Transforming growth factor beta contributes to lung leak in rats given interleukin-1 intratracheally

Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute lung injury (ALI) and administering recombinant human IL-1alpha (rhIL-1alpha) (50 ng) intratracheally causes an acute, neutrophil-dependent, oxidative lung leak in rats that closely resembles human ALI. In the present work, the authors tested the hypothesis that transforming growth factor beta (TGFbeta) contributes to the lung inflammation and injury that develops in rats given IL-1 intratracheally. They found that intravenous administration of a monoclonal antibody to TGFbeta (1.D.11.16, 0.5 mg/kg) attenuated lung injury responses, specifically lung leak index, lung lavage protein concentrations, and blood oxygenation abnormalities, that are observed 5 hours after intratracheal instillation of IL-1 in rats, but did not decrease indices of lung inflammation, specifically myeloperoxidase (MPO) activity in lung tissue, neutrophil counts in lung lavage, and cytokine-induced neutrophil chemoattractant (CINC) levels in lung lavage, in rats given IL-1 intratracheally. The results suggest that TGFbeta contributes to lung leak, but not lung inflammation, following intratracheal administration of IL-1 in rats.     

Relationship between maternal and fetal lung growth

This study analyzes the relationship between the maternal and fetal lungs, in rats in relation to litter size, to determine whether the enlargement of maternal lung during pregnancy is concurrent with that of the fetal lung. Pregnant albino rats were sacrificed on gestation day 21 (term 22 days). Maternal lung growth was assessed by measuring the lung weight, lung air volume and lung DNA content, and the fetal lung growth by lung DNA content. The findings were as follows: (1) no differences were noted between the lungs of non-pregnant rats and pregnant rats with small litter size (1-4); (2) pregnant rats with large litter size (10-18) had larger lungs than rats with small litter size; (3) there was a direct relationship between cellularity (DNA content) of the fetal lung and maternal lung when the latter underwent a growth change during pregnancy; (4) no relationship in cellularity was found between the maternal lung and placenta nor between the fetal lung and placenta. The results suggest that factors or processes which regulate the growth and dictate the size of the maternal lung during pregnancy similarly influence the fetal lung.     

Alterations in pulmonary function of premature lambs due to positive end-expiratory pressure.

These studies compare lung mechanics and volumes of premature lambs delivered at 139 days of gestation by cesarean section and ventilated by either intermittent positive pressure (IPP) or positive end-expiratory pressure (PEEP). During the first few hours of life, sequential determinations of lung compliance, specific lung compliance; lung resistance, specific lung conductance and functional residual capacity were made at half-hour intervals. Measurements in 5 lambs ventilated with PEEP demonstrated that lung compliance (p less than 0.005), specific lung compliance (p less than 0.001) and specific lung conductance (p less than 0.005) decreased; while lung resistance (p less than 0.10) and functional residual capacity (p less than 0.02) increased as compared to 7 lambs ventilated with IPP.     

Influence of maternal pneumonectomy on fetal lung growth

This study was conducted to test the hypothesis that the compensatory growth of the maternal lung during pregnancy influences fetal lung growth, specifically the fetal lung DNA content. A left pneumonectomy (PN) was performed in pregnant albino rats at different gestation days (GD 3, 7, 9, 10, 12, 14, 16 and 18) and the rats sacrificed at GD 21. Only mothers with litter size of 9-14 fetuses were used for this study. Maternal lung growth was assessed by measuring lung weight, lung air volume and lung DNA content, and the fetal lung growth by lung DNA content. The findings were: (1) pregnancy did not influence the rate of compensatory growth of the remaining lung following PN; (2) neither thoracotomy nor PN had any effect on placental weight or DNA content; (3) lung DNA content for body weight was larger in fetuses of PN rats when PN was performed in the first half of gestation; (4) there was a direct relationship between DNA content of the fetal lung and maternal lung in PN rats; and (5) neither thoracotomy nor PN in pregnant rats influenced the maturation of the fetal lung. The results suggest that a growth factor(s), specific for lungs, is released into maternal circulation following PN, crosses the placenta and enhances the fetal lung growth without affecting its maturation.     

