was not detected in any of the samples examined. However, 3 patients with various clinical phases showed a decrease of DPC4 expression. These results suggest that DPC4 alteration is not a crucial event in the development or the progression of myelogenous leukemias.

DNA-Binding Proteins↗
PubMed1998

Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction.

In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor. Expression of the two genes is first detected widely in the prospective neuroectoderm at the beginning of gastrulation, following the onset of Chordin expression and preceding that of Neurogenin (Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. In contrast, Sox-2 alone is not sufficient to cause neural differentiation, but can work synergistically with FGF signaling to initiate neural induction. Thus, Zic-r1 acts in the pathway bridging the neural inducer with the downstream proneural genes, while Sox-2 makes the ectoderm responsive to extracellular signals, demonstrating that the early phase of neural induction involves simultaneous activation of multiple functions.

Animals↗
PubMed1998

[Clinical study on the inhibitory effect of a 5-HT3 antagonist, granisetron, for nausea and vomiting induced by chemotherapy (CHOP, VEPA, high-dose ETP) for non-Hodgkin's lymphoma].

The antiemetic effect of granisetron on nausea and vomiting induced by cancer chemotherapy (CHOP, VEPA, VEPA-B, massive dose of ETP) was studied in fifty patients with non-Hodgkin's lymphoma. There was almost no difference in the inhibitory effect by regimen, with the rates of perfect inhibition of nausea and vomiting standing at 55.6% to 60%. Nausea and vomiting was perfectly controlled in 60% of 35 patients receiving CHOP therapy. As a part of this study, a comparison was made of perfect inhibitory effect on nausea and vomiting by potency of chemotherapy under the potency scale of 750 mg/m2 of CPA as 1, revealing no significant difference in the rates of complete inhibition as 71.4% for a drug potency of less than 0.8 vs 52.4% for 0.8 or above (p = 0.26). However, it was clear that the higher the dose of chemotherapy, the lower the rate of complete inhibition. The results confirmed the high efficacy and safety of granisetron in the treatment of nausea and vomiting induced by cancer chemotherapy.

Adult↗
PubMed1998

[t(3;5) (q21;q31) chromosomal abnormality in a patient with acute myelogenous leukemia with trilineage myelodysplasia].

A 60-year-old woman was admitted in June 1993, because of anemia and purpura and given a diagnosis of acute myelogenous leukemia with trilineage dysplasia. She entered partial remission (PR) after three courses of low-dose Ara-C and G-CSF, but never reached complete remission (CR) in spite of additional chemotherapy. In October 1994, the number of leukocytes, myeloblasts, and erythroblasts in the patient's peripheral blood increased, and her clinical condition deteriorated. The disease was resistant to other therapy. The patient had pneumonia and died of septic shock in December 1994. A chromosomal analysis performed on admission showed 46,XX,t(3;5) (q21;q31) [9/9]. As an additional chromosomal abnormality, deletion of the X chromosome was observed in January, 1994. Analysis of the p53 gene by the polymerase chain reaction-single strand conformation polymorphism method showed one base transposition, from TAT to TGT (Tyr to Cys), at codon 220 of exon 6. Karyotype evolution and p53 gene mutation were observed during the disease course and may have been related to progression of the disease.

Chromosomes, Human, Pair 3↗
PubMed1998

[Clinical evaluation of cefozopran for infections associated with hematological malignancies].

Cefozopran (CZOP) was used as an initial antibacterial therapy for infections in patients with hematological malignancies. CZOP was given at a daily dose of 4 g by drip intravenously to patients who were febrile over 38 degrees C and were suspected as having bacterial infections. As underlying diseases, 8 patients had acute lymphoblastic leukemia (ALL), 9 acute myeloblastic leukemia (AML), 2 aplastic anemia (AA), 2 adult T cell leukemia/lymphoma (ATLL), 28 non Hodgkin lymphoma (NHL), and 2 multiple myeloma (MM). Bacterial infections diagnosed were sepsis in 7 patients, suspected sepsis in 32, bronchitis in 6, pneumonia in 5 and acute peritonitis in 1. Clinical responses among 51 evaluable cases were excellent in 14, good in 15, fair in 3, poor in 19 and the overall response rate was 57%. The overall response rates for AML, ALL, AA, ATLL, NHL and MM were 56%, 63%, 100%, 50%, 50%, and 100%, respectively. Those for sepsis, suspected sepsis, bronchitis, pneumonia and acute peritonitis were 14%, 63%, 100%, 40%, and 0%, respectively. This therapy was effective in 53% (9/17) of patients whose granulocyte count remained below 500/microliter throughout the course of CZOP therapy. Six bacterial and one fungal strains were isolated from blood and sputum of six patients including five sepsis cases; two bacteria were eradicated and bacterial change was observed in one case. As side adverse effects, 10 patients had liver dysfunction, 1 anemia, 2 proteinemia, 1 indirect bilirubinemia, 2 thrombocytopenia, and 1 eosinophilia. We tried to establish a scoring system for the severities of patients with their infections, underlying diseases, treatments for the underlying disease, and granulocyte counts in order to evaluate the efficacy of CZOP more precisely. This scoring system was consisted of three grades; severe, moderate, and mild. CZOP was effective on mild and moderate grades. These results indicate that the initial antibacterial therapy by CZOP is useful for the treatment of mild and moderate grade infections complicated with hematological malignancies.

Acute Disease↗