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用单克隆抗体在体内抑制人体血小板功能。以新死亡者为实验对象进行观察。

Inhibition of human platelet function in vivo with a monoclonal antibody. With observations on the newly dead as experimental subjects.

作者信息

Coller B S, Scudder L E, Berger H J, Iuliucci J D

机构信息

State University of New York, Stony Brook.

出版信息

Ann Intern Med. 1988 Oct 15;109(8):635-8. doi: 10.7326/0003-4819-109-8-635.

Abstract

The F(ab')2 fragment of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor (7E3) is a potent inhibitor of both in-vitro platelet aggregation and in-vivo platelet thrombus formation in animal studies. As a first step in assessing the potential of 7E3-F(ab')2 as an antithrombotic agent for use in humans, we administered 7E3-F(ab')2 intravenously at increasing doses to a person who had just died and was being maintained on a respirator (neomort). At 0.1 and at 0.2 mg/kg body weight, 74% and 92% of the glycoprotein IIb/IIIa receptors were blocked, respectively; adenosine-diphosphate-induced platelet aggregation was inhibited by 84% and 100% at these same doses. Platelet glycoprotein Ib function remained intact, even at 0.6 mg/kg. Acute hemodynamic or hemorrhagic toxicity was not noted. This antibody fragment, a potent, immediate-acting inhibitor of platelet aggregation, may be of benefit in vaso-occlusive and thromboembolic disorders.

摘要

抗血小板糖蛋白IIb/IIIa受体单克隆抗体(7E3)的F(ab')2片段在动物研究中是体外血小板聚集和体内血小板血栓形成的有效抑制剂。作为评估7E3-F(ab')2作为用于人类的抗血栓药物潜力的第一步,我们对一名刚死亡且靠呼吸机维持(濒死)的人静脉注射递增剂量的7E3-F(ab')2。在体重0.1和0.2 mg/kg时,糖蛋白IIb/IIIa受体分别有74%和92%被阻断;在相同剂量下,二磷酸腺苷诱导的血小板聚集分别被抑制84%和100%。即使在0.6 mg/kg时,血小板糖蛋白Ib功能仍保持完整。未观察到急性血流动力学或出血毒性。这种抗体片段是血小板聚集的强效速效抑制剂,可能对血管闭塞和血栓栓塞性疾病有益。

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