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

Asthma is associated with dysfunction of the beta-adrenergic receptor adenylyl cyclase signal transduction pathway. It has been argued that this results from receptor down-regulation by beta-agonist therapy. This study examined the relationship between nonspecific bronchial responsiveness (NSBR) to methacholine (Newcastle dosimeter method) and beta-adrenergic receptor density (Bmax) and affinity (%KH) in membranes from peripheral blood mononuclear leukocytes (MNL) in 12 male (27.3 +/- 1.7 yr old) and 14 female (31.4 +/- 1.7 yr old) drug-naive subjects with and without symptoms of mild intermittent wheezing. None had ever smoked or received any antiasthma medication. "Hyperresponsive" subjects were defined as those (n = 11) whose simplified slope of FEF50 (calculated as the percent fall in FEF50 divided by the dose of methacholine) was more than one SD above the mean for asymptomatic subjects. The log of the slope was reproducible (repeatability coefficient = 0.43) on two nonconsecutive days. Multiple regression analysis (overall R2 = 0.57) revealed negative relationships between the log of the slope and both Bmax (p = 0.016) and %KH (p = 0.011). Analysis of variance confirmed a lower mean (+/- SEM) value of %KH in "hyperresponsives" (45.7 +/- 5.5%) than in "normoresponsives" (60.4 +/- 4.1%, p = 0.04) with a similar trend for Bmax (hyperresponsives = 33.5 +/- 4.1 fmol/mg, normoresponsives = 45.9 +/- 7.1 fmol/mg, p = 0.18). These relationships between bronchial responsiveness, Bmax, and %KH cannot be explained by drug therapy, and they provide further evidence that there is an intrinsic impairment in the function of beta-adrenergic receptors on peripheral MNLs from subjects with high levels of nonspecific bronchial responsiveness.
 ...
PMID:Relationship between nonspecific bronchial responsiveness to methacholine and peripheral mononuclear leukocyte beta-adrenergic receptor function in young drug-naive subjects. 132 48

Asthma morbidity increases in the Canadian autumn coincident with the beginning of home heating. To test the hypothesis that forced air heating exacerbates asthma, 51 subjects were randomly assigned to one of two groups: the intervention (off1-on2) group was instructed to keep their home forced air heating off from September 9 to 17 and then to set the thermostat to 22 degrees C from 8 PM to 8 AM between September 18 and 25. The concurrent control (off1-off2) group was instructed to keep their forced air heating off during the entire study period. Forty-eight of the 51 subjects randomized recorded morning peak flows, asthma symptoms, and bronchodilator use during the study period. For the intervention group, results before compared with during home heating, respectively, were as follows: mean nocturnal awakenings 0.36 versus 0.36; any breathing difficulties an awakening 82% versus 73%; mean morning peak flows 406 lpm versus 409 lpm, a difference of 3.3% +/- 6.7% (SEM), p = 0.6. There was a 95% probability that the true change in peak flows with forced air was less than 2%. For the control group, the comparable results were as follows: mean nocturnal awakening 0.40 versus 0.47; breathing difficulties on awakening 40% versus 47%; mean morning peak flows 400 lpm versus 399 lpm (p = 0.9). The commencement of forced air heating did not exacerbate asthma in this clinical population and is therefore unlikely to be an important problem for most people suffering from asthma.
 ...
PMID:Does forced air heating exacerbate asthma? 143 Jul 5

This study was undertaken to investigate the effect of theophylline on serum uric acid levels in children with asthma. Twenty-seven asthmatic children, including 21 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Serum uric acid levels were increased in the asthmatic children treated with theophylline compared to those not receiving this agent (6.28 +/- 0.29 mg/dl, mean +/- SEM, vs. 4.82 +/- 0.52 mg/dl, p < 0.05). A significant positive correlation between the serum levels of uric acid and theophylline was demonstrated in the patients of this study (rs = 0.596, p < 0.01). All the patients in whom theophylline administration was stopped showed significant decreases in serum uric acid levels (p < 0.05). From these results, we conclude that theophylline increases serum uric acid levels in children with asthma, just as it does in adult asthmatics.
J Asthma 1994
PMID:Effect of theophylline on serum uric acid levels in children with asthma. 792 34

In the present study, we evaluated the effect of roxithromycin, a semisynthetic macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma. Ten hospitalized asthmatic children (8 boys and 2 girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. All the patients underwent AA inhalation challenge before and 2, 4, and 8 weeks after the administration of roxithromycin. Seven of the 10 patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent UNDW inhalation challege at the same time. The cough threshold values, the lowest concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20% fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05). No significant change was observed in baseline FEV1 or serum theophylline concentrations throughout the study. These results support the notion that administration of roxithromycin may have favorable results in the treatment of childhood asthma.
J Asthma 1997
PMID:Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction in children with asthma. 916 48

