Cytology and immunocytochemistry of bronchioloalveolar carcinoma

A study of the value of cytologic examination in the diagnosis of bronchioloalveolar carcinoma showed that fine needle aspiration (FNA) cytology is a definitive means of making the diagnosis of bronchioloalveolar carcinoma. In experienced hands, FNA cytology approached a diagnostic accuracy of 100%. With exfoliative cytology, technically adequate sputum samples offered an 82% diagnostic yield; sputum cytology should thus be considered as an adjunct method in establishing the diagnosis. Several cytologic features that strongly suggest the diagnosis of bronchioloalveolar carcinoma and help to differentiate it from adenocarcinomas of other body sites are outlined. It is also concluded that immunocytochemical stains have limited value in differentiating bronchioloalveolar carcinoma and other types of clear cell malignant neoplasms, including mesothelioma, unless a panel of antibodies is used, and are of no value in ascertaining whether the cells are benign or malignant.     

Prognostic value of bronchioloalveolar carcinoma component in lung adenocarcinoma

BAC is a common pattern in conventional lung adenocarcinoma. In the past, however, there were no well-defined criteria for BAC. As a result, it was difficult to evaluate the prognosis on this type of lung adenocarcinoma. Though the 1999 WHO classification of BAC provides a useful framework, it does not provide detailed enough information to predict prognosis in lung adenocarcinomas with BAC feature. The aim of this study was to address the prognostic value of bronchioloalveolar carcinoma (BAC) component in lung adenocarcinoma. Ninety-one consecutive surgically treated patients with adenocarcinoma exhibiting various degrees of BAC features and complete follow-up records were retrospectively studied. According to the percentage of BAC component designed as less than 50%, 50%-79%, 80%-99%, and 100%, tumors were classified as type I, type II, type III, and type IV respectively. The overall 5-year survival rate was 64.84%. Multivariate analysis revealed that the four classified types are independent prognostic factors (P=0.0008), as is tumor stage (P=0.0000). The 5-year survival rates were 39.29%, 58.82%, 81.25%, 85.71% for the four classified types respectively, and were 88.89% for stage I, 46.15% for stage II, and 23.81% for stage III. However, the size of tumor (>2 cm) was significant only in the univariate analysis (P=0.0275). In the patients with tumor size exceeding 2 cm in diameter, the BAC component was also significant to predict prognosis (p=0.0008). In lung adenocarcinoma, the BAC component may prove to be useful to predict the outcome of the patients, and the percentage of BAC pattern and pathological stage appear to be two independent prognostic factors.     

受体型酪氨酸激酶RON在人细支气管肺泡癌发病机理中的作用

细支气管肺泡癌（bronchioloalveolar carcinoma,BAC）是一种以在肺泡和终末细支气管生长为主要特征的肺癌,占全部肺癌的5％-10％。近期BAC的发病率呈上升趋势。绵羊肺腺病是一种在病理形态上与人BAC极其类似的肺恶性肿瘤,病因是Jaagsiekte绵羊逆转录病毒。然而,人BAC的病因及发病机理至今不明。受体型酪氨酸激酶RON是原癌基因MET家族的一员,RON及其变异体在人BAC样品中呈高度的异常表达。转基因小鼠的实验进一步证明,定向性的在肺泡二型上皮细胞中表达RON,能诱发具有人BAC特征的小鼠肺肿瘤,RON致癌的基础是其传导的异常信息途径。采用特异性siRNA和单克隆抗体干扰RON的表达,能抑制RON介导的BAC的生长。因此,RON的异常表达是特异性药物作用的靶点,阐明原癌基因RON在BAC发病机理中的作用具有重要的临床意义。     

Relation between chemical constituents of tobacco and mutagenic activity of cigarette smoke condensate.

Mutagenic activities of cigarette smoke condensate were assayed in the presence of S-9 Mix using Salmonella typhimurium TA 98. The results were examined in relation to chemical data of tobacco leaves. Among the nitrogenous constituents examined, the contents of total nitrogen and protein nitrogen and the soluble nitrogenous fraction were positively and significantly related to an increase in mutagenic activity of the smoke condensate, whereas nicotine and nitrate were not important in contributing to mutagenic potency of such condensates. The age of tobacco leaves influenced the mutagenic potency of the condensate, which was lowest in leaves from the lower stalk position and increased with ascending leaf position on the stalk. Smoke condensate from tobacco with higher sugar content resulted in lower mutagenic activity. The present results, together with the previous study on the mutagenicity of the amino acid pyrolyzates, suggest that potent mutagens in cigarette smoke condensate are nitrogen-containing compounds, which may be formed from proteins and amino acids during the burning of a cigarette.     

