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)

Severe, largely irreversible obstructive lung disease, compatible with emphysema, was found in a 14-yr-old white girl who had been considered to have chronic asthma. She also presented a serum alpha-1 antitrypsin deficiency. Serum values for alpha-1 antitrypsin on two occassions were 95 and 105 mg/100 ml; Pi type was SZ. A family survey disclosed a 13-yr-old brother with the same pattern of alpha-1 antitrypsin deficiency. His serum value was 122.5 mg/100 ml; Pi type was SZ. He was asymptomatic and showed minimal pulmonary function abnormalities.
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PMID:Clinical conference: Severe obstructive lung disease in a 14-year-old girl with alpha-1 antitrypsin deficiency. 108 59

A 76-year-old man, whose carotid bodies had been resected for treatment of bronchial asthma 40 years previously was admitted for evaluation of abnormal arterial blood gases and exertional dyspnea. The case was diagnosed clinically as chronic pulmonary emphysema. His peripheral chemoreceptor function, estimated by hypoxic ventilatory and P0.1 response tests and withdrawal test was non-functioning. His PaCO2 value tended to rise over 50 Torr either after light exercise or during airway infection, though it was normal at rest. In addition his dyspnea had continued for 40 years in spite of carotid body resection. It was concluded that the effect of carotid body resection lasts more than 40 years and it does not have a good effect on COPD.
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PMID:[A case of chronic pulmonary emphysema with a past history of bilateral carotid body resection]. 175 14

Three patients with chronic respiratory failure of various etiology, who have (had) been in the hospital for some years, were presented. The case 1 is male and was 57 years old on admission. He has been suffered from right thoracic emphysema from October '83, which is under chronic infection of Pseudomonas aeruginosa, with bronchial fistula and aortic valve insufficiency. His pulmonary function is severely restrictive and the grade of his dyspnea has been V of Hugh-Jone's criteria and he is now unable to leave from bed. The case 2 is male and was 41 y.o. on admission. He has been ill with diffuse cystic bronchiectasis from 33 y.o. and bronchorrhea (greater than 200 ml/day) with chronic infection of Pseudomonas aeruginosa has been lasting and recurrent attacks of infection have progressively worsened of his pulmonary and cardiac functions. He is now indispensable to assist ventilation by artificial respirator every 2-3 days. The case 3 was male and 27 y.o. on admission. He had admitted because of severe dyspnea due to familial pulmonary fibrosis on August '86. His disorder had been progressive and resistant against repeated corticosteroid therapy. He died of respiratory failure at 30 years old. The transplantations of lung and heart-lung for critical patients with respiratory failure have been challenged in North America and Europe, but in Japan, many social and medical problems about transplantation have yet been unresolved. The indications for and against lung or heart-lung transplantation to these three patients was discussed with reference to English literatures.
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PMID:[Three cases of chronic respiratory failure]. 262 Jan 34

Isocoumarins are potent mechanism-based heterocyclic irreversible inhibitors for a variety of serine proteases. Most serine proteases are inhibited by the general serine protease inhibitor 3,4-dichloroisocoumarin, whereas isocoumarins containing hydrophobic 7-acylamino groups are potent inhibitors for human leukocyte elastase and those containing 7-alkylureidogroups are inhibitors for procine pancreatic elastase. Isocoumarins containing basic side chains that resemble arginine are potent inhibitors for trypsin-like enzymes. A number of 3-alkoxy-4-chloro-7-guanidinoisocoumarins are potent inhibitors of bovine thrombin, human factor Xa, human factor XIa, human factor XIIa, human plasma kallikrein, porcine pancreatic kallikrein, and bovine trypsin. Another cathionic derivative, 4-chloro-3-(2-isothiureidoethoxy) isocoumarin, is less reactive toward many of these enzymes but is an extremely potent inhibitor of human plasma kallikrein. Several guanidinoisocoumarins have been tested as anticoagulants in human plasma and are effective at prolonging the prothrombin time. The mechanism of inhibition by this class of heterocyclic inactivators involves formation of an acyl enzyme by reaction of the active site serine with the isocoumarin carbonyl group. Isocoumarins with 7-amino or 7-guanidino groups will then decompose further to quinone imine methide intermediates, which react further with an active site residue (probably His-57) to form stable inhibited enzyme derivatives. Isocoumarins should be useful in further investigations of the physiological function of serine proteases and may have future therapeutic utility for the treatment of emphysema and coagulation disorders.
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PMID:Mechanism-based isocoumarin inhibitors for serine proteases: use of active site structure and substrate specificity in inhibitor design. 265 46

Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.
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PMID:Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution. 291 84

