Nasal nitric oxide concentration in paranasal sinus inflammatory diseases. (1/317)

In normal upper airways, nitric oxide is generated by the paranasal sinus epithelium and then diffuses into the nasal cavities. This study examined whether or not nasal NO concentration is affected by paranasal sinus inflammatory diseases. The influence of obstruction (nasal polyposis) and/or inflammation (allergy or chronic sinusitis) of the paranasal sinuses on nasal NO concentration was evaluated in nasal allergic (n=7 patients) or nonallergic (n=20) polyposis, nonallergic chronic sinusitis (n=10) and Kartagener's syndrome (n=6) and compared with control subjects (n=42). A score of alteration of the paranasal sinus (number of altered and occluded sinuses) was determined by a computed tomography scan. The nasal NO concentration in nasal nonallergic polyposis (150+/-20 parts per billion (ppb)) was significantly decreased compared with both controls (223+/-6 ppb, p=0.01) and polyposis with allergy (272+/-28 ppb, p<0.0001). In each group, the nasal NO concentration was inversely correlated with the extent of tomodensitometric alteration of the paranasal sinuses. In Kartagener's syndrome, the nasal NO concentration (14+/-2 ppb) was drastically decreased compared with all other groups, despite the presence of open paranasal sinuses. Thus, the nasal NO concentration in patients with nasal polyposis appeared to be dependent on both the allergic status and the degree of obstruction of the paranasal sinuses.  (+info)

DeltaF508 CFTR protein expression in tissues from patients with cystic fibrosis. (2/317)

Heterologous expression of the cystic fibrosis transmembrane conductance regulator (CFTR) provided evidence that the major cystic fibrosis (CF) mutation DeltaF508 leads to defective protein folding in the endoplasmic reticulum, which prevents its processing and targeting to the cell surface. In this study, we investigated endogenous CFTR expression in skin biopsies and respiratory and intestinal tissue specimens from DeltaF508 homozygous and non-CF patients, using immunohistochemical and immunoblot analyses with a panel of CFTR antibodies. CFTR expression was detected at the luminal surface of reabsorptive sweat ducts and airway submucosal glands, at the apex of ciliated cells in pseudostratified respiratory epithelia and of isolated cells of the villi of duodenum and jejunum, and within intracellular compartments of intestinal goblet cells. In DeltaF508 homozygous patients, expression of the mutant protein proved to be tissue specific. Whereas DeltaF508 CFTR was undetectable in sweat glands, the expression in the respiratory and intestinal tracts could not be distinguished from the wild-type by signal intensity or localization. The tissue-specific variation of DeltaF508 CFTR expression from null to apparently normal amounts indicates that DeltaF508 CFTR maturation can be modulated and suggests that determinants other than CFTR mislocalization should play a role in DeltaF508 CF respiratory and intestinal disease.  (+info)

Role of allergy in nasal polyps of Thai patients. (3/317)

As distinct from many countries, allergy in Thailand is of the perennial type which may play a role in the formation of nasal polyps. Forty consecutive patients with nasal polyps and 30 normal subjects as control were studied at the Allergy Clinic, Department of Otolaryngology, Pramongkutklao Hospital. A positive clinical history and skin allergy testing are diagnostic criteria for allergy. In the nasal polyps group, these were 28 males and 12 females, aged between 12-65 years, with an average age of 38.5 years. In the control group, there were 18 males and 12 females, aged between 15-53 yeas, with an average age of 34 years. All had received prick skin testing with 6 common aeroallergens. The prick skin test was considered positive when the wheal was > or = 3 mm with surrounding erythema. Twenty-four of 40 patients (60%) with nasal polyps had a positive prick skin test, while 6 in the 30 control cases (20%) had a positive prick skin test. This difference was statistically significant (P = 0.0019), Odd's ratio = 6.0 which means allergic persons were 6 times more prone to have polyps form than normal persons.  (+info)

Glucocorticosteroids inhibit mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 in human airway inflammation with eosinophilia. (4/317)

