Arbus G S
Department of Pediatrics, University of Toronto, Hospital for Sick Children, Ontario, Canada.
Kidney Int Suppl. 1997 Mar;58:S91-6.
It has been over 10 years since we first showed an association [1] between classical hemolytic uremic syndrome (hemolytic anemia, thrombocytopenia, and uremia, following a diarrheal prodome) and certain E. coli [1] capable of producing a toxin, initially called verotoxin (VT) because of its cytopathic effect on Vero cells [2] and later Shiga-like toxin (SLT) because of the toxin's close biological and structural similarity to Shiga toxin. Although we initially reported that 75% of children with idiopathic hemolytic uremic syndrome (HUS) [1] had evidence of a verotoxin-producing E. coli (VTEC) [1], a later study showed that over a seven year period (1980-86), of 86 children seen with HUS, 91% had a classical presentation and 88% of these had evidence of a VTEC infection [3]. This paper traces the path of the incriminating organisms (VTEC) from the time of ingestion, up to and including internalization of the toxin into a target cell; in vitro experiments demonstrating the effect of toxin on endothelial cells are included. It is hoped that we might gain a clearer insight into factors that might predispose an individual to contracting HUS. Once a better understanding of the pathogenesis of VTEC associated HUS is known, areas for therapeutic intervention might be realized.
自我们首次发现经典溶血尿毒综合征(腹泻前驱症状后出现溶血性贫血、血小板减少和尿毒症)与某些能够产生毒素的大肠杆菌之间存在关联[1]以来,已经过去了10多年。这种毒素最初因其对Vero细胞的细胞病变效应而被称为维罗毒素(VT)[2],后来由于其与志贺毒素在生物学和结构上的密切相似性而被称为志贺样毒素(SLT)。尽管我们最初报告称,75%的特发性溶血尿毒综合征(HUS)患儿[1]有产维罗毒素大肠杆菌(VTEC)感染的证据[1],但后来的一项研究表明,在1980年至1986年的七年期间,86例患溶血尿毒综合征的患儿中,91%有典型症状,其中88%有产维罗毒素大肠杆菌感染的证据[3]。本文追溯了致病微生物(产维罗毒素大肠杆菌)从摄入时起,直至毒素内化进入靶细胞的整个过程,包括毒素对内皮细胞作用的体外实验。希望我们能更清楚地了解可能使个体易患溶血尿毒综合征的因素。一旦对产维罗毒素大肠杆菌相关溶血尿毒综合征的发病机制有了更好的理解,就可能找到治疗干预的方向。