36 S. G. ANDERSON 



associates (1950a) and Chu (1951) believed that the RDE must be used in 

 the crude state and Appleby and Stuart-Harris (1950) supported this, report- 

 ing that purified preparations were inactive. Tyrrell and Horsfall (1952) 

 confirmed the action of crude RDE. 



Against this background, Sampaio and Isaacs (1953), working with rabbit 

 sera, decided the active agent in crude RDE was the trypsin-like component 

 described by Stone (1949a). Pure trypsin also destroyed Chu inhibitor. 



The action of periodate ion on Chu inhibitor has been discussed by various 

 authors. Chu (1951) claimed it did not destroy this inhibitor. McCrea (1948) 

 found both the specific antibody and Chu inhibitor in rabbit serum were 

 reduced only slightly in titer by periodate ion, but Hirst (1948a) had reported 

 a considerable reduction of inhibitor, possibly Chu inhibitor, in rabbit 

 serum. 



Burnet and Lind (1954) modified a method of Davoli for the removal of 

 Chu inhibitor by periodate. Large concentrations of periodate reduced 

 specific antibody in rabbit sera, but a concentration of M/150 left the 

 specific antibody intact, while removing all nonspecific inhibitor. 



3. Mucoid Inhibitors 



The development of a precise chemical approach to the mucoid inhibitors 

 of hemagglutination by Gottschalk, Blix, Klenk, and others (see Chapter 4) in 

 recent years has rendered it unnecessary to recapitulate the large amount of 

 work carried out on this theme between 1946 and 1952. Chemical aspects are 

 discussed by Gottschalk in the following chapter; here it is only necessary to 

 outline the main phenomena encountered in the earlier work done with a 

 primarily biological orientation. 



a. Sources of Inhibitor. Mucoid inhibitors are found in a wide variety of 

 vertebrate tissues and secretions. Originally described in mammalian sera 

 (McCrea, 1948), they are also present in egg white (ovomucin) (Gottschalk 

 and Lind, 1949), tears (Anderson, 1948), saliva (Francis and Minuse, 1948; 

 Seltsam et al., 1949), urine (Tamm and Horsfall, 1952; Perlmann et al., 1952), 

 and many mucinous secretions. They were found in high concentration in 

 salivary glands of man, ferret, mouse, and sheep, and in lower concentrations 

 in salivary glands of other species (Anderson, 1950; McCrea, 1953). Mucoid 

 inhibitors in various degrees of purity have been recovered from ovomucin, 

 human urine, bovine submaxillary gland (Curtain and Pye, 1955), sheep 

 salivary gland (McCrea, 1953), and human meconium (Curtain et al., 1953). 



b. Biological Properties. As originally studied, mucoid inhibitors had little 

 or no action on active virus but strongly inhibited hemagglutination by 

 heated (indicator) virus. The inhibitory power can be destroyed by the action 

 of active virus or RDE (Anderson, 1948). The optimal conditions for the 

 reaction include the presence of calcium ions and a pH of about 6.0. 



