血清肿瘤标记物在肺癌诊断中的意义

目的　明确癌胚抗原 (CEA)、大分子糖蛋白抗原 (CA1 2 5)、细胞角蛋白 (Cyfra2 1 - 1 )在肺癌诊断中的意义。方法　收集血清标本 74份 ,其中肺部良性病变组 2 8例 ,肺腺癌组 19例 ,肺鳞癌组 16例 ,小细胞肺癌组 11例。CEA、CA1 2 5、Cyfra2 1 - 1 均用电化学发光分析技术检测 ,结果以均值±标准差和特异度及灵敏度两种方式评价。结果　 CEA的水平 ,良性病变组在正常参考范围内 ;腺癌、鳞癌、小细胞癌组均明显高于正常值上限 ,而各肺癌组间比较无显著差异 ,各肺癌组与肺部良性病变相比 ,均有显著性差异 (P<0 .0 0 1)。 CA1 2 5各组病变中均高于正常参考值 ,各组比较 ,只有肺腺癌组与良性病变组有显著性差异。 Cyfra2 1 - 1 在肺腺癌组、鳞癌组明显高于正常值 ,统计学上有显著性差异 ,良性病变组和小细胞癌组其值均在正常参考值范围内 ,但两组之间有显著性差异。 CEA的特异性高达 82 .14 % ,灵敏度为 5 8.6 9% ;CA1 2 5的灵敏度较高 ,但特异性很低 ,仅 4 2 % ;Cyfra2 1 - 1 的特异性近 90 % ,但灵敏度仅 4 5 %。对不同病理类型各肿瘤标记物的灵敏度亦不同 ,CEA、CA1 2 5在各型间无差别 ;Cyfra2 1 - 1 在非小细胞肺癌和小细胞肺癌间差别有统计学意义。结论　 CEA在肺部恶性病变中的特异性较高 ,灵敏度亦可     

Decreased Selenium Concentration and Glutathione Peroxidase Activity in Blood and Increase of These Parameters in Malignant Tissue of Lung Cancer Patients

We studied the selenium (Se) concentration in whole blood and plasma, glutathione peroxidase (GSH-Px) activity in red blood cells and plasma, as well as both of these parameters in cancerous and tumor-free lung tissue of lung cancer patients. Blood samples were taken from 84 cancer patients and 61 healthy controls. Normal and neoplastic lung tissues were obtained from 57 patients at the time of surgery. Se concentrations in whole blood and palsma were lower by 23% (p < 0.001) in patients compared with controls. GSH-Px activity in red cells was lower by 20.2% (p < 0.004) and in plasma by 11.7% (p < 0.05) in patients than in the control group. On the other hand, the tumor Se level was higher by 66.6% (p < 0.0001) and GSH Px activity by 49.5% (p < 0.0001) than in adjacent tumor-free tissue. No differences in Se concentrations and GSH-Px activities were found between squamous cell carcinoma and adenocarcinoma nor among the clinical stages of the disease. In the whole blood and plasma of cancer patients significantly lower Se concentrations were found in smokers than in nonsmokers. Significantly lower Se concentrations were also found among cancer patients who were smokers compared with controls. These findings show that in the blood of cancer the antioxidant ability, as measured by Se and GSH-Px, is reduced significantly. The cause of increased Se and GSH-Px in the malignant part of the lung is not understood and requires further studies. Accepted for publication: 17 April 1997     

Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer

OBJECTIVE: To assess the value of Cyfra 21-1, carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) combined, all three together as prognostic factors in advanced stage non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Serum samples from untreated NSCLC patients were prospectively collected. All assays were performed using commercial kits blind to clinical information. Serum levels of CEA, NSE and Cyfra 21-1 higher than 10, 13 and 3.5 ng/ml, respectively, were considered as elevated. RESULTS: 264 patients (men, 87%), with Performans Status (PS) of 0/1 in 80% and stage IV disease in 65% were studied. Cyfra 21-1, CEA and NSE were elevated in 52.5%, 41.8% and 33.2% of patients, respectively. Median survival was 9 months (range, 1-77). Cyfra 21-1, age, PS, stage as well as the combination of the three markers together correlated with prognosis in univariate analysis. Multivariate analysis demonstrated that age > or = 65 years (HR = 1.3 [1.02-1.70], p = 0.03), PS 2 (HR = 4.3 [3.13-6.11], p < 0.0001), Cyfra 21-1 > or = 3.5 ng/ml (HR = 1.3 [1.06-1.78], p = 0.01) and the combination of the three markers (HR = 1.06 [1.009-1.13], p = 0.02) remained prognostic determinants. CONCLUSION: Combining Cyfra 21-1, NSE and CEA correlated with prognosis in a significant and independent manner.     

