Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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1. A specific method is described for the measurement of angiotensin I converting enzyme activity in plasma with 125 I-labelled angiotensin I used as substrate. 2. Converting enzyme activity in plasma from fifteen normal subjects, eleven patients with sarcoidosis, twelve patients with chronic obstructive pulmonary disease and three patients with shock lung was assayed by this technique. 3. Patients with sarcoidosis had increased plasma converting enzyme activity whether or not they were receiving steroid therapy. 4. Patients with chronic obstructive pulmonary disease and shock lung had decreased plasma converting enzyme activity, but extent of conversion did not correlate with the severity of the lung disease. 5. Converting enzyme activity in normal plasma could be completely inhibited by addition of exogenous angiotensin I in 0.5-2.5x107 times physiological concentration. Twice as much exogenous angiotensin I was needed to inhibit conversion completely in plasma from patients with sarcoidosis; one tenth as much in chronic obstructive pulmonary disease. These results indicate that plasma has a high capacity for angiotensin I conversion even in patients with pulmonary parenchymal disease. 6. Results suggest that plasma converting enzyme activity may be a reflection of pulmonary conversion and can be altered by pulmonary disease. 7. Measurement of plasma converting enzyme activity may be useful in studies designed to characterize the regulatory role of converting enzyme in the renin-angiotensin system and in cardiovascular homeostasis.
Clin Sci Mol Med 1976 Dec
PMID:Altered angiotensin I conversion in pulmonary disease. 18 91

1. We have studied the extensibility of circumferential strips of main pulmonary artery and large pulmonary veins obtained at post mortem from patients of all ages, dying from conditions other than heart and lung disease. 2. The vessel strips were submitted to increasing loads in a tension balance. The pulmonary arteries were found to be readily extensible. This extensibility became less with increasing age. The pulmonary veins were virtually inextensible at all ages. 3. It is postulated that the large extraparenchymal pulmonary veins have a capacitative role in supplying blood from the lungs to the left atrium. This may be accomplished by their collapsible nature, as they have little capability of distension.
Clin Sci Mol Med 1978 Nov
PMID:The physcial properties of human pulmonary arteries and veins. 72 1

1. Pulmonary and systemic haemodynamics during repeated exercise were studied in 28 patients with chronic lung disease of various etiology, 16 of whom suffered from chronic bronchitis. They performed a moderate exercise repeated after a 20 min rest period. Ventilatory variables, blood gas tensions, cardiac output and vascular pressures (right ventricular end-diastolic, pulmonary arterial, wedge and systemic arterial) were measured at rest, during exercise and again at rest and during the same exercise. 2. Ventilation and blood gas tensions were similar during the two rest and exercise periods; there was, however, a slightly significant difference in oxygen consumption and hydrogen ion concentration between the first and the second exercise period. Pulmonary arterial and wedge pressures were lower during the second rest and exercise, right ventricular filling pressure was lower at rest, and systemic arterial pressure during the second exercise. Cardiac output and pulmonary vascular resistance were unchanged. 3. Changes in systemic arterial pressure were significantly different in a group of patients with arterial oxygen desaturation or perfusion defects, compared with those patients without such impairment.
Clin Sci Mol Med 1978 Nov
PMID:Haemodynamic variables during repeated exercise in chronic lung disease. 72 2

1. The breathing pattern in normal subjects during exercise was compared with that in patients with obstructive and restrictive lung defects. 2. In most normal women and patients with obstructive or restrictive lung disease, as the frequency of breathing increased both inspiratory and expiratory duration fell. However, in most normal men (74 per cent) inspiratory duration did not fall as ventilation increased. 3. Women breathed faster than men, and both obstructed and restricted patients breathed faster than normal subjects. 4. The airflow patterns in normal men and women were similar, but most patients with restrictive or obstructive lung disease showed an approximately exponential fall in flow during expiration.
Clin Sci Mol Med 1976 Dec
PMID:Regulation of breathing during exercise in normal subjects and in chronic lung disease. 107 Apr 21

Lung diseases such as cystic fibrosis (CF) might be treated by gene therapy using viral vectors delivered to the airway. One potential vector is the defective human parvovirus, adeno-associated virus (AAV). We examined the AAV p5 transcription promoter for gene expression in immortalized cell lines derived from the airway (IB3-1) or pancreas (CFPAC-1) of CF patients. AAV vectors expressing the prokaryotic genes cat (pAAVp5cat) or neo (pAAVp5neo) from the p5 promoter were evaluated after introduction into IB3-1 or CFPAC-1 cells by lipofection. In transient assays in both cell lines, the cat gene was expressed 5- to 10-fold more efficiently from the p5 promoter than from a simian virus 40 early gene promoter (pSVcat). IB3-1 cells were transformed stably to geneticin resistance by pAAVp5neo at a 5-fold higher efficiency than by an SVneo vector. The AAV inverted terminal repeat (ITR) region immediately upstream of the p5 promoter appears to have an enhancer effect and the promoter also contains a CREB site which confers a response to forskolin. In IB3-1 cells, expression of the cat gene from a p5 promoter was decreased about 5-fold by deletion of both the upstream ITR and the CREB site. The AAVp5neo vector was also packaged into AAV particles and used to infect IB3-1 cells as a transducing virus. Under these conditions, 60 to 70% of the cells could be stably transformed to geneticin resistance. Thus, AAV transducing vectors appear to be a highly efficient delivery system for stable integration and expression of genes in cultured airway epithelial cells.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Gene expression from adeno-associated virus vectors in airway epithelial cells. 132 13