Radiation diagnosis of bronchioloalveolar cancer

The paper analyzes the results of examination of 260 patients with bronchioloalveolar cancer (BAC) who were followed up at the Russian Research Center of Radiology and Roentgenology for 30 years. It provides its clinical, X-ray, and morphological manifestations and classification and the methodological aspects of differential diagnosis. An optimum radiation diagnosis programme has been drawn up, which involves currently available procedures, including computed tomography. The morphological forms of BAC are given in detail.     

Fine needle aspiration cytology of sclerosing hemangioma of the lung, a mimicker of bronchioloalveolar carcinoma

A rare "sclerosing hemangioma" of the lung in a 24-year-old man was initially interpreted as a bronchioloalveolar carcinoma by fine needle aspiration (FNA) cytology. The similarity of these two tumors in fine needle aspirates is discussed. Benign sclerosing hemangioma should be considered in the differential diagnosis when numerous atypical proliferating bronchiolar or alveolar cells are obtained by FNA.     

Binding of tobacco mosaic virus to membrane material isolated from tobacco leaves.

Binding of tobacco mosaic virus (TMV) to disrupted tobacco leaf membrane was studied. Membrane isolated from tobacco leaves was treated successively with (NH4)2SO4, Li-diiodosalicylate and then pronase. TMV-binding substance was thus isolated in a soluble form. From enzymatic digestion experiments, it was suggested that the binding substance was composed of lipid and carbohydrate.     

Polyacrylic acid-induced resistance to tobacco mosaic virus in tobacco cv. Xanthi

Polyacrylic acid (PA) of molecular weight 1700A, 1700B and 3500 caused resistance to infection with tobacco mosaic virus in tobacco cv. Xanthi-nc, when sprayed on the leaves or watered into the soil. The numbers of lesions produced in the treated plants were between 27 and 97% fewer than in the untreated plants depending on the concentration of PA, its molecular weight and the method of application. Some resistance was caused against potato virus X and potato virus Y but only at concentrations that were harmful to the plants. It appears that PA activates a mechanism responsible for localizing viruses in hypersensitive plants.     

Morphologic and immunocytochemical studies of bronchioloalveolar carcinoma at Duke University Medical Center, 1968-1986

Between 1968 and 1986, the tumor registries at Duke University Medical Center and Durham VA Medical Center accumulated a total of 193 patients with a diagnosis of bronchioloalveolar carcinoma (BAC). All available histologic sections of primary lung tumors and all available respiratory and pleural cytologic material were reviewed for 135 cases having an initial histologic diagnosis of BAC and no history of a primary nonpulmonary adenocarcinoma. Thirty-nine cases showed a pure BAC pattern in histologic sections; 76 showed a dominant BAC pattern with focal areas of fibrosis and acinar differentiation; 16 were carcinomas with a focal BAC pattern; and 4 were adenocarcinomas lacking a BAC pattern. Of the 115 cases with at least a dominant BAC pattern, 51 showed predominantly mucinous differentiation while 64 showed predominantly nonmucinous differentiation. Adequate cytologic material was available for review from 111 patients. For cases having at least a dominant BAC pattern, tumor cells were present in 77 of 172 adequate sputums (44.8%), 36 of 133 bronchoscopy specimens (27.1%), 15 of 18 needle aspirates (83.3%) and 14 of 15 pleural fluids (93.3%). Of all patients in this group, 60.2% had at least one specimen positive for malignancy. No cytologic features clearly distinguished adenocarcinomas having only focal bronchioloalveolar differentiation from those with a pure or dominant BAC pattern. A significant degree of overlap was observed in the cytologic features of mucinous and nonmucinous tumors. Histologic sections from 19 mucinous and 16 nonmucinous tumors were stained with monoclonal antibody B72.3: all showed some staining, with no significant difference in degree of staining between the two groups. This suggests that expression of the tumor-associated glycoprotein TAG-72 is independent of mucinous differentiation.     

