生物物理化学
Online ISSN : 1349-9785
Print ISSN : 0031-9082
ISSN-L : 0031-9082
44 巻, 4 号
選択された号の論文の15件中1~15を表示しています
  • 杉村 隆
    2000 年 44 巻 4 号 p. 231-239
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
  • 三木 一正
    2000 年 44 巻 4 号 p. 241-246
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    As the lecture of Predisent of the 50th Spring Meeting of the Japanese Electrophoresis Society, covered the own group's research field during the past about 20 years periods. Basic aspect and clinical significance of pepsinogens were reviewed. Contents of the lecture were the cellular localization of pepsinogen granules in the one cell, the activation mechanism of it, the entire human pepsinogen A and C genes, and the nucleotide sequence of all the exon and the 5'-and 3'-flanking regions. Topics of isozymes of human pepsinogen A (I), the schema of pepsinogen-producing mechanisms from mRNA, and electrophoretic pattern of pepsinogen A (I) from human gastric mucosa using agargel, were included. On the other hand, as for the clinical significance of pepsinogens, the first case report of pepsinogen producing gastric carcinoma with high pepsinogen II levels in both serum and ascites, and pepsinogen I and II immunohistochemical staining in gastric carcinoma tissues using the monoclonal antibodies, were presented. Finally, the clinical application of the serum pepsinogen levels in the research of Helicobacter pylori infection, gastric cancer development in the course of carcinogenesis from atrophic gastritis to gastric cancer in the population level, gastric cancer screening using serum pepsinogen test kits, which were commercially available now in Japan, and the significance of low serum pepsinogen levels to detect stomach cancer associated with extentive chronic gastritis, which was a precancerous condition of gastric cancer, were discussed.
  • 立松 正衞
    2000 年 44 巻 4 号 p. 247-250
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    Helicobacter pylori (Hp) has been classified as a stomach carcinogen on the basis of epidemiological findings. For detailed analysis of the role of Hp in stomach carcinogenesis, it is essential to establish a small animal model. Hirayama et al. first demonstrated that Mongolian gerbils (MGs) can be infected with Hp. We have established experimental models of stomach carcinogenesis in MGs using the chemical carcinogens, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU). In the present study, male MGs were infected with Hp before or after MNU administration. Glandular stomach adenocarcinomas not only of well-differentiated but also poorly differentiated and signet-ring cell types were induced. The incidence of adenocarcinomas was significantly higher in animals treated with before or after MNU administration than in the controls. Hp infection also enhances glandular stomach carcinogenesis in MGs treated with MNNG. To further assess this latter possibility, male MGs were treated with MNU followed by inoculation with Hp, or infected with Hp followed by MNU administration, then Hp was eradicated in half of the infected animals. The incidence of tumor development in infected animals was significantly higher than in Hp eradicated animals. The incidence was significantly suppressed by the eradication procedure. Our studies have shown that Hp enhances glandular stomach carcinogenesis of MGs treated with chemical carcinogens. Moreover, Hp eradication may be useful as a prevention approach.
  • 一瀬 雅夫
    2000 年 44 巻 4 号 p. 251-256
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    胃粘膜上皮組織は, 各個体の生涯を通じて, 不断の増殖分化の営みを続ける高度に統制された組織である. 胃の特異的機能を担う上皮組織の増殖分化は, 他の臓器における実質細胞の増殖分化調節機構と同様に, 各細胞内に内蔵された遺伝的なプログラムに基づく調節機構と, それに働きかける生体内因子および外的な環境因子の複雑な相互作用により調節されており, その結果, 臓器特異的な機能を果たす高次構造が形成, 維持されていることが想定されている.
