Robert G. Green

Characterization of milk influence in spontaneous mammary carcinoma.

Previous studies 1 , 2 , 3 , 4 , 5 , 6 indicate the presence, in at least certain tissues of high cancer strain mice, of a substance or substances whose presence is essential to spontaneous mammary carcinoma. In these studies lactating mammary tissues inclusive of their contained milk have been brought into suspension and partial solution by micro-homogenization and the resulting fluid separated into several fractions by the use of an ultracentrifuge. Procedure. Fostered female C3H mice 1 month old were employed as test animals. Lactating breast tissues were obtained immediately after death by etherization, from high cancer C3H and A strain mice. The material was immediately homogenized with addition of between one and two times its volume of sterile distilled water. The resulting fluid was spun in the centrifuge at 15,000 rpm, giving a maximum accelerational force of 15,000 x g, for 30 minutes. Three layers resulted, a fatty top layer, designated as the fat fraction, a middle aqueous layer, the first supernatant fluid, and a bulky precipitate, the first sediment. The fat fraction was removed and employed as noted below. The aqueous layer was removed by suction without disturbing the sediment. The first supernatant fluid was then spun at 40,000 rpm, corresponding to 110,000 x g, for a period of 60 minutes. The final supernatant fluid was removed without disturbing the second sediment. The materials used for feeding or injection were (1) homogenized tissue, (2) fat fraction, (3) first sediment, (4) second sediment, and (5) final supernatant fluid. The amount of material of each fraction which was injected or fed was usually that which was obtained in that fraction from 1 g of original tissue.

A DEFICIENCY DISEASE OF FOXES

A common and highly destructive dietary disease of silver foxes in captivity is pathologically the counter-part of Wernickes hemorrhagic polioencephalitis of man. The disease in foxes is caused by feeding fish as 10 per cent., or more, of the diet. It is probable that the fish induce a B1 avitaminosis which causes the characteristic pathology and the resultant symptoms.

Antigenic Character of the Cancer Milk Agent in Mice.

Conclusions The milk factor of mammary mouse carcinoma is highly antigenic and stimulates the formation of antibodies in both rabbits and rats. The mouse cancer antiserum neutralizes and renders inactive mouse cancer centrifugates. Equally effective antiserums are prepared from spontaneous and from transplant tumors. Normal rabbit and rat serums have a slight effect in inactivating the mouse cancer virus. The finding that antiserum against normal mouse tissue does not have any neutralizing or adverse effect on the milk agent indicates that the agent is a virus of exogenous origin.

Cytotoxic Property of Mouse Cancer Antiserum.

Conclusions An immune serum prepared in rabbits against the mouse mammary carcinoma milk factor, or Bittner virus, when mixed with cancer cells for a period of 6 hours completely inhibits their growth so that transplant tumors do not develop. Control tumors developed after similar treatment of tumor cells with serum from normal rabbits and with serum from rabbits immunized with normal lactating mouse breast tissue.

A precipitin test for antigens present in mouse tissues containing the milk agent.

Summary The data presented in this report describe a precipitin test for mouse tissues containing the milk agent. Antiserum produced in rabbits against mouse mammary cancer reacts in high titre with tissues containing the cancer agent and in low titre with tissues lacking the agent. Antiserum prepared against normal mammary gland tissues abundant with milk agent will precipitate mammary cancer antigen in high serum dilutions. Antiserum prepared against normal mammary gland tissues lacking the agent will precipitate mammary cancer antigen in low serum dilutions. Precipitin-adsorption reactions show that the removal of antibodies against mammary gland tissues without the agent in mouse mammary cancer antiserum will not remove antibodies which react with the common antigen or antigens found in mouse mammary cancer and mouse mammary gland tissues containing the milk agent.

Distemperoid Virus Interference in Canine Distemper

A distemper virus modified by ferret passage so as to become a harmless vaccine for foxes and dogs exhibits the interference or cell-blockade phenomenon with respect to a virulent distemper infection in foxes. Ten control foxes receiving virulent distemper virus died, while 30 foxes receiving distemperoid virus in addition lived.

Serial Transmission of the Milk Agent of Mouse Mammary Carcinoma

Summary In serial passage of the milk agent, or virus, through highly susceptible ZBC hybrid mice by the intraperitoneal injection of mammary gland filtrates, the number of tumors declined in the first and second passages, and no tumors developed in the third and fourth passages.

SUSCEPTIBILITY OF THE YOUNG WHITE MOUSE (MUS MUSCULUS) TO EXPERIMENTAL LEPTOSPIROSIS.

The failure of even special methods to induce infection indicates that not all strains of young white laboratory mice (Mus musculus) are uniformly susceptible to fatal infection with Leptospira icterohemorrhagiae. Some strains of this species develop early pathological changes characteristic of the infection and harbor the organism in their kidneys, but do not succumb. Therefore not all strains of white mice are suitable for use in the diagnostic mouse protection test for leptospirosis described by Larson.

Susceptibility of the gray fox to fox encephalitis.

Summary The results indicate that the gray fox is relatively resistant to fox encephalitis virus virulent for red foxes. It appears that the virus will regularly infect the gray fox to produce a symptomless infection, but only occasionally will symptoms appear that resemble the disease in red foxes. A virulence gradient of this virus for related species can be postulated whereby in the family Canidae the closely related dogs and coyotes (Cants) and red foxes (Vulpes) are most susceptible, the more distantly related gray fox (Urocyon) less susceptible, and those species which are earlier offshoots of the canines, such as the black bear and the raccoon, are the least susceptible to fox encephalitis.

Susceptibility of the bear to fox encephalitis.

Conclusions The intra-oeular inoculation of two bears and the intramuscular injection of a third with fox encephalitis virus indicate that the black bear (Euarctos americanus) is only slightly susceptible to this virus infection. Since the bear, like the raccoon, is an offshoot of the canines, the pathogenic properties of fox encephalitis virus derived from foxes seem sharply confined to the canine family.