Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats and guinea pigs, pretreated with intratracheally administered elastase or saline, were exposed to 1.03 mg/m3 (NH4)2SO4; MMAD, 0.42 micron. Identically treated controls were sham exposed. Measurements and evaluation of structural changes were conducted using morphometric techniques on SEM photographs and by applying subjective ratings. Pathology studies were conducted by light and electron microscopy. All examination methods confirmed elastase-induced emphysema, which was aggravated by (NH4)2SO4 exposure in the rat. Ammonium sulfate exposure of saline-treated animals produced measurable degrees of enlargement of alveoli, and alveolar ducts and sacs. Electron microscopy revealed increased interstitial collagen in affected lung areas of elastase-treated, (NH4)2SO4-exposed animals. Alveolar-pore size was significantly increased in elastase-treated animals (control and exposed) but not in saline-treated, exposed animals. The data suggest a possible difference between elastase and (NH4)2SO4 in the mechanisms responsible for the increased diameter of alveolar structures. Hypertrophy and hyperplasia of nonciliated epithelial cells of the small airways and of the Type II alveolar cells were observed in otherwise untreated guinea pigs exposed to (NH4)2SO4 but not in elastase-treated guinea pigs, nor in any of the rats.
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PMID:Effects of ammonium sulfate aerosol exposure on lung structure of normal and elastase-impaired rats and guinea pigs. 656 15

It has been suggested that oxidants from pulmonary inflammatory cells may contribute to the development of emphysema by (i) direct tissue toxicity and (ii) inhibition of alpha 1-antitrypsin, thus diminishing protection of the lung from proteolytic damage. The extracellular release of hydrogen peroxide (H2O2) by human alveolar macrophages (AM) has been measured. AM were obtained by bronchoalveolar lavage and adherence from 24 smokers and 17 non-smokers. Smokers' AM released significantly more H2O2 (3.83 nmol h-1 micrograms-1 of DNA; SEM 0.44) than those of non-smokers' (2.33 nmol h-1 microgram-1 of DNA; SEM 0.40) (P less than 0.05). AM from donors with a recent lower respiratory tract infection released increased quantities of H2O2 (5.22 nmol h-1 microgram-1 of DNA; SEM 0.72; P less than 0.01) even when allowance was made for smoking habits. These findings are consistent with the hypothesis that H2O2 of AM origin contributes to the development of emphysema in smokers.
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PMID:Extracellular release of hydrogen peroxide by human alveolar macrophages: the relationship to cigarette smoking and lower respiratory tract infections. 662 51

Emphysema mortality is higher in Colorado than in the nation as a whole despite the younger age of Colorado's population Colorado death records from 1959 to 1976 were examined to determine if emphysema mortality increases with altitude within the state and if altitude adversely affects survival from chronic lung disease. Because the proportion of persons older than 65 yr of age in Colorado decreases with altitude (r = -0.6, p less than 0.01), emphysema mortality was age-standardized. The age-standardized rate increases with altitude among males (r = 0.9, p less than 0.01; y = 0.003(x) + 42.1). Emphysema deaths at higher altitudes in Colorado (greater than or equal to 7,000 ft) occur at a younger age (68.1 +/- 0.6 yr (mean +/- SEM) versus 70.1 +/- 0.6 yr at lower altitudes), after a shorter duration of illness, and more commonly from cor pulmonale than at lower altitudes (less than or equal to 4,500 ft) where pneumonia is more common as the immediate cause of death. The mechanism by which high altitude residence interacts unfavorably with survival is not known but may stem from augmented pulmonary hypertension caused by the hypoxia of lung disease added to the hypoxia of high altitude.
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PMID:Emphysema mortality is increased in Colorado residents at high altitude. 710 48

The aim of the study was to evaluate the protease and antiprotease activity in the fluid obtained from the culture of cells isolated from the lungs of animals with experimental emphysema. An attempt was made to correlate the results of biochemical examinations with adherence degree and ultrastructural changes of the surface of BAL-isolated cells. The experiment was carried out on male Wistar rats, of 180-220 g b.w. Two i.p. injections of BCG-vaccine (4 x 10(8) microorganisms) on the 1st and 14th day were applied as macrophage mobilizing and activating agent. Papain (2 mg/l ml/100 g b.w.) was given once i.t. on the 21st day. The animals were sacrificed on the 28th day of the experiment. We found a correlation between the increase in the cell adherence and ultrastructural changes (in SEM), suggesting an increased activity of the cells isolated from BCG-treated rats. In the culture medium of cells isolated from the rats which were given BCG or papain and BCG+papain we observed an increased base protease activity and decreased Cathepsin D activity comparing with the control group. Increased antitrypsin activity in the BCG and BCG+papain-treated rats and decreased antitrypsin activity in papain-treated rats only was observed, too. There was no obvious difference in the levels of the antiplasmin and antichymotrypsin activities between the groups. The present results indicate that activated pulmonary macrophages are one of the sources of the protease-antiprotease intraalveolar imbalance. However, an increased production of proteolytic enzymes may not be the only factor responsible for the progression of lung emphysema in BCG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of morphological and biochemical changes of BAL-isolated cells in experimental lung emphysema. 749 38

