THE CONVERSION OF FIBRINOGEN TO FIBRIN: EVENTS AND RECOLLECTIONS FROM 1942 TO 1982 *
THE CONVERSION OF FIBRINOGEN TO FIBRIN: EVENTS AND RECOLLECTIONS FROM 1942 TO 1982 *
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纤维蛋白原向纤维蛋白的转化：1942 年至 1982 年的事件和回忆*
DOI：
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发表时间：
1983
影响因子：
5.2
通讯作者：
J. Ferry
中科院分区：
文献类型：
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作者：
J. Ferry
该叙述始于1942年，因为那是纤维蛋白原首次从大规模血浆分离中大量获得的时候。如果说这一发现彻底改变了凝血研究的进程，那就太过分了，因为大多数最好的研究工作都是由那些在自己控制的条件下直接从全血中分离和纯化纤维蛋白原的人完成的。然而，从商业或机构来源获得人或牛组分I的容易性肯定刺激了研究。许多研究者直接使用来自这些来源的级分I或将其用作进一步纯化的起始材料，如通过检查从那时起的文献可以看到的。也是在1942年，我从另一个战时任务中被召回哈佛医学院，以研究人类第一部分的实际应用。这种物质作为Edwin J. Cohn及其同事开发的血浆分离程序的副产物而积累。这个战时企业的故事是众所周知的。来自红十字会的血浆通过在低温下使用乙醇分级分离，具有精确的pH值、离子强度和其他条件。这些方法首先在哈佛的试验工厂中制定出来，经过逐步的修改和改进，最终被七家工业公司采用，以商业规模生产蛋白质组分，供军队使用。主要产品为治疗休克的血浆白蛋白。将其包装为无菌且稳定的25%溶液，可立即注射，而不会延迟干血浆的复溶。副产物包括馏分I，其中含有大部分纤维蛋白原;免疫球蛋白;和其他物质，包括凝血酶，少量。参与血液凝固的成分的研究，包括通过组分I的亚分级获得的更高纯度的纤维蛋白原、抗血友病因子、冷不溶性球蛋白和凝血酶，由John T.埃德塞尔Peter R.莫里森和我被提供了大量的组分I，其中约60%的蛋白质是Cloprotein，用于探索这种材料的实际应用的实验。第一个建议是在烧伤表面治疗中使用纤维蛋白凝块。我们发现凝块对表面的粘附性及其易碎性、韧性和脱水收缩可以通过其形成的条件如pH、离子强度和添加剂如甘油的存在来调节。虽然预期的临床应用没有发展得很远，但我们详细探索了这些变量对凝块物理性质的影响，主要使用折射材料，
This account begins in 1942 because that is when fibrinogen first became available in ample quantities from large-scale plasma fractionation. It would be too much to say that this revolutionized the course of research on blood coagulation, since much of the best work has always been done by people who isolated and purified their own fibrinogen directly from whole blood, collected under their own controlled conditions. However, research was certainly stimulated by the ease of obtaining either human or bovine Fraction I from commercial or institutional sources. Many investigators used Fraction I from these sources either directly or as starting material for further purification, as one can see by examining the literature from that time forward. It was also in 1942 that I was called back part time from another war assignment to the Harvard Medical School to examine possible practical applications of human Fraction I. This material was accumulating as a by-product of the plasma fractionation procedure developed by Edwin J. Cohn and his associates. The story of that wartime enterprise is well known. Plasma from the Red Cross was fractionated by use of ethanol at low temperatures, with precise specification of pH, ionic strength, and other conditions. The methods were worked out first at the Harvard Pilot Plant, with progressive modification and improvement, and were eventually employed at seven industrial firms to produce protein fractions on a commercial scale for use by the armed forces. The primary product was plasma albumin for treatment of shock. It was packaged as a sterile and stable 25% solution that could be injected immediately without the delay involved in reconstitution of dried plasma. Byproducts included Fraction I, which contained most of the fibrinogen; immunoglobulins; and others, including thrombin, in smaller amounts. Investigations of the components involved in blood clotting, including more highly purified fibrinogen obtained by subfractionation of Fraction I, antihemophilic factor, cold-insoluble globulin, and thrombin, were coordinated by John T. Edsall. Peter R. Morrison and I were supplied with Fraction I, of which about 60% of the protein was clottable, in ample amounts for experiments to explore practical applications of this material. The fist proposal was to use fibrin clots in the surface therapy of burns. We found that the adherence of a clot to a surface and its friability, toughness, and syneresis could be regulated by the conditions of its formation such as pH, ionic strength, and the presence of additives such as glycerol. Although the intended clinical use did not develop very far, we explored the effects of these variables on the physical properties of clots in detail, using mostly refractionated material with a higher