  • 吉田 謙一, 水上 洋一, 秋 利彦
    2000 年 44 巻 4 号 p. 257-259
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    We review on the involvement of intracellular signaling molecules in the protection against myocardial ischemia-reperfusion injury. Ischemia or repeated brief ischemia-reperfusion (ischemic preconditioning, IP) induces translocation of PKC isoforms to the membrane or nucleus. PKC-ε isoform is involved in the IP's protective effect in the perfused heart and in vivo infarction model. In the in vivo model, IP upregulates VEGF mRNA and subsequent angiogenesis. Additionally, NO generated during reperfusion activates PKC-α, δ and ε isoforms, thereby alleviating contractile dysfunction by reperfusion. On the other hand, ischemia induces PKC-ζ translocation through PI3 kinase activation. Ischemia also induces MAP kinase, c-Jun-N-terminal kinase (JNK) to the nucleus, and reperfusion activates MAP kinase and JNK, thereby inducing c-fos and c-jun. The pathway of PI3 kinase, PKC-ζ, and MAP kinase protects myocardial cells against ischemia-reperfusion injury through apoptosis inhibition. Ischemia also induces translocation of small heat shock proteins HSP27 and MKBP to the nucleus and myofibrils, which would protect myofibrils and nucleus against oxidative stress induced by reperfusion.
  • 蛋白新規合成阻害下での血管内皮細胞に対する好中球/癌細胞の接着性の亢進
    鈴木 敬一郎, 江口 裕伸, 大河原 知水, 谷口 直之
    2000 年 44 巻 4 号 p. 261-264
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    Adhesion of colon cancer cells (colo 201) and neutrophils to endothelial cells which had been briefly treated with hypoxanthine/xanthine oxidase, hydrogen peroxide, or peroxynitrite was analyzed in the absence of de novo protein synthesis using actinomycin D or cycloheximide. Hypoxanthine/xanthine oxidase treatments accelerated the adhesion of both colo 201 cells and neutrophils to endothelial cells, and these effects were blocked by SOD/catalase or EDTA. These data provided preliminary evidence for the fact that hydroxyl radicals directly affect the cell surface of endothelial cells and accelerate cell adhesion.
  • 酸化ストレス産物および酸化ストレス源としての反応性アルデヒド
    内田 浩二
    2000 年 44 巻 4 号 p. 265-269
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    There is increasing evidence that aldehydes generated endogenously during the degradation process of biological molecules are involved in many of the pathophysiologies associated with cardiovasular diseases such as atherosclerosis and the long-term complications of diabetes. Major sources of reactive aldehydes in vivo are lipid peroxidation, glycation, and amino acid oxidation. Although the types of aldehydes are varied, the important aldehydes that can exert biological effects relevant to the pathobiology of oxidant injury are represented by 2-alkenals, 4-hydroxy-2-alkenals, and ketoaldehydes. These aldehydes exhibit facile reactivity with proteins, generating stable products at the end of a series of reactions. On the other hand, a number of reactive aldehydes have been implicated as inducers in generating intracellular oxidative stress and activation of stress signaling pathways, that integrate with other signaling pathways to control cellular responses to the extracellular stimuli.
  • 新井 博文, 長坂 祐二, 柏木 史郎, 古元 礼子, 中村 和行
    2000 年 44 巻 4 号 p. 271-275
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    銅イオン (Cu2+) による超低密度リポタンパク質 (VLDL) の酸化に対するアスコルビン酸およびグリコサミノグリカン (GAG) の抑制効果について検討した. VLDL中のアポリポプロテインE (apoE) は脂質過酸化反応にともなって酸化修飾を受けて高分子化し, 凝集を形成した. 酸化修飾を受けたapoEのヘパリン結合能は著しく低下していたことから, 細胞の脂質の取り込みを調節するapoEの機能がVLDLめ酸化によって障害される可能性が示唆された. Cu2+が誘導するVLDLの脂質過酸化およびapoEの酸化修飾をアスコルビン酸およびGAGは強く抑制した. アスコルビン酸およびGAGは酸化ストレスによるapoEの機能障害を抑制することが明らかとなった.
