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At least 415 records · Page 23Linked to original sources
PubMed1998

Ischemic preconditioning enhances donor lung preservation in canine lung transplantation.

OBJECTIVE: To prove the protective effect of lung ischemic preconditioning on enhancing the canine lung preservation and reducing allograft lung dysfunction after transplantation. METHODS: Ten pairs of adult canines underwent left lung allotransplantation. Five donors were treated with ischemic preconditioning [their left hilus was clamped for 10 minutes and released for 15 minutes (Group IP)], and five donors were not treated with ischemic preconditioning (Group C). The donor lungs were flushed with 4 degrees C Euro-Collin's solution (ECS) and stored in the same solution for two and a half hour, then transplanted to the recipient canines, who were observed for one to two hours after transplantation. The lung venous blood of the recipient and the donor lung tissue were collected just after thoracotomy and one hour after reperfusion of the transplanted lung in both groups. RESULTS: The number of polymorphonuclear (PMN) was significantly higher in Group IP than in Group C (P < 0.05). However, the number of PMN in lung interstitium under microscope was less in Group IP than in Group C. The thromboxane (TXB2), malondialdehyde (MDA) and mean pulmonary artery pressure (MPAP) contents were significantly lower in Group IP than in Group C (P < 0.05). The superoxide dismutase (SOD) and the lung venous blood oxygen tension (PvO2) contents were significantly higher in Group IP than in Group C (P < 0.05). Histological findings showed less damages in Group IP than in Group C. CONCLUSIONS: The protective effect of ischemic preconditioning together with ECS flush and storage is superior to using ECS alone. The possible mechanisms may be that ischemic preconditioning inhibits the accumulation and activation of PMN in lung tissue and reduces the production of oxygen free radicals.

Animals↗
PubMed1999

[Open lung biopsy in diagnosis of interstitial lung disease].

OBJECTIVE: To evaluate the role of open lung biopsy in diagnosis of interstitial lung disease. METHODS: 24 patients with interstitial lung disease who underwent open lung biopsy from 1993 to June 1998 were reviewed. RESULTS: The documented pathologic diagnosis in 24 patients with interstitial lung disease who underwent open lung biopsies were: 7 IPF (UIP), 1 acute interstitial pneumonia (AIP), 3 BOOP, 2 DPB, 3 sarcoidosis, 2 tuberculosis, 1 histiocytosis-X and 1 lung cancer. Most of these patients did not definitely diagnosed through their clinical evaluation including history, chest X-ray, pulmonary function tests and TBLB. CONCLUSIONS: Open lung biopsy, is a useful method, as it is sensitive and specific in diagnosis of interstitial lung disease. It is helpful in defining the site and extent of interstitial lung disease and diagnosing rare and atypical interstitial lung disease.

Adult↗
PubMed2002

The synthetic retinoid CD437 selectively induces apoptosis in human lung cancer cells while sparing normal human lung epithelial cells.

The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induces apoptosis in a variety of cancer cells including lung cancer cells. Our previous studies have demonstrated that cancer cells with wild-type p53 are more sensitive to CD437 than those having mutant p53, although CD437 can induce both p53-dependent and -independent apoptosis. Because normal human lung epithelial cells have wild-type p53, the question arose as to whether they are also sensitive to CD437-induced apoptosis. To address this question, we compared and contrasted the effects of CD437 on apoptosis induction and the expression of several p53-regulated apoptosis-related genes between normal human lung epithelial cells and human lung cancer cells containing wild-type p53. CD437 induced apoptosis as evidenced by apoptotic morphological changes, increased DNA fragmentation, and activation of caspase cascades in two lung cancer cell lines but not in two normal human lung epithelial cells. CD437 selectively increased the p53 protein level and concomitantly induced the expression of several p53-regulated apoptosis-related genes including Bax, Fas, DR4, and DR5 only in the two lung cancer cell lines. Furthermore, the normal lung epithelial cells, which expressed constitutively higher levels of two antiapoptotic decoy receptors DcR1 and DcR2 than lung cancer cells, exhibited an increase in the expression of these receptors after CD437 treatment, whereas no increase was detected in lung cancer cells. These results predict a differential effect of CD437 on tumor and normal cells in vivo and strongly suggest that CD437 may be a useful agent for chemoprevention and/or treatment of human cancer, especially lung cancer.