多种肿瘤标志物水平与与非小细胞肺癌靶向动脉灌注治疗效果及预后的相关性分析

目的探讨癌胚抗原(CEA),神经元特异性烯醇化酶(NSE),胃泌素释放肽前体(Pro-GRP),细胞角蛋白19片断(Cyfra)21-1,鳞状细胞癌抗原(SCC-Ag)检测水平与非小细胞肺癌(NSCLC)靶向动脉灌注治疗有效性及预后的相关性。方法回顾性分析110例接受靶向动脉灌注治疗的晚期NSCLC患者的临床资料,根据治疗效果将其分为有效组和无效组,对比2组治疗前后血清肿瘤标志物水平:CEA,NSE,Pro-GRP,Cyfra21-1,SCCAg,通过绘制受试者工作曲线(ROC),分析各血清肿瘤标志物与NSCLC靶向治疗效果一致性;随访1年,根据患者预后情况将其分为生存组和死亡组,对比2组治疗后血清肿瘤标志物水平,并对比2组可能影响预后死亡因素的差异,采用Logistic回归分析法明确相关危险因素。结果靶向动脉灌注治疗有效率50.91%,治疗后有效组血清CEA,NSE,Pro-GRP,Cyfra21-1,SCCAg水平均低于治疗前,且均低于无效组(P<0.05);治疗后无效组血清CEA,NSE,Pro-GRP,SCCAg水平与治疗前相比无明显变化(P>0.05),而血清Cyfra21-1水平较治疗前升高(P<0.05);CEA,NSE,Pro-GRP,Cyfra21-1,SCCAg对NSCLC靶向治疗疗效诊断最佳截断点分别为20.0μg/L、13.3μg/L、10.7 ng/L、3.1μg/L、1.2μg/L,AUC分别为0.470、0.513、0.702、0.710、0.683。随访1年生存率40.91%;死亡组血清CEA,NSE,Pro-GRP,Cyfra21-1,SCCAg水平均高于生存组(P<0.05);死亡组TNMⅣ期、CEA>5μg/L、NSE>16.3μg/L,Pro-GRP>40.0 ng/L,Cyfra21-1>3.3μg/L,SCCAg>1.4μg/L患者构成比均高于生存组(P<0.05),且经Logistic回归分析,上述指标均是导致预后死亡的危险因素(P<0.05)。结论血清CEA,NSE,Pro-GRP,Cyfra21-1,SCCAg检测与NSCLC靶向动脉灌注治疗有效性和预后密切相关,且Cyfra21-1对疗效有较高诊断效能。     

Evaluation of squamous cell carcinoma antigen (SCC-Ag) in the diagnosis and follow-up of patients with non-small cell lung carcinoma.

The usefulness of squamous cell carcinoma (SCC) antigen as a tumor marker was investigated in 72 patients with histologically verified non-small cell lung carcinoma (NSCLC). Increased level of SCC-Ag was observed in 41%, mostly in patients with squamous cell carcinoma (69%). Positive serum SCC-Ag was correlated with lymph node metastases and with the stage of disease. The positive rate of SCC-Ag observed in patients without and with nodal metastases was 52.9% and 84.2%, respectively. Positive SCC-Ag level was observed in 50% of Stage I, 71.4% of Stage II and 78.9% of Stage III patients with squamous cell carcinoma of the lung. The study proved that preoperative SCC-Ag determination in patients with squamous cell carcinoma of the lung and the course of levels of this marker during postoperative follow-up was of importance. A high preoperative and postoperative SCC-Ag value suggested a worse prognosis.     

