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)

From January 1991 to September 1993 we evaluated 49 patients (27 males and 22 females--mean age 42 years) with chronic respiratory failure as possible candidates for lung transplantation. 27 patients had idiopathic pulmonary fibrosis, 9 emphysema, 4 bronchiectasis, 3 cystic fibrosis, 3 primary pulmonary hypertension and 1 respectively lymphangiomatosis, thromboembolism and vanishing lung. 16 patients were considered suitable for single or double lung transplantation. 4 patients died waiting, 4 underwent single lung transplantation and 8 are still on the waiting list. The mean survival of patients in the waiting list was 145 days (52 for patients with idiopathic pulmonary fibrosis), ranging between 35 and 398 days.
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PMID:[The selection of patients who are candidates for lung transplantation]. 867 46

Right ventricular cardiac function is altered by abnormalities affecting primarily the left-sided cardiac structures, the lungs, or the right-sided cardiac structures themselves. The most common cardiac causes for right ventricular dysfunction are chronic left ventricular ischemia and rheumatic mitral valvular disease. Pulmonary diseases that result in right ventricular dysfunction include pulmonary air-space disease, including emphysema, and pulmonary interstitial and parenchymal diseases, including idiopathic pulmonary fibrosis and cystic fibrosis. Chronic pulmonary vascular disease, including chronic thromboembolism and PPH have a significant effect on right ventricular performance. Common to all of these diseases is elevation of pulmonary vascular resistance with a commensurate increase in right ventricular pressure, resulting in right ventricular hypertrophy. The limited ability of right ventricular myocardium to function in the face of increased pulmonary resistance results in right ventricular dilatation, tricuspid regurgitation, and ultimately right ventricular failure. MR imaging provides direct, noninvasive visualization of the right ventricular chamber as well as the myocardium itself, allowing reliable demonstration of morphologic changes in the size and shape of the ventricle, thickness of the myocardium, and presence of abnormal infiltration by fat or edema. Furthermore, because MR imaging techniques do not depend upon geometric assumptions about the complex shape of the right ventricle, they may be used for accurate and reproducible quantitation of right ventricular volume and myocardial mass.
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PMID:MR imaging of pulmonary hypertension and right ventricular dysfunction. 872 68

The number of heart transplant operations performed in the United States has grown modestly as indicated by an 11% increase from 1990 (n=2,108) to 1994 (n=2,340). From 1987 (n=18) to 1993 (n=666), lung transplant procedures have increased by 3600%. This trend continued with 722 procedures performed in 1994 and 760 (22% increase from 1993) currently reported for 1995. Non-US heart transplants have also leveled during recent years. The number of new heart transplant programs in the United States has not increased during the last 2 years with no change from 1993-1994 and a decrease of 2 heart programs from 1994-1995. From 1990 (n=37) to 1995 (n=71), the number of centers performing lung transplantation increased by 92%. No significant changes were noted in the number non-US heart or lung programs from 1993-1994. The most frequently reported US indications for thoracic transplantation were coronary artery disease (43.5%) for heart, cystic fibrosis (37.9%) for double lung, emphysema/COPD (44.1 %) for single lung and congenital lung disease (40%) for heart-lung. The most frequently reported non-US diagnoses for thoracic transplantation included cardiomyopathy (48.8%) for heart, cystic fibrosis (39.4%) for double lung, idiopathic pulmonary fibrosis (31.4%) for single lung and primary pulmonary hypertension (24.3%) for heart-lung. US heart transplant recipients were predominantly male (77.9%), over 50 years of age (54.3%) and white (83.3%); while US lung transplant recipients were predominantly female (53.2%), between 35- 64 years of age (73.2%) and white (90.7%). No significant variance from the US recipient demographic profile was noted for non-US recipients in this analysis. Differences were noted in the percent distribution of non-US and US donor causes of death. The top US causes of donor death were motor vehicle accidents (31.7%), cerebrovascular/strokes (24.0%), gunshot/stab wounds (23.2%) and non-motor vehicle head traumas (11.8%). The leading causes of donor death for non-US cases included cerebrovascular/strokes (55.7%), non-motor vehicle head traumas (28.7%), motor vehicle accidents (7.7%) and central nervous system tumors (3.0%). Gunshot/stab wounds accounted for only 0.9% of donor deaths. A leveling of US heart transplant one-year survival during recent years was indicated by a 1.5% increase from 1988-1994. Improvement in one-year US lung transplant survival was indicated by a rise from 35.3% in 1987 to 74.1 % in 1994. Non-US one-year survival rates were 77.5% for heart and 67.5% for lung in 1994. The long-term thoracic patient survival rates in the United States were: 36.9% at 11 years for heart, 41 % at 5 years for lung and 24.7% at 10 years for heart-lung recipients. Long-term survival rates for non-US cases were 37.1 % at 11 years for heart, 39.7% at 5 years for lung and 16.8% at 10 years for heart-lung. The most important risk factor for US heart recipients at one month, one year, 2 years and 3 years posttransplant was receipt of a previous heart transplant. Other substantial risk factors included congenital diagnosis, donor age greater than 50 years and recipient on a ventilator at the time of transplant. The most important risk factor for mortality in US lung recipients was the transplant number (primary or repeat). Diagnosis and ventilator use were also highly influential risk factors for mortality.
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PMID:Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation. 879 53

