Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LUNGS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2005

Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer.

CONTEXT: Evidence exists that lung cancer aggregates in families and recent findings of a chromosomal region linked to lung cancer susceptibility support a genetic component to risk. Family studies of early-onset lung cancer patients offer a unique opportunity to evaluate lifetime risk of lung cancer in relatives. OBJECTIVE: To measure lung cancer aggregation and estimate lifetime risk among relatives of early-onset cases and population-based controls. DESIGN AND SETTING: Familial aggregation and cumulative risk estimates from interview data of incident cases and concurrently ascertained controls between 1990 and 2003 in metropolitan Detroit, Mich. PARTICIPANTS: The study included 7576 biological mothers, fathers, and siblings of 692 early-onset cases and 773 frequency-matched controls. One third of the population was black. MAIN OUTCOME MEASURES: Cumulative lifetime risk of lung cancer, stratified by race and smoking behavior in relatives of early-onset cases and controls. RESULTS: Smokers with a family history of early-onset lung cancer in a first-degree relative had a higher risk of developing lung cancer with increasing age than smokers without a family history. An increase in risk occurs after age 60 years in these individuals, with 17.1% (SE 2.4%) of white case relatives and 25.1% (SE 5.8%) of black case relatives diagnosed with lung cancer by age 70 years. Relatives of black cases were at statistically significant increased risk of lung cancer compared with relatives of white cases (odds ratio, 2.07, 95% confidence interval, 1.29-3.32) after adjusting for age, sex, pack-years, pneumonia, and chronic obstructive lung disease. CONCLUSIONS: First-degree relatives of black individuals with early-onset lung cancer have greater risk of lung cancer than their white counterparts, and these risks are further amplified by cigarette smoking. These data provide estimates of lung cancer risk that can be used to offer counseling to family members of patients with early-onset lung cancer.

Adult↗
PubMed1986

Formation of reactive 1-nitropyrene metabolites by lung microsomes and isolated lung cells.

The metabolism and activation of 1-nitropyrene (1-NP) to reactive intermediates by lung microsomes and isolated lung cells was studied. Mutagenicity of 1-NP metabolites was assayed in Salmonella typhimurium TA98NR, a strain lacking a major component of nitroreductase activity. In the presence of NADPH, microsomes from rabbit, rat and hamster lung metabolized 1-NP to mutagenic products to a similar degree. Pretreatment with a mixture of polychlorinated biphenyls (PCB) decreased the formation of mutagenic metabolites by rabbit lung microsomes, but did not affect the production of mutagens by rat or hamster lung microsomes. 3H-1-NP was metabolized to covalently bound protein products at a rate of 82 and 10 pmol/mg by rabbit and hamster lung microsomes, respectively, whereas no binding was detected in rat lung microsomes. PCB-pretreatment increased covalent protein binding of 3H-1-NP in lung microsomes from hamster and rat, but decreased the binding in rabbit lung microsomes. High performance liquid chromatography analysis indicated that 3H-1-NP was readily converted to ring-hydroxylated products by rabbit and hamster lung microsomes; the rate was much lower with rat lung microsomes. 3H-1-NP was activated to metabolites that covalently bound to protein in isolated rabbit lung cells, with the following rates being observed: Clara cells greater than lung digest greater than type II cells. In contrast, covalent protein binding in cells isolated from rat lung was very low. 1-NP was not activated to products mutagenic for S. typhimurium TA 98NR when co-incubated with cells isolated either from rabbit or rat lung.

Animals↗
PubMed2006

Definitions of primary graft dysfunction after lung transplantation: differences between bilateral and single lung transplantation.