  • 金光 房江, 武田 和久
    2000 年 44 巻 4 号 p. 277-282
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    74歳腎梗塞の女性に認められたCK結合性IgG, IgM共存例について報告した. 腎梗塞によりCK-BBが腎組織より逸脱し, 血中CK-BBはLD, ASTなどとともに一過性に上昇した. IgG, IgMともにCK-Bサブユニットに親和性をもっていた. 当初, IgGとIgMは同程度に優位だったが, 1週間後にはIgMが優位となり, 1年後にはIgGが優位となった. IgGサブクラスは半年間でIgG1優位からIgG3優位に変化しており, CK-BサブユニットとはFab部分で結合した. CKは腎組織中には16.4±7.6IU/g湿重量 (平均±SD) 程度あり, CK-BBが優位であった. CK-BBは腎組織中では細動脈内皮細胞, 細動脈内腔, 糸球体毛細血管内腔, 小葉間静脈内腔と, 腎の血管系にそって検出され, 一方で尿細管細胞, 尿細管内腔には検出されなかった. これらの結果より, 本症例はすでに存在するCK-Bサブユニット結合性IgGに加えて, 腎梗塞により逸脱したCK-BBがトリガーとなってCK-Bサブユニット結合性IgMが産生され, 二次抗体のIgGが既存のCK-Bサブユニット結合性IgGとは別に生成されたと考えられた. また, 虚血性心疾患においてCK-BB-IgG複合体を形成するCK-BBの由来は, 血管内皮細胞, 平滑筋細胞, 動脈硬化部位などが考えられた.
  • 奥村 伸生, 寺澤 文子
    2000 年 44 巻 4 号 p. 283-288
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    Fibrinogen Matsumoto II is a hereditary dysfibrinogenemia with heterozygous missense mutation, γ308 Asn->Lys. The propositus's fibrinogen analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) using the Laemmli's buffer system under reducing conditions and Western blotting revealed two distinct bands corresponding to the γ-chain; one with an apparently normal molecular weight (MW) (47, 500) and the other with a lower MW (45, 500). To better define the characteristics on SDS-PAGE of γ308 Lys mutant γ-chain, we synthesized three fibrinogens with single amino acid substitution at this residue: γ308 Lys, γ308 Ile, γ308 Ala. We found the MW of the γ-chains derived from recombinant fibrinogens, γ308 Asn, γ308 Ala, γ 308Ile, and γ308 Lys, were 48.5, 48.5, 47.0, and 46.0kDa, respectively. These results demonstrated the lower MW of mutant γ-chain derived from plasma fibrinogen of Matsumoto II and Baltimore III (γ308 Asn->Ile) propositus due to the single amino acid substitution. The increased mobility of the mutant γ-chain could be attributed to the binding properties of SDS to the peptide. It is well-known that the increased or decreased SDS binding induces complicated changes in the electrophoretic mobility, however, we speculate the mechanism of the increased mobility of the protein is followings. Since SDS preferentially binds either basic or hydrophobic amino acids, the mutant peptide increased basicity or hydrophobicity bind much more SDS. Then the increased SDS binding may lead to complicated change of conformation and/or net charge of the peptide. Finally these phenomena may result in faster mobility on SDS-PAGE and lead decreased MW of the peptide.
  • 宮西 節子, 竹岡 加陽, 奥村 敦子, 赤坂 尚司, 大野 仁嗣, 小橋 陽一郎
    2000 年 44 巻 4 号 p. 289-293
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    T-cell-rich B-cell lymphoma はびまん性の形態, 反応性T細胞が優位で腫瘍性のB細胞が少なく, 一見T細胞性リンパ腫様であることから形態学や免疫学的検索によっても診断が困難な腫瘍である. われわれは他院にてホジキン病の診断を受け, 4年後, 二度目の再発で来院した症例が, 腫瘍細胞が形態学的に同定し難く診断困難であったことから, サザン法によりIgH, BCL-2遺伝子の再構成を検索し, faint band を検出した. 剖検時の再構成バンドが全く同じサイズであったことから, この症例は T-cell-rich B-cell lymphoma の形で発症したものと考えられた. さらに, レトロスペクティブではあるが, 腫瘍細胞の免疫グロブリン重鎖可変部の complementarity determining region (CDR) I, CDR II, CDR III領域のクロナリティをPCR法で検出することにより, 微量の腫瘍細胞からモノクロナリティを検出することができた. サザン法とPCR法という特異性と感度に優れた二つの方法を組み合わせることにより, モノクロナリティの証明, 細胞起源の同定および癌遺伝子の関与を明らかにできることを示した. また, リンパ腫細胞のCDR II領域の体細胞変異を同定し, 腫瘍が胚中心由来のB細胞であることを証明した. これらの方法はプロスペクティブに, 診断困難な症例に応用できる.
