Antiviral effects on bacteriophages and rotavirus by cranberry juice.

Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.

Purification of a syngeneic cross-reactive autotumorolytic factor.

An autotumorolytic fraction (ATF) derived from sera of mice bearing spontaneous mammary adenocarcinoma has been purified by sequential chromatography on Sephacryl 200 SF, DEAE Sephacel, hydroxylapatite, and Sephacryl 200 SF. At each stage of the purification, tumorolytic activity was assessed by the ability of the active material to induce lysis of a 2-week-old mammary tumor, and verified by histopathological analysis. Active fractions obtained during the stages of purification were capable of inducing lysis of tumors in both the original donor mice and the syngeneic tumor-bearing mice. Lytic activity was specific only for tumor tissue. This syngeneic crossreactivity of partially purified materials permitted pooling of serum samples for purification purposes. The resultant final preparation of ATF is an homogenous protein fraction, as verified by gradient SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance liquid chromatography. The molecular weight of active ATF is approximately 50,000 Da, as determined by gradient SDS-PAGE.

Studies on the anemia of the Shay chloroleukemia.

The pathogenesis of the anemia which occurs in rats bearing the Shay chloroleukemia (SCL) was investigated. Severe anemia, shown not to result from hemodilution, developed in the terminal stage of the disease. The rapid progression of the anemia suggested that reduced erythropoiesis was of no more than minor importance in the development of this anomaly. No evidence for a major hemolytic event was observed. Data are presented which suggest that hemostatic defects may be primarily responsible for the anemia of SCL. Because of many similarities with the pathogenesis of human myelogenous leukemia, SCL is proposed as a useful model for further studies on interreactions between the leukemic environment and the erythrocyte population.

Prostaglandins activation of erythropoietin production and erythroid progenitor cells.

A model is presented postulating a role for prostaglandins E and prostacyclin in kidney generation of erythropoietin and the activation of the erythroid progenitor cell (CFU-E) compartment by erythropoietin (Ep). Several criteria have been met to prove that prostanoids mediate erythropoiesis: 1) several E-type prostaglandins (PGE2, 15-methyl prostaglandin E2, 16,16-dimethyl E2, 6-keto-E1 and PGE1) produced a significant increase in radioiron incorporation in red cells of exhypoxic polycythemic mice; 2) prostaglandin E2 increased kidney production of erythropoietin in the isolated perfused dog kidney; 3) arachidonic acid, a precursor for all bisenoic prostaglandins, increased kidney production of erythropoietin in the isolated perfused dog kidney which was blocked by pretreatment with the cyclo-oxygenase inhibitor drug indomethacin; 4) hypoxemic perfusion of the isolated perfused dog kidney increased kidney production of erythropoietin and produced an elevation in prostacyclin in the perfusates; 5) albuterol, a beta-2 adrenergic agonist, produced a significant increase in perfusate levels of erythropoietin and PGE in the isolated perfused dog kidney; 6) renal ischemia increased Ep and PGE levels in renal venous plasma which was blocked by pretreatment with indomethacin; 7) prostaglandin E2 and arachidonic acid produced a significant increase in erythroid colonies (CFU-E) in vitro in normal mouse bone marrow; 8) E-type prostaglandins (15-methyl E2) increased in vivo erythroid colony (CFU-E) formation in bone marrows of post-hypoxic polycythemic mice; and 9) injections of 15-methyl E2 daily for six weeks in normal and hypoxic mice produced a significant elevation in the total circulating red cell mass. These studies indicate that hypoxic stimulation of kidney production of erythropoietin may be related to the generation of prostacyclin (PGI2). On the other hand, albuterol and ischemic (reduction in renal blood flow) stimulation of kidney production of erythropoietin involves prostaglandins of the E type. In addition, E-type prostaglandins were found to enhance the effects of erythropoietin in activating erythroid progenitor cells (CFU-E) in the bone marrow. We postulate from our model that prostaglandins E and prostacyclins are involved in the mechanism of kidney production of erythropoietin as well as the activation of the Ep-responsive cell (ERC) compartment.

Hepatic regeneration and erythropoietin production in the rat.

The regenerating liver produces erythropoietin in response to hypoxia. The amounts of erythropoietin produced in animals subjected to hepatectomy are significantly higher than those observed in sham-operated animals. Hepatic erythropoietin production appears to be dependent upon the stage of regeneration with the highest levels being produced during the period of greatest proliferation and increase in liver mass.