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)

The effects of cigarette smoke on the microanatomic deposition and retention pattern of exogenous mineral particles is unknown. To determine how cigarette smoke affects long-term particle retention in those with minimal smoke-related disease, we selected autopsy lungs from ten smokers without evidence of emphysema at autopsy, and used analytical electron microscopy to examine exogenous mineral particle concentration in the mucosa of seven different bronchi of varying sizes and four parenchymal sites fed by those bronchi. These data were compared with values from twelve lifetime nonsmokers. Overall, total mean particle burden in the parenchyma in the smokers and nonsmokers was similar, but there was a markedly decreased particle load retained in the smokers' airways. The consistent increase in particle burden seen in nonsmokers as airways became narrower and more distant from the carina was lost in many, but not all, of the smokers, especially for particles larger than 1 micron, and this effect did not appear to depend on amount of smoking. Rare polonium particles were found but were too sparse to use as a smoke distribution marker. However, calcium-containing particles, previously suggested by us to represent calcium carbonate actually derived from the smoke, were present in greatest concentration in the larger airways and distal parenchyma. These observations indicate the following in smokers without parenchymal smoke-induced structural damage: (1) Overall, cigarette smoking disrupts the normal retention (? deposition) pattern of particles in the airways. (2) Cigarette smoking leads to markedly decreased long-term retention of exogenous mineral particles in the airways without significantly affecting overall tissue particle retention. (3) The distribution of calcium particles in the airways and parenchyma in smokers is similar to that predicted in a recently published model of smoke particle deposition, and further supports the idea that calcium-containing particles can be used as a direct tracer of smoke particle deposition. In the present study this distribution indicates that the large airways and parenchyma receive the greatest smoke deposition. (4) Within the group of smokers, some people appear resistant to the disruptive effects of smoke on particle retention patterns, whereas other people smoking comparable amounts show markedly abnormal retention patterns. The latter may have unusual sensitivity to cigarette smoke and perhaps susceptibility to smoke-induced diseases.
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PMID:Mineral particles in the human bronchial mucosa and lung parenchyma. II. Cigarette smokers without emphysema. 139 13

A large series of variously substituted anthraquinones has been synthesized and assayed for inhibitory capacity against human leukocyte elastase (HLE) and cathepsin G (CatG), two serine proteinases implicated in diseases characterized by the abnormal degradation of connective tissue, such as pulmonary emphysema and rheumatoid arthritis. It was found that 2-alkyl-1,8-dihydroxyanthraquinone analogues are competitive inhibitors of HLE with IC50 values ranging from 4 to 10 microM, and also inhibit CatG with IC50 values ranging from 25 to 55 microM. Consequently, analogues containing the 2-alkyl-1-hydroxy-8-methoxyanthraquinone substitution pattern inhibit HLE to the same magnitude as for the compounds above, but show very little inhibition of CatG. Anthraquinones containing long, hydrophobic n-butyl carbonate moieties in the 1- and 8-positions in conjunction with a third hydrophobic substituent in the 2- or 3-position are highly selective for HLE, with Ki values in the range of 10(-7) M. All of the inhibitors described are completely reversible, with no evidence of acyl-enzyme formation detected.
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PMID:Novel anthraquinone inhibitors of human leukocyte elastase and cathepsin G. 157 86

Factors which could influence serum erythropoietin (s-EPO) levels in patients with chronic pulmonary diseases were investigated, paying special attention to the role of changes in acid-base balance (PaCO2, HCO3- and base excess levels) in EPO production. Data from 30 patients with chronic pulmonary diseases (chronic pulmonary emphysema, chronic bronchitis and post-tuberculosis status) were obtained in the morning and were analyzed with a stepwise forward multiple regression analysis, evaluating the statistical significance of seven factors which may potentially influence s-EPO levels: arterial pH, PaCO2, PaO2, HCO3-, base excess (BE), SaO2 and hemoglobin (Hb). Significant simple correlations (P < 0.01) of log(s-EPO) were obtained with PaO2 (r = -0.66), PaCO2 (r = 0.59), HCO3- (r = 0.67), BE (r = 0.71) and SaO2 (r = -0.77). The stepwise forward multiple regression analysis revealed that significant correlate variables for the outcome variable of log(s-EPO) were SaO2 and BE, with r = 0.823 (P < 0.0001). In patients with chronic pulmonary diseases it was shown that SaO2 was a negative correlate and BE was a positive correlate of s-EPO levels. It was speculated that s-EPO levels in the morning reflected daytime hypoxemia (SaO2) and nocturnal desaturation evoked by hypopnea during sleep (indicated as BE) in these patients.
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PMID:Erythropoietin and base excess levels in patients with chronic pulmonary diseases. 908 92

The microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics. In addition, it has a potential role in sexual development and bile acid transport, and it is associated with a number of diseases such as emphysema, spontaneous abortion, eclampsia, and several forms of cancer. Toward developing chemical tools to study the biological role of mEH, we designed and synthesized a series of absorbent and fluorescent substrates. The highest activity for both rat and human mEH was obtained with the fluorescent substrate cyano(6-methoxy-naphthalen-2-yl)methyl glycidyl carbonate (11). An in vitro inhibition assay using this substrate ranked a series of known inhibitors similarly to the assay that used radioactive cis-stilbene oxide but with a greater discrimination between inhibitors. These results demonstrate that the new fluorescence-based assay is a useful tool for the discovery of structure-activity relationships among mEH inhibitors. Furthermore, this substrate could also be used for the screening chemical library with high accuracy and with a Z' value of approximately 0.7. This new assay permits a significant decrease in labor and cost and also offers the advantage of a continuous readout. However, it should not be used with crude enzyme preparations due to interfering reactions.
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PMID:Development of fluorescent substrates for microsomal epoxide hydrolase and application to inhibition studies. 2137 18