Quantitative and morphological analyses (in SEM) of blood platelets collected from the left and right ventricles of the rat heart in the course of experimental lung emphysema were done. Platelet aggregation index was estimated, too. Emphysema was induced by a single intratracheal instillation of papain solution in a dose of 20 mg/kg b.w/1 ml PBS. The animals were sacrificed after 2 and 24 hours and 7, 14, 28 days later. Within 24 hours of the experiment a slight decrease was observed in the number of platelets in the blood collected from the left ventricle compared to the right one as well as to control animals. Also a reduction in platelet aggregation coefficient value was noted. However, in the later period of emphysema progression (after 7th day), a statistically significant increase was found in the number of blood platelets in the left ventricle. A relation was noted between quantitative changes of blood platelets and emphysema progression evaluated morphometrically. The ultrastructural examinations in SEM suggest the occurrence of platelet satellitosis in animals intratracheally injected with papain solution. The present results indicate the possibility of a significant contribution of blood platelets to the pathogenesis of experimental lung emphysema.
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PMID:Blood platelets in experimental lung emphysema. Comparative analysis of the number and aggregation abilities of platelets in left and right ventricular blood of the heart. 769 33

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

Resistance to collateral flow of gas is high in the normal human lung but may be lower in emphysema. However, the contribution of collateral ventilation to gas exchange in emphysema remains unclear. This study evaluates the role and magnitude of collateral ventilation between bronchopulmonary segments in six patients with clinical, functional, and computed tomographic evidence of emphysema, compared with our previous findings in 12 normal subjects. To assess collateral flow, a balloon-tipped catheter with a lumen that opened distal to the balloon was inflated in segmental bronchi during fiberoptic bronchoscopy. Respiratory gas tensions were sampled by mass spectrometer from beyond the occlusion via the catheter lumen. Subjects breathed air until occlusion was established and then switched to 79% helium/21% oxygen. The rate of rise of helium concentration was measured within occluded segments and used as an index of collateral ventilation. The mean (+/- SEM) rate of rise of helium concentration was ten times greater in emphysema patients (9.5 +/- 2.7%/min) compared with normal subjects (0.8 +/- 0.3%/min) (p = 0.009). The mean PO2 within occluded segments was similar in normal subjects and emphysema patients: 45.4 +/- 1.8 mm Hg and 44.8 +/- 3.6 mm Hg, respectively. Mean PCO2 within occluded segments was lower in patients (40.1 +/- 1.9 mm Hg) than in normal subjects (46.4 +/- 1.3 mm Hg), probably due to higher regional ventilation-perfusion ratios in emphysema patients rather than collateral ventilation. In emphysema patients there was a positive correlation between rate of rise of helium concentration and final PO2 within an occluded segment (r = 0.73; p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Collateral ventilation and gas exchange in emphysema. 808 31

Elastinolytic enzymes derived from alveolar macrophages (AM) are considered to play an important role in the development of emphysema associated with cigarette smoking. In this study, the enzyme activity and mRNA expression of cathepsin L were quantitated in AM and bronchoalveolar lavage (BAL) fluid obtained from current smokers and compared with those from nonsmokers. Activity was measured with the synthetic substrate Z-Phe-Arg-MCA combined with a novel cathepsin B inhibitor, CA-074. We found that the specific activity of cathepsin L was significantly elevated in BAL cells from smokers (7.1 +/- 0.7 mumol/mg protein/h, mean +/- SEM) compared with cells from nonsmokers (2.9 +/- 0.3) (p < 0.01). The expression of cathepsin L mRNA in BAL cells as determined by dot-blot analysis was also higher in BAL cells from smokers, which was comparable to the increase in the enzyme activity. About 5 to 6% of the specific activity of cathepsin L in BAL cell lysates was detected in unconcentrated BAL fluid; specific activity was also significantly higher in samples from smokers (0.38 +/- 0.04 mumol/mg protein/h) than from nonsmokers (0.14 +/- 0.02). In addition, procathepsin L (42 kD) and the mature form of cathepsin L (33 kD) were demonstrated in BAL fluid by immunoblot analyses. These data suggest that cigarette smoking induces mRNA expression and the synthesis of cathepsin L in AM and the release of procathepsin from AM into extracellular milieu. Furthermore, increased activity levels of cathepsin L in extracellular compartments may contribute to the proteolysis of elastin in the process of lung destruction associated with cigarette smoking.
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PMID:Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. 850 70

In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.
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PMID:Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. 852 Jul 85

Neutrophil accumulation in the lung is implicated in the pathogenesis of pulmonary emphysema and chronic bronchitis associated with cigarette smoking. To determine whether nicotine contributes to this accumulation through the prolongation of neutrophil survival, we examined the survival rates of isolated neutrophils cultured with or without nicotine. We found that nicotine prolonged neutrophil survival in a dose-dependent fashion, with a maximum effect at 10(-6) mol/L. The survival rate at 72 hours was 35.6% +/- 1.2% in medium with 10(-6) mol/L nicotine, compared with 15.5% +/- 0.5% in control medium (mean +/- SEM; p < 0.01), as determined by trypan blue dye exclusion. This prolongation was brought about by suppression of apoptosis, as evidenced by both transmission electron and fluorescence microscopy, and was associated with the preservation of neutrophil functions such as chemotaxis and O2- generation. The prolongation of survival caused by nicotine was abrogated by the addition of Pro-Lys-Arg-NH2, a competitive inhibitor of the specific binding of nicotine to noncholinergic receptors on neutrophils. However, the prolongation of survival caused by nicotine was not suppressed in the presence of K-252b, an inhibitor of protein kinase C. These findings suggest that nicotine prolongs neutrophil survival through noncholinergic nicotine receptors and new protein synthesis, without activation of protein kinase C.
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PMID:Nicotine prolongs neutrophil survival by suppressing apoptosis. 863 47


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