FURTHER STUDIES ON THE INFLUENCE OF TESTICLE EXTRACT UPON THE EFFECT OF TOXINS, BACTERIA, AND VIRUSES, AND ON THE SHWARTZMAN AND ARTHUS PHENOMENA

The lesions produced by the Shwartzman and Arthus phenomena, as well as those produced by bacterial toxin and foreign sera in the normal rabbit, are spread by testicle extract over a larger area than would normally take place. With this spreading of the lesions there is a definite reduction in their intensity. Lesions produced by invasive strains of staphylococcus at high dilutions or non-invasive staphylococci at moderate dilutions are definitely lessened in severity or even suppressed by the spreading action of testicle extract. Virus lesions are consistently enhanced by the spreading factor regardless of the dilution

STUDIES ON A CERTAIN SPREADING FACTOR EXISTING IN BACTERIA AND ITS SIGNIFICANCE FOR BACTERIAL INVASIVENESS

Invasive strains of staphylococcus and streptococcus contain a soluble factor which markedly increases tissue permeability and enhances the infections produced by these organisms, by other bacteria, and by vaccine virus as well. The non-invasive strains of the same species of staphylococci and streptococci do not contain this factor. The enhancing substance elaborated locally by organisms passes into the circulating blood and bringing about a general increase of tissue permeability may act to enhance local infections elsewhere. The factor is similar in the phenomena it elicits to the spreading factor extracted from many animal tissues, especially from testicle

THE EXTENT OF LOCAL DISPERSION OF INFECTIOUS AGENTS AS A FACTOR IN RESISTANCE TO INFECTION

Progressively decreasing quantities of bacteria of some 20 strains were utilized in experiments upon the effect of dispersing the organisms in the rabbit skin through the agency of an extract of testicle or an invasive staphylococcus. The same was done with 6 strains of filterable viruses. The bacterial lesions were enhanced by spreading when the organisms introduced were above a certain number or quantity (minimal effective concentration) and on the other hand were partially or totally suppressed when their number was less than this. Virulence and minimal effective concentration were observed to be in inverse relationship. The lesions due to the filterable viruses studied were, on the other hand, enhanced by the spreading factor even when the quantity of virus approached the minimal infective dose. This happened irrespective of whether the virus caused severe lesions or slight ones. The highly virulent Pneumococcus Type I, injected into normal rabbits together with the spreading factor, yielded enhanced lesions even at practically its minimal infective dose; but when the resistance of the animal was raised with specific antiserum the lesions were totally suppressed by the experimental dispersion of the bacteria. When such an experiment was repeated on a filterable virus, vaccinia, no suppression took place as a result of the dispersion of the infective agent. The significance of the differences in the bacterial and virus phenomena is discussed

STUDIES ON THE INACTIVATION OF VACCINE VIRUS AND THE ACTION OF CERTAIN SUBSTANCES UPON THE INFECTING POWER OF THE INACTIVATED VIRUS

Vaccine virus, obtained from testicular inoculation shows a high susceptibility to chloroform as compared with ether, toluene, 95 per cent alcohol and acetone. Vaccine virus, after treatment with an amount of chloroform sufficient to render it incapable or only barely capable of originating an eruption in the rabbit's skin, produces a characteristic eruption when injected with the supernatant fluid of embryonic tissue or sarcoma tissue "cultures" or kieselguhr, substances all of which are markedly irritative to the rabbit's skin. Reactivation of the chloroformed vaccine virus is not possible when chloroform has been added to it in such quantity that the injection of large amounts of the treated virus fails to cause an eruption. Whenever reactivation has been accomplished it has been possible to get a vaccine eruption of greater or less intensity by the injection of large amounts of the chloroformed vaccine alone. Embryo and chicken sarcoma "culture" fluids when injected intradermally make the skin susceptible to the localization of the virus introduced intravenously. The bearing of these experiment on the interpretation of Gye' theory of cancer causation is discussed

THE EFFECT OF EXTRACTS OF CERTAIN ORGANS FROM NORMAL AND IMMUNIZED ANIMALS ON THE INFECTING POWER OF VACCINE VIRUS

Brain and testicle tissue from immune rabbits brought in contact with the Levaditi or Noguchi strains of vaccine virus will fix or inactivate the virus. Extracts of normal testicles from susceptible animals enhance to an extraordinary degree the infectivity of both the neuro- and dermal strains of vaccine virus. The Noguchi virus is not affected by testicle extracts when injected into the skin, but kidney extract has a definite enhancing power on the strain when injected into either skin or testicle. The effect of tissue extracts seems to be on the cells of the host rather than on the virus. This is indicated by the fact that virus injected intravenously localizes most readily in an area of skin previously injected with testicle extract. Furthermore an enhanced lesion results if the virus is injected into an area as long as 3 days after the area has been injected with testicle extract. The augmenting substance of the tissue extracts is little affected by high dilutions, passes through a Berkefeld V candle and is carried down with the proteins precipitated by weak acids. Rabbits with enhanced lesions show general symptoms and about 25 per cent die with generalized vaccinia. Kidney, and probably skin, brain and liver extracts possess enhancing properties, but to a much less degree than the testicle. On the other hand, spleen, blood and probably lymph nodes and bone marrow not only fail to produce enhancement, but actually restrain or even suppress entirely the vaccinal skin infection