Immunological Competence and Nutritional Status in Patients with Lung Cancer

The rate of infection in patients with malignant disease is significantly higher than in patients with benign disease. To investigate whether immunological competence is impaired in patients with lung cancer, we assessed neutrophil function (chemotaxis, phagocytosis, bacterial killing activity, and superoxide production), monocyte function (phagocytosis and killing activity), lymphocyte subsets using flow cytometry, and proliferation of lymphocytes stimulated by phytohemagglutinin, concanavalin A, and pokeweed mitogen. Studies were performed on 22 untreated patients with lung cancer and 21 age-matched healthy volunteers. Nutritional status was assessed by Niederman's nutritional index. In patients with lung cancer neutrophil chemotaxis, monocyte phagocytosis and killing, proliferation of lymphocytes stimulated by phytohemagglutinin and concanavalin A, but not pokeweed mitogen, and the number of natural killer cells were significantly lower than in healthy volunteers, whereas γδ T cells were increased (p < 0.05). The mean score on Niederman's nutritional index was worse in patients than in healthy volunteers (p < 0.001). Our results suggest that the impaired immunological competence and undernutrition may be among the mechanisms causing increased susceptibility to infection in patients with lung cancer. Accepted for publication: 21 May 1998     

CA50、CEA、Cyfra21-1和SCC在肺癌患者中的表达及其临床意义

目的探讨血清肿瘤标志物CA50、CEA、Cyfra21-1和SCC在肺癌诊断中的价值。方法采用电化学发光法检测260例肺癌患者、65例肺良性病变患者及117例健康体检者血清CA50、CEA、Cyfra21-1和SCC的含量。结果肺癌患者CA50、CEA、Cyfra21-1和SCC在肺癌患者中的阳性率分别为46.9%、66.5%、57.7%和58.1%,显著高于肺部良性病变患者和健康对照组(P0.05)。CA50、CEA、Cyfra21-1和SCC小细胞肺癌患者较非小细胞肺癌患者表达水平低。CA50和CEA在肺腺癌高表达;而Cyfra21-1在肺鳞癌高表达。结论血清CA50、CEA、Cyfra21-1和SCC检测对于肺癌诊断敏感性和特异性强,并有助于判断病理类型。     

血清CYFRA21—1在非小细胞肺癌诊断中的价值

本研究用酶免方法检测了66人血清CYFRA21—1水平,其中肺腺癌20例,肺鳞癌24例,小细胞肺癌(SCLC)10例,以12例肺良性疾病(BPD)为对照;同时检测了6例患者手术前后血清CYFRA21-1水平。结果:鳞癌组和腺癌组血清CYFRA21—1水平均明显高于SCLC组和BPD组;鳞癌组则明显高于腺癌组。不同病期非小细胞肺癌(NSCLC)血中CYFRA21—1水平也明显不同,Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期。6例患者血清CYFRA21—1水平术后均有明显下降。结果表明:血清CYFRA21—1水平对NSCLC特别是肺鳞癌有较高的特异性,在NSCLC特别是肺鳞癌的诊断和鉴别诊断有重要意义;治疗前后血清CYFRA21—1水平的变化有助于疗效的判断。     