How eosinophils are preferentially recruited to inflammatory sites remains elusive, but increasing evidence suggests that chemokines that bind to the CCR3 participate in this process. In this study, we investigated the transcript levels and chemotactic activity of CCR3-binding chemokines in nasal polyps, a disorder often showing prominent eosinophilia. We found that mRNA expression for eotaxin, eotaxin-2, and monocyte-chemotactic protein-4 was significantly increased in nasal polyps compared with turbinate mucosa from the same patients, or histologically normal nasal mucosa from control subjects. Interestingly, the novel CCR3-specific chemokine, eotaxin-2, showed the highest transcript levels. Consistent with these mRNA data, polyp tissue fluid exhibited strong chemotactic activity for eosinophils that was significantly inhibited by a blocking Ab against CCR3. When patients were treated systemically with glucocorticosteroids, the mRNA levels in the polyps were reduced to that found in turbinate mucosa for all chemokines. Together, these findings suggested an important role for CCR3-binding chemokines in eosinophil recruitment to nasal polyps. Such chemokines, therefore, most likely contribute significantly in the pathogenesis of eosinophil-related disorders; and the reduced chemokine expression observed after steroid treatment might reflect, at least in part, how steroids inhibit tissue accumulation of eosinophils.  (+info)

Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. (5/317)

BACKGROUND: Remarkable overlap exists in symptoms between asthma and chronic obstructive pulmonary disease (COPD), and the symptoms of the patients with mild asthma are often falsely thought to be caused by smoking. The objective of the study was to determine the prevalence of doctor-diagnosed asthma, asthmatic symptoms and doctor-diagnosed COPD in an adult population. The prevalence and relation to asthma of aspirin intolerance, nasal polyposis, allergic rhinitis and smoking habits were also examined. METHODS: Postal questionnaire survey of a population-based random sample (4300) of adult women and men aged 18-65 years served by the Paijat-Hame Central Hospital in southern Finland (a region with 208 000 inhabitants) was performed. RESULTS: The non-response-adjusted prevalence (Drane's linear method) of doctor-diagnosed asthma was 4.4% (95% CI: 3.3-5.5%) and of COPD 3.7% (95% CI: 2.7-4.8%). The prevalence of allergic rhinitis was 37.3% (95% CI: 33.3-41.2%), and of overall aspirin intolerance 5.7% (95% CI: 4.4-7.1%). The observed prevalence of aspirin intolerance causing shortness of breath or attacks of asthma was 1.2% and it was higher in patients with doctor-diagnosed asthma than without (8.8% versus 0.8%, relative risk [RR] = 11.4, P < 0.0001), and higher in those with allergic-like rhinitis than without (2.6% versus 0.3%, RR = 7.7, P < 0.0001). The prevalence of nasal polyposis was 4.3% (95% CI : 2.8-5.8%). CONCLUSIONS: The current prevalence of doctor-diagnosed asthma among adults is 4.4%, and allergic rhinitis, nasal polyposis and aspirin intolerance are associated with an increased risk of asthma. There is also association between aspirin-induced asthma and allergic-like rhinitis.  (+info)

Polyglutamylation and polyglycylation of alpha- and beta-tubulins during in vitro ciliated cell differentiation of human respiratory epithelial cells. (6/317)

Tubulins are the major proteins within centriolar and axonemal structures. In all cell types studied so far, numerous alpha- and beta-tubulin isoforms are generated both by expression of a multigenic family and various post-translational modifications. We have developed a primary culture of human nasal epithelial cells where the ciliated cell differentiation process has been observed and quantified. We have used this system to study several properties concerning polyglutamylation and polyglycylation of tubulin. GT335, a monoclonal antibody directed against glutamylated tubulins, stained the centriole/basal bodies and the axonemes of ciliated cells, and the centrioles of non-ciliated cells. By contrast, axonemal but not centriolar tubulins were polyglycylated. Several polyglutamylated and polyglycylated tubulin isotypes were detected by two-dimensional electrophoresis, using GT335 and a specific monoclonal antibody (TAP952) directed against short polyglycyl chains. Immunoelectron microscopy experiments revealed that polyglycylation only affected axonemal tubulin. Using the same technical approach, polyglutamylation was shown to be an early event in the centriole assembly process, as gold particles were detected in fibrogranular material corresponding to the first cytoplasmic structures involved in centriologenesis. In a functional assay, GT335 and TAP952 had a dose-dependent inhibitory effect on ciliary beat frequency. TAP952 had only a weak effect while GT335 treatment led to a total arrest of beating. These results strongly suggest that in human ciliated epithelial cells, tubulin polyglycylation has only a structural role in cilia axonemes, while polyglutamylation may have a function both in centriole assembly and in cilia activity.  (+info)

