Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Maximal binding capacity (Bmax) and the dissociation constant (KD) for the beta-adrenoceptor antagonist 125I-cyanopindol were estimated in membrane preparations of hilar, lobar/main bronchi (level I) and peripheral lung (level II) of grossly normal lungs resected for bronchial carcinoma. The tissue distribution of 125I-cyanopindol-binding sites was assessed by autoradiography of complementary cryostat sections. The data obtained from the resections for carcinoma and bronchiectasis were used as disease controls for comparison with those obtained from patients with cystic fibrosis and asthma. 2. In carcinoma controls, mean Bmax values (+/- SEM) for airway levels I and II were 89 +/- 4 and 133 +/- 6 fmol/mg of protein, respectively (P less than 0.01). The corresponding KD values at each airway level were similar, i.e. 29 +/- 2 and 33 +/- 1 pmol/l, respectively. Autoradiography revealed that there was dense labelling of bronchial and bronchiolar epithelium and most strikingly of the alveolar wall. 3. Compared with carcinoma controls, mean Bmax values in cystic fibrosis were significantly reduced in membrane preparations of both airway levels I and II (P less than 0.01). Autoradiography showed the reduction was most apparent in alveolar wall and bronchial epithelium. 4. There was a tendency to reduction of Bmax in membrane preparations from patients with bronchiectasis at airway level I, but this failed to reach statistical significance. Autoradiography demonstrated that the density of labelling was significantly reduced in bronchial epithelium and bronchial smooth muscle as compared with carcinoma controls (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Airway beta-adrenoceptor number in cystic fibrosis and asthma. 197 Dec 4

Digital clubbing and pulmonary function tests were measured in children, adolescents, and adults with chronic lung diseases to determine pulmonary function correlates with a quantitative measure of clubbing. The group had a mean age of 13.8 +/- 6.0 (SD) years, mean PaO2 of 81 +/- 21 mm Hg, and mean FEV1 of 60% +/- 26% predicted. Digital clubbing was diagnosed in 43 cases when the distal phalangeal depth to interphalangeal depth (DPD/IPD) ratio, measured on a finger cast, was greater than or equal to 1 (greater than 3 SD above mean from 85 controls; no history of pulmonary disease; mean age, 14.8 +/- 7.6). The PaO2 of patients with digital clubbing was 69.4 +/- 2.1 (SEM) mm Hg compared with 88.3 +/- 1.3 mm Hg in those without digital clubbing (P less than 0.0001). Digital clubbing was present in 39 of the 84 (46%) hypoxic patients (PaO2 less than or equal to 88) but only four of the 78 (5%) normoxic patients (P less than 0.0001). The DPD/IPD ratio was negatively correlated with PaO2 in subjects with cystic fibrosis and interstitial fibrosis. Weak negative correlations were seen for all other subjects except asthmatics. Overall, the DPD/IPD ratio was significantly correlated with PaO2 (r = -0.53; P less than 0.0001). The DPD/IPD ratio was correlated with other lung function abnormalities (increased RV, decreased FEV1, and FEF25%-75%) only for the subjects with cystic fibrosis. We conclude that digital clubbing is associated with hypoxemia and airway obstruction. The relation is seen most clearly in subjects with cystic fibrosis, possibly reflecting the prolonged duration of hypoxemia. Digital clubbing is rarely seen in normoxic subjects.
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PMID:Digital clubbing and pulmonary function abnormalities in children with lung disease. 200 43

Measurement of the potential difference (PD) across the airways provides an indication of the viability and integrity of the lining epithelium. PD was recorded from the lower airways in "diseased controls" and in patients following heart-lung transplantation. Diseased controls showed a high PD centrally which fell (became less negative) peripherally (trachea -15.8 mV (SEM 1.0), lobar bronchi -12.6 mV (1.2), segmental bronchi -9.8 mV (1.2]. Following heart-lung transplantation (HLT) the profile of PD with airway size was altered in comparison to non-transplanted patients with reduced values in the large airways. Host tracheal values above the anastomosis were similarly reduced. Two episodes of rejection were associated with a lower mean airway PD; no significant changes were found with infection. In patients with cystic fibrosis (CF), values in the donor lung did not differ from those in non-CF transplanted patients up to one year following transplantation, although nasal PD in the host remained elevated. HLT selectively alters the PD profile only of larger airways, which may relate to the interruption of the bronchial arterial supply to these sites.
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PMID:Effect of heart-lung transplantation on airway potential difference in patients with and without cystic fibrosis. 202 38