Changes in Pulmonary Mechanics after Lung Volume Reduction Surgery

Lung volume reduction surgery (LVRS) is a promising new treatment for emphysema and leads to increased flow rates. We investigated the mechanisms by which flow rates could increase and the correlates of lessened dyspnea in patients undergoing LVRS before and 3 months after LVRS in patients with severe emphysema. The following were done: routine pulmonary function testing, measurements of elastic recoil (Pel), tidal breathing patterns, inspiratory work of breathing (W_insp), construction of static recoil-maximum flow curves, and measurement of baseline and transitional dyspnea index (TDI). There were increases in forced vital capacity (FVC: 2.24 ± 0.71 to 2.92 ± 0.63 liters; p < 0.05), forced expired volume in 1 (FEV₁: 0.64 ± .16 to 1.03 ± 0.28 liters; p < 0.01), and decreases in all divisions of lung volume, e.g. total lung capacity (TLC: 6.86 ± 1.41 to 5.96 ± 1.49 liters; p < 0.01). Maximum Pel increased (11.7 ± 3.7 to 19.8 ± 7.8 cmH₂O; p < 0.02) as did the coefficient of retraction (C_R= Pel/TLC: 1.8 ± 0.7 to 3.6 ± 3.6 ± 2.2 cmH₂O/liter). However, the individual responses in other parameters were markedly different among patients. There was no consistent trend in changes in the slope or position of the static recoil-maximum flow curve or W_insp. The only positive correlate of improved dyspnea (TDI = 3.22 ± 2.22; p < 0.01) was improvement in C_R, FEV₁ being a weak negative correlate and change in lung volume not being a correlate at all. We conclude that there is a heterogeneous response of the airways to LVRS. Increased elastic recoil was the primary determinant of improved flow rates after LVRS and is the only positive correlate for improvement in dyspnea. Accepted for publication: 14 July 1997     

Fibroblasts as Target and Effector Cells in Japanese Patients with Sarcoidosis

Fibroblasts play a crucial role in progressive lung fibrosis, acting not only as target cells but also as effector cells. To clarify these functions in sarcoidosis, lung fibroblasts from Japanese sarcoid patients were studied for their proliferative capacity and cytokine productivity. Fibroblasts were cultured from transbronchial lung biopsy specimens from seven patients with sarcoidosis. As a comparison, fibroblasts from open lung biopsy specimens of four patients with idiopathic pulmonary fibrosis (IPF) were studied. For controls, fibroblasts were cultured from specimens of normal resected lung tissue of five patients with localized lung cancer. The proliferative activity of cultured fibroblasts from patients with sarcoidosis was highest among the three groups (p < 0.05). However, the proliferative capacity in all groups was suppressed when fibroblasts were cultured with interleukin-1β (IL-1β). No significant differences were noted in the degree of inhibition among the three groups. Addition of interferon-γ (IFN-γ) also resulted in inhibition of fibroblast growth in all groups, but the degree of inhibition was significantly greater in both the sarcoid and IPF groups than in controls (p < 0.05). The amount of interleukin-6 (IL-6) in the culture supernatants from sarcoid fibroblasts cocultured with IL-1β was significantly higher than in controls. Sarcoid fibroblasts are not only proliferatively active but also possess effector cell function to produce cytokines. IL-6 may enhance the immunologic reaction to sarcoidosis and cause the disease to become chronic. IFN-γ suppresses proliferation of sarcoid fibroblasts and may prevent fibrotic changes of the lungs in the Japanese sarcoid patients. Accepted for publication: 4 June 1997     

LTA，CEA，NSE，Cyfra 21—1对肺癌诊断价值的探讨

目的 探讨LTA、CEA、NSE和Cyfra21-1对肺癌诊断价值。方法 清晨空腹抽取临床确诊肺癌患者124例、转移性肺癌9例和良性肺部疾病34例患者静脉血7ml,分别用放射免疫法和乳胶凝集试验法,检测血清中上述癌性标志物水平。结果：LTA、CEA、NSE和Cyfra21-1,在肺癌的阳性率分别为60％、8％、31％和43％;特异性分别为88％、100％、84％和97％,CEA和Cyfra21-1较高;阳性率和敏感性组间差异有统计学意义。LTA对肺癌细胞类型和是否手术无诊断意义 结论 LTA对肺癌具有一定的诊断价值,但特异性差于Cyfra21-1;多种癌性标志物同时检测有助提高阳性率。     

Serum Lysozyme Levels and Clinical Features of Sarcoidosis

Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0.05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases. Accepted for publication: 19 November 1998     

Health-Related Quality of Life in Long Term Oxygen-Treated Chronic Obstructive Pulmonary Disease Patients