  • 新井 雅信, 中津 雅美
    2000 年 44 巻 4 号 p. 295-300
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    髄液のオリゴクローナルバンド (OCB) を検出するため, アガロース電気泳動とイムノブロッティングを組み合わせた, 簡便で感度のよい方法を工夫した. 本法では髄液を濃縮する必要がない. 髄液のような低濃度の蛋白の分離に効果的であり, 特異性に優れている. 私達は髄液のIgGが低濃度の例や, 髄液のIgGが高濃度でポリクローナルのIgGのスメアにマスクされるような例でも, 髄液のOCBを明瞭に検出できた. 私達の方法は髄液のOCBの同定に有用である.
  • 日本人家系と最近の研究成果
    千葉 仁志, 和田 典男
    2000 年 44 巻 4 号 p. 301-302
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    A Japanese family with familial dysalbuminemic hyperthyroxinemia (FDH) was presented and recent research progress concerning FDH was reviewed. Two mutations in the albumin gene have been reported as a cause of FDH; Arg 218 His in Caucasian and Chinese cases, and Arg 218 Pro in a Japanese family. In the latter, higher thyroxine levels are observed than those for the former, possibly due to a conformational change favorable to the binding with thyroxine. A recent study suggested that FDH might result in altered warfarin metabolism.
  • 鈴木 光行, 浅原 勝, 岡崎 登志夫, 中川 孝幸, 近藤 明, 菅野 剛史
    2000 年 44 巻 4 号 p. 303-307
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    We examinied the differentiation of lipoprotein in human serum using polyacrylamide gradient gel (PAGG) electrophoresis to analyze the lipid components and to quantify the small, dense LDL. Electrophoretic patterns were classified into three types, which included two types reported by Krauss et al. and one new type containing equal same amounts of regular and small size LDL. We devised a direct staining method to stain triglyceride (TG) and cholesterol (Cho) in lipoprotein separated by the polyacrylamide gel electrophoresis and components of lipoprotein was quantitaivety analyzed with the densitogram. At the same time, the presence of apoproteins LP (a) and B in the lipoprotein was confirmed. As a result of the staining, we observed more amounts of Cho containing in the fraction of regular size LDL than small dense LDL, and more amounts of TG containing in the fraction of small dense LDL than regular size LDL. Apo B was detected in both fractions of regular size LDL and small dense LDL, but no LP (a) was detected.
  • 橋本 寿美子, 福田 嘉明, 岩田 進, 橋本 正勝, 林 国樹, 矢内 充, 熊坂 一成, 河野 均也, 山崎 哲男
    2000 年 44 巻 4 号 p. 309-312
    発行日: 2000/12/15
    公開日: 2009/03/31
    ジャーナル フリー
    A case of multiple myeloma with various kinds of paraproteins is described in this report. IgG 3-λ type monoclonal protein, γ3-heavy chain and Bence Jones protein-λ were detected in the serum of a 60-year-old male patient. Also, γ3-heavy chain and Bence Jones protein-λ were detected in the urine. The final diagnosis of this case seems to be multiple myeloma with whole molecule and its fragments of monoclonal immunoglobulin G. More interestingly, these paraproteins partly had a characteristics to react with the agar gel, not reaction with the agarose gel.
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