Human airway tissue has been used in vitro to study mechanisms of airway disease. However, there has never been a comprehensive study that has looked at the influence of disease on the subsequent in vitro responsiveness of human airways. In this study, we obtained airway tissue from patients who were undergoing resection of the lung for carcinoma. We then compared the airway responsiveness in these tissues and in tissues from patients who had undergone lung transplantation for alpha-1-antitrypsin deficiency, emphysema, or cystic fibrosis with the responsiveness in tissues obtained from donor lungs, i.e., nondiseased. When the relationships between concentration and response were compared, we found that for histamine, electrical field stimulation, levcromakalim, and isoproterenol similar responses could be expected in tissues obtained from all the sources studied. This was not true for acetylcholine in that there were significantly lower responses in tissues from patients with alpha-1-antitrypsin deficiency (P = 0.02; n = 9) or from patients having a lung resected for carcinoma (P = 0.01; n = 6) compared with that of the nondiseased group (n = 6). Similarly, for carbachol, the responses were significantly lower in the alpha-1-antitrypsin deficiency group (P = 0.001; n = 10) and in specimens resected for carcinoma (P = 0.001; n = 6) than in the nondiseased group (n = 9). We conclude that, apart from acetylcholine and carbachol, contractile and relaxant agonists give similar responses when used in human airway tissues from various sources. Our results highlight the importance of stating the source of tissue when human airways are to be studied.
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PMID:Does the disease state influence the responsiveness of human airways studied in vitro? 880 32

Secretory leukoprotease inhibitor (SLPI) is a low molecular weight serine proteinase inhibitor, notably of neutrophil elastase (NE), which is synthesised and secreted by the pulmonary epithelium. SLPI plays an important role in limiting NE-induced pulmonary inflammation and, significantly, it also possesses anti-HIV activity. SLPI is a significant component of the anti-NE shield in the lung which has different reactivity from, and is therefore complementary to, the anti-NE action of alpha 1-proteinase inhibitor (alpha 1-PI). Inhaled recombinant SLPI (rSLPI) could prove beneficial in partnership with alpha 1-PI in the treatment of a number of inflammatory lung disorders including emphysema, chronic bronchitis, cystic fibrosis, and adult respiratory distress syndrome.
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PMID:Secretory leukoprotease inhibitor: partnering alpha 1-proteinase inhibitor to combat pulmonary inflammation. 899 29

Over the last years lung-transplantation has evolved into an effective therapy for patients with end-stage disease pulmonary parenchyma or vessels. The main indications for lung-transplantation are pulmonary emphysema, cystic fibrosis, idiopathic pulmonary fibrosis or pulmonary hypertension. All diseases associated with chronic infections such as cystic fibrosis or bilateral bronchiectasis need a bilateral lung-transplantation. In addition we transplant bilaterally all patients with pulmonary hypertension and young patients with pulmonary emphysema. In all other cases, a unilateral lung-transplantation is the treatment of choice. Heart-lung-transplantation is generally applied in patients with Eisenmenger-syndrome. At the time of transplantation patients suffer from dyspnea NY-HA III-IV and are mostly oxygen dependent. Life expectancy is limited to 6 to 18 months. Over the last years nearly 5000 lung-transplantations were performed worldwide. Survival rate after 1 year was 70 to 90% and 60 to 70% after 3 years respectively. In Switzerland there were approximately 80 lung-transplants performed since 1992 with a one year survival rate of approximately 75%.
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PMID:[Lung transplantation]. 914 85