The purpose of this study was to determine the characteristics of predominantly nonwhite patients with recurrent visits to the emergency department (ED) and admissions to an inner-city hospital in Chicago for acute asthma. Over a 21-month period, two groups of age and gender-matched individuals with asthma seen at the University of Illinois at Chicago Medical Center were studied: group I included 26 patients with frequent visits to the ED and no more than one admission for acute asthma/year; and group II included 28 patients with recurrent visits to the ED and two or more admissions for acute asthma/year. We found that 70% of all patients (38/54) were females and 72% (39/54) were African-Americans. The latter predominated in group II (25/28; 89%). There were no significant differences in public aid recipients, baseline FEV1, type of antiasthma medications used, and illicit drug use between the two groups. However, group II reported more asthma onset before the age of 11 years and used higher daily doses of inhaled corticosteroids than group I (p < 0.05). The average duration of hospital stay in group II was significantly longer (3.3 +/- 0.4 days vs. 2.4 +/- 0.3 days, respectively, mean +/- SEM, p < 0.05), and the average cost per hospitalization in group II significantly exceeded that of group I ($5122 +/- $590 vs. $3740 +/- $450, respectively, p < 0.05). We conclude that African-American females are seen more frequently in the ED for acute asthma and admitted to the hospital in Chicago. They develop asthma before the age of 11 years, use higher daily doses of inhaled corticosteroids, and contribute significantly to the high cost of asthma care.
J Asthma 1997
PMID:Characteristics of predominantly nonwhite patients with frequent hospitalizations for acute asthma in Chicago. 916 52

Taking advantage of a natural experimental situation, we compared, retrospectively, functional results after nasalization and ethmoidectomy for diffuse nasal polyposis. Nasalization was a radical ethmoidectomy systematically removing all the bony lamellae and mucosa within the labyrinth, with large antrostomy, sphenoidotomy, frontotomy, and middle turbinectomy (Surgeon 1, 39 consecutive patients operated on between March and September 1991). Ethmoidectomy was a less systematic procedure, that was adapted to the extent of the pathology (Surgeon 2, 37 consecutive patients, operated on between October 1991 and November 1994). In May 1994, a third physician mailed a questionnaire simultaneously to all patients including 10-point visual analog scales 34/39 patients in the nasalization group (age: 28-71 years: 20 asthmatics; follow-up: 32-36 months), and 29/37 patients in the ethmoidectomy group (age: 26-65 years: 9 asthmatics: follow-up: 18-31 months) participated in the study. The overall nasal improvement was 8.8 +/- 0.2 (mean +/- SEM) after nasalization and 5.9 +/- 0.6 after ethmoidectomy (p = 0.0001). Olfaction improvement was similar in both groups 6 months after surgery, remained at the same level 36 months after nasalization (6.9 +/- 0.7), but decreased to 4.2 +/- 1 points 24 months after ethmoidectomy (p = 0.02). Asthma improvement remained significantly better after nasalization (p = 0.05), and the need for systemic steroids was also lower (p = 0.03). Results of this study suggest that when dealing with nasal polyposis, the more radical the surgery, the better the functional results.
 ...
PMID:Comparison of functional results after ethmoidectomy and nasalization for diffuse and severe nasal polyposis. 928 20

It is well known that workers occupationally exposed to grain dust have a high prevalence of respiratory symptoms, but their pathogenesis remains obscure when sensitization to cereal flour cannot be demonstrated. Storage mites, tenebroids, and cockroaches are stored-grain pests found in grain and cereal products frequently in our area, where the cereal industry is the most important industry. An epidemiological analysis of sensitization of these stored-grain pests was performed on 4379 patients residing in an area of cereal industries. Fifty grain workers were selected for in vivo diagnostic tests with nine genera of mites, Tenebrio molitor and Blatta orientalis. Specific IgE antibodies to the extracts were demonstrated by prick tests and RAST. Association between respiratory symptoms and occupational exposure was confirmed by challenge tests (specific and methacholine). The prevalence of mite sensitization in the total sample studied (4379) was 18.96% (SEM 0.58, 95% CI 16.93-19.19). The prevalence of sensitization to storage mites among mite-sensitive patients was 11.88% (SEM 1.15, 95% CI 9.63-14.3). Among the 50 selected patients the most frequent sensitization was that to Dermatophagoides pteronyssinus (58%), followed by Dermatophagoides frinae (48%), Lepidoglyphus destructor and Tyrophagus putrescentiae (38%), Blomia kulagini (34%), and Acarus siro and Chortoglyphus arcuatus (24%). In addition, 22% of the patients presented negative prick tests and RAST for Dermatophagoides species with positive test to storage mites. Fifty percent of the 50 patients were sensitizated to Tenebrio molitor (SEM 0.7, CI 95% 36-64), and 36% to Blatta orientalis (SEM 0.67, CI 95% 23-49). The identification of mites, tenebroids, and cockroaches in dust samples yields useful data for the diagnosis of our patients.
J Asthma 1997
PMID:Occupational allergic disease in cereal workers by stored grain pests. 935 Jan 53