Antineoplastic Agents↗
PubMed1991

[Clinical value of perfusion lung scanning in the surgical treatment of lung cancer].

Perfusion lung scanning was performed in 49 patients with lung cancer. The relationships among the percent of tumor-bearing lung perfusion, invasion of the lung cancer, and operability of the tumor were studied. The results showed that the reduction in perfusion was related to involvement of the hilum (t = 4.1, P less than 0.001), and that when the relative perfusion of the tumor-bearing lung was less than one third (33%) of the total lung perfusion, the lung cancer was most likely inoperable (chi 2 = 13.9, P less than 0.0002). In this paper, predictive postoperative FEV1.0 calculated by combining the result of spirometry with quantitative measurement of lung perfusion was compared with actual postoperative FEV1.0 in 19 (19/49) patients. FEV1.0 after pneumonectomy was accurately predicted by the modified Neuhaus' equation (r = 0.929 3, P less than 0.001). Postlobectomy FEV1.0 could be predicted effectively by direct quantitative equation (r = 0.850 2, P less than 0.001), Our results showed that perfusion lung scanning is a very valuable method for preoperative examination of lung cancer. It may enable patients with unresectable lung cancer to save the trouble of exploratory thoracotomy and those with poor pulmonary function to seize the opportunity of surgical treatment.

Adult↗
PubMed1991

A morphometric quantitation of developmental changes in elastic fibers in rat lung parenchyma: variability with lung region and postnatal age.

Elastin has long been thought to play a pivotal role in alveolar septal development by providing the structural framework around which new alveoli develop in the immature lung. This theory was derived from observations that the dramatic increase in lung elastin and alveolar septal development occurred during the same time period, days 4 to 13 in the rat. Using stereologic techniques, we evaluated volume density of respiratory tissue in parenchyma and total length of parenchymal elastic fibers in the lungs of neonatal rats ranging in age from 4 to 26 days. Lung tissue was obtained from each of the four right lung lobes and from the upper, middle, and lower regions of the left lung. When changes in these two parameters in the lung as a whole were considered by averaging values for each of the seven regions, a continuous increase was observed in both the volume of parenchymal tissue in parenchyma and the total length of elastic fibers from days 4 to 22. A significant correlation was found between the volume of respiratory tissue in parenchyma and the length of parenchymal elastic fibers from days 4 to 26, supporting the existing theory that a causal relationship exists between these two parameters. A comparison of the ratios of elastic fiber length to volume density of respiratory tissue in parenchyma (Lv/Vrp) from each of the seven lung regions sampled indicated a significant variability in Lv/Vrp within different regions of the same lung. In addition, the effects of postnatal age and lung region on Lv/Vrp were interdependent; the lung regions that differed with respect to the length density of elastic fibers varied with postnatal age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Generation of monoclonal antibodies against human lung squamous cell carcinoma and adenocarcinoma using mice rendered tolerant to normal human lung.

