Yosuke Ejima
Kyoto University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Yosuke Ejima.
Mutation Research | 2002
Masao S. Sasaki; Yosuke Ejima; Akira Tachibana; Toshiko Yamada; Kanji Ishizaki; Takashi Shimizu; Taisei Nomura
Radioadaptive response is a biological defense mechanism in which low-dose ionizing irradiation elicits cellular resistance to the genotoxic effects of subsequent irradiation. However, its molecular mechanism remains largely unknown. We previously demonstrated that the dose recognition and adaptive response could be mediated by a feedback signaling pathway involving protein kinase C (PKC), p38 mitogen activated protein kinase (p38MAPK) and phospholipase C (PLC). Further, to elucidate the downstream effector pathway, we studied the X-ray-induced adaptive response in cultured mouse and human cells with different genetic background relevant to the DNA damage response pathway, such as deficiencies in TP53, DNA-PKcs, ATM and FANCA genes. The results showed that p53 protein played a key role in the adaptive response while DNA-PKcs, ATM and FANCA were not responsible. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), mimicked the priming irradiation in that the inhibitor alone rendered the cells resistant against the induction of chromosome aberrations and apoptosis by the subsequent X-ray irradiation. The adaptive response, whether it was afforded by low-dose X-rays or wortmannin, occurred in parallel with the reduction of apoptotic cell death by challenging doses. The inhibitor of p38MAPK which blocks the adaptive response did not suppress apoptosis. These observations indicate that the adaptive response and apoptotic cell death constitute a complementary defense system via life-or-death decisions. The p53 has a pivotal role in channeling the radiation-induced DNA double-strand breaks (DSBs) into an adaptive legitimate repair pathway, where the signals are integrated into p53 by a circuitous PKC-p38MAPK-PLC damage sensing pathway, and hence turning off the signals to an alternative pathway to illegitimate repair and apoptosis. A possible molecular mechanism of adaptive response to low-dose ionizing irradiation has been discussed in relation to the repair of DSBs and implicated to the current controversial observations on the expression of adaptive response.
Human Genetics | 1988
Yosuke Ejima; Masao S. Sasaki; Akihiro Kaneko; Hiroshi Tanooka
SummaryA cytogenetic survey of 200 retinoblastoma (Rb) patients revealed that approximately 8.5% of the fresh germinal mutations were microscopically detectable chromosome mutations, either interstitial deletions or rearrangements, involving 13q14. They showed a strong bias toward paternal origin, indicating a significant contribution of errors in paternal meiotic processes. The incidence of patients with Rb due to such chromosome mutations was estimated to be 1.9 x 10-6 of live births. Age-specific incidence of Rb tumors suggested that the Rb mutations by such chromosomal mechanisms had a lower carcinogenic potential, as indicated by the later onset of disease, than other Rb mutations of germinal origin.
International Journal of Cancer | 2000
Yosuke Ejima; Lichun Yang; Masao S. Sasaki
Inherited mutations of the ATM gene are responsible for the human autosomal recessive disorder ataxia‐telangiectasia (A‐T) characterized by pleiotropic clinical manifestations. ATM mutations are also involved in the development of sporadic human cancers such as T‐cell prolymphocytic leukemia and B‐cell chronic lymphocytic leukemia. Little is known, however, on the association of ATM mutations with non‐lymphoid malignancy. Here, we analyzed a panel of cell lines derived from human solid tumors for the presence of ATM mutations. PCR‐SSCP analysis of 25 tumor cell lines revealed 50 sequence alterations in 16 cell lines. The most striking feature was a high frequency of deletions within the intronic mononucleotide tracts exclusively in the 5 colon tumor cell lines with microsatellite instability, which accounted for 62% of the sequence alterations observed here. Generation of aberrant splicing variants (497del22 or 1236del372) was associated with 2 such intronic deletions at splice acceptor sites preceding ATM exon 8 or exon 12, respectively. The level of ATM protein was partially depressed in the 3 cell lines where expression of protein‐truncating 497del22 transcripts dominated. This implies that ATM is a novel mutation target of microsatellite instability where abnormal transcripts are generated indirectly by intronic mutations, which is distinct from the other mutation targets such as the type II TGF‐β receptor gene or BAX, where exonic repeats are directly affected. Int. J. Cancer 86:262–268, 2000.
