A novel tool for detecting amyloid deposits in systemic amyloidosis in vitro and in vivo |
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Authors: | Ando Yukio Haraoka Katsuki Terazaki Hisayasu Tanoue Yutaka Ishikawa Kensuke Katsuragi Shoichi Nakamura Masaaki Sun Xuguo Nakagawa Kazuko Sasamoto Kazumi Takesako Kazuhiro Ishizaki Takashi Sasaki Yutaka Doh-ura Katsumi |
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Institution: | Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan. |
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Abstract: | We synthesized (trans,trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) and used this compound to detect amyloid fibrils in autopsy and biopsy samples from patients with localized amyloidosis, such as familial prion disease, and systemic amyloidosis, such as familial amyloidotic polyneuropathy, amyloid A (AA) amyloidosis, light chain (AL) amyloidosis, and dialysis-related amyloidosis. BSB showed reactions in all Congo red-positive and immunoreactive regions of the samples examined in the study, and some amyloid fibrils in the tissues could be detected more precisely with BSB than with the other methods. In the mouse model of AA amyloidosis, injected BSB reacted with amyloid in all regions in the serial sections in which Congo red staining was positive. A highly sensitive 27-MHz quartz crystal microbalance analysis revealed that BSB showed a significant affinity for amyloid fibrils purified from familial amyloidotic polyneuropathy and dialysis-related amyloidosis samples and suppressed formation of transthyretin amyloid in vitro. These results suggest that BSB may become a valuable tool for detection of amyloid deposits in amyloidosis and of the mechanism of amyloid formation. |
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