Four murine monoclonal antibodies against human lung carcinoma were generated using a novel immunization procedure. BALB/c mice were rendered neonatally tolerant to normal human lung tissues and subsequently immunized with human lung tumor tissues. The lower level of antibody-reactivity to the tolerogen was seen in the sera of mice rendered neonatally tolerant as compared with the level of reactivity in the sera of nontolerant mice. The mice which maintained a sufficiently tolerant state were selected for hybridoma production. Two monoclonal antibodies, KM-32 and KM-34, were developed from mice immunized with lung squamous cell carcinoma tissues and two other monoclonal antibodies, KM-52 and KM-93, were developed from mice immunized with lung adenocarcinoma tissues. Distribution of antigens detected by the monoclonal antibodies were investigated by enzyme-linked immunosorbent assay using membrane fractions prepared from a number of tumorous and normal tissues and various human normal and tumor cell lines. KM-32 recognized a carbohydrate antigen expressed predominantly on lung squamous cell carcinoma cells and its carbohydrate structure appeared to be associated with blood group A antigen. KM-93 recognized a sialylated carbohydrate epitope on the antigen expressed on lung adeno-carcinoma cells and a few other tumor cells. KM-34 and KM-52 detected protein or glycoprotein antigens and they showed predominant reactivity to lung squamous cell carcinoma and lung adenocarcinoma, respectively. KM-32 and KM-34 antibodies showed complement-dependent cytotoxicity against a lung tumor cell line. These results suggest that the tolerance technique is useful for efficient screening of murine monoclonal antibodies specific to human tumors. The efficacy of these four monoclonal antibodies in diagnosis and therapy of lung cancer will be the subject of a sequential study.

Adenocarcinoma↗
PubMed1998

Immunohistochemical detection of NAD(P)H:quinone oxidoreductase in human lung and lung tumors.

NAD(P)H:quinone oxidoreductase (NQO1) is a flavoenzyme that catalyzes the two-electron reduction of quinones and related compounds. With the use of biochemical assays, NQO1 has been shown to be overexpressed in many types of cancer, including non-small cell lung cancer (NSCLC). NQO1 can bioactivate antitumor quinones such as mitomycin C, and new quinone-based drugs are currently being developed to target this enzyme in tumors such as NSCLC. Because there is no information on the cell-specific expression of NQO1 in lung, the purpose of this study was to examine the expression of NQO1 in human NSCLC, small cell lung cancer, carcinoid lung tumors, and normal lung using immunohistochemistry. A high level of NQO1 protein expression was detected by immunohistochemistry in NSCLC (adenocarcinoma, squamous cell carcinoma, and bronchoalveolar carcinoma), but no NQO1 protein could be detected in small cell lung cancer or carcinoid lung tumors. In addition, NQO1 protein expression was examined by immunohistochemistry in normal lung tissue. A high level of NQO1 protein expression was detected by immunohistochemistry in normal lung respiratory epithelium, with the highest levels of expression observed in ciliated columnar epithelial cells. Significant amounts of NQO1 protein were also detected in the vascular endothelium and adipocytes. These data demonstrate that NQO1 is overexpressed in NSCLC. Cells in normal lung also contain marked NQO1 protein and may be damaged by drugs activated by NQO1. These data validate NSCLC as a target for NQO1-directed agents and suggest that the potential for lung toxicity be considered in the preclinical development of quinone-based antitumor drugs.

Humans↗
PubMed1995

The effect of irradiation on lung function and perfusion in patients with lung cancer.

PURPOSE: To prospectively study the changes in lung function in patients with lung carcinoma treated with relatively high doses of irradiation. METHODS AND MATERIALS: Lung function was assessed prior to and at 6 and 12 months following radiation therapy by a clinical dyspnea score, formal pulmonary function tests (lung volume spirometry and diffusion capacity) as well as an ipsilateral hemithorax lung perfusion scan. Changes in dyspnea score were evaluated by the chi-square and the Fishers exact test. Changes in formal lung function tests were compared with the t-test for dependent data and correlations with the t-test for independent data. Fifty-one patients were entered into the study. There were 42 evaluable patients at 6 months after irradiation and 22 evaluable patients at 12 months after irradiation. RESULTS: A worsening of dyspnea score from 1 to 2, which is clinically acceptable, occurred in 50% or more of patients. However, a dyspnea score of 3, which is a serious complication, developed in only 5% of patients. The diffusion capacity (DLCO) decreased by 14% at 6 months and 12% at 12 months) (p < 0.0001). The forced vital capacity and total lung capacity decreased between 6% and 8% at 6 months and 12 months, which was statistically significant. The forced expiratory volume in 1 s decreased between 2 and 3% at 6 month and 12 months, which was not statistically significant. The ipsilateral hemithorax perfusion decreased by 17 and 20% at 6 and 12 months (p < 0.0001). There was no correlation between the initial hemithorax perfusion, or its decrease at follow up and the decrease in DLCO. CONCLUSION: Lung irradiation results in some loss of lung function in patients with lung cancer with a projected survival of 6 months or more. The pretreatment DLCO assessment should be useful in predicting clinical tolerance to irradiation.