Effects of partial liquid ventilation on unilateral lung injury in dogs

STUDY OBJECTIVE: The overall physiologic effect of partial liquid ventilation (PLV) in the setting of unilateral lung injury remains unclear. Therefore, we evaluated the effect of PLV on gas exchange in unilateral lung injury. DESIGN AND METHODS: Left unilateral lung injury was induced in 14 adult dogs by oleic acid instillation into a left pulmonary artery. The animals were divided into two groups: gas ventilation (GV) and PLV. During both GV and PLV, systemic blood gas levels were analyzed. Oxygen consumption (O(2)), carbon dioxide production (CO(2)) and pulmonary blood flow (Q) of both the right lung (uninjured lung) and left lung (injured lung) were measured. RESULTS: During PLV, O(2) of the injured left lung (o(2)-injured), CO(2) of the injured left lung (CO(2)-injured), and Q of the injured left lung (Q-injured) were greater than those in GV (O(2)-injured, 41.6 mL/min vs 23.4 mL/min, p = 0.006; CO(2)-injured, 34.4 mL/min vs 25.5 mL/min, p = 0.026; and Q-injured, 0.47 L/min vs 0.22 L/min, p = 0.002, respectively). However, overall PaO(2) during PLV was less than that during GV, likely due to either a redistribution of Q toward the injured lung (PLV Q-injured, 0.47 L/min vs GV Q-injured, 0.22 L/min; p = 0.002) or reduced gas exchange efficiency in the healthy lung. CONCLUSIONS: We conclude that in our model, PLV increases O(2) and VCO(2) in the injured lung. However, over all gas exchange efficiency is reduced.     

Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats

In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO.     

肺癌标志物芳烃羟化酶的临床应用意义探讨

目的　寻找较为理想的肺癌标志物 ,为肺癌的早期诊断提供帮助。方法　采用荧光分光光度仪对 5 1名正常人、30例良性肺病患者及 93例不同病理分型、不同分期的肺癌患者 (腺癌 30例 ,鳞癌 30例 ,小细胞癌 33例 ;Ⅰ、Ⅱ期患者 2 8例 ,Ⅲ期患者 35例 ,Ⅳ期患者 30例 )外周血淋巴细胞芳烃羟化酶 (AHH)活性及变化进行了观察并与癌胚抗原 (CEA)进行了对比。结果　肺癌患者外周血淋巴细胞AHH活性为 (4 9± 2 1)pmol·min 1·10 6细胞 ,其中鳞癌患者、正常人和良性肺病患者分别为(7 3± 1 9)、(1 1± 0 7)和 (1 2± 0 6 )pmol·min-1·10 -6细胞 ,提示肺癌患者外周血淋巴细胞AHH活性显著高于正常人及良性肺病患者 ,尤以鳞癌为著。此外 ,Ⅰ、Ⅱ期患者外周血淋巴细胞AHH活性为(3 7± 1 4)pmol·min-1·10 -6细胞 ,Ⅲ期患者为 (5 1± 2 1)pmol·min-1·10 -6细胞 ,Ⅳ期患者为 (7 1±1 8)pmol·min-1·10 -6细胞 ,而且 ,病情恶化时AHH活性升高 ,病情改善时AHH活性降低。诊断评价提示 :AHH灵敏度和特异性均在 80 %以上 ,对鳞癌的灵敏度达 90 %以上。AHH对肺癌相对危险度为2 83。结论　AHH是一个较为理想的肺癌标志物 ,尤其对肺鳞癌有较好的灵敏度和特异性 ,可用于肺癌的临床诊断、病情监测和预后估计     

氧合导向最佳呼气末正压对急性呼吸窘迫综合征犬肺局部气体分布和炎症反应的影响

目的 探讨氧合导向最佳呼气末正压(PEEP)对急性呼吸窘迫综合征(ARDS)犬肺组织局部气体分布和炎症反应的影响.方法 静脉注射油酸(油酸组,8只)、肺泡灌洗生理盐水(生理盐水组,8只)复制犬ARDS模型.模型成功后给予氧合导向最佳PEEP进行机械通气,基础状态、模型复制成功及机械通气4 h后均行肺部CT扫描,观察肺局部气体分布.4 h后处死犬,留取肺组织观察病理改变,凝胶迁移率改变电泳(EMSA)测肺组织NF-κB活性,比色法测肺组织髓过氧化物酶(MPO)和丙二醛(MDA)含量,ELISA测肺组织IL-6、IL-10含量.结果 (1)与基础状态比,2组犬模型复制成功后,总肺容积均显著减少,不通气区肺容积明显增加;与模型复制成功时比,2组犬在最佳氧合法确定PEEP水平,CT扫描显示低通气区及不通气区肺容积明显减少,正常通气肺组织增加,但过度膨胀区肺容积也显著增加,以腹侧(非重力依赖区)肺泡过度膨胀明显.与油酸组比,在最佳氧合法确定PEEP水平,生理盐水组过度膨胀区肺容积增多更显著.(2)2组犬肺右下叶腹侧组织损伤评分均明显高于右上叶,肺右下叶背侧组织损伤评分均明显高于右上叶、右下叶腹侧;肺右下叶背侧组织NF-κB活性均明显高于右上叶;肺右下叶背侧、右下叶腹侧组织MPO和MDA含量均明显高于右上叶;肺右下叶背侧组织IL-6、IL-10含量均明显高于右上叶、右下叶腹侧.结论 以氧合导向最佳PEEP致ARDS肺非重力依赖区过度膨胀,加重局部肺损伤.生理盐水组犬肺过度膨胀更显著.     

