126 research outputs found
An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.
Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations
Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI
IntroductionEpidermal growth factor receptor (EGFR) mutation T790M accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Because T790M is mediated by TKI exposure, its penetration and “on–off” may affect T790M status.MethodsWe retrospectively reviewed T790M status and clinical course of patients who had undergone multiple rebiopsies after acquired resistance to EGFR-TKI.ResultsOf 145 patients with EGFR-mutant NSCLC receiving rebiopsy after acquired resistance, 30 underwent multiple site rebiopsies, and 24 received repeated rebiopsies at the same lesion. In 22 patients who underwent rebiopsies from both central nervous system (CNS; 20 cerebrospinal fluids [CSF] and 2 brain tumoral tissues) and thoracic lesions (7 lung tissues, 14 pleural effusions, and 1 lymph node), 12 were thoracic-T790M-positive. Of these 12 patients, 10 were CNS-T790M-negative, despite exhibiting thoracic-T790M-positive. All 10 thoracic-T790M-negatives were CNS-T790M-negative. Three patients revealed a spatial heterogeneous T790M status among their thoracic lesions. In 24 patients receiving repeated rebiopsies at the same lesion (12 lung tissues, 6 CSFs, and 6 pleural effusions), T790M status of lung lesions varied in five patients after TKI-free interval. In all five patients whose T790M status changed from positive to negative, EGFR-TKI rechallenge was effective. In three of these five patients, after further TKI exposure, T790M status changed from negative to positive again. There was also a patient whose CSF T790M status changed from negative to positive after high-dose erlotinib therapy.ConclusionsT790M status in an individual patient can be spatiotemporally heterogeneous because of selective pressure from EGFR-TKI
豆類中のビタミンE含有量におよぼす加熱の影響(自然科学)
ビタミンEは食品中に広く分布しているが,調理中に酸化をうけて含有量に変化が起こることが知られている。これらの変化に関する報告の大部分は食用油中のビタミンEについてであり,その他の食品中のビタミンEの変化についての報告は少ない。特に豆類は組織が堅いため加熱時間が長いので,ビタミンE量の変化は大きいと考えられる。大豆,黒大豆,小豆中のビタミンE含有量が加熱によってどのように変化するかを高速液体クロマトグラフィー法によって定量したところ,大豆では生の49%,黒大豆では15%,小豆は27%まで減少した。また大豆に食塩や重曹を添加して加熱した場合,あるいは黒大豆に鉄ミョウバンを添加した場合は,いずれも無添加にくらべて高い残存率を示し,これらの添加はビタミンB含有量の減少を抑制した
高速液体クロマトグラフィーによる緑茶浸出液のカテキン類の定量 : 浸出方法及び保存方法の比較(自然科学)
上級煎茶を70℃と90℃の湯でそれぞれ0.5分,1分,2分,3分間浸出した試料と6ヶ月間異なる条件で保存した茶を,70℃で3分間浸出した試料を高速液体クロマトグラフィー(HPLC)を用いてカフェイン,カテキン類の定量を行った。浸出温度が高く,浸出時間が長くなるにしたがって,カフェイン,カテキン類の溶出量は増加し,特に,90℃で2分間以上浸出すると,エステル型カテキンの溶出が多くなった。6ヶ月間保存後の緑茶の浸出液では,貯蔵温度が低いほどカフェイン,カテキン類の含有量が多く,室温で保存すると含有量が少なくなったことから,これらの成分は保存中に分解することがわかった。茶液への浸出は(-)-EGCが最も多く(+)-C, (-)-ECGが少なかった。官能検査では70℃で2分間,90℃では1分間浸出した場合が香りもよく,総合評価においても有意に好まれ,70℃浸出では1分間浸出では淡すぎ,90℃では3分間浸出すると濃すぎるため有意に好まれないと評価された。6ヶ月間異なった条件で保存した緑茶は,冷凍庫保存(-40℃)で有意に好まれ,室温保存は有意に好まれないと評価された
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