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)

To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases.
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PMID:Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases. 128 Sep 28

Of 65 patients presenting with pulmonary eosinophilia to one Respiratory Unit during a 20-year period, 12 (18%) had systemic features associated with their pulmonary disease. Eleven had fever, three night sweats, three arthralgia, three vasculitic rashes and two weight loss. Anaemia, myalgia, peripheral neuropathy, mononeuritis, pericardial effusion and photosensitivity rash were each recorded in single patients. None had evidence of hypersensitivity to drugs, helminthes or other allergens. Ten of the 12 patients could be classified as cryptogenic pulmonary eosinophilia and two as Churg Strauss syndrome. Ten were female. The maximum recorded eosinophil counts were higher in the 12 patients with systemic features compared with the remaining 53 patients [mean (SD) 5613 (3883) vs. 2359 (3046) x 10(6) 1(-1), P < 0.02], whereas both asthma and recurrent episodes of eosinophilia were significantly less common. Steroid therapy achieved a good clinical response and radiological clearing in the majority of patients. All 12 patients were treated with prolonged duration oral prednisolone [mean (SEM) dose 8.5 (3.8) mg day-1 duration 5.5 (1.3) years]. The two patients with Churg Strauss syndrome required azathioprine in addition to long-term prednisolone. There were no deaths and currently four patients are off all steroids and six receive less than 5 mg day-1. During a median follow-up period of 11 years, there was no significant decline in FEV1 or VC, measured as percent predicted values. Persistent radiographic abnormalities consistent with fibrosis or bronchiectasis were not seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary eosinophilia with systemic features: therapy and prognosis. 147 Jul 5

An enzyme-linked immunosorbent assay (ELISA) was developed to measure total amoxicillin concentrations penetrating lung secretions, which were compared with "active" concentrations measured by conventional bioassay. An antibody was raised in rabbits to amoxicillin conjugated to bovine serum albumin and used in a competitive binding ELISA (sensitivity, 10 ng/ml; precision [coefficient of variation], 9%). The measurement of amoxicillin in lung secretions by using the ELISA method was verified by high-performance liquid chromatography. Amoxicillin concentrations were found to be similar in both whole sonicated sputum and sol-phase sputum obtained by ultracentrifugation following single oral doses of 3 g (4.6 mg/liter for sonicated and 4.7 mg/liter for sol-phase preparations) and 250 mg (0.23 mg/liter for both preparations). Eight patients with bronchiectasis received 500 mg of amoxicillin three times daily. On the second day of therapy (4 h after the morning dose), the mean concentration of amoxicillin in sputum was 0.88 mg/liter (standard error of the mean [SEM], 0.11) by ELISA and 0.40 mg/liter (SEM, 0.05) by bioassay, suggesting a significant degree of local inactivation. This difference between total and active amoxicillin levels was found to correlate significantly (r = 0.693; P less than 0.05) with beta-lactamase levels (mean, 29.5 mU/ml; SEM, 9.4). A pharmacokinetic study on day 3 revealed maximum levels in secretions 2 to 4 h after dosing (mean, 1.36 mg/liter; SEM, 0.26). At the end of successful therapy (day 14), total and active levels were lower (mean, 0.48 mg/liter; SEM, 0.11 [total]; mean, 0.21 mg/liter; SEM, 0.06 [active]); this result was associated with a reduction in lung inflammation (decreased serum-derived albumin in the lung secretions). In conclusion, antibiotic penetration is partly dependent on the degree of lung inflammation. The differences observed in total and active levels of amoxicillin and the relationship to beta-lactamase activity in sputum suggest why higher doses of antibiotic may be required to produce a therapeutic response in some patients.
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PMID:Use of an enzyme-linked immunosorbent assay to assess penetration of amoxicillin into lung secretions. 151 Apr 53