肺癌组织中微卫星DNA的改变

目的研究微卫星ＤＮＡ在肺癌组织中的改变以及其对肺癌的诊断价值。方法应用聚合酶链反应（ＰＣＲ）银染法,对５０例原发性肺癌及自身正常肺组织３Ｐ１３２６上的５个微卫星位点进行检测。结果５０例肺癌中,微卫星不稳定发生率为５２％（２６／５０）,杂合性丢失３８％（１９／５０）;低分化肺癌微卫星不稳定发生率（７７％）明显高于高、中分化（３６％）;微卫星不稳定联合杂合性丢失对肺癌的诊断阳性率达７２％。结论微卫星不稳定和杂合性丢失在肺癌发生、发展中可能起一定作用。在肺癌诊断上可能有一定价值     

Serial scintigraphic assessment of iodine-123 metaiodobenzylguanidine lung uptake in a patient with high-altitude pulmonary edema.

Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) can be considered an indicator of pulmonary endothelial cell function. Serial (123)I-MIBG images of the chest were acquired in a patient with high altitude pulmonary edema (HAPE). The initial evaluation was performed 7 days after admission. The lung to upper mediastinum ratios (LMRs) of (123)I-MIBG uptake were 1.33 (for the right lung) and 1.12 (for the left lung). The second examination of (123)I-MIBG lung uptake, which was performed 2 months later, showed LMRs of 1.39 (right lung) and 1.33 (left lung). We speculated that the decreased lung uptake of (123)I-MIBG at the early recovery stage could reflect an impairment in pulmonary endothelial cell metabolic function in the development of HAPE.     

Total body irradiation with or without lung shielding for allogeneic bone marrow transplantation.

From June 1986 to June 1990, 64 patients with leukaemia (25 acute myelogenous leukaemia, 21 acute lymphoblastic leukaemia and 18 chronic myeloid leukaemia) undergoing marrow transplantation were randomized to receive cyclophosphamide (CY) and fractionated total body irradiation (TBI) without lung shielding (n = 33) or CY and fractionated TBI with lung shielding (n = 31, control group) as conditioning. Patients conditioned with TBI without lung shielding received a significantly higher total lung dose compared with the control group (p less than 0.0001). The 3-year leukaemia-free survival for patients receiving TBI without lung shielding is 54 +/- 18% versus 51 +/- 18% for patients receiving TBI with lung shielding (p = ns). There was no significant difference in the probability of leukaemia relapse (22 +/- 18% for TBI without lung shielding versus 24 +/- 18% for control group; p = ns). The probability of interstitial pneumonitis is 15 +/- 14% for TBI without lung shielding and 5 +/- 5% for TBI with lung shielding (p = ns). A higher incidence of lung fungal infection (15 versus 3%) and interstitial pneumonitis (12 versus 3%) has been documented in patients receiving TBI without lung shielding compared with the control group. The results indicate that higher radiation dose to the lung did not increase antileukaemic efficacy of TBI but seemed to be associated with the increased pulmonary toxicity.     