Chronic obstructive pulmonary disease (COPD) induces changes in daily activities and mood. Health-related quality of life (HRQL) measures are of particular relevance in the management of such patients, but predictors of HRQL have rarely been investigated. The aim of this study was to seek factors predicting HRQL in severe COPD patients under long term oxygen therapy (LTOT). The pulmonary function parameters at the start of LTOT were studied as potential predictors of future HRQL. HRQL was assessed after an average of 40 months follow-up by the Duke Health Profile (Duke) and by the St. George Respiratory Questionnaire (SGRQ). Sixty-one patients (47 males and 14 females) with a mean age of 66 years were included in the study. Stepwise multiple regression analyses conducted in each HRQL dimension identified few significantly predictive factors. By the Duke, higher Self-esteem scores were associated with higher Pao ₂ (p < 0.01) and with older age (p < 0.05); higher Social Health scores were associated with older age (p < 0.005), and higher Pain scores were associated with a higher FEV₁/FVC ratio (p < 0.05). By the SGRQ, the Activity score correlated with FEV₁/FVC (p < 0.05). The proportion of the variance in each score accounted for by covariates in the model did not exceed 10%. No other significant regression models could be identified using the other HRQL dimensions. Our findings demonstrated weak relations between lung function at the start of LTOT and some dimensions of HRQL measured by the Duke and the SGRQ at the end of follow-up. Accepted for publication: 9 July 1996     

Incomplete Upper Esophageal Sphincter Relaxation: Association with Achalasia but Not Other Esophageal Motility Disorders

Incomplete upper esophageal sphincter (UES) relaxation is not well understood. We compared clinical and manometric characteristics of patients with normal and abnormal UES relaxation. Consecutive patients (n = 208) underwent manometric evaluation of the lower esophageal sphincter (LES), esophageal body, and UES/pharynx. The patients were divided into those with abnormal UES relaxation (residual pressure >6.7 mmHg) (n = 21) and normal relaxation (n = 187). Clinical and manometric profiles were compared. Sex, age, and presenting complaint did not correlate with UES relaxation. Normal esophageal peristaltic sequences were more frequently present in the normal UES group (73.6%) compared with the abnormal (55.8%) (p < 0.01). The UES relaxation was shorter in the group with abnormal relaxation (410.0 ms vs. 510.2 ms, p < 0.001). All other manometric parameters were not different between the two groups. When individual manometric diagnoses were analyzed, only achalasia was noted to be more common in the abnormal UES group (23.8% vs. 9.1%, p < 0.05), and a trend was noted toward diffuse esophageal spasm being more common (14.3% vs. 9.6%, not significant). We conclude that incomplete UES relaxation is a rare manometric finding, associated with achalasia and not specifically associated with any other motility disturbance. This finding may represent a secondary response to the poor esophageal emptying seen in achalasia.     

Development of Monocrotaline-Induced Pulmonary Hypertension Is Attenuated by a Serotonin Receptor Antagonist

The significance of serotonin in the pathogenesis of monocrotaline-induced pulmonary hypertension (MCT-PH) in rats, plasma serotonin concentrations, and the effect of a serotonin receptor antagonist administration in association with the number of proliferative cells were investigated. The thickness of the media of the small pulmonary arteries and the weight ratio of the RV to that of LV + S (RV/[LV + S] weight ratio) were used as indices of the severity of PH. Plasma serotonin concentrations were measured by high-performance liquid chromatography. Histopathologic analysis of the lung tissue was performed by hematoxylin-eosin and elastin van Gieson staining. Immunohistopathologic staining for proliferating cell nuclear antigen (PCNA) was performed to identify proliferative cells. The severity of PH as determined by the medial thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in rats with MCT-PH was significantly reduced after treatment with MCI-9042 (p < 0.01 and p < 0.05, respectively). The serotonin concentration was significantly greater in MCT-PH rats than in normal control rats (p < 0.05). The scores for histopathologic changes, such as thickening of the alveolar walls and interstitial inflammatory cell infiltration in MCT-PH rats, were significantly reduced after treatment with MCI-9042 (p < 0.05 and p < 0.01, respectively). The number of PCNA-positive cells was significantly greater in MCT-PH rats than in normal control rats (p < 0.0001) and was reduced after treatment with MCI-9042 (p < 0.0001). Treatment with MCI-9042 significantly inhibited the development of MCT-PH along with a decrease in the number of PCNA-positive cells, suggesting a pivotal role of serotonin in the development of PH induced by MCT. Accepted for publication: 10 November 1999     