Adult↗
PubMed1996

Contralateral lung injury associated with single-lung ischemia-reperfusion injury.

BACKGROUND: There have been very few studies on the effect of single-lung ischemia-reperfusion on the function of the contralateral lung. This study was designed to clarify the effect. METHODS: Fifteen mongrel dogs were divided into two groups. In group 1 (n = 7), the left lung was subjected to ischemia without ventilation for 90 minutes, and then reperfused. In group II (n = 8), the lung was not subjected to ischemia, and was ventilated during the 90-minute ischemia of group I. Arterial blood gas, hemodynamics, extravascular lung water, and airway pressure were measured. Pulmonary biopsy was performed to evaluate adenine nucleotide levels. The protein concentration and phosphorous concentration of phospholipids in bronchoalveolar lavage fluid were measured. RESULTS: Group I, with perfusion and ventilation of the right lung alone, was significantly inferior to group II with respect to arterial blood gas, right pulmonary compliance, extravascular lung water of the right lung, and the protein concentration in the bronchoalveolar lavage fluid of the right lung after the 90-minute period. CONCLUSIONS: These results indicate that 90 minutes of warm ischemia and reperfusion of the left lung caused deterioration of not only the left but also contralateral right pulmonary function.

Adenine Nucleotides↗
PubMed2003

Living-donor lobar lung transplantation for various lung diseases.

OBJECTIVE: We report on our early experience in living-donor lobar lung transplantation for patients with various lung diseases including restrictive, obstructive, septic, and hypertensive lung diseases. METHODS: From October 1998 to March 2002, living-donor lobar lung transplantation was performed in 14 patients with end-stage lung diseases. There were 11 female patients and 3 male patients, with ages ranging from 8 to 53 years, including 4 children and 10 adults. Diagnoses included primary pulmonary hypertension (n = 6), idiopathic interstitial pneumonia (n = 2), bronchiolitis obliterans (n = 2), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and cystic fibrosis (n = 1). Bilateral living-donor lobar lung transplantation was performed in 13 patients and right single living-donor lobar lung transplantation was performed for a 10-year-old boy with primary pulmonary hypertension. RESULTS: All the 14 patients are currently alive with a follow-up period of 4 to 45 months. Although their forced vital capacity (1327 +/- 78 mL, 50.2% of predicted) was limited at discharge, arterial oxygen tension on room air (98.5 +/- 1.8 mm Hg) and systolic pulmonary artery pressure (24.8 +/- 1.6 mm Hg) were excellent. Forced vital capacity improved gradually and reached 1894 +/- 99 mL, 67.4% of predicted, at 1 year. All donors have returned to their previous lifestyles. CONCLUSIONS: Living-donor lobar lung transplantation can be applied to restrictive, obstructive, septic, and hypertensive lung diseases. This type of procedure can be an alternative to conventional cadaveric lung transplantation for both pediatric and adult patients who would die soon otherwise.

Adolescent↗
PubMed2000

Czech Study on Lung Cancer Screening: post-trial follow-up of lung cancer deaths up to year 15 since enrollment.