Radiation Research | 1999
Takeo Ohnishi; Xinjiang Wang; Akihisa Takahashi; Ken Ohnishi; Yosuke Ejima
Acute low-dose irradiation (0.1-1 Gy, 1.33 Gy/min) of cells of a human glioblastoma cell line, A-172, induced a dose-dependent monophasic accumulation of TP53 (formerly known as p53) and CDKN1A (formerly known as WAF1). In contrast, chronic gamma irradiation (0.001 Gy/min) produced a clear biphasic response of accumulation TP53 with the first peak at 1.5 h (0.09 Gy) and the second peak at 10 h (0.54 Gy). Significantly, when the cells were preirradiated with a chronic dose of gamma irradiation for 24 h (1.44 Gy) or 50 h (3 Gy), they no longer responded to an acute challenging dose to produce a dose-dependent response of the TP53 pathway. These findings suggest that chronic irradiation at low dose rate alters the TP53-dependent signal transduction pathway. Wearing away of the TP53 pathway by chronic exposure to radiation may have important implications for radiation protection.
Human Genetics | 1994
Mitsuo Kato; Kanji Ishizaki; Takashi Shimizu; Yosuke Ejima; Hiroshi Tanooka; Jun Takayama; Akihiro Kaneko; Junya Toguchida; Masao S. Sasaki; Michitaka Kato
Segregation analysis of polymorphic sites within the retinoblastoma (RB) gene and on chromosome 13, as well as the parental origin of the lost allele in the tumor, were analyzed in 24 families with RB patients. Four mutant alleles transmitted through the germ-line and seven de novo germ-line mutant alleles were identified in 11 patients with hereditary RB. Segregation analysis within the RB gene and on chromosome 13 was useful for DNA diagnosis of susceptibility to RB in relatives of hereditary patients, even if mutations were not identified. All seven de novo germ-line mutant alleles were paternally derived. The bias toward the paternal allele for de novo germ-line mutations of the RB gene was statistically significant. Seven paternal alleles and six maternal alleles were lost in 13 non-hereditary RB tumors with no bias in the parental origin of the somatic allele loss. These results suggest that the physical environment or a deficiency in DNA repair during spermatogenesis may be associated with significant risk factors for de novo germ-line mutations.
Human Mutation | 1999
Akira Tachibana; Takesi Kato; Yosuke Ejima; Toshiko Yamada; Takashi Shimizu; Lichun Yang; Yukiko Tsunematsu; Masao S. Sasaki
Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA‐A to FA‐H) have been identified with their relative prevalence varying among the ethnical backgrounds. Recently, responsible genes, FANCA and FANCC, have been cloned. This report describes mutations of the FANCA gene, which we studied by direct sequencing of cDNA with confirmation on genomic DNA in 15 unclassified Japanese FA patients. A total of 19 sequence alterations were identified, of which 10 (six missense and four silent alterations) were likely to be nonpathogenic polymorphism. The remaining nine alterations, of which eight were novel mutations, were assumed to be pathogenic and consisted of two missense mutations and seven mutations resulting in truncation of gene product, demonstrating a wide allelic heterogeniety. The pathogenic mutations were found in 12 patients (80%); they were either homozygous or compound heterozygous in 10 patients, apparently heterozygous in two patients and none in three patients. We conclude that the sequence variability is intrinsic to the FANCA gene and that the relative prevalence of the FA‐A subtype is unusually high in Japanese FA patients. Hum Mutat 13:237–244, 1999.
