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)

It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elastin and collagen degradation products in urine of smokers with and without chronic obstructive pulmonary disease. 769 72

Pulmonary emphysema was induced in rats by a single intratracheal instillation of pancreatic elastase. The short-term effects of elastase instillation on basement membrane components were evaluated using immunohistochemical and biochemical methods. Lung alveoli showed a decrease in heparan sulphate proteoglycan content (especially of its heparan sulphate chains) 3 h to 7 days after induction. Type IV collagen, laminin and fibronectin were not affected. The glycosaminoglycan content of the lung was decreased during the first 3 days after induction, while the glycosaminoglycan concentration in urine was increased during the first 4 days by an increase of heparan sulphate and dermatan sulphate. The increase in urinary glycosaminoglycan content was positively correlated with the extent of emphysema developed after 40 days. We conclude that proteoglycans are target molecules for elastase, and may be involved in the pathogenesis of emphysema.
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PMID:Digestion of proteoglycans in porcine pancreatic elastase-induced emphysema in rats. 775 58

Nutritional impairment can adversely affect the respiratory system. The structure of the lung is altered by severe calorie-protein restriction in rodents producing an emphysema-like lesion after several weeks of severe caloric restriction. Biochemical and morphological evidence suggests destruction of collagen and elastin in nutritional emphysema. Impaired lung growth may explain the biochemical changes in growing animals. Although the molecular basis of nutritional emphysema is not known, altered gene expression by nutrients affects several metabolic pathways, and examples of the effects of nutrients on gene expression are given. Nutritional emphysema in animals may be relevant to humans because malnutrition may accelerate the progression of the disease in patients with advanced emphysema.
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PMID:Effect of diet on lung structure, connective tissue metabolism and gene expression. 778 21

We have previously shown that chronic cigarette smoke exposure produces emphysema and airflow obstruction in the guinea pig. To further examine the changes in the connective tissue matrix associated with emphysema in this model, we used ultrastructural morphometry to determine the volume proportions of collagen and elastin in the alveolar walls of animals exposed to smoke or air (control) for 1, 3, 6, and 12 mo. After 1 mo of smoke exposure, there was a statistically significant (P < 0.001) decrease in the volume proportion of collagen in the smoke-exposed animals, whereas by 6 and 12 mo of smoke exposure, the proportion of collagen had significantly (P < 0.02, P < 0.03, respectively) increased. The volume proportion of elastin was increased in the smoke-exposed animals at the 12-mo time period. While our results do not exclude reorganization of elastin within the alveolar wall, we conclude that, in this model, cigarette smoke-induced emphysema appears to be associated with collagen breakdown and repair. We suggest that the currently accepted proteolysis-antiproteolysis theory is too narrow in its focus on elastin destruction as the major contributor to emphysema and should be broadened to the concept that smoke-induced emphysema reflects breakdown and resynthesis (possibly overproduction in the form of scarring) of a variety of connective tissue proteins in addition to elastin.
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PMID:Smoke-induced emphysema in guinea pigs is associated with morphometric evidence of collagen breakdown and repair. 784 Feb 23

The tight skin (Tsk/+) mouse represents a murine model of heritable fibrosis with some similarities to the skin fibrosis seen in human scleroderma. Tsk/+ animals display alterations in connective tissue in some internal organs. Skin fibrosis can be adoptively transferred to normal recipients with Tsk/+ bone marrow or spleen cells and older Tsk/+ animals develop autoantibodies against topoisomerase suggesting that some of the pathogenesis in the Tsk/+ mouse may be mediated by autoimmunity. To determine the role of T cell subsets in the pathogenesis of fibrotic disease, Tsk/+ mice were bred with CD4- and CD8-deficient (CD4-/- and CD8-/-) mice. Tsk/+ CD4-/- mice showed a marked reduction in skin fibrosis as well as decreased cellularity and only mild collagen disorganization as compared to Tsk/+ CD4+ CD8+ control mice yet did not differ from Tsk controls in the level of serum anti-topoisomerase activity. In contrast, Tsk/+ CD8-/- mice exhibited the same histology in the skin as Tsk/+ controls yet had significantly reduced levels of serum anti-topoisomerase activity. Lung pathology, i.e. emphysema, was unaffected by both the CD4 or CD8 mutations. These data show that only some of the pathological effects of the Tsk mutation are T cell dependent and that different T cell subsets affect different parameters in this multi-organ model of fibrotic disease.
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PMID:A role for CD4+ T cells in the pathogenesis of skin fibrosis in tight skin mice. 791 25

