Different effects of the immunostimulatory drug Stimforte on infections of hepatitis C virus and herpes simplex virus type 1.

Stimforte, an immune response-stimulating preparation, is active with respect to hepatitis C virus (HCV) and herpes simplex virus type I (HSV-1). The effects of Stimforte in animals infected with either HCV or HSV-1 are fundamentally different. In mice with acute herpes virus infection, Stimforte administration leads to a higher activity of natural killer cells and cytotoxic lymphocytes, and the amount of interferon (IFN) λ grows. In mice infected with HCV, Stimforte administration results in a significant increase in IFN-ß but not IFN-λ in blood and affected organs. Stimforte has been found to affect directly HCV reproduction that causes the infected cell death, but it does not affect HSV-1 reproduction in the Vero cells (V).

[The mechanism of stimforte action on herpesvirus infection.]

Increased protease activity and a significant amount of granzyme B were observed in in organs of mice infected with acute herpes simplex virus HSV-1 with the introduction of Stimforte (100 or 250 µg/mouse). Thus, this drug activates killer cells, which play an extremely important role in the suppression of HSV-1 infection. Although the administration of Stimforte (100 µg/mouse) to intact mice results in the activation of IFN-ß production and does not activate the production of IFN-λ, Stimforte administration to animals infected with HSV-1 reduces production of IFN-ß in serum, brain and lungs, whereas the production of IFN-λ considerably increases as the result of administration of 100 µg/mouse of Stimforte.

Identification and characterization of serum protein in patients with ovarian cancer.

A 36 kDa protein was isolated from the sera of patients with ovarian cancer and rabbit antisera to this protein were prepared. Precipitation test with these antisera detected an antigen with electrophoretic mobility corresponding to alpha-1-globulins and molecular weight of 36 kDa. Direct comparison of precipitating test systems showed that this antigen is not identical to the known carcinoembryonic, placental, and reactive proteins. Serum alpha-1-globulin was not detected in the sera of healthy humans, pregnant women, newborns, and in human adult and fetal visceral tissues at the level of precipitating test system sensitivity 1 mg/liter. It was detected in the sera of patients with ovarian cancer, in ovarian tumor (cancer) tissues, in the contents of ovarian tumor cavities, and in concentrated specimens of amniotic fluid. The antigen was not detected in ascitic fluid of patients with ovarian cancer, but it was present in 75% serum samples from these patients. The antigen was called serum oncoovarian alpha-1-globulin. SDS-PAAG electrophoresis showed that this antigen is an oligomer consisting of subunits (monomers) with molecular weight of 36 kDa. Under denaturing conditions in the presence of 2-mercaptoethanol these monomers dissociate into polypeptide chains with a molecular weight of 18 kDa. The protein is liable to oligomerization. Comparative characteristics of serum oncoovarian alpha-1-globulin and CA-125 antigen are presented.

TNF alpha-induced aerobic synthesis of ATP on plasma membranes of target cells. The relation to the expression of the nuclear oncogene c-myc.

The accumulation of ATP by preparations of plasma membranes enriched particles (PMEP) isolated from rat hepatocytes, murine splenocytes and human T-lymphocytes has been investigated after the binding of human and murine tumour necrosis factors (TNF alpha) to their specific receptors. The TNF alpha-induced expression of the nuclear oncogene c-myc in intact hepatocytes has been also studied. TNF alpha induced the marked biosynthesis of ATP on PMEP of hepatocytes and splenocytes within the first minute of incubation. The biosynthesis of ATP was independent of the activity of adenylate kinase and only occurred in the presence of all the components of aerobic phosphorylation and the electron acceptor, cytochrome C or diferric transferrin. The level of ATP on PM correlated with the degree of expression of the nuclear oncogene c-myc in the same target cells. Adriamycin totally suppressed the biosynthesis of ATP on PM and simultaneously inhibited the expression of c-myc. The ATP synthesized on PM is suggested to be involved in transduction of the proliferative or growth signal to the cell nucleus.