The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Kenichi Matsubara - One of the best experts on this subject based on the ideXlab platform.
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copy number loss of src homology 2 domain containing Transforming Protein 2 shc2 gene discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy
Molecular Brain, 2011Co-Authors: Hidenao Sasaki, Mitsuru Emi, Hiroshi Iijima, Noriko Ito, Hidenori Sato, Ichiro Yabe, Takeo Kato, Jun Utsumi, Kenichi MatsubaraAbstract:Background: Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. Results: By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-Transforming Protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10 -8 , odds ratio = 89.8, Pearson’s chi-square test). Conclusions: Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
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Copy number loss of (src homology 2 domain containing)-Transforming Protein 2 ( SHC2 ) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy
Molecular brain, 2011Co-Authors: Hidenao Sasaki, Mitsuru Emi, Hiroshi Iijima, Noriko Ito, Hidenori Sato, Ichiro Yabe, Takeo Kato, Jun Utsumi, Kenichi MatsubaraAbstract:Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-Transforming Protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10-8, odds ratio = 89.8, Pearson's chi-square test). Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
Ian H. Frazer - One of the best experts on this subject based on the ideXlab platform.
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expression purification and immunological characterization of the Transforming Protein e7 from cervical cancer associated human papillomavirus type 16
Clinical and Experimental Immunology, 1999Co-Authors: Germain J. P. Fernando, B. Murray, Jian Zhou, Ian H. FrazerAbstract:E7 is the major oncogenic Protein produced in cervical cancer-associated human papillomavirus type 16 (HPV16). This Protein was expressed in Escherichia coli as a glutathione-S-transferase (GST) fusion Protein. E7-enriched inclusion bodies were collected from bacterial lysates, were solubilized in 10 M urea, and the Protein was purified using anion exchange column chromatography. After removal of endotoxin with serial Triton X-114 extractions, material of high purity (about 90%) was obtained, which is suitable for use in a human clinical trial. This material was immunogenic, and when used as a vaccine, protected mice against challenge with an HPV16 E7 DNA transfected tumour cell line. Based on this observation, the E7GST fusion Protein is currently being used in a human clinical trial of a vaccine against HPV16-induced cervical cancer. This fusion Protein could be cleaved with thrombin to remove the GST fusion part and further purified by preparative SDS gel electrophoresis to obtain free E7 with > 98% purity.
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Expression, purification and immunological characterization of the Transforming Protein E7, from cervical cancer‐associated human papillomavirus type 16
Clinical and experimental immunology, 1999Co-Authors: Germain J. P. Fernando, B. Murray, Jian Zhou, Ian H. FrazerAbstract:E7 is the major oncogenic Protein produced in cervical cancer-associated human papillomavirus type 16 (HPV16). This Protein was expressed in Escherichia coli as a glutathione-S-transferase (GST) fusion Protein. E7-enriched inclusion bodies were collected from bacterial lysates, were solubilized in 10 M urea, and the Protein was purified using anion exchange column chromatography. After removal of endotoxin with serial Triton X-114 extractions, material of high purity (about 90%) was obtained, which is suitable for use in a human clinical trial. This material was immunogenic, and when used as a vaccine, protected mice against challenge with an HPV16 E7 DNA transfected tumour cell line. Based on this observation, the E7GST fusion Protein is currently being used in a human clinical trial of a vaccine against HPV16-induced cervical cancer. This fusion Protein could be cleaved with thrombin to remove the GST fusion part and further purified by preparative SDS gel electrophoresis to obtain free E7 with > 98% purity.
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T-helper epitopes of the E7 Transforming Protein of cervical cancer associated human papillomavirus type 18 (HPV18)
Virus research, 1995Co-Authors: Germain J. P. Fernando, Robert W. Tindle, Ian H. FrazerAbstract:Abstract The presence of T-helper epitopes within the E7 Transforming Protein of human papillomavirus type 18 (HPV18) was sought using a series of overlapping synthetic 15–20 mer peptides spanning the entire 105 amino acid sequence of this Protein. Two H-2 k restricted T-helper epitopes were defined, comprising 44 VNHQHLPARRA 55 and 81 DDLRAFQQLF 90 as the minimal T proliferative epitopes. Peptides containing these epitopes were able to provide cognate help to B epitopes from HPV18E7 Protein for production of antibody to this Protein in vivo in CBA/CaH mice. No H-2 b or H-2 d restricted epitopes were demonstrable, and in H-2 d mice this was associated with poor antibody response to the E7 Protein. There is no “promiscuous” T-helper epitope in HPV18 E7 comparable to the 49 DRAHYNI 55 sequence in HPV16 E7, and restricted T-helper epitope availability may be a determinant of poor immune responses to this Protein after natural infection.