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

Chronic pulmonary infection/colonization caused by Pseudomonas aeruginosa accounts for much of the morbidity and mortality in cystic fibrosis (CF). The effect of chronic pulmonary P. aeruginosa infection on the pulmonary circulation has not been studied. Therefore, we investigated the effect of chronic P. aeruginosa infection on pulmonary hemodynamics in a rat model. Two groups of rats were inoculated with either agar beads containing 1.0 x 10(4) colony-forming units of P. aeruginosa (infected) or an equal volume of sterile beads alone (control). In vivo, pulmonary vasoreactivity measured as the percent change in total pulmonary resistance during hypoxia was decreased at 1 wk (22 +/- 7% versus 57 +/- 3%), 2 wk (29 +/- 5% versus 73 +/- 17%), 3 wk (41 +/- 8% versus 77 +/- 14%), and 6 to 9 wk (23 +/- 10 versus 53 +/- 7; p less than 0.05 all time points; mean +/- SEM) postinoculation in infected animals when compared with that in time-matched control animals. At 6 to 9 wk postinoculation, pulmonary artery pressure was significantly elevated in infected rats (25.8 +/- 1.6 versus 21.0 +/- 1.0 mm Hg; p less than 0.05) when compared with that in control animals. Histopathologic findings were characterized by bronchiectasis as well as by chronic bronchial, parenchymal, and perivascular inflammation at all time points in infected animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased pulmonary vasoreactivity in an animal model of chronic Pseudomonas pneumonia. 236 72

The long-term pulmonary consequences of right middle lobe syndrome (RMLS) in childhood are not known. Therefore, outcome was evaluated in 17 children with RMLS diagnosed in early childhood (mean age, 3.3 years; SD, 1.1 year). Mean age at follow-up was 10.1 years (SD, 2.6 years). RMLS was defined as atelectasis of the right middle lobe (RML) of at least 1 month's duration and visible on the lateral view of the chest radiograph as a wedge-shaped density extending from the hilum anteriorly and downward. Seventeen children without personal history of allergy or respiratory tract disease were studied as control group. Five of 17 study group children had ongoing respiratory problems: symptoms of asthma were present in 4 patients, and cylindrical bronchiectasis was present in one patient. Chest radiograph at follow-up was abnormal in six patients. Pulmonary function tests, including mean and SEM for vital capacity (VC) (82% of predicted +/- 7 vs 94% predicted +/- 3), FEV1 (77% of predicted +/- 12 vs 96% of predicted +/- 4) and their ratio (75 +/- 5 vs 85 +/- 3) were significantly lower in patients with ongoing respiratory symptoms than in the control children. The provocative dose causing a 20% decrease in FEV1 (PD20) of methacholine was significantly lower in patients with ongoing symptoms at follow-up than in control children and in patients without symptoms at follow-up (2.8[2.2 to 3.1] vs 4.5[2.2 to 8.8] and 9.2[2.3 to 24] mg/mL; median and P25-75, p < 0.05). Age at initial diagnosis tended to be younger in patients with ongoing symptoms at follow-up (2.3 +/- 0.7 years vs 3.8 +/- 0.4 years; p < 0.08).
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PMID:Outcome after right middle lobe syndrome. 760 50

It is hypothesized that emphysema develops in some severely alpha 1-antitrypsin (AAT)-deficient persons because endogenous elastases are not adequately controlled by AAT, and accelerated elastin degradation occurs. It is not known whether augmentation therapy with AAT diminishes degradation of lung elastin in severely deficient persons with lung disease. Two severely deficient, PiZ patients were studied, a 63-year-old never-smoking woman with bronchiectasis and a 41-year-old smoking man with emphysema. Urinary desmosine (DES) was determined before and after augmentation therapy with AAT, 260 mg/kg/month. Mean +/- SEM pretreatment urinary DES was elevated in both patients, 19.7 +/- 0.9 (n = 2) and 10.8 +/- 0.2 (n = 2) micrograms/g creatinine, respectively, compared to normal values of 7.5 +/- 0.3 (n = 22) micrograms/g creatinine. Following augmentation therapy, urinary DES values decreased 40 and 36%, respectively, to 11.9 +/- 0.3 (n = 8) and 6.9 +/- 0.4 (n = 7) microgram/g creatinine (p < 0.05). We conclude that monthly AAT augmentation therapy decreased DES excretion in the urine of these PiZ patients. We speculate that since there was lung disease in both patients, a decrease in degradation of lung elastin is the most likely explanation for this observation.
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PMID:Preliminary evidence that augmentation therapy diminishes degradation of cross-linked elastin in alpha-1-antitrypsin-deficient humans. 778 13