The continuing discovery and development of beta-lactams as antibiotics has had an unparalleled impact on the overall health and well-being of society. Recently, appropriately substituted cephalosporins were shown to be potent inhibitors of elastase, suggesting a novel therapeutic role for the beta-lactams in the control of emphysema and other degenerative diseases. We have now solved and partially refined at atomic resolution the structure of a complex of porcine pancreatic elastase with the time-dependent irreversible inhibitor 3-acetoxymethyl-7-alpha-chloro-3-cephem-4-carboxylate-1,1-dioxide tert-butyl ester (I), the most potent of the beta-lactam elastase inhibitors yet reported. (Porcine pancreatic elastase is a close relative of the desired drug target, human polymorphonuclear leukocyte elastase.) A mechanism of action is presented, based on the structure and on biochemical evidence (T.-Y.L. et al., in preparation), which clarifies the operational similarities and differences between beta-lactam elastase inhibitors and antibiotics. Features of the reaction include the expulsion of a leaving group at the cephalosporin 3' position and the formation of two covalent bonds with the active site of porcine pancreatic elastase at residues Ser 195 and His 57.
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PMID:Crystallographic study of a beta-lactam inhibitor complex with elastase at 1.84 A resolution. 364 81

A patient with pronounced dyspnoea and cyanosis was found to have severe hypoxaemia with normal spirographic values. His past history included arterial hypertension, myocardial infarction and phlebitis of the lower limb. Airways resistance was normal, but maximal expiratory flow rates at low lung volume (Flow-volume curves) were reduced, suggesting "peripheral" airways obstruction. This was confirmed by the presence of pulmonary hyperinflation and mechanical non-homogeneity accompanied by unevenly distributed ventilation, as shown by alveolar nitrogen gradient. There was marked hyperventilation with hypocapnia. Since transfer values (measured by the CO single-breath method) and lung distensibility values were normal, emphysema could be ruled out as a cause of obstruction. Analysis of pressure-flow relationship confirmed that the obstruction of peripheral airways was "intrinsic" in character. It could be due to an increase in lung extravascular fluid (interstitial oedema due to left cardiac failure), or to repeated micro-emboli in the lungs, or to hypocapnia, these three mechanisms possibly being associated.
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PMID:[Peripheral airway obstruction involving cardiovascular factors. A case report (author's transl)]. 677 51

A case of erythroleukemia coexistent with pulmonary emphysema is reported. A 67-year-old male was admitted to our hospital in May 1981, with a few year history of cough, sputum and fatigue. He had already been diagnosed as having pulmonary emphysema and moderate anemia. On physical examination, except for pallor, no other findings were remarkable. The initial hematological examination showed hemoglobin, 9.6 g/dl, red cell count, 251 x 10(4)/microliters, platelet count, 7.3 x 10(4)/microliters, white cell count, 2600/microliters with neither myeloblasts nor erythroblasts. A sternal marrow aspiration revealed 21% myeloblasts and 40% erythroblasts including 7.5% megaloblastoids. Periodic Acid Schiff staining was strongly positive for a part of erythroblasts. A chest X-P finding was typical for pulmonary emphysema. Pulmonary function was moderately damaged. He was started on chemotherapy with AAAP (ACNU 50 mg/d i.v. drip over 4 hr x 4d, adriamycin 20 mg/d i.v. push x 4d, Methotrexate 20 mg i.v. push x 4d). The first course of AAAP brought him a complete remission with both disappearance of myeloblasts and erythroid precursors with megaloblastoid nuclei in the marrow and the normalization of white cell count and platelet count in the blood. He was discharged in September 1981 after completion of a consolidation chemotherapy with AAAP. Since then, he received two courses of AAAP as an intensification chemotherapy and has been in complete remission for more than 13 months. His pulmonary function has not been affected and no myocardial damage has been seen throughout AAAP therapy. Thus, AAAP therapy seems to be an excellent chemotherapy even for an aged patient with erythroleukemia.
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PMID:[A case report of an aged patient with erythroleukemia coexistent with pulmonary emphysema, responding well to AAAP therapy]. 696 34

An elderly man presented with hypoxemic respiratory failure and pulmonary hypertension. He was a heavy cigarette smoker and had been treated previously for pleuro-pulmonary tuberculosis. His lung volumes and airway function were normal. High resolution computer tomographic (HRCT) examination revealed combined upper lobe emphysema and lower lobe fibrosis. Routine pulmonary function tests may underestimate the degree of functional impairment in patients with combined emphysema and fibrosis. The HRCT examination however provided valuable information.
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PMID:Respiratory failure from combined emphysema and pulmonary fibrosis. 826 63

A 76-year-old man was admitted for recurrent hemoptysis of 3 weeks' duration. Chest X-ray revealed lung emphysema, but no findings of thoracic aortic aneurysm. The patient's physician attributed to bronchoectasia, and he underwent angiography for the purpose of embolization of bronchial arteries. Angiography showed a small saccular thoracic descending aortic aneurysm and an aortopulmonary fistula. So aneurysmectomy and patch angioplasty was done under partial cardiopulmonary bypass. Lobectomy or wedge pulmonary resection was not necessary. His postoperative course was uneventful. In case of the patients with hemoptysis, the possibility of aortopulmonary fistula should be considered, and computed tomography or aortography should be done to rule out other pulmonary diseases.
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PMID:[Hemoptysis due to aortopulmonary fistula: a case report of successful surgical treatment]. 853 9


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