Maternal lung growth in surgically reduced litter size pregnancy

In our previous study (Faridy et al., this issue) we observed that pregnant rats with large litter size have larger lungs than rats with small litter size. The present study was conducted to test the hypothesis that in large litter size pregnancy, the maternal lung may not enlarge if, during pregnancy, the large litter size of 11-18 is surgically reduced to a small litter size of 3. A laparotomy was performed in pregnant albino rats at gestation day 7 (R7) or 14 (R14), all fetuses except 3 were removed and the rats were sacrificed at gestation day 21 (term 22 days). Maternal lung growth was assessed by measuring lung weight, lung DNA content and lung air volume, and the fetal lung growth by lung DNA content. The results were then compared with control pregnant rats of large (11-18) and small (1-3) litter size. The findings were: (1) reduction of litter size hindered maternal lung enlargement; (2) the earlier in pregnancy the surgical reduction was performed the smaller was the maternal lung, such that control (11-18) greater than R14 greater than R7 = control (1-3); (3) fetuses of R14 rats had larger lungs per body weight than R7 rats; (4) oxygen consumption of sham-operated rats with large litter size was higher (by 8-12%) than R7 rats. The results suggest that enlargement of maternal lung during pregnancy is related to litter size and perhaps to VO2. The fact that R14 fetal lung is larger than that of R7, supports our previous notion (Faridy et al., this tissue) that factors regulating the maternal lung growth similarly influence the fetal lung.     

Oxygen-induced lung damage. Relationship to lung mitochondrial glutathione levels.

Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen-induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen-induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)     

肺泡蛋白沉积症十例临床分析及全肺灌洗治疗体会

目的总结肺泡蛋白沉积症（PAP）的临床资料以及全肺灌洗的疗效和安全性,丰富PAP的诊治经验.方法10例PAP患者,经支气管肺活检（TBLB）和支气管肺泡灌洗液（BALF）过碘酸夫雪（PAS）染色检查确诊,均行全肺灌洗治疗.结果10例PAP患者均表现为渐进性呼吸困难.肺部高分辨率CT有特征的毛玻璃样改变,全肺灌洗治疗后临床症状、肺功能、动脉血气及高分辨率CT等指标均显著改善.结论渐进性呼吸困难和毛玻璃样在高分辨率CT改变是PAP患者的最重要临床特征,大容量全肺灌洗治疗PAP安全有效.     

Notch1蛋白在人肺腺癌组织中的表达及意义

目的 研究Notch1蛋白在人肺腺癌组织中的表达及意义,探讨Notch1受体在人肺腺癌发生中的作用.方法 前期研究初步筛选出Notch1蛋白在肺腺癌组织中有强表达,本研究收集我院及新华医院2009年1月至2010年5月胸外科肺癌手术并经术后病理切片明确为肺腺癌的标本以及正常肺组织标本,以实时荧光定量PCR及Wester...     

Serum anti-p53 autoantibodies from patients with idiopathic pulmonary fibrosis associated with lung cancer

Mutations of the tumour suppressor gene p53 lead to accumulation of the mutated p53 protein and subsequent production of antoantibodies against p53 proteins, which are also detected in lung cancer. Lung cancer is frequently associated with idiopathic pulmonary fibrosis (IPF). Therefore, we hypothesized that there might be a relationship between the p53 mutation and high prevalence of lung cancer in IPF. To test this hypothesis, we measured serum p53 antibody levels by an ELISA in various lung diseases including lung cancer (n=98), IPF (n=46; with lung cancer, n=14 and without lung cancer, n=32), pulmonary emphysema (PE, n=23) and healthy controls (HC, n=93). The median values of the serum anti-p53 antibody in each group were 8.78, 9.18, 8.08 and 4.95 for patients with lung cancer, IPF with lung cancer, IPF without lung cancer and PE, respectively, and 2.2 for the healthy control group. The groups of IPF (with and without lung cancer) showed a similar level of median values to the lung cancer group and a tendency for a higher level than the PE group. When the cut-off value was set at 7.7 according to the 95% specificity level for normal control, the incidence of positive anti-p53 antibody was significantly higher in lung cancer (61.2%), IPF with lung cancer (57.1%) and IPF without lung cancer (53.1%) than PE (21.7%). These results suggest that p53 mutations occur frequently and substantially in IPF, resulting in a high prevalence of lung cancer.     

Effect of aminophylline and caffeine on total and surfactant phospholipid in fetal rabbit lung

Aminophylline treatment of pregnant rabbits for 2 days, beginning at 25.5 days gestation, produced a significant increase in total phospholipid in fetal lung tissue at 27.5 days gestation, 8.92 +/- 0.76 (mean +/- SEM) mg/g wet lung weight, compared with 5.46 +/- 0.83 in saline-injected control animals (p less than 0.005). Three lines of evidence suggest this was not related to the surfactant system: (1) there was no increase in disaturated phosphatidylcholine in fetal lung tissue, (2) there was no increase in total phospholipid harvested by lung lavage after static lung inflation, and (3) there was no change in the lung deflation pressure-volume curve or stability index. Aminophylline treatment produced no acceleration in general anatomic lung development, as reflected in the ratio of lung air-space capacity to lung tissue weight. Under similar experimental conditions, maternal caffeine treatment had no effect on fetal rabbit lungs.     