BACKGROUND: The study was launched in the mid-1970s to explore the capability of screening by chest X-ray and sputum cytology to be used as an effective component of the lung cancer control program in the Czech Republic, a Central European country with a high and increasing occurrence of lung cancer in men at that time. A complementary objective of this report is to ascertain whether the cumulative numbers of lung cancer deaths would equalize in the two randomized groups during a prolonged follow-up period. METHODS: Six thousand three hundred sixty-four males who were heavy cigarette smokers, aged 40-64 years, were enrolled during a general health survey in 6 districts of the Czech Republic. At initial X-ray and sputum examination, 19 prevalent lung carcinoma cases were diagnosed. After stratified randomization, the remaining subjects entered a 3-year study: the intervention group (3171 participants) was subjected to semiannual chest X-rays and sputum investigation whereas the controls (3174 participants) had 1 examination only by chest X-rays and sputum investigation, 3 years after entry. During a further 3-year follow-up, a chest X-ray was taken at the end of Years 4, 5, and 6 for both the intervention and control groups. Subjects in both groups who were suspected to have lung carcinoma or other disease on the basis of screening results or symptoms were subjected to appropriate diagnostic studies and treatment. Data on all causes of death in Years 1-6 and on deaths from the lung cancer in Years 7-15 of participants in the intervention and control groups were compared. RESULTS: The incidence rate of lung carcinoma from the intervention group was significantly higher than from the controls in the initial 3-year study period (P < 0.05), but not for the initial 6-year period (P = 0.06). Lung carcinoma cases detected by screening were identified at an earlier stage, were more often resectable, and had a significantly better survival than interval cases diagnosed mainly because of symptoms. There was no significant difference in the lung cancer mortality rate between the 2 groups in the initial 3-year study period or during follow-up prolonged up to Year 15 since enrollment. CONCLUSIONS: The study gave no evidence that screening for lung cancer by chest X-ray is beneficial in terms of reducing mortality. Based on the results of this study, there is no justification to recommend semiannual screening as a component of a comprehensive lung cancer control program.

Adult↗
PubMed1986

Comparison of cell-mediated and humoral immunity in the dog lung after localized lung immunization.

This study evaluated cell-mediated immunity (CMI) and antibody production serially in control and immunized lung lobes of beagle dogs. A fiberoptic bronchoscope was used to immunize selected airways in the left cardiac lung lobe with 10(10) sheep red blood cells (SRBC); the right cardiac lobe received saline as control. The immune responses produced by this localized lung immunization were evaluated in cells and fluids obtained from blood and serial bronchial washings of the immunized and control lung lobes from 5 to 21 days after immunization. The antigen-specific production of procoagulant activity (LPCA) and inhibition of migration of alveolar macrophages by SRBC antigen were used to measure CMI in lavage cells from immunized and control lung lobes. The level of specific IgM and IgG antibody in lavage fluid from the control and immunized lung lobes was evaluated with the enzyme-linked immunosorbent assay (ELISA). The results of this study showed a significantly greater percentage of neutrophils and lymphocytes in the lavage fluid from the immunized lung lobes than from the control lung lobes. The increased number of lymphocytes in the immunized lung lobes showed a positive correlation with increased antibody concentrations. In contrast to the antibody response, CMI as measured by LPCA and MIF assays was positive, with nearly equal responses in control and immunized lung lobes. Even though there were only a few lymphocytes in the control lung lobes, there were apparently enough specific immune lymphocytes present that produced mediators after antigen stimulation to result in positive CMI responses.

Animals↗
PubMed1987

Identification of plasma cells in lung alveoli and interstitial tissues after localized lung immunization.

Large numbers of antibody-forming cells (AFC) can be identified with the Jerne plaque assay in immunized lung lobes of the beagle dog after localized instillation of particulate antigen. Published data suggest that these AFC are secreting antibody and are responsible for increased levels of specific antibody in immunized lung lobes. If AFC in the lung are actively secreting antibody, there should be an increase in the number of mature plasma cells in lung lobes exposed to antigen. The purposes of this study were to evaluate the number of lymphoid cells present in immunized and control lung lobes and to determine if lung immunization produces a localized increase in the number of plasma cells. Sheep red blood cells (SRBC), autologous dog red blood cells, and saline were instilled into specific lung lobes of beagle dogs with the aid of a fiberoptic bronchoscope. Light and transmission electron microscopy studies of tissues from lung lobes instilled with SRBC showed perivascular infiltrates and intra-alveolar accumulations of lymphoid cells which were not present in control lung lobes. The morphology of these lymphoid cells ranged from small lymphocytes through mature plasma cells. From 5% to 15% of the cells present in the interstitial tissues and alveoli of immunized lung lobes were plasma cells. These observations suggest that lymphoid cells which entered the SRBC immunized lung can mature to plasma cells which are probably responsible for the local production of antigen-specific antibody.