PKC signaling in CF/T43 cell line: regulation of NKCC1 by PKC-delta isotype. (7/317)

Cystic fibrosis (CF) airway epithelial cells have a reduced mass of ether-linked diacylglycerols which might alter protein kinase C (PKC)-regulated Cl secretion. PKC regulation of basolateral Na-K-2Cl cotransport (NKCC1) was investigated in CF nasal polyp epithelial cells and a CF/T43 cell line to ascertain whether PKC signaling was altered in CF. NKCC1 was detected as bumetanide-sensitive (86)Rb influx. Methoxamine, a alpha(1)-adrenergic agonist, increased PKC activity in cytosol and a particulate fraction for a prolonged time period, as predicted from previous studies on the generation of diglycerides induced with methoxamine. Short-term stimulation of CF/T43 cells for 40 s promoted a shift in PKC-delta and -zeta to a particulate fraction, increased activity of immune complexes of cytosolic PKC-delta and of particulate PKC-zeta and increased activity of NKCC1. Pretreatment with antisense oligonucleotide to PKC-delta blocked methoxamine-stimulated PKC-delta activity, reduced PKC-delta mass by 61.4%, and prevented methoxamine-stimulated activity of NKCC1. Sense and missense oligonucleotide to PKC-delta and antisense oligonucleotide to PKC-zeta did not alter expression of PKC-delta or the effects of methoxamine. These results demonstrate that PKC-delta-dependent activation of NKCC1 is preserved in CF cells and suggest that regulation of NKCC1 is independent of low ether-linked diglyceride mass.  (+info)

Inflammatory cells as well as epithelial cells in nasal polyps express vascular endothelial growth factor. (8/317)

In nasal polyps (NPs), locally secreted growth factors are involved in the remodelling of the epithelium and extracellular matrix but little is known concerning vessel remodelling. The in situ expression of vascular endothelial growth factor (VEGF) in NPs and control nasal mucosa (CM) were evaluated and in vitro secretion of VEGF from primary human cultures of nasal epithelial cells (HNECs) was quantified. VEGF expression was evaluated in NP (n=14) and CM (n=6) after immunolabelling. In supernatants from HNECs cultured at air/liquid interface, VEGF was quantified by immunoassay, under baseline conditions and after transforming growth factor-beta1 (TGF-beta1) stimulation. In HNEC lysates, VEGF and VEGF messenger ribonucleic acid (mRNA) were detected using Western blot analysis and reverse transcriptase polymerase chain reaction respectively. VEGF positivity was more frequent in inflammatory cells in NPs (14 of 14) than in CM (three of six) (p<0.05) and in the epithelium in NPs (six of 14) than in CM (two of six) (nonsignificant). Under baseline conditions, the VEGF concentration in HNEC culture medium increased from day 2 to 4, then decreased and became undetectable. VEGF concentrations increased significantly after TGF-beta1 stimulation. In HNEC lysates, VEGF and VEGF mRNA were detected on days 4 and 14 of culture. It was concluded that vascular endothelial growth factor is intensely expressed in situ in nasal polyps, mainly in inflammatory cells but also in epithelial cells. Human nasal epithelial cells are able to secrete in vitro vascular endothelial growth factor. Transforming growth factor-beta1 upregulates this secretion. This suggests that vascular endothelial growth factor, inducing oedema and angiogenesis, could be involved in the pathogenesis of nasal polyps.  (+info)

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