Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human tracheal gland serous (HTGS) cells are now considered one principal pulmonary target for the gene therapy of cystic fibrosis (CF). We developed a CF tracheal gland serous cell line, CF-KM4, obtained by the transformation of primary cultures of CF tracheal gland serous cells homozygous for the DeltaF508 mutation by using the wild-type SV40 virus. This cell line retained epithelial and secretory features of the native CF-HTGS cells in primary culture, namely, presence of cytokeratin, constitutive secretion of secretory leukocyte proteinase inhibitor, absence of responsiveness to carbachol and isoproterenol, and defective cyclic adenosine monophosphate-dependent chloride channel activity. Adenovirus-mediated CF transmembrane conductance regulator (CFTR) gene transfer into CF-KM4 cells corrected the defective chloride channel activity as well as the responsiveness to adrenergic and cholinergic agonists. In contrast, control transfection using adenovirus-mediated beta-galactosidase gene transfer was totally ineffective. In conclusion, these results present a stable CF tracheal gland cell line that has retained its epithelial and CF-specific defective secretory characteristics which are corrected after CFTR gene transfer. This cell line therefore appears to be a useful tool for large-scale molecular and cellular pharmacologic investigations designed to test potential therapies of the disease CF.
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PMID:A cystic fibrosis tracheal gland cell line, CF-KM4. Correction by adenovirus-mediated CFTR gene transfer. 1010 Oct

Adenovirus-mediated gene transfer is a novel treatment strategy for head and neck squamous cell carcinoma (HNSCC) that may improve the unacceptable morbidity and mortality associated with conventional treatment. Efficient adenoviral (AdV) infection largely depends on cellular expression of the human coxsackie and adenovirus receptor (hCAR); however, the relatively recent identification of this receptor precludes a comprehensive description of its tissue distribution. We have created tissue culture model systems that approximate the differentiation and three-dimensional structure of stratified squamous epithelium characteristic of head and neck mucosa. Using these systems, we have found that expression of hCAR in native and modeled normal oropharyngeal epithelium decreased as cells differentiated with the most superficial and differentiated cells expressing no detectable hCAR. In contrast, modeled stratified HNSCC cells, which did not differentiate morphologically and did not express cytokeratin markers of differentiation, had equivalent expression of hCAR in superficial and basal layers. The expression of hCAR in our models correlated not only with the undifferentiated state, but also with efficiency of AdV infection. Despite expression of hCAR in underlying basal and suprabasal cells, topical application of AdV to normal modeled epithelium resulted in inefficient transduction of the most superficial cell layer without any infection of underlying cells. These data suggest that in normal epithelium the overlying squamous cells act as a barrier preventing infection of underlying cells that would otherwise be easily infected. In modeled stratified HNSCC, transduction was much more efficient and occurred up to four cell layers deep, suggesting that unlike normal superficial epithelial cells, the superficial cells of stratified HNSCC do not act as an effective barrier to adenoviral infection. The distribution of hCAR in native tissue and the enhanced susceptibility of undifferentiated oropharyngeal epithelial cells, including undifferentiated cancer cells, to AdV infection has important implications for the development of AdV-based targeting strategies for the treatment of head and neck cancer or premalignancies.
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PMID:Efficiency of adenovirus-mediated gene transfer to oropharyngeal epithelial cells correlates with cellular differentiation and human coxsackie and adenovirus receptor expression. 1109 41

Adenovirus infection is not uncommon in pediatric small bowel transplant recipients. Histopathologic findings include characteristic epithelial changes of intranuclear inclusions and smudging of nuclei. We present a case of adenovirus within stromal cells of the lamina propria in a biopsy from a small bowel allograft. Immunohistochemistry and double-labeled immunofluorescence were performed using antibodies against adenovirus, CD31, vimentin, cytokeratin, and CD163 on the allograft intestinal biopsy. Electron microscopy was done to confirm the presence of viral particles and to attempt to confirm the origin of the infected cells. The index biopsy showed scant cells within the lamina propria double-labeled with vimentin and adenovirus. Several cells showed predominantly cytoplasmic staining for adenoviral antigen. Intranuclear adenoviral particles were found in several cells of the lamina propria by electron microscopy. A subsequent biopsy showed typical adenoviral intranuclear inclusions within surface enterocytes. Adenovirus may infect stromal cells within the lamina propria. Although the typical location of adenoviral inclusions in small bowel is the surface epithelial cell nuclei, some cases may show inclusions within stromal cells. This observation may be important in the pathobiology of adenoviral infection, especially in the setting of pediatric transplantation. This finding should alert pathologists examining small bowel transplant biopsies, particularly those biopsies with extensive ulceration, to include careful surveillance of the lamina propria.
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PMID:Adenovirus infection within stromal cells in a pediatric small bowel allograft. 1694 84