OBJECTIVE: The primary graft dysfunction definition has been applied to both bilateral lung transplantation and single lung transplantation. However, the differences between bilateral and single lung transplantation in terms of primary graft dysfunction remain unknown. This study aims to investigate the features and utility of the new primary graft dysfunction grading system by comparing early outcomes from bilateral and single lung transplantation. METHODS: The primary graft dysfunction grade of 228 consecutive lung transplants (149 bilateral and 79 single lung transplants) at multiple postoperative time points was analyzed. Subgroup analysis with chronic obstructive pulmonary disease was performed to further validate the difference between bilateral lung transplantation and single lung transplantation. RESULTS: The percentage of grade 3 primary graft dysfunction in bilateral and single lung transplants was 32% and 37% at 0 hours (T0), 9% and 33% at 12 hours (T12), 7% and 26% at 24 hours (T24), and 9% and 18% at 72 hours (T72), respectively. The prevalence of the grade 3 primary graft dysfunction (T24) was significantly different between those undergoing bilateral lung transplantation and those undergoing single lung transplantation (P = .02). The primary graft dysfunction grade (T0) significantly correlated with the duration of intubation in both bilateral (r = 0.35, P < .0001) and single (r = 0.42, P = .001) lung transplantation and length of intensive care unit stay in both bilateral (r = 0.31, P = .0002) and single (r = 0.33, P = .006) lung transplantation. These differences were validated by the subgroup analysis. CONCLUSIONS: The prevalence of primary graft dysfunction grade is different between bilateral and single lung transplantation and varies with time. Although the primary graft dysfunction grade correlated with the early posttransplantation outcomes, for the purposes of description and further studies, primary graft dysfunction in bilateral and single lung transplantation should be considered separately.

Adult↗
PubMed2001

Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes containing cholesterol or DOPE as a helper lipid in the single-pass rat lung perfusion system.

Plasmid DNA-cationic liposome complexes (lipoplexes) accumulate in the lung to a great extent immediately after intravenous administration, and gene expression occurs predominantly in the lung. However, the detailed mechanisms underlying the lung accumulation of lipoplexes are not fully understood. In this study, we investigated the effect of blood components on the lung accumulation of lipoplexes using a single-pass rat lung perfusion system. Two types of lipoplexes, Chol-containing lipoplex ([(32)P]DNA-DOTMA/Chol liposome complex) and DOPE-containing lipoplex ([(32)P]DNA-DOTMA/DOPE liposome complex), pre-incubated with whole blood, serum, or erythrocytes, were injected into the perfused lung via an artery. Similarly to in vivo observations, extensive lung accumulation was observed for both types of lipoplexes after incubation with whole blood during a single passage. The (32)P-labeled lipoplexes pre-incubated with erythrocytes showed similar lung accumulation, whereas their lung accumulation after incubation with serum was significantly reduced, suggesting that erythrocytes would be more responsible blood components for extensive uptake by the perfused lung. However, there was a clear difference in the amounts of the accumulated erythrocytes after intra-arterial injection between the two lipoplex formulations. A significant degree of erythrocyte accumulation was observed when the DOPE-containing lipoplex was injected, whereas the Chol-containing lipoplex failed to induce any significant erythrocyte accumulation in the lung. In vitro experiments showed that the major fraction of both lipoplexes was bound to erythrocytes. These data suggested that Chol-containing lipoplexes bound to erythrocytes before injection dissociate from the erythrocytes and are transferred to the lung capillary endothelial cells during their passage through the lung. In contrast, DOPE-containing lipoplexes bound to erythrocytes cause aggregation and are embolized in the lung capillary with erythrocytes. Thus, the present study demonstrated that the interaction with erythrocytes plays an important role in the lung accumulation of lipoplexes and that neutral helper lipid significantly affects this interaction.

Animals↗
PubMed1994

Pulmonary artery occlusion and lung collapse depletes rabbit lung adenosine triphosphate.

BACKGROUND: Although the bronchial circulation has traditionally been thought to provide adequate blood flow for the lung when the pulmonary artery is obstructed, recent studies have demonstrated that pulmonary artery occlusion results in lung injury. We hypothesized that after pulmonary artery occlusion, aerobic lung metabolic function is altered. We studied the changes in the concentration of adenine nucleotides as markers of injury in the intact rabbit lung after pulmonary artery occlusion in the presence and absence of pneumothorax. METHODS: A thoracotomy was performed on the rabbits, and on occlusive microvascular clamp was placed on the left pulmonary artery. The rabbit lungs were studied after 24 h of in vivo left pulmonary artery occlusion (n = 5), 24 h of left pulmonary artery occlusion with the lung collapsed by pneumothorax (n = 6), or 24 h of lung collapse alone (n = 5). RESULTS: Adenosine triphosphate concentrations of the occluded left lung decreased dramatically at 24 h in the group with pulmonary artery occlusion and collapse (adenosine triphosphate concentration 196 +/- 32 ng/g for the left lung and 1,479 +/- 197 ng/g for the right lung; P < 0.001). There were no differences between the lungs in the rabbits undergoing occlusion alone or collapse alone. CONCLUSIONS: After pulmonary artery occlusion or lung collapse, adenine nucleotides are preserved if ventilation is continued. The increased permeability of rabbit lungs after 24 h of left pulmonary artery occlusion alone cannot be explained on the basis of depletion of high-energy phosphates. In the absence of ventilation due to lung collapse, pulmonary artery occlusion results in decreased adenosine triphosphate concentrations, demonstrating that the residual circulations (bronchial and pulmonary venous flow) are inadequate to support normal lung aerobic metabolism.

