14 LOCAL TLSSUE REACTIVITY 



Protocol 9: A group of 24 rabbits was employed. The skin-preparatory 

 injection of a B. lyj)liosus tryptic digest broth culture filtrate was made 

 sinuiltaneously into the upper right, lower right, upper left and lower left 

 (juadrants of the skin of the abdominal wall. The doses employed for the 

 intradermal injection were either 0.25 c.c. or 0.5 c.c. Positively reacting ani- 

 mals showed iniiiormly extremely severe hemorrhagic reactions in prepared 

 skin sites following intravenous injections of B. typhosus culture filtrates in 

 various doses. The only variation observed was in the size of the reaction. 

 The smallest reaction was 1 x 1 cm., and the largest 4x4 cm. The size of 

 the reaction did not clearly depend on the amoimt of filtrate used for the 

 skin prejjaration. For the same animals variations in the size in different 

 areas lay between 1 cm. and 3 cm. in diameter. Ordinarily, the difference 

 was 1 cm. to 2 cm. Occasionally, confluent reactions were obtained. No well 

 marked relationship between the intravenous dose and the size of the re- 

 action of the skin was observed. 



The reaction following the intravenous injection is not strictly 

 localized to the site of the preparatory injection. Some of the sites 

 may have a tendency to spread more than others, i.e., the central 

 portion of the skin of the abdominal wall. The skin of the upper 

 left quadrant invariably shows reactions smaller than those of 

 the right cpiadrant. The question of spreading of the reaction 

 was recently investigated by Bier (1932, 1933) , and Diiran-Reynals 

 (1933) in an attempt to determine the effect of the Reynals 

 factors iq)on the phenomenon. 



In 1928 I^iiran-Reynals (1929, 1933) reported that extracts 

 of normal animal testicles enhance to a marked degree the activ- 

 ity of nenro and dermal strains of vaccinia virus. The author as- 

 sumed that the effect of the tissue extract was apparently on the 

 cells of the host rather than on the virus. This was indicated by 

 the fact that virus injected intravenously localized most readily in 

 an area of skin previously injected with testicle extract. Enhanced 

 lesions also resulted when a virus was injected into an area as long 

 as three days prior to the injection of the testicle extract into the 

 same area. Kidney and probably skin, brain, and liver extracts 

 were reported by him to possess the enhancing properties but to 

 a much lesser degree. McClean (1930) brought additional e\i- 

 dence to the fact that Reynals factors produce the enhancing 

 effect not through modification of the virus biu through some 

 change in the receptivity of the host. He showed that the activity 

 of the extract is associated \vith an increase of the dermal perme- 

 ability ^vhich persists for at least t^venty-four hours. Accordingly, 

 this increase of dermal permeability allo\vs the spreading of tiie 

 virus over a large skin area. Pijoan (1931) foimd tiiat the in- 