Published articles on the radiologic aspects of Proteus syndrome are sparse. This report highlights the features of this disease with specific attention to the serious pulmonary manifestations that may occur at an early age. Two cases of Proteus syndrome and severe lung disease are presented, with complete autopsy in one case and correlative surgical pathologic data in the other. Multiple superficial and visceral vascular abnormalities were present in both cases. Both patients developed rapidly progressive diffuse cystic emphysematous pulmonary disease leading to the death of one patient at age 18 years and a heart-lung transplant in the other at age 8 1/2 years. Extensive gross pulmonary cysts were evident pathologically with diffuse panlobar emphysema microscopically. Studies of collagen and cultured fibroblasts in one patient revealed no abnormality. The early presentation, rapid progression and potentially lethal nature of lung involvement has not previously been emphasized.
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PMID:Proteus syndrome: emphasis on the pulmonary manifestations. 793 96

Human leucocyte elastase is a serine proteinase involved in phagocytosis, defence against invading micro-organisms, degradation of elastin, collagen, proteoglycans, fibrinogen and fibrin, being also responsible for the digestion of damaged tissues and of the bacterial degradation products. Lack of the enzyme regulation is at the basis of pathological states, such as pulmonary emphysema, cystic fibrosis, rheumatoid arthritis, atherosclerosis and glomerulonephritis. A detailed characterisation of the enzyme:inhibitor recognition process, based on extensive thermodynamic, kinetic and structural information, as well as on the comparative analysis with the homologous proteinase from porcine pancreas, is reported in the present review.
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PMID:Molecular bases for human leucocyte elastase inhibition. 804 99

The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema. In this mouse, right ventricular hypertrophy (RVH) starts to develop at approximately 8 months of age, probably as a consequence of the emphysema. The aim of the present study was to investigate cardiac collagen synthesis, content, and types both before and during the development of RVH. Collagen synthesis, assessed by the [3H]proline incorporation method, was significantly increased in the right ventricle of 3-month-old Tsk mice. This was accompanied by a marked increase in right ventricle collagen content. Collagen typing showed no difference from controls. At 8 months of age collagen synthesis had returned to control values, right ventricular collagen content was elevated but held lower values than at 3 months, and collagen typing showed a prevalence of the more compliant type III. By 16 months of age, right ventricular collagen content had returned to control values and there was a shift in collagen types due to a relative increase of the more rigid type I. At 24 months of age right ventricular collagen content was increased again and collagen type I continued to predominate. These results suggest a dynamic role for collagen both before and during the development of RVH secondary to emphysema.
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PMID:Cardiac collagen changes during the development of right ventricular hypertrophy in tight-skin mice with emphysema. 807 May 38

Ehlers-Danlos syndrome derives from some defect collagen synthesis or structure. It collects several disorders, clinically and genetically different. The young woman history with silent disease until lethal spontaneous arterial rupture is presented. Post-mortem examination shows type IV syndrome aspects: arterial fragility and right vertebral aneurisma rupture into pleural cavity with consequent fatal emothorax. Moreover there are mitral valve myxomatous degeneration, ascending aorta dilatation, lungs emphysema and meningioma.
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PMID:[Multiple vascular lesions in a patient with Ehlers-Danlos type IV]. 807 4

Elastic fibers in 15 blebs and 17 bullae with spontaneous pneumothorax were studied by means of electron microscopy and light and electron microscopic immunohistochemistry for elastin and alpha 1-antitrypsin. Blebs were formed in association with focal organized alveoli, and bullae were formed in association with pulmonary emphysema. Both blebs and bullae had abnormal elastic fibers. Ultrastructurally, abnormal elastic fibers of blebs and bullae consisted of accumulated thick and fine fibers. Accumulated thick elastic fibers showed vacuolar changes and electron-dense granular deposits, and they were associated with spiraling collagen fibrils. These thick elastic fibers reacted evenly with antielastin antibody and also reacted with anti-alpha 1-antitrypsin antibody. They are thought to be degraded elastic fibers. Accumulated fine elastic fibers consisted of bundles of microfibrils and granular amorphous components, and they reacted with anti-elastin and anti-alpha 1-antitrypsin antibody. These fine elastic fibers are thought to be not only newly formed in the process of organization but also degraded. It is suggested that elastic fibers of blebs and bullae are degraded due to an imbalance between elastase and alpha 1-antitrypsin.
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PMID:Histogenesis of abnormal elastic fibers in blebs and bullae of patients with spontaneous pneumothorax: ultrastructural and immunohistochemical studies. 810 49


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