Adenosine Triphosphate↗
PubMed2000

Single-breath CO2 analysis as a predictor of lung volume change in a model of acute lung injury.

OBJECTIVE: To examine the utility of single-breath CO2 analysis as a measure of lung volume change in a model of acute lung injury. SETTING: Animal laboratory in a university-affiliated medical center. DESIGN: Prospective, animal cohort study comparing 21 variables derived from single-breath CO2 analysis with lung volume measurements determined by nitrogen washout. SUBJECTS: Seven lambs with saline lavage-induced acute lung injury. METHODS: Animals were treated with repetitive saline lavage to achieve a uniform degree of acute lung injury (PaO2 < 100 torr [13.32 kPa] on FiO2 of 1.0). Twenty-one derived components of the CO2 expirogram were evaluated as predictors of lung volume change. Lung volume was manipulated by 3-cm H2O incremental increases in positive end-expiratory pressure from 0 to 21 cm H2O and ranged between 90 and 765 mL. MEASUREMENTS AND MAIN RESULTS: Fifty-five measurements of lung volume were available for comparison with derived variables from the CO2 expirogram. Stepwise linear regression identified five variables that were most predictive of lung volume change: a) dynamic lung compliance; b) the slope of phase III; c) the slope of phase II divided by the mixed expired CO2 concentration; d) airway deadspace; and e) PaO2/FIO2 ratio. The multivariate equation was highly statistically significant and explained 94% of the variance (adjusted r2 = .94, p < .0001). The bias and precision of the calculated lung volume were 10.9 and 55.9, respectively. The mean percentage difference for the lung volume estimate derived from the single-breath CO2 analysis station was 3.3%. CONCLUSIONS: Our data indicate that analysis of the CO2 expirogram can yield accurate information about lung volume in animals with saline lavage-induced acute lung injury. Specifically, five variables derived from a plot of expired CO2 concentration vs. expired volume predict changes in lung volume in healthy lambs with an adjusted coefficient of determination of 0.94. We hope to further define the utility of this technique by prospective application of this methodology in the clinical setting.

Animals↗
PubMed2005

Prone position delays the progression of ventilator-induced lung injury in rats: does lung strain distribution play a role?

OBJECTIVE: To investigate if prone position delays the progression of experimental ventilator-induced lung injury, possibly due to a more homogeneous distribution of strain within lung parenchyma. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory of a university hospital. SUBJECTS: Thirty-five Sprague Dawley male rats (weight 257 +/- 45 g). INTERVENTIONS: Mechanical ventilation in either supine or prone position and computed tomography scan analysis. MEASUREMENTS: : Animals were ventilated in supine (n = 15) or prone (n = 15) position until a similar ventilator-induced lung injury was reached. To do so, experiments were interrupted when respiratory system elastance was 150% of baseline. Ventilator-induced lung injury was assessed as lung wet-to-dry ratio and histology. Time to reach lung injury was considered as a main outcome measure. In five additional animals, computed tomography scans (GE Light Speed QX/I, thickness 1.25 mm, interval 0.6 mm, 100 MA, 100 Kv) were randomly taken at end-expiration and end-inspiration in both positions, and quantitative analysis was performed. Data are shown as mean +/- sd. MEASUREMENTS AND MAIN RESULTS: Similar ventilator-induced lung injury was reached (respiratory system elastance, wet-to-dry ratio, and histology). The time taken to achieve the target ventilator-induced lung injury was longer with prone position (73 +/- 37 mins vs. 112 +/- 42, supine vs. prone, p = .011). Computed tomography scan analysis performed before lung injury revealed that at end-expiration, the lung was wider in prone position (p = .004) and somewhat shorter (p = .09), despite similar lung volumes (p = .455). Lung density along the vertical axis increased significantly only in supine position (p = .002). Lung strain was greater in supine as opposed to prone position (width strain, 7.8 +/- 1.8% vs. 5.6 +/- 0.9, supine vs. prone, p = .029). CONCLUSIONS: Prone position delays the progression of ventilator-induced lung injury. Computed tomography scan analysis suggests that a more homogeneous distribution of strain may be implicated in the protective role of prone position against ventilator-induced lung injury.

