Bronchial dentures as a cause of airway actinomycosis.

A 65-year-old man was referred to the respiratory clinic with recurrent chest infections on a background of stage 3 chronic obstructive pulmonary disease. On examination, there was wheeze bilaterally more marked on the left lower lobe. Subsequent imaging revealed an obstruction of the left main bronchus that was concerning for malignancy.

Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment.

Recent advances in basic science have greatly expanded our understanding of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the chloride and bicarbonate channel that is encoded by the gene, which is mutated in patients with CF. We review the structure, function, biosynthetic processing, and intracellular trafficking of CFTR and discuss the five classes of mutations and their impact on the CF phenotype. The therapeutic discussion is focused on the significant progress toward CFTR mutation-specific therapies.

The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. The most common CF-associated mutation is ΔF508, which deletes a phenylalanine in position 508. In vitro studies indicate that the resultant protein, CFTR-ΔF508, is misprocessed, although the in vivo consequences of this mutation remain uncertain.

Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth.

People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation.

Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.

Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). Understanding the pathogenesis of this disease has been hindered, however, by the lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with mutated CFTR genes.

Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs.

Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles.

Fatal miliary Coccidioidomycosis in a patient receiving infliximab therapy: a case report.

A 78-year-old white male from Iowa in the United States of America receiving the anti- tumor necrois factor (TNF) agent infliximab therapy for rheumatoid arthritis developed a cheek ulcer which failed to respond to empiric antibiotic therapy. He subsequently presented with progressive respiratory failure from miliary coccidioidomycosis which proved fatal. The patient vacationed in Arizona 6 months previously and likely contracted the organism there as Iowa is not an endemic area for coccidioidomycosis.

Neutrophil elastase up-regulates cathepsin B and matrix metalloprotease-2 expression.

Neutrophil elastase (NE) activity is increased in many diseases. Other families of proteases, including cathepsins and matrix metalloproteases (MMPs), are also present at elevated levels in similar disease conditions. We postulated that NE could induce expression of cathepsins and MMPs in human macrophages.

Migraine with aura following atrial septostomy for pulmonary arterial hypertension.

Background: A 34-year-old woman with known familial pulmonary arterial hypertension presented with syncope. Despite medical therapy with an endothelin-receptor antagonist and a phosphodiesterase inhibitor, the patient had NYHA class III symptoms, with exertional dyspnea. Right heart catheterization revealed severe pulmonary hypertension (right atrial pressure 15 mmHg, right ventricular pressure 80/15 mmHg, pulmonary artery pressure 80/35 mmHg, mean pulmonary artery pressure 52 mmHg).

Antimicrobial proteins and polypeptides in pulmonary innate defence.

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen.

Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis.

Intractable formation of biofilm by and infection with the opportunistic pathogen Pseudomonas aeruginosa are hallmarks of cystic fibrosis (CF). Lactoferrin, an innate immunity protein, has recently been shown to inhibit the formation of P. aeruginosa biofilm.