The Journal of Experimental Medicine

Rivers, Thomas M.; Ward, S. M.

doi: 10.1084/jem.66.1.1pmid: 19870643

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. Footnotes Submitted: 4 April 1937

Sabin, Albert B.; Olitsky, Peter K.

doi: 10.1084/jem.66.1.15pmid: 19870647

1. After intracerebral injection or nasal instillation of vesicular stomatitis virus in young or old mice, there was no evidence of a generalized, systemic or blood infection. 2. Within 1 hour after nasal instillation of as much as 100,000 M.C.L.D. in young or old mice, no virus ( i.e ., less than 60 to 70 M.C.L.D. ) could be demonstrated in the nasal mucosa. 2 days later and thereafter virus was abundant in the nasal mucosa of young mice, while among old mice it remained undemonstrable in some and present in small amount in others. 3. Virus was not detected in the anterior rhinencephalon of young and old mice within a few minutes and 5 hours after nasal instillation, but was almost uniformly demonstrable in this region, although not in the rest of the brain, on the 2nd day. This indicated that the primary invasion of the brain occurred by the olfactory rather than the fifth nerve pathway. 4. The essential difference in the further pathogenesis of the disease between the young mice which succumb with encephalomyelitis (5th day) and the old mice which survive without showing clinical signs of brain involvement, is in the progression of the virus from the anterior rhinencephalon. In the young the rest of the brain is invaded, while in the old resistant mice it is not, the progression of virus being arrested somewhere in the anterior rhinencephalon. 5. Since minimal amounts of virus injected intracerebrally were shown to be disseminated quickly through the entire brain, killing old as well as young mice, it was clear that virus so inoculated must spread differently from that which reaches the brain by the olfactory pathway. 6. That the arrest of virus progression in the brains of certain old mice is the result of a preexisting, localized barrier, developed with age, and is not due to a rapidly acquired, specific, cerebral immunity was shown by the failure of old mice to resist an intracerebral injection of 1 to 10 M.C.L.D. , 2, 3, 4, or 5 days after preliminary nasal instillation. Footnotes Submitted: 23 March 1937

Sabin, Albert B.; Olitsky, Peter K.

doi: 10.1084/jem.66.1.35pmid: 19870648

1. Injection of vesicular stomatitis virus into the leg muscles of young mice gives rise to flaccid paralysis of the inoculated extremity as the first clinical sign of a disease which is invariably fatal; old mice similarly injected with the largest doses of virus survive without exhibiting any signs of illness. 2. In young mice the virus was shown to multiply at the site of inoculation and to invade the sciatic nerve and spinal cord; there was no evidence of multiplication of virus in the blood or viscera. 3. In old mice, after intramuscular injection of as much as 10 million M.C.L.D. , there was no evidence of either local or systemic multiplication; in spite of the persistence of thousands of M.C.L.D. of virus at the site of inoculation for at least 4 days, there was no detectable invasion of the sciatic nerve or the central nervous system. 4. Injection of the virus directly into the sciatic nerve of old mice led to the typical paralytic disease in half the number of animals. 5. For 3 days after intrasciatic injection the virus could be demonstrated in the nerve but not in the spinal cord or brain. At the onset of paralysis (6th day) virus was detectable in the spinal cord but no longer in the inoculated nerve. 6. The capacity of the virus to invade the central nervous system from the nerve but not from the muscle suggested the existence of a barrier in the muscle or myoneural junction. 7. Injection of the virus into the vitreous humor of the eye is followed by a fatal encephalitis in 15 day old mice, but 1 year old mice, with few exceptions, survive without showing signs of disease. 8. The spread of virus in the brains of intraocularly injected, 15 day old mice was too rapid to indicate the pathways which were pursued, but in 21 day old mice there was evidence that the primary pathway was probably along the axons of the optic nerve with decussation to the contralateral diencephalon and mesencephalon, and subsequent early spread to the corresponding occipital cortex. In resistant, old mice, however, no virus was found in any part of the brain. Footnotes Submitted: 23 March 1937

Claude, Albert

doi: 10.1084/jem.66.1.59pmid: 19870649

1. The agent causing Chicken Tumor I can be separated from the other constituents of the tumor filtrate by means of high speed centrifugation. The separation was practically complete when a filtrate of average viscosity (0.018 poise) was submitted to a centrifugal field of 14,000 times gravity for 2 hours. 2. Relative purification of the agent was obtained by means of differential centrifugation and washing in Tyrode's solution or in distilled water. The washed sediment gave opalescent solutions composed of minute particles of approximately, but not exactly, the same size. The dry weight of the active material separated by high speed centrifugation was 0.0008 mg. per cc. of filtrate, or about 1 part per 2800 parts of the total filtrate. 3. The tumor-producing activity of the washed sediment was significantly greater than that of the entire original filtrate. It is suggested that the gain in tumor-producing power was effected by the removal of an inhibiting factor, known to occur normally in chicken tumor extracts. Footnotes Submitted: 21 March 1937

McMaster, Philip D.; Kidd, John G.

doi: 10.1084/jem.66.1.73pmid: 19870650

An antiviral principle is elaborated within the regional lymph nodes draining skin into which vaccinia is injected. The immunity conferred by clinical Jennerian vaccination may be largely of lymph node origin. Footnotes Submitted: 8 March 1937

Dubos, René J.

doi: 10.1084/jem.66.1.101pmid: 19870644

Pneumococci, living or dead, are soluble in bile when: ( a ) the autolytic enzymes are still present in a potentially active form; ( b ) conditions are favorable for enzymatic action. Bile solubility of pneumococci involves as a necessary step one, or a few, of the many stages of the autolytic complex. These observations hold true for the disruption of pneumococci by freezing and thawing, by previous desiccation with cold acetone, and by dilute solutions of antiseptics. A possible mechanism is discussed to account for these forms of lysis. Footnotes Submitted: 23 March 1937

Dubos, René J.

doi: 10.1084/jem.66.1.113pmid: 19870645

1. Mice immunized with heat-killed cells of virulent pneumococci (Type I) which have been treated with active preparations of the bacteriolytic enzyme, develop a certain degree of type specific resistance to subsequent infection. This active immunity, however, appears to be due to the small amount of free acetyl polysaccharide present in the suspension of digested bacteria, and is always of a less pronounced degree than that obtained with intact heat-killed cells. 2. Virulent pneumococci killed by heat or iodine when subjected to the action of active preparations of the bacteriolytic enzyme lose the antigenic property of stimulating in rabbits the formation of precipitating antibodies for the type specific polysaccharide. 3. The enzyme prepared from S or R pneumococci, irrespective of type derivation, is equally effective against the capsular polysaccharide antigen of any specific type of this bacterial species. 4. The inactivation of the capsular polysaccharide antigen is observed when the cells are merely rendered Gram-negative, without being caused to undergo actual disintegration or lysis. 5. These observations emphasize the importance of minimizing the chances of alterations due to the action of cellular enzymes in the course of preparation of the cell suspension to be used as immunizing agents. Footnotes Submitted: 23 March 1937

Webster, Leslie T.; Clow, Anna D.

doi: 10.1084/jem.66.1.125pmid: 19870646

Rabies virus has been propagated in serum-Tyrode solution containing either embryo mouse brain or embryo chick brain. The culture virus reached a titre of 3 x 10 –5 cc. after 4 days' incubation at 37°C., and survived at least 2 months at 5°C. in the liquid or dry state. Footnotes Submitted: 14 April 1937