Animals↗
PubMed2005

Outcomes of extended donor lung recipients after lung transplantation.

BACKGROUND: Lung transplantation is currently limited by the number of suitable donor organs. Many lung-transplant programs use lungs that do not meet the formal criteria for acceptability; however, the immediate and long-term consequences of this approach remain unclear. METHODS: We performed a retrospective cohort study of all patients who underwent lung transplantation at the Columbia University Medical Center from July 2001 to July 2003. We assessed the outcomes of recipients of extended donor lungs compared with those of recipients of optimal donor lungs after adjusting for confounding variables. RESULTS: Fifty-one patients underwent lung transplantation, of which 27 (53%) received extended donor lungs. Recipients of extended donor lungs had fewer intensive care unit-free days at 30 days (P=0.002) and a longer time to hospital discharge (P=0.007) than did recipients of optimal donor lungs. Extended donor recipients also had lower forced expiratory volume in 1 second % predicted at 1 year than did optimal donor recipients (P=0.03). There were no differences in the 30-day or longer-term survival of extended and optimal donor lung recipients. CONCLUSIONS: Recipients of extended donor lungs have a longer intensive care unit course, a prolonged hospital stay, and lower pulmonary function at 1 year than recipients of optimal lungs. Despite these differences, survival is similar between the two groups. The criteria for the optimal lung donor should be re-evaluated considering the current shortage of acceptable organs. Although some outcomes may differ with the use of extended donor lungs, the clinical impact of these differences should be assessed in future prospective multicenter studies.

Adult↗
PubMed2001

[Clinical study of ischemic preconditioning on isolated lung perfusion with chemotherapeutic agents in the treatment of unresectable lung cancer].

OBJECTIVE: To determine the effect of ischemic preconditioning on isolated lung perfusion (ILP) with chemotherapeutic agents in the treatment of unresectable lung cancer. METHODS: Eight patients with unresectable cancer or metastatic sarcomas in lungs underwent isolated single lung perfusion with doxorubicin. Eight patients were randomly divided into two groups: control group (Group C) and ischemic preconditioning group(Group IP). Group C was only performed isolated lung perfusion with doxorubicin; Group IP was performed isolated lung perfusion with doxorubicin after ischemic preconditioning (in ischemic preconditioning procedure, right or left pulmonary artery was clamped for 10 minutes, then released for 15 minutes). RESULTS: The mean pulmonary artery pressure (MpaP) after ILP in Group IP was much lower than that in Group C (P < 0.05). The PaO2 after ILP in Group IP was much higher than that in Group C(P < 0.01). The lung histologic examination after ILP showed that pulmonary edema, inflammatory cell infiltration, mild focal hemorrhage and alveolar disruption in Group C were significantly serious than those in Group IP, but there was no hospital death in Group C or in Group IP. The complications included hypovolemia shock and acute lung injury. Following up 2 months to 10 months, no death was observed, and the tumours diminished in various degrees or disappeared in the two groups. CONCLUSION: Isolated lung perfusion with chemotherapy can be done safely and effectively in patients with unresectable lung malignancies and metastatic sarcoma in the lung, and ILP can cause lung injury, but lung ischemic preconditioning can reduce the lung injury after isolated lung perfusion.

Adult↗
PubMed1995

Lung fluid restriction affects growth but not airway branching of embryonic rat lung.

During the later stages of fetal life lung growth and development is dependent upon a variety of factors, including a normal amount of liquid within the lung's lumen. To investigate whether embryonic lung epithelium secretes fluid and whether lung liquid is essential for proper embryonic airway lung growth and branching, we incubated 12-day rat lung primordia (term=22 days) in submersion culture in serum-free medium for 48 h in room air (21% O2/5% CO2). Under these conditions, lung growth and branching proceeded but at a slower rate when compared to growth and branching in vivo. Neither addition of serum nor incubation in a fetal O2 concentration (=3% O2) changed the growth rate or the degree of branching in vitro. The luminal area of the explant increased progressively with time in culture. Inhibitors of active Cl- secretion (200 microM bumetanide and 1 mM furosemide) significantly reduced the lumen size compared with control. A similar effect was noted with lung explants of 13-15 days of gestation. Branching morphogenesis was not impaired by lung fluid reduction. Reduction of luminal liquid significantly increased DNA synthesis of 12-day embryonic lung explants, but this effect of bumetanide and furosemide on DNA synthesis was reversed when 13-15 day lung explants were used. These data suggest that embryonic lung epithelium secretes fluid and that the secretion is chloride dependent. Lung fluid is involved in controlling lung growth but not branching of the embryonic rat lung.

