Biomedical subjects

Takehiro Kobayashi

Publications and source records attributed to Takehiro Kobayashi.

4 recordsLinked to original sources

PubMed2004

A gene homologous to human endogenous retrovirus overexpressed in childhood acute lymphoblastic leukemia.

To clarify the mechanism of progression and acquired drug resistance of leukemia, we searched for an overexpressed gene in drug-resistant leukemia cells and identified an approximately 5-kb transcript by using the subtraction method. The nucleotide sequence of the gene was highly homologous to those of human endogenous retrovirus (HERV) transcripts. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the gene was overexpressed in cells from 6 childhood acute lymphoblastic leukemia patients (60%) but not in bone marrow cells at remission. Peripheral blood mononuclear cells from normal controls (n=11) and bone marrow cells from non-leukemia patients (n=13) did not express the gene. These findings indicate that the gene may play a role in leukemogenesis and may be a novel leukemia marker. Further studies on the functional role of the gene are needed.

Adolescent↗

PubMed2004

[Dialysis machine].

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Dialysis Solutions↗

PubMed2003

Characterization of assembly of recombinant type IV collagen alpha3, alpha4, and alpha5 chains in transfected cell strains.

BACKGROUND: Alport syndrome is caused by mutations in type IV collagen alpha3, alpha4, and alpha5 genes. Immunohistochemical analyses of kidney sections from normal individuals and Alport syndrome patients have suggested that the alpha3(IV), alpha4(IV), and alpha5(IV) chains form a heterotrimer in the glomerular basement membrane (GBM) and that a defect in any one of the chains disrupts the assembly of the three chains, resulting in Alport syndrome. METHODS: We established stable transformants of HEK293 cells that expressed mouse alpha3(IV) and/or alpha4(IV) and/or alpha5(IV) chains. Using cell extracts and culture media of these cells, experiments were performed to determine whether or not the alpha3(IV) and alpha4(IV) chains were coimmunoprecipitated with the alpha5(IV) chain. Moreover, we examined complex formation of mutant alpha5(IV) chain containing either a deletion or substitution mutation with the alpha3(IV) and alpha4(IV) chains. RESULTS: The established cell strains were named according to their transfected alpha(IV) chains. The alpha3(IV) and alpha4(IV) chains were coimmunoprecipitated with the alpha5(IV) chain in alpha345 cells but not in alpha35 and alpha45 cells. These chains were not coimmunoprecipitated with the alpha5(IV) chain, which lacked either a collagenous domain or NC1 domain. The ability of the alpha5(IV) chain with either a G1182R or C1573R substitution, corresponding to previously reported mutations in Alport syndrome patients, to form a complex with alpha3(IV) and alpha4(IV) chains was diminished. CONCLUSION: The findings indicate that alpha3(IV), alpha4(IV), and alpha5(IV) chains form a complex, which is a heterotrimer, and that a defect in complex formation might be one of the molecular mechanisms underlying the pathogenesis of Alport syndrome.

Amino Acid Substitution↗

PubMed2002

Mutations in the XPD gene in xeroderma pigmentosum group D cell strains: confirmation of genotype-phenotype correlation.

Xeroderma pigmentosum (XP) is a sun-sensitive and cancer-prone genetic disorder consisting of seven genetically distinct complementation groups (groups A-G). XP group D (XP-D) is a heterogeneous group. Mutations in the XPD gene (XPD) can exhibit three distinct clinical phenotypes: XP, trichothiodystrophy (TTD), or XP combined with Cockayne syndrome. XPD protein is required for both nucleotide excision repair (NER) and basal transcription. Therefore, different mutations in XPD may affect NER and transcription activities to various degrees and result in such diverse phenotypes. In this study, we identified six causative mutations, two of which have not been described, in five XP-D cell strains tested. The cell strains were all compound heterozygotes with different mutations. In all cell strains, one allele was thought to be functionally null and the other was a less severe allele with R683W, R683Q, and R666W substitutions. The second allele in each strain was specific to the XP phenotype. The findings are consistent with the hypothesis that the site of mutation of the XPD gene determines the clinical phenotype, XP or TTD.

Adult↗