18 research outputs found
Automated determination of cardiac rest period on whole-heart coronary magnetic resonance angiography by extracting high-speed motion of coronary arteries
13301乙第2094号博士(保健学)金沢大学博士論文本文Full 以下に掲載:Clinical Imaging 52 Nov-Dec pp.183-188 2018. Elsevier. 共著者:Hiroya Asou, Naoyuki Imada, Yuichi Nishiyama, Tomoyasu Sato, Katsuhiro Ichikaw
Haploinsufficiency of SAMD9L, an Endosome Fusion Facilitator, Causes Myeloid Malignancies in Mice Mimicking Human Diseases with Monosomy 7
SummaryMonosomy 7 and interstitial deletion of 7q (−7/7q−) are well-recognized nonrandom chromosomal abnormalities frequently found among patients with myelodysplastic syndromes (MDSs) and myeloid leukemias. We previously identified candidate myeloid tumor suppressor genes (SAMD9, SAMD9-like = SAMD9L, and Miki) in the 7q21.3 subband. We established SAMD9L-deficient mice and found that SAMD9L+/− mice as well as SAMD9L−/− mice develop myeloid diseases resembling human diseases associated with −7/7q−. SAMD9L-deficient hematopoietic stem cells showed enhanced colony formation potential and in vivo reconstitution ability. SAMD9L localizes in early endosomes. SAMD9L-deficient cells showed delays in homotypic endosome fusion, resulting in persistence of ligand-bound cytokine receptors. These findings suggest that haploinsufficiency of SAMD9L and/or SAMD9 gene(s) contributes to myeloid transformation
Cytokines direct the regulation of Bim and p27^KIP1 mRNA stability by Heat shock cognate protein 70
Previous gene-targeting studies indicated that Bim, a BIB-only death activator, and p27^KIP1, a cydin-dependent kinase inhibitor, regulate total cell number in the body. Cytokines contribute to this process primarily by negatively regulating the steady-state levels of Bim and p27 mRNAs. Here we present a novel mechanism for cytokine-mediated post-transcriptional regulation of Bim and p27 mRNA levels via the activity of Heat shock cognate protein 70 (Hsc70), which enhances the stability of specific mRNAs by binding to AU-rich elements (AREs) in their 3' -untranslated regions. The RNA-binding potential of Hsc70 is regulated by co-chaperones, including Bag-4 (also SODD), CHIP, Hip and Hsp40. Cytokines that down-regulate Bim and p27 operate via Ras-activated signaling pathways, which in turn control the expression or function of these co-chaperones. Thus, exposure of cells to cytokines ultimately leads to the destabilization of Bim and p27 mRNAs and the promotion of cell division and survival. This unanticipated role for a chaperone/co-chaperone complex in the control of mRNA stability appears to be critical for hematopoiesis and leukemogenesis
Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome
Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common non-random chromosomal abnormality found frequently in rnyeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion Cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q
Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome
セミパラチンスク核実験場近郊住民の被爆線量推定方法の確立と健康影響研究
研究期間:平成11-12年度 ; 研究種目:基盤研究A2 ; 課題番号:11694282原著には既発表論文の別刷を含む
セミパラチンスク核実験場近郊の放射線汚染と被曝線量推定および住民の健康影響研究
研究期間:平成13-14年度 ; 研究種目:基盤研究B2 ; 課題番号:13575037原著には既発表論文の別刷を含む