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Yoshikazu Arai

Publications and source records attributed to Yoshikazu Arai.

6 recordsLinked to original sources

PGC7/Stella protects against DNA demethylation in early embryogenesis.

DNA methylation is an important means of epigenetic gene regulation and must be carefully controlled as a prerequisite for normal early embryogenesis. Although global demethylation occurs soon after fertilization, it is not evenly distributed throughout the genome. Genomic imprinting and epigenetic asymmetry between parental genomes, that is, delayed demethylation of the maternal genome after fertilization, are clear examples of the functional importance of DNA methylation. Here, we show that PGC7/Stella, a maternal factor essential for early development, protects the DNA methylation state of several imprinted loci and epigenetic asymmetry. After determining that PGC7/Stella binds to Ran binding protein 5 (RanBP5; a nuclear transport shuttle protein), mutant versions of the two proteins were used to examine exactly when and where PGC7/Stella functions within the cell. It is likely that PGC7/Stella protects the maternal genome from demethylation only after localizing to the nucleus, where it maintains the methylation of several imprinted genes. These results demonstrate that PGC7/Stella is indispensable for the maintenance of methylation involved in epigenetic reprogramming after fertilization.

Animals↗

Can the detection of misery perfusion in chronic cerebrovascular disease be based on reductions in baseline CBF and vasoreactivity?

PURPOSE: The aim of this study was to clarify whether decreases in baseline regional cerebral blood flow (rCBF) and in residual cerebral vasoreactivity (CVR), assessed by the acetazolamide (ACZ) challenge, can detect misery perfusion in patients with chronic cerebrovascular disease (CVD). METHODS: Oxygen extraction fraction (OEF) and other haemodynamic parameters were measured in 115 patients (64+/-9 years old) with unilateral cerebrovascular steno-occlusive disease (>70% stenosis) using (15)O-gas and water PET. A significant elevation of OEF, by greater than the mean+2SD compared with healthy controls, was defined as misery perfusion. CBF, CVR determined by percent change in CBF after ACZ administration, OEF and other haemodynamic parameters in the territories of the bilateral middle cerebral arteries were analysed. Diagnostic accuracy for the detection of misery perfusion using the criteria determined by baseline CBF and CVR was evaluated in all patients and in only those patients with occlusive lesions. RESULTS: Ten of 24 patients with misery perfusion showed a significant reduction in CVR. Using criteria determined by significant decreases in CVR and baseline CBF, misery perfusion was detected with a sensitivity of 42% and a specificity of 95% in all patients. In patients with occlusive lesions (n=50), sensitivity was higher but specificity was slightly lower. The diagnostic accuracy of the threshold determined by baseline CBF alone was similar in all patients and in only those patients with occlusive lesions, and was higher than that achieved using the asymmetry index of OEF. CONCLUSION: Reductions in CVR and baseline CBF in the ACZ challenge for CVD would detect misery perfusion with high specificity. Reduction in baseline rCBF is more accurate than reduction in CVR alone for the detection of misery perfusion.

Acetazolamide↗

Enantioselective construction of quaternary carbon centers by catalytic [2 + 2 + 2] cycloaddition of 1,6-enynes and alkynes.

[reaction: see text] The enantioselective [2 + 2 + 2] cycloaddition of 1,6-enynes and alkynes using chiral rhodium catalysts gave cycloadducts containing quaternary carbon stereocenters. Both symmetrical and unsymmetrical alkynes and acetylene could be used as coupling partners, and the corresponding bicyclic cyclohexa-1,3-dienes were obtained in good to excellent ee.

Journal Article↗

Stage-by-stage change in DNA methylation status of Dnmt1 locus during mouse early development.

