Simon's "Adenovirus-Mediated Transfer of the CFTR Gene to Lung of non-human primates: toxicity study" 1993
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===Abstract=== | ===Abstract=== | ||
- | * | + | *Prepared a pre-clinical study of gene transfer into the lungs of baboons. |
- | ** | + | **Recombinant adenovirus vectors containing expression cassettes for human cystic fibrosis transmembrane conductance regulator (CFTR) and Escherichia coli ~-galactosidase (lacZ) were instilled through a bronchoscope into limited regions of lung in 14 baboons |
- | * | + | *Results of toxicity studies were found using clinical laboratory tests, chest radiographs, and necropsy tests were used |
- | * | + | **These were used to detect adverse effects |
+ | *** The only adverse effect noted was a mononuclear cell inflammatory response within the alveolar compartment of animals receiving doses of virus that were required to induce detectable gene expression. | ||
+ | **Minimal inflammation was seen and 107 and 108 pfu (plaque forming units) per ml (infectious units per volume) but perivascular lymphocytic and histocytic infiltrate was seen at 109 and 1010 | ||
+ | ***Intensity of inflammation increased between 4 and 21 days | ||
+ | **** At its greatest intensity, there was diffuse alveolar wall damage with intra-alveolar edema (the airways were relatively spared) | ||
+ | **Chest radiographs revealed alveolar infiltrates, but only in regions of lung having the greatest intensity inflammation | ||
+ | * Concluded that adenovirus-mediated gene transfer into the lungs of baboons is associated with development of alveolar inflammation at high doses of virus | ||
===Introduction=== | ===Introduction=== |
Revision as of 00:17, 5 March 2010
Abstract
- Prepared a pre-clinical study of gene transfer into the lungs of baboons.
- Recombinant adenovirus vectors containing expression cassettes for human cystic fibrosis transmembrane conductance regulator (CFTR) and Escherichia coli ~-galactosidase (lacZ) were instilled through a bronchoscope into limited regions of lung in 14 baboons
- Results of toxicity studies were found using clinical laboratory tests, chest radiographs, and necropsy tests were used
- These were used to detect adverse effects
- The only adverse effect noted was a mononuclear cell inflammatory response within the alveolar compartment of animals receiving doses of virus that were required to induce detectable gene expression.
- Minimal inflammation was seen and 107 and 108 pfu (plaque forming units) per ml (infectious units per volume) but perivascular lymphocytic and histocytic infiltrate was seen at 109 and 1010
- Intensity of inflammation increased between 4 and 21 days
- At its greatest intensity, there was diffuse alveolar wall damage with intra-alveolar edema (the airways were relatively spared)
- Intensity of inflammation increased between 4 and 21 days
- Chest radiographs revealed alveolar infiltrates, but only in regions of lung having the greatest intensity inflammation
- These were used to detect adverse effects
- Concluded that adenovirus-mediated gene transfer into the lungs of baboons is associated with development of alveolar inflammation at high doses of virus