M.J. Welsh and A.E. Smith, RAC Application 
Stool culture. Stools were collected every week and cultured for virus; all were negative. 
Adenovirus antibody titers. Both monkeys had a significant rise in adenovirus 2 antibody 
titers. 
Conclusions 
Both monkeys developed a transient low grade fever after infection with the recombinant 
virus. The procedures that these monkeys were exposed to may have contributed to the 
fever. About 10% of the human patients that undergo bronchoalveolar lavage develop 
fever within 24 hours. The bronchial instillation of a large number of viral particles may 
have been responsible for the fever and increase in WBC. Even though significant 
eosinophilia was observed in bronchial brushings and bronchoalveolar lavage, we do not 
believe that the eosinophilia is related to the virus for the reasons considered above in b. 
(Ad2/CFTR-1 applied to the nasal epithelium). Both monkeys had a significant rise in 
antibody titer to adenovirus. After a week we could no longer detect the presence of a live 
virus. Finally, Ad2/6Gal- 1 was not detected in stool samples suggesting that ingestion of 
virus followed by replication in the gut does not occur. 
d. Sentinel monkey. 
Procedure 
Monkey F was housed in the same room and was immediately adjacent to and surrounded 
by monkeys C, D, E, G, and H. Besides being used as sentinel, monkey F had exactly the 
same procedures as did monkey G and H, except that tris buffered saline was instilled in the 
right bronchus intermidius instead of Ad2/6Gal-l. The monkey was completely evaluated 
on days 1, 4, 7, 14, 21, 28, and 35. The monkey was also observed daily for any abnormal 
behavior or physical signs. 
Results 
Examination. The monkey tolerated the mock infection procedure well, and did not 
become cyanotic or bradycardic. Visual inspection of the nasal epithelium revealed no 
inflammatory response. The monkey had no evidence of coryza, conjunctivitis or diarrhea. 
There were no changes in behavior. There was no cough or sneezing. Physical 
examination revealed no evidence of lymphadenopathy, fever, tachypnea or tachycardia. 
Appetite and weight were not affected. Flexible fiberoptic bronchoscopy revealed a normal 
appearance of the bronchial mucosa throughout the experiment. 
Blood counts and serology. 
Blood leukocytosis was seen on days 1 and 4 post infection, with neutrophil counts of 
7,460 and 5,800/mm 3 , respectively. Serum electrolytes, transaminases, BUN, ESR, and 
creatinine were normal throughout. 
Cytology of the bronchial epithelium and bronchoalveolar lavage. We assessed epithelial 
inflammation by cytological examination of Wright-stained cells obtained from brushings 
of the bronchial mucosa of the right bronchus intermidius and bronchoalveolar lavage. A 
significant percentage of eosinophils in samples from right bronchial mucosa was noted on 
days 1, 4, post instillation of placebo. Bronchoalveolar lavage from the right middle lobe 
revealed significant number of eosinophils throughout the experiment (12-52%). No 
significant lymphocytosis or increase in neutrophils was observed. 
Presence of virus on the airway epithelium. At each of the time points, we tested for the 
presence of virus in the supernatant of the cell suspension from bronchial brushings and 
bronchoalveolar lavage. No virus was detected at any point of the experiment. 
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Recombinant DNA Research, Volume 16 