Methylation of DNA is involved in tissue-specific gene control, and establishment of DNA methylation pattern in the genome is thought to be essential for embryonic development. Three isoforms of Dnmt1 (DNA methyltransferase 1) transcripts, Dnmt1s, Dnmt1o, and Dnmt1p, are produced by alternative usage of multiple first exons. Dnmt1s is expressed in somatic cells. Dnmt1p is found only in pachytene spermatocytes, whereas Dnmt1o is specific to oocytes and preimplantation embryos. Here we determined that there is a tissue-dependent differentially methylated region (T-DMR) in the 5' region of Dnmt1o but not in that of the Dnmt1s/1p. The methylation status of the Dnmt1o T-DMR was distinctively different in the oocyte from that in the sperm and adult somatic tissues and changed at each stage from fertilization to blastocyst stage, suggesting that active methylation and demethylation occur during preimplantation development. The T-DMR was highly methylated in somatic cells and embryonic stem cells. Analysis using Dnmt-deficient embryonic stem cell lines revealed that Dnmt1, Dnmt3a, and Dnmt3b are each partially responsible for maintenance of methylation of Dnmt1o T-DMR. In particular, there are compensatory and cooperative roles between Dnmt3a and Dnmt3b. Thus, the regulatory region of Dnmt1o, but not of Dnmt1s/1p, appeared to be a target of DNA methylation. The present study also suggested that the DNA methylation status of the gene region dynamically changes during embryogenesis independently of the change in the bulk DNA methylation status.

5' Untranslated Regions↗

Oscillatory reaction using immobilized catalase.

Oscillation is found in many biological systems, and among them the enzymatic oscillatory reaction has been well studied using an enzyme solution. We show in this study for the first time that oscillation occurs when catalase is immobilized to controlled pore glass (CPG). The oscillatory wave mode changes with the distance among the CPG, electrode, or dialysis membrane. The lower substrate concentration results in oscillation with a longer period. This tendency agrees with a previous study using an enzyme solution. Furthermore, we show that the oscillation occurs when no dialysis membrane is used. These results show the wider applicability of the system to analysis or novel device fabrication.

Catalase↗

Evaluation of prognostic factors and clinical outcome in elderly patients in whom expansive laminoplasty is performed for cervical myelopathy due to multisegmental spondylotic canal stenosis. A retrospective comparison with younger patients.

OBJECT: It remains unclear whether elderly patients with compressive cervical myelopathy can be expected to experience a promising surgery-related outcome after undergoing expansive laminoplasty. The purposes of this study were to evaluate the efficacy of expansive laminoplasty in elderly patients with cervical myelopathy due to multisegmental spondylotic canal stenosis and to analyze the effect of preoperative prognostic factors on outcome in elderly compared with younger patients. METHODS: The authors reviewed the cases of 22 elderly (> 70 years of age) and 39 younger patients in whom expansive open-door laminoplasty was performed for cervical myelopathy due to multisegmental spondylotic canal stenosis. The pre- and 12-month postoperative clinical symptoms were evaluated using the Japanese Orthopaedic Association (JOA) disability scale. Factors affecting the clinical outcome were statistically analyzed by evaluating the recovery rate calculated from the JOA scale. There were no significant differences in the mean value of the preoperative factors, especially preoperative duration of symptoms and severity of preoperative disease, between the elderly and younger patient groups. In all patients, age at the time of the operation was shown to exert no significant influence on clinical outcome. The mean recovery rate was 58.8% in the elderly group and 61.8% in the younger group, and there was no significant intergroup difference. Improvement or attenuation in impaired upper- and lower-leg motor function was shown in all patients as was an absence in decline of sensory impairment of the extremities. In the elderly group, both the duration of symptoms and the severity of canal stenosis significantly (p < 0.05) affected the clinical outcome. In the younger group, the severity of preoperative symptoms had a significant (p < 0.05) influence on clinical outcome, whereas duration of the symptoms did not appreciably affect clinical improvement. CONCLUSIONS: Open-door expansive laminoplasty showed a promising effect on clinical outcome in elderly and younger patients with multisegmental cervical canal stenosis. Significant predictive factors for clinical outcome in the elderly patients were the duration of symptoms and the severity of stenosis, which may involve the static factor causing the cervical myelopathy. To improve the elderly patients' disability, surgery must be performed as early as possible before irreversible changes in the spinal cord develop.

Adolescent↗