NUCLEAR INCLUSIONS IN THE TESTICLES OF MONKEYS INJECTED WITH THE TISSUE OF HUMAN VARICELLA LESIONS

Eosin-staining nuclear inclusions resembling those deemed characteristic of a certain well known group of filterable viruses, amongst which is varicella, were found in vervets' testicles inoculated with emulsified tissue of human varicella lesions

VARICELLA IN MONKEYS : NUCLEAR INCLUSIONS PRODUCED BY VARICELLA VIRUS IN THE TESTICLES OF MONKEYS.

The eosin-staining nuclear inclusions found in the monkeys' testicles inoculated with emulsified tissue of human chicken-pox lesions are specifically associated with the virus of varicella

SKIN INFECTION OF RABBITS WITH HEMOLYTIC STREPTOCOCCI ISOLATED FROM A PATIENT WITH ERYSIPELAS : I. METHOD OF DEMONSTRATING PROTECTIVE ACTION OF IMMUNE SERA.

Cultures of a hemolytic streptococcus isolated from a human case of erysipelas were tested for ability to produce lesions by injecting various amounts intradermally in shaved rabbits. Severe lesions could be developed at will in this way despite the fact that intravenous or intraperitoneal inoculations of large doses of the cultures failed to kill. The lesions were of two sorts, phlegmonous and erysipelas-like. A serum capable of warding off the injurious action of the streptococcus on the skin was procured from animals receiving repeated intracutaneous inoculations of the organism. Normal serum by contrast had no protective effect. By intradermal injections at several points in the same normal rabbit of small quantities of mixtures of equal parts of serum and various dilutions of a suspension of streptococci it proved possible to test sera for the presence of substances protective against the streptococcus

EFFECT OF A FILTERABLE VIRUS (VIRUS III) ON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE NEOPLASM OF THE RABBIT

A study of a malignant disease in rabbits has been made with reference to the presence or absence of a filterable virus, Virus III, in the tumor. The results are analyzed from the standpoint of certain characteristic features of the tumor process in order to determine any differences in degrees of malignancy. It was found that a more severe disease developed in the series in which the virus-bearing tumor was used than in the series in which the tumor was free of the virus, although the differences were not very marked and were not entirely constant. The influence of Virus III as a factor affecting malignancy has been discussed from the standpoint of its possible effect upon (α) the tumor cells and (b) the host reaction. It has been suggested that the greater malignancy of the pathological process usually induced by the virus-bearing tumor is attributable to a change in the response of the host to the tumor, which change is of the nature of a decreased resistance associated with the reaction of the host to the virus infection

EFFECT OF HOST IMMUNITY TO A FILTERABLE VIRUS (VIRUS III) ON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE RABBIT NEOPLASM

Experiments are reported in which were studied the course and character of a transplantable malignant neoplasm in normal rabbits and in rabbits immunized with a filterable virus, Virus III. The disease which developed in immunized rabbits was extremely mild and much less severe than in normal animals. The effect upon the tumor process displayed by Virus III immune rabbits in the direction of diminished malignancy is considered to be entirely non-specific in character, and the suggestion is made that it is accomplished through a more effective resistance of the host

GROWTH AND PERSISTENCE OF FILTERABLE VIRUSES IN A TRANSPLANTABLE RABBIT NEOPLASM

Virus III and vaccine virus multiply in a transplantable rabbit tumor of epithelial origin; are carried along with the tumor through an indefinite number of transplants; and despite an immunity developed by the rabbit host survive longer in the tumor than when injected into the testicles of normal rabbits

INFECTIOUS MYXOMATOSIS OF RABBITS : PREPARATION OF ELEMENTARY BODIES AND STUDIES OF SEROLOGICALLY ACTIVE MATERIALS ASSOCIATED WITH THE DISEASE