In 1997 the NHLBI updated guidelines for the diagnosis and management of asthma. We hypothesized that not all components of the updated guidelines are well understood by the physicians who care for asthmatics. To develop appropriate educational interventions that address areas of physician misunderstanding, it is important to identify these components. Based upon NHLBI guidelines, we developed a multiple-choice test of asthma knowledge that was distributed to physicians at the University of Iowa; 108 physicians completed the test, including 20 asthma specialists, 11 asthma specialty fellows, 11 General Medicine faculty, five Family Medicine faculty, 51 Internal Medicine residents, and five Family Medicine residents. The mean correct total score for all physicians was 60 +/- 2% (mean +/- SEM). Asthma specialists scored higher in total score and in pharmacology and prevention. However, no group performed well on estimating disease severity. We further identified deficits in the use of spirometry and anti-inflammatory agents in caring for asthmatic patients. Thus, deficits exist in physician understanding and implementation of the NHLBI guidelines for the diagnosis and management of asthma. By identifying specific areas of misunderstanding, we can design better educational interventions. Clearly, educational programs should emphasize new models for estimating chronic disease severity.
 ...
PMID:Asthma guidelines: an assessment of physician understanding and practice. 1061 37

Nitric oxide (NO) is an important endogenous regulatory molecule implicated in both proinflammatory and antiinflammatory processes in the lung. Previously, we demonstrated that in human alveolar macrophages (AM), NO decreased inflammatory cytokine production, including that of interleukin-1beta, tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha. One mechanism by which NO could regulate such diverse cytokine production is through effects on the transcription factor nuclear factor-kappaB (NF-kappaB), which controls the expression of the genes for these inflammatory cytokines and growth factors. We therefore investigated whether NO affects NF-kappaB activation in AM in vitro and in vivo. In vitro studies with AM showed that NF-kappaB activation by lipopolysaccharide (LPS) is decreased by NO in a dose-dependent manner. NO prevented an LPS-mediated decrease in the NF-kappaB inhibitory protein IkappaB-alpha. In asthma, airway NO levels are increased, whereas in primary pulmonary hypertension (PPH), airway NO levels are lower than in healthy lungs. In vivo investigations were conducted with freshly isolated AM from healthy controls, asthmatic individuals, and PPH patients. Healthy individuals had airway NO levels of 8 +/- 2 ppb (mean +/- SEM), which is associated with low NF-kappaB activation. Asthma patients with airway NO levels > 17 ppb showed minimal NF-kappaB activation, whereas asthmatic individuals with NO levels </= 17 ppb showed greater NF-kappaB activation. PPH patients with low NO (1 +/- 1 ppb) had prominent NF-kappaB activation. These in vivo studies in asthma and PPH support the in vitro observation of an inverse relationship between NO and NF-kappaB activation. One mechanism by which NO blocks cytokine production involves IkappaB.
 ...
PMID:Nitric oxide blocks nuclear factor-kappaB activation in alveolar macrophages. 1046 Jul 48

Asthma is characterized by airway inflammation and shows a circadian variation with nocturnal exacerbations. Because exhaled nitric oxide (ENO) measurement appears to be a noninvasive marker of airway inflammation, we examined the hypothesis that ENO would increase at night. In five nocturnal and five non-nocturnal asthmatics, ENO was measured at 4 P.M., 10 P.M., and 4 A.M. before and after bronchodilator. Both pre- and post-bronchodilator ENO (mean pre- and post-bronchodilator +/- SEM, ppb) unexpectedly fell significantly in nocturnal asthma from 4 P.M. (77.2 +/- 8.2) compared to 10 P.M. (68.4 +/- 8.7, p < 0.003) and 4 A.M. (66.0 +/- 8.5, p < 0.001) with no significant difference between 10 P.M. and 4 A.M.. In contrast, there were no significant differences in mean ENO at 4 P.M., 10 P.M., and 4 A.M. in non-nocturnal asthma. (51.3 +/- 10.8, 57.7 +/- 13.4, 53.8 +/- 12.5 ppb, respectively). Following bronchodilator, ENO rose significantly by 10.5 +/- 1.8 ppb in the nocturnal asthma group alone. The circadian rhythm of ENO differed greatly between nocturnal and non-nocturnal asthma. The significant decrease in ENO in nocturnal asthma may reflect an important chronobiological defect in the endogenous production and/or increased disposition of nitric oxide, which in view of its bronchodilator action, could play a role in nocturnal exacerbations of asthma.
J Asthma 1999 Aug
PMID:Circadian variation in exhaled nitric oxide in nocturnal asthma. 1046 36


1 2 Next >>