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Xiaojie Luan Verónica A. Campanucci Manoj Nair Orhan Yilmaz George Belev Terry E. Machen Dean Chapman Juan P. Ianowski 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(35):12930-12935
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding for the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Several organs are affected in CF, but most of the morbidity and mortality comes from lung disease. Recent data show that the initial consequence of CFTR mutation is the failure to eradicate bacteria before the development of inflammation and airway remodeling. Bacterial clearance depends on a layer of airway surface liquid (ASL) consisting of both a mucus layer that traps, kills, and inactivates bacteria and a periciliary liquid layer that keeps the mucus at an optimum distance from the underlying epithelia, to maximize ciliary motility and clearance of bacteria. The airways in CF patients and animal models of CF demonstrate abnormal ASL secretion and reduced antimicrobial properties. Thus, it has been proposed that abnormal ASL secretion in response to bacteria may facilitate the development of the infection and inflammation that characterize CF airway disease. Whether the inhalation of bacteria triggers ASL secretion, and the role of CFTR, have never been tested, however. We developed a synchrotron-based imaging technique to visualize the ASL layer and measure the effect of bacteria on ASL secretion. We show that the introduction of Pseudomonas aeruginosa and other bacteria into the lumen of intact isolated swine tracheas triggers CFTR-dependent ASL secretion by the submucosal glands. This response requires expression of the bacterial protein flagellin. In patients with CF, the inhalation of bacteria would fail to trigger ASL secretion, leading to infection and inflammation.The human airway is normally protected from injury caused by microbial colonization and viral infection by a complex immune defense system. The cornerstone of airway defense is mucociliary clearance. Particles, including bacteria, are captured in mucus and removed by an efficient mucociliary clearance mechanism. Airway host defense is compromised in individuals with cystic fibrosis (CF), whose lungs are thus prone to chronic bacterial infections, frequently with Pseudomonas aeruginosa, and inflammation that may eventually cause lung tissue damage and respiratory failure (1, 2). The events leading from cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation to airway disease are incompletely understood, but accumulating evidence suggests that CF airway disease results from abnormal microbial clearance (3, 4).Although chronic inflammation is a major aspect of CF lung disease, recent data show that the initial consequence of CFTR mutation is impaired ability to eradicate bacteria. In previous studies, lungs from animal models of CF (F508del and CFTR−/− pigs) (5, 6) did not eradicate bacteria as effectively as lungs from WT littermates before the development of inflammation (3, 4). These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs (4).The failure to clear bacteria likely results from abnormal airway surface liquid (ASL) secretion and properties (6–10). The ASL consists of a layer of mucus that traps inhaled particles and a periciliary liquid layer that keeps the mucus an optimum distance from the underlying epithelia to maximize ciliary mobility (10, 11). The mucus layer is a complex mixture of water, salts, gel-forming mucins, and antimicrobial compounds that helps inactivate, kill, and trap pathogens and facilitates mucociliary clearance (10, 11). In CF airways, both the bacteria-killing properties and ASL secretion are abnormal (3, 9). The airway liquid produced by CFTR−/− swine has weaker bactericidal properties compared with that produced by WT littermates, owing to abnormal pH (3, 4). In addition, human CF airways, 1-d-old CF piglets, newborn CFTR−/− ferrets, and CFTR−/− mice fail to respond to stimulatory signals that normally elicit strong ASL secretion (6–9). Consequently, it has been proposed that abnormal secretion of fluid and mucin in response to bacterial infection may contribute to the pathogenesis of CF lung disease (7–10, 12–15); however, the central questions of whether bacteria trigger ASL secretion in the airways, and the role of CFTR in such a process, have not been explored previously, owing to the lack of a suitable experimental technique.We have developed a novel synchrotron-based method to measure the height of the ASL layer covering the epithelium of intact, isolated swine trachea. We show that the introduction of P. aeruginosa into the lumen of intact isolated swine tracheas triggers CFTR-dependent ASL secretion by the submucosal glands. This is a local response that affects only the glands in close proximity to the bacteria and requires expression of the bacterial protein flagellin. We also show that Staphylococcus aureus and Haemophilus influenzae trigger CFTR-dependent ASL secretion, indicating that this response is not unique to P. aeruginosa. In patients with CF, the inhalation of bacteria would fail to trigger ASL secretion by submucosal glands, facilitating infection and inflammation. 相似文献