Aerobiosis↗
PubMed1995

Lung preservation threshold in a compromised septic lung injury model.

BACKGROUND: Discrepancy between clinical and research works in lung transplantation could be due to differences between compromised clinical donor lungs and intact research lungs. The purpose of this laboratory study was to produce compromised lungs to compare with normal ones. METHODS: Sprague-Dawley rats were continuously infused with lipopolysaccharide (5 mg/kg) for 24 hours before organ harvest. Lungs were stored in University of Wisconsin solution at 4 degrees C for the following period: group 1: intact lungs, no storage (n = 12); group 2: septic lungs, no storage (n = 6); group 3: septic lungs for 6 hours (n = 5); and group 4: septic lungs for 12 hours (n = 5). All lungs were reperfused for 2 hours with venous blood using an isolated, pulsatile perfused lung system. RESULTS: Experimental variables were comparable between groups 1, 2, and 3. All septic lungs stored for 12 hours (group 4) failed within 1 hour of perfusion. CONCLUSIONS: These results indicate that compromised lungs with septic injury functioned at near control levels after 6 hours of preservation. Six hours may be a safe limit for human donor lungs, all of which are compromised in some way by the time of harvest.

Animals↗
PubMed2004

Regional differences in lung radiosensitivity after radiotherapy for non-small-cell lung cancer.

PURPOSE: To study regional differences in lung radiosensitivity by evaluating the incidence of radiation pneumonitis (RP) in relation to regional dose distributions. METHODS AND MATERIALS: Registered chest CT and single photon emission CT lung perfusion scans were obtained in 106 patients before curative or radical radiotherapy for non-small-cell lung cancer. The mean lung dose (MLD) was calculated. The single photon-emission CT perfusion data were used to weigh the MLD with perfusion, resulting in the mean perfusion-weighted lung dose. In addition, the lungs were geometrically divided into different subvolumes. The mean regional dose (MRD) for each region was calculated and weighted with the perfusion of each region to obtain the mean perfusion-weighted regional dose. RP was defined as respiratory symptoms requiring steroids. The incidence of RP for patients with tumors in a specific subvolume was calculated. The normal tissue complication probability (NTCP) parameter values for the TD(50), and an offset NTCP parameter for tumor location were fitted for both lungs and for each lung subvolume to the observed data using maximum likelihood analysis. RESULTS: The incidence of RP correlated significantly with the MLD and MRD of the posterior, caudal, ipsilateral, central, and peripheral lung subvolumes (p between 0.05 and 0.002); no correlation was seen for the anterior, cranial, and contralateral regions Similarly, a statistically significant correlation was observed between the incidence of RP and the perfusion-weighted MLD and perfusion-weighted MRD for all regions, except the anterior lung region. For this region, the dose-effect relation improved remarkably after weighting the local dose with the local perfusion. A statistically significant difference (p = 0.01) in the incidence of RP was found between patients with cranial and caudal tumors (11% and 40%, respectively). Therefore, a dose-independent offset NTCP parameter for caudal tumors was included in the NTCP model, improving most correlations significantly, confirming that patients with caudal tumors have a greater probability of developing RP. CONCLUSION: The incidence of RP correlated significantly with the MLD and MRD of most lung regions, except for the anterior, cranial, and contralateral regions. Weighting the local dose with the local perfusion improved the dose-effect relation for the anterior lung region. Irradiation of caudally located lung tumors resulted in a greater risk of RP than irradiation of tumors located in other parts of the lungs.

Adult↗
PubMed1992

Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1996

Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux.

