M.J. Welsh and A.E. Smith, RAC Application 
for several years; monkeys C and D were from Cleveland. We interpret the eosinophilia as 
an unrelated occurrence because: it was present in all of the San Francisco monkeys 
irrespective of the treatment group, it did not occur in the Iowa or Cleveland monkeys, and 
the eosinophilia preceded the virus administration. There were no other signs or 
manifestations of a significant inflammatory response. There was no evidence of viral 
replication. Finally, Ad2/CFTR-1 was not detected in stool samples suggesting that 
ingestion of virus followed by replication in the gut does not occur. We conclude that 
Ad2/CFTR-1 appears to be safe for topical application in the nasal mucosa. 
c. Ad2/BGal-l applied to the bronchial epithelium. 
Procedure 
The procedure for two monkeys (G and H) was described above, point B.2.b.(3). The 
monkeys were completely evaluated on days 1, 4, 7, 14, 21, 28, and 35. The monkeys were 
also observed daily for any abnormal behavior or physical signs. 
Results 
Examination. The two monkeys tolerated the infection procedure well. Neither monkey 
became cyanotic or bradycardic. We looked for a systemic inflammatory response by daily 
visual inspection of the nasal epithelium. Neither of the monkeys developed any evidence 
of coryza, conjunctivitis or diarrhea. There was no cough or sneezing. Physical 
examination revealed no evidence of lymphadenopathy, tachypnea or tachycardia. Monkey 
G had a rectal temperature 39.1° C on day 4 post infection and Monkey H had a rectal 
temperature of 39.4° C on day 1 and 39.2° C on day 4 post infection. Appetites and 
weights were not affected by virus administration in either monkey. Both monkeys 
underwent flexible fiberoptic bronchoscopy on each evaluation day. The bronchial mucosa 
from monkey H appeared normal throughout the experiment. Bronchial examination of 
monkey G revealed erythematous mucosa at the right main bronchus on days 1 and 4 post 
infection and appeared normal thereafter. 
Blood counts and serology. Monkey H had a blood leukocytosis on day 4 post infection; 
the WBC increased to 1 1,300 with 8,380 neutrophils. No other abnormalities were found 
in the hematology, ESR, serum electrolytes, transaminases, BUN or creatinine. 
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, the left main bronchus and 
bronchoalveolar lavage. At baseline Monkey H had 7% eosinophils in the tracheal 
brushings. Both monkeys had a significant percentage of eosinophils in samples from right 
and left bronchial mucosa at all time points. Bronchoalveolar lavage from the right middle 
lobe revealed a significant number of eosinophils throughout the experiment in monkey G 
(10-46%) and on days 1, 4, and 7 in monkey H (29 - 39%). No significant lymphocytosis or 
increase in neutrophils was observed. 
Presence of virus replication on the airway epithelium. At each of the time points we 
tested for the presence of live virus in the supernatant of the cell suspension from bronchial 
brushings and bronchoalveolar lavage as described above, using the virus-sensitive 293 cell 
line. In both monkeys, live virus was detected from the right bronchial brushings and 
bronchoalveolar lavage on day 1 post infection. On day 4 post infection live virus was 
detected in samples from bilateral bronchial brushings and bronchoalveolar lavage from 
monkey H. No live virus was detected from monkey G on day 4. There was no live virus 
from either monkey on day 7 or after. 
Recombinant DNA Research, Volume 16 
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