Relation of insulin receptors to insulin resistance.

The status of insulin-receptor interactions in a variety of insulin-resistant states is reviewed. Utilizing large adipocytes from adult rats and small fat cells from young rats, we have conducted a series of in vitro experiments in an attempt to determine the cellular alteration(s) responsible for the insulin resistance associated with obesity. Stimulation of glucose oxidation by insulin is reduced in large cells. Studies using a mimicker of insulin action, spermine, as well as measurements of 125I-insulin binding to large and small cells indicate that receptor number and affinity are not responsible for hormone resistance. Furthermore, when rapid and direct measurements of sugar uptake were made, insulin stimulation was virtually identical in both cell types. These findings indicate that large adipocytes have an efficient insulin-responsive D-glucose transport system and suggest that the apparent hormone resistance may be due to alterations in intracellular glucose metabolism. It has been proposed that altered insulin-receptor interaction underlies the insulin resistance of human obesity. We have investigated this particular aspect of insulin action by 125I-insulin binding studies. Similar numbers of insulin receptors per cell and affinity for insulin were observed in adipocytes obtained from normal weight subjects and morbidly obese patients. Thus, the initial step in insulin action is unaltered in human obesity.     

Relation of the heat resistance of bacterial spores to chemical composition and structure. II. Relation to cortex and structure

The relation between the amount of cortex, measured as total hexosamine, as diaminopimelic acid and as muramic lactam, and the heat resistance of spores of five different strains of Bacillus stearothermophilus was studied. Electron micrographs of thin sections of the spores were made to relate the structure of the spores to chemical and thermal characteristics. It was found that the amount of the cortex was significantly related to heat resistance of the spores. Strains with more electron-dense and better organized cortices were found to express higher heat resistance.     

烟草对烟粉虱的抗性与烟草化学成分的相关性

为探明烟草对烟粉虱Bemisia tabaci(Gennadius)的抗性机制,分别测定了不同烟草品种的叶绿素相对含量、鲜烟叶及烤后烟叶的化学成分含量,并分析了烟草抗虫性与烟草化学成分的关系.结果表明,中部叶片叶绿素含量与烟粉虱数量呈负相关,相关系数达到了显著水平;鲜烟叶化学成分钾氯比、糖碱比、氮碱比、还原糖、烟碱、蛋...     

Damage to DNA in cervical epithelium related to smoking tobacco.

OBJECTIVE--To determine whether tobacco smoking causes increased DNA modification (adducts) in human cervical epithelium. DESIGN--Comparison of DNA adducts measured by the technique of postlabelling with phosphorus-32 in normal ectocervical epithelium of smokers and non-smokers. A questionnaire on smoking habit and a urinary cotinine assay were used to identify smokers and non-smokers. SETTING--Cytology unit in large teaching hospital. SUBJECTS--39 women (11 current smokers, seven former smokers, and 21 who had never smoked) undergoing gynaecological treatment (colposcopy or hysterectomy). Nineteen members of staff who did not smoke as controls. INTERVENTIONS--Biopsy of normal ectocervical epithelium. Urine sample. MAIN OUTCOME MEASURES--Measurement of DNA adducts in cervical epithelial tissue of smokers and non-smokers. Smoking habit derived from results of questionnaire and urinary cotinine:creatinine ratio. Proportion of adducts in women with abnormal and normal results of cervical smear test. RESULTS--DNA samples from smokers (identified from questionnaire) had significantly higher median proportions of DNA adducts that non-smokers (4.62 (95% confidence interval 4.04 to 7.74) v 3.47 (2.84 to 4.78) adducts/10(8) nucleotides; p = 0.048). Exclusion of women whose urinary cotinine:creatinine ratio did not confirm their self reported smoking habit (smoker or non-smoker) increased this difference (4.7 (3.85 to 8.08) v 3.52 (2.32 to 4.95) adducts/10(8) nucleotides; p = 0.03). Women who had abnormal results of cervical smear tests had significantly higher proportions of adducts than those with normal results (4.7 (3.90 to 8.13) v 3.47 (3.06 to 5.36) adducts/10(8) nucleotides; p = 0.03). CONCLUSIONS--Tobacco smoking by women leads to increased modification of DNA in cervical epithelium, suggesting biochemical evidence consistent with smoking as a cause of cervical cancer.