Neutral endopeptidase (NEP; CALLA, CD10, EC 3.4.24.11) is a cell surface endopeptidase that hydrolyses bioactive peptides, including the bombesin-like peptides, as well as other neuropeptides. Bombesin-like peptides and other neuropeptides are autocrine growth factors for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Low expression of NEP has been reported in SCLC and NSCLC cell lines. NEP inhibition has been shown to increase proliferation in one cell line. To date, NEP expression has not been quantitatively evaluated in normal adult lung, SCLC or NSCLC tumors, paired uninvolved lung from the same patient, or in other pulmonary neoplasms such as mesotheliomas and carcinoids. We examined the expression of NEP in these tissues and human cell lines using immunohistochemistry, flow cytometry, enzyme activity, ELISA, Western blot, and reverse transcription (RT)-PCR. Uninvolved lung tissue from different individuals displayed considerable variation in NEP activity and protein. By immunohistochemistry, NEP expression was detectable in alveolar and airway epithelium, fibroblasts of normal lung, and in mesotheliomas, whereas it was undetectable in most SCLC, adenocarcinoma, squamous cell carcinoma, and carcinoid tumors of the lung. NEP activity and protein levels were lower in all SCLC and adenocarcinoma tumors when compared to adjacent uninvolved lung, often at levels consistent with expression derived from contaminating stroma. NEP expression and activity were reduced or undetectable in most SCLC and lung adenocarcinoma cell lines. NEP mRNA by RT-PCR was not expressed or was in low abundance in the majority of lung cancer cell lines. The majority of lung tumors did not express NEP by RT-PCR as compared with normal adjacent lung. In addition, recombinant NEP abolished, whereas an NEP inhibitor potentiated, the calcium flux generated by neuropeptides in some lung cancer cell lines, demonstrating potential physiological significance for low NEP expression. NEP, therefore, is a signal transduction and possibly a growth modulator for both SCLC and NSCLC, emphasizing the role of neuropeptides in the pathogenesis of the major histological forms of lung cancer.

Adenocarcinoma↗
PubMed2006

PEEP has beneficial effects on inflammation in the injured and no deleterious effects on the noninjured lung after unilateral lung acid instillation.

OBJECTIVE: In clinical lung injury areas of inflammation and structural alveolar alteration are unevenly distributed and interspaced between healthy or less injured lung areas. Positive end-expiratory pressure (PEEP) applied with mechanical ventilation (MV) may affect injured and healthy lung areas differently. We compared the effects of PEEP on the inflammatory response in injured and noninjured regions of the lung in an animal model of unilateral lung acid instillation. SUBJECTS: Anesthetized, paralyzed, and ventilated rats. INTERVENTIONS: Rats underwent left-endobronchial instillation with either hydrochloric acid or isotonic saline and were randomized 24 h later to MV using constant tidal volume (16 ml/kg) with either ZEEP, PEEP at 5 mmHg, or PEEP at 10 mmHg. After 4 h of MV the animals (n=9 or 10 per group) were killed and inflammatory markers assessed in left- and right-lung lavage fluid samples. In four additional animals per group differential lung perfusion was assessed. RESULTS: Unilateral acid injury alone worsened oxygenation, decreased left-lung perfusion, and increased left-lung lavage neutrophil and macrophage counts and cytokine levels. MV with ZEEP further impaired oxygenation and further decreased left-lung perfusion in acid-injured animals. MV with high PEEP preserved oxygenation and significantly decreased left-lung lavage protein content and cell counts in acid-injured animals and had no deleterious effect on the right (noninjured) lung. CONCLUSION: In this model of unilateral lung acid injury high PEEP attenuates the inflammatory cell response in the acid-injured lung, preserved oxygenation and has no deleterious effects in the opposite lung.

Administration, Inhalation↗
PubMed1991

[Hemodynamic effects of lung inflation during bilateral and single lung ventilation--a clinical investigation].

Hemodynamic changes during positive airway pressure ventilation is well known. To compare changes of hemodynamic variables during one-lung inflation with those during two-lung inflation, we studied the effects of lung inflation on hemodynamic changes in 15 anesthetized patients who were intubated endobronchially. When the airway pressure was increased from 0 cmH2O to 10, 20, 30 cmH2O, systolic pressure decreased gradually and central venous pressure increased during both two-lung and one-lung inflations (P less than 0.05). During one-lung inflation, the decrease in arterial pressure relative to apneic arterial pressure was significantly less than those during two-lung inflation at each level of airway pressure (P less than 0.05). During one-lung inflation, central venous pressure which was higher relative to apneic central venous pressure, and was less than that during two-lung inflation at 30 cmH2O (P less than 0.05). Heart rate was unchanged during both two and one-lung inflations compared with apneic heart rate. We conclude that during one-lung inflation, systolic pressure and central venous pressure are influenced less by the increased airway pressure than during two-lung inflation. The results indicate that during one lung ventilation, lungs inflated with clinically accepted levels of airway pressure do not depress the systemic circulation, but when the airway pressure during one-lung inflation (like a leak test) exceeded over 30 cmH2O, a significant depression of the systemic circulation occurs.

