Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered terminal glycosylation, with increased fucosylation and decreased sialylation is a hallmark of the cystic fibrosis (CF) glycosylation phenotype. Oligosaccharides purified from the surface membrane glycoconjugates of CF airway epithelial cells have the Lewis x, selectin ligand in terminal positions. This review is focused on the investigations of the glycoconjugates of the CF airway epithelial cell surface. Two of the major bacterial pathogens in CF, Pseudomonas aeruginosa and Haemophilus influenzae, have binding proteins which recognize fucose in alpha-1,3 linkage and asialoglycoconjugates. Therefore, consideration has been given to the possibility that the altered terminal glycosylation of airway epithelial glycoproteins in CF contributes to both the chronic infection and the robust, but ineffective, inflammatory response in the CF lung. Since the glycosylation phenotype of CF airway epithelial cells have been modulated by the expression of wtCFTR, the hypotheses which have been proposed to relate altered function of CFTR to the regulation of the glycosyltransferases are discussed. Understanding the effects of mutant CFTR on glycosylation may provide further insight into the regulation of glycoconjugate processing as well as new approaches to the therapy of CF.
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PMID:Terminal glycosylation in cystic fibrosis (CF): a review emphasizing the airway epithelial cell. 1238 52

Inflammation plays a major role in the pathophysiology of lung disease in CF. This response is probably triggered primarily as a reaction to the inability of the affected lung to resist the invasion of the most common bacterial pathogens seen in this disease, namely, Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. Debate continues as to whether there may or may not be a pre-inflammation of the lungs as part of the basic functional defect of CFTR. The anti-inflammatory treatment modalities most tested to date are: oral corticosteroids, effective but associated with significant long-term side effects, inhaled corticosteroids, so far not proven to be effective probably because of difficulty with absorption through the viscid surface secretions of the lung and ibuprofen, potentially effective but inhibited by the need to monitor drug levels invasively and potential gastrointestinal side effects. The most promising newcomer is macrolide antibiotics such as azithromycin acting as a long-term anti-inflammatory agent with an excellent safety profile.
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PMID:Anti-inflammatory therapy in cystic fibrosis. 1600 66

Cystic fibrosis (CF) is one of the most common lethal inherited diseases in the caucasian population. The hope of understanding the physiopathology of CF appeared after identification of the gene which encodes CF. The alteration in CFTR protein breaks the hydric balance of the mucosal secretions, producing mucus with increased viscosity. Broncho-pulmonary infections are constant encountered because of the stasis of the mucus. The most common bacterial pathogens in the sputum of patients with MV are Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia. MV remains a severe, incurable disease, but the evolution is getting better because of the improvements of care methods.
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PMID:[Physiopathology of cystic fibrosis and of infections associated to this disease]. 1832 Jul 96

Well-differentiated human airway epithelia present formidable barriers to efficient siRNA delivery. We previously reported that treatment of airway epithelia with specific small molecules improves oligonucleotide uptake and facilitates RNAi responses. Here, we exploited the platelet activating factor receptor (PAFR) pathway, utilized by specific bacteria to transcytose into epithelia, as a trigger for internalization of Dicer-substrate siRNAs (DsiRNA). PAFR is a G-protein coupled receptor which can be engaged and activated by phosphorylcholine residues on the lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae and the teichoic acid of Streptococcus pneumoniae as well as by its natural ligand, platelet activating factor (PAF). When well-differentiated airway epithelia were simultaneously treated with either nontypeable Haemophilus influenzae LOS or PAF and transduced with DsiRNA formulated with the peptide transductin, we observed silencing of both endogenous and exogenous targets. PAF receptor antagonists prevented LOS or PAF-assisted DsiRNA silencing, demonstrating that ligand engagement of PAFR is essential for this process. Additionally, PAF-assisted DsiRNA transfection decreased CFTR protein expression and function and reduced exogenous viral protein levels and titer in human airway epithelia. Treatment with spiperone, a small molecule identified using the Connectivity map database to correlate gene expression changes in response to drug treatment with those associated with PAFR stimulation, also induced silencing. These results suggest that the signaling pathway activated by PAFR binding can be manipulated to facilitate siRNA entry and function in difficult to transfect well-differentiated airway epithelial cells.
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PMID:Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia. 2502 65