The follicular form of bronchiectasis originally described by Whitwell (1) has been associated with adenoviral infection. The present study compares resected lungs from 16 patients with follicular bronchiectasis (in 10 of whom a nonviral etiology was identified) with those from eight patients with a nonfollicular histologic pattern. DNA isolated from sections of 45 paraffin-embedded lung samples was subjected to the polymerase chain reaction (PCR) using primers for the E1A region of the adenovirus genome and the human HLA DQ alpha gene. In situ hybridization (ISH) was performed on separate sections cut from the same blocks using a probe for the entire adenovirus 5 genome. E1A was demonstrated in six of eight patients (75%) with non-follicular bronchiectasis (non-FB) and in four of 16 (25%) with follicular bronchiectasis (FB) (p < 0.03, Fisher's exact test). The optical density ratio for the E1A product of PCR (ratio of E1A product from specimen to that from 1 pg adenovirus DNA) was significantly lower in FB than in non-FB (0.057 +/- 0.054 versus 0.365 +/- 0.223 [mean +/- SEM], p < 0.05). Moreover, the duration of symptoms of bronchiectasis in patients without E1A in bronchial specimens was significantly shorter than that of patients with positive E1A PCR products (3.09 +/- 1.44 versus 14.41 +/- 3.33 yr; p < 0.05). By ISH, adenovirus was demonstrated in three patients with FB and in two with non-FB (17.2 and 18.8% of tissue blocks, respectively; NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Latent adenoviral infection in follicular bronchiectasis. 919 25

To investigate the mechanisms of eosinophil activation in the airways of patients with asthma, we attempted to detect eosinophil-activating cytokines in sputum extracts obtained from asthmatic patients during acute attacks or in remission by eosinophil survival assay. Purified guinea pig eosinophils were cultured in the presence or absence of sputum extracts, and the eosinophil viability was measured on Day 4. Eosinophil viability in the presence of sputum extracts derived from patients during moderate or severe attacks was significantly higher than that for sputum obtained from patients in remission or during mild attacks or from those with other respiratory diseases, including bronchiectasis and diffuse panbronchiolitis (p < 0.05). The total symptom score during the week prior to sputum collection correlated with the eosinophil viability (rs = 0.79, p < 0.01). Eosinophil viability-enhancing activity (EVEA) in the sputum of asthmatic patients with moderate or severe attacks was neutralized by anti-IL-5 antibody and by anti-GM-CSF antibody by 19.9 +/- 13.7% and 76.9 +/- 8.2% (mean +/- SEM, n = 7), respectively. EVEA was completely neutralized by a combination of anti-IL-5 and anti-GM-CSF antibodies. There was a significant correlation between the concentration of eosinophil cationic protein (ECP) in sputum extracts and the eosinophil viability (rs = 0.54, p < 0.05). These findings suggest that IL-5 and GM-CSF are present in the sputum during asthma attacks and that these cytokines are at least partially responsible for eosinophil activation in asthma.
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PMID:Eosinophil viability-enhancing activity in sputum from patients with bronchial asthma, Contributions of interleukin-5 and granulocyte/macrophage colony-stimulating factor. 788 46

Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.
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PMID:In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion. 857 72


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