Oxygen-mediated lung injury can stimulate a fibroproliferative response resulting in the alteration of the pulmonary extracellular matrix and subsequent scarring of parenchymal tissue. Fibronectin (FN), a component of the extracellular matrix, appears in increased quantities in fibrotic lung disease. Alveolar macrophages (AMs) are a potential source of this molecule. Using quantitative in situ hybridization, we demonstrated that AMs from rabbits acutely exposed to 100% oxygen (hyperoxia) for up to 64 h have 20-fold greater levels of FN mRNA relative to cells from control animals. When animals were allowed to recover in room air for up to 72 h after maximal oxygen exposure, AM FN mRNA abundance approached baseline levels. Furthermore, in oxygen-exposed animals, the fraction of lavaged cells expressing FN mRNA was increased 10-fold relative to controls. Although there was marked cell-to-cell variation, we conclude that the AM is a potential source of FN in the events leading to hyperoxia-induced pulmonary fibrosis.
Am J Respir Cell Mol Biol 1992 Nov
PMID:Increased fibronectin mRNA in alveolar macrophages following in vivo hyperoxia. 141 30

Because granulocyte colony-stimulating factor (G-CSF) is known to induce granulopoiesis and activate mature neutrophils, this factor could be important in determining the number and functional activity of neutrophils at sites of lung disease. The purpose of this study was to evaluate the ability of lung immune and inflammatory cells to produce G-CSF, and to seek evidence for the spontaneous production of this factor by cells recovered by lavage from controls and patients with lung diseases in which neutrophils may play a pathogenetic role. Lavage cells from controls produced little G-CSF spontaneously. Alveolar macrophages (AM), but not lymphocytes, produced large amounts following endotoxin stimulation. Lavage cells from patients with respiratory failure associated with bacterial pneumonia, but not those with respiratory failure from noninfectious causes, spontaneously released G-CSF (32 +/- 24 and less than 1 U/10(6) AM, respectively). Lavage cells from five of 15 patients with sarcoidosis and one of five patients with diffuse pulmonary fibrosis also spontaneously released G-CSF, which could not be explained by endotoxin exposure. The release of G-CSF by endotoxin-dependent and -independent mechanisms could play a role in the recruitment and activation of neutrophils in bacterial pneumonia and participate in the pathogenesis of some interstitial lung diseases.
Am J Respir Cell Mol Biol 1991 Feb
PMID:Spontaneous release of granulocyte colony-stimulating factor (G-CSF) by alveolar macrophages in the course of bacterial pneumonia and sarcoidosis: endotoxin-dependent and endotoxin-independent G-CSF release by cells recovered by bronchoalveolar lavage. 170 67

Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Aug
PMID:Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease. 189 44

Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.
Am J Respir Cell Mol Biol 1991 Aug
PMID:Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies. 189 47

The severity of bleomycin (BLM)-induced pulmonary fibrosis in mice varies markedly among several different murine strains. We have examined the DNA from lungs of sensitive (i.e., C57BL/6N) and resistant (i.e., BALB/c) strains of mice using a nucleoid sedimentation technique to detect early in vivo changes in the integrity of DNA after intravenous BLM. Mice received intravenous injections of BLM (80 mg/kg) or vehicle; lung nucleoids were prepared 15 min to 6 hr later. BLM produced striking decreases in nucleoid sedimentation distance versus paired controls in both strains within 15 min after injection, indicating extensive DNA scission. Repair of DNA strand breaks was complete in the resistant (BALB/c) mice by 5 hr; in contrast, only partial repair occurred in the sensitive (C57BL/6N) strain during that time. We then examined lungs for subsequent changes in steady state poly-(A)+ RNA levels and mRNA levels for lung matrix proteins (type I procollagen, type III procollagen, and fibronectin). Steady state levels of poly-(A)+ RNA were depressed to 50% of control 1 through 6 days after BLM injection in the lungs of sensitive mice. Resistant mice had pulmonary poly-(A)+ RNA levels similar to those of C57BL/6N mice, except for a 2-fold elevation 1 day after BLM injection. BLM injection affected the steady state levels of mRNA encoding lung matrix proteins differently than total poly-(A)+ RNA. Fibronectin mRNA/poly(A)+ RNA was elevated 2-fold 1 day after BLM treatment only in the sensitive strain and remained elevated at 3 and 6 days. In contrast, alpha 2I procollagen mRNA increased in both murine strains and alpha 1III procollagen mRNA decreased in both strains. Thus, a 7-fold or greater increase in the type I: type III procollagen mRNA ratio was seen in both strains 3 to 6 days after BLM injection. These data demonstrate that BLM treatment rapidly produces extensive pulmonary DNA damage in vivo, that persistence of DNA damage rather than the initial level of strand scission is associated with sensitivity to BLM lung disease in these mice, and that changes in the levels of mRNA encoding pulmonary matrix proteins occur in vivo within 1 to 3 days after intravenous BLM treatment.
Mol Pharmacol 1989 Aug
PMID:Acute pulmonary toxicity of bleomycin: DNA scission and matrix protein mRNA levels in bleomycin-sensitive and -resistant strains of mice. 247 58


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