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Biomedical subjects

Tomoko Hata

Publications and source records attributed to Tomoko Hata.

9 recordsLinked to original sources
PubMed2006

The relationship between sperm morphology and in vitro fertilization ability in mice.

In vitro fertilization (IVF) is widely used in reproduction research, but the sperm of some inbred strains of mice yield low fertilization rates in IVF. To determine the cause of this problem, we examined the effect of epididymal sperm morphology, in particular, tail bending and the presence and type of cytoplasmic droplet (CD), on fertilizability in vitro. Sperm suspensions were obtained from the following five strains: C57BL/6J, BALB/cA, C3H/HeN, DBA/2J, and 129 x 1/SvJ. The sperm were fixed in 10% formalin and three parts of the sperm, namely the head, tail, and CD, were examined. We recorded the proportion of abnormal sperm heads and hairpins at the neck; tails were categorized as straight, proximal bent, or distal bent; and the CDs were categorized as none, light-type, and heavy-type. Based on these parameters, we determined the correlations between sperm morphology and fertilizability in vitro, as judged by IVF using ICR oocytes. The proportion of sperm with a hairpin neck was higher in strain C57BL/6J, while abnormal head morphology occurred significantly more often in strain BALB/cA. The percentage of sperm with a proximal bent tail was highest in strain DBA/2J and lowest in strain 129 x 1/SvJ. A heavy-type CD was observed more frequently in the 129 x 1/SvJ and C57BL/6J strains than in the other three strains in which a light-type CD predominated. The rank order of the fertilization rates was 129 x 1/SvJ < C57BL/6J < C3H/HeN < BALB/cA < DBA/2J. In addition, fertilization rate was positively correlated with a proximal bent tail, but negatively correlated with a heavy-type CD and distal bent tail. This new classification system establishes that the morphological characteristics of epididymal sperm differ among inbred strains of mice and that tail and CD morphology are closely related to fertilization ability in IVF. Thus, our results provide a novel method for assessing the quality of mouse sperm used for IVF.

Animals↗
PubMed2006

Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates to the prognosis of acute myeloid leukemia.

We previously reported that the percentage of myeloperoxidase (MPO) positive blasts had a prognostic impact on survival of patients with acute myeloid leukemia (AML). To extend this observation, we quantitatively measured the level of the MPO gene in AC133 positive leukemia cells that would contain a putative AML stem/progenitor compartment. AML cases were divided into the MPO gene high (MPOg-H) and MPO gene low (MPOg-L) groups. Only patients belonging to the MPOg-H group had a favorable chromosomal translocation, t(8;21), and having no morphological dysplasia that was associated with MPOg-L. The difference in the survival of MPOg-H and MPOg-L was statistically meaningful, demonstrating the possible prognostic impact of the expression of MPO gene in AC133 positive leukemia cells.

AC133 Antigen↗
PubMed2006

Transgene insertion pattern analysis using genomic walking in a transgenic mouse line.

A transgene mapping technique (Noguchi et al., Exp. Anim. 53:103-111, 2004) is described that can be used to analyze transgene integration patterns in transgenic mice. The technique was used to reveal that a transgenic mouse line (GM1-sy#116) harbored inverted and direct tandem repeats of both intact and partial pCAGGS-based transgenes in the G2 region of chromosome 1. This complicated concatenation of transgenes may have been caused by simple end-joining of DNA constructs fragmented by exposure to UV transillumination during gel-purification, and by nuclease digestion inside zygote pronuclei. The results suggest that care should be taken to avoid unwanted fragmentation during the preparation of vector constructs.

Animals↗
PubMed2006

[Plasmodium vivax malaria with clinical presentation mimicking acute type idiopathic thrombocytopenic purpura].

Causes of thrombocytopenia are diverse, and infection with plasmodia often brings about thrombocytopenia. Japan is not an endemic area of malaria infection at present and most cases are travelers to endemic areas. In some cases, initial clinical diagnoses may not be correct because of a variety of symptoms, physical findings and laboratory abnormalities. A 67-year-old female, who had traveled to South American countries 2 months before the onset of the disease, presented with a case of vivax malaria. Because of the patient's high fever, profound thrombocytopenia (1.5 x 10(4)/microl), and elevated platelet-associated IgG on admission, our initial diagnosis was acute type idiopathic thrombocytopenic purpura (ITP). However, we recognized her tertian fever and plasmodial vivax in erythrocytes 4 days later. She responded promptly to anti-parasitic therapy after diagnosis of malaria and her laboratory data also improved. Travel history is indicative of malaria infection in some cases with thrombocytopenia mimicking acute ITP.