Airway Eosinophilic Inflammation and Bronchial Hyperresponsiveness after Allergen Inhalation Challenge in Asthma

Allergen exposure in atopic asthmatic patients is associated with recruitment and activation of eosinophils in the airways. Once activated, eosinophils release toxic products, including the eosinophil cationic protein (ECP), able to damage bronchial structures and to increase bronchial hyperresponsiveness. With this background, the present study was designed to evaluate whether ECP levels in bronchoalveolar lavage (BAL) fluid could reflect, better than BAL eosinophil counts, the cellular activation that follows allergen exposure in atopic asthmatics. Twenty-two atopic patients attended the laboratory on two separate days. On the 1st day, they underwent methacholine (MCh) inhalation challenge to detect the degree of nonspecific bronchial hyperresponsiveness. On the 2nd day, they underwent fiberoptic bronchoscopy and BAL, at baseline or 4–6 h after allergen inhalation challenge. In this latter patient group, MCh challenge was repeated 3–5 h after allergen challenge, 1 h before fiberoptic bronchoscopy. The analysis of the mean baseline FEV₁ values and the degree of bronchial reactivity to MCh (MCh Pd₂₀) on the 1st study day did not demonstrate differences between the two patient groups (p > 0.1, each comparison). In addition, in the allergen-challenged group, MCh Pd₂₀ was decreased significantly after allergen challenge (151.4 μg/ml and 67.6 μg/ml, respectively, before and after challenge; p < 0.05). Evaluation of the different BAL cell types demonstrated that the proportions of eosinophils and epithelial cells were increased significantly in the allergen-challenged group compared with the group evaluated at baseline (p < 0.01 and p < 0.05, respectively). Moreover, ECP levels, corrected by the correspondent albumin levels (ECP/Alb), were higher in the allergen-challenged group compared with the group evaluated at baseline (p < 0.05). In addition, although a positive correlation was demonstrated between BAL eosinophil percentages and ECP/Alb values (r= 0.72, p < 0.05) in the group evaluated at baseline, no links were found between these parameters in the allergen-challenged group (p > 0.1). However, in this latter group, a weak positive correlation was demonstrated between eosinophil percentages and ΔMch, i.e., the increased nonspecific bronchial reactivity, which is observed after allergen challenge (r= 0.55; p < 0.05). Thus, in stable asthmatic patients an ongoing activation of eosinophils parallels their migration, but this eosinophilic inflammation is not strictly related to bronchial reactivity to Mch. By contrast, after allergen inhalation challenge, eosinophil recruitment and activation seem to follow different temporal kinetics, and eosinophilic inflammation may be partially associated with the degree of airway hyperresponsiveness. Accepted for publication: 15 September 1997     

Frequent loss of the short arm of chromosome 9 in resected non-small-cell lung cancers from Japanese patients and its association with squamous cell carcinoma

We analyzed 87 Japanese non-small-cell lung carcinomas (NSCLC), including 30 squamous cell, 51 adenocarcinomas and 6 large-cell carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome 9, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9S126, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%). Concordance among the four markers was high (87%), indicating that the deletions often were relatively large. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shift in band mobility. We noted a high frequency of LOH at 9p especially in, squamous cell carcinoma (17 of 29 informative cases or 59%) and in poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Our findings demonstrate that LOH at the short arm of chromosome 9 is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.Abbreviations SCLC small-cell lung cancer - NSCLC non-small-cell lung cancer - LOH loss of heterozygosity - PCR polymerase chain reaction - (CA) _n cytosine adenine - n number of repeats - IFNA interferon A gene     

Guinea Pig Pulmonary Mechanics: Altered Sensitivity to Carbachol by Cadmium and/or Selenium