Animals↗
PubMed2003

Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma.

Fas (CD95) and its ligand FasL signal apoptosis and are involved in tissue homeostasis and the elimination of target cells by cytotoxic T cells. Corruption of this signalling pathway in tumour cells, for example by reduced Fas expression or increased FasL expression, can participate in tumour development and immune escape. The present study has analysed Fas/FasL expression and Fas death signalling function in vivo in lung tumour tissues [57 non-small cell lung carcinomas and 64 neuroendocrine lung tumours including small cell lung carcinoma (SCLC)] in comparison with normal lung tissue, and in vitro in neuroendocrine tumour cell lines in comparison with normal human bronchial epithelial cells. The Fas expression score was markedly decreased compared with normal lung tissue in 90% of the 121 lung tumours and was completely lost in 24%. The Fas staining pattern suggested cytoplasmic Fas expression in tumours, whereas membrane expression was observed in normal lung tissue. Loss of Fas at the cell surface was also shown in vitro by FACS analysis of neuroendocrine tumour cell lines and was concomitant with the resistance of tumour cells to FasL-mediated apoptosis according to in vitro cell viability. The lack of cell surface Fas expression in tumour cell lines resulted from the lack of intracellular Fas protein due to impaired Fas gene transcription. The FasL expression score was also decreased in most non-small cell lung carcinomas compared with normal bronchial cells, whereas 91% of SCLCs had higher expression than normal cells. FasL overexpression was related to advanced tumour stage as well as to a Fas/FasL ratio less than 1. It is concluded that a marked decrease in Fas expression may be part of lung tumourigenesis allowing tumour cells to escape from apoptosis. FasL overexpression in the context of Fas down-regulation in SCLC predicts the ability of SCLC cells to induce paracrine killing of Fas-expressing cytotoxic T cells. In lung tumours, Fas restoration may represent a key, although not unique, step in therapeutic strategies to reconstitute the ability of tumour cells to undergo apoptosis.

Apoptosis↗
PubMed2004

Lung growth induced by prenatal instillation of perfluorocarbon into the fetal rabbit lung.

The study's aim was to evaluate whether prenatal instillation of perfluorooctylbromide (PFOB, a perfluorocarbon) into the lungs of fetal rabbits leads to increased lung growth. Hysteroamniotomy was performed in eight pregnant New Zealand white rabbits on gestational day 27. In each mother, four fetuses were randomized to undergo either 1) endotracheal intubation and intrapulmonary instillation of 1 ml PFOB, 2) intrapulmonary instillation of 1 ml 0.9% NaCl solution (saline), 3) no fetal manipulation (control), or 4) tracheal occlusion (TO). The distribution of PFOB was documented radiographically. The fetuses were born by cesarean section after 48 h, sacrificed, weighed, and their lungs excised. Fetal lung to body weight ratios (FLBW) were determined, and the lungs were snap frozen for histomorphologic analysis and lung tissue distillation. On macroscopic inspection, PFOB-filled and tracheally-occluded lungs were markedly larger than saline-filled and control lungs. Mean FLBW was higher in fetuses treated with intrapulmonary instillation of PFOB (0.037+/-0.009), compared with fetuses receiving saline (0.027+/-0.008) or the unmanipulated controls (0.028+/-0.008). FLBW was highest after TO (0.049+/-0.008). After 48 h, in-vivo radiographs did not demonstrate any residual PFOB. Average dry fetal left lung weight (in g) was much higher in the TO (0.064+/-0.029) and PFOB (0.062+/-0.016) fetuses compared with the saline (0.054+/-0.017) and control (0.043+/-0.012) groups. Alveolar architecture on microscopy was similar between all groups, although the alveolar septae appeared thicker and more cellular after PFOB treatment and TO. We concluded that prenatal intrapulmonary PFOB instillation leads to increased lung growth in the late gestation rabbit model. Although PFOB instillation resulted in lower wet FLBW than TO, the increase in dry lung weight is comparable. This novel technique may be a less invasive and less noxious treatment strategy for pulmonary hypoplasia associated with diaphragmatic hernia.

