Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa.
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Cystic fibrosis (CF) patients develop chronic airway infections with Pseudomonas aeruginosa (PA). Pseudomonas aeruginosa synthesized lipopolysaccharide (LPS) with a variety of penta- and hexa-acylated lipid A structures under different environmental conditions. CF patient PA synthesized LPS with specific lipid A structures indicating unique recognition of the CF airway environment. CF-specific lipid A forms containing palmitate and aminoarabinose were associated with resistance to cationic antimicrobial peptides and increased inflammatory responses, indicating that they are likely to be involved in airway disease. (+info)
Airway injury during anesthesia: a closed claims analysis.
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BACKGROUND: Airway injury during general anesthesia is a significant source of morbidity for patients and a source of liability for anesthesiologists. To identify recurrent patterns of injury, the authors analyzed claims for airway injury in the American Society of Anesthesiologists (ASA) Closed Claims Project database. METHODS: The ASA Closed Claims database is a standardized collection of case summaries derived from professional liability insurance companies closed claims files. All claims for airway injury were reviewed in depth and were compared to other claims during general anesthesia. RESULTS: Approximately 6% (266) of 4,460 claims in the database were for airway injury. The most frequent sites of injury were the larynx (33%), pharynx (19%), and esophagus (18%). Injuries to the esophagus and trachea were more frequently associated with difficult intubation. Injuries to temporomandibular joint and the larynx were more frequently associated with nondifficult intubation. Injuries to the esophagus were more severe and resulted in a higher payment to the plaintiff than claims for other sites of airway injury. Difficult intubation (odds ratio = 4.53, 95% confidence interval [CI] = 2.36, 8.71), age older than 60 yr (odds ratio = 2.97, 95% CI = 1.51, 5.87), and female gender (odds ratio = 2.43, 95% CI = 1.09, 5.42) were associated with claims for pharyngoesophageal perforation. Early signs of perforation, e.g., pneumothorax and subcutaneous emphysema, were present in only 51% of perforation claims, whereas late sequelae, e.g., retropharyngeal abscess and mediastinitis, occurred in 65%. CONCLUSION: Patients in whom tracheal intubation has been difficult should be observed for and told to watch for the development of symptoms and signs of retropharyngeal abscess, mediastinitis, or both. (+info)
Cell elongation induces laminin alpha2 chain expression in mouse embryonic mesenchymal cells: role in visceral myogenesis.
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Bronchial smooth muscle (SM) mesenchymal cell precursors change their shape from round to spread/elongated while undergoing differentiation. Here we show that this change in cell shape induces the expression of laminin (LM) alpha2 chain not present in round mesenchymal cells. LM alpha2 expression is reversible and switched on and off by altering the cell's shape in culture. In comparison, the expression of LM beta1 and gamma1 remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation into SM are inhibited by an antibody against LM alpha2. Dy/dy mice express very low levels of LM alpha2 and exhibit congenital muscular dystrophy. Lung SM cells isolated from adult dy/dy mice spread defectively and synthesized less SM alpha-actin, desmin, and SM-myosin than controls. These deficiencies were completely corrected by exogenous LM-2. On histological examination, dy/dy mouse airways and gastrointestinal tract had shorter SM cells, and lungs from dy/dy mice contained less SM-specific protein. The intestine, however, showed compensatory hyperplasia, perhaps related to its higher contractile activity. This study therefore demonstrated a novel role for the LM alpha2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM. (+info)
The Xenopus tadpole gut: fate maps and morphogenetic movements.
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We have produced a comprehensive fate map showing where the organs of the gut and respiratory system are derived from in the early Xenopus laevis endoderm. We also show the origin of the associated smooth muscle layer on a separate fate map. Comparison of the two maps shows that for most organs of the gut the prospective epithelium and smooth muscle do not overlie each other in the early embryo but come together at a later stage. These fate maps should be useful for future studies into endoderm specification. It was not previously known how the elongation of the endoderm occurs, how the single-layered dorsal and many-layered ventral endoderm gives rise to the single layered epithelium, and whether or not the archenteron cavity actually gives rise to the gut lumen. Using a variety of labelling procedures we show firstly, that radial intercalation occurs in the gut transforming a short thick tube into a long thin tube; secondly, that the archenteron lining does not become the definitive gut lumen. Instead the archenteron cavity almost closes at tailbud stages before providing a nucleus for the definitive gut cavity, which opens up during elongation. Based on this work we present a model explaining the morphogenesis of the gut. (+info)
Ventilatory mechanics and the effects of water depth on breathing pattern in the aquatic caecilian Typhlonectes natans.
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The breathing pattern in the aquatic caecilian Typhlonectes natans was investigated by recording airflow via a pneumotachograph under unrestrained normal physiological conditions. Ventilatory mechanics were assessed using airflow and pressure measurements from the buccal cavity and trachea. The breathing pattern consisted of an expiratory phase followed by a series of 10-15 small buccal pumps to inflate the lung, succeeded by a long non-ventilatory period. T. natans separate the expiratory and inspiratory gases in the buccal cavity and take several inspiratory pumps, distinguishing their breathing pattern from that of sarcopterygians. Hydrostatic pressure assisted exhalation. The tracheal pressure was greater than the water pressure at that depth, suggesting that pleuroperitoneal pressure as well as axial or pulmonary smooth muscles may have contributed to the process of exhalation. The frequency of lung ventilation was 6.33+/-0.84 breaths h(-)(1), and ventilation occurred via the nares. Compared with other amphibians, this low ventilatory frequency suggests that T. natans may have acquired very efficient pulmonary respiration as an adaptation for survival in their seasonally fluctuating natural habitat. Their respiratory pathway is quite unique, with the trachea separated into anterior, central and posterior regions. The anterior region serves as an air channel, the central region is attached to the tracheal lung, and the posterior region consists of a bifurcated air channel leading to the left and right posterior lungs. The lungs are narrow, elongated, profusely vascularized and compartmentalized. The posterior lungs extend to approximately two-thirds of the body length. On the basis of their breathing pattern, it appears that caecilians are phylogenetically derived from two-stroke breathers. (+info)
Comparison of Pasteurella spp. simultaneously isolated from nasal and transtracheal swabs from cattle with clinical signs of bovine respiratory disease.