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?zdemir S G?rgülü O Akba? Y Sel?uk T Sayar H Tarkan ? 《Journal of cranio-maxillo-facial surgery》2012,40(5):e137-e139
Rhinoliths are nasal stones that result from mineralisation of salts around an endogenous or exogenous nidus within the nasal cavity. They are uncommon nasal masses and usually unilateral and single, situated in the floor of the nose. The patient typically presents with nasal obstruction, facial pain and foul-smelling nasal secretion. To the best of our knowledge, the occurrence of squamous cell carcinoma with rhinolithiasis has not been previously reported in the English-language literature. In this article, we present a 63-year-old man, who had unilateral rhinolithiasis with squamous cell carcinoma within the nasal cavity. 相似文献
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Aim: This study examined and classified patients who were treated at the Faculty of Dentistry at Ankara University Dentistry to determine the incidence of different types of stylohyoid ligament calcification (SLC) using panoramic radiographs. In addition, it also assessed the possible causative symptoms and Eagle’s syndrome in cases of styloid process elongation. Methods: The study consisted of 2000 patients (1161 females and 839 males), aged 3–88 years, who were treated at our clinic. The panoramic radiographs were evaluated as part of this study. Results: Panoramic radiography examination revealed SLC in 1350 patients. Both‐sided (right and left), type 1 SLC was observed in 345 patients, while types 2–4 were found in 203, 418, and 384 patients, respectively. Conclusion: The incidence of SLC was found to be higher in female patients when compared to male patients. In addition, calcifications were seen more often at age 50–59 years, and the incidence of calcification was found to increase with age. Two Eagle’s syndrome cases were diagnosed among a total of 2000 patients. Finally, it was determined that the incidence of calcified stylohyoid ligament is higher in patients with systemic diseases. 相似文献
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Mehmet Sayarlioglu Nergis Yuzbasioglu Murat Inanc Sevil Kamali Ayse Cefle Ozcan Karaman Ahmet Mesut Onat Rustem Avan Gozde Yildirm Cetin Ahmet Gul Lale Ocal Orhan Aral 《Rheumatology international》2012,32(1):177-182
The objective was to investigate the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). The records of 868 patients with SLE from four centers were reviewed retrospectively. Forty-nine patients with AVN were identified. A total of 154 patients with SLE who did not have clinically apparent AVN during the follow-up were evaluated as a control group. The demographic, clinical, laboratory and management characteristics of these two groups of patients were recorded according to predefined protocol and compared. The prevalence of AVN was detected 6% in our SLE population. The highest dose corticosteroid administered within 4?months and total cumulative prednisolone dose were significantly higher in the SLE patients with AVN. The use of cytotoxic agent significantly higher proportion of patients with AVN. AVN tends to develop more frequently in male gender and younger patients. Oral ulcer, pleuritis, Raynaud??s phenomenon, cutaneous vasculitis, lymphadenopathy, autoimmune thyroiditis, peripheral neuropathy and Sj?gren??s syndrome were higher incidence in SLE patients with AVN. The bilateral femoral heads were the commonest site of involvement of AVN in our patients with SLE. 相似文献
80.
Yilmaz HH Yildirim D Ugan Y Tunc SE Yesildag A Orhan H Akdag C 《Rheumatology international》2012,32(5):1171-1178
The aim of this study was to investigate the clinical, radiographic, and magnetic resonance imaging (MRI) findings of temporomandibular
joint (TMJ) and masticatory muscles in rheumatoid arthritis (RA) patients. Twenty-eight RA patients and 29 healthy subjects
were participated in the study. The patient underwent clinical and laboratory investigation. DAS28 scores were calculated.
Lateral panoramic radiography was performed to evaluate condylar erosion and condylar movement. Craniofacial MRI was performed
to evaluate TMJ and masseter, medial and lateral pterygoid muscles’ thickness, and cross-sectional area. It was found that
the mean maximal interincisal distance, range of lateral, retrusive (P < 0.05) and protrusive motion were all lesser in RA group. Lateral panoramic radiography revealed a distinct erosion in 10.7%
(3/28) and restricted condylar movement in 53.6% (15/28) of RA patients. Two RA patients demonstrating marked condylar erosion
in lateral panoramic radiographs were RF negative and had DAS28 scores 3.41 and 4.61. MRI findings revealed condylar erosion
and effusion in one RA patient and atrophic changes of masticatory muscles in another patient. There was no statistical significance
between RA and healthy groups for the thickness and cross-sectional areas of the masticatory muscles. RA group revealed a
strong linear relationship for the right and left muscle thickness and cross-sectional areas in regression analysis. TMJ symptoms
are frequent findings and thought to be affected from mean disease duration in RA. Laboratory findings should be considered
for disease activity–related TMJ involvement. RA patients did not present muscular atrophy or hypertrophy. 相似文献