Animals↗
PubMed1995

Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors.

We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low-potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Array CGH analysis reveals chromosomal aberrations in mouse lung adenocarcinomas induced by the human lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

Exposure to genotoxic carcinogens in tobacco smoke is a major cause of lung cancer. However, the effect this has on DNA copy number and genomic stability during lung carcinogenesis is unclear. Here we used bacterial artificial chromosome array-based comparative genomic hybridization to examine the effect of NNK, a potent human lung carcinogen present in tobacco smoke, on the major genomic changes occurring during mouse lung adenocarcinogenesis. Observed were significantly more gross chromosomal changes in NNK-induced tumors compared with the spontaneous tumors. An average of 5.6 chromosomes were affected by large-scale changes in DNA copy number per NNK-induced tumor compared with only 2.0 in spontaneous lung tumors (p = 0.017). Further analysis showed that gains on chromosomes 6 and 8, and losses on chromosomes 11 and 14 were more common in NNK-induced tumors (p <or= 0.002). The changes on chromosomes 8, 11, and 14 were positively (p <or= 0.001) associated with the degree of chromosome instability (CIN). This association was less significant for gains on chromosomes 6 and 12 (p = 0.035). In contrast, loss of distal chromosome 4 was very frequent (71%) in both NNK-induced and spontaneous tumors, and showed no association with CIN phenotype. Each of these chromosomes contains sites of orthology with those altered in human lung adenocarcinomas, suggesting similar roles in human lung cancer. We next investigated the mechanism of NNK-induced CIN and found that a genotoxic metabolite of this carcinogen causes numerous karyotypic changes in lung epithelial cells. With similar changes evident in NNK-induced tumors, this suggests that the persistence of such damage in exposed lung epithelia may initiate CIN during lung carcinogenesis. These results show for the first time that NNK potently induces gross chromosomal alterations in lung adenocarcinogenesis and modulates the evolutionary pathway of these tumors through the recruitment of genes with altered DNA copy number.

Adenocarcinoma↗
PubMed2004

Lobar transplantation, split lung transplantation and peripheral segmental resection--reliable procedures for downsizing donor lungs.

OBJECTIVES: The increasing scarcity of donor lungs, especially for small and pediatric recipients has stimulated the development of new operative techniques, which allow larger lungs to be downsized for use in smaller recipients. This approach has only recently gained widespread use-especially for highly urgent recipients-however, it is still not considered a standard procedure. METHODS: This report reviews the Vienna University experience with cadaveric split lung transplantation, lobar transplantation and by means of peripheral resection size reduced lung transplantation within the years 2001-2002. Peri-operative complications and outcome of those patients were retrospectively analysed and compared to the patients undergoing standard single or double lung transplantation during the observation period. RESULTS: During the observation period 98 primary lung transplantations were performed, of which 27 (27.6%) were size reduced transplantations. Size reduction was achieved by lobar transplantation (n=9), split lung transplantation (n=2) or peripheral segmental resection (n=16). There was no statistically significant difference between the size reduced and standard lung transplantation group with regard to the rate of bronchial healing problems (n=3/7; P=0.85) and the rate of post-operative bleeding (n=5/12; P=0.85). No other major thoracic surgical complications were observed. Three months survival rate was 85.2% in the size reduced group, compared to 92.9% in the standard group (P=0.13). CONCLUSIONS: Size reduced lung transplantation, including split lung transplantation, lobar transplantation and peripheral segmental resection, is a reliable procedure providing equal results compared to standard lung transplantation.

Adolescent↗