Dean W Ballard - One of the best experts on this subject based on the ideXlab platform.
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persistent activation of nf κb by the tax Transforming Protein involves chronic phosphorylation of iκb kinase subunits ikkβ and ikkγ
Journal of Biological Chemistry, 2001Co-Authors: Robert S Carter, Brian C Geyer, Minhui Xie, Carlos A Acevedosuarez, Dean W BallardAbstract:Abstract The Tax Transforming Protein encoded by human T-cell leukemia virus type 1 (HTLV1) persistently activates transcription factor NF-κB and deregulates the expression of downstream genes that mediate cell cycle entry. We recently found that Tax binds to and chronically stimulates the catalytic function of IκB kinase (IKK), a cellular enzyme complex that phosphorylates and inactivates the IκB inhibitory subunit of NF-κB. We now demonstrate that the IKKβ catalytic subunit and IKKγ regulatory subunit of IKK are chronically phosphorylated in HTLV1-infected and Tax-transfected cells. Alanine substitutions at Ser-177 and Ser-181 in the T loop of IKKβ protect both of these IKK subunits from Tax-directed phosphorylation and prevent the induction of IκB kinase activity. Each of these inhibitory effects is recapitulated in Tax transfectants expressing the bacterial Protein YopJ, a potent in vivo agonist of T loop phosphorylation. Moreover, ectopically expressed forms of IKKβ that contain glutamic acid substitutions at Ser-177 and Ser-181 have the capacity to phosphorylate a recombinant IKKγ substrate in vitro. We conclude that Tax-induced phosphorylation of IKKβ is required for IKKβ activation, phosphoryl group transfer to IKKγ, and acquisition of the deregulated IKK phenotype.
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persistent activation of nf κb by the tax Transforming Protein of htlv 1 hijacking cellular iκb kinases
Oncogene, 1999Co-Authors: Shao Cong Sun, Dean W BallardAbstract:Persistent activation of NF-κB by the Tax Transforming Protein of HTLV-1: hijacking cellular IκB kinases
Jun Utsumi - One of the best experts on this subject based on the ideXlab platform.
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copy number loss of src homology 2 domain containing Transforming Protein 2 shc2 gene discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy
Molecular Brain, 2011Co-Authors: Hidenao Sasaki, Mitsuru Emi, Hiroshi Iijima, Noriko Ito, Hidenori Sato, Ichiro Yabe, Takeo Kato, Jun Utsumi, Kenichi MatsubaraAbstract:Background: Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. Results: By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-Transforming Protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10 -8 , odds ratio = 89.8, Pearson’s chi-square test). Conclusions: Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
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Copy number loss of (src homology 2 domain containing)-Transforming Protein 2 ( SHC2 ) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy
Molecular brain, 2011Co-Authors: Hidenao Sasaki, Mitsuru Emi, Hiroshi Iijima, Noriko Ito, Hidenori Sato, Ichiro Yabe, Takeo Kato, Jun Utsumi, Kenichi MatsubaraAbstract:Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-Transforming Protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10-8, odds ratio = 89.8, Pearson's chi-square test). Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
Hidenao Sasaki - One of the best experts on this subject based on the ideXlab platform.
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copy number loss of src homology 2 domain containing Transforming Protein 2 shc2 gene discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy
Molecular Brain, 2011Co-Authors: Hidenao Sasaki, Mitsuru Emi, Hiroshi Iijima, Noriko Ito, Hidenori Sato, Ichiro Yabe, Takeo Kato, Jun Utsumi, Kenichi MatsubaraAbstract:Background: Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. Results: By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-Transforming Protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10 -8 , odds ratio = 89.8, Pearson’s chi-square test). Conclusions: Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
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Copy number loss of (src homology 2 domain containing)-Transforming Protein 2 ( SHC2 ) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy
Molecular brain, 2011Co-Authors: Hidenao Sasaki, Mitsuru Emi, Hiroshi Iijima, Noriko Ito, Hidenori Sato, Ichiro Yabe, Takeo Kato, Jun Utsumi, Kenichi MatsubaraAbstract:Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA. By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-Transforming Protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (p = 1.04 × 10-8, odds ratio = 89.8, Pearson's chi-square test). Copy number loss of SHC2 strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.