Clinical Genetics | 2008
Yosuke Ejima; Masao S. Sasaki; Akihiro Kaneko; Hiroshi Tanooka; Yutaka Hara; Tetsuo Hida; Yoshihiro Kinoshita
Chromosome examination of a female patient with 13/X translocation associated with retinoblastoma was carried out using peripheral blood lymphocytes and cultured skin fibroblasts. The constitutional karyotype was 46,X,t(l 3;X) (q12;p22). Q‐banding analysis showed that the translocated chromosomes were of paternal origin. Studies on DNA replication pattern with Giemsa banding using the bromodeoxyuridine substitution technique revealed that the derivative X chromosome was late replicating, and the translocated chromosome 13 was affected by the spreading of lyonization. Such a functional monosomy of 13q14 may also be involved in retinal blasts, and be related to the development of retinoblastoma.
Mutation Research Letters | 1982
Yosuke Ejima; Masao S. Sasaki; Hiroshi Utsumi; Akihiro Kaneko; Hiroshi Tanooka
Diploid fibroblast cell strains derived from 14 patients with various forms of retinoblastoma (RB) and 5 non-RB patients with constitutional chromosome anomalies involving chromosome 13 were assayed for their clonogenic survival after X-irradiation. Cells from a patient with ataxia telangiectasia (AT) was used as a radiosensitive reference strain. When compared with cell strains from 7 healthy persons as normal controls, a marked radiosensitivity was observed in strain from an AT patient. However, none of the cell strains derived from RB patients or patients with inborn anomalies in chromosome 13 showed pronounced deviation from the normal range of radiosensitivity. The findings thus did not warrant either the RB as radiosensitive genetic disease or the presence of repair locus on chromosome 13, deletion or triplication of which was previously suggested to link to radiosensitivity.
Human Genetics | 1998
Yosuke Ejima; Masao S. Sasaki
The ATM (A-T, mutated) gene on human chromosome 11q22.3 has recently been identified as the gene responsible for the human recessive disease ataxia-telangiectasia (A-T). In order to define the types of disease-causing ATM mutations in Japanese A-T patients as well as to look for possible mutational hotspots, reverse-transcribed RNA derived from ten patients belonging to eight unrelated Japanese A-T families was analyzed for mutations by the restriction endonuclease fingerprinting method. As has been reported by others, mutations that lead to exon skipping or premature protein truncation were also predominant in our mutants. Six different mutations were identified on 12 of the 16 alleles examined. Four were deletions involving a loss of a single exon: exon 7, exon 16, exon 33 or exon 35. The others were minute deletions, 4649delA in exon 33 and 7883del5 in exon 55. The mutations 4612del165 and 7883del5 were found in more than two unrelated families; 44% (7 of 16) of the mutant alleles had one of the two mutations. The 4612del165 mutations in three different families were all ascribed to the same T→A substitution at the splice donor site in intron 33. Microsatellite genotyping around the ATM locus also indicated that a common haplotype was shared by the mutant alleles in both mutations. This suggests that these two founder mutations may be predominant among Japanese ATM mutant alleles.
Radiation Research | 1998
Masao S. Sasaki; Toshihiro Takatsuji; Yosuke Ejima
The F value, the ratio of inter- to intrachromosomal interchanges, as a biomarker for densely ionizing radiation which was proposed by Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) has been a matter of repeated discussion. We examined our experimental data on radiation-induced chromosome aberrations in human peripheral blood lymphocytes for the F value as measured by the ratio of dicentrics to centric rings. Because of the rarity of aberrations, the F value showed a considerable variability, with a large error range particularly in the low-dose range of low-LET radiation. However, the data showed a general trend that the F value tended to be lower for high-LET than low-LET radiations. The differential F value was more pronounced at low doses and diminished with increasing dose; the F values of all radiations tended to converge toward a similar value at high doses. The limiting F value at the lowest doses, or the F0 value, was dependent on LET for high-energy radiations that can produce an array of DNA double-strand breaks along the track of the charged particle. However, LET and dose dependence were not seen for the low-energy photons, where spatially uncorrelated random breaks were produced by independent photoabsorption events.