Indications for unilateral, bilateral, heart-lung, and lobar transplant procedures for emphysema, cystic fibrosis, primary pulmonary hypertension, and pulmonary fibrosis are presented, and a brief historical perspective of the procedures is supplied.
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PMID:Indications. Unilateral, bilateral, heart-lung, and lobar transplant procedures. 918 16

Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor found in human plasma and is a potent elastase inhibitor in various tissues, including lung. A1-Pi is expressed and induced in liver during inflammatory responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the role of these cytokines in regulating A1-Pi in lung epithelial cells. We show that OM, a monocyte and T cell product, can specifically and potently induce A1-Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was also able to stimulate the expression of tissue inhibitor of metalloproteinase-1 in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF) had little or no effect on A549 cells, and proinflammatory cytokines, such as IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6 production was synergistically enhanced. OM was also able to stimulate A1-Pi production from a bronchial epithelial primary cell line, whereas an intestinal epithelial cell line HT29 responded to IL-6 but not OM. These results suggest that lung levels A1-Pi could be derived not only from liver and inflammatory cells but also from epithelial cells, which can be upregulated on stimulation by OM. This may have implications for regulation of local activity of human neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis.
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PMID:Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial cells. 919 1

1. The number of heart transplant operations performed in the United States grew modestly as indicated by a 12% increase from 1990 (n = 2,108) to 1995 (n = 2,360). From 1990 (n = 203) to 1995 (n = 871), lung transplant procedures increased by 329%. This trend has continued with 723 procedures performed in 1994 and 871 (21% increase from 1994) reported for 1995. As in the US, the number of non-US heart transplants has leveled during recent years. 2. The number of heart transplant programs in the United States has remained relatively constant over the last 3 years with a decrease of 5 heart programs from 1995 to 1996. The number of centers performing lung transplantation has also leveled during the last 3 years with an increase of only 4 programs from 1994 to 1996. Non-US lung programs increased 90% from 1994 to 1995. 3. The most frequently reported indication for heart transplantation in the US has changed from coronary artery disease (40.9%) in previous registry reports to all cardiomyopathies (44.7%). For other thoracic transplants, the most frequently reported indications included cystic fibrosis (36.7%) for double-lung, emphysema/COPD (46.8%) for single-lung and congenital lung disease (41.2%) for heart-lung transplants. The most frequently reported diagnoses for thoracic transplantation outside the US included cardiomyopathy (48.5%) for heart, cystic fibrosis (36.0%) for double-lung, idiopathic pulmonary fibrosis (26.5%) for single-lung and primary pulmonary hypertension (25.0%) for heart-lung transplants. 4. US heart transplant recipients were predominantly male (77.8%), 50-64 years old (51.1%) and white (82.7%). In contrast, US lung transplant recipients were predominantly female (52.9%), 35-64 years old (73.1%) and white (89.9%). No significant variance from the US recipient demographic profile was noted for non-US recipients in these analyses. 5. The one-year survival rate for US heart transplant recipients during recent years was fairly consistent, with only a 0.4% increase from 1990-1995. Improvement in the one-year US lung transplant survival rate was demonstrated by a rise from 35.3% in 1987 to 74.0% in 1995. The one-year survival rates at non-US centers were 76.0% for heart recipients and 64.5% for lung recipients in 1995. 6. The long-term thoracic patient survival rates in the United States were: 33.3% at 12 years for heart, 43.7% at 5 years for lung and 27.6% at 10 years for heart-lung recipients. Long-term survival rates for non-US cases were: 30.3% at 12 years for heart, 44.8% at 6 years for lung and 19.8% at 10 years for heart-lung. 7. The most important risk factor for US heart recipients at 1 month, 1 year, 3 years and 5 years after transplantation was receipt of a previous heart transplant. Other substantial long-term risk factors included recipient age less than 1 year, donor aged 45-54, and non-white recipient. 8. The most important mortality risk factor in US lung recipients was the order of the transplant (primary or repeat). Diagnosis and ventilator use remained highly influential risk factors for mortality.
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PMID:Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation. 928 57

The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses--for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease.
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PMID:Gene therapy for lung inflammatory diseases: not so far away? 933 37


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