Male Hartley guinea pigs (480–610 g) were treated intratracheally as follows: saline, cadmium (Cd, 0.3 mg), selenium (Se, 0.3 or 0.06 mg), or Se (0.06 mg) and Cd (0.3 mg) simultaneously. Selenium and Cd were administered as sodium selenite and cadmium chloride, respectively. Twenty-four h later, dynamic lung compliance (C_dyn) and pulmonary resistance (R_p) were measured before (baseline C_dyn and R_p) and after carbachol administration (0.0001, 0.001, 0.01, and 0.1 μmol/kg, intravenously). Results indicated a significant decrease in baseline C_dyn caused by 0.3 mg of Cd, 0.3 mg or 0.06 mg of Se, and 0.3 mg of Cd with 0.06 mg of Se (p < 0.05). A significant increase in baseline R_p due to 0.3 mg of Se was observed (p < 0.05). Carbachol decreased C_dyn significantly below baseline, evident after lower doses of carbachol, in guinea pigs pretreated with 0.3 mg of Se, whereas a significant improvement in C_dyn was seen after 0.0001 μmol/kg carbachol in the group pretreated with Se and Cd simultaneously (p < 0.05) compared with the respective baseline values of the saline-treated group. Similarly, a significant increase in R_p was observed after carbachol in groups pretreated with 0.3 mg of Cd or Se (p < 0.05). Results also indicated a significant increase in large airway constriction caused by Cd and/or Se (p < 0.05). A leftward shift in the carbachol dose-response curve indicated increased sensitivity to carbachol in Cd- and/or Se-pretreated guinea pigs. Accepted for publication: 14 March 1997     

Oxidative Inactivation of Surfactants

Reactive oxygen species (ROS) may play an important role in the chronic pulmonary morbidity of preterm infants. We therefore studied the magnitude and mechanisms of oxidative inactivation of a natural lung surfactant (NLS) and of two surfactants used for treatment of respiratory distress syndrome, beractant and KL₄ surfactant (KL₄). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO⁻) or 0.5 mM hypochlorous acid (OCl⁻), resulted in an increased minimum surface tension (MST) of all surfactants; the order of effect on MST was beractant > KL₄ > NLS. After incubation with Fenton reagents, NLS contained a higher concentration of conjugated dienes (p < 0.01) but lower concentration of malondialdehyde (p < 0.001) than beractant. Protein carbonyl concentrations after treatment with Fenton reagents were higher in NLS and KL₄ than in beractant (p < 0.05). Surface area cycling for 24 h with 2 mM ONOO⁻ or 0.5 mM OCl⁻ caused both beractant and KL₄ to increase the proportion of light subtypes from 8–10% to 26–29%; with Fenton reagents, there was disappearance of the light subtype and formation of ultraheavy subtype 74–91% with poor MST. Natural and therapeutic surfactants differ markedly in their sensitivity to ROS, which may be important for surfactants in therapeutic use because oxidative inactivation may limit their effect. Oxidation of natural surfactant may result in reduced function and contribute to chronic lung disease. Accepted for publication: 8 January 1999     

Transient Increase in Alveolar Epithelial Permeability Induced by Volatile Anesthesia with Isoflurane

Fifteen patients undergoing surgery and receiving volatile anesthesia with isoflurane were enrolled as the study group. At the same time, 15 patients undergoing surgery with intravenous anesthesia drugs were included as a control group to compare each other. Before surgery, 1 h after surgery, and 1 week after surgery, we investigated these two groups of patients with technetium-99m–labeled diethylene triamine pentaacetic acid radioaerosol inhalation lung scan (DTPA lung scan), a test to evaluate lung ventilation (LV), which was evaluated by the first and equilibrium lung ventilation image and alveolar epithelial permeability (AP) which was evaluated by the half time (T1/2, minutes) of Tc-99m DTPA radioaerosol lung clearance. No significant change and abnormality of LV before surgery, 1 h after surgery, or 1 week after surgery was found in either group of patients. In addition, no significant change in AP before surgery (T1/2 = 64.0 ± 17.3 min), 1 h after surgery (64.5 ± 19.6 min), or 1 week after surgery (63.6 ± 17.6 min) was found among the control group patients (p values > 0.05). However, a significant transient increase in AP was found in the study group 1 h after surgery (71.7 ± 17.5 versus 51.2 ± 16.4 min), but it recovered 1 week after surgery (51.2 ± 16.4 versus 70.9 ± 16.0 min) (p values < 0.05). We conclude that volatile anesthesia with isoflurane can induce transient increase of AP. Accepted for publication: 23 February 2000