Mechanisms by which fibrinogen synthesis is regulated will be investigated. The effects of purified species of fibrinogen-fibrin degradation products and their asialo-derivatives upon production of fibrinogen, in vivo and in vitro, will be studied. The carbohydrate content and the primary structure of the carbohydrate associated with fibrinogen will be identified. Thrombopoietin, obtained from the plasma of thrombocytopenic rabbits, will be further purified using ammonium sulfate precipitation and DEAE cellulose as the initial chromatographic steps. Attempts will be made to utilize in vitro cultures of hematopoietic cells for the direct study of the effects of thrombopoietin on megakaryocyte numbers, size, and DNA content. The frequency and mechanism of potentiation of the hypoprothrombinemic effect of warfarin by cimetidine will be determined. Studies to establish the optimal dose of thrombolytic agents for maximum clot lysis will be conducted. The presence of bacterial endotoxin in the cerebrospinal fluids of patients with various forms of meningitis will be sought and correlated with other clinical and laboratory measurements.