The effect of positive expiratory pressure breathing, alone and in combination with coughing, was investigated in eight patients with cystic fibrosis. Functional residual capacity and total lung capacity was measured with a body plethysmograph before, during, and immediately after breathing with expiratory pressure of 5 and 15 cm H2O, and after a coughing period. The positive expiratory pressure breathing was carried out five times for two minutes with a two minute interval between each period. Mucus transport was measured in a peripheral lung region and over the whole lung by a radioactive aerosol tracer technique. Clearance measurements were carried out continuously during positive expiratory pressure breathing and during a control period. Two minutes' breathing with an expiratory pressure of 5 and 15 cm H2O caused an increase in mean (SEM) functional residual capacity from 2.6 (0.1) to 3.6 (0.3) and 4.4 (0.5) 1 and an increase in total lung capacity from 5.1 (0.2) to 5.9 (0.3) and 6.9 (0.4) 1. Lung volumes were higher during breathing with an expiratory pressure of 15 cm H2O than with 5 cm H2O; both returned to baseline values immediately after positive expiratory pressure breathing. Spontaneous mucus clearance and mucus clearance by coughing were not influenced by positive expiratory pressure breathing at either expiratory pressure. Thus in patients with cystic fibrosis positive expiratory pressure breathing increases lung volumes in relation to the expiratory pressure imposed; these changes in lung volume did not, however, lead to an improvement of mucus transport.
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PMID:Effect of positive expiratory pressure breathing in patients with cystic fibrosis. 153 53

Basic research into cystic fibrosis (CF) has been hampered by the lack of a suitable animal model. Reserpinized or isoproterenol-treated rats have been proposed as models because they exhibit certain morphological and physiological features characteristic of CF. Recent evidence suggests that abnormal epithelial transport of Na+ [corrected] and Cl- may underlie pathogenesis, defects that may contribute to the markedly more negative transepithelial electrical potential differences (PD) recorded in CF airways compared with controls. To test the models further, we measured tracheal PD in vivo in treated rats (reserpinized - 6.9 mV, SEM 0.7 mV, n = 7; isoproterenol-treated -10.2 mV, SEM 1.5 mV, n = 12) and found it to be no different from that of controls (-8.7 mV, SEM 0.6 mV, n = 25). The animals did, however, demonstrate a reduced gain in body weight as well as increased submaxillary gland weight, which reflected an increased mucus content in the acini. These observations suggest that although the reserpinized or isoproterenol-treated rat may be useful in the study of the pathogenesis of exocrine disturbances in disease, their use as models for the effect of the basic defect of CF in the airways may be limited.
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PMID:Tracheal potential difference in the reserpine and isoproterenol rat models of cystic fibrosis. 208 7

Retrospective studies have reported that tracheal enlargement is common in patients with cystic fibrosis (CF). To determine whether significant tracheal enlargement occurs in these patients, we used the acoustic reflection technique to prospectively measure the tracheal cross-sectional area near functional residual capacity (FRC) in 39 stable outpatients with CF and 39 age- and sex-matched normal control subjects. The patients with CF had a mean age of 19.0 yr with a mean percent predicted FEV1 of 69%. The mean +/- SEM tracheal area of the patients with CF was 1.99 +/- 0.13 cm2, compared with a mean tracheal area of 1.87 +/- 0.10 cm2 in the control subjects (t = 0.79, NS). CF tracheal area was not a function of age nor of disease severity, as assessed by percent predicted FEV1. To determine whether tracheomegaly might occur only in older patients, we examined the six patients with CF who were 28 yr of age or older. Mean tracheal area for these older patients with CF was 2.46 +/- 0.26 cm2, compared with 2.27 +/- 0.10 cm2 for the control subjects (t = 0.70, NS). Eleven patients with CF also had their tracheal area measured near TLC. At this high lung volume, the tracheal area of the patients with CF was 2.62 +/- 0.23 cm2, significantly larger than the 1.91 +/- 0.13 cm2 in 11 control subjects (t = 2.68, p less than 0.02). The increase in tracheal area per change in lung volume was also significantly greater in the patients with CF than in the control subjects (t = 3.33, p less than 0.01). We conclude that near FRC the tracheal size of patients with CF is not different from that of age- and sex-matched control subjects. The tracheas of patients with CF expand more than do the tracheas of control subjects when higher lung volumes are attained, suggesting increased airway distensibility.
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PMID:Tracheal size and distensibility in patients with cystic fibrosis. 225 68

It has been shown that pulmonary macrophage (PM) phagocytosis of Pseudomonas aeruginosa (PA) is inhibited in the presence of serum from cystic fibrosis (CF) patients colonized by Pseudomonas, and that these sera contain high concentrations of IgG2 antibodies. The goal of these studies was to investigate the role that IgG2-containing immune complexes (IC) play in this inhibition of both PM and neutrophil phagocytosis. We found that serum IgG2 concentrations were elevated significantly in CF patients with chronic PA colonization and that in selected sera from CF patients with chronic PA colonization (CF + IC, n = 10), the mean IC level was significantly elevated (2.90 +/- 0.22 mg/dl [SEM]). IgG2 comprised 74.5% of IgG precipitated in IC from CF + IC sera. An invitro phagocytic assay of [14C]PA uptake using CF + IC whole-sera opsonins confirmed that endocytosis by normal PM and neutrophils was significantly depressed. Removal of IC from CF + IC sera resulted in significantly decreased serum IgG2 concentrations without a significant change in the other subclass concentrations, and enhanced [14C]PA uptake by PM (26.6% uptake increased to 47.3%) and neutrophils (16.9% increased to 52.6%). Return of the soluble IgG2 IC to the original CF sera supernatants and the positive control sera resulted in return of the inhibitory capacity of the CF + IC sera. We conclude that immune sera from patients with chronic Pseudomonas infections characterized by elevated IgG2 subclass level functions poorly as an opsonin. In these individuals, IgG2 contributes significantly to circulating IC and removal of IC, matched by a simultaneous fall in IgG2, improves bacterial uptake by neutrophil and mononuclear phagocytes. IgG2 antibodies exert antiphagocytic effects by both direct inhibition and the formation of IC.
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PMID:The immunoglobulin G subclass composition of immune complexes in cystic fibrosis. Implications for the pathogenesis of the Pseudomonas lung lesion. 212 Feb 86

