Molecular biological, histopathological, and clinnical study on plasma renin in pediatric kidney lesions.

小儿肾脏病变血浆肾素的分子生物学、组织病理学和临床研究。

• 批准号: 05454481
• 负责人: YOKOMORI Kinji
• 金额: $ 4.22万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454481/
• 关键词: plasma renin; pediatric kidney lesion; Wilms tumor; monoclonal antibody; histochemical staining; 異形成腎; 抗レニン抗体; 血漿中レニン測定

In this study, we raised 4 kinds of monoclonal antibodies against human renin, which recognized 4 different epitopes, respectively. However, all 4 andtibodies recognized both the active and inactive forms of renin, i.e., total renin, and none of them were specific to the active form only, or to the inactive form only. Hence, we established an immuno-radiometric assay (IRMA) system, which can determine the plasma levels of total renin (active+inactive form) using two monoclonal antibodies (clone numbers 12-12 and 69-30), Of the 4 antibodies raised, the only one (69-30) was shown to react with the renin within the formalin-fixed, paraffin-enbedded pathology specimens.Using this particular antibody, we performed immunohistochemical studies on various renal lesions, such as Wilms tumors, congenital mesoblastic nephromas (CMN), clear cell sarcomas of kidney (CCSK), and multicystic dysplastic kidneys (MCDK), which revealed the primiary reninism in Wilms tumor and MCDK,and secondary reninism in CMN and CCSK,respectively.Plasma renin levels (PRL) were determined by the IRMA system in normal children, and it was shown that PRL was high in early infancy, and was gradually decreasing with age. It alsw demonstrated that PRLs in Wilms tumor patients well reflected the extent and the volume of the tumor, indicating that PRL can be utilized as a tumor marker.

本研究制备了4种抗人肾素单克隆抗体，分别识别4种不同的表位。然而，所有4种抗体都能识别肾素的活性形式和失活形式，即总肾素，没有一种抗体只针对活性形式，也没有一种抗体只针对失活形式。因此，我们建立了一种免疫辐射测定（IRMA）系统，该系统可以使用两种单克隆抗体（克隆号12-12和69-30）来测定血浆中总肾素（活性+非活性形式）的水平，在4种抗体中，只有一种抗体（69-30）在福尔马林固定的石蜡包埋病理标本中显示与肾素反应。利用该抗体，我们对肾母细胞瘤、先天性间质肾瘤（CMN）、肾透明细胞肉瘤（CCSK）和多囊发育不良肾（MCDK）等多种肾脏病变进行了免疫组化研究，发现肾母细胞瘤和MCDK分别为原发性肾性肾病，CMN和CCSK为继发性肾性肾病。用IRMA系统测定正常儿童血浆肾素水平（PRL），结果显示PRL在婴儿期早期较高，随着年龄的增长逐渐降低。研究还表明，Wilms肿瘤患者的PRL能很好地反映肿瘤的范围和体积，表明PRL可以作为肿瘤标志物。

项目成果

Inoue A, Yokomori K et al.: "Extensive genetic heterogeneity in the newroblastoma cell line NB (TU) 1." Int J Cancer. 72. 1070-1077 (1997)

Inoue A、Yokomori K 等人：“新生细胞瘤细胞系 NB (TU) 1 中存在广泛的遗传异质性。”

Komuro H,Li P,Tsuchida Y,Yokomori K,et al: "Effects of CPT-11(a unique DNA topoisomerase I inhibitor)on a highly malignant xeno-transplanted neuroblastoma." Med Pediatr Oncol. 23. 487-492 (1994)

Komuro H、Li P、Tsuchida Y、Yokomori K 等人：“CPT-11（一种独特的 DNA 拓扑异构酶 I 抑制剂）对高度恶性的异种移植神经母细胞瘤的影响”。

LiP, Yokomori K, Tsuchida Y,et al.: "Flow cytometric nuclear DNA content analysis of renal tumors in children : Prognostic significance of nuclear DNA proidy." Tumor Biology. 16. 385-393 (1995)

LiP、Yokomori K、Tsuchida Y 等人：“儿童肾肿瘤的流式细胞术核 DNA 含量分析：核 DNA 蛋白的预后意义。”

Inoue A,Yokomori K,Tanabe H,et al: "Extensive genetic heterogeneity in the neuroblastoma Cell line NB(TU)1." Int J Cancer. 72. 1070-1077 (1997)

Inoue A、Yokomori K、Tanabe H 等人：“神经母细胞瘤细胞系 NB(TU)1 中存在广泛的遗传异质性。”

Katoh H, Suzuki T, Yokomori K et al: "A novel immeinoassay of smooth meesde myosin heavy choin in senum." J Immund Methods. 185. 57-63 (1995)

Katoh H、Suzuki T、Yokomori K 等人：“一种新颖的血清中平滑米德肌球蛋白重蛋白的免疫测定法。”