Aged↗
PubMed1995

High frequency of K-ras mutations in normal appearing lung tissues and sputum of patients with lung cancer.

To evaluate the possible use of mutant ras as a biomarker for lung cancer, we have analyzed "normal appearing" lung tissue, lung tumor, lung metastases and sputum samples from patients with non-small cell lung cancer (NSCLC). As a control, we used lung tissue and sputum samples from patients without oncological diseases or lung disorders. Our analyses were performed with the aid of enriched PCR (EPCR), a method which enables detection of ras mutation even if present at low incidence. EPCR identified K-ras codon 12 mutations in 10% of lung tissues obtained from patients with no lung diseases, whereas the same mutation was detected in 60% of samples of normal appearing lung tissues obtained from patients with NSCLC, 62% of NSCLC tumors and 80% of metastases. Analysis of sputum samples of patients with NSCLC identified 47% to harbor mutant ras allele, whereas 12.5% of controls diagnosed with non-oncological lung diseases carried this mutation. Most of these mutations were detected with the aid of EPCR only, indicating that a minority of cells in a given sample harbor this mutation. The ability to detect K-ras codon 12 mutation in 60% of lung tissue samples and in 47% of sputum samples taken from patients with lung cancer (as compared with 10% and 12.5% of respective controls) points to the potential use of ras mutation as a biomarker for exposure and possible identification of patients who may be at higher risk of developing lung cancer.

Aged↗
PubMedDate not supplied

Carcinogen metabolism and DNA adducts in human lung tissues as affected by tobacco smoking or metabolic phenotype: a case-control study on lung cancer patients.

Individual variations in activity of pulmonary enzymes that metabolize tobacco-derived carcinogens may affect an individual's cancer risk from cigarette smoking. To investigate whether some of these enzymes (e.g., cytochrome P450IA-related) can serve as markers for carcinogen-induced DNA damage accumulating in the lungs of smokers, non-tumorous lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (n = 54) or non-neoplastic lung disease (n = 20). Phase I (AHH, ECDE) and phase II (EH, UDPGT, GST) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were analyzed for DNA adducts, using 32P-postlabeling. Data analysis of subsets or the whole group of patients yielded the following results. (1) Phase I and II drug-metabolizing enzyme (AHH, EH, UDPGT, GST) activities in histologically normal surgical specimens of lung parenchyma were correlated with the respective enzyme activities in bronchial tissues of the same subject. (2) In lung parenchyma, enzyme (AHH, ECDE, EH, UDPGT) activities were significantly and positively related to each other, implying a similar regulatory control of their expression. (3) Mean activities of pulmonary enzymes (AHH, ECDE) were significantly (2- and 7-fold, respectively) higher in lung cancer patients who had smoked within 30 days before surgery (except GST, which was depressed) than in cancer-free subjects with a similar smoking history. (4) In the cancer patients, the time required for AHH, EH and UDPGT activities to return to the level found in non-smoking subjects was several weeks. (5) Bronchial tree and peripheral lung parenchyma preparations exhibited a poor efficiency in activating promutagens to bacterial mutagens in Salmonella. However, they decreased the mutagenicity of several direct-acting mutagens, an effect which was more pronounced in tissue from recent smokers. GSH concentration and GST activity were positively correlated with mutagen inactivation in the same sample. (6) In recent smokers, AHH activity in lung parenchyma was positively correlated with the level of tobacco smoke-derived DNA adducts. (7) Pulmonary AHH and EH activity had prognostic value in tobacco-related lung cancer patients. (8) An enhanced level of pro-oxidant state in the lungs was associated with recent cigarette smoking. Malondialdehyde level in lung parenchyma was associated with the degree of small airway obstruction, suggesting a common free radical-mediated pathway for both lung cancer induction and small airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