From the results of the experiments described in this paper it is obvious that large amounts of elementary bodies of myxoma can be obtained in a relatively pure state by means of the methods used. Furthermore, it is evident that infectious myxomatosis is a viral disease in which elementary bodies of the same order of magnitude as vaccinal elementary bodies play a conspicuous rô1e in that they either represent the etiological agent or are intimately associated with it. The bodies are specifically agglutinated by antimyxoma serum and are agglutinated to a less extent by serum from rabbits convalescing from fibroma, a disease closely related to myxoma. In virus-free filtrates of emulsions prepared from infected skin there is a soluble precipitinogen or precipitinogens specific for the malady. Moreover, a specific precipitinogen or precipitinogens are demonstrable in virus-free serum of animals acutely ill as a result of extensive infection with myxoma virus. It is believed that this is the second viral disease, yellow fever (14) being the first, in which a specific soluble antigen free from virus has been found in the serum of ill animals

FURTHER OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS FOR JENNERIAN PROPHYLAXIS IN MAN

A dermal strain of vaccine virus has been passed through 99 successive culture passages. This procedure led to a diminution in the pathogenicity of the active agent for the rabbit. By repeated testicular passages in rabbits, however, the virus regained its pathogenicity for that host. New cultures were initiated with the revived virus. A culture strain of virus that has been twice revived in this manner has remained fairly stable for the rabbit through 60 culture passages and it produces mild, yet effective vaccinal reactions in man. Virus in early cultures was not attenuated for man, but later cultures of the original strain and cultures of the 2nd and 3rd revived strains produced mild reactions without fever and discomfort to the patients. Intradermal vaccinations with the culture virus are safe and satisfactory. With the culture virus 118 infants and children have been inoculated and in 100 of them a positive reaction occurred. The culture virus produced a refractory state to a standard dermal strain of calf lymph and vice versa. Culture virus stored in 50 per cent neutral glycerol at –10°C. or at +3°C. maintained a considerable amount of its activity for at least 1 year. Desiccated culture virus sealed in tubes maintained some of its activity when stored at 37°C. for 5 weeks. Fresh cultures can be initiated without difficulty from desiccated virus or from virus that has been stored with or without glycerol

FURTHER OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS IN LIFELESS MEDIA

We have made ten attempts to cultivate vaccine virus in tissue extracts prepared according to the method described by Eagles and Kordi (4). Renal, testicular, and chick embryo extracts were employed with a dermal strain of vaccine virus and with the Levaditi strain of neuro-vaccine virus. In no instance were we able to show that the virus multiplied in the extract media. Both of these strains of virus, however, multiplied in media containing bits of minced viable tissue. Furthermore, treatment of rabbit testicular tissue and chick embryo tissue in the manner described by Eagles and Kordi for the preparation of the extracts leaves some cells not only alive but capable of proliferation. Although the results of our work are not in accord with those obtained by Eagles and Kordi, we offer no explanation for the discrepancy. Nevertheless, one cannot examine the results of our work recorded in the six tables without recognizing the fact that in the types of media used the presence of viable cells appears to be essential for the multiplication of vaccine virus. Rabbit testicular tissue and bits of chick embryos support the regeneration of the active agent more efficiently than does rabbit renal tissue

IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS : III. RESPONSE OF RABBITS TO INACTIVE ELEMENTARY BODIES OF VACCINIA AND TO VIRUS-FREE EXTRACTS OF VACCINE VIRUS

Humoral antibodies and a certain degree of resistance to infection with vaccinia, probably not enduring, are produced in rabbits by the repeated injections of inactive formolized (0.3 per cent) elementary bodies of vaccinia and virus-free filtrates of dermal vaccine virus. Single injections of large amounts of elementary bodies are not as effective as similar amounts administered in small repeated doses. Drastic treatment (10 per cent formaldehyde or boiling for 2 hours) almost completely alters or destroys the antigenicity of elementary bodies. It appears that the production of precipitins and agglutinins does not parallel that of neutralizing antibodies and that the mere presence of such antibodies in the serum of a rabbit as the result of injections of inactive elementary bodies does not necessarily indicate that the animal possesses a great degree of resistance to infection with a potent vaccine virus. The fact that some neutralizing antibodies appeared in the sera of rabbits that had received injections of inactive elementary bodies can be interpreted as indicating that at least not all neutralizing antibodies for vaccine virus are the result of a reaction to an antigen produced by the host in consequence of a vaccinal infection. No evidence was obtained to show that elementary bodies inactivated by our methods (0.3 per cent formaldehyde) would serve as a suitable vaccine for the protection of human beings against smallpox