@article{oai:twinkle.repo.nii.ac.jp:00018819,
 author = {IIZUKA, Aiko and HASEGAWA, Kiyoshi and TORII, Nobuyuki and HAYASHI, Naoaki},
 issue = {12},
 journal = {東京女子医科大学雑誌},
 month = {Dec},
 note = {これまでに,HBs抗原の肝細胞への蓄積は肝障害の重症度と関連していることが,トランスジェニックマウスを用いた実験モデルで証明されている.またenvelope蛋白の分泌の制御の一部は,large S,middle S,small Sなどによって担われていることが知られている.従って,preS領域の塩基変異によるenvelope蛋白の産生の変化は,envelope蛋白の分泌と細胞内の蓄積に影響を与えることが予想される.我々は,B型慢性肝炎患者における肝細胞内のHBs抗原の蓄積,preS領域の塩基配列の関連について検討した.慢性B型肝炎患者15例を対象とし血清よりDNAを抽出後,PreS領域をPCR増幅した.肝細胞中のHBs抗原強陽性は9例で変異はSP1結合部周辺に強くみられ,それらの症例は,肝細胞内にエンベロープ蛋白の蓄積を多く認めた.SP1結合部周囲の変異は,HBs抗原プロモーターと他のエンベロープ蛋白との活性化に影響を与える可能性が示唆された., It has been shown that accumulation of hepatitis B surface antigen (HBsAg) in hepatocytes is associated with liver cell damage. Release and retention of envelope protein is controlled by the major surface antigen promoter and the balance of large, middle and small envelope proteins. To investigate the mechanism of accumulation of envelope protein in vivo, we analyzed the relationship between the sequence of the preS region and retention of envelope protein histologically in patients with chronic hepatitis B. We studied 15 patients with histologically diagnosed chronic hepatitis B. Accumulation of envelope protein was studied immunohistochemically using polyclonal anti-HBs antibody. Sequence analysis was performed using direct sequencing methods following polymerase chain reaction (PCR) amplification. Strongly positive HBsAg staining was observed in 9 patients, and the remaining patients were negative for HBsAg. Sequence analysis revealed that the mutations were clustered in and around the Sp1 binding site within the major surface promoter region in the patients who exhibited accumulation of envelope protein. Mutations in and around the Sp1 binding site may affect activity of the major surface antigen promoter and the balance between the various envelope proteins, resulting in accumulation of envelope protein in hepatocytes.},
 pages = {503--512},
 title = {Relationship Between Mutation in PreS Region and Intracellular Retention of Envelope Protein in Patients with Chronic Hepatitis B},
 volume = {72},
 year = {2002}
}