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Twenty-four matched pairs of isolates of Pasteurella haemolytica and three matched pairs of isolates of Pasteurella multocida were isolated by using a nasal swab and a transtracheal swab from individual calves with clinical signs of bovine respiratory disease. The identity of each matched pair was confirmed biochemically and serologically. The similarity of the isolates obtained from a nasal swab and from a transtracheal swab was compared by using ribotyping and antibiotic susceptibility analyses. Although the calves were sampled only once with a nasal and a transtracheal swab, when both samples were bacteriologically positive the nasal swab identified the same bacterial species as the transtracheal swab 96% of the time. The nasal swab isolate was genetically identical to the transtracheal isolate in 70% of the matched pairs. Six different ribotypes were observed for the P. haemolytica isolates, while only one ribotype was observed for the limited number of P. multocida isolates. Of the six P. haemolytica ribotypes, two ribotypes predominated. All the paired isolates displayed similar susceptibility to ceftiofur, erythromycin, tilmicosin, trimethoprim-sulfamethoxazole, and florfenicol, with some minor variations for ampicillin and spectinomycin. These results suggest that a nasal swab culture can be predictive of the bacterial pathogen within the lung when the isolates are from an acutely ill animal and can be used to determine antibiotic susceptibility. (+info)
Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer.
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BACKGROUND: Activation of gastrin-releasing peptide receptor (GRPR) in human airways has been associated with a proliferative response of bronchial cells to gastrin-releasing peptide and with long-term tobacco use. The GRPR gene is located on the X chromosome and escapes X-chromosome inactivation, which occurs in females. Increasing evidence demonstrates that women are more susceptible than men to tobacco carcinogenesis. We hypothesized that the susceptibility of women to the effects of tobacco may be associated with airway expression of GRPR. METHODS: We analyzed GRPR messenger RNA (mRNA) expression in lung tissues and cultured airway cells from 78 individuals (40 males and 38 females) and in lung fibroblasts exposed to nicotine in vitro. Nicotinic acetylcholine receptors in airway cells were assayed by use of radioactively labeled nicotine and nicotine antagonists. A polymorphism in exon 2 of the GRPR gene was used to detect allele-specific GRPR mRNA expression in some individuals. Statistical tests were two-sided. RESULTS: GRPR mRNA expression was detected in airway cells and tissues of more female than male nonsmokers (55% versus 0%) and short-term smokers (1-25 pack-years [pack-years = number of packs of cigarettes smoked per day multiplied by the number of years of smoking]) (75% versus 20%) (P =.018 for nonsmoking and short-term smoking females versus nonsmoking and short-term smoking males). Female smokers exhibited expression of GRPR mRNA at a lower mean pack-year exposure than male smokers (37.4 pack-years versus 56.3 pack-years; P =.037). Lung fibroblasts and bronchial epithelial cells exhibited high-affinity, saturable nicotinic acetylcholine-binding sites. Expression of GRPR mRNA in lung fibroblasts was elevated following exposure to nicotine. CONCLUSIONS: Our results suggest that the GRPR gene is expressed more frequently in women than in men in the absence of smoking and that expression of this gene is activated earlier in women in response to tobacco exposure. The presence of two expressed copies of the GRPR gene in females may be a factor in the increased susceptibility of women to tobacco-induced lung cancer. (+info)
Distinct pathogenesis of hong kong-origin H5N1 viruses in mice compared to that of other highly pathogenic H5 avian influenza viruses.
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In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian influenza viruses were analyzed for their pathogenicity in 6- to 8-week-old BALB/c mice. Both the avian and human HK H5 influenza virus isolates caused severe disease in mice, characterized by induced hypothermia, clinical signs, rapid weight loss, and 75 to 100% mortality by 6 to 8 days postinfection. Three of the non-HK-origin isolates caused no detectable clinical signs. One isolate, A/tk/England/91 (H5N1), induced measurable disease, and all but one of the animals recovered. Infections resulted in mild to severe lesions in both the upper and lower respiratory tracts. Most consistently, the viruses caused necrosis in respiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles with accompanying inflammation. The most severe and widespread lesions were observed in the lungs of HK avian influenza virus-infected mice, while no lesions or only mild lesions were evident with A/ck/Scotland/59 (H5N1) and A/ck/Queretaro/95 (H5N2). The A/ck/Italy/97 (H5N2) and the A/tk/England/91 (H5N1) viruses exhibited intermediate pathogenicity, producing mild to moderate respiratory tract lesions. In addition, infection by the different isolates could be further distinguished by the mouse immune response. The non-HK-origin isolates all induced production of increased levels of active transforming growth factor beta following infection, while the HK-origin isolates did not. (+info)