高分辨CT扫描技术在肺间质性病变中的应用价值

目的 探讨高分辨CT扫描技术,对肺间质性病变的诊断价值.方法 采用Philips MX8000 Dual 螺旋CT机对30例肺间质性病变患者,行高分辨CT技术扫描.结果 高分辨CT可清晰显示肺间质性病变的各种征象,肺间质性病变的高分辨CT主要表现为:(1)磨玻璃样密度影;(2)肺小叶间隔增厚;(3)小叶内间质增生;(4)网格状影;(5)胸膜下弧线影;(6)蜂窝肺;(7)牵拉支气管扩张;(8)胸膜增厚.病变分布以两肺中外带、胸膜下为主,病灶自肺尖向肺底逐渐加重,两肺基底部病变明显.结论 高分辨CT扫描具有良好的空间分辨率,能细致、准确地反映肺间质病变的影像特征,对肺间质性病变具有重要的诊断价值.     

Static inflation attenuates ischemia/reperfusion injury in an isolated rat lung in situ

STUDY OBJECTIVES: Ischemia (I)/reperfusion (R) lung injury is an important clinical issue in lung transplantation. In the present study, we observed the effects of lung static inflation, different perfusates, and ventilatory gas with nitrogen or oxygen on the I/R-induced pulmonary damage. DESIGN AND SETTING: A total of 96 male Sprague-Dawley rats were used. The lung was isolated in situ. METHODS: In an isolated lung, the capillary filtration coefficient (Kfc), lung weight gain (LWG), lung weight (LW)/body weight (BW) ratio, and protein concentration in BAL fluid (PCBAL) were measured or calculated to evaluate the degree of lung injury. Histologic examinations with hematoxylin-eosin staining were performed. RESULTS: I/R caused lung injury, as reflected by increases in Kfc, LWG, LW/BW, and PCBAL. The histopathologic picture revealed the presence of hyaline membrane formation and the infiltration of inflammatory cells. These values were significantly attenuated by static lung inflation. The I/R lung damage appeared to be less in the lung perfused with whole blood than in the lung perfused with an isotonic solution. Therapy with ventilatory air (ie, nitrogen or oxygen) did not alter the I/R lung damage. CONCLUSIONS: The data suggest that lung inflation is protective to I/R injury, irrespective of the type of ventilatory air used for treatment. The preservation of the lung for transplantation is better kept at a static inflation state and perfused with whole blood instead of an isotonic physiologic solution.     

Role of hyperventilation in hypoxia on lung growth in rats

This study was conducted in an attempt to differentiate the contribution of hyperventilation, if any, from that of low PO2 on adaptive lung growth in response to hypoxia. Male albino rats were exposed to one of the following: (1) Room air for 7 days, as control; (2) 10% O2 in N2 for 7 days; (3) 10% O2 for 6 h, 1 day or 2 days and air for the remaining of 7 days; (4) 10% O2 for 2 days and 7% CO2 in air for 5 days; (5) air for 2 days and 7% CO2 for 5 days; or (6) 7% CO2 in air for 7 days. Lung growth was assessed by measuring the lung weight, lung air volume, lung DNA content and rate of DNA synthesis in lung explants. Hypoxia stimulated lung DNA synthesis even when administered for only 6 h, and the effects persisted for a few days after discontinuation of hypoxia. Hypercapnia did not stimulate DNA synthesis in lung. In 2 day hypoxic 5 day air rats the lung weight and lung DNA content increased, in 2 day air 5 day hypercapnic rats only the lung volume increased, and in 2 day hypoxic 5 day hypercapnic rats all parameters of lung growth, i.e., lung weight, DNA content and air volume increased as in 7 day hypoxic rats. The results suggest that adaptive or compensatory lung growth in hypoxia is brought about on one hand by the direct effect of low PO2 on lung cells, resulting in lung hyperplasia, and on the other hand by the mechanical stimulation of lung tissue by hyperventilation, causing lung distension.