Increase in the degree of phosphorylation of circulating fibrinogen under thrombolytic therapy with urokinase

Human fibrinogen is phosphorylated in vivo to an equal extent at two positions, one at Ser 3 located on fibrinopeptide A, the other at Ser 345 of the A alpha-chain. As has been shown previously, the degree of phosphorylation of the circulating fibrinogen pool can be determined in vitro from the ratio between the HPLC peaks formed by phosphorylated and non-phosphorylated fibrinopeptide A which has been cleaved from plasma fibrinogen by thrombin or reptilase. Plasma samples were obtained from patients with venous thrombosis undergoing fibrinolytic therapy with urokinase (n = 8). The degree of phosphorylation increased from about 35% before treatment to values between 50% and 70% within 48 hours. It remained at these high levels as long as urokinase was administered and declined slowly thereafter. This behaviour of the degree of phosphorylation of fibrinogen is explained by a model which assumes that fibrinogen is secreted in the phosphorylated form and then dephosphorylated in the circulation by an up to now unidentified phosphatase by first order kinetics. When this system is in steady state, the degree of phosphorylation is about 25% under normal conditions. If the elimination rate of fibrinogen is greatly enhanced by fibrinogenolysis the system will approach a new steady state with a higher degree of phosphorylation, the magnitude of which will depend on the new ratio of dephosphorylation and elimination.     

Interferonogenic and antiviral effect of extracts from Erodium cicutarium

Extracts from Erodium cicutarium L. Herit were tested for antiviral and interferon inducing properties. Both water extract and methanol extract as well as its fractions were observed to exert antiviral effect in relation to myxoviruses, Herpes virus type 1, Vesicular stomatitis and vaccinia virus. None of these extracts did induce interferon in a suspension of human leukocytes.     

The results of topical application of 13-cis-retinoic acid on basal cell carcinoma. A correlation of the clinical effect with histopathological examination and serum retinol level

A group of 50 patients with basal cell carcinoma of the face was treated by 13-cis-retinoic acid. The treatment resulted in diminution of the tumors. Complete regression was observed in 4 cases. Histological examination revealed necrosis of cancer cells and mononuclear infiltration into the treated tumors. In the group with weak clinical and histological reaction to the treatment all basal cell carcinomas were of adenoid type. A better effect was observed in the group with lower serum retinol level. This treatment method seems to be supplementary to surgery in prevention of the tumor recurrence.     

IFN-alpha-induced murine B16 melanoma cancer vaccine cells: induction and accumulation of cell-associated IL-15.

Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and natural killer (NK) cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Long-term IFN-alpha treatment of B16alpha vaccine cells induced both interleukin-15 (IL-15) mRNA and IL-15 protein. The bulk of the induced IL-15 remained cell associated, either cytoplasmic or associated with the cell membrane. Immunofluorescence microscopy studies showed that the cell-associated IL-15 was broadly distributed throughout the cytoplasm. These observations suggest that long-term IFN-alpha treatment may induce primarily the truncated isoform of IL-15. Vaccination with irradiated B16alpha vaccine cells may promote tumor immunity by releasing high levels of cell-associated IL-15 when spontaneously lysed or directly killed by innate immune cells. The release of accumulated cell-associated IL-15 may then trigger a host T cell response to tumor antigens and cause host development of immunity to the B16 tumor cells.