Excessive active absorption of sodium is a unique abnormality of the airway epithelium in patients with cystic fibrosis. This defect is associated with thickened mucus and poor clearance of airway secretions and may contribute to the pulmonary disease in these patients. To study whether the inhibition of excessive absorption of sodium might affect the course of lung disease in cystic fibrosis, we performed a double-blind, crossover trial comparing aerosolized amiloride (5 mmol per liter; 3.5 ml four times daily), a sodium-channel blocker, with vehicle alone. Fourteen of the 18 adult patients initially enrolled in the study completed the one-year trial (25 weeks for each treatment). The mean (+/- SEM) loss of forced vital capacity (FVC) was reduced from 3.39 +/- 1.13 ml per day during treatment with vehicle alone to 1.44 +/- 0.67 ml per day during treatment with amiloride (P less than 0.04). A measured index of sputum viscosity and elasticity was abnormal during treatment with vehicle alone and improved during treatment with amiloride. Calculated indexes of mucociliary and cough clearance also improved during amiloride treatment. No systemic, respiratory, or subjective toxic effects of amiloride were noted. We conclude from this preliminary study that aerosolized amiloride can be safely administered to adults with cystic fibrosis. The slowing of the loss of FVC and the improvement in sputum viscosity and elasticity suggest a beneficial clinical effect. Aerosolized amiloride deserves further evaluation in the treatment of lung disease in patients with cystic fibrosis.
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PMID:A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis. 240 69

Peripheral blood monocytes were obtained from 19 patients with cystic fibrosis (CF) and age-matched paired normal individuals. The oxidative metabolic response of these cells was measured by superoxide anion production before and after stimulation with Salmonella typhimurium or Pseudomonas aeruginosa lipopolysaccharide (LPS). CF monocytes showed slightly greater spontaneous superoxide anion production (14.1 +/- 2.1 SEM nanomoles superoxide anion/10(6) monocytes/180 min; n = 12) than normal monocytes (9.5 +/- 1.4; n = 12), P = 0.009. No differences between CF and normals were found in LPS-stimulated superoxide anion production (CF = 33.5 +/- 4.6, n = 13; normal = 33.8 +/- 4.2, n = 13). Furthermore, CF monocytes responded to both P. aeruginosa and S. typhimurium LPS stimulation as well as to recombinant interferon-gamma. Superoxide anion production of CF monocytes was comparable in autologous serum and in normal serum, and responses of patients colonized with P. aeruginosa and P. cepacia did not differ. We conclude that CF monocytes have a slightly increased metabolic level and, despite chronic infection, are capable of a further response to exogenous microbial stimuli.
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PMID:Monocytes in cystic fibrosis: responsiveness to microbial stimuli. 216 9

Lithium is known to affect several aspects of cellular regulation which may be related to ion channel function in epithelial cells. To determine whether the ion transport abnormality in cystic fibrosis (CF) is affected by lithium with resultant changes in clinical status, 36 CF patients, 12-37 years old, were enrolled in a 14 week, double-blind, placebo-controlled trial. Eighteen patients were randomly assigned to receive lithium carbonate for 10 weeks. At the end of therapy their average serum lithium concentration was 0.56 +/- 0.06 mmol (SEM) per liter. Their sweat chloride concentration fell from 92.1 +/- 4.8 mmol per liter to 87.4 +/- 4.0 mmol per liter after 10 weeks of therapy (P = 0.07) and rose to 94.4 +/- 3.5 mmol per liter 4 weeks after end of therapy (P less than 0.001 compared to results at end of therapy). Their forced vital capacity (FVC) fell from 72 +/- 5.3% of predicted to 66 +/- 5.1% of predicted after 4 weeks of therapy (P less than 0.01), and their forced expiratory volume in one second (FEV1) fell from 56 +/- 5.5% of predicted to 51 +/- 5.5% of predicted after 4 weeks of therapy (P less than 0.01). In a non-blind assessment, performed 19 weeks after the end of therapy, their FVC and FEV1 had risen and were not significantly different from baseline. Sweat chloride, FVC, and FEV1 remained unchanged in the placebo group throughout the period of study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does lithium carbonate affect the ion transport abnormality in cystic fibrosis? 219 Dec 60


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