Acute Disease↗
PubMed2005

Methylation analysis of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma.

We investigated methylation status of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma (ATL). APC methylation was found in 15 of 31 (48%) primary samples, and 2 of 4 (50%) ATL cell lines. Methylation of the APC gene occurred more frequently in acute ATL (12/21) (57%) than chronic ATL (1/8) (13%) (P = 0.03). APC was not expressed in the APC-methylated ATL cell line ST1. Demethylation with 5-azacytidine treatment restored APC expression in the ST1 cell line. Our data show that hypermethylation of the APC gene is involved in the pathogenesis of ATL.

Adenomatous Polyposis Coli Protein↗
PubMed2004

Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated Type I (slow twitch/red muscle) fiber genes, and impaired glycemic control.

FOXO1, a member of the FOXO forkhead type transcription factors, is markedly up-regulated in skeletal muscle in energy-deprived states such as fasting and severe diabetes, but its functions in skeletal muscle have remained poorly understood. In this study, we created transgenic mice specifically overexpressing FOXO1 in skeletal muscle. These mice weighed less than the wild-type control mice, had a reduced skeletal muscle mass, and the muscle was paler in color. Microarray analysis revealed that the expression of many genes related to the structural proteins of type I muscles (slow twitch, red muscle) was decreased. Histological analyses showed a marked decrease in size of both type I and type II fibers and a significant decrease in the number of type I fibers in the skeletal muscle of FOXO1 mice. Enhanced gene expression of a lysosomal proteinase, cathepsin L, which is known to be up-regulated during skeletal muscle atrophy, suggested increased protein degradation in the skeletal muscle of FOXO1 mice. Running wheel activity (spontaneous locomotive activity) was significantly reduced in FOXO1 mice compared with control mice. Moreover, the FOXO1 mice showed impaired glycemic control after oral glucose and intraperitoneal insulin administration. These results suggest that FOXO1 negatively regulates skeletal muscle mass and type I fiber gene expression and leads to impaired skeletal muscle function. Activation of FOXO1 may be involved in the pathogenesis of sarcopenia, the age-related decline in muscle mass in humans, which leads to obesity and diabetes.

Adenosine Triphosphatases↗
PubMed2004

Rapid isolation of viral integration site reveals frequent integration of HTLV-1 into expressed loci.

Although there is tight association of the human T-cell leukemia virus type-1 (HTLV-1) with adult T-cell leukemia/lymphoma (ATLL), it has remained unresolved whether the HTLV-1 integration into the host genome has any role in the development of this disease. We isolated a total of 58 HTLV-1 integration sites using newly developed, adaptor-ligated PCR from 33 ATLL patients and five ATLL cell lines. We compared our data as well as the previously reported ones with the complete human genomic sequence for the location of its placement, structure, and expression of genes nearby the integration site. The chromosomal target for integration was selected at random, but the integration favorably occurred within the transcription units; more than 59.5% of total integration was observed within the transcriptional unit. All inserted genes by HTLV-1 integration were expressed in normal T cells. Upregulation of genes due to viral integration was found in two out of nine ATLL cases; about 4.4- and 102-fold elevated ankyrin-1 ( ANK-1) and gephyrin ( GPHN) gene expressions were observed, respectively. These data suggest that the preferential integration of HTLV-1 into an expressed locus occasionally causes deregulation of corresponding gene, which may lead to leukemogenesis of a fraction of ATLL.

Ankyrins↗
PubMed2003

[Intensive multi-drug chemotherapy for acute myeloid leukemia in a renal allograft recipient].

A Fifty-two year old male, who had received a renal transplantation from his sibling 14 years previously, was referred to our hospital because of leukocytosis, anemia and thrombocytopenia. A bone marrow examination revealed an increase of leukemic blasts with morphological dysplasia of mature hematopoietic cells. The diagnosis of acute myeloid leukemia (AML) with multilineage dysplasia without antecedent myelodysplastic syndrome was made. Since the patient's general condition and the function of the transplanted kidney were well maintained, intensive therapy for his AML was chosen. The dosage of the immune suppressive reagents that were administered to prevent the rejection of the transplanted kidney were reduced during chemotherapy to minimize the adverse effect of immune suppression, and G-CSF was administrated to shorten the neutropenic period. Along with these supportive strategies, cytosine arabinoside and idarubicin-based induction therapy followed by four courses of intensive consolidation therapy were successfully performed without disturbing his renal function. It is suggested that intensive chemotherapy is feasible for post-transplant AML patients when their general condition and transplanted renal functions are well maintained.

